FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Taborsky, GJ Mei, Q Hackney, DJ Mundinger, TO AF Taborsky, G. J., Jr. Mei, Q. Hackney, D. J. Mundinger, T. O. TI The search for the mechanism of early sympathetic islet neuropathy in autoimmune diabetes SO DIABETES OBESITY & METABOLISM LA English DT Review DE glucagon; hypoglycaemia; neuropathy; P75 neurotrophin receptor; sympathetic; type 1 diabetes ID INSULIN-INDUCED HYPOGLYCEMIA; AUTONOMIC NERVOUS-SYSTEM; INCREASED GLUCAGON-SECRETION; P75 NEUROTROPHIN RECEPTOR; GROWTH-FACTOR; B-CELLS; NERVES; RESPONSES; PANCREAS; RELEASE AB This review outlines our search for the mechanism causing the early loss of islet sympathetic nerves in autoimmune diabetes. Since our previous work has documented the importance of autonomic stimulation of glucagon secretion during hypoglycaemia, the loss of these nerves may contribute to the known impairment of this specific glucagon response early in human type 1 diabetes. We therefore briefly review the contribution that autonomic activation, and sympathetic neural activation in particular, makes to the subsequent glucagon response to hypoglycaemia. We also detail evidence that animal models of autoimmune diabetes mimic both the early loss of islet sympathetic nerves and the impaired glucagon response seen in human type 1 diabetes. Using data from these animal models, we examine mechanisms by which this loss of islet nerves could occur. We provide evidence that it is not due to diabetic hyperglycaemia, but is related to the lymphocytic infiltration of the islet. Ablating the p75 neurotrophin receptor, which is present on sympathetic axons, prevents early sympathetic islet neuropathy (eSIN), but, interestingly, not diabetes. Thus, we appear to have separated the immune-related loss of islet sympathetic nerves from the immune-mediated destruction of islet -cells. Finally, we speculate on a way to restore the sympathetic innervation of the islet. C1 [Taborsky, G. J., Jr.] Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA USA. [Taborsky, G. J., Jr.; Mei, Q.; Mundinger, T. O.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Hackney, D. J.] Seattle Inst Biomed & Clin Res, Seattle, WA USA. RP Taborsky, GJ (reprint author), VA Puget Sound Hlth Care Syst, Res 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM taborsky@u.washington.edu FU Medical Research Service of the Department of Veterans Affairs; National Institutes of Health [R01-DK-50154, P30-DK-017047] FX This work was supported by the Medical Research Service of the Department of Veterans Affairs and National Institutes of Health grants R01-DK-50154 and P30-DK-017047. The authors wish to thank Trish Banik for technical assistance and Pam Henderson for administrative assistance (both of the VA Puget Sound Health Care System). NR 48 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD SEP PY 2014 VL 16 SU 1 BP 96 EP 101 DI 10.1111/dom.12341 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP2EY UT WOS:000341886600014 PM 25200302 ER PT J AU Burge, SK Becho, J Ferrer, RL Wood, RC Talamantes, M Katerndahl, DA AF Burge, Sandra K. Becho, Johanna Ferrer, Robert L. Wood, Robert C. Talamantes, Melissa Katerndahl, David A. TI Safely Examining Complex Dynamics of Intimate Partner Violence SO FAMILIES SYSTEMS & HEALTH LA English DT Article DE spouse abuse; battered women; domestic violence; nonlinear dynamics; longitudinal studies ID DOMESTIC VIOLENCE; PRIMARY-CARE; HEALTH; RELIABILITY; WOMEN; DISORDERS; VALIDITY; STRESS; ADULT; ABUSE AB The overall goal of this study is to use complexity science to gain a deeper understanding of the nonlinear day-to-day dynamics of intimate partner violence, with implications for clinical interventions. This report describes research methods for gathering information about partner violence in real time and assesses recruitment and retention, adherence to study protocol, data validity, and participant safety. Research assistants enrolled 200 women in moderately violent intimate relationships and asked them to report about their relationships every day for 12 weeks. Daily, participants telephoned an Interactive Voice Response (IVR) system and responded to 34 survey questions. They also completed baseline and end-of-study surveys and maintained telephone contact with the study team weekly. Forty-two participants completed qualitative end-of-study interviews to describe their relationships and the impact of the study on their lives. Of 200 enrollees, 145 women provided enough data for nonlinear analyses, averaging 63.5 daily reports of 84 possible. Participants submitted 9,201 daily reports, documenting partner's verbal or physical aggression on 39.4% of days, and their own aggression on 23.1%. Two women were withdrawn from the study for safety reasons; the remainder reported that study participation posed no additional threat. Eighty women sought assistance from community resources. Violence severity did not appear to change over the 12 weeks. The research team successfully and safely recruited and retained 145 women who provided valuable data for a study of complex dynamics of intimate partner violence. C1 [Burge, Sandra K.; Becho, Johanna; Ferrer, Robert L.; Wood, Robert C.; Katerndahl, David A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Talamantes, Melissa] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Burge, SK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, 7703 Floyd Curl Dr,Mail Code 7795, San Antonio, TX 78229 USA. EM burge@uthscsa.edu FU "Dynamics of Human Behavior" program, National Science Foundation [0525026] FX This study was funded with a grant from the "Dynamics of Human Behavior" program, National Science Foundation, Award 0525026. Automated data collection was provided by the University of Colorado, Department of Family Medicine Information Services group. We thank Stephanie Mitchell, Kelli Giacomini, and Wilson Pace for their invaluable assistance with IVR. We also express appreciation to Norma Cantu and Diandrea Garza for their commitment to screening and enrolling women for this study. NR 36 TC 9 Z9 9 U1 2 U2 13 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1091-7527 EI 1939-0602 J9 FAM SYST HEALTH JI Fam. Syst. Health PD SEP PY 2014 VL 32 IS 3 BP 259 EP 270 DI 10.1037/fsh0000013 PG 12 WC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health GA AP1QF UT WOS:000341845300002 PM 24911769 ER PT J AU Martin, WJ Shim, M Paulus, HE Chaudhari, S Feng, JY Elashoff, D Hahn, TJ Ranganath, VK AF Martin, William J. Shim, Man Paulus, Harold E. Chaudhari, Sandeep Feng, JingYuan Elashoff, David Hahn, Theodore J. Ranganath, Veena K. CA RADIUS Investigators TI Older Age at Rheumatoid Arthritis Onset and Comorbidities Correlate With Less Health Assessment Questionnaire-Disability Index and Clinical Disease Activity Index Response to Etanercept in the RADIUS 2 Registry SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; age; outcomes; disease activity; functional status; etanercept ID ANTIRHEUMATIC DRUG INTERVENTION; ELDERLY-PATIENTS; SERIOUS INFECTIONS; YOUNGER; THERAPY; POPULATION; BIOLOGICS; REMISSION; CRITERIA; OUTCOMES AB Background: Controversy exists in understanding the effects of age at onset and comorbidities in predicting rheumatoid arthritis (RA) response to biologic therapy. Objective: The objective of this study was to investigate the influence of age at onset and number of comorbidities on Health Assessment Questionnaire-Disability Index (HAQ-DI) and Clinical Disease Activity Index (CDAI) responses in active RA patients after 6 months of treatment with etanercept. Methods: One thousand eight hundred ninety-nine RA patients were assessed after 6 months of etanercept therapy. Patients met the following inclusion criteria: initiated etanercept, continued therapy for at least 6 months, and were not in CDAI low disease activity (LDA) at baseline (CDAI <= 10.0). Changes in HAQ-DI and CDAI scores over 6 months were analyzed across age of onset quintiles. Multivariate regression models evaluated the independent association between both age at onset and number of comorbidities with change in HAQ-DI/CDAI scores or achieving LDA, while accounting for other covariates. Results: Significant improvements in HAQ-DI and CDAI scores were observed in all age-onset groups, although HAQ-DI improvements were less in older-onset patients. Results of multiple linear regression demonstrated that younger age at onset, higher baseline HAQ-DI/CDAI score, rheumatoid factor positivity, shorter disease duration, and fewer comorbidities at baseline were independently associated with improvement in both HAQ-DI and CDAI scores. Similarly, achieving CDAI LDA after 6 or more months of etanercept was associated with younger age at onset, higher baseline CDAI, shorter disease duration, and fewer comorbidities. Conclusions: These patients with older-onset RA and more comorbidities clinically improved with etanercept, but had lower odds of achieving CDAI LDA. Age of onset and number of comorbidities may be important in determining RA tumor necrosis factor inhibitor response. C1 [Martin, William J.; Shim, Man; Paulus, Harold E.; Elashoff, David; Hahn, Theodore J.; Ranganath, Veena K.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Chaudhari, Sandeep] PharmaNet i3 Strateg Resourcing, Tampa, FL USA. [Feng, JingYuan] Amgen Inc, Thousand Oaks, CA 91320 USA. [Hahn, Theodore J.] VA Greater Los Angeles Geriatr Res Educ & Clin Ct, Los Angeles, CA USA. RP Ranganath, VK (reprint author), Univ Calif Los Angeles, 1000 Vet Ave,Rehab Bldg 32-59, Los Angeles, CA 90095 USA. EM vranganath@mednet.ucla.edu FU Immunex, a wholly owned subsidiary of Amgen Inc; Wyeth; ACR/REF/ASP; UCLA Older Americans Independence Center, NIA [AG028748] FX This study was sponsored by Immunex, a wholly owned subsidiary of Amgen Inc, and by Wyeth, which was acquired by Pfizer in October 2009.; V.K.R. received the ACR/REF/ASP Junior Career Development Award in Geriatric Medicine and UCLA Older Americans Independence Center, NIA AG028748. The remaining authors declare no conflict of interest. NR 42 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD SEP PY 2014 VL 20 IS 6 BP 301 EP 305 DI 10.1097/RHU.0000000000000152 PG 5 WC Rheumatology SC Rheumatology GA AO7WJ UT WOS:000341563000006 PM 25160011 ER PT J AU Boehme, AK Rawal, PV Lyerly, MJ Albright, KC Shahripour, RB Palazzo, P Kapoor, N Alvi, M Houston, JT Harrigan, MR Cava, L Sisson, A Alexandrov, AW Alexandrov, AV AF Boehme, Amelia K. Rawal, Pawan V. Lyerly, Michael J. Albright, Karen C. Shahripour, Reza Bavarsad Palazzo, Paola Kapoor, Niren Alvi, Mohammad Houston, J. Thomas Harrigan, Mark R. Cava, Luis Sisson, April Alexandrov, Anne W. Alexandrov, Andrei V. TI Investigating the Utility of Previously Developed Prediction Scores in Acute Ischemic Stroke Patients in the Stroke Belt SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Stroke; epidemiology; stroke recovery; outcome ID TISSUE-PLASMINOGEN ACTIVATOR; TOTALED HEALTH-RISKS; EVENTS THRIVE SCORE; INTRAARTERIAL THERAPY; UNITED-STATES; THROMBOLYSIS; VALIDATION; EXPERIENCE; OUTCOMES AB Background: To assess the utility of previously developed scoring systems, we compared SEDAN, named after the components of the score (baseline blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign on admission computed tomography scan, Age, and National Institutes of Health Stroke Scale on admission), Totaled Health Risks in Vascular Events (THRIVE), Houston Intra-arterial Therapy (HIAT), and HIAT-2 scoring systems among patients receiving systemic (intravenous [IV] tissue plasminogen activator [tPA]) and endovascular (intra-arterial [IA]) treatments. Methods: We retrospectively reviewed all IV tPA and IA patients presenting to our center from 2008-2011. The scores were assessed in patients who were treated with IV tPA only, IA only, and a combination of IV tPA and IA (IV-IA). We tested the ability of THRIVE to predict discharge modified Rankin scale (mRS) 3-6, HIAT and HIAT-2 discharge mRS 4-6, and SEDAN symptomatic intracerebral hemorrhage (sICH). Results: Of the 366 patients who were included in this study, 243 had IV tPA only, 89 had IA only, and 34 had IV-IA. THRIVE was predictive of mRS 3-6 in the IV-IA (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.30-2.91) and the IV group (OR, 1.71; 95% CI, 1.43-2.04), but not in the IA group. HIAT was predictive of mRS 4-6 in the IA (OR, 3.55; 95% CI, 1.65-7.25), IV (OR, 3.47; 95% CI, 2.26-5.33), and IV-IA group (OR, 6.48; 95% CI, 1.41-29.71). HIAT-2 was predictive of mRS 4-6 in the IA (OR, 1.39; 95% CI, 1.03-1.87) and IV group (OR, 1.36; 95% CI, 1.18-1.57), but not in the IV-IA group. SEDAN was not predictive of sICH in the IA or the IV-IA group, but was predictive in the IV group (OR, 1.54; 95% CI, 1.01-2.36). Conclusions: Our study demonstrated that although highly predictive of outcome in the original study design treatment groups, prediction scores may not generalize to all patient samples, highlighting the importance of validating prediction scores in diverse samples. C1 [Boehme, Amelia K.; Rawal, Pawan V.; Lyerly, Michael J.; Shahripour, Reza Bavarsad; Palazzo, Paola; Kapoor, Niren; Alvi, Mohammad; Houston, J. Thomas; Sisson, April; Alexandrov, Andrei V.] Univ Alabama Birmingham, Dept Neurol, Stroke Ctr, Birmingham, AL 35294 USA. [Boehme, Amelia K.; Albright, Karen C.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Lyerly, Michael J.] Birmingham Vet Affairs Med Ctr, Stroke Ctr, Birmingham, AL USA. [Harrigan, Mark R.] Univ Alabama Birmingham, Sch Med, Dept Neurosurg, Birmingham, AL USA. [Cava, Luis] Univ Colorado, Dept Neurosurg, Denver, CO 80202 USA. [Alexandrov, Anne W.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. RP Boehme, AK (reprint author), 1240 Jefferson Tower,619 19th St South, Birmingham, AL 35294 USA. EM akboehme@gmail.com OI Alexandrov, Andrei V/0000-0001-8871-1023; Lyerly, Michael/0000-0003-4236-1018 FU Agency for Healthcare Research and Quality (AHRQ) [5 T32 HS013852-10]; National Institute on Minority Health and Health Disparities (NIMHD), National Institutes of Health (NIH) [3 P60 MD000502-08S1]; American Heart Association (AHA) [13PRE13830003] FX The project described was supported by award numbers 5 T32 HS013852-10 from The Agency for Healthcare Research and Quality (AHRQ), 3 P60 MD000502-08S1 from The National Institute on Minority Health and Health Disparities (NIMHD), National Institutes of Health (NIH) and 13PRE13830003 from the American Heart Association (AHA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHA, AHRQ, or the NIH. NR 22 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD SEP PY 2014 VL 23 IS 8 BP 2001 EP 2006 DI 10.1016/j.jstrokecerebrovasdis.2014.02.003 PG 6 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AO6TQ UT WOS:000341484900011 PM 25113079 ER PT J AU Jacobus, J Squeglia, LM Sorg, SF Nguyen-Louie, TT Tapert, SF AF Jacobus, Joanna Squeglia, Lindsay M. Sorg, Scott F. Nguyen-Louie, Tam T. Tapert, Susan F. TI Cortical Thickness and Neurocognition in Adolescent Marijuana and Alcohol Users Following 28 Days of Monitored Abstinence SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID SPATIAL WORKING-MEMORY; HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; ADULT CANNABIS USERS; WHITE-MATTER; NEUROPSYCHOLOGICAL PERFORMANCE; SUBSTANCE-ABUSE; BINGE DRINKING; COMPLEX FIGURE; FMRI RESPONSE AB Objective: Adolescent marijuana use continues to increase in prevalence as harm perception declines. Better understanding of marijuana's impact on neurodevelopment is crucial. This prospective study aimed to investigate cortical thickness and neurocognitive performance before and after 28 days of monitored abstinence in adolescent marijuana and alcohol users. Method: Subjects (N = 54; >70% male) were adolescent marijuana users (ages 15-18 years) with regular alcohol use (MJ + ALC; n = 24) and non-using controls (CON; n = 30) who were compared before and after 4 weeks of sequential urine toxicology to confirm abstinence. Participants underwent magnetic resonance imaging, neuropsychological assessment, and substance use assessment at both time points. Repeated-measures analysis of covariance was used to look at the main effects of group, time, and Group x Time interactions on cortical thickness and neurocognitive functioning. Bivariate correlations estimated associations between cortical thickness, substance use severity, and cognitive performance. Results: Marijuana users showed thicker cortices than controls in the left entorhinal cortex (ps < .03) before and after monitored abstinence, after adjusting for lifetime alcohol use. More lifetime marijuana use was linked to thinner cortices in temporal and frontal regions, whereas more lifetime alcohol use and heavy episodic drinking episodes was linked to thicker cortices in all four lobes (ps < .05). Age of onset of regular marijuana use was positively related to cortical thickness (ps < .03). Conclusions: Adolescent alcohol and marijuana use may be linked to altered longer-term neurodevelopmental trajectories and compromised neural health. Cortical thickness alterations and dose-dependent associations with thickness estimates were observed both before and after monitored abstinence and suggest neural differences continue to persist 28 days after cessation of marijuana use. Neural recovery may be identified with longer follow-up periods; however, observed changes related to use severity could have implications for future psychosocial outcomes. C1 [Jacobus, Joanna; Tapert, Susan F.] VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Jacobus, Joanna; Squeglia, Lindsay M.; Nguyen-Louie, Tam T.; Tapert, Susan F.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Sorg, Scott F.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Nguyen-Louie, Tam T.] Univ Calif San Diego, San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92103 USA. RP Tapert, SF (reprint author), VA San Diego Healthcare Syst, Psychol Serv 116B, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM stapert@ucsd.edu FU National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism [P20 DA024194, R01 DA021182, F32 DA032188, R01 AA013419, T32 AA013525, U01 AA021692] FX This study was supported by National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism Grants P20 DA024194, R01 DA021182, F32 DA032188, R01 AA013419, T32 AA013525, and U01 AA021692. NR 96 TC 14 Z9 14 U1 4 U2 21 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD SEP PY 2014 VL 75 IS 5 BP 729 EP 743 PG 15 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA AO8PA UT WOS:000341615500001 PM 25208190 ER PT J AU Narayana, S Wong, CJ AF Narayana, Sirisha Wong, Christopher J. TI Office-Based Screening of Common Psychiatric Conditions SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Screening; Depression; Anxiety; Cost-effectiveness; Outcomes ID PATIENT HEALTH QUESTIONNAIRE; PRIMARY-CARE PATIENTS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; COMORBIDITY SURVEY REPLICATION; GENERALIZED ANXIETY DISORDER; CASE-FINDING INSTRUMENTS; UTAH RATING-SCALE; DSM-IV DISORDERS; MAJOR DEPRESSION AB Depression and anxiety disorders are common conditions with significant morbidity. Many screening tools of varying length have been well validated for these conditions in the office-based setting. Novel instruments, including Internet-based and computerized adaptive testing, may be promising tools in the future. The best evidence for cost-effectiveness currently is for screening of major depression linked with the collaborative care model for treatment. Data are not conclusive regarding comparative cost-effectiveness of screening for multiple conditions at once or for other conditions. This article reviews screening tools for depression and anxiety disorders in the ambulatory setting. C1 [Narayana, Sirisha] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Gen Internal Med, Seattle, WA 98108 USA. [Wong, Christopher J.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98105 USA. RP Wong, CJ (reprint author), Univ Washington, Dept Med, Div Gen Internal Med, 4245 Roosevelt Way Northeast,Box 354760, Seattle, WA 98105 USA. EM cjwong@uw.edu NR 77 TC 4 Z9 4 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2014 VL 98 IS 5 BP 959 EP + DI 10.1016/j.mcna.2014.06.002 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA AO8OO UT WOS:000341614300005 PM 25134868 ER PT J AU Lin, Y Luo, J Zhu, WE Srivastava, M Schaue, D Elashoff, DA Dubinett, SM Sharma, S Wu, B St John, MA AF Lin, Yuan Luo, Jie Zhu, Weichao Eric Srivastava, Minu Schaue, Dorthe Elashoff, David A. Dubinett, Steven M. Sharma, Sherven Wu, Benjamin St John, Maie A. TI A Cytokine-Delivering Polymer Is Effective in Reducing Tumor Burden in a Head and Neck Squamous Cell Carcinoma Murine Model SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE head and neck cancer; squamous cell carcinoma; polymer; novel therapeutics ID LYMPHOID-TISSUE CHEMOKINE; CC-CHEMOKINE; RECEPTOR CCR7; GENE-THERAPY; MOUSE MODEL; CANCER; RADIOTHERAPY; CCL21; ACTIVATION; MECHANISMS AB Objective This study aimed to evaluate the therapeutic efficacy of a novel polymer platform delivering cisplatin and cytokines in the treatment of head and neck squamous cell carcinoma (HNSCC). Study Design In vivo study. Setting Academic research laboratory. Subjects and Methods Mice were randomized to receive implantation of (1) no polymer, (2) plain polymer, (3) plain polymer with local cisplatin injection, or (4) cisplatin polymer. The 2 groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive (1) 4 Grays external beam radiation for 4 days or (2) no radiation. For cytokine studies, mice were grouped into (1) no polymer, (2) plain polymer, (3) plain polymer with intratumoral injection of recombinant CCL21 twice a week, (4) polymer containing parental dendritic cells, or (5) polymer containing dendritic cells secreting CCL21 (DC-CCL21). Results The cisplatin-secreting polymer effectively reduced tumors in the mice by more than 16-fold (P < .01). We also observed a statistically significant lower tumor weight among mice treated with cisplatin polymer and concomitant radiation compared to control groups. The DC-CCL21 polymer reduced SCCVII/SF tumors in the C3H/HeJ mice by more than 41% (P < .01). Conclusion Herein, we demonstrate the efficacy of a novel polymer platform in delivering cisplatin and cytokines. We also demonstrate that we can effectively grow dendritic cells in the polymer that can actively secrete CCL21 for a minimum of 5 days. This polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized, we will plan to pursue prospective trials in patients with HNSCC. C1 [Lin, Yuan; Luo, Jie; St John, Maie A.] Univ Calif Los Angeles, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Lin, Yuan; Luo, Jie; St John, Maie A.] Univ Calif Los Angeles, UCLA Head & Neck Canc Program, Los Angeles, CA 90095 USA. [Lin, Yuan; Luo, Jie; Srivastava, Minu; Dubinett, Steven M.; Sharma, Sherven] Univ Calif Los Angeles, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. [Zhu, Weichao Eric; Wu, Benjamin] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA. [Srivastava, Minu; Dubinett, Steven M.; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Schaue, Dorthe] Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90095 USA. [Elashoff, David A.; Dubinett, Steven M.; St John, Maie A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Elashoff, David A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. [Wu, Benjamin] Univ Calif Los Angeles, Div Adv Prosthodont Biomat & Hosp Dent, Los Angeles, CA 90095 USA. [Wu, Benjamin] Univ Calif Los Angeles, Dept Mat Sci & Engn, Los Angeles, CA 90095 USA. [Wu, Benjamin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthoped Surg, Los Angeles, CA 90095 USA. RP St John, MA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mstjohn@mednet.ucla.edu FU American Academy of Otolaryngology-American Head & Neck Society Surgeon Scientist Career Development Award; Tobacco-Related Disease Research Program of the University of California; STOP Cancer Foundation; Jonsson Cancer Center; NIDCR K23 FX Funding source: This study was supported by the American Academy of Otolaryngology-American Head & Neck Society Surgeon Scientist Career Development Award (M.A.S.J.), the Tobacco-Related Disease Research Program of the University of California (M.A.S.J.), the STOP Cancer Foundation (M.A.S.J.), The Jonsson Cancer Center, and NIDCR K23 (M.A.S.J.). NR 35 TC 2 Z9 2 U1 1 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2014 VL 151 IS 3 BP 447 EP 453 DI 10.1177/0194599814533775 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AP0MU UT WOS:000341757000014 PM 24825873 ER PT J AU Bibas, L Levi, M Bendayan, M Mullie, L Forman, DE Afilalo, J AF Bibas, Lior Levi, Michael Bendayan, Melissa Mullie, Louis Forman, Daniel E. Afilalo, Jonathan TI Therapeutic Interventions for Frail Elderly Patients: Part I. Published Randomized Trials SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Frailty; Sarcopenia; Randomized clinical trials ID PHYSICAL-ACTIVITY INTERVENTION; JAPANESE SARCOPENIC WOMEN; PLACEBO-CONTROLLED TRIAL; DWELLING OLDER-ADULTS; FUNCTIONAL DECLINE; BODY-COMPOSITION; CLINICAL-TRIAL; DOUBLE-BLIND; MUSCLE MASS; HEART-FAILURE AB The body of literature for frailty as a prognostic marker continues to grow, yet the evidence for frailty as a therapeutic target is less well defined. In the setting of cardiovascular disease, the prevalence of frailty is elevated and its impact on mortality and major morbidity is substantial. Therapeutic interventions aimed at improving frailty may impart gains in functional status and survival. Randomized clinical trials that tested one or more therapeutic interventions in a population of frail older adults were reviewed. The interventions studied were exercise training in 13 trials, nutritional supplementation in 4 trials, combined exercise plus nutritional supplementation in 7 trials, pharmaceutical agents in 8 trials, multi-dimensional programs in 5 trials, and home-based services in 1 trial. The main findings of these trials are explored along with a discussion of their relative merits and limitations. (c) 2014 Elsevier Inc. All rights reserved. C1 [Bibas, Lior; Levi, Michael; Mullie, Louis] McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. [Bibas, Lior; Levi, Michael; Afilalo, Jonathan] McGill Univ, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Bendayan, Melissa; Afilalo, Jonathan] McGill Univ, Dept Physiol, Montreal, PQ H3T 1E2, Canada. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Sect Geriatr Cardiol, Pittsburgh, PA USA. [Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Geratr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Clin Epidemiol, Montreal, PQ H3T 1E2, Canada. RP Afilalo, J (reprint author), McGill Univ, Jewish Gen Hosp, Div Cardiol, 3755 Cote Ste Catherine Rd,E-222, Montreal, PQ H3T 1E2, Canada. EM jonathan.afilalo@mcgill.ca NR 48 TC 33 Z9 33 U1 4 U2 29 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 EI 1873-1740 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD SEP-OCT PY 2014 VL 57 IS 2 BP 134 EP 143 DI 10.1016/j.pcad.2014.07.004 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP1AN UT WOS:000341798900003 PM 25216612 ER PT J AU Bendayan, M Bibas, L Levi, M Mullie, L Forman, DE Afilalo, J AF Bendayan, Melissa Bibas, Lior Levi, Michael Mullie, Louie Forman, Daniel E. Afilalo, Jonathan TI Therapeutic Interventions for Frail Elderly Patients: Part II. Ongoing and Unpublished Randomized Trials SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Frailty; Sarcopenia; Randomized clinical trials ID MUSCLE STRENGTH; OLDER-ADULTS; SARCOPENIA; MEN; SUPPLEMENTATION; METAANALYSIS; EXERCISE; HEALTH; PEOPLE AB There is increasing momentum to measure frailty in clinical practice given its proven value as a predictor of outcomes, particularly in elderly patients with cardiovascular disease. The number of randomized clinical trials targeting frail older adults has been modest to date. Therefore, we systematically searched the ClinicalTrials.gov registry in order to review the frailty intervention trials that had been actively initiated or completed but not yet published. The interventions studied were exercise training in 2 trials, nutritional supplementation in 3 trials, combined exercise plus nutritional supplementation in 5 trials, pharmaceutical agents in 5 trials, multidimensional programs in 2 trials, and home-based services in 3 trials. Their respective study designs, populations, interventions, and planned outcomes are presented in this article. (c) 2014 Elsevier Inc. All rights reserved. C1 [Bendayan, Melissa] McGill Univ, Dept Physiol, Montreal, PQ H3T 1E2, Canada. [Bibas, Lior; Levi, Michael; Mullie, Louie; Afilalo, Jonathan] McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. [Bibas, Lior; Levi, Michael; Afilalo, Jonathan] McGill Univ, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Sect Geriatr Cardiol, Pittsburgh, PA USA. [Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Geratr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Clin Epidemiol, Montreal, PQ H3T 1E2, Canada. RP Afilalo, J (reprint author), McGill Univ, Jewish Gen Hosp, Div Cardiol, 3755 Cote Ste Catherine Rd,E-222, Montreal, PQ H3T 1E2, Canada. EM jonathan.afilalo@mcgill.ca NR 16 TC 14 Z9 14 U1 1 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 EI 1873-1740 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD SEP-OCT PY 2014 VL 57 IS 2 BP 144 EP 151 DI 10.1016/j.pcad.2014.07.005 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP1AN UT WOS:000341798900004 PM 25216613 ER PT J AU Bradley, SM Stanislawski, MA Bekelman, DB Monteith, LL Cohen, BE Schilling, JH Hunt, SC Milek, D Maddox, TM Ho, PM Shore, S Varosy, PD Matthieu, MM Rumsfeld, JS AF Bradley, Steven M. Stanislawski, Maggie A. Bekelman, David B. Monteith, Lindsey L. Cohen, Beth E. Schilling, John H. Hunt, Stephen C. Milek, Debra Maddox, Thomas M. Ho, P. Michael Shore, Supriya Varosy, Paul D. Matthieu, Monica M. Rumsfeld, John S. TI Invasive coronary procedure use and outcomes among veterans with posttraumatic stress disorder: Insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program SO AMERICAN HEART JOURNAL LA English DT Article ID GENERALIZED ANXIETY DISORDER; MAJOR DEPRESSIVE DISORDER; HEART-DISEASE; CART PROGRAM; MYOCARDIAL-INFARCTION; PSYCHIATRIC-DISORDERS; CARDIOVASCULAR EVENTS; HEALTH BEHAVIORS; ARTERY-DISEASE; RISK-FACTOR AB Background Posttraumatic stress disorder (PTSD) is prevalent in the general population and US veterans in particular and is associated with an increased risk of developing coronary artery disease (CAD). We compared the patient characteristics and postprocedural outcomes of veterans with and without PTSD undergoing coronary angiography. Methods This is a multicenter observational study of patients who underwent coronary angiography in Veterans Affairs hospitals nationally from October 2007 to September 2011. We described patient characteristics at angiography, angiographic results, and after coronary angiography, we compared risk-adjusted 1-year rates of all-cause mortality, myocardial infarction (MI), and revascularization by the presence or absence of PTSD. Results Overall, of 116,488 patients undergoing angiography, 14,918 (12.8%) had PTSD. Compared with those without PTSD, patients with PTSD were younger (median age 61.9 vs 63.7; P < .001), had higher rates of cardiovascular risk factors, and were more likely to have had a prior MI (26.4% vs 24.7%; P < .001). Patients with PTSD were more likely to present for stable angina (22.4% vs 17.0%) or atypical chest pain (58.5% vs 48.6%) and less likely to have obstructive CAD identified at angiography (55.9% vs 62.2%; P < .001). After coronary angiography, PTSD was associated with lower unadjusted 1-year rates of MI (hazard ratio (HR), 0.86; 95% CI [0.75-1.00]; P = 0.04), revascularization (HR, 0.88; 95% CI [0.83-0.93]; P < .001), and all-cause mortality (HR, 0.66; 95% CI [0.60-0.71]; P < .001). After adjustment for cardiovascular risk, PTSD was no longer associated with 1-year rates of MI or revascularization but remained associated with lower 1-year all-cause mortality (HR, 0.91; 95% CI [0.84-0.99]; P = .03). Findings were similar after further adjustment for depression, anxiety, alcohol or substance use disorders, and frequency of outpatient follow-up. Conclusions Among veterans undergoing coronary angiography in the Veterans Affairs, those with PTSD were more likely to present with elective indications and less likely to have obstructive CAD. After coronary angiography, PTSD was not associated with adverse 1-year outcomes of MI, revascularization, or all-cause mortality. C1 [Bradley, Steven M.; Stanislawski, Maggie A.; Bekelman, David B.; Monteith, Lindsey L.; Maddox, Thomas M.; Ho, P. Michael; Shore, Supriya; Varosy, Paul D.; Rumsfeld, John S.] VA Eastern Colorado Hlth Care Syst, Denver, CO 80220 USA. [Bradley, Steven M.; Bekelman, David B.; Schilling, John H.; Maddox, Thomas M.; Ho, P. Michael; Shore, Supriya; Varosy, Paul D.; Rumsfeld, John S.] Univ Colorado, Sch Med, Aurora, CO USA. [Bradley, Steven M.; Stanislawski, Maggie A.; Bekelman, David B.; Maddox, Thomas M.; Ho, P. Michael; Shore, Supriya; Varosy, Paul D.; Rumsfeld, John S.] Colorado Cardiovasc Outcomes Res Consortium, Denver, CO USA. [Cohen, Beth E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Hunt, Stephen C.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Hunt, Stephen C.; Milek, Debra] Univ Washington, Seattle, WA 98195 USA. [Matthieu, Monica M.] St Louis VA Med Ctr, St Louis, MO USA. [Matthieu, Monica M.] St Louis Univ, St Louis, MO 63103 USA. RP Bradley, SM (reprint author), VA Eastern Colorado Hlth Care Syst, Dept Vet Affairs, 1055 Clermont St,111B, Denver, CO 80220 USA. EM Steven.Bradley@va.gov FU VA Health Services Research Development [HSRD-CDA2 10-199] FX Dr Bradley is supported by a Career Development Award (HSR&D-CDA2 10-199) from VA Health Services Research & Development. The authors report no relevant relationships with industry or other disclosures. NR 47 TC 1 Z9 1 U1 2 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD SEP PY 2014 VL 168 IS 3 BP 381 EP U200 DI 10.1016/j.ahj.2014.05.015 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO4QY UT WOS:000341327200020 PM 25173551 ER PT J AU Koyner, JL Cerda, J Goldstein, SL Jaber, BL Liu, KD Shea, JA Faubel, S AF Koyner, Jay L. Cerda, Jorge Goldstein, Stuart L. Jaber, Bertrand L. Liu, Kathleen D. Shea, Judy A. Faubel, Sarah CA Amer Soc Nephrology TI The Daily Burden of Acute Kidney Injury: A Survey of US Nephrologists on World Kidney Day SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Acute kidney injury (AKI); survey; nephrology; dialysis; dialysis dosing; World Kidney Day; epidemiology; workload; public health ID ACUTE-RENAL-FAILURE; CRITICALLY-ILL PATIENTS; REPLACEMENT THERAPY; AKI; DISEASE; OUTCOMES; DIALYSIS; RISK; CKD; HEMODIALYSIS AB Background: World Kidney Day 2013 focused on raising awareness of the impact and consequences of acute kidney injury (AKI). Although many studies have examined rates of AKI in hospitalized patients, we were interested in the impact of AKI on the workload of nephrologists. Study Design: Cross-sectional forced-choice internet-based survey. Setting & Participants: 598 survey respondents who were US-based nephrologist members of the American Society of Nephrology. Outcomes: Numbers of inpatients and outpatients seen on World Kidney Day 2013 for the management of AKI or other conditions (and specifically in-hospital renal replacement therapies [RRTs]), based on self-report of number/percentage of patients seen on World Kidney Day and in the prior year. Results: Of 598 physician respondents (response rate, 12%), 310 saw patients in the hospital on World Kidney Day. Of 3,285 patients seen by respondents, 1,500 were seen for AKI (46%); 1,233, for end-stage renal disease (37%); and 552, for non-AKI/end-stage renal disease-related problems (17%). Of patients with AKI, 688 (46%) were in the intensive care unit and 415 (28%) received RRT. Intermittent hemodialysis was performed in 315 patients (76%) who received RRT. Delivered dialysis dose was quantified in only 48 (15%) of those receiving intermittent hemodialysis. 260 respondents saw 2,380 patients in the ambulatory setting, of whom 207 (9%) were seen for follow-up of AKI. Limitations: There was a low response rate to the survey. Numbers of patients were self-reported. Conclusions: This is the first physician survey examining the care of patients and impact of AKI on current in-hospital and ambulatory nephrology practices. In our sample, AKI was the most common reason for in-hospital nephrology consultation. Furthermore, our findings point to significant areas in which improvement is needed, including inadequate quantification of dialysis delivered dose. Finally, our survey highlights that AKI is a major public health issue. (C) 2014 by the National Kidney Foundation, Inc. C1 [Koyner, Jay L.] Univ Chicago, Nephrol Sect, Chicago, IL 60637 USA. [Cerda, Jorge] Albany Med Coll, Albany, NY 12208 USA. [Goldstein, Stuart L.] Cincinnati Childrens Hosp Med Ctr, Ctr Acute Care Nephrol, Cincinnati, OH 45229 USA. [Jaber, Bertrand L.] Tufts Univ, Sch Med, St Elizabeths Med Ctr, Dept Med,Div Nephrol, Boston, MA 02111 USA. [Liu, Kathleen D.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shea, Judy A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Faubel, Sarah] Univ Colorado, Denver Vet Affairs Med Ctr, Div Nephrol, Aurora, CO 80045 USA. RP Faubel, S (reprint author), Univ Colorado, Denver Vet Affairs Med Ctr, Div Nephrol, 12700 19th Ave,Box C281, Aurora, CO 80045 USA. EM sarah.faubel@ucdenver.edu FU ASN FX Support: The study was supported by the ASN, which had no role in the development of the survey, analysis and interpretation of data, writing the report, or the decision to submit the report for publication. NR 38 TC 10 Z9 10 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2014 VL 64 IS 3 BP 394 EP 401 DI 10.1053/j.ajkd.2014.03.018 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AO5BV UT WOS:000341357100016 PM 24815216 ER PT J AU Backus, LI Belperio, PS Loomis, TP Mole, LA AF Backus, Lisa I. Belperio, Pamela S. Loomis, Timothy P. Mole, Larry A. TI Impact of Race/Ethnicity and Gender on HCV Screening and Prevalence Among US Veterans in Department of Veterans Affairs Care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEPATITIS-C VIRUS; UNITED-STATES; AFRICAN-AMERICANS; INFECTION; EPIDEMIOLOGY; MORTALITY AB Objectives. We assessed HCV screening and prevalence among veterans and estimated the potential impact of complete birth cohort screening, accounting for the disparate HCV disease burden by race/ethnicity and gender. Methods. We used the Department of Veterans Affairs (VA) Corporate Data Warehouse to identify birth dates, gender, race/ethnicity, and laboratory tests for veterans with at least 1 VA outpatient visit in 2012. We calculated HCV screening rates, prevalence, and HCV infection incident diagnosis. Results. Among 5 499 743 veterans, 54.7% had HCV screening through the VA. In more than 2.9 million veterans screened, HCV prevalence was 6.1% overall and highest among Blacks (11.8%), particularly Black men born in 1945 to 1965 (17.7%). HCV infection incident diagnosis in 2012 was 5.9% for men and 2.3% for women. An estimated additional 48 928 male veterans, including 12 291 Black men, and 1484 female veterans would potentially be identified as HCV infected with full birth cohort screening. Conclusions. HCV prevalence was markedly elevated among veterans born in 1945 to 1965, with substantial variation by race/ethnicity and gender. Full adoption of birth cohort screening may reveal substantial numbers of veterans with previously unknown HCV infection. C1 [Backus, Lisa I.; Belperio, Pamela S.; Loomis, Timothy P.; Mole, Larry A.] Off Publ Health Populat Hlth, Dept Vet Affairs, Washington, DC USA. [Backus, Lisa I.] VA Palo Alto Hlth Care Syst, Dept Med, Palo Alto, CA USA. [Belperio, Pamela S.] VA Greater Los Angeles Hlth Care Syst, Dept Pharm, Los Angeles, CA USA. RP Backus, LI (reprint author), 3801 Miranda Ave,Mail Code 132, Palo Alto, CA 94304 USA. EM Lisa.Backus@va.gov NR 22 TC 13 Z9 13 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S555 EP S561 DI 10.2105/AJPH.2014.302090 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000014 PM 25100421 ER PT J AU Blosnich, JR Mays, VM Cochran, SD AF Blosnich, John R. Mays, Vickie M. Cochran, Susan D. TI Suicidality Among Veterans: Implications of Sexual Minority Status SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID OF-LIFE SURVEY; HEALTH; INDIVIDUALS; GAY; ORIENTATION; MILITARY; DISORDER; IDEATION; RISK AB Using the California Quality of Life surveys, we examined suicidal ideation and attempts in 129 lesbian, gay, and bisexual (LGB) veterans and in 315 heterosexual veterans in 2008-2009 and 2012-2013. Although there were no significant differences in the past 12-month suicidal ideation and lifetime attempts, LGB veterans had higher odds of lifetime suicidal ideation than heterosexual veterans (adjusted odds ratio = 3.00; 95% confidence interval = 1.38, 6.53). Suicide assessment and prevention efforts in LGB veterans could benefit from a life-course perspective regarding suicide risk. C1 [Blosnich, John R.] Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Pittsburgh, PA USA. [Blosnich, John R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15260 USA. [Mays, Vickie M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Mays, Vickie M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cochran, Susan D.] Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Cochran, Susan D.] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM John.blosnich@va.gov FU Office of Academic Affiliations in the Department of Veterans Affairs; Center for Health Equity Research and Promotion in the VA Pittsburgh Healthcare System; National Center for Minority Health and Health Disparities [MD006923]; National Institute on Drug Abuse [DA20826] FX This work was supported by a postdoctoral fellowship to J. R. B. from the Office of Academic Affiliations in the Department of Veterans Affairs and the Center for Health Equity Research and Promotion in the VA Pittsburgh Healthcare System. This work was supported by a grant from the National Center for Minority Health and Health Disparities (MD006923) to V. M. M. and a grant from the National Institute on Drug Abuse (DA20826) to S. D. C. NR 19 TC 5 Z9 5 U1 0 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S535 EP S537 DI 10.2105/AJPH.2014.302100 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000011 PM 25100418 ER PT J AU Blosnich, JR Gordon, AJ Bossarte, RM AF Blosnich, John R. Gordon, Adam J. Bossarte, Robert M. TI Suicidal Ideation and Mental Distress Among Adults With Military Service History: Results From 5 US States, 2010 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; OEF/OIF VETERANS; HEALTH SYSTEM; WAR VETERANS; RISK-FACTORS; FOLLOW-UP; MORTALITY; SAMPLE; BEHAVIOR AB Objectives. We examined the association of military service history with past-year suicidal ideation and past-30-days mental distress in a probability-based sample of adults. Methods. We gathered 2010 Behavioral Risk Factor Surveillance System data from 5 states that asked about past-year suicidal ideation. Military service was defined as current or former active-duty service or National Guard or Reserves service. We stratified analyses into 18 to 39 years, 40 to 64 years, and 65 years and older age groups and used multiple logistic regression analyses, adjusted for demographic confounders, to discern the association of military service history with past-year suicidal ideation and past-30-days mental distress. Results. Among the 26 736 respondents, 13.1% indicated military service history. After adjusting for several confounders, we found military history status among those aged 40 to 64 years was associated with both past-year suicidal ideation and past-30-days mental distress. We found no significant associations among the younger or older age groups. Conclusions. Differences in suicidal ideation between military and nonmilitary individuals may occur in midlife. Future research should examine the possibility of cohort effects, service era effects, or both. C1 [Blosnich, John R.; Gordon, Adam J.] US Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Blosnich, John R.; Bossarte, Robert M.] Univ Rochester, Dept Psychiat, Rochester, NY 14627 USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Bossarte, Robert M.] VISN 2 Ctr Excellence Suicide Prevent, Canandaigua, NY USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM John.blosnich@va.gov FU VISN 2 Center of Excellence for Suicide Prevention; US Department of Veterans Affairs Office of Academic Affiliations; Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System FX This work was partially supported by the VISN 2 Center of Excellence for Suicide Prevention and a postdoctoral fellowship to J. R. Blosnich through the US Department of Veterans Affairs Office of Academic Affiliations and the Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System. NR 56 TC 5 Z9 5 U1 5 U2 11 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S595 EP S602 DI 10.2105/AJPH.2014.302064 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000019 PM 25100426 ER PT J AU Copeland, LA McIntyre, RT Stock, EM Zeber, JE MacCarthy, DJ Pugh, MJ AF Copeland, Laurel A. McIntyre, Raphael T. Stock, Eileen M. Zeber, John E. MacCarthy, Daniel J. Pugh, Mary Jo TI Prevalence of Suicidality Among Hispanic and African American Veterans Following Surgery SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID QUALITY-OF-LIFE; OLDER-ADULTS; PAIN; MECHANISMS; ETHNICITY; IMPACT; RISK AB Objectives. We evaluated factors associated with suicidal behavior and ideation (SBI) during 3 years of follow-up among 89 995 Veterans Health Administration (VHA) patients who underwent major surgery from October 2005 to September 2006. Methods. We analyzed administrative data using Cox proportional hazards models. SBI was ascertained by International Classification of Disease, 9th Revision codes. Results. African Americans (18% of sample; 16 252) were at an increased risk for SBI (hazard ratio [HR] = 1.21; 95% confidence interval [CI] = 1.10, 1.32), whereas Hispanics were not (HR = 1.10; 95% CI = 0.95, 1.28). Other risk factors included schizophrenia, bipolar disorder, depression, posttraumatic stress disorder, pain disorders, postoperative new-onset depression, and postoperative complications; female gender and married status were protective against SBI. Conclusions. The postoperative period might be a time of heightened risk for SBI among minority patients in the VHA. Tailored monitoring and postoperative management by minority status might be required to achieve care equity. C1 [Copeland, Laurel A.; McIntyre, Raphael T.; Stock, Eileen M.; Zeber, John E.] Cent Texas Vet Hlth Care Syst Scott & White Healt, Ctr Appl Hlth Res, Temple, TX USA. [MacCarthy, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Pugh, Mary Jo] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Copeland, LA (reprint author), Ctr Appl Hlth Res, 2102 Birdcreek Dr, Temple, TX 76502 USA. EM LaurelACopeland@gmail.com OI Pugh, Mary Jo/0000-0003-4196-7763; Copeland, Laurel/0000-0002-9478-0209 FU Veterans Health Administration, Health Services Research Development [IIR-09-335]; Center for Applied Health Research - Central Texas Veterans Health Care System; Center for Applied Health Research - Scott & White Healthcare, in Temple, Texas, Scott & White Minority Health Research Predoctoral Fellowship FX This work was supported by a research award from Veterans Health Administration, Health Services Research & Development #IIR-09-335 to Central Texas Veterans Health Care System to partially support the salaries of L. A. Copeland, J. E. Zeber, M. J. Pugh, and D. J. MacCarthy. Additional support was provided by the Center for Applied Health Research, a center jointly sponsored by Central Texas Veterans Health Care System and Scott & White Healthcare, in Temple, Texas, including the Scott & White Minority Health Research Predoctoral Fellowship awarded to R. T. McIntyre. NR 39 TC 2 Z9 2 U1 2 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S603 EP S608 DI 10.2105/AJPH.2014.301938 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000020 PM 25100427 ER PT J AU Ibrahim, SA Egede, LE Uchendu, US Fine, MJ AF Ibrahim, Said A. Egede, Leonard E. Uchendu, Uchenna S. Fine, Michael J. TI The Struggle for Health Equity: The Sustained Effort by the VA Healthcare System SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID QUALITY-OF-CARE C1 [Ibrahim, Said A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ibrahim, Said A.] Ctr Hlth Equ Res & Promot, Dept Vet Affairs VA, Philadelphia, PA USA. [Egede, Leonard E.] Med Univ S Carolina, Charleston, SC USA. [Egede, Leonard E.] Charleston Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Uchendu, Uchenna S.] VA Cent Off, Vet Hlth Adm Off Hlth Equ, Washington, DC USA. [Fine, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Fine, Michael J.] Ctr Hlth Equ Res & Promot, VA, Pittsburgh, PA USA. RP Ibrahim, SA (reprint author), Philadelphia VA Med Ctr ANNEX, Ctr Hlth Equ Res & Promot, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM said.ibrahim2@va.gov FU NIAMS NIH HHS [K24 AR055259]; NIDDK NIH HHS [K24 DK093699] NR 16 TC 0 Z9 0 U1 2 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S514 EP S516 DI 10.2105/AJPH.2014.302199 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000003 PM 25100410 ER PT J AU Lynch, J Whatley, A Uchendu, US Ibrahim, SA AF Lynch, Julie Whatley, Angela Uchendu, Uchenna S. Ibrahim, Said A. TI Race and Genomics in the Veterans Health Administration SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID GROWTH-FACTOR RECEPTOR; WIDE ASSOCIATION; PROSTATE-CANCER; UNITED-STATES; ANCESTRY; MEN C1 [Lynch, Julie] CHOIR, Vet Hlth Adm, Bedford, MA 01730 USA. [Lynch, Julie] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Whatley, Angela] Vet Hlth Adm, Washington, DC USA. [Uchendu, Uchenna S.] Off Hlth Equ, Dept Vet Affairs, Washington, DC USA. [Ibrahim, Said A.] Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Lynch, J (reprint author), CHOIR, Vet Hlth Adm, 200 Springs Ave, Bedford, MA 01730 USA. EM julie.lynch@va.gov FU NIAMS NIH HHS [K24 AR055259] NR 10 TC 3 Z9 3 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S522 EP S524 DI 10.2105/AJPH.2014.302202 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000006 PM 25100413 ER PT J AU Feemster, LC Au, DH AF Feemster, Laura C. Au, David H. TI Chronic Obstructive Pulmonary Disease Readmissions and Medicare Reimbursement Reply SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter C1 [Feemster, Laura C.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Feemster, LC (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. FU NHLBI NIH HHS [K23 HL111116, K23HL111116] NR 2 TC 1 Z9 1 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 1 PY 2014 VL 190 IS 5 BP 591 EP 592 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AO7TB UT WOS:000341554400018 PM 25171313 ER PT J AU Busch, RA Heneghan, AF Pierre, JF Wang, XY Kudsk, KA AF Busch, Rebecca A. Heneghan, Aaron F. Pierre, Joseph F. Wang, Xinying Kudsk, Kenneth A. TI The Enteric Nervous System Neuropeptide, Bombesin, Reverses Innate Immune Impairments During Parenteral Nutrition SO ANNALS OF SURGERY LA English DT Article DE antimicrobial peptides; bombesin; enteric nervous system; parenteral nutrition; Paneth cells ID RESPIRATORY-TRACT IMMUNITY; POLYMERIC IMMUNOGLOBULIN RECEPTOR; INTESTINAL PANETH CELLS; MAJOR ABDOMINAL-TRAUMA; LECTIN REGIII-GAMMA; MUCOSAL IMMUNITY; LYMPHOID-TISSUE; PHOSPHOLIPASE A(2); BARRIER FUNCTION; FED MICE AB Background: Lack of enteral stimulation during parenteral nutrition (PN) impairs mucosal immunity. Bombesin (BBS), a gastrin-releasing peptide analogue, reverses PN-induced defects in acquired immunity. Paneth cells produce antimicrobial peptides (AMPs) of innate immunity for release after cholinergic stimulation. Objective: Determine if BBS restores AMPs and bactericidal function during PN. Methods: Intravenously cannulated male ICR mice were randomized to Chow, PN, or PN+BBS (15 mu g 3 times daily, n = 7 per group) for 5 days. Ileum was analyzed for AMPs (Protein: sPLA2 by fluorescence, lysozyme and RegIII-gamma by western andcryptdin-4 by ELISA; mRNA: all by RT-PCR). Cholinergic stimulated (100 mu M bethanechol) ileal specimens assessed Pseudomonas bactericidal activity. Ileum (Chow: n = 7; PN: n = 9; PN+BBS: n = 8) was assessed for Escherichia coli invasion in ex-vivo culture. Results: PN significantly decreased most AMPs versus Chow while BBS maintained Chow levels (sPLA(2):Chow: 107 + 14*, PN: 44.6 + 7.2, PN+BBS: 78.7 + 13.4* Fl/min/mu L/total protein; Lysozyme: Chow: 63.9 + 11.9*, PN: 26.8 + 6.2; PN+BBS: 64.9 + 13.8* lysozyme/total protein; RegIII-gamma: Chow: 51.5 + 10.0*, PN: 20.4 + 4.3, PN+BBS: 31.0 + 8.4 RegIII-gamma/total protein; Cryptdin-4: Chow: 18.4 + 1.5*, PN: 12.7 + 1.6, PN+BBS: 26.1 + 2.4*dagger pg/mg [all *P < 0.05 vs PN and dagger P < 0.05 vs Chow]). Functionally, BBS prevented PN loss of bactericidal activity after cholinergic stimulation (Chow: 25.3 + 3.6*, PN: 13.0 + 3.2; PN+BBS: 27.0 + 4.7* percent bacterial killing, *P < 0.05 vs PN). BBS reduced bacterial invasion in unstimulated tissue barely missing significance (P = 0.06). Conclusions: The enteric nervous system (ENS) controls AMP levels in Paneth cells during PN but mucosal protection by innate immunity requires both ENS and parasympathetic stimulation. C1 [Busch, Rebecca A.; Heneghan, Aaron F.; Pierre, Joseph F.; Wang, Xinying; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Wang, Xinying] Nanjing Univ, Dept Surg, Jinling Hosp, Sch Med, Nanjing, Peoples R China. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Kudsk, KA (reprint author), Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU Biomedical Laboratory Research & Development Service of the VA Office of Research and Development [I01BX001672]; National Institute of Health [T32 CA090217-13] FX Supported by award No. I01BX001672 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development. Also based upon work supported in part by National Institute of Health grant T32 CA090217-13. The contents of this article do not represent the views of the Department of Veterans Affairs or the US government. The authors have no conflicts of interest to declare. NR 100 TC 8 Z9 8 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2014 VL 260 IS 3 BP 432 EP 444 DI 10.1097/SLA.0000000000000871 PG 13 WC Surgery SC Surgery GA AO2SJ UT WOS:000341175600004 PM 25115419 ER PT J AU Ju, MH Chung, JW Kinnier, CV Bentrem, DJ Mahvi, DM Ko, CY Bilimoria, KY AF Ju, Mila H. Chung, Jeanette W. Kinnier, Christine V. Bentrem, David J. Mahvi, David M. Ko, Clifford Y. Bilimoria, Karl Y. TI Association Between Hospital Imaging Use and Venous Thromboembolism Events Rates Based on Clinical Data SO ANNALS OF SURGERY LA English DT Article DE ACS NSQIP; clinical registry data; hospital quality performance; surveillance bias; venous thromboembolism (VTE) ID DEEP-VEIN THROMBOSIS; QUALITY IMPROVEMENT PROGRAM; TRAUMA DATA-BANK; PATIENT SAFETY INDICATORS; FACTORS-AN ANALYSIS; REPORTED DVT RATES; SURVEILLANCE BIAS; SURGICAL QUALITY; OF-CARE; TEACHING STATUS AB Objective: The objective was to assess the presence and extent of venous thromboembolic (VTE) surveillance bias using high-quality clinical data. Background: Hospital VTE rates are publicly reported and used in pay-for-performance programs. Prior work suggested surveillance bias: hospitals that look more for VTE with imaging studies find more VTE, thereby incorrectly seem to have worse performance. However, these results have been questioned as the risk adjustment and VTE measurement relied on administrative data. Methods: Data (2009-2010) from 208 hospitals were available for analysis. Hospitals were divided into quartiles according to VTE imaging use rates (Medicare claims). Observed and risk-adjusted postoperative VTE event rates (regression models using American College of Surgeons National Surgical Quality Improvement Project data) were examined across VTE imaging use rate quartiles. Multivariable linear regression models were developed to assess the impact of hospital characteristics (American Hospital Association) and hospital imaging use rates on VTE event rates. Results: The mean risk-adjusted VTE event rates at 30 days after surgery increased across VTE imaging use rate quartiles: 1.13% in the lowest quartile to 1.92% in the highest quartile (P < 0.001). This statistically significant trend remained when examining only the inpatient period. Hospital VTE imaging use rate was the dominant driver of hospital VTE event rates (P < 0.001), as no other hospital characteristics had significant associations. Conclusions: Even when examined with clinically ascertained outcomes and detailed risk adjustment, VTE rates reflect hospital imaging use and perhaps signify vigilant, high-quality care. The VTE outcome measure may not be an accurate quality indicator and should likely not be used in public reporting or pay-for-performance programs. C1 [Ju, Mila H.; Ko, Clifford Y.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Ju, Mila H.; Chung, Jeanette W.; Kinnier, Christine V.; Bentrem, David J.; Mahvi, David M.; Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM kbilimoria@facs.org FU AHRQ [R21HS021857]; National Institutes of Health [5T32HL094293]; American College of Surgeons Clinical Scholar in Residence program FX Dr Bilimoria is partially supported by AHRQ R21HS021857. Dr Ju is supported by National Institutes of Health #5T32HL094293 and American College of Surgeons Clinical Scholar in Residence program. No conflict of interest related to this work. NR 40 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2014 VL 260 IS 3 BP 558 EP 566 DI 10.1097/SLA.0000000000000897 PG 9 WC Surgery SC Surgery GA AO2SJ UT WOS:000341175600017 PM 25115432 ER PT J AU Li, J Echevarria, KL Hughes, DW Cadena, JA Bowling, JE Lewis, JS AF Li, Julius Echevarria, Kelly L. Hughes, Darrel W. Cadena, Jose A. Bowling, Jason E. Lewis, James S., II TI Comparison of Cefazolin versus Oxacillin for Treatment of Complicated Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIMICROBIAL THERAPY; RISK-FACTORS; ENDOCARDITIS; NAFCILLIN; OUTCOMES AB Contrary to prior case reports that described occasional clinical failures with cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infections, recent studies have demonstrated no difference in outcomes between cefazolin and antistaphylococcal penicillins for the treatment of MSSA bacteremia. While promising, these studies described low frequencies of high-inoculum infections, such as endocarditis. This retrospective study compares clinical outcomes of cefazolin versus oxacillin for complicated MSSA bacteremia at two tertiary care hospitals between January 2008 and June 2012. Fifty-nine patients treated with cefazolin and 34 patients treated with oxacillin were included. Osteoarticular (41%) and endovascular (20%) sources were the predominant sites of infection. The rates of clinical cure at the end of therapy were similar between cefazolin and oxacillin (95% versus 88%; P = 0.25), but overall failure at 90 days was higher in the oxacillin arm (47% versus 24%; P = 0.04). Failures were more likely to have received surgical interventions (63% versus 40%; P = 0.05) and to have an osteoarticular source (57% versus 33%; P = 0.04). Failures also had a longer duration of bacteremia (7 versus 3 days; P = 0.0002), which was the only predictor of failure. Antibiotic selection was not predictive of failure. Rates of adverse drug events were higher in the oxacillin arm (30% versus 3%; P = 0.0006), and oxacillin was more frequently discontinued due to adverse drug events (21% versus 3%; P = 0.01). Cefazolin appears similar to oxacillin for the treatment of complicated MSSA bacteremia but with significantly improved safety. The higher rates of failure with oxacillin may have been confounded by other patient factors and warrant further investigation. C1 [Li, Julius; Echevarria, Kelly L.; Cadena, Jose A.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Li, Julius; Echevarria, Kelly L.; Hughes, Darrel W.; Lewis, James S., II] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Li, Julius; Echevarria, Kelly L.; Hughes, Darrel W.; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Echevarria, Kelly L.; Cadena, Jose A.; Bowling, Jason E.; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. [Hughes, Darrel W.; Lewis, James S., II] Univ Hlth Syst, Dept Pharm, San Antonio, TX USA. RP Li, J (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM juli@ochsner.org NR 30 TC 16 Z9 16 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2014 VL 58 IS 9 BP 5117 EP 5124 DI 10.1128/AAC.02800-14 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AO3UV UT WOS:000341262700015 PM 24936596 ER PT J AU Pape, TLB Mallinson, T Guernon, A AF Pape, Theresa Louise-Bender Mallinson, Trudy Guernon, Ann TI Psychometric Properties of the Disorders of Consciousness Scale SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Brain injuries; Consciousness disorders; Outcome measures; Rehabilitation ID PERSISTENT VEGETATIVE STATE; COMA; PRECISION; ATTENTION; VALIDITY; INJURY AB Objective: To provide evidence for psychometric properties of the Disorders of Consciousness Scale (DOCS). Design: Prospective observational cohort. Settings: Seven rehabilitation facilities. Participants: Patients (N=174) with severe brain injury. Interventions: Not applicable. Main Outcome Measure: DOCS. Results: Initial analyses suggested eliminating 6 items to maximize psychometrics, resulting in the DOCS-25. The 25 items form a unidimensional hierarchy, rating scale categories are ordered, there are no misfitting items, and differential item functioning was not found according to sex, type of brain injury, veteran status, and days from onset. Person separation reliability (.91) indicates that the DOCS-25 is appropriate for individual patient measurement. Items are well targeted to the sample, with the difference between mean person and item calibrations less than 1 logit. DOCS-25 Rasch measures result in a 62% gain in relative precision over total raw scores. Internal consistency is very good (Cronbach alpha=.86); interrater agreement is excellent (intracIass correlation coefficient =.90) for both the DOCS-25 and the sensory subscales. The DOCS-25 total measure, but not subscale measures, correlates with the Glasgow Coma Scale and the Coma/Near-Coma Scales and distinguishes significantly between vegetative and minimally conscious states, indicating concurrent validity. Conclusions: The DOCS-25 is psychometrically strong. It has excellent measurement precision and captures a broad range of patient function, which is critical for capturing recovery of consciousness. The sensory subscales are clinically informative but should not be reported as separate measures. The Keyform synthesizes clinical observations to visualize response patterns with potential for informing clinical decision-making Future studies should determine sensitivity to change, examine issues of rater severity, and explore the usefulness of the Keyform in clinical practice. (c) 2014 by the American Congress of Rehabilitation Medicine C1 [Pape, Theresa Louise-Bender] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL 60141 USA. [Pape, Theresa Louise-Bender] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Dept Vet Affairs, Hines, IL 60141 USA. [Pape, Theresa Louise-Bender] Northwestern Univ, Feinberg Sch Med, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. [Mallinson, Trudy] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Guernon, Ann] Marianjoy Rehabil Hosp, Wheaton, IL USA. RP Pape, TLB (reprint author), Edward Hines Jr Vet Hosp, Res & Dev Serv, POB 5000,MC 151H, Hines, IL 60141 USA. EM Theresa.Pape@va.gov OI Pape, Theresa/0000-0001-7738-5963; Mallinson, Trudy/0000-0002-4888-5579 FU United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development [CCN 07-133-1]; Rehabilitation Research and Development Career Development Transition Award [B4949N] FX Supported by the United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development (merit grant no. CCN 07-133-1) and Rehabilitation Research and Development Career Development Transition Award (no. B4949N). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the United States Department of Veterans Affairs or the United States Government. NR 55 TC 2 Z9 2 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 2014 VL 95 IS 9 BP 1672 EP 1684 DI 10.1016/j.apmr.2014.04.015 PG 13 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AO4TU UT WOS:000341335100010 PM 24814459 ER PT J AU Bartels, CM Johnson, H Voelker, K Thorpe, C McBride, P Jacobs, EA Pandhi, N Smith, M AF Bartels, Christie M. Johnson, Heather Voelker, Katya Thorpe, Carolyn McBride, Patrick Jacobs, Elizabeth A. Pandhi, Nancy Smith, Maureen TI Impact of Rheumatoid Arthritis on Receiving a Diagnosis of Hypertension Among Patients With Regular Primary Care SO ARTHRITIS CARE & RESEARCH LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CARDIOVASCULAR RISK-FACTORS; QUALITY-OF-CARE; EULAR RECOMMENDATIONS; ADMINISTRATIVE DATA; DISEASE; MEDICARE; COMORBIDITIES; POPULATION; MORTALITY AB Objective. Despite numerous studies reporting increased cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA), the impact of RA on managing modifiable CVD risk factors remains understudied. We tested the hypothesis that RA is a risk factor for not receiving a hypertension diagnosis. Methods. Using a cohort design, we studied adult patients with and without RA/inflammatory arthritis from a large academic multispecialty practice. All were seen regularly in primary care and met clinical guideline hypertension criteria, but lacked prior hypertension diagnosis/treatment. The primary outcome was time to International Classification of Diseases, Ninth Revision code for hypertension or elevated blood pressure, or antihypertensive medication prescription. Kaplan-Meier survival curve analysis and Cox proportional hazards modeling were used to examine the impact of RA on diagnosis of hypertension. Results. Among 14,974 patients with undiagnosed hypertension, 201 patients had RA codes. RA patients had equivalent primary care visits and more total visits compared to patients without RA. At the end of the study, the likelihood of hypertension diagnosis was 36% in RA patients compared to 51% in patients without RA. In adjusted Cox models, RA patients had a 29% lower hypertension diagnosis hazard (hazard ratio 0.71, 95% confidence interval 0.55-0.93), reflecting more undiagnosed hypertension than with other comorbidities. Conclusion. Among patients meeting guideline-based hypertension criteria, RA patients were less likely to be diagnosed despite more visits than those without RA. Given heightened CVD risks in RA and the importance of hypertension diagnosis as a first step toward controlling risk, rheumatologists should collaborate to improve rates of diagnosis for this modifiable CVD risk factor. C1 [Bartels, Christie M.; Johnson, Heather; Voelker, Katya; McBride, Patrick; Jacobs, Elizabeth A.; Pandhi, Nancy; Smith, Maureen] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Voelker, Katya] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Thorpe, Carolyn] Univ Pittsburgh, Pittsburgh, PA USA. RP Bartels, CM (reprint author), 1685 Highland Ave,Room 4132, Madison, WI 53705 USA. EM cb4@medicine.wisc.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH [K23-AR062381]; NIH/National Heart, Lung, and Blood Institute [1-K23-HL112907]; National Center for Advancing Translational Sciences, NIH [9U54TR000021]; Health Innovation Program/Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research/Clinical and Translational Science Award; Shapiro Student Research Program FX Dr. Bartels's work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH (award K23-AR062381). Dr. Johnson's work was supported by the NIH/National Heart, Lung, and Blood Institute (grant 1-K23-HL112907). Additional project support was provided through the National Center for Advancing Translational Sciences, NIH (grant 9U54TR000021) and the Health Innovation Program/Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research/Clinical and Translational Science Award and the Shapiro Student Research Program. NR 48 TC 10 Z9 10 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2014 VL 66 IS 9 BP 1281 EP 1288 DI 10.1002/acr.22302 PG 8 WC Rheumatology SC Rheumatology GA AO3OK UT WOS:000341241200002 PM 24585741 ER PT J AU Li, J Hsu, HC Ding, YN Li, H Wu, Q Yang, PA Luo, B Rowse, AL Spalding, DM Bridges, SL Mountz, JD AF Li, Jun Hsu, Hui-Chen Ding, Yana Li, Hao Wu, Qi Yang, PingAr Luo, Bao Rowse, Amber L. Spalding, David M. Bridges, S. Louis, Jr. Mountz, John D. TI Inhibition of Fucosylation Reshapes Inflammatory Macrophages and Suppresses Type II Collagen-Induced Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; T-CELLS; SYNOVIAL FIBROBLASTS; ANTIGEN PRESENTATION; LYMPH-NODES; E-SELECTIN; FUCT-VII; ACTIVATION; FUCOSE; IL-10 AB Objective. Fucosylation catalyzed by fucosyltransferases (FUTs) is an important posttranslational modification involved in a variety of biologic processes. This study was undertaken to determine the roles of fucosylation in rheumatoid arthritis (RA) and to assess the efficacy of reestablishing immune homeostasis with the use of 2-deoxy-D-galactose (2-D-gal), a fucosylation inhibitor. Methods. Quantitative polymerase chain reaction was performed to determine the expression of FUT genes in synovial tissue from RA and osteoarthritis (OA) patients and in fluorescence-activated cell-sorted cells from RA synovial fluid. The in vivo inhibitory effect of 2-D-gal was evaluated in a murine collagen-induced arthritis (CIA) model. The in vitro effects of 2-D-gal on differentiation of inflammatory macrophages, production of cytokines, and antigen uptake, processing, and presentation functions were analyzed. Results. FUTs that are involved in terminal or subterminal fucosylation, but not those involved in core fucosylation or O-fucosylation, were up-regulated in RA compared to OA synovial tissue. The expression of terminal FUTs was highly positively correlated with the expression of TNF (encoding for tumor necrosis factor alpha). Terminal FUTs were predominantly expressed in M1 macrophages. In vivo, 2-D-gal treatment of mice precluded the development of CIA by reducing inflammatory macrophages and Th17 cells in the draining lymph nodes and decreasing the levels of TNF alpha, interleukin-6 (IL-6), and antibodies to type II collagen in the serum. In vitro, treatment with 2-D-gal skewed the differentiation of M1 macrophages to IL-10-producing M2 macrophages. Furthermore, 2-D-gal significantly inhibited the antigen-presenting function of M1 macrophages. Conclusion. Terminal fucosylation is a novel hallmark of inflammatory macrophages. Inhibition of terminal FUTs reshapes the differentiation and functions of M1 macrophages, leading to resolution of inflammation in arthritis. C1 [Hsu, Hui-Chen; Wu, Qi; Yang, PingAr; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Hsu, Hui-Chen; Wu, Qi; Yang, PingAr; Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Mountz, JD (reprint author), Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Dept Med, SHEL Bldg,Suite 307,1825 Univ Blvd, Birmingham, AL 35294 USA. EM jdmountz@uab.edu RI Li, Hao/N-7406-2015 OI Li, Hao/0000-0002-2171-8826 FU Arthritis Foundation; Lupus Research Institute; Daiichi Sankyo Co., Ltd; NIH [1R01-AI-083705, 1R01-AI-071110, P30-AR-048311, P30-AI-027767, P30-AR-46031]; Rheumatology Research Foundation; Department of Veterans Affairs [1I01BX000600] FX Supported by the Arthritis Foundation (grant to Dr. J. Li), the Lupus Research Institute (grant to Dr. Hsu), and Daiichi Sankyo Co., Ltd (grant to Dr. Mountz), the NIH (grants 1R01-AI-083705 to Dr. Hsu and 1R01-AI-071110 and P30-AR-048311 to Dr. Mountz), a Rheumatology Research Foundation grant to Dr. Mountz, and the Department of Veterans Affairs (Merit Review grant 1I01BX000600 to Dr. Mountz). Portions of the study were performed at the University of Alabama at Birmingham Rheumatic Diseases Core Center (Analytical Genomics and Transgenics Core, Comprehensive Flow Cytometry Core, and Analytic Imaging and Immunoreagents Core), supported by NIH grant P30-AR-048311, the Center for AIDS Research flow cytometry facility, supported by NIH grant P30-AI-027767, and the Center for Metabolic Bone Disease-Histomorphometry and Molecular Analysis Core Laboratory, supported by NIH grant P30-AR-46031. NR 46 TC 6 Z9 6 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD SEP PY 2014 VL 66 IS 9 BP 2368 EP 2379 DI 10.1002/art.38711 PG 12 WC Rheumatology SC Rheumatology GA AO3RD UT WOS:000341251100009 PM 24838610 ER PT J AU Ding, YN Li, J Yang, PA Luo, B Wu, Q Zajac, AJ Wildner, O Hsu, HC Mountz, JD AF Ding, Yanna Li, Jun Yang, PingAr Luo, Bao Wu, Qi Zajac, Allan J. Wildner, Oliver Hsu, Hui-Chen Mountz, John D. TI Interleukin-21 Promotes Germinal Center Reaction by Skewing the Follicular Regulatory T Cell to Follicular Helper T Cell Balance in Autoimmune BXD2 Mice SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FOXP3 EXPRESSION; B-CELLS; GENERATION; IL-21; DIFFERENTIATION; RECEPTOR; SUBSET; MTOR; TH17 AB Objective. Follicular regulatory T (Tfr) cells act as the regulatory counterpart of follicular helper T (Tfh) cells to suppress germinal center (GC) B cell differentiation. We recently showed that interleukin-21 (IL-21) promoted Tfh cell differentiation in autoimmune BXD2 mice that develop spontaneous GCs. This study was undertaken to determine the modulatory effects of IL-21 on Tfr cells and the Tfr cell to Tfh cell balance in BXD2 mice. Methods. The percentage and phenotype of Tfr cells were determined in BXD2 and BXD2-IL21(-/-) mice. The effects of IL-21 on Tfr cells and the Tfr cell:Tfh cell ratio were evaluated. Sorted Tfr cells from BXD2-IL21(-/-) mice were cocultured with Tfh cells and B cells, or transferred into BXD2 mice to determine their function. Results. The percentages and numbers of GC B cells and Tfh cells were significantly reduced, but the percentage of Tfr cells was 2-fold higher in BXD2-IL21(-/-) mice than in wild-type BXD2 mice. Administration of AdIL-21 to BXD2-IL21(-/-) mice decreased the percentages and numbers of Tfr cells and the Tfr cell:Tfh cell ratio but increased the number of GC B cells in the spleen. Recombinant murine IL-21 suppressed FoxP3 and significantly reduced Tgfb1, Il2, and Gitr but enhanced Il21, Il6, Pd1, Cxcr5, and Icos expression in Tfr cells. IL-21 also counteracted Tfr cell-mediated inhibition of antibody secretion in the Tfh cell-B cell coculture system. Transfer of Tfr cells into young BXD2 mice reduced GC size and decreased the numbers of autoantibody-producing B cells. Conclusion. Our findings indicate that high levels of IL-21 selectively enhance Tfh cell differentiation but inhibit Tfr cell commitment and the suppressive function of Tfr cells on Tfh cells and B cells, suggesting that IL-21 skews the balance from Tfr cells to Tfh cells to promote autoreactive GC reactions in BXD2 mice. C1 [Ding, Yanna; Li, Jun; Yang, PingAr; Luo, Bao; Wu, Qi; Zajac, Allan J.; Hsu, Hui-Chen; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Wildner, Oliver] Swissmedic, Swiss Agcy Therapeut Prod, Bern, Switzerland. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Hsu, HC (reprint author), Univ Alabama Birmingham, Dept Med, 1825 Univ Blvd, Birmingham, AL 35294 USA. EM rheu078@uab.edu; jdmountz@uab.edu FU Arthritis Foundation; NIH (National Institute of Allergy and Infectious Diseases) [U01-AI-082966, 1R01-AI-0837051, R01-AI-071110]; Lupus Research Institute; Rheumatology Research Foundation; Department of Veterans Affairs [1I01BX000600]; NIH [P30-AR-048311, P30-A-I027767] FX Supported by the Arthritis Foundation (grant to Dr. Li), the NIH (National Institute of Allergy and Infectious Diseases grants U01-AI-082966 to Dr. Zajac, 1R01-AI-083705 to Dr. Hsu, and 1R01-AI-071110 to Dr. Mountz), the Lupus Research Institute (grant to Dr. Hsu), a Disease Targeted Research Grant from the Rheumatology Research Foundation (to Dr. Mountz), and the Department of Veterans Affairs (Merit Review grant 1I01BX000600 to Dr. Mountz). Flow cytometry and confocal imaging data acquisition were performed at the University of Alabama at Birmingham Comprehensive Flow Cytometry Core (supported by NIH grants P30-AR-048311 and P30-A-I027767) and Analytic Imaging and Immunoreagents Core (supported by NIH grant P30-AR-048311). NR 40 TC 22 Z9 25 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD SEP PY 2014 VL 66 IS 9 BP 2601 EP 2612 DI 10.1002/art.38735 PG 12 WC Rheumatology SC Rheumatology GA AO3RD UT WOS:000341251100031 PM 24909430 ER PT J AU Swenson, ER AF Swenson, Erik R. TI New Insights into Carbonic Anhydrase Inhibition, Vasodilation, and Treatment of Hypertensive-Related Diseases SO CURRENT HYPERTENSION REPORTS LA English DT Article DE Sulfonamide; Acetazolamide; Hypoxic pulmonary vasoconstriction; Arterial hypertension; Thiazide; Loop diuretic ID INTRACELLULAR PH REGULATION; CHRONIC KIDNEY-DISEASE; CEREBRAL-BLOOD-FLOW; THIAZIDE DIURETICS; SMOOTH-MUSCLE; NITRIC-OXIDE; IN-VITRO; IMMUNOHISTOCHEMICAL LOCALIZATION; CARDIOMYOCYTE HYPERTROPHY; PULMONARY VASODILATION AB Carbonic anhydrase (CA) and its inhibitors are relevant to many physiological processes and diseases. The enzyme is differentially expressed throughout the body, in concentration and subcellular location, and as 13 catalytically active isoforms. Blood vessels contain small amounts of CA, but the enzyme's role in vascular physiology and blood pressure regulation is uncertain. However, considerable recent evidence points to vasodilation by CA inhibitors. CA inhibition in vascular smooth muscle, endothelium, heart, blood cells, and nervous system could all contribute. It is equally plausible that other targets besides CA for all known CA inhibitors may account for their vascular effects. I will review this knowledge and important remaining gaps relating to treatment of hypertensive-related diseases with potent sulfonamide inhibitors, such as acetazolamide; but also the possibility that CA inhibition by thiazides and loop diuretics, although generally weaker, may have antihypertensive effects beyond their inhibition of renal sodium transporters. C1 Univ Washington, Dept Vet Affairs Pulm & Crit Care Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Swenson, ER (reprint author), Univ Washington, Dept Vet Affairs Pulm & Crit Care Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98195 USA. EM eswenson@u.washington.edu NR 108 TC 9 Z9 9 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1522-6417 EI 1534-3111 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD SEP PY 2014 VL 16 IS 9 AR 467 DI 10.1007/s11906-014-0467-3 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AO6AE UT WOS:000341428700002 PM 25079851 ER PT J AU Beam, CA Gitelman, SE Palmer, JP AF Beam, Craig A. Gitelman, Stephen E. Palmer, Jerry P. CA Type 1 Diabet TrialNet Study Grp TI Recommendations for the Definition of Clinical Responder in Insulin Preservation Studies SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; C-PEPTIDE; COMPLICATIONS TRIAL; MEASUREMENT ERROR; DIABETES CONTROL; TEPLIZUMAB; MISCLASSIFICATION; IMPACT AB Clinical responder studies should contribute to the translation of effective treatments and interventions to the clinic. Since ultimately this translation will involve regulatory approval, we recommend that clinical trials prespecify a responder definition that can be assessed against the requirements and suggestions of regulatory agencies. In this article, we propose a clinical responder definition to specifically assist researchers and regulatory agencies in interpreting the clinical importance of statistically significant findings for studies of interventions intended to preserve -cell function in newly diagnosed type 1 diabetes. We focus on studies of 6-month -cell preservation in type 1 diabetes as measured by 2-h-stimulated C-peptide. We introduce criteria (bias, reliability, and external validity) for the assessment of responder definitions to ensure they meet U.S. Food and Drug Administration and European Medicines Agency guidelines. Using data from several published TrialNet studies, we evaluate our definition (no decrease in C-peptide) against published alternatives and determine that our definition has minimum bias with external validity. We observe that reliability could be improved by using changes in C-peptide later than 6 months beyond baseline. In sum, to support efficacy claims of -cell preservation therapies in type 1 diabetes submitted to U.S. and European regulatory agencies, we recommend use of our definition. C1 [Beam, Craig A.] Univ S Florida, Dept Pediat, Div Epidemiol & Biostat, Tampa, FL 33620 USA. [Gitelman, Stephen E.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Palmer, Jerry P.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Palmer, Jerry P.] Univ Washington, Seattle, WA 98195 USA. RP Beam, CA (reprint author), Western Michigan Univ, Homer Stryker MD Sch Med, Dept Biomed Sci, Div Epidemiol & Biostat, Kalamazoo, MI 49008 USA. EM craig.beam@med.wmich.edu FU National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, U01-DK-085509, HHSN267200800019C]; National Center for Research Resources [UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, UL1-RR-031986, M01-RR-00400]; Juvenile Diabetes Research Foundation International; American Diabetes Association FX Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute of Allergy and Infectious Diseases; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreements U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, and U01-DK-085509 and contract HHSN267200800019C; the National Center for Research Resources, through Clinical and Translational Science Awards UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, and UL1-RR-031986 and General Clinical Research Center Award M01-RR-00400; the Juvenile Diabetes Research Foundation International; and the American Diabetes Association. NR 25 TC 5 Z9 5 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2014 VL 63 IS 9 BP 3120 EP 3127 DI 10.2337/db14-0095 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AO7AV UT WOS:000341505300029 PM 24722251 ER PT J AU Grossbard, JR Malte, CA Saxon, AJ Hawkins, EJ AF Grossbard, Joel R. Malte, Carol A. Saxon, Andrew J. Hawkins, Eric J. TI Clinical monitoring and high-risk conditions among patients with SUD newly prescribed opioids and benzodiazepines SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Opioid therapy; Substance use disorders; Clinical monitoring; Veterans; Benzodiazepines ID SUBSTANCE USE DISORDER; CHRONIC NONCANCER PAIN; PRESCRIPTION OPIOIDS; ELDERLY PERSONS; UNITED-STATES; VETERANS; THERAPY; CARE; PREVALENCE; ALCOHOL AB Background: Opioid therapy alone or in combination with benzodiazepines poses safety concerns among patients with substance use disorders (SUD). Guidelines for opioid therapy recommend SUD treatment and enhanced monitoring, especially in patients with additional risk factors, but information on monitoring practices is sparse. This study estimated high-risk conditions - psychiatric comorbidity, suicide risk, and age <35 and >= 65 - and described clinical monitoring among patients with SUD who were newly prescribed opioids alone and concurrent with benzodiazepines long-term. Methods: This study included VA Northwest Veterans Network patients with SUD who started opioids only (n = 980) or benzodiazepines and opioids concurrently (n = 353) long-term (>= 90 days) in 2009-2010. Clinical characteristics, outpatient visits and urine drug screens (UDS) documented within 7-months after starting medications were extracted from VA data. Results: Approximately 67% (95% CI: 64-70) of opioids only and 94% (92-97) of concurrent medications groups had >= 1 psychiatric diagnoses. Prevalences of suicide risk and age <35 and >= 65 were 7% (5-8), 6% (5-8) and 18% (15-20) among the opioids only group, and 20% (16-24), 8% (5-11) and 13% (9-16) among the concurrent medications group. Among patients prescribed opioids only and medications concurrently, 87% and 91% attended primary care, whereas 28% and 26% attended SUD specialty-care. Overall, 30% and 48% of opioids only and concurrent medications groups engaged in mental health or SUD care, and 35% and 39% completed UDS. Conclusions: Improvements in clinical monitoring are needed as many VA patients with SUD and comorbid risks who initiate opioid therapy do not receive sufficient mental health/SUD care or UDS monitoring. Published by Elsevier Ireland Ltd. C1 [Grossbard, Joel R.; Malte, Carol A.; Hawkins, Eric J.] VA Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Malte, Carol A.; Saxon, Andrew J.; Hawkins, Eric J.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Saxon, Andrew J.; Hawkins, Eric J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Grossbard, JR (reprint author), VA Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM joel.grossbard@va.gov FU VA Puget Sound Health Services Research and Development Service (PhD Postdoctoral Fellowship Program) [TPP 61-025]; Department of Veterans Affairs, Veterans Health Administration, Center of Excellence in Substance Abuse Treatment Education FX The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or University of Washington. The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Center of Excellence in Substance Abuse Treatment & Education, and VA Puget Sound Health Services Research and Development Service (PhD Postdoctoral Fellowship Program, TPP 61-025) and these organizations had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. We certify that we have no affiliation with or financial involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the manuscript (e.g., employment, consultancies, stock, ownership, honoraria). NR 40 TC 2 Z9 2 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 24 EP 32 DI 10.1016/j.drugalcdep.2014.03.020 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700003 PM 24969956 ER PT J AU Lapham, GT Rubinsky, AD Williams, EC Hawkins, EJ Grossbard, J Chavez, LJ Kivlahan, DR Bradley, KA AF Lapham, Gwen T. Rubinsky, Anna D. Williams, Emily C. Hawkins, Eric J. Grossbard, Joel Chavez, Laura J. Kivlahan, Daniel R. Bradley, Katharine A. TI Decreasing sensitivity of clinical alcohol screening with the AUDIT-C after repeated negative screens in VA clinics SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Unhealthy alcohol use; Alcohol screening; Validation; AUDIT-C ID DISORDERS IDENTIFICATION TEST; US GENERAL-POPULATION; PRIMARY-CARE PATIENTS; RISK DRINKING; VETERANS-AFFAIRS; COUNSELING INTERVENTIONS; CONSUMPTION QUESTIONS; DIAGNOSTIC-TESTS; MISUSE; PROBABILITY AB Background: Routine screening for unhealthy alcohol use is widely recommended in primary care settings. However, the validity of repeat screening among patients who have previously screened negative remains unknown. This study aims to evaluate the performance of a clinical alcohol screen compared to a confidential comparison alcohol screen among patients with previous negative alcohol screens. Methods: This study included four nested samples of Veteran Health Administration (VA) outpatients with at least one (N=18,493) and up to four (N=714) prior negative annual clinical AUDIT-C screens who completed the AUDIT-C the following year, both in a VA clinic (clinical screen) and on a confidential mailed survey (comparison screen). AUDIT-C screens were categorized as either negative (0-3 points men; 0-2 women) or positive (>= 4 men; >= 3 women). For each sample, the performance of the clinical screen was compared to the comparison screen, the reference measure for unhealthy alcohol use. Results: The sensitivity of clinical screens decreased as the number of prior negative screens in a sample increased (40.0-17.4%) for patients with 1-4 negative screens. The positive predictive value also decreased as the number of prior negative screens in a sample increased (67.7-33.3%) while specificity was consistently high for all samples (>= 97.8%). Conclusions: Repeat clinical alcohol screens became progressively less sensitive for identifying unhealthy alcohol use among patients who repeatedly screened negative over several years. Alternative approaches for assessing unhealthy alcohol use may be needed for these patients. Published by Elsevier Ireland Ltd. C1 [Lapham, Gwen T.; Rubinsky, Anna D.; Williams, Emily C.; Hawkins, Eric J.; Grossbard, Joel; Chavez, Laura J.; Kivlahan, Daniel R.; Bradley, Katharine A.] Denver Seattle Ctr Innovat Vet Ctr & Value Driven, Vet Hlth Adm VA, Seattle, WA 98101 USA. [Lapham, Gwen T.; Rubinsky, Anna D.; Williams, Emily C.; Hawkins, Eric J.; Grossbard, Joel; Chavez, Laura J.; Kivlahan, Daniel R.; Bradley, Katharine A.] VA Puget Sound Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Rubinsky, Anna D.; Hawkins, Eric J.; Grossbard, Joel; Kivlahan, Daniel R.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Williams, Emily C.; Chavez, Laura J.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Hawkins, Eric J.; Kivlahan, Daniel R.; Bradley, Katharine A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Lapham, Gwen T.; Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Rubinsky, Anna D.] VA Palo Alto Hlth Care Syst, HSR&D Ctr Innovat Implementat Ci2i, Menlo Pk, CA 94304 USA. RP Lapham, GT (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM lapham.g@ghc.org FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSRD) [RRP 11-021]; National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, HSRD QUERI; Agency for Healthcare Research and Quality (AHRQ) [NIH 1R36HS022800-01] FX The research reported here was funded by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSR&D) Substance Use Disorders Quality Enhancement Research Initiative (QUERI) RRP 11-021. A preliminary version of this work was presented at both the 36th Annual Research Society for Alcoholism Scientific Meeting in Orlando, FL, June 25, 2013 and the Addiction Health Services Conference in Portland, OR, October 24, 2013. Dr. Williams is supported by a Career Development Award from the VA Health Services Research & Development (CDA 12-276) and a fellowship from the Implementation Research Institute (IRI) at the George Warren Brown School of Social Work at Washington University. IRI is supported through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, HSR&D QUERI. Ms. Chavez is supported by an Agency for Healthcare Research and Quality (AHRQ) dissertation grant (NIH 1R36HS022800-01). These funding sources had no influence on the study's design, data collection, analyses or interpretation and reporting of results. NR 53 TC 2 Z9 2 U1 3 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 209 EP 215 DI 10.1016/j.drugalcdep.2014.06.017 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700029 PM 25034900 ER PT J AU Baumeister, SE Gelberg, L Leake, BD Yacenda-Murphy, J Vahidi, M Andersen, RM AF Baumeister, Sebastian E. Gelberg, Lillian Leake, Barbara D. Yacenda-Murphy, Julia Vahidi, Mani Andersen, Ronald M. TI Effect of a primary care based brief intervention trial among risky drug users on health-related quality of life SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Primary care clinics; Illicit drug use; Screening; Brief intervention; Quality of life ID OPIATE-DEPENDENT INDIVIDUALS; SCREENING-TEST ASSIST; CLINICALLY IMPORTANT DIFFERENCE; STARTING METHADONE TREATMENT; RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE-ABUSE TREATMENT; ALCOHOL; SETTINGS; OUTCOMES; SMOKING AB Background: Improvement in quality of life (QOL) is a long term goal of drug treatment. Although some brief interventions have been found to reduce illicit drug use, no trial among adult risky (moderate non-dependent) drug users has tested effects on health-related quality of life. Methods: A single-blind randomized controlled trial of patients enrolled from February 2011 to November 2012 was conducted in waiting rooms of five federally qualified health centers. 413 adult primary care patients were identified as risky drug users using the WHO-ASSIST and 334 (81% response; 171 intervention, 163 control) consented to participate in the trial. Three-month follow-ups were completed by 261 patients (78%). Intervention patients received the QUIT intervention of brief clinician advice and up to two drug-use health telephone sessions. The control group received usual care and information on cancer screening. Outcomes were three-month changes in the Short Form Health Survey (SF-12) mental health component summary score (MCS) and physical health component summary score (PCS). Results: The average treatment effect (ATE) was non-significant for MCS (0.2 points, p-value = 0.87) and marginally significant for PCS (1.7 points, p-value = 0.08). The average treatment effect on the treated (ATT) was 0.1 (p-value = 0.93) for MCS and 1.9 (p-value = 0.056) for PCS. The effect on PCS was stronger at higher (above median) baseline number of drug use days: ATE = 2.7, p-value = 0.04; ATT = 3.21, p-value = 0.02. Conclusions: The trial found a marginally significant effect on improvement in PCS, and significant and stronger effect on the SF-12 physical component among patients with greater frequency of initial drug use. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Baumeister, Sebastian E.] Univ Med Greifswald, Inst Community Med, D-17489 Greifswald, Germany. [Gelberg, Lillian; Leake, Barbara D.; Yacenda-Murphy, Julia; Vahidi, Mani] Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90095 USA. [Gelberg, Lillian; Andersen, Ronald M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA. [Gelberg, Lillian] VA Greater Angeles Healthcare Syst, Off Healthcare Transformat & Innovat, Los Angeles, CA 90073 USA. RP Baumeister, SE (reprint author), Univ Med Greifswald, Inst Community Med, Walther Rathenau Str 48, D-17489 Greifswald, Germany. EM sebastian.baumeister@uni-greifswald.de FU NIDA ("Preventing Drug Use in Low Income Clinic Populations") [R01 DA022445-01]; UCLA/DREW Project EXPORT, National Center on Minority Health and Health Disparities [P20MD000148/P20MD000182] FX This research was funded primarily by a grant from NIDA ("Preventing Drug Use in Low Income Clinic Populations." R01 DA022445-01). Ronald Andersen received additional support from the UCLA/DREW Project EXPORT, National Center on Minority Health and Health Disparities, P20MD000148/P20MD000182. Sebastian E. Baumeister received travel expenses for short stays at UCLA from the International Office at the University of Greifswald. NR 56 TC 6 Z9 6 U1 1 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 254 EP 261 DI 10.1016/j.drugalcdep.2014.06.034 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700035 PM 25042213 ER PT J AU Durazzo, TC Mattsson, N Weiner, MW Korecka, M Trojanowski, JQ Shaw, LM AF Durazzo, Timothy C. Mattsson, Niklas Weiner, Michael W. Korecka, Magdalena Trojanowski, John Q. Shaw, Leslie M. CA Alzheimer's Dis Neuroimaging Initi TI History of cigarette smoking in cognitively-normal elders is associated with elevated cerebrospinal fluid biomarkers of oxidative stress SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cigarette smoking; Oxidative stress; Isoprostanes; Hippocampus; Cerebrospinal fluid; Elder adults ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; TOBACCO-SMOKE; CARDIOVASCULAR-DISEASE; LIPID-PEROXIDATION; UNITED-STATES; HUMAN URINE; RISK-FACTOR; BACOSIDE-A AB Background: Cigarette smoking in adults is associated with abnormalities in brain neurobiology. Smoking-induced central nervous system oxidative stress (OxS) is a potential mechanism associated with these abnormalities. The goal of this study was to compare cognitively-normal elders on cerebrospinal fluid (CSF) levels of F-2-isoprostane biomarkers of OxS. Methods: Elders with a lifetime history of smoking (smokers; n = 50; 75 +/- 5 years of age; 34 +/- 28 pack-years; approximately 12% were actively smoking at the time of study) were compared to never-smokers (n = 61; 76 +/- 6 years of age) on CSF iPF(2 alpha)-III and 8,12, iso-iPF(2 alpha)-VI F-2-isoprostanes levels. F-2-isoprostanes levels were quantitated with HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry. Associations between F-2-isoprostanes levels, hippocampal volumes, and cigarette exposure measures were also evaluated. Results: Smokers showed higher iPF(2 alpha)-III level than never-smokers. An age x smoking status interaction was observed for 8,12, iso-iPF(2 alpha)-VI, where smokers demonstrate a significantly greater concentration with increasing age than never-smokers. In smokers only, higher 8,12, iso-iPF(2 alpha)-VI concentration was associated with smaller hippocampal volume, and greater iPF(2 alpha)-III level was related to greater pack years. Conclusions: This is the first study to demonstrate that a history of cigarette smoking in cognitively-normal elders was associated with significantly elevated CSF F-2-isoprostane levels and greater age-related increases in F-2-isoprostanes, and that higher F-2-isoprostane levels in smokers were related to smaller hippocampal volume. These findings provide additional novel evidence that a history of chronic smoking during adulthood is associated with adverse effects on the human brain that are potentially enduring even with extended smoking cessation. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis CIND, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Mattsson, Niklas] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Korecka, Magdalena; Trojanowski, John Q.; Shaw, Leslie M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Korecka, Magdalena; Trojanowski, John Q.; Shaw, Leslie M.] Univ Penn, Ctr Neurodegenerat Dis Res, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438 FU National Institutes of Health [NIH DA24136]; ADNI; National Institute on Aging [U01 AG024904]; National Institute of Biomedical Imaging and Bioengineering; Abbott; AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; GlaxoSmithKline; Innogenetics; Johnson and Johnson; Eli Lilly and Co.; Medpace, Inc.; Merck and Co.,Inc.; Novartis AG; Pfizer Inc; F. Hoffman-La Roche; Schering-Plough; Synarc, Inc.; Wyeth; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; U.S. Food and Drug Administration; Northern California Institute for Research and Education; NIH [P30 AG010129, K01 AG030514, R01 AG010897, R01 AG012435]; Dana Foundation FX This work was supported by the National Institutes of Health (NIH DA24136 to TCD) and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. All data collection and sharing for this project was supported by ADNI. ADNI is funded by the National Institute on Aging (U01 AG024904; PI MWW), the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co.,Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., and Wyeth, as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org; http://www.fnih.org; http://www.fnih.org; http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University Southern California. This research was also supported by NIH grants P30 AG010129, K01 AG030514, R01 AG010897, R01 AG012435, and The Dana Foundation and by resources. The above funding agencies had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript. Original data used in preparation of this article were obtained from the ADNI database (www.loni.usc.edu/ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNLAuthorship_ List.pdf. NR 83 TC 5 Z9 5 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 262 EP 268 DI 10.1016/j.drugalcdep.2014.06.030 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700036 PM 25037769 ER PT J AU McCauley, JL Mercer, MA Barth, KS Brady, KT Back, SE AF McCauley, Jenna L. Mercer, Mary Ashley Barth, Kelly S. Brady, Kathleen T. Back, Sudie E. TI Pain management perceptions among prescription opioid dependent individuals SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Prescription opioid; Pain management; Addictive behaviors; Substance abuse ID MOTIVES; ABUSE AB Background: Nearly two-thirds of prescription opioid dependent individuals report chronic pain conditions as both an initial and current motivation for prescription opioid use. However, to date, limited information exists regarding perceptions of the adequacy of pain management and pain management behaviors among prescription opioid dependent individuals with a history of treatment for chronic pain. Methods: The current study examined perceptions of the medical management of chronic pain among community-recruited individuals (N = 39) who met DSM-IV-TR criteria for current prescription opioid dependence and reported a history of treatment for chronic pain. Prescription opioid dependence, symptoms of depression, and pain management perceptions were assessed using the Structured Clinical Interview for DSM disorders, Beck Depression Inventory, and the Pain Management Questionnaire, respectively. Results: Reports of insufficient pain management were common (46.2%), as was utilization of emergency room services for pain management (56.4%). Nearly half reported a physician as their initial source (46.2%) and pain management as their primary initial reason for prescription opioid use (53.8%), whereas 35.9% reported pain relief as their primary reason for current prescription opioid use. Symptoms of depression were common (51.3%), as was comorbid abuse of other substances and history of treatment for substance abuse. Conclusions: Results highlight the complicated clinical presentation and prevalent perception of the under-treatment of pain among this population. Findings underscore the importance of interdisciplinary approaches to managing the complex presentation of chronic pain patients with comorbid prescription opioid dependence. Implications for future research are discussed. Published by Elsevier Ireland Ltd. C1 [McCauley, Jenna L.; Mercer, Mary Ashley; Barth, Kelly S.; Brady, Kathleen T.; Back, Sudie E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Brady, Kathleen T.; Back, Sudie E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP McCauley, JL (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St MSC 861, Charleston, SC 29425 USA. EM mccaule@musc.edu OI Mercer, Mary/0000-0001-9538-5019 FU NIDA [K23 DA021228, K12 DA031794]; MUSC Clinical & Translational Research Center (CTRC) NIH/NCRR [UL1 RR029880] FX Funding for this study was provided by NIDA grant K23 DA021228 (PI: Back), NIDA grant K12 DA031794 (PI: Brady; Sub-Award PI: McCauley), and the MUSC Clinical & Translational Research Center (CTRC) NIH/NCRR Grant number UL1 RR029880 (PI: Brady). The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 28 TC 1 Z9 1 U1 2 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 354 EP 358 DI 10.1016/j.drugalcdep.2014.06.024 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700050 PM 25034899 ER PT J AU McMillan, GP AF McMillan, Garnett P. TI On Reliability SO EAR AND HEARING LA English DT Editorial Material ID SPEECH; THRESHOLD; CHILDREN; NOISE C1 Natl Ctr Rehabil Auditory Res, Portland VA Med Ctr, Portland, OR 97239 USA. RP McMillan, GP (reprint author), Natl Ctr Rehabil Auditory Res, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 12 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD SEP-OCT PY 2014 VL 35 IS 5 BP 589 EP 590 PG 2 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AO7BI UT WOS:000341506600018 PM 24722511 ER PT J AU Cai, CC Huang, H Whelan, S Liu, L Kautza, B Luciano, J Wang, GL Chen, GQ Stratimirovic, S Tsung, A Billiar, TR Zuckerbraun, BS AF Cai, Changchun Huang, Hai Whelan, Sean Liu, Li Kautza, Benjamin Luciano, Jason Wang, Guoliang Chen, Guoqiang Stratimirovic, Sladjana Tsung, Allan Billiar, Timothy R. Zuckerbraun, Brian S. TI Benzyl Alcohol Attenuates Acetaminophen-Induced Acute Liver Injury in a Toll-Like Receptor-4-Dependent Pattern in Mice SO HEPATOLOGY LA English DT Article ID GROUP BOX-1 PROTEIN; INDUCED HEPATOTOXICITY; CELL-DEATH; MITOCHONDRIAL DYSFUNCTION; ISCHEMIA-REPERFUSION; STERILE INFLAMMATION; HEPATIC-INJURY; UNITED-STATES; RECEPTOR 4; HMGB1 AB Acetaminophen (APAP) toxicity is the most common cause of acute liver failure in industrialized countries. Understanding the mechanisms of APAP-induced liver injury as well as other forms of sterile liver injury is critical to improve the care of patients. Recent studies demonstrate that danger signaling and inflammasome activation play a role in APAP-induced injury. The aim of these investigations was to test the hypothesis that benzyl alcohol (BA) is a therapeutic agent that protects against APAP-induced liver injury by modulation of danger signaling. APAP-induced liver injury was dependent, in part, on Toll-like receptor (TLR) 9 and receptor for advanced glycation endproducts (RAGE) signaling. BA limited liver injury over a dose range of 135-540 mu g/g body weight or when delivered as a pre-, concurrent, or post-APAP therapeutic. Furthermore, BA abrogated APAP-induced cytokines and chemokines as well as high-mobility group box 1 release. Moreover, BA prevented APAP-induced inflammasome signaling as determined by interleukin (IL)-1 beta, IL-18, and caspase-1 cleavage in liver tissues. Interestingly, the protective effects of BA on limiting liver injury and inflammasome activation were dependent on TLR4 signaling, but not TLR2 or CD14. Cell-type-specific knockouts of TLR4 were utilized to further determine the protective mechanisms of BA. These studies found that TLR4 expression specifically in myeloid cells (LyzCre-tlr4(-/-)) were necessary for the protective effects of BA. Conclusion: BA protects against APAP-induced acute liver injury and reduced inflammasome activation in a TLR4-dependent manner. BA may prove to be a useful adjunct in the treatment of APAP and other forms of sterile liver injury. C1 [Cai, Changchun; Chen, Guoqiang] Cent Hosp Wuhan, Wuhan, Peoples R China. [Cai, Changchun; Huang, Hai; Whelan, Sean; Liu, Li; Kautza, Benjamin; Luciano, Jason; Wang, Guoliang; Chen, Guoqiang; Stratimirovic, Sladjana; Tsung, Allan; Billiar, Timothy R.; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Stratimirovic, Sladjana; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, Dept Surg, F1271 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu RI Huang, Hai/F-4286-2012 OI Huang, Hai/0000-0001-7430-0119 FU NIGMS NIH HHS [R01 GM082830] NR 39 TC 11 Z9 11 U1 0 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD SEP PY 2014 VL 60 IS 3 BP 990 EP 1002 DI 10.1002/hep.27201 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO3NV UT WOS:000341239200025 PM 24798499 ER PT J AU Ju, MH Cohen, ME Bilimoria, KY Latus, MS Scholl, LM Schwab, BJ Byrd, CM Ko, CY Dellinger, EP Hall, BL AF Ju, Mila H. Cohen, Mark E. Bilimoria, Karl Y. Latus, Melissa S. Scholl, Lisa M. Schwab, Bradley J. Byrd, Claudia M. Ko, Clifford Y. Dellinger, E. Patchen Hall, Bruce L. TI Effect of Wound Classification on Risk Adjustment in American College of Surgeons NSQIP SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SURGICAL QUALITY; ACS-NSQIP; INFECTIONS AB BACKGROUND: Surgical wound classification has been used in risk-adjustment models. However, it can be subjective and could potentially improperly bias hospital quality comparisons. The objective is to examine the effect of wound classification on hospital performance risk-adjustment models. STUDY DESIGN: Retrospective review of the 2011 American College of Surgeons NSQIP database was conducted for the following wound classification categories: clean, clean-contaminated, contaminated, and dirty-infected. To assess the influence of wound classification on risk adjustment, 2 models were developed for all outcomes: 1 including and 1 excluding wound classification. For each model, hospital postoperative complications were estimated using hierarchical multivariable regression methods. Absolute changes in hospital rank, correlations of odds ratios, and outlier status agreement between models were examined. RESULTS: Of the 442,149 cases performed in 315 hospitals: 53.6% were classified as clean; 34.2% as clean-contaminated; 6.7% as contaminated; and 5.5% as dirty-infected. The surgical site infection rate was highest in dirty-infected (8.5%) and lowest in clean (1.8%) cases. For overall surgical site infection, the absolute change in risk-adjusted hospital performance rank between models, including vs excluding wound classification, was minimal (mean 4.5 of 315 positions). The correlations between odds ratios of the 2 performance models were nearly perfect (R 0.9976, p < 0.0001), and outlier status agreement was excellent (kappa = 0.95ss08, p < 0.0001). Similar findings were observed in models of subgroups of surgical site infections and other postoperative outcomes. CONCLUSIONS: In circumstances where alternate information is available for risk adjustment, there appear to be minimal differences in performance models that include vs exclude wound classification. Therefore, the American College of Surgeons NSQIP is critically evaluating the continued use of wound classification in hospital performance risk-adjustment models. (C) 2014 by the American College of Surgeons C1 [Ju, Mila H.; Cohen, Mark E.; Bilimoria, Karl Y.; Latus, Melissa S.; Scholl, Lisa M.; Schwab, Bradley J.; Byrd, Claudia M.; Ko, Clifford Y.; Hall, Bruce L.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Ju, Mila H.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Ju, Mila H.; Bilimoria, Karl Y.] NW Mem Hosp, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dellinger, E. Patchen] Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce L.] BJC Healthcare, St Louis VA Med Ctr, St Louis, MO USA. RP Ju, MH (reprint author), Amer Coll Surg, 633 North St Clair St,22nd Fl, Chicago, IL 60611 USA. EM mju@facs.org FU NIH [5T32HL094293]; AHRQ; NCCN; ACS; ACoS; BCBS-IL; Tetraphrase; Applied Medical; Health and Human Services; Michigan Hospital Association; Louisiana Woman's Hospital FX Dr Ju is supported by NIH Grant #5T32HL094293, and is a Scholar in Residence at the ACS. Dr Bilimoria receives grants from NIH, AHRQ, NCCN, ACS, ACoS, and BCBS-IL; and lecture payments from hospitals and professional societies for grand rounds. Dr Dellinger is a paid consultant to Merck, Targanta, Astellas, Care Fusion, Durata, Pfizer, Rib-X, Affinium, and 3M; receives grants from Tetraphrase and lecture payments from Applied Medical; and other expenses paid by Health and Human Services, Michigan Hospital Association, and Louisiana Woman's Hospital. Dr Hall is a paid consultant to the ACS. This study received no outside funding. NR 20 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2014 VL 219 IS 3 BP 371 EP + DI 10.1016/j.jamcollsurg.2014.04.009 PG 16 WC Surgery SC Surgery GA AO5VW UT WOS:000341415100008 PM 25053222 ER PT J AU Dawes, AJ Sacks, GD Russell, MM Lin, AY Maggard-Gibbons, M Winograd, D Chung, HR Tillou, A Hiatt, JR Ko, C AF Dawes, Aaron J. Sacks, Greg D. Russell, Marcia M. Lin, Anne Y. Maggard-Gibbons, Melinda Winograd, Deborah Chung, Hallie R. Tillou, Areti Hiatt, Jonathan R. Ko, Clifford TI Preventable Readmissions to Surgical Services: Lessons Learned and Targets for Improvement SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; HOSPITAL READMISSION; RISK-FACTORS; MEDICARE BENEFICIARIES; UNPLANNED READMISSION; PATIENT READMISSION; 30-DAY READMISSIONS; COLORECTAL SURGERY; ILEOSTOMY CREATION; DEHYDRATION AB BACKGROUND: Hospital readmissions are under intense scrutiny as a measure of health care quality. The Center for Medicare and Medicaid Services (CMS) has proposed using readmission rates as a benchmark for improving care, including targeting them as nonreimbursable events. Our study aim was to describe potentially preventable readmissions after surgery and to identify targets for improvement. STUDY DESIGN: Patients discharged from a general surgery service over 8 consecutive quarters (Q4 2009 to Q3 2011) were selected. A working group of attending surgeons defined terms and created classification schemes. Thirty-day readmissions were identified and reviewed by a 2-physician team. Readmissions were categorized as preventable or unpreventable, and by target for future quality improvement intervention. RESULTS: Overall readmission rate was 8.3% (315 of 3,789). The most common indication for initial admission was elective general surgery. Among readmitted patients in our sample, 28% did not undergo an operation during their index admission. Only 21% (55 of 258) of readmissions were likely preventable based on medical record review. Of the preventable readmissions, 38% of patients were discharged within 24 hours and 60% within 48 hours. Dehydration occurred more frequently among preventable readmissions (p < 0.001). Infection accounted for more than one-third of all readmissions. Among preventable readmissions, targets for improvement included closer follow-up after discharge (49%), management in the outpatient setting (42%), and avoidance of premature discharge (9%). CONCLUSIONS: A minority of readmissions may potentially be preventable. Targets for reducing readmissions include addressing the clinical issues of infection and dehydration as well as improving discharge planning to limit both early and short readmissions. Policies aimed at penalizing reimbursements based on readmission rates should use clinical data to focus on inappropriate hospitalization in order to promote high quality patient care. (C) 2014 by the American College of Surgeons C1 [Dawes, Aaron J.; Sacks, Greg D.; Russell, Marcia M.; Lin, Anne Y.; Maggard-Gibbons, Melinda; Winograd, Deborah; Chung, Hallie R.; Tillou, Areti; Hiatt, Jonathan R.; Ko, Clifford] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Sacks, Greg D.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Russell, Marcia M.; Maggard-Gibbons, Melinda; Ko, Clifford] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Dawes, AJ (reprint author), Univ Calif Los Angeles, Ronald Reagan UCLA Med Ctr, David Geffen Sch Med, Dept Surg, 757 Westwood Plaza B7-11, Los Angeles, CA 90095 USA. EM adawes@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 FU VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program FX Dr Dawes was supported by the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program. NR 33 TC 21 Z9 21 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2014 VL 219 IS 3 BP 382 EP 389 DI 10.1016/j.jamcollsurg.2014.03.046 PG 8 WC Surgery SC Surgery GA AO5VW UT WOS:000341415100009 PM 24891209 ER PT J AU Friedlander, AH Bertolami, CN AF Friedlander, Arthur H. Bertolami, Charles N. TI The ethics of managing incidental findings Implications and challenges for the profession SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material C1 [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Friedlander, Arthur H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Bertolami, Charles N.] NYU, Coll Dent, New York, NY USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 4 TC 2 Z9 2 U1 0 U2 2 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2014 VL 145 IS 9 BP 910 EP 911 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AO5IV UT WOS:000341378700001 PM 25169990 ER PT J AU Clapp, JD Grubaugh, AL Allen, JG Oldham, JM Fowler, JC Hardesty, S Frueh, BC AF Clapp, Joshua D. Grubaugh, Anouk L. Allen, Jon G. Oldham, John M. Fowler, J. Christopher Hardesty, Susan Frueh, B. Christopher TI Interpersonal Change Following Intensive Inpatient Treatment SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID THERAPEUTIC ALLIANCE; PSYCHOMETRIC PROPERTIES; PSYCHODYNAMIC THERAPY; PERSONALITY-DISORDERS; SYMPTOM IMPROVEMENT; TREATMENT RESPONSE; PSYCHOTHERAPY; BEHAVIOR; OUTCOMES; INVENTORY AB Objective: Persons admitted for inpatient psychiatric care often present with interpersonal difficulties that disrupt adaptive social relations and complicate the provision of treatment. Whereas domains of psychosocial functioning in this population demonstrate clear growth in response to intervention, the impact of treatment on more complex patterns of interpersonal behavior has been largely overlooked within the existing literature. Interpersonal profiles characteristic of psychiatric inpatients were identified in the current study to determine rates of transition to adaptive functioning following hospitalization. Methods: Personality disturbance was assessed in 513 psychiatric inpatients using the Inventory of Interpersonal Problems. Scores were analyzed within a series of latent profile models to isolate unique interpersonal profiles at admission and at discharge. Longitudinal modeling was then employed to determine rates of transition from dysfunctional to adaptive profiles. Relationships with background characteristics, clinical presentation, and treatment response were explored. Results: Normative, Submissive, and Hostile/Withdrawn profiles emerged at both admission and discharge. Patients in the Normative profile demonstrated relatively moderate symptoms. Submissive and Hostile/Withdrawn profiles were related to known risk factors and elevated psychopathology. Approximately half of the patients who had been identified as Submissive or Hostile/Withdrawn transitioned to the Normative profile by discharge. Transition status evidenced modest associations with background characteristics and clinical presentation. Treatment engagement and reduction of clinical symptoms were strongly associated with adaptive transition. Conclusion: Maladaptive interpersonal profiles characteristic of psychiatric inpatients demonstrated categorical change following inpatient hospitalization. Enhanced therapeutic engagement and overall reductions in psychiatric symptoms appear to increase potential for interpersonal change. C1 [Clapp, Joshua D.] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Grubaugh, Anouk L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Grubaugh, Anouk L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Allen, Jon G.; Oldham, John M.; Fowler, J. Christopher; Hardesty, Susan; Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Allen, Jon G.; Oldham, John M.; Fowler, J. Christopher; Hardesty, Susan] Baylor Coll Med, Houston, TX 77030 USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. RP Clapp, JD (reprint author), Univ Wyoming, Dept Psychol, 1000 E Univ Ave, Laramie, WY 82071 USA. EM jclapp@uwyo.edu FU Menninger Foundation; McNair Medical Institute; National Institute of Mental Health; NIMH [T32-MH18869] FX Research was supported in part by funding from the Menninger Foundation, the McNair Medical Institute, and the National Institute of Mental Health. Dr. Clapp was an NIMH-sponsored psychology intern at the Medical University of South Carolina (T32-MH18869) during the development of this project. Dr. Frueh is a McNair Scholar. We are grateful for the assistance of Steve Herrera, MA, and all the research assistants at the Menninger Clinic. NR 44 TC 1 Z9 1 U1 0 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD FAL PY 2014 VL 77 IS 3 BP 247 EP 262 PG 16 WC Psychiatry SC Psychiatry GA AO4WF UT WOS:000341341400007 PM 25162133 ER PT J AU Szafranski, DD Gros, DF Menefee, DS Wanner, JL Norton, PJ AF Szafranski, Derek D. Gros, Daniel F. Menefee, Deleene S. Wanner, Jill L. Norton, Peter J. TI Predictors of Length of Stay Among OEF/OIF/OND Veteran Inpatient PTSD Treatment Noncompleters SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHOMETRIC PROPERTIES; BEHAVIORAL ACTIVATION; PROLONGED EXPOSURE; AFGHANISTAN; DEPRESSION; THERAPY; DROPOUT; SAMPLE; IRAQ AB High rates of attrition occur in outpatient and inpatient evidence-based treatments (EBTs) targeting newly returning veterans from Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF) and Operation New Dawn (OND) with posttraumatic stress disorder (PTSD). Traditionally, research has examined attrition as a dichotomous variable (i.e., noncompleters vs. completers) and focused almost exclusively on outpatient EBTs for PTSD. These studies have provided little information to inpatient psychiatric providers about timing-related predictors of treatment discontinuation. The present study attempted to mend these gaps by examining attrition as a continuous variable and investigated predictors of length of stay (LOS) among 282 OEF/OIF/OND male veterans, 69 of which did not complete the full 25-day intensive, multimodal inpatient PTSD EBT program. At admission, participants completed a series of clinician-rated, biological, and self-report assessments. Linear regression analyses were used to identify predictors of shorter LOS. The results demonstrated that less improvement in symptom reduction, overall functioning, and greater number of drugs used at admission were significant and unique predictors of shorter LOS. Overall, these findings reveal clinically relevant, timing-related predictors of attrition and provide generalizable clinical information to inpatient psychiatric providers. C1 [Szafranski, Derek D.; Norton, Peter J.] Univ Houston, Dept Psychol, Houston, TX 77204 USA. [Szafranski, Derek D.; Menefee, Deleene S.; Wanner, Jill L.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Menefee, Deleene S.; Wanner, Jill L.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Szafranski, DD (reprint author), Univ Houston, Dept Psychol, 126 Heyne Bldg, Houston, TX 77204 USA. EM ddszafranski@gmail.com NR 38 TC 3 Z9 3 U1 0 U2 6 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD FAL PY 2014 VL 77 IS 3 BP 263 EP 274 PG 12 WC Psychiatry SC Psychiatry GA AO4WF UT WOS:000341341400008 PM 25162134 ER PT J AU Cicero, DC Martin, EA Becker, TM Docherty, AR Kerns, JG AF Cicero, David C. Martin, Elizabeth A. Becker, Theresa M. Docherty, Anna R. Kerns, John G. TI Correspondence Between Psychometric and Clinical High Risk for Psychosis in an Undergraduate Population SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE schizotypy; psychometric high risk; clinical high risk; psychotic-like experiences; prodrome ID WISCONSIN SCHIZOTYPY SCALES; PERSISTENT NEGATIVE SYMPTOMS; AGE-OF-ONSET; UNTREATED PSYCHOSIS; PRODROMAL SYNDROMES; SOCIAL ANHEDONIA; SELF-REPORT; AT-RISK; 1ST-EPISODE SCHIZOPHRENIA; INTERRATER RELIABILITY AB Despite the common use of either psychometric or clinical methods for identifying individuals at risk for psychosis, previous research has not examined the correspondence and extent of convergence of these 2 approaches. Undergraduates (n = 160), selected from a larger pool, completed 3 self-report schizotypy scales: the Magical Ideation Scale, the Perceptual Aberration Scale, and the Revised Social Anhedonia Scale. They were administered the Structured Interview for Prodromal Syndromes. First, high correlations were observed for self-report and interview-rated psychotic-like experiences (rs between .48 and .61, p < .001). Second, 77% of individuals who identified as having a risk for psychosis with the self-report measures reported at least 1 clinically meaningful psychotic-like experience on the Structured Interview for Prodromal Syndromes. Third, receiver operating characteristic curve analyses showed that the self-report scales can be used to identify which participants report clinically meaningful positive symptoms. These results suggest that mostly White undergraduate participants who identify as at risk with the psychometric schizotypy approach report clinically meaningful psychotic-like experiences in an interview format and that the schizotypy scales are moderately to strongly correlated with interview-rated psychotic-like experiences. The results of the current research provide a baseline for comparing research between these 2 approaches. C1 [Cicero, David C.] Univ Hawaii Manoa, Dept Psychol, Honolulu, HI 96822 USA. [Martin, Elizabeth A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Becker, Theresa M.] Univ Washington, Inst Learning & Brain Sci, Seattle, WA 98195 USA. [Docherty, Anna R.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Stat Genet, Richmond, VA 23284 USA. [Kerns, John G.] Univ Missouri, Dept Psychol Sci, Columbia, MO 65211 USA. RP Cicero, DC (reprint author), Univ Hawaii Manoa, Dept Psychol, Sakamaki Hall,C400,2530 Dole St, Honolulu, HI 96822 USA. EM dcicero@hawaii.edu RI Cicero, David/E-2046-2016 OI Cicero, David/0000-0002-5666-9139; Docherty, Anna/0000-0001-7139-7007 FU NIMH NIH HHS [F31 MH086190, MH086190, T32 MH020030] NR 85 TC 14 Z9 14 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 EI 1939-134X J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD SEP PY 2014 VL 26 IS 3 BP 901 EP 915 DI 10.1037/a0036432 PG 15 WC Psychology, Clinical SC Psychology GA AO6WA UT WOS:000341491800020 PM 24708081 ER PT J AU Schacht, JP Anton, RF Randall, P Li, XB Henderson, S Myrick, H AF Schacht, Joseph P. Anton, Raymond F. Randall, PatrickK. Li, Xingbao Henderson, Scott Myrick, Hugh TI Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals SO PSYCHOPHARMACOLOGY LA English DT Article DE Varenicline; Alcohol; fMRI; Neuroimaging; Craving ID PARTIAL AGONIST VARENICLINE; RECEPTOR PARTIAL AGONIST; NICOTINIC ACETYLCHOLINE-RECEPTORS; INDUCED BRAIN ACTIVATION; ETHANOL-CONSUMPTION; DOPAMINE RELEASE; CUE REACTIVITY; DOUBLE-BLIND; NALTREXONE; RESPONSES AB The alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas. This pilot study tested varenicline's effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals. Thirty-five such individuals (mean age = 30, 57 % male, 76 % heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC). Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas. These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption. C1 [Schacht, Joseph P.; Anton, Raymond F.; Randall, PatrickK.; Li, Xingbao; Henderson, Scott; Myrick, Hugh] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Myrick, Hugh] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schacht, JP (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. EM schacht@musc.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); Charleston Alcohol Research Center [P50 AA010761]; [K99 AA021419]; [K05 AA017435] FX Portions of this work were presented at the 34th Annual Meeting of the Research Society on Alcoholism (June 2011, Atlanta) and the 52nd Annual Meeting of the American College on Neuropsychopharmacology (December 2013, Hollywood, FL). This research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), including the Charleston Alcohol Research Center (P50 AA010761). NIAAA had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the paper, or in the decision to submit for publication. Drs. Schacht and Anton are supported by K99 AA021419 and K05 AA017435, respectively. NR 45 TC 14 Z9 14 U1 7 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2014 VL 231 IS 18 BP 3799 EP 3807 DI 10.1007/s00213-014-3518-1 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AO5GG UT WOS:000341371300013 PM 24647921 ER PT J AU Williams, EC Rubinsky, AD Chavez, LJ Lapham, GT Rittmueller, SE Achtmeyer, CE Bradley, KA AF Williams, Emily C. Rubinsky, Anna D. Chavez, Laura J. Lapham, Gwen T. Rittmueller, Stacey E. Achtmeyer, Carol E. Bradley, Katharine A. TI An early evaluation of implementation of brief intervention for unhealthy alcohol use in the US Veterans Health Administration SO ADDICTION LA English DT Article DE Alcohol; brief intervention; implementation; unhealthy alcohol use; veterans ID RANDOMIZED CONTROLLED-TRIAL; ELECTRONIC CLINICAL REMINDER; PRIMARY-CARE PHYSICIANS; SERVICES-TASK-FORCE; RE-AIM FRAMEWORK; AT-RISK DRINKING; PREVENTIVE-SERVICES; USE DISORDERS; AUDIT-C; COUNSELING INTERVENTIONS AB Aims The US Veterans Health Administration [Veterans Affairs (VA)] used performance measures and electronic clinical reminders to implement brief intervention for unhealthy alcohol use. We evaluated whether documented brief intervention was associated with subsequent changes in drinking during early implementation. Design Observational, retrospective cohort study using secondary clinical and administrative data. Setting Thirty VA facilities. Participants Outpatients who screened positive for unhealthy alcohol use [Alcohol Use Disorders Identification Test Consumption (AUDIT-C >= 5)] in the 6 months after the brief intervention performance measure (n = 22 214) and had follow-up screening 9-15 months later (n = 6210; 28%). Measurements Multi-level logistic regression estimated the adjusted prevalence of resolution of unhealthy alcohol use (follow-up AUDIT-C < 5 with <= 2 point reduction) for patients with and without documented brief intervention (documented advice to reduce or abstain from drinking). Findings Among 6210 patients with follow-up alcohol screening, 1751 (28%) had brief intervention and 2922 (47%) resolved unhealthy alcohol use at follow-up. Patients with documented brief intervention were older and more likely to have other substance use disorders, mental health conditions, poor health and more severe unhealthy alcohol use than those without (P-values < 0.05). Adjusted prevalences of resolution were 47% [95% confidence interval (CI) = 42-52%] and 48% (95% CI = 42-54%) for patients with and without documented brief intervention, respectively (P = 0.50). Conclusions During early implementation of brief intervention in the US Veterans Health Administration, documented brief intervention was not associated with subsequent changes in drinking among outpatients with unhealthy alcohol use and repeat alcohol screening. C1 [Williams, Emily C.; Rubinsky, Anna D.; Chavez, Laura J.; Lapham, Gwen T.; Rittmueller, Stacey E.; Achtmeyer, Carol E.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev HSR&D, Seattle, WA 98101 USA. [Williams, Emily C.; Chavez, Laura J.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Lapham, Gwen T.; Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. [Achtmeyer, Carol E.] VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98101 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM emily.williams3@va.gov FU US Department of Veterans Affairs (VA) Quality Enhancement Research Initiative [RRP 11-268]; VA Health Services Research and Development [IIR 08-314, CDA 12-276]; National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative (QUERI); VA Center of Excellence for Substance Abuse Treatment and Education (CESATE) FX This study was supported by funding from the US Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (RRP 11-268; Principle Investigator E.C.W.) and VA Health Services Research and Development (IIR 08-314; Principle Investigator K.A.B.). E.C.W. is supported by El Career Development Award from VA Health Services Research and Development (CDA 12-276) and is an investigator with the Implementation Research Institute (IRI) at the George Warren Brown School of Social Work at Washington University in St Louis. IRI is supported through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative (QUERI). K.A.B. and A.D.R. were supported by the VA Center of Excellence for Substance Abuse Treatment and Education (CESATE) for their work on this project. The views expressed in this paper are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the University of Washington or Group Health Research Institute. NR 91 TC 13 Z9 13 U1 4 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD SEP PY 2014 VL 109 IS 9 BP 1472 EP 1481 DI 10.1111/add.12600 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AN4OE UT WOS:000340566600015 PM 24773590 ER PT J AU Khan, NH Almukhtar, RM AF Khan, N. H. Almukhtar, R. M. TI Editorial: early corticosteroids in ulcerative colitis - authors' reply SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID REMISSION; DISEASE C1 [Khan, N. H.; Almukhtar, R. M.] Southeast Louisiana Vet Hlth Care Syst, Gastroenterol Sect, Dept Internal Med, New Orleans, LA 70112 USA. [Khan, N. H.] Univ Penn, Gastroenterol Sect, Perelman Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Almukhtar, R. M.] Tulane Univ, Hlth Sci Ctr, Dept Internal Med, Sect Gastroenterol & Hepatol, New Orleans, LA 70118 USA. [Almukhtar, R. M.] Louisiana State Univ, Hlth Sci Ctr, Dept Epidemiol, New Orleans, LA USA. RP Khan, NH (reprint author), Southeast Louisiana Vet Hlth Care Syst, Gastroenterol Sect, Dept Internal Med, New Orleans, LA 70112 USA. EM nabeel.khan@va.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 EI 1365-2036 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD SEP PY 2014 VL 40 IS 6 BP 728 EP 728 DI 10.1111/apt.12898 PG 1 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA AN4LS UT WOS:000340559900015 PM 25123385 ER PT J AU Liu, YN Yuan, JZ Tan, TY Jia, WZ Lugea, A Mareninova, O Waldron, RT Pandol, SJ AF Liu, Yannan Yuan, Jingzhen Tan, Tanya Jia, Wenzhuo Lugea, Aurelia Mareninova, Olga Waldron, Richard T. Pandol, Stephen J. TI Genetic inhibition of protein kinase C epsilon attenuates necrosis in experimental pancreatitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE apoptosis; necrosis; inhibitors of apoptotic proteins (IAPs); Bcl-2 family proteins; receptor-interacting protein kinase (RIP) ID NF-KAPPA-B; RECEPTOR-INTERACTING PROTEIN; MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; CELL-DEATH; ACINAR-CELLS; PROGRAMMED NECROSIS; ZYMOGEN ACTIVATION; INDUCED APOPTOSIS; TNF-ALPHA; BCL-2 AB Understanding the regulation of death pathways, necrosis and apoptosis, in pancreatitis is important for developing therapies directed to the molecular pathogenesis of the disease. Protein kinase C epsilon (PKC epsilon) has been previously shown to regulate inflammatory responses and zymogen activation in pancreatitis. Furthermore, we demonstrated that ethanol specifically activated PKCe in pancreatic acinar cells and that PKCe mediated the sensitizing effects of ethanol on inflammatory response in pancreatitis. Here we investigated the role of PKCe in the regulation of death pathways in pancreatitis. We found that genetic deletion of PKCe resulted in decreased necrosis and severity in the in vivo cerulein-induced pancreatitis and that inhibition of PKCe protected the acinar cells from CCK-8 hyperstimulation-induced necrosis and ATP reduction. These findings were associated with upregulation of mitochondrial Bak and Bcl-2/Bcl-xL, proapoptotic and prosurvival members in the Bcl-2 family, respectively, as well as increased mitochondrial cytochrome c release, caspase activation, and apoptosis in pancreatitis in PKCe knockout mice. We further confirmed that cerulein pancreatitis induced a dramatic mitochondrial translocation of PKCe, suggesting that PKCe regulated necrosis in pancreatitis via mechanisms involving mitochondria. Finally, we showed that PKCe deletion downregulated inhibitors of apoptosis proteins, c-IAP2, survivin, and c-FLIPs while promoting cleavage/inactivation of receptor-interacting protein kinase (RIP). Taken together, our findings provide evidence that PKCe activation during pancreatitis promotes necrosis through mechanisms involving mitochondrial proapoptotic and prosurvival Bcl-2 family proteins and upregulation of nonmitochondrial pathways that inhibit caspase activation and RIP cleavage/inactivation. Thus PKCe is a potential target for prevention and/or treatment of acute pancreatitis. C1 [Liu, Yannan; Yuan, Jingzhen; Tan, Tanya; Jia, Wenzhuo; Lugea, Aurelia; Mareninova, Olga; Waldron, Richard T.; Pandol, Stephen J.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Liu, Yannan; Yuan, Jingzhen; Tan, Tanya; Jia, Wenzhuo; Lugea, Aurelia; Mareninova, Olga; Waldron, Richard T.; Pandol, Stephen J.] South Calif Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. [Liu, Yannan; Jia, Wenzhuo] Beijing Hosp, Beijing, Peoples R China. [Tan, Tanya] St Georges Univ, Sch Med, St Georges, Grenada. [Lugea, Aurelia; Waldron, Richard T.; Pandol, Stephen J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Yuan, JZ (reprint author), UCLA VA Greater Los Angeles Healthcare Syst, West Los Angeles VA Healthcare Ctr, South Calif Res Ctr Alcohol Liver & Pancreat Dis, 11301 Wilshire Blvd,Bldg 258,Rm 340, Los Angeles, CA 90073 USA. EM jzyuan@ucla.edu FU Southern California Research Center for Alcoholic Liver and Pancreatic Diseases (NIH) [P50-A11999]; UCLA Center of Excellence in Pancreatic Diseases (NIH) [1P01AT0003960-01]; Department of Veterans Affairs Merits Grant; Southern California Research Center for Liver and Pancreatic Diseases FX This study was supported by the Southern California Research Center for Alcoholic Liver and Pancreatic Diseases (NIH Grant P50-A11999); UCLA Center of Excellence in Pancreatic Diseases (NIH Grant 1P01AT0003960-01); the Department of Veterans Affairs Merits Grant; and Lee Summer Student Research Award from Southern California Research Center for Liver and Pancreatic Diseases (to T. Tan). NR 57 TC 5 Z9 5 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP G550 EP G563 DI 10.1152/ajpgi.00432.2013 PG 14 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA AO1SP UT WOS:000341094700006 PM 25035113 ER PT J AU Yarbrough, WM Baicu, C Mukherjee, R Van Laer, A Rivers, WT McKinney, RA Prescott, CB Stroud, RE Freels, PD Zellars, KN Zile, MR Spinale, FG AF Yarbrough, William M. Baicu, Catalin Mukherjee, Rupak Van Laer, An Rivers, William T. McKinney, Richard A. Prescott, Corey B. Stroud, Robert E. Freels, Parker D. Zellars, Kia N. Zile, Michael R. Spinale, Francis G. TI Cardiac-restricted overexpression or deletion of tissue inhibitor of matrix metalloproteinase-4: differential effects on left ventricular structure and function following pressure overload-induced hypertrophy SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE remodeling; tissue inhibitors of metalloproteinase; pressure-overload hypertrophy ID AORTIC-VALVE REPLACEMENT; MYOCARDIAL FIBROSIS; HEART-FAILURE; MICE; DISEASE; REGRESSION; INDUCTION; DYSFUNCTION; INFARCTION; EXPRESSION AB Historically, the tissue inhibitors of matrix metalloproteinases (TIMPs) were considered monochromatic in function. However, differential TIMP profiles more recently observed with left ventricular (LV) dysfunction and matrix remodeling suggest more diverse biological roles for individual TIMPs. This study tested the hypothesis that cardiac-specific overexpression (TIMP-4OE) or deletion (knockout; TIMP-4KO) would differentially affect LV function and structure following pressure overload (LVPO). LVPO (transverse aortic constriction) was induced in mice (3.5 +/- 0.1 mo of age, equal sex distribution) with TIMP-4OE (n = 38), TIMP4-KO (n = 24), as well as age/strain-matched wild type (WT, n = 25), whereby indexes of LV remodeling and function such as LV mass and ejection fraction (LVEF) were determined at 28 days following LVPO. Following LVPO, both early (7 days) and late (28 days) survival was similar to 25% lower in the TIMP-4KO group (P < 0.05). While LVPO increased LV mass in all groups, the relative hypertrophic response was attenuated with TIMP-4OE. With LVPO, LVEF was similar between WT and TIMP-4KO (48 +/- 2% and 45 +/- 3%, respectively) but was higher with TIMP-4OE (57 +/- 2%, P < 0.05). With LVPO, LV myocardial collagen expression (type I, III) increased by threefold in all groups (P < 0.05), but surprisingly this response was most robust in the TIMP-4KO group. These unique findings suggest that increased myocardial TIMP-4 in the context of a LVPO stimulus may actually provide protective effects with respect to survival, LV function, and extracellular matrix (ECM) remodeling. These findings challenge the canonical belief that increased levels of specific myocardial TIMPs, such as TIMP-4 in and of themselves, contribute to adverse ECM accumulation following a pathological stimulus, such as LVPO. C1 [Freels, Parker D.; Zellars, Kia N.; Spinale, Francis G.] Univ S Carolina, Sch Med, WJB Dorn Vet Affairs Med Ctr, Columbia, SC USA. [Baicu, Catalin; Mukherjee, Rupak; Van Laer, An; Rivers, William T.; McKinney, Richard A.; Prescott, Corey B.; Stroud, Robert E.; Zile, Michael R.] Med Univ S Carolina, Div Cardiothorac Surg & Adult Cardiol, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Yarbrough, William M.] Sisters Char Providence Hosp, Columbia, SC USA. RP Spinale, FG (reprint author), Univ S Carolina, Sch Med, Cardiovasc Translat Res Ctr, CBA, 6439 Garners Ferry Rd, Columbia, SC 29208 USA. EM cvctrc@uscmed.sc.edu FU National Institutes of Health [HL-11090, HL-089944]; Veterans Affairs Health Administration; Research Service of the Department of Veterans Affairs FX This work was supported by National Institutes of Health Grants HL-11090 and HL-089944 and a Merit Award from the Veterans Affairs Health Administration. F. G. Spinale and M. R. Zile are supported by the Research Service of the Department of Veterans Affairs. NR 37 TC 3 Z9 3 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP H752 EP H761 DI 10.1152/ajpheart.00063.2014 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA AO1NZ UT WOS:000341081200013 PM 24993046 ER PT J AU Gooz, MB Maldonado, EN Dang, YJ Amria, MY Higashiyama, S Abboud, HE Lemasters, JJ Bell, PD AF Gooz, Monika Beck Maldonado, Eduardo N. Dang, Yujing Amria, May Y. Higashiyama, Shigeki Abboud, Hanna E. Lemasters, John J. Bell, P. Darwin TI ADAM17 promotes proliferation of collecting duct kidney epithelial cells through ERK activation and increased glycolysis in polycystic kidney disease SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE ADAM17; glycolysis; ERK; cell proliferation; polycystic kidney disease (PKD) ID CONVERTING-ENZYME TACE; GROWTH; ALPHA; EGFR; RECEPTORS; POLARIS; CANCER; CILIA; MICE AB Polycystic kidney disease (PKD) is a common genetic disorder leading to cyst formation in the kidneys and other organs that ultimately results in kidney failure and death. Currently, there is no therapy for slowing down or stopping the progression of PKD. In this study, we identified the disintegrin metalloenzyme 17 (ADAM17) as a key regulator of cell proliferation in kidney tissues of conditional knockout Ift88(-/-) mice and collecting duct epithelial cells from Ift88(orpk) mice, animal models of autosomal recessive polycystic kidney disease (ARPKD). Using Western blotting, an enzyme activity assay, and a growth factor-shedding assay in the presence or absence of the specific ADAM17 inhibitor TMI-005, we show that increased expression and activation of ADAM17 in the cystic kidney and in collecting duct epithelial cells originating from the Ift88(orpk) mice (designated as PKD cells) lead to constitutive shedding of several growth factors, including heparin-binding EGF-like growth factor (HB-EGF), amphiregulin, and transforming growth factor-alpha (TGF-alpha). Increased growth factor shedding induces activation of the EGFR/MAPK/ERK pathway and maintains higher cell proliferation rate in PKD cells compared with control cells. PKD cells also displayed increased lactate formation and extracellular acidification indicative of aerobic glycolysis (Warburg effect), which was blocked by ADAM17 inhibition. We propose that ADAM17 is a key promoter of cellular proliferation in PKD cells by activating the EGFR/ERK axis and a proproliferative glycolytic phenotype. C1 [Gooz, Monika Beck; Dang, Yujing; Amria, May Y.; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Maldonado, Eduardo N.; Lemasters, John J.] Med Univ S Carolina, Dept Drug Discovery & Pharmaceut Sci, Charleston, SC 29425 USA. [Higashiyama, Shigeki] Ehime Univ, Dept Biochem & Mol Genet, Matsuyama, Ehime 790, Japan. [Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Nephrol, San Antonio, TX 78229 USA. [Lemasters, John J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Bell, P. Darwin] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Gooz, MB (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,CSB829,MS 629, Charleston, SC 29425 USA. EM beckm@musc.edu FU National Institutes of Health (NIH) [NIDDK P30 DK074038, R01 DK32032]; Veterans Administration (Ralph H. Johnson VA Medical Center); Dialysis Clinic, Inc. FX This work was supported by grants from the National Institutes of Health (NIH NIDDK P30 DK074038 and R01 DK32032), a Merit Grant from the Veterans Administration (Ralph H. Johnson VA Medical Center), and grants from the Dialysis Clinic, Inc. NR 26 TC 7 Z9 7 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP F551 EP F559 DI 10.1152/ajprenal.00218.2014 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AO1QA UT WOS:000341086900007 ER PT J AU Siroky, BJ Yin, H Dixon, BP Reichert, RJ Hellmann, AR Ramkumar, T Tsuchihashi, Z Bunni, M Dillon, J Bell, PD Sampson, JR Bissler, JJ AF Siroky, Brian J. Yin, Hong Dixon, Bradley P. Reichert, Ryan J. Hellmann, Anna R. Ramkumar, Thiruvamoor Tsuchihashi, Zenta Bunni, Marlene Dillon, Joshua Bell, P. Darwin Sampson, Julian R. Bissler, John J. TI Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE tuberous sclerosis complex; angiomyolipoma; angiotensin II type 1 receptor; pericyte; perivascular epithelioid cell tumor; mammalian target of rapamycin ID TUBEROUS SCLEROSIS COMPLEX; GROWTH-FACTOR; ER STRESS; CELLS; LYMPHANGIOLEIOMYOMATOSIS; EXPRESSION; NEOPLASMS; PROTEIN; KIDNEY; MICE AB Nearly all patients with tuberous sclerosis complex (TSC) develop renal angiomyolipomas, although the tumor cell of origin is unknown. We observed decreased renal angiomyolipoma development in patients with TSC2- polycystic kidney disease 1 deletion syndrome and hypertension that were treated from an early age with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers compared with patients who did not receive this therapy. TSC-associated renal angiomyolipomas expressed ANG II type 1 receptors, platelet-derived growth factor receptor-beta, desmin, alpha-smooth muscle actin, and VEGF receptor 2 but did not express the adipocyte marker S100 or the endothelial marker CD31. Sera of TSC patients exhibited increased vascular mural cell-secreted peptides, such as VEGF-A, VEGF-D, soluble VEGF receptor 2, and collagen type IV. These findings suggest that angiomyolipomas may arise from renal pericytes. ANG II treatment of angiomyolipoma cells in vitro resulted in an exaggerated intracellular Ca2+ response and increased proliferation, which were blocked by the ANG II type 2 receptor antagonist valsartan. Blockade of ANG II signaling may have preventative therapeutic potential for angiomyolipomas. C1 [Siroky, Brian J.; Dixon, Bradley P.; Reichert, Ryan J.; Hellmann, Anna R.] Cincinnati Childrens Hosp Med Ctr, Div Nephrol & Hypertens, Cincinnati, OH 45229 USA. [Yin, Hong] Cincinnati Childrens Hosp Med Ctr, Div Pathol, Cincinnati, OH 45229 USA. [Ramkumar, Thiruvamoor] Novartis Inst Biomed Res, Cambridge, MA USA. [Tsuchihashi, Zenta] Daiichi Sankyo, Parsippany, NJ USA. [Bunni, Marlene; Dillon, Joshua; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Tsuchihashi, Zenta] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Hellmann, Anna R.; Sampson, Julian R.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff CF10 3AX, S Glam, Wales. [Bissler, John J.] Univ Tennessee, Le Bonheur Childrens Hosp, Coll Med, Tuberous Sclerosis Complex Ctr Excellence, Memphis, TN USA. RP Bissler, JJ (reprint author), Le Bonheur Childrens Hosp, Div Pediat, 848 Adams Ave, Memphis, TN 38138 USA. EM jbissler@uthsc.edu FU Rothberg Courage Award from Tuberous Sclerosis Alliance; Tuberous Sclerosis Alliance; Wales Gene Park FX This work was supported by a Rothberg Courage Award from the Tuberous Sclerosis Alliance (to J. J. Bissler), a Fellowship Award from the Tuberous Sclerosis Alliance (to B. J. Siroky), and the Wales Gene Park (to J. R. Sampson). NR 56 TC 9 Z9 9 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP F560 EP F570 DI 10.1152/ajprenal.00569.2013 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AO1QA UT WOS:000341086900008 PM 24920756 ER PT J AU Tregellas, JR AF Tregellas, Jason R. TI Right Versus Left Hippocampal Activity as a Biomarker in Schizophrenia Response SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Tregellas, Jason R.] Univ Colorado, Sch Med, Denver VA Med Ctr, Res Serv, Aurora, CO 80204 USA. [Tregellas, Jason R.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO USA. RP Tregellas, JR (reprint author), Univ Colorado, Sch Med, Denver VA Med Ctr, Res Serv, Aurora, CO 80204 USA. RI Tregellas, Jason/J-3637-2015 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2014 VL 171 IS 9 BP 1001 EP 1001 DI 10.1176/appi.ajp.2014.14050687r PG 1 WC Psychiatry SC Psychiatry GA AO1MU UT WOS:000341077000020 PM 25178756 ER PT J AU Weisbord, SD Mor, MK Sevick, MA Shields, AM Roffman, BL Palevsky, PM Arnold, RM Green, JA Fine, MJ AF Weisbord, Steven D. Mor, Maria K. Sevick, Mary Ann Shields, Anne Marie Roffman, Bruce L. Palevsky, Paul M. Arnold, Robert M. Green, Jamie A. Fine, Michael J. TI Associations of Depressive Symptoms and Pain with Dialysis Adherence, Health Resource Utilization, and Mortality in Patients Receiving Chronic Hemodialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; MANAGEMENT STRATEGIES; HOSPITALIZATION; PREVALENCE; SEVERITY; TERM; METAANALYSIS; VALIDATION; FLUOXETINE AB Background and objectives Depressive symptoms and pain are common in patients receiving chronic hemodialysis, yet their effect on dialysis adherence, health resource utilization, and mortality is not fully understood. This study sought to characterize the longitudinal associations of these symptoms with dialysis adherence, emergency department (ED) visits, hospitalizations, and mortality. Design, setting, participants, & measurements As part of a trial comparing symptom management strategies in patients receiving chronic hemodialysis, this study prospectively assessed depressive symptoms using the Patient Health Questionnaire 9, and pain using the Short-Form McGill Pain Questionnaire, monthly between 2009 and 2011. This study used negative binomial, Poisson, and proportional hazards regression to analyze the longitudinal associations of depressive symptoms and pain, scaled based on 5-point increments in symptom scores, with missed and abbreviated hemodialysis treatments, ED visits, hospitalizations, and mortality, respectively. Results Among 286 patients, moderate-to-severe depressive symptoms were identified on 788 of 4452 (18%) assessments and pain was reported on 3537 of 4459 (79%) assessments. Depressive symptoms were independently associated with missed (incident rate ratio [IRR], 1.21; 95% confidence interval [95% CI], 1.10 to 1.33) and abbreviated (IRR, 1.08; 95% CI, 1.03 to 1.14) hemodialysis treatments, ED visits (IRR, 1.24; 95% CI, 1.12 to 1.37), hospitalizations (IRR, 1.19; 95% CI, 1.10 to 1.30), and mortality (IRR, 1.40; 95% CI, 1.11 to 1.77). Pain was independently associated with abbreviated hemodialysis treatments (IRR, 1.03; 95% CI, 1.01 to 1.06) and hospitalizations (IRR, 1.05; 95% CI, 1.00 to 1.10). Severe pain was independently associated with abbreviated hemodialysis treatments (IRR, 1.16; 95% CI, 1.06 to 1.28), ED visits (IRR, 1.58; 95% CI, 1.28 to 1.94), and hospitalizations (IRR, 1.22; 95% CI, 1.03 to 1.45), but not mortality (hazard ratio, 1.71; 95% CI, 0.81 to 2.96). Conclusions Depressive symptoms and pain are independently associated with dialysis nonadherence and health services utilization. Depressive symptoms are also associated with mortality. Interventions to alleviate these symptoms have the potential to reduce costs and improve patient-centered outcomes. C1 [Weisbord, Steven D.; Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Med Serv Line, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Mor, Maria K.; Shields, Anne Marie; Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Arnold, Robert M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Sch Med, Div Palliat Care, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann; Roffman, Bruce L.] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Green, Jamie A.] Geisinger Med Ctr, Dept Nephrol, Danville, PA 17822 USA. RP Weisbord, SD (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Med Serv Line, 7E Room 120,111F-U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU US Department of Veterans Affairs Health Services Research and Development Merit Review award [IIR 07-190] FX This work was supported by a US Department of Veterans Affairs Health Services Research and Development Merit Review award (IIR 07-190). The opinions expressed in this article are those of the authors and do not represent the views of the US Department of Veterans Affairs or the US Government. NR 43 TC 13 Z9 14 U1 2 U2 10 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2014 VL 9 IS 9 BP 1594 EP 1602 DI 10.2215/CJN.00220114 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AO3ZE UT WOS:000341275200015 PM 25081360 ER PT J AU Berns, JS Ellison, DH Linas, SL Rosner, MH AF Berns, Jeffrey S. Ellison, David H. Linas, Stuart L. Rosner, Mitchell H. TI Training the Next Generation's Nephrology Workforce SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID LUPUS NEPHRITIS; NEXT-GENERATION; KIDNEY-DISEASE; RHEUMATOLOGISTS; COMPETENCE; FELLOWS; REQUIREMENTS; ULTRASOUND; PROGRAMS AB The subspecialty of nephrology faces several critical challenges, including declining interest among medical students and internal medicine residents and worrisome declines in the number of applicants for nephrology fellowships. There is an urgent need to more clearly define the subspecialty and its scope of practice, reinvigorate meaningful research training and activities among trainees, and ensure that fellows who complete training and enter the practice of nephrology are experts in the broad scope of nephrology. This need requires a critical look at fellowship training programs and training requirements. A new workforce analysis is also needed that is not focused on primarily meeting estimated future clinical needs but rather, ensuring that there is alignment of supply and demand for nephrology trainees, which will ensure that those entering nephrology fellowships are highly qualified and capable of becoming outstanding nephrologists and that there are desirable employment opportunities for them when they complete their training. C1 [Berns, Jeffrey S.] Univ Penn, Hosp Univ Penn, Renal Electrolyte & Hypertens Div, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ellison, David H.] Oregon Hlth & Sci Univ, Div Nephrol, Portland, OR 97201 USA. [Ellison, David H.] Portland VA Med Ctr, Portland, OR USA. [Linas, Stuart L.] Univ Colorado, Div Nephrol, Denver Hlth Med Ctr, Denver, CO 80202 USA. [Rosner, Mitchell H.] Univ Virginia, Sch Med, Div Nephrol, Charlottesville, VA 22908 USA. RP Berns, JS (reprint author), Hosp Univ Penn, 3400 Spruce St,1 Founders Pavil, Philadelphia, PA 19104 USA. EM bernsj@uphs.upenn.edu NR 35 TC 6 Z9 6 U1 1 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2014 VL 9 IS 9 BP 1639 EP 1644 DI 10.2215/CJN.00560114 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AO3ZE UT WOS:000341275200020 PM 24970877 ER PT J AU Tafti, BA Mandelkern, M Berenji, GR AF Tafti, Bashir Akhavan Mandelkern, Mark Berenji, Gholam Reza TI Subclinical Seizures as a Pitfall in F-18-FDG PET Imaging of Temporal Lobe Epilepsy SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE PET; epilepsy; subclinical seizure; MRI; electroencephalography ID POSITRON-EMISSION-TOMOGRAPHY; STATUS EPILEPTICUS C1 [Tafti, Bashir Akhavan; Mandelkern, Mark; Berenji, Gholam Reza] Vet Adm Greater Los Angeles Hlth Care Syst, Dept Nucl Med, Los Angeles, CA 90073 USA. RP Berenji, GR (reprint author), Vet Adm Greater Los Angeles Hlth Care Syst, Dept Nucl Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gholam.berenji@va.gov NR 8 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 EI 1536-0229 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD SEP PY 2014 VL 39 IS 9 BP 819 EP 821 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AN6SU UT WOS:000340728300023 PM 24873791 ER PT J AU Arney, J Street, RL Naik, AD AF Arney, Jennifer Street, Richard L., Jr. Naik, Aanand D. TI Factors Shaping Physicians' Willingness to Accommodate Medication Requests SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article DE patient-provider relationships; physician behavior; prescribing patterns/practices; patient-centered care; primary care ID GENERAL-PRACTITIONERS; DECISION-MAKING; COMMUNICATION; PRESCRIBE AB Medical decisions, including physicians' prescribing behaviors, are shaped by a complex interplay of clinical and nonclinical factors. We aim to determine how physician, patient, and relationship characteristics influence physicians' decisions to accommodate brand-name prescription drug requests. We applied multivariate logistic regression to data from the Attitudinal and Behavioral Effects of Direct-to-Consumer Promotion of Prescription Drugs physician survey. We used a national probability sample of 500 primary care and specialty physicians reporting on a clinical encounter that involved a prescription drug request. Independent variables include physician's assessment of the patient's understanding of risks and benefits of a requested medication, whether the patient had the condition the drug treats, duration of the clinical relationship, and physician's age, area of practice, years of experience, and gender. These variables were used to predict whether the physician prescribed the requested drug. Physicians were more willing to accommodate requests when they believed that patients had a clear understanding of the drug's risks and when patients had the condition the drug treats. Primary care practitioners, compared to specialists, had higher odds of prescribing a requested drug. We conclude that clinical and communicative factors shape physicians' decisions to prescribe requested brand-name drugs. Findings offer insight into the influence that direct-to-consumer advertising can have in medical encounters, and may guide efforts to enhance physician-patient communication and shared decision making. C1 [Arney, Jennifer] Univ Houston Clear Lake, Dept Sociol, Houston, TX 77058 USA. [Arney, Jennifer; Street, Richard L., Jr.; Naik, Aanand D.] Michael E DeBakey Dept Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Arney, Jennifer; Street, Richard L., Jr.; Naik, Aanand D.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX USA. RP Arney, J (reprint author), Univ Houston Clear Lake, Dept Sociol, 2700 Bay Area Blvd, Houston, TX 77058 USA. EM Arney@bcm.edu FU Division of Graduate Studies at Arizona State University; National Science Foundation's Division of Social, Behavioral, and Economic Sciences [0828582]; Houston VA HSR&D Center of Excellence [HFP90-020]; National Institute on Aging [K23AG027144] FX The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the Division of Graduate Studies at Arizona State University and by the National Science Foundation's Division of Social, Behavioral, and Economic Sciences (Award ID 0828582). Additional support was provided by the Houston VA HSR&D Center of Excellence (HFP90-020), and the National Institute on Aging (K23AG027144). NR 24 TC 2 Z9 2 U1 0 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0163-2787 EI 1552-3918 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD SEP PY 2014 VL 37 IS 3 BP 349 EP 365 DI 10.1177/0163278712468756 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AN6PE UT WOS:000340716700004 PM 23232050 ER PT J AU Copeland, LA Sako, EY Zeber, JE Pugh, MJ Wang, CP MacCarthy, AA Restrepo, MI Mortensen, EM Lawrence, VA AF Copeland, Laurel A. Sako, Edward Y. Zeber, John E. Pugh, Mary Jo Wang, Chen-Pin MacCarthy, Andrea A. Restrepo, Marcos I. Mortensen, Eric M. Lawrence, Valerie A. TI Mortality after cardiac or vascular operations by preexisting serious mental illness status in the Veterans Health Administration SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Cardiovascular surgical procedures; Comorbidity; Mental disorders; Mortality; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; CARDIOVASCULAR-DISEASE; SCHIZOPHRENIC-PATIENTS; MAJOR DEPRESSION; BIPOLAR DISORDER; NATIONAL SAMPLE; CARE; AFFAIRS; PREVALENCE; ANESTHESIA AB Objective: To estimate 1-year mortality risk associated with preoperative serious mental illness (SMI) as defined by the Veterans Health Administration (schizophrenia, bipolar disorder, posttraumatic stress disorder [PTSD], major depression) following nonambulatory cardiac or vascular surgical procedures compared to patients without SMI. Cardiac/vascular operations were selected because patients with SMI are known to be at elevated risk of cardiovascular disease. Method: Retrospective analysis of system-wide data from electronic medical records of patients undergoing nonambulatory surgery (inpatient or day-of-surgery admission) October 2005-September 2009 with 1-year follow-up (N=55,864; 99% male; <30 days of postoperative hospitalization). Death was hypothesized to be more common among patients with preoperative SMI. Results: One in nine patients had SMI, mostly PTSD (6%). One-year mortality varied by procedure type and SMI status. Patients had vascular operations (64%; 23% died), coronary artery bypass graft (26%; 10% died) or other cardiac operations (11%; 15%-18% died). Fourteen percent of patients with PTSD died, 20% without SMI and 24% with schizophrenia, with other groups intermediate. In multivariable stratified models, SMI was associated with increased mortality only for patients with bipolar disorder following cardiac operations. Bipolar disorder and PTSD were negatively associated with death following vascular operations. Conclusions: SMI is not consistently associated with postoperative mortality in covariate-adjusted analyses. Published by Elsevier Inc. C1 [Copeland, Laurel A.; Zeber, John E.] Baylor Scott & White Hlth, Ctr Appl Hlth Res, Cent Texas Vet Hlth Care Syst, Temple, TX USA. [Copeland, Laurel A.; Zeber, John E.] Texas A&M Hlth Sci Ctr, Dept Med, Bryan Coll Stn, TX USA. [Copeland, Laurel A.; Zeber, John E.] Sch Rural Publ Hlth, Bryan Coll Stn, TX USA. [Sako, Edward Y.; Pugh, Mary Jo; Wang, Chen-Pin; MacCarthy, Andrea A.; Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Sako, Edward Y.; Pugh, Mary Jo; Wang, Chen-Pin; Restrepo, Marcos I.; Lawrence, Valerie A.] UT Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Mortensen, Eric M.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Copeland, LA (reprint author), Scott & White Healthcare, Ctr Appl Hlth Res, Cent Texas Vet Hlth Care Syst, 2102 Birdcreek Dr, Temple, TX 76502 USA. EM LaurelACopeland@gmail.com OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563; Copeland, Laurel/0000-0002-9478-0209 FU VHA, Health Services Research Development [IIR-09-335]; Center for Applied Health Research - Central Texas Veterans Health Care System, Temple, TX; VERDICT Research Center at South Texas Veterans Health Care System, San Antonio, TX; VA North Texas Health Care System, Dallas, TX FX This research was supported by the VHA, Health Services Research & Development, Grant No. IIR-09-335 (L.A. Copeland, principal investigator), with additional support from Center for Applied Health Research jointly sponsored by Central Texas Veterans Health Care System, Temple, TX, and Scott & White Healthcare System, Temple, TX; VERDICT Research Center at South Texas Veterans Health Care System, San Antonio, TX; and VA North Texas Health Care System, Dallas, TX. Views are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs. NR 53 TC 9 Z9 9 U1 5 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP PY 2014 VL 36 IS 5 BP 502 EP 508 DI 10.1016/j.genhosppsych.2014.04.003 PG 7 WC Psychiatry SC Psychiatry GA AN8RT UT WOS:000340872400014 PM 24957928 ER PT J AU Buchanan, R Beckett, RD AF Buchanan, Rachel Beckett, Robert D. TI Assessment of vaccination-related information for consumers available on Facebook (R) SO HEALTH INFORMATION AND LIBRARIES JOURNAL LA English DT Article DE consumer health information; health information needs; information seeking behaviour; social media; social networking ID PERTUSSIS; VACCINES; RUBELLA; AUTISM AB Objectives: To assess the magnitude, interest, purpose and validity of vaccination-related information on Facebook and to determine whether information varies by site viewpoint. Methods: The 10 largest vaccination-focused Facebook (R) pages, groups and places in each category were identified and classified by viewpoint (i.e. anti-, pro-, neutral) and purpose. Number of members, posts per week, likes, comments and shares per post were recorded. Posts were assessed for concordance with CDC and FDA recommendations. Results: Of 30 sites, 43% (n = 13) were anti-vaccination, 7% (n = 2) neutral and 50% (n = 15) pro-vaccination. Most sites were most popular with American users. Median members were similar between anti-vaccination (2703 members, range 337-33 631 members) and pro-vaccination sites (2142 members, range 456-61 565 members, P = 0.262); however, anti-vaccination sites accumulated more posts per week by authors (median 15 vs. 3, P = 0.031) and members (median 33 vs. 1, P < 0.001). Pro-vaccination sites more commonly had commercial purpose (53% [n = 8] vs. 8% [n = 1], P = 0.02). Anti-vaccination sites more commonly gave medical advice (54% [n = 7] vs. 0%, P = 0.004). Overall, 48% (n = 22) of author posts were concordant with regulatory recommendations; concordance was more common on pro-vaccination sites (78% [n = 21] vs. 5% [n = 1], P = 0.0002). Conclusion: Vaccination-related information is prevalent on Facebook regardless of viewpoint; however, anti-vaccination information generates more interest. Anti-vaccination sites were likely to provide medical advice and disagree with regulatory bodies. C1 [Buchanan, Rachel] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Beckett, Robert D.] Univ Manchester, Coll Pharm, Ft Wayne, IN 46845 USA. RP Beckett, RD (reprint author), Univ Manchester, Coll Pharm, 10627 Diebold Rd, Ft Wayne, IN 46845 USA. EM rdbeckett@manchester.edu NR 15 TC 4 Z9 4 U1 8 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1471-1834 EI 1471-1842 J9 HEALTH INFO LIBR J JI Heatlth Info. Libr. J. PD SEP PY 2014 VL 31 IS 3 BP 227 EP 234 DI 10.1111/hir.12073 PG 8 WC Information Science & Library Science SC Information Science & Library Science GA AO2KV UT WOS:000341151500006 PM 25041499 ER PT J AU Peralta, CA Katz, R Newman, AB Psaty, BM Odden, MC AF Peralta, Carmen A. Katz, Ronit Newman, Anne B. Psaty, Bruce M. Odden, Michelle C. TI Systolic and Diastolic Blood Pressure, Incident Cardiovascular Events, and Death in Elderly Persons The Role of Functional Limitation in the Cardiovascular Health Study SO HYPERTENSION LA English DT Article DE activities of daily living; aged; hypertension ID OLDER-ADULTS; HYPERTENSION; MORTALITY; ASSOCIATION; SURVIVAL; STROKE; DISEASE; FRAILTY; SPEED; RISK AB Whether limitation in the ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic and diastolic blood pressure (DBP) with cardiovascular events (CVDs) and death differs is unclear. We evaluated whether limitation in ADL or gait speed modifies the association of systolic blood pressure or DBP with incident CVD (n=2358) and death (n=3547) in the Cardiovascular Health Study. Mean age was 78 +/- 5 and 21% reported limitation in >= 1 ADL. There were 778 CVD and 1289 deaths over 9 years. Among persons without and those with ADL limitation, systolic blood pressure was associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95% confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR 0.49 (0.25, 0.94) for DBP >80, compared with DBP <= 65. Among people with ADL limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91), compared with a DBP of <= 65. Associations did not vary by 15-feet walking speed. ADL can identify elders in whom diastolic hypotension is associated with higher cardiovascular risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders. C1 [Peralta, Carmen A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Peralta, Carmen A.] San Francisco VA Med Ctr, Div Nephrol, San Francisco, CA USA. [Katz, Ronit] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Odden, Michelle C.] Oregon State Univ, Coll Publ Hlth & Human Sci, Corvallis, OR 97331 USA. RP Peralta, CA (reprint author), San Francisco VA Med Ctr, Box 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM carmenalicia.peralta@ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute on Aging [AG023629, K01AG039387]; National Institutes of Diabetes and Digestive and Kidney Diseases [K23SK082793]; Robert Wood Johnson Harold Amos Award; American Heart Association Western States Affiliate [CRP7210088] FX This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by the National Institute on Aging (AG023629). A full list of principal Cardiovascular Health Study (CHS) investigators and institutions can be found at https://CHS-NHLBI.org. C.A. Peralta is supported by the National Institutes of Diabetes and Digestive and Kidney Diseases (K23SK082793) and a Robert Wood Johnson Harold Amos Award. M. C. Odden is supported by the American Heart Association Western States Affiliate (CRP7210088) and the National Institute on Aging (K01AG039387). The content is solely our responsibility and does not necessarily represent the official views of the National Institutes of Health. NR 28 TC 11 Z9 13 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD SEP PY 2014 VL 64 IS 3 BP 472 EP 480 DI 10.1161/HYPERTENSIONAHA.114.03831 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AN9MB UT WOS:000340929900009 PM 24935945 ER PT J AU Dubberke, ER Carling, P Carrico, R Donskey, CJ Loo, VG McDonald, LC Maragakis, LL Sandora, TJ Weber, DJ Yokoe, DS Gerding, DN AF Dubberke, Erik R. Carling, Philip Carrico, Ruth Donskey, Curtis J. Loo, Vivian G. McDonald, L. Clifford Maragakis, Lisa L. Sandora, Thomas J. Weber, David J. Yokoe, Deborah S. Gerding, Dale N. TI Strategies to Prevent Clostridium difficile Infections in Acute Care Hospitals: 2014 Update SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; HIGH-RISK ANTIBIOTICS; ENVIRONMENTAL CONTAMINATION; HYPOCHLORITE SOLUTION; COLONIZED PATIENTS; CONTACT ISOLATION; TOXIN PRODUCTION; ISOLATION ROOMS; UNITED-STATES; NORTH-AMERICA C1 [Dubberke, Erik R.] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Carling, Philip] Boston Univ, Sch Med, Boston, MA 02118 USA. [Carrico, Ruth] Univ Louisville, Sch Med, Div Infect Dis, Louisville, KY 40292 USA. [Donskey, Curtis J.] Case Western Reserve Univ, Louis Stokes Cleveland Vet Affairs Med Ctr, Cleveland, OH 44106 USA. [Loo, Vivian G.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [McDonald, L. Clifford] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA USA. [Maragakis, Lisa L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sandora, Thomas J.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Weber, David J.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Yokoe, Deborah S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yokoe, Deborah S.] Harvard Univ, Sch Med, Boston, MA USA. [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Gerding, Dale N.] Loyola Univ, Stritch Sch Med, Chicago, IL 60611 USA. RP Dubberke, ER (reprint author), Washington Univ, Sch Med, 660 South Euclid Ave,Box 8051, St Louis, MO 63110 USA. EM edubberk@dom.wustl.edu FU Sanofi Pasteur; ViroPharma; Optimer; Merck; Rebiotix; Steris; Pfizer; GOJO Industries FX E.R.D. reports serving as an advisor/consultant for Sanofi Pasteur, Merck, and Pfizer and receiving research grants/contracts from Sanofi Pasteur, ViroPharma, Optimer, Merck, and Rebiotix. P.C. reports serving as an advisor/consultant for Steris and holding a patent/copyright/license with Ecolab. R.C. reports serving on the speakers' bureau for Sanofi Pasteur, MedImmune, Abbott Diabetes Care, and 3M; performing technical writing for Ketchum; and receiving research grants/contracts from Sanofi Pasteur. C.J.D. reports serving as an advisor/consultant for Steris, GOJO Industries, and 3M; receiving honoraria from Ecolab; and receiving research grants/contracts from Merck, ViroPharma, Steris, and Pfizer. V.G.L. reports serving as an advisor/consultant for Optimer Pharmaceuticals. D.J.W. reports serving as an advisor/consultant for Johnson & Johnson and Clorox. D.N.G. reports serving as an advisor/consultant for Merck, Cubist, Novartis, Cangene, Actelion, ViroPharma, Rebiotix, and Sanofi Pasteur; receiving honoraria from Robert Michael; holding a patent/license (no royalties) with ViroPharma; and receiving research grant/contracts from GOJO Industries. L.C.M., L.L.M., T.J.S., and D.S.Y. report no conflicts of interest. NR 120 TC 0 Z9 0 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2014 VL 35 SU 2 BP 628 EP 645 DI 10.1086/676023 PG 18 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AO0QB UT WOS:000341014500008 ER PT J AU Yin, J Reisinger, HS Vander Weg, M Schweizer, ML Jesson, A Morgan, DJ Forrest, G Graham, M Pineles, L Perencevich, EN AF Yin, Jun Reisinger, Heather Schacht Vander Weg, Mark Schweizer, Marin L. Jesson, Andrew Morgan, Daniel J. Forrest, Graeme Graham, Margaret Pineles, Lisa Perencevich, Eli N. TI Establishing Evidence-Based Criteria for Directly Observed Hand Hygiene Compliance Monitoring Programs: A Prospective, Multicenter Cohort Study SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HEALTH-CARE SETTINGS; HAWTHORNE; INFECTIONS; RECOMMENDATIONS; PRECAUTIONS; GUIDELINE; HOSPITALS; FEEDBACK; TIME AB OBJECTIVE. Hand hygiene surveillance programs that rely on direct observations of healthcare worker activity may be limited by the Hawthorne effect. In addition, comparing compliance rates from period to period requires adequately sized samples of observations. We aimed to statistically determine whether the Hawthorne effect is stable over an observation period and statistically derive sample sizes of observations necessary to compare compliance rates. DESIGN. Prospective multicenter cohort study. SETTING. Five intensive care units and 6 medical/surgical wards in 3 geographically distinct acute care hospitals. METHODS. Trained observers monitored hand hygiene compliance during routine care in fixed 1-hour periods, using a standardized collection tool. We estimated the impact of the Hawthorne effect using empirical fluctuation processes and F tests for structural change. Standard sample-size calculation methods were used to estimate how many hand hygiene opportunities are required to accurately measure hand hygiene across various levels of baseline and target compliance. RESULTS. Exit hand hygiene compliance increased after 14 minutes of observation (from 56.2% to 60.5%; P<.001) and increased further after 50 minutes (from 60.5% to 66.0%; P<.001). Entry compliance increased after 38 minutes (from 40.4% to 43.4%; P=.005). Between 79 and 723 opportunities are required during each period, depending on baseline compliance rates (range, 35%-90%) and targeted improvement (5% or 10%). CONCLUSIONS. Limiting direct observation periods to approximately 15 minutes to minimize the Hawthorne effect and determining required number of hand hygiene opportunities observed per period on the basis of statistical power calculations would be expected to improve the validity of hand hygiene surveillance programs. C1 [Yin, Jun] Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA. [Reisinger, Heather Schacht; Vander Weg, Mark; Schweizer, Marin L.; Jesson, Andrew; Perencevich, Eli N.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Reisinger, Heather Schacht; Schweizer, Marin L.; Graham, Margaret; Perencevich, Eli N.] Iowa City Vet Affairs Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA 52246 USA. [Vander Weg, Mark] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Morgan, Daniel J.; Pineles, Lisa] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Morgan, Daniel J.] Vet Affairs Maryland Hlth Care Syst, Baltimore, MD USA. [Forrest, Graeme] Portland VA Med Ctr, Portland, OR USA. RP Perencevich, EN (reprint author), Iowa City Vet Affairs Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA 52246 USA. EM eli-perencevich@uiowa.edu FU Veterans Affairs Health Services Research and Development [09-099] FX Veterans Affairs Health Services Research and Development Investigator Initiated research grant 09-099 (to E.N.P.). NR 22 TC 5 Z9 7 U1 3 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2014 VL 35 IS 9 BP 1163 EP 1168 DI 10.1086/677629 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AN6TI UT WOS:000340729900011 PM 25111925 ER PT J AU Yanke, E Carayon, P Safdar, N AF Yanke, Eric Carayon, Pascale Safdar, Nasia TI Translating Evidence into Practice Using a Systems Engineering Framework for Infection Prevention SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID CLOSTRIDIUM-DIFFICILE INFECTION; CARE-ASSOCIATED INFECTIONS; PATIENT SAFETY; ICU; ACQUISITION; MANAGEMENT; COMMUNITY; QUALITY; UNIT C1 [Yanke, Eric] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. [Carayon, Pascale] Univ Wisconsin, Ctr Qual & Prod Improvement, Dept Ind & Syst Engn, Madison, WI USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Sch Med, Dept Med, Div Infect Dis, Madison, WI USA. RP Safdar, N (reprint author), UWMF Centennial Bldg,1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu FU NCATS NIH HHS [9U54TR000021, UL1 TR000427]; NCRR NIH HHS [1UL1RR025011] NR 40 TC 3 Z9 3 U1 4 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2014 VL 35 IS 9 BP 1176 EP 1182 DI 10.1086/677638 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AN6TI UT WOS:000340729900013 PM 25111927 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Time Trends of US Hospitalization for Esophageal Disease SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE achalasia; dyskinesia; epidemiology of digestive disease; gastroesophageal reflux disease; Mallory-Weiss syndrome ID GASTROESOPHAGEAL-REFLUX DISEASE; PEPTIC-ULCER; ADENOCARCINOMA; METAANALYSIS; OBESITY AB Background and Aims: The occurrence of reflux disease seems to be rising in the United States. The aim of the present study was to follow the time trends of hospitalization for gastroesophageal reflux disease (GERD) and other esophageal disease during the past 4 decades. Methods: US hospital utilization data were available for individual years from 1970 to 2010 through the National Hospital Discharge Survey. Esophageal diagnoses were stratified by their ninth revision of the International Classification of Diseases codes. Annual hospitalizations were expressed as rates per 100,000 living US population. Results: GERD was by far the most common esophageal disorder resulting in hospitalization. However, in only 5% of instances did GERD-related diagnoses constitute the primary cause of hospitalization. Between 1970 and 2010 the rates of GERD-related hospitalizations increased in an exponential manner almost 10-fold. This rise affected both sex and all age groups alike. A 3-fold rise was noted in hospitalizations for esophageal adenocarcinoma. Other esophageal diagnoses, such as achalasia, dyskinesia, or stricture were characterized by falling or stable trends. Conclusions: US hospitalization data show a continued exponential rise in the occurrence of GERD without any signs of leveling off. These trends are likely to represent ongoing changes in the underlying incidence and prevalence of the disease. C1 [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr GI P3, Div Gastroenterol, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 20 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 EI 1539-2031 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD SEP PY 2014 VL 48 IS 8 BP E71 EP E75 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AN6TC UT WOS:000340729100002 PM 24440940 ER PT J AU Langevin, JP Srikandarajah, N Krahl, SE Gorgulho, A Behnke, E Malkasian, D DeSalles, AAF AF Langevin, Jean-Philippe Srikandarajah, Nisaharan Krahl, Scott E. Gorgulho, Alessandra Behnke, Eric Malkasian, Dennis DeSalles, Antonio A. F. TI Eyelid apraxia associated with deep brain stimulation of the periaqueductal gray area SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Deep brain stimulation; Eyelid apraxia; Periaqueductal gray area AB We report a patient with eyelid apraxia following deep brain stimulation of the periaqueductal gray area. Based on the position of our electrode, we argue that the phenomenon is linked to inhibition of the nearby central caudal nucleus of the oculomotor nucleus by high frequency stimulation. Published by Elsevier Ltd. C1 [Langevin, Jean-Philippe; Krahl, Scott E.; Gorgulho, Alessandra; Behnke, Eric; Malkasian, Dennis; DeSalles, Antonio A. F.] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. [Langevin, Jean-Philippe] Greater Los Angeles VA Healthcare Syst, Neurosurg Serv, Los Angeles, CA 90073 USA. [Srikandarajah, Nisaharan] Walton Ctr, Liverpool, Merseyside, England. RP Langevin, JP (reprint author), Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. EM jlangevin@mednet.ucla.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2014 VL 21 IS 9 BP 1652 EP 1653 DI 10.1016/j.jocn.2014.03.002 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN7XZ UT WOS:000340815600038 PM 24726237 ER PT J AU Frank, JW Linder, JA Becker, WC Fiellin, DA Wang, EA AF Frank, Joseph W. Linder, Jeffrey A. Becker, William C. Fiellin, David A. Wang, Emily A. TI Increased Hospital and Emergency Department Utilization by Individuals with Recent Criminal Justice Involvement: Results of a National Survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE vulnerable populations; emergency medicine; hospital medicine; health care costs ID HEALTH-CARE; CORRECTIONAL FACILITIES; NICOTINE DEPENDENCE; FORMER INMATES; PUBLIC-HEALTH; HIGH-RISK; PRISON; RELEASE; PREVALENCE; SERVICES AB Individuals involved with the criminal justice system have increased health needs and poor access to primary care. To examine hospital and emergency department (ED) utilization and related costs by individuals with recent criminal justice involvement. Cross-sectional survey. Non-institutionalized, civilian U.S. adult participants (n = 154,356) of the National Survey on Drug Use and Health (2008-2011). Estimated proportion of adults who reported past year 1) hospitalization or 2) ED utilization according to past year criminal justice involvement, defined as 1) parole or probation, 2) arrest without subsequent correctional supervision, or 3) no criminal justice involvement; estimated annual expenditures using unlinked data from the Medical Expenditure Panel Survey. An estimated 5.7 million adults reported parole or probation and an additional 3.9 million adults reported an arrest in the past year. Adults with recent parole or probation and those with a recent arrest, compared with the general population, had higher rates of hospitalization (12.3 %, 14.3 %, 10.5 %; P < 0.001) and higher rates of ED utilization (39.3 %, 47.2 %, 26.9 %; P < 0.001). Recent parole or probation was an independent predictor of hospitalization (adjusted odds ratio [AOR], 1.21; 95 % confidence interval [CI], 1.02-1.44) and ED utilization (AOR, 1.35; 95 % CI, 1.12-1.63); Recent arrest was an independent predictor of hospitalization (AOR, 1.26; 95 % CI, 1.08-1.47) and ED utilization (AOR, 1.81; 95 % CI, 1.53-2.15). Individuals with recent criminal justice involvement make up 4.2 % of the U.S. adult population, yet account for an estimated 7.2 % of hospital expenditures and 8.5 % of ED expenditures. Recent criminal justice involvement is associated with increased hospital and ED utilization and costs. The criminal justice system may offer an important point of contact for efforts to improve the healthcare utilization patterns of a large and vulnerable population. C1 [Frank, Joseph W.] Univ Colorado, Sch Med, Div Gen Internal Med, Aurora, CO 80045 USA. [Frank, Joseph W.] Denver VA Med Ctr, Denver, CO USA. [Linder, Jeffrey A.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Linder, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA USA. [Becker, William C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Becker, William C.; Fiellin, David A.; Wang, Emily A.] Yale Univ, Sch Med, Gen Internal Med Sect, New Haven, CT USA. RP Frank, JW (reprint author), Univ Colorado, Sch Med, Div Gen Internal Med, 8th Floor,Acad Off 1,12631 E 17th Ave, Aurora, CO 80045 USA. EM joseph.frank@ucdenver.edu OI Fiellin, David/0000-0002-4006-010X FU Health Resources and Services Administration [T32 HP10251]; Veterans Health Administration Health Services Research & Development Career Development Award [08-276]; National Heart, Lung and Blood Institute [K23 HL103720] FX Dr. Frank was supported by the Health Resources and Services Administration through an institutional National Research Service Award (T32 HP10251). Dr. Becker is supported by a Veterans Health Administration Health Services Research & Development Career Development Award (08-276). Dr. Wang is supported by the National Heart, Lung and Blood Institute (K23 HL103720). NR 38 TC 11 Z9 11 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2014 VL 29 IS 9 BP 1226 EP 1233 DI 10.1007/s11606-014-2877-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AN9OO UT WOS:000340936600007 PM 24817280 ER PT J AU Dattalo, M Nothelle, S Tackett, S Larochelle, M Porto-Carreiro, F Yu, E Hanyok, LA AF Dattalo, Melissa Nothelle, Stephanie Tackett, Sean Larochelle, Marc Porto-Carreiro, Fernanda Yu, Eunice Hanyok, Laura A. TI Frontline Account: Targeting Hot Spotters in an Internal Medicine Residency Clinic SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE medical education graduate; primary care redesign; patient-centered care ID SATISFACTION C1 [Dattalo, Melissa; Nothelle, Stephanie; Tackett, Sean; Porto-Carreiro, Fernanda; Yu, Eunice; Hanyok, Laura A.] Johns Hopkins Bayview Med Ctr, Dept Internal Med, Baltimore, MD USA. [Dattalo, Melissa] Univ Wisconsin, Sch Med & Publ Hlth, Div Geriatr & Gerontol, Madison, WI USA. [Dattalo, Melissa] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI 53792 USA. [Larochelle, Marc] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Larochelle, Marc] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. RP Dattalo, M (reprint author), Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI 53792 USA. EM mdattalo@uwhealth.org OI Tackett, Sean/0000-0001-5369-7225 FU NCATS NIH HHS [UL1 TR000427] NR 4 TC 4 Z9 4 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2014 VL 29 IS 9 BP 1305 EP 1307 DI 10.1007/s11606-014-2861-6 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AN9OO UT WOS:000340936600021 PM 24830738 ER PT J AU Bischoff, K Shah, SM Dhaliwal, G Hollander, H AF Bischoff, Kara Shah, Shilpa M. Dhaliwal, Gurpreet Hollander, Harry TI A Heart-Breaking Case of Fever and Rash SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE clinical problem solving; rash; fever ID KAWASAKI-DISEASE; MEDICINE C1 [Bischoff, Kara; Shah, Shilpa M.; Dhaliwal, Gurpreet; Hollander, Harry] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Shah, SM (reprint author), Univ Calif San Francisco, Dept Med, 1545 Divisadero St, San Francisco, CA 94121 USA. EM shilpa.shah@ucsf.edu NR 13 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2014 VL 29 IS 9 BP 1310 EP 1314 DI 10.1007/s11606-014-2775-3 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AN9OO UT WOS:000340936600024 PM 24687288 ER PT J AU Deyo, RA Dworkin, SF Amtmann, D Andersson, G Borenstein, D Carragee, E Carrino, J Chou, R Cook, K DeLitto, A Goertz, C Khalsa, P Loeser, J Mackey, S Panagis, J Rainville, J Tosteson, T Turk, D Von Korff, M Weiner, DK AF Deyo, Richard A. Dworkin, Samuel F. Amtmann, Dagmar Andersson, Gunnar Borenstein, David Carragee, Eugene Carrino, John Chou, Roger Cook, Karon DeLitto, Anthony Goertz, Christine Khalsa, Partap Loeser, John Mackey, Sean Panagis, James Rainville, James Tosteson, Tor Turk, Dennis Von Korff, Michael Weiner, Debra K. TI REPORT OF THE NATIONAL INSTITUTES OF HEALTH TASK FORCE ON RESEARCH STANDARDS FOR CHRONIC LOW BACK PAIN SO JOURNAL OF MANIPULATIVE AND PHYSIOLOGICAL THERAPEUTICS LA English DT Article DE Low Back Pain; Chronic Pain; Patient Outcome Assessment; Research Design ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM PROMIS; FUNCTION ITEM BANK; PRIMARY-CARE; PROGNOSTIC APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES; INTERVENTIONAL THERAPIES AB Objectives: Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed nonspecific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. The purpose of this article is to disseminate the report of the National Institutes of Health (NIH) task force on research standards for cLBP. Methods: The NIH Pain Consortium charged a research task force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. Results: The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimal data set to describe research subjects (drawing heavily on the Patient Reported Outcomes Measurement Information System methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved these recommendations, which investigators should incorporate into NIH grant proposals. Conclusions: The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of cLBP. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect the RTF recommendations will become a dynamic document and undergo continual improvement. C1 [Deyo, Richard A.] OHSU, Dept Family Med, Portland, OR 97239 USA. [Deyo, Richard A.; Chou, Roger] OHSU, Dept Med, Portland, OR 97239 USA. [Deyo, Richard A.] OHSU, Dept Publ Hlth & Community Med, Portland, OR 97239 USA. [Dworkin, Samuel F.] Univ Washington, Dept Psychiat & Behav Sci, Dept Oral Med, Seattle, WA 98195 USA. [Amtmann, Dagmar] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Andersson, Gunnar] Rush Univ, Dept Orthopaed Surg, Med Ctr, Chicago, IL 60612 USA. [Borenstein, David] George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. [Carragee, Eugene] Stanford Univ, Dept Orthopaed Surg, Sch Med, Stanford, CA 94305 USA. [Carrino, John] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Chou, Roger] OHSU, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Cook, Karon] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [DeLitto, Anthony] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA USA. [Goertz, Christine] Palmer Coll Chiropract, Palmer Ctr Chiropract Res, Davenport, IA USA. [Khalsa, Partap] NIH, Div Extramural Res, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Loeser, John] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Loeser, John; Turk, Dennis] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Mackey, Sean] Stanford Univ, Dept Anesthesia & Pain Management, Stanford, CA 94305 USA. [Panagis, James] NIAMSD, NIH, Orthopaed Res Program, Bethesda, MD 20892 USA. [Rainville, James] New England Baptist Hosp, Dept Phys Med & Rehabil, Roxbury Crossing, MA USA. [Tosteson, Tor] Geisel Sch Med Dartmouth, Dept Community & Family Med, Hanover, NH USA. [Tosteson, Tor] Geisel Sch Med Dartmouth, Dartmouth Inst, Hanover, NH USA. [Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Deyo, RA (reprint author), OHSU, Mail Code FM,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM deyor@ohsu.edu FU NCCAM; National Institute for Arthritis, Musculoskeletal, and Skin Diseases, NIH FX This study was supported by the NCCAM and the National Institute for Arthritis, Musculoskeletal, and Skin Diseases, NIH. No conflicts of interest were reported for this study. NR 125 TC 4 Z9 4 U1 8 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-4754 J9 J MANIP PHYSIOL THER JI J. Manip. Physiol. Ther. PD SEP PY 2014 VL 37 IS 7 BP 449 EP 467 DI 10.1016/j.jmpt.2014.07.006 PG 19 WC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation SC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation GA AO2XD UT WOS:000341189600001 PM 25127996 ER PT J AU Pantilat, S Bragg, A O'Riordan, D Ferrell, B Lindenauer, P Lorenz, K Stoneberg, J AF Pantilat, Steven Bragg, Ashley O'Riordan, David Ferrell, Betty Lindenauer, Peter Lorenz, Karl Stoneberg, Jeffrey TI Palliative Care Quality Network: Toward Quality Improvement in Palliative Care SO JOURNAL OF PALLIATIVE CARE LA English DT Meeting Abstract C1 [Pantilat, Steven; Bragg, Ashley; O'Riordan, David] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ferrell, Betty] City Hope Natl Med Ctr, Los Angeles, CA USA. [Lindenauer, Peter] Bay State Med Ctr, Springfield, MA USA. [Lorenz, Karl] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Stoneberg, Jeffrey] Alta Bates Summit Med Ctr, Oakland, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL PI MONTREAL PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD FAL PY 2014 VL 30 IS 3 MA B08-D BP 204 EP 205 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AO3IQ UT WOS:000341223300045 ER PT J AU Onur, T Dang, A AF Onur, Tarik Dang, Alexis TI Reduction of Environmental Temperature Mitigates Local Anesthetic Cytotoxicity in Bovine Articular Chondrocytes SO JOURNAL OF SPORTS SCIENCE AND MEDICINE LA English DT Article DE Clinical hypothermia; local anesthetics; articular cartilage; osteoarthritis; chondrolysis ID IN-VITRO; BUPIVACAINE; CARTILAGE; CHONDROTOXICITY; HYPOTHERMIA; CHONDROLYSIS; ROPIVACAINE; CRYOTHERAPY; EPINEPHRINE; EXPOSURE AB The purpose of this study was to assess whether reducing environmental temperature will lead to increased chondrocyte viability following injury from a single-dose of local anesthetic treatment. Bovine articular chondrocytes from weight bearing portion s of femoral condyles were harvested and cultured. 96-well plates were seeded with 15,000 chondrocytes per well. Chondrocytes were treated with one of the following conditions: ITS Media, 1x PBS, 2% lidocaine, 0.5% bupivacaine, or 0.5% ropivacaine. Each plate was then incubated at 37 degrees C, 23 degrees C, or 4 degrees C for one hour and then returned to media at 37 degrees C. Chondrocyte viability was assessed 24 hours after treatment. Chondrocyte viability is presented as a ratio of the fluorescence of the treatment group over the average of the media group at that temperature (ratio +/- SEM). At 37 degrees C, lidocaine (0.35 +/- 0.04) and bupivacaine (0.30 +/- 0.05) treated chondrocytes show low cell viability when compared to the media (1.00 +/- 0.03) control group (p < 0.001). Lidocaine treated chondrocytes were significantly more viable at 23 degrees C (0.84 +/- 0.08) and 4 degrees C (0.86 +/- 0.085) than at 37 degrees C (p < 0.001). Bupivacaine treated chondrocytes were significantly more viable at 4 degrees C (0.660 +/- 0.073) than at 37 degrees C or 23 degrees C (0.330 +/- 0.069) (p < 0.001 and p = 0.002 respectively). Reducing the temperature from 37 degrees C to 23 degrees C during treatment with lidocaine increases chondrocyte viability following injury. Chondrocytes treated with bupivacaine can be rescued by reducing the temperature to 4 degrees C. C1 [Onur, Tarik; Dang, Alexis] San Francisco VA Med Ctr, Dept Orthopaed Surg, San Francisco, CA 91458 USA. RP Onur, T (reprint author), San Francisco VA Med Ctr, Dept Orthopaed Surg, 1700 Owens St,366, San Francisco, CA 91458 USA. EM t.s.onur17@gmail.com; alexis.dang@gmail.com NR 25 TC 1 Z9 1 U1 0 U2 0 PU JOURNAL SPORTS SCIENCE & MEDICINE PI BURSA PA MEDICAL FACULTY ULUDAG UNIV, DEPT SPORTS MEDICINE, BURSA, 16059, TURKEY SN 1303-2968 J9 J SPORT SCI MED JI J. Sport. Sci. Med. PD SEP PY 2014 VL 13 IS 3 BP 516 EP 521 PG 6 WC Sport Sciences SC Sport Sciences GA AN7BL UT WOS:000340753400008 PM 25177176 ER PT J AU Semkova, K Lott, JP Lazova, R AF Semkova, Kristina Lott, Jason P. Lazova, Rossitza TI Clinicopathologic features and survival in Spitzoid malignant melanoma and conventional malignant melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE conventional melanoma; melanoma; metastasis; prognosis; sentinel lymph node; sentinel lymph node biopsy; Spitzoid malignant melanoma; survival ID MELANOCYTIC TUMORS; BRAF; NRAS; DIAGNOSIS; MUTATION; NEVUS AB Background: Although recent advances in genetics have revealed distinct mutational profiles and molecular signaling pathways associated with Spitzoid malignant melanoma (SMM), less is known about the clinicopathologic characteristics and behavior of SMM compared with conventional melanoma. Objective: We sought to determine the clinicopathologic characteristics and mortality risk associated with SMM and conventional malignant melanoma. Methods: We conducted a retrospective study of 30 patients with SMM and 30 patients with conventional melanoma. The two groups were matched by age, gender, and depth of tumor invasion. Additional patient- and tumor-level characteristics were compared between groups and regression modeling was used to assess relative mortality risk. Results: Unadjusted analyses of SMM and conventional malignant melanoma revealed no significant differences in clinical impression, anatomic location, mitotic rate, and presence of ulceration. Sentinel lymph node biopsy, completion lymphadenectomy, and visceral metastases did not differ between groups. Cox proportional hazards regression showed no differences in mortality between Spitzoid and conventional melanoma. Limitations: Small sample size, short follow-up duration, and residual confounding may limit the accuracy and generalizability of our results. Conclusions: SMM and conventional malignant melanoma differ in some clinicopathologic features. We did not find a statistically significant difference in mortality between the two. C1 [Semkova, Kristina] Med Univ Sofia, Dept Dermatol & Venereol, Sofia, Bulgaria. [Lott, Jason P.; Lazova, Rossitza] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Lott, Jason P.] Yale Univ, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT USA. [Lott, Jason P.] US Dept Vet Affairs, West Haven, CT USA. [Lazova, Rossitza] Yale Canc Ctr, New Haven, CT USA. RP Lazova, R (reprint author), Dermatopathol Lab, 15 York St,POB 208059, New Haven, CT 06520 USA. EM rossitza.lazova@yale.edu OI Lott, Jason/0000-0002-4097-7225 NR 14 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2014 VL 71 IS 3 BP 516 EP 520 DI 10.1016/j.jaad.2014.04.012 PG 5 WC Dermatology SC Dermatology GA AO2JH UT WOS:000341146700042 PM 24836544 ER PT J AU Li, XZ Dai, Y Chuang, PY He, JC AF Li, Xuezhu Dai, Yan Chuang, Peter Y. He, John Cijiang TI Induction of Retinol Dehydrogenase 9 Expression in Podocytes Attenuates Kidney Injury SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; VITAMIN-A; TRANSGENIC MICE; KEY REGULATOR; ACID; DIFFERENTIATION; NEPHROPATHY; RECEPTOR; PROTEIN; NEF AB The intracellular concentration of retinoic acid is determined by two sequential oxidation reactions that convert retinol to retinoic acid. We recently demonstrated that retinoic acid synthesis is significantly impaired in glomeruli of HIV-1 transgenic mice (Tg26), a murine model of HIV-associated nephropathy. This impaired retinoic acid synthesis correlates with reduced renal expression of retinol dehydrogenase 9, which catalyzes the rate-limiting step of retinoic acid synthesis by converting retinol to retinal. Because retinoic acid has renal protective effects and can induce podocyte differentiation, we hypothesized that restoration of retinoic acid synthesis could slow the progression of renal disease. Herein, we demonstrate that overexpression of retinol dehydrogenase 9 in cultured podocytes induces the expression of podocyte differentiation markers. Furthermore, we confirm that podocyte-specific overexpression of retinol dehydrogenase 9 in mice with established kidney disease due to either HIV-associated nephropathy or adriamycin-induced nephropathy decreases proteinuria, attenuates kidney injury, and restores podocyte differentiation markers. Our data suggest that restoration of retinoic acid synthesis could be a new approach to treat kidney disease. C1 [Li, Xuezhu; Dai, Yan; Chuang, Peter Y.; He, John Cijiang] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA. [Li, Xuezhu] Tongji Univ, Sch Med, Shanghai East Hosp, Dept Nephrol, Shanghai 200092, Peoples R China. [Dai, Yan; He, John Cijiang] James J Peters Vet Affairs Med Ctr, Renal Sect, Bronx, NY USA. RP He, JC (reprint author), Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM cijiang.he@mssm.edu FU National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [1R01-DK078897, 1R01-DK088541, P01-DK56492, 5K08-DK082760]; Chinese 973 fund [2012CB517601] FX J.C.H. and P.Y.C. are supported by grants from the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (1R01-DK078897, 1R01-DK088541, and P01-DK56492 to J.C.H.; 5K08-DK082760 to P.Y.C.). J.C.H. is also supported by the Chinese 973 fund (2012CB517601). NR 39 TC 1 Z9 1 U1 1 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2014 VL 25 IS 9 BP 1933 EP 1941 DI 10.1681/ASN.2013111150 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AO1FY UT WOS:000341059200010 PM 24652806 ER PT J AU Leonardis, RL Duvvuri, U Mehta, D AF Leonardis, Rachel L. Duvvuri, Umamaheswar Mehta, Deepak TI Transoral Robotic-Assisted Laryngeal Cleft Repair in the Pediatric Patient SO LARYNGOSCOPE LA English DT Article DE Robotic; pediatric robotics; transoral robotics; laryngeal cleft repair ID SURGERY; SAFETY AB Objectives/Hypothesis: To assess the feasibility of performing robotic-assisted laryngeal cleft repair in the pediatric population. Study Design: Retrospective chart review at a tertiary academic children's hospital. Methods: All patients underwent transoral robotic-assisted laryngeal cleft repair from March 2011 to June 2013. Demographics, robotic docking time, operative time, and postoperative course and swallowing function were collected and analyzed. Results: Five children, three male and two female, underwent successful transoral robotic-assisted laryngeal cleft repair for closure of a type I laryngeal cleft. Mean age at time of surgery was 21.6 months (standard deviation 6.1 months; range, 15-29 months). From case 1 to case 5, robotic docking time (18-10 minutes), robotic operative time (102-36 minutes), and total operating room time (173-105 minutes) decreased. There were no complications with time until extubation (range, 2-3 days), length of intensive care unit stay (range, 3-4 days), and total hospital stay (range, 3-5 days) within acceptable range following laryngeal cleft repair. Modified barium swallow (two patients) or fiberoptic endoscopic evaluation of swallowing (three patients) was performed postoperatively, with all patients showing complete resolution of penetration and aspiration. In addition, all patients experienced subjective resolution of dysphagia and/or choking with feeds postoperatively. Conclusions: Transoral robotic-assisted laryngeal cleft repair may offer specific advantages over a traditional endoscopic approach. In our experience, the procedure was well tolerated and associated with definitive surgical cure in all patients. The scope of robotic technology continually expands and should be considered a feasible tool at an institution-based level. C1 [Leonardis, Rachel L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] Univ Pittsburgh, Dept Otolaryngol, Med Ctr, Pittsburgh, PA 15260 USA. [Mehta, Deepak] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. RP Duvvuri, U (reprint author), Univ Pittsburgh, Inst Eye & Ear, Suite 300,203 Lothrop St, Pittsburgh, PA 15213 USA. EM duvvuriu@upmc.edu FU Department of Veterans Affairs; PNC foundation FX This work was funded in part by the Department of Veterans Affairs, and the PNC foundation (U.D.). NR 9 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2014 VL 124 IS 9 BP 2167 EP 2169 DI 10.1002/lary.24680 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AO1UM UT WOS:000341100500047 PM 24648210 ER PT J AU Korn, LL Thomas, HL Hubbeling, HG Spencer, SP Sinha, R Simkins, HMA Salzman, NH Bushman, FD Laufer, TM AF Korn, L. L. Thomas, H. L. Hubbeling, H. G. Spencer, S. P. Sinha, R. Simkins, H. M. A. Salzman, N. H. Bushman, F. D. Laufer, T. M. TI Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid cells SO MUCOSAL IMMUNOLOGY LA English DT Article ID COMMENSAL BACTERIA; MICROBIAL COMMUNITIES; NKP46(+) CELLS; DEFICIENT MICE; HOMEOSTASIS; IMMUNITY; INFLAMMATION; HOST; MICROFLORA; INFECTION AB The innate and adaptive immune systems in the intestine cooperate to maintain the integrity of the intestinal barrier and to regulate the composition of the resident microbiota. However, little is known about the crosstalk between the innate and adaptive immune systems that contribute to this homeostasis. We find that CD4 + Tcells regulate the number and function of barrier-protective innate lymphoid cells (ILCs), as well as production of antimicrobial peptides (AMPs), Reg3 gamma and Reg3 beta. RAG1 - / - mice lacking T and B cells had elevated ILC numbers, interleukin-22 (IL-22) production, and AMP expression, which were corrected by replacement of CD4 + Tcells. Major histocompatibility class II - / - (MHCII - / -) mice lacking CD4 + T cells also had increased ILCs, IL- 22, and AMPs, suggesting that negative regulation by CD4 + T cells occurs at steady state. We utilized transfers and genetically modified mice to show that reduction of IL- 22 is mediated by conventional CD4 + Tcells and is T- cell receptor dependent. The IL-22-AMP axis responds to commensal bacteria; however, neither the bacterial repertoire nor the gross localization of commensal bacteria differed between MHCII + / - and MHCII - / - littermates. These data define a novel ability of CD4 + T cells to regulate intestinal IL-22-producing ILCs and AMPs. C1 [Korn, L. L.; Thomas, H. L.; Hubbeling, H. G.; Spencer, S. P.; Simkins, H. M. A.; Laufer, T. M.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Hubbeling, H. G.; Laufer, T. M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Sinha, R.; Bushman, F. D.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Salzman, N. H.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. RP Laufer, TM (reprint author), Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. EM tlaufer@mail.med.upenn.edu OI Salzman, Nita/0000-0003-0939-6139; Bushman, Frederic/0000-0003-4740-4056 FU Penn-CHOP Joint Center for Digestive, Liver and Pancreatic Medicine [P30-DK050306]; Penn Genome Frontiers Institute; University of Pennsylvania Center for AIDS Research (CFAR) [P30 AI 045008, R01-AI57757]; Training Program in Rheumatic Disease [5T32AR007442-25] FX This work was supported by a pilot grant from the Penn-CHOP Joint Center for Digestive, Liver and Pancreatic Medicine P30-DK050306, the Penn Genome Frontiers Institute, and the University of Pennsylvania Center for AIDS Research (CFAR) P30 AI 045008, and R01-AI57757 (NHS). LLK was supported by the Training Program in Rheumatic Disease 5T32AR007442-25. NR 45 TC 19 Z9 19 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2014 VL 7 IS 5 BP 1045 EP 1057 DI 10.1038/mi.2013.121 PG 13 WC Immunology SC Immunology GA AO3FW UT WOS:000341215600003 PM 24448096 ER PT J AU Bethoux, F Rogers, HL Nolan, KJ Abrams, GM Annaswamy, TM Brandstater, M Browne, B Burnfield, JM Feng, WW Freed, MJ Geis, C Greenberg, J Gudesblatt, M Ikramuddin, F Jayaraman, A Kautz, SA Lutsep, HL Madhavan, S Meilahn, J Pease, WS Rao, N Seetharama, S Sethi, P Turk, MA Wallis, RA Kufta, C AF Bethoux, Francois Rogers, Helen L. Nolan, Karen J. Abrams, Gary M. Annaswamy, Thiru M. Brandstater, Murray Browne, Barbara Burnfield, Judith M. Feng, Wuwei Freed, Mitchell J. Geis, Carolyn Greenberg, Jason Gudesblatt, Mark Ikramuddin, Farha Jayaraman, Arun Kautz, Steven A. Lutsep, Helmi L. Madhavan, Sangeetha Meilahn, Jill Pease, William S. Rao, Noel Seetharama, Subramani Sethi, Pramod Turk, Margaret A. Wallis, Roi Ann Kufta, Conrad TI The Effects of Peroneal Nerve Functional Electrical Stimulation Versus Ankle-Foot Orthosis in Patients With Chronic Stroke: A Randomized Controlled Trial SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE functional electrical stimulation; stroke rehabilitation; foot drop; gait speed; quality of life; ankle-foot orthosis ID AMERICAN-HEART-ASSOCIATION; PERFORMANCE-MEASURES; WALKING PERFORMANCE; CHRONIC HEMIPARESIS; DROP STIMULATOR; GAIT; RELIABILITY; NEUROPROSTHESIS; SCALE; REHABILITATION AB Background. Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle-foot orthoses (AFO) for treatment of foot drop poststroke, but few randomized controlled comparisons exist. Objective. To compare changes in gait and quality of life (QoL) between FES and an AFO in individuals with foot drop poststroke. Methods. In a multicenter randomized controlled trial (ClinicalTrials.gov#NCT01087957) with unblinded outcome assessments, 495 Medicare-eligible individuals at least 6 months poststroke wore FES or an AFO for 6 months. Primary endpoints: 10-Meter Walk Test (10MWT), a composite of the Mobility, Activities of Daily Living/Instrumental Activities of Daily Living, and Social Participation subscores on the Stroke Impact Scale (SIS), and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test, GaitRite Functional Ambulation Profile (FAP), Modified Emory Functional Ambulation Profile (mEFAP), Berg Balance Scale (BBS), Timed Up and Go, individual SIS domains, and Stroke-Specific Quality of Life measures. Multiply imputed intention-to-treat analyses were used with primary endpoints tested for noninferiority and secondary endpoints tested for superiority. Results. A total of 399 subjects completed the study. FES proved noninferior to the AFO for all primary endpoints. Both the FES and AFO groups improved significantly on the 10MWT. Within the FES group, significant improvements were found for SIS composite score, total mFEAP score, individual Floor and Obstacle course time scores of the mEFAP, FAP, and BBS, but again, no between-group differences were found. Conclusions. Use of FES is equivalent to the AFO. Further studies should examine whether FES enables better performance in tasks involving functional mobility, activities of daily living, and balance. C1 [Bethoux, Francois] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Rogers, Helen L.; Kufta, Conrad] Innovat Neurotron, Austin, TX USA. [Nolan, Karen J.] Kessler Fdn, Res Ctr, W Orange, NJ USA. [Nolan, Karen J.] Rutgers New Jersey Med Sch, Newark, NJ USA. [Abrams, Gary M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Annaswamy, Thiru M.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Annaswamy, Thiru M.] UT Southwestern Med Ctr, Dallas, TX USA. [Brandstater, Murray] Loma Linda Univ, Med Ctr, Loma Linda, CA USA. [Browne, Barbara] Magee Mem Rehabilitat Ctr, Philadelphia, PA USA. [Burnfield, Judith M.] Madonna Rehabil Hosp, Lincoln, NE USA. [Feng, Wuwei] Med Univ S Carolina, Charleston, SC 29425 USA. [Freed, Mitchell J.] Florida Hosp, Neurosci & Orthoped Res Inst, Orlando, FL USA. [Geis, Carolyn] Halifax Hlth Ctr Neurosci, Daytona Beach, FL USA. [Greenberg, Jason] Helen Hayes Hosp, New York, NY USA. [Gudesblatt, Mark] South Shore Neurol Associates, Patchogue, NY USA. [Ikramuddin, Farha] Univ Minnesota Fairview, Minneapolis, MN USA. [Jayaraman, Arun] Rehabil Inst Chicago, Chicago, IL 60611 USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Lutsep, Helmi L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Madhavan, Sangeetha] Univ Illinois, Chicago, IL USA. [Meilahn, Jill] Marshfield Clin Res Fdn, Marshfield, WI 54449 USA. [Pease, William S.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA. [Rao, Noel] Marianjoy Rehabil Hosp, Wheaton, IL USA. [Seetharama, Subramani] Hartford Hosp, Hartford, CT 06115 USA. [Sethi, Pramod] Guilford Neurol Associates, Greensboro, NC USA. [Turk, Margaret A.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Wallis, Roi Ann] West Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Bethoux, F (reprint author), Cleveland Clin Fdn, Desk U10,9500 Euclid Ave, Cleveland, OH 44195 USA. EM bethouf@ccf.org OI Nolan, PhD, Karen J/0000-0002-4667-0873 FU Innovative Neurotronics FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by Innovative Neurotronics. NR 38 TC 16 Z9 19 U1 6 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 EI 1552-6844 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD SEP PY 2014 VL 28 IS 7 BP 688 EP 697 DI 10.1177/1545968314521007 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AN6ST UT WOS:000340728100008 PM 24526708 ER PT J AU Bramlett, HM Dietrich, WD Marcillo, A Mawhinney, LJ Furones-Alonso, O Bregy, A Peng, Y Wu, Y Pan, J Wang, J Guo, XE Bauman, WA Cardozo, C Qin, W AF Bramlett, H. M. Dietrich, W. D. Marcillo, A. Mawhinney, L. J. Furones-Alonso, O. Bregy, A. Peng, Y. Wu, Y. Pan, J. Wang, J. Guo, X. E. Bauman, W. A. Cardozo, C. Qin, W. TI Effects of low intensity vibration on bone and muscle in rats with spinal cord injury SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone loss; Bone marrow cells; Low intensity vibration; Spinal cord injury ID WHOLE-BODY VIBRATION; LEVEL MECHANICAL VIBRATIONS; MINERAL DENSITY; LOW-MAGNITUDE; SKELETAL-MUSCLE; HIGH-FREQUENCY; GROWING RATS; RISK-FACTORS; SOST GENE; STIMULATION AB Spinal cord injury (SCI) causes rapid and marked bone loss. The present study demonstrates that low-intensity vibration (LIV) improves selected biomarkers of bone turnover and gene expression and reduces osteoclastogenesis, suggesting that LIV may be expected to benefit to bone mass, resorption, and formation after SCI. Sublesional bone is rapidly and extensively lost following spinal cord injury (SCI). Low-intensity vibration (LIV) has been suggested to reduce loss of bone in children with disabilities and osteoporotic women, but its efficacy in SCI-related bone loss has not been tested. The purpose of this study was to characterize effects of LIV on bone and bone cells in an animal model of SCI. The effects of LIV initiated 28 days after SCI and provided for 15 min twice daily 5 days each week for 35 days were examined in female rats with moderate severity contusion injury of the mid-thoracic spinal cord. Bone mineral density (BMD) of the distal femur and proximal tibia declined by 5 % and was not altered by LIV. Serum osteocalcin was reduced after SCI by 20 % and was increased by LIV to a level similar to that of control animals. The osteoclastogenic potential of bone marrow precursors was increased after SCI by twofold and associated with 30 % elevation in serum CTX. LIV reduced the osteoclastogenic potential of marrow precursors by 70 % but did not alter serum CTX. LIV completely reversed the twofold elevation in messenger RNA (mRNA) levels for SOST and the 40 % reduction in Runx2 mRNA in bone marrow stromal cells resulting from SCI. The findings demonstrate an ability of LIV to improve selected biomarkers of bone turnover and gene expression and to reduce osteoclastogenesis. The study indicates a possibility that LIV initiated earlier after SCI and/or continued for a longer duration would increase bone mass. C1 [Bramlett, H. M.; Dietrich, W. D.; Marcillo, A.; Mawhinney, L. J.; Furones-Alonso, O.; Bregy, A.] Univ Miami, Miller Sch Med, Miami Project Cure Paralysis, Dept Neurol Surg, Miami, FL 33136 USA. [Bramlett, H. M.] Bruce W Carter Miami VA Med Ctr, Miami, FL USA. [Peng, Y.; Wu, Y.; Pan, J.; Bauman, W. A.; Cardozo, C.; Qin, W.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY 10468 USA. [Wang, J.; Guo, X. E.] Columbia Univ, Dept Biomed Engn, New York, NY USA. [Bauman, W. A.; Cardozo, C.; Qin, W.] Mt Sinai Sch Med, New York, NY USA. RP Qin, W (reprint author), James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Weiping.Qin@mssm.edu FU Veterans Health Administration; Biomedical Laboratory Research and Development Service [BX000521]; Department of Defense [SC090504]; Miami Project to Cure Paralysis; Rehabilitation Research and Development Service [B9212-C, B0687-R] FX This work was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (B9212-C and B0687-R), Biomedical Laboratory Research and Development Service (BX000521), the Department of Defense (#SC090504), and The Miami Project to Cure Paralysis. We wish to thank Drs. Edelle Field-Fote and Mark Nash for critical reading of the manuscript. NR 59 TC 5 Z9 6 U1 1 U2 8 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD SEP PY 2014 VL 25 IS 9 BP 2209 EP 2219 DI 10.1007/s00198-014-2748-8 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN6AK UT WOS:000340675200006 PM 24861907 ER PT J AU Inslicht, SS Richards, A Madden, E Rao, MN O'Donovan, A Talbot, LS Rucker, E Metzler, TJ Hauger, RL Neylan, TC AF Inslicht, Sabra S. Richards, Anne Madden, Erin Rao, Madhu N. O'Donovan, Aoife Talbot, Lisa S. Rucker, Evelyn Metzler, Thomas J. Hauger, Richard L. Neylan, Thomas C. TI Sex differences in neurosteroid and hormonal responses to metyrapone in posttraumatic stress disorder SO PSYCHOPHARMACOLOGY LA English DT Article DE Sex differences; Posttraumatic stress disorder; Progesterone; Allopregnanolone; ACTH; Metyrapone ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; GABA(A) RECEPTOR FUNCTION; DEXAMETHASONE-SUPPRESSION; PARAVENTRICULAR NUCLEUS; GLUCOCORTICOID-RECEPTOR; GENDER-DIFFERENCES; RAT HYPOTHALAMUS; COMBAT VETERANS; MESSENGER-RNA AB Mechanisms contributing to sex differences in the regulation of acute stress responsivity and their effect on the increased incidence of posttraumatic stress disorder (PTSD) in women are poorly understood. The reproductive hormone, progesterone, through conversion to allopregnanolone (ALLO), suppresses the hypothalamic pituitary adrenal (HPA) axis and has potent anxiolytic effects. The potential that progesterone and allopregnanolone reactivity modulate HPA axis responses and account for sex differences in PTSD has not been previously examined. The present study examined the effects of sex and PTSD on adrenocorticotropic hormone (ACTH), progesterone, and allopregnanolone responses to metyrapone and whether progesterone and allopregnanolone reactivity could affect the ACTH response in PTSD. Healthy medication-free male and premenopausal follicular phase female participants with chronic PTSD (n = 43; 49 % female) and controls (n = 42; 50 % female) completed an overnight metyrapone challenge and ACTH, progesterone, and allopregnanolone were obtained by repeated blood sampling. The increase in ACTH response to metyrapone was higher in PTSD subjects compared to controls and in women compared to men. Contrary to our initial prediction of an inverse relationship, progesterone and allopregnanolone were positively associated with ACTH. Progesterone and allopregnanolone partially mediated the relationship between PTSD and ACTH. Our findings of increased ACTH to metyrapone in PTSD and in women may reflect heightened hypothalamic CRF hypersecretion. Progesterone and allopregnanolone partially mediated the ACTH response in PTSD. Further characterizing sex differences in these processes will advance our understanding of the pathophysiology of PTSD, and may ultimately lead to better-targeted, more effective treatment. C1 [Inslicht, Sabra S.; Richards, Anne; Madden, Erin; Rao, Madhu N.; O'Donovan, Aoife; Talbot, Lisa S.; Rucker, Evelyn; Metzler, Thomas J.; Neylan, Thomas C.] San Francisco VA Med Ctr, Stress & Hlth Res Program, San Francisco, CA 94121 USA. [Inslicht, Sabra S.; Richards, Anne; Madden, Erin; O'Donovan, Aoife; Talbot, Lisa S.; Rucker, Evelyn; Metzler, Thomas J.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Inslicht, Sabra S.; Richards, Anne; Madden, Erin; Rao, Madhu N.; O'Donovan, Aoife; Talbot, Lisa S.; Rucker, Evelyn; Metzler, Thomas J.; Neylan, Thomas C.] Vet Hlth Res Inst, NCIRE, San Francisco, CA 94121 USA. [Rao, Madhu N.] Univ Calif San Francisco, Dept Med, Div Endocrinol, San Francisco, CA 94143 USA. [Hauger, Richard L.] San Diego VA Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA 92161 USA. [Hauger, Richard L.] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. RP Inslicht, SS (reprint author), San Francisco VA Med Ctr, Stress & Hlth Res Program, 4150 Clement St 116P, San Francisco, CA 94121 USA. EM sabra.inslicht@ucsf.edu FU National Institute for Mental Health [5R01MH073978-04, 5R34MH077667-03]; Veterans Health Research Institute; Mental Illness Research and Education Clinical Center of the US Veterans Health Administration; Clinical Research Center of the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 RR024131]; BLR&D Merit Review grant from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; VA Center of Excellence for Stress and Mental Health (CESAMH); NIH/NIMH [MH074697] FX This research and development project was conducted by the Stress and Health Research Program at the San Francisco VA Medical Center and is made possible by a research grant that was awarded and administered by the US Army Medical Research and Materiel Command (USAMRMC) and the Telemedicine & Advanced Technology Research Center (TATRC), at Fort Detrick, MD (SI: W81XWH-05-2-0094). This study was also supported by the National Institute for Mental Health (TCN: 5R01MH073978-04, 5R34MH077667-03), the Veterans Health Research Institute, the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration, and the Clinical Research Center of the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. RLH was supported by a BLR&D Merit Review grant from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, the VA Center of Excellence for Stress and Mental Health (CESAMH), and a NIH/NIMH (MH074697) RO1 grant. NR 106 TC 3 Z9 3 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2014 VL 231 IS 17 BP 3581 EP 3595 DI 10.1007/s00213-014-3621-3 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AN6DN UT WOS:000340684300030 PM 24952092 ER PT J AU Montgomery, AE Fargo, JD Kane, V Culhane, DP AF Montgomery, Ann Elizabeth Fargo, Jamison D. Kane, Vincent Culhane, Dennis P. TI Development and Validation of an Instrument to Assess Imminent Risk of Homelessness Among Veterans SO PUBLIC HEALTH REPORTS LA English DT Article ID PREVENTION; ASSISTANCE AB Objectives. Veterans are overrepresented within the homeless population compared with their non-veteran counterparts, particularly when controlling for poverty. The U.S. Department of Veterans Affairs (VA) aims to prevent new episodes of homelessness by targeting households at greatest risk; however, there are no instruments that systematically assess veterans' risk of homelessness. We developed and tested a brief screening instrument to identify imminent risk of homelessness among veterans accessing VA health care. Methods. The study team developed initial assessment items, conducted cognitive interviews with veterans experiencing homelessness, refined pilot items based on veterans' and experts' feedback and results of psychometric analyses, and assigned weights to items in the final instrument to indicate a measure of homelessness risk. Results. One-third of veterans who responded to the field instrument reported imminent risk of homelessness (i.e., housing instability in the previous 90 days or expected in the next 90 days). The reliability coefficient for the instrument was 0.85, indicating good internal consistency. Veterans who had a recent change in income, had unpaid housing expenses, were living temporarily with family and friends, needed help to get or keep housing, and had poor rental and credit histories were more likely to report a risk of homelessness than those who did not: Conclusion. This study provides the field with an instrument to identify individuals and households at risk of or experiencing homelessness, which is necessary to prevent and end homelessness. In addition, it supports VA's investment in homelessness prevention and rapid rehousing services for veterans who are experiencing or are at risk for homelessness. C1 [Montgomery, Ann Elizabeth; Fargo, Jamison D.; Kane, Vincent; Culhane, Dennis P.] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Philadelphia, PA 19104 USA. [Fargo, Jamison D.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Culhane, Dennis P.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Montgomery, AE (reprint author), US Dept Vet Affairs, Natl Ctr Homelessness Vet, 4100 Chester Ave,Ste 201, Philadelphia, PA 19104 USA. EM ann.montgomery2@va.gov NR 16 TC 2 Z9 2 U1 0 U2 9 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 2014 VL 129 IS 5 BP 428 EP 436 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO2DC UT WOS:000341124700005 PM 25177054 ER PT J AU Sprangers, MAG Thong, MSY Bartels, M Barsevick, A Ordonana, J Shi, QL Wang, XS Klepstad, P Wierenga, EA Singh, JA Sloan, JA AF Sprangers, Mirjam A. G. Thong, Melissa S. Y. Bartels, Meike Barsevick, Andrea Ordonana, Juan Shi, Qiuling Wang, Xin Shelley Klepstad, Pal Wierenga, Eddy A. Singh, Jasvinder A. Sloan, Jeff A. TI Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update SO QUALITY OF LIFE RESEARCH LA English DT Review DE Biological pathways; Genes; Molecular markers; Quality of life; Patient-reported outcomes (PROs) ID GENOME-WIDE ASSOCIATION; BREAST-CANCER SURVIVORS; METHYLTRANSFERASE GENOTYPE VAL158MET; SINGLE NUCLEOTIDE POLYMORPHISMS; MAJOR DEPRESSIVE DISORDER; FUNCTIONAL POLYMORPHISM; PERSONALITY DIMENSIONS; SLEEP DISTURBANCE; SYMPTOM CLUSTER; MENTAL-HEALTH AB There is compelling evidence of a genetic foundation of patient-reported quality of life (QOL). Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. The objective was to provide an updated overview of the biological pathways, candidate genes, and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception, and the catechol-O-methyltransferase (COMT) gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients' QOL. C1 [Sprangers, Mirjam A. G.; Thong, Melissa S. Y.] Univ Amsterdam, Acad Med Ctr, Dept Med Psychol J3 211, NL-1105 AZ Amsterdam, Netherlands. [Thong, Melissa S. Y.] Tilburg Univ, Ctr Res Psychol Somat Dis CoRPS, NL-5000 LE Tilburg, Netherlands. [Bartels, Meike] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Barsevick, Andrea] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Ordonana, Juan] Univ Murcia, Dept Human Anat & Psychobiol, Murcia, Spain. [Shi, Qiuling; Wang, Xin Shelley] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. [Klepstad, Pal] St Olavs Univ Hosp, Chair Dept Intens Care Med, Trondheim, Norway. [Wierenga, Eddy A.] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Rochester, MN USA. [Sloan, Jeff A.] Mayo Clin, Sect Canc Ctr Stat, Dept Hlth Sci, Div Biomed Stat & Informat, Rochester, MN USA. RP Sprangers, MAG (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Med Psychol J3 211, Meibergdreef 15, NL-1105 AZ Amsterdam, Netherlands. EM m.a.sprangers@amc.uva.nl RI Ordonana, Juan/M-1196-2014; Bartels, Meike/D-4492-2014 OI Ordonana, Juan/0000-0001-7779-6017; Bartels, Meike/0000-0002-9667-7555; Barsevick, Andrea/0000-0003-1829-6826 FU Social Psychology Fellowship from the Dutch Cancer Society [UVT2011-4960] FX The present research is supported in part by a Social Psychology Fellowship from the Dutch Cancer Society to Melissa Thong (#UVT2011-4960). NR 66 TC 15 Z9 15 U1 1 U2 21 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD SEP PY 2014 VL 23 IS 7 BP 1997 EP 2013 DI 10.1007/s11136-014-0656-1 PG 17 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AN4ZF UT WOS:000340597900009 PM 24604075 ER PT J AU Gonzalez, S Camarillo, C Rodriguez, M Ramirez, M Zavala, J Armas, R Contreras, SA Contreras, J Dassori, A Almasy, L Flores, D Jerez, A Raventos, H Ontiveros, A Nicolini, H Escamilla, M AF Gonzalez, Suzanne Camarillo, Cynthia Rodriguez, Marco Ramirez, Mercedes Zavala, Juan Armas, Regina Contreras, Salvador A. Contreras, Javier Dassori, Albana Almasy, Laura Flores, Deborah Jerez, Alvaro Raventos, Henriette Ontiveros, Alfonso Nicolini, Humberto Escamilla, Michael TI A Genome-Wide Linkage Scan of Bipolar Disorder in Latino Families Identifies Susceptibility loci at 8q24 and 14q32 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetics; family studies; Mexican; Mexican-American; Central-American; bipolar disorder ID AFFECTIVE PUERPERAL PSYCHOSIS; DNA-BINDING ACTIVITY; ASSOCIATION ANALYSIS; SLEEP DISTURBANCE; CHROMOSOME 8Q24; I DISORDER; SCHIZOAFFECTIVE DISORDER; GENETIC-HETEROGENEITY; TRANSCRIPTION FACTOR; FRONTAL-CORTEX AB A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5 cM grid with an average genetic coverage of 0.67 cM. Multipoint analyses were conducted across the genome using non-parametric Kong & Cox LOD scores along with S-all statistics for all relative pairs. Suggestive and significant genome-wide thresholds were calculated based on 1000 simulations. Single-marker association tests in the presence of linkage were performed assuming a multiplicative model with a population prevalence of 2%. We identified two genome-wide significant susceptibly loci for BP at 8q24 and 14q32, and a third suggestive locus at 2q13-q14. Within these three linkage regions, the top associated single marker (rs1847694, P = 2.40 x 10(-5)) is located 195 Kb upstream of DPP10 in Chromosome 2. DPP10 is prominently expressed in brain neuronal populations, where it has been shown to bind and regulate Kv4-mediated A-type potassium channels. Taken together, these results provide additional evidence that 8q24, 14q32, and 2q13-q14 are susceptibly loci for BP and these regions may be involved in the pathogenesis of BP in the Latino population. (C) 2014 Wiley Periodicals, Inc. C1 [Gonzalez, Suzanne; Camarillo, Cynthia; Rodriguez, Marco; Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael] Texas Tech Univ, Hlth Sci Ctr, Ctr Excellence Neurosci, Paul L Foster Sch Med, El Paso, TX 79905 USA. [Gonzalez, Suzanne; Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael] Texas Tech Univ, Hlth Sci Ctr, Dept Psychiat, Paul L Foster Sch Med, El Paso, TX 79905 USA. [Armas, Regina] Univ Calif San Francisco, Langley Porter Psychiat Inst, San Francisco, CA USA. [Contreras, Salvador A.; Dassori, Albana] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Contreras, Javier; Raventos, Henriette] Univ Costa Rica, Ctr Invest Biol Celular & Mol & Escuela Biol, San Jose, Costa Rica. [Dassori, Albana] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Almasy, Laura] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Flores, Deborah] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Ctr Harbor, Torrance, CA 90509 USA. [Jerez, Alvaro] Ctr Int Trastornos Afect & Conducta Adict, Guatemala City, Guatemala. [Ontiveros, Alfonso] Inst Informac & Invest Salud Mental AC, Monterrey, Nuevo Leon, Mexico. [Nicolini, Humberto] Grp Estudios Med & Familiares Carracci SC, Mexico City, DF, Mexico. [Nicolini, Humberto] Inst Nacl Med Genom, Mexico City, DF, Mexico. RP Escamilla, M (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Psychiat, Paul L Foster Sch Med, 4800 Alberta, El Paso, TX 79905 USA. EM m.escamilla@ttuhsc.edu OI Nicolini, Humberto/0000-0003-2494-0067; Raventos, Henriette/0000-0001-9423-8308; Jerez Magana, Alvaro Antonio/0000-0002-1208-3769 FU NIMH Genetics Initiative study: Genetics of Bipolar Disorder in Latino Populations [5RO1MH069856] FX Grant sponsor: NIMH Genetics Initiative study: Genetics of Bipolar Disorder in Latino Populations; Grant number: 5RO1MH069856. NR 130 TC 4 Z9 5 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP PY 2014 VL 165 IS 6 BP 479 EP 491 DI 10.1002/ajmg.b.32251 PG 13 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AN3OF UT WOS:000340497100004 PM 25044503 ER PT J AU Van Horn, DHA Rennert, L Lynch, KG McKay, JR AF Van Horn, Deborah H. A. Rennert, Lior Lynch, Kevin G. McKay, James R. TI Social Network Correlates of Participation in Telephone Continuing Care for Alcohol Dependence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID DRINKING OUTCOMES; SUBSTANCE-ABUSE; USE DISORDERS; SUPPORT; AFTERCARE; COCAINE; PREDICTORS AB Background and Objectives: Research on face-to-face treatment for substance misuse suggests that patients' social networks may impact treatment entry and participation, but there has been no similar research on entry and participation in telephone-based continuing care. We examined whether alcohol-specific social support predicted engagement and participation in telephone continuing care for alcohol dependence, and whether treatment participation resulted in beneficial changes in participants' social networks. Methods: Participants were 252 adults (162 male) enrolled in a randomized clinical trial testing the effectiveness of telephone continuing care for alcohol dependence. Participants who completed 3 weeks of intensive outpatient treatment were randomly assigned to treatment as usual, telephone monitoring (TM; N = 83), or telephone monitoring and brief counseling (TMC; N = 83). TM and TMC included 18 months of telephone treatment. Alcohol-specific social support was measured with the Important People Inventory at baseline and 6, 12, 18, and 24-month follow-up. Results: Alcohol-specific social support did not predict entry into TM or TMC. Among those who entered telephone treatment (N = 127), participants with higher network percentage of daily drinkers, higher percentage of network members who accept drinking, and lower percentage of network members who do not accept drinking completed more continuing care calls. There was no effect of continuing care participation on alcohol-specific social support over 24 months of follow-up. Conclusion: Participants with more problematic social networks may self-select additional support in the form of telephone continuing care. Telephone continuing care does not appear to result in social network change. C1 [Van Horn, Deborah H. A.; Rennert, Lior; Lynch, Kevin G.; McKay, James R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [McKay, James R.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Van Horn, DHA (reprint author), Univ Penn, Ctr Continuum Care Addict, Perelman Sch Med, Dept Psychiat, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. EM dvh@mail.med.upenn.edu FU NIAAA NIH HHS [R01 AA14850, R01 AA014850]; NIDA NIH HHS [K24 DA029062] NR 27 TC 0 Z9 0 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2014 VL 23 IS 5 BP 447 EP 452 DI 10.1111/j.1521-0391.2014.12128.x PG 6 WC Substance Abuse SC Substance Abuse GA AN4BR UT WOS:000340533100006 PM 24628884 ER PT J AU Irons, JG Babson, KA Bergeria, CL Bonn-Miller, MO AF Irons, Jessica G. Babson, Kimberly A. Bergeria, Cecilia L. Bonn-Miller, Marcel O. TI Physical Activity and Cannabis Cessation SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID MODERATE-INTENSITY EXERCISE; MARIJUANA USE; ACTIVITY QUESTIONNAIRE; SUBSTANCE USE; DEPENDENCE; VALIDITY; ABSTINENCE; MOTIVES; METAANALYSIS; ADOLESCENTS AB Background and Objectives: Based on recent empirical and theoretical work suggesting that physical activity (PA) activates many of the same physiological systems as cannabis, the present study sought to investigate the impact of PA level (ie, low [including none] vs. moderate/high) on a cannabis cessation attempt during the first 7 days post-quit. Methods: The present study was a 2 time-point prospective study of 84 cannabis dependent military veterans (3 female) who responded to study flyers, within a Veterans Affairs Medical Center, seeking individuals interested in engaging in a self-guided cessation attempt. All study measures were self-report. Results: Though no baseline differences between those with low and those with moderate/high levels of physical activity were observed, results revealed that participants who reported low levels of physical activity, versus moderate/high levels, were significantly more likely to report a cannabis lapse during the week following a quit attempt, particularly within the first 4 days of the cessation period. Further, individuals with low levels of PA were also more likely to report greater mean cannabis use during the first 4 days of the cessation period. Conclusions and Scientific Significance: Findings suggest that early interventions aimed at increasing physical activity may be useful among individuals with cannabis dependence who are engaged in a cessation attempt. C1 [Irons, Jessica G.] James Madison Univ, Dept Psychol, Harrisonburg, VA 22807 USA. [Babson, Kimberly A.; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA. [Babson, Kimberly A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Menlo Pk, CA USA. [Bergeria, Cecilia L.] Univ Vermont, Burlington, VT USA. [Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA. [Bonn-Miller, Marcel O.] Philadelphia VA Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA. [Bonn-Miller, Marcel O.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Irons, JG (reprint author), James Madison Univ, Dept Psychol, MSC 7704, Harrisonburg, VA 22807 USA. EM ironsjg@jmu.edu OI Babson, Kimberly/0000-0002-9233-8230 NR 45 TC 6 Z9 6 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2014 VL 23 IS 5 BP 485 EP 492 DI 10.1111/j.1521-0391.2014.12135.x PG 8 WC Substance Abuse SC Substance Abuse GA AN4BR UT WOS:000340533100012 PM 24629045 ER PT J AU Wu, GC Chan, ED Chou, YC Yu, CY Hsieh, TY Hsieh, CB Chian, CF Ke, FC Dai, YL Su, WL AF Wu, Geng-Chin Chan, Edward D. Chou, Yu-Ching Yu, Chih-Yung Hsieh, Tsai-Yuan Hsieh, Chung-Bao Chian, Chih-Feng Ke, Fu-Chang Dai, Yu-Ling Su, Wen-Lin TI Risk factors for the development of pulmonary oil embolism after transcatheter arterial chemoembolization of hepatic tumors SO ANTI-CANCER DRUGS LA English DT Article DE hepatocellular carcinoma; pulmonary oil embolism; transcatheter arterial chemoembolization ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; RESPIRATORY-DISTRESS-SYNDROME; TRANSARTERIAL CHEMOEMBOLIZATION; LIPIODOL EMBOLISM; EMBOLIZATION; COMPLICATIONS; DOXORUBICIN; INFUSION; FAILURE; SHUNT AB Pulmonary oil embolism (POE) is a rare fatal complication after transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE). As risk factors have not been clearly delineated, the aim of the present study was to identify the risk factors for development of POE after TACE. A retrospective analysis was carried out on patients with unresectable hepatocellular carcinoma who received TAE or TACE at the Tri-Service General Hospital (Taiwan) between January 2005 and December 2008. The diagnosis of TAE-induced or TACE-induced POE was based on development of respiratory signs and symptoms relatively soon after the procedure, as well as based on characteristic radiographic findings. Of the 219 enrolled patients in this study, 20 were diagnosed with POE after TAE or TACE. On univariate logistic regression analysis, patients developing POE were found to be older (67.95+/-15.95 vs. 61.44+/-12.59 years, P=0.033), with a lower serum albumin level (3.25+/-0.58 vs. 3.62+/-0.57 g/dl, P=0.009), a higher grade of liver cirrhosis as classified on the basis of Child's criteria (P<0.006), a larger tumor size (8.55+/-4.52 vs. 4.78+/-3.97 cm in diameter, P<0.001), a higher lipioidol dose (22.35+/-11.01 vs. 13.69+/-7.66 ml, P=0.003), and a higher doxorubicin dose (50.27+/-7.05 vs. 40.75+/-13.61 mg, P<0.001). Following multivariate logistic regression analysis, only lipiodol dose was found to be a significant risk factor for POE (odds ratio=1.133, 95% confidence interval: 1.004, 1.279; P=0.044). The receiver operator characteristic curve cutoff point for lipiodol dose level was 14.5 ml, with a sensitivity of 80% and a specificity of 66.3%. In conclusion, the lipiodol dose could be considered as a predictive factor for POE after TAE or TACE in hepatic malignant tumor patients. On the basis of this retrospective study, the safe lipiodol dose to minimize the risk for POE is 14.5 ml or lower; however, larger, prospective studies are needed to determine the optimally safe and yet efficacious dose. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Wu, Geng-Chin; Ke, Fu-Chang] Taoyuan Armed Forces Gen Hosp, Div Pulm Med, Dept Internal Med, Taoyuan, Taiwan. [Chou, Yu-Ching; Su, Wen-Lin] Natl Def Med Ctr, Sch Publ Hlth, Taipei, Taiwan. [Yu, Chih-Yung] Triserv Gen Hosp, Dept Radiol, Taipei, Taiwan. [Hsieh, Tsai-Yuan] Triserv Gen Hosp, Div Gastroenterol, Dept Internal Med, Taipei, Taiwan. [Hsieh, Chung-Bao] Triserv Gen Hosp, Div Organ Transplantat, Dept Surg, Taipei, Taiwan. [Chian, Chih-Feng; Dai, Yu-Ling; Su, Wen-Lin] Triserv Gen Hosp, Div Pulm & Crit Care Med, Dept Med, Taipei, Taiwan. [Su, Wen-Lin] Buddhist Tzu Chi Med Fdn, Taipei Tzu Chi Hosp, Div Pulm & Crit Care Med, Dept Med, New Taipei City 231, Taiwan. [Chan, Edward D.] Univ Colorado, Anschutz Med Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Chan, Edward D.] Natl Jewish Hlth, Div Mycobacterial & Resp Infect, Dept Med, Denver, CO USA. RP Su, WL (reprint author), Buddhist Tzu Chi Med Fdn, Taipei Tzu Chi Hosp, Div Pulm & Crit Care Med, Dept Med, 289 Jianguo Rd, New Taipei City 231, Taiwan. EM williamsu2007@gmail.com NR 32 TC 1 Z9 2 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 EI 1473-5741 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD SEP PY 2014 VL 25 IS 8 BP 976 EP 981 DI 10.1097/CAD.0000000000000113 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AN4LD UT WOS:000340558400014 PM 24736105 ER PT J AU Bulson, R Jun, W AF Bulson, Ryan Jun, Weon TI Metastatic disease producing internuclear ophthalmolplegia: a case report SO CLINICAL AND EXPERIMENTAL OPTOMETRY LA English DT Editorial Material ID OPHTHALMOPLEGIA C1 [Bulson, Ryan] Portland VA Med Ctr, Portland, OR 97239 USA. Univ Pacific, Coll Optometry, Portland, OR USA. RP Bulson, R (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. EM ryan.bulson@pacificu.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0816-4622 EI 1444-0938 J9 CLIN EXP OPTOM JI Clin. Exp. Optom. PD SEP PY 2014 VL 97 IS 5 BP 468 EP 470 DI 10.1111/cxo.12176 PG 3 WC Ophthalmology SC Ophthalmology GA AN4EU UT WOS:000340541200016 PM 24989875 ER PT J AU Northcut, TB Kienow, A AF Northcut, Terry B. Kienow, Amy TI The Trauma Trifecta of Military Sexual Trauma: A Case Study Illustrating the Integration of Mind and Body in Clinical Work with Survivors of MST SO CLINICAL SOCIAL WORK JOURNAL LA English DT Article DE Military sexual trauma; Posttraumatic stress disorder; Mindfulness; Cognitive behavioral; Self harm; Integrative psychotherapy ID DELIBERATE SELF-HARM; POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; FEMALE VETERANS; NEGATIVE AFFECT; WOMEN VETERANS; RISK-FACTORS; LIFE-COURSE; SERVICE; VICTIMIZATION AB Military sexual trauma (MST) has recently received much attention from the media in contemporary society. With the ever-increasing population of United States service members returning from the Iraq and Afghanistan wars, it is vital for any mental health practitioner to be aware of the epidemic that is sexual assault in the military, the unique trauma experiences of the MST survivor, and treatment implications incorporating multiple psychological theories. This article explores three factors, referred to as the trauma trifecta, in which the effects of MST are exacerbated: the loss of professional and personal identity, the regulatory functions of self harm behaviors, and the retraumatization that many service members endure as a result of the distinctive characteristics of the military culture and its service to veterans. A case study with clinical interventions will be utilized to demonstrate this concept of "the trauma trifecta" and the unique challenges in treating the PTSD symptoms that can result from MST in clinical therapy. Drawing from multiple theories in clinical treatment, this paper illustrates the strengths and limitations of cognitive-behavioral techniques, highlights the integration of feminist theory to illustrate the obstacles of power structures, and mind-body interventions, bridging the gap between talk therapy and body therapy. Through this unique integration of multiple therapies, the case study illustrates the veteran's reengagement with her body and the reformulation of her identity post MST. C1 [Northcut, Terry B.] Loyola Univ Chicago, Sch Social Work, Chicago, IL 60611 USA. [Kienow, Amy] US Dept Vet Affairs, Orland Pk Vet Ctr, Orland Pk, IL 60462 USA. RP Northcut, TB (reprint author), Loyola Univ Chicago, Sch Social Work, 820 N Michigan Ave, Chicago, IL 60611 USA. EM tnorthc@luc.edu; kienow.amy@gmail.com NR 78 TC 0 Z9 0 U1 1 U2 19 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0091-1674 EI 1573-3343 J9 CLIN SOC WORK J JI Clin. Soc. Work J. PD SEP PY 2014 VL 42 IS 3 SI SI BP 247 EP 259 DI 10.1007/s10615-014-0479-0 PG 13 WC Social Work SC Social Work GA AN3SB UT WOS:000340507800006 ER PT J AU Horan, W Pineda, J Wynn, J Iacoboni, M Green, M AF Horan, William P. Pineda, Jaime A. Wynn, Jonathan K. Iacoboni, Marco Green, Michael F. TI Some markers of mirroring appear intact in schizophrenia: evidence from mu suppression SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article DE mu suppression; Schizophrenia; Mirror neuron system; Empathy ID AUTISM SPECTRUM DISORDERS; PSYCHIATRIC RATING-SCALE; BORDERLINE PERSONALITY-DISORDER; SOCIAL COGNITION; NEURON DYSFUNCTION; EMPATHIC ACCURACY; IMITATION; NEUROSCIENCE; MECHANISMS; PSYCHOSIS AB Although schizophrenia is associated with impairments in social cognition, the scope and neural correlates of these disturbances are largely unknown. In this study, we investigated whether schizophrenia patients show impaired functioning of the mirror neuron system (MNS), as indexed by electroencephalographic (EEG) mu (8-13 Hz) suppression, a hypothesized biomarker of MNS activity that is sensitive to the degree of social interaction depicted in visual stimuli. A total of 32 outpatients and 26 healthy controls completed an EEG paradigm that included six action observation or execution conditions that differed in their degrees of social interaction. Participants also completed a validated empathy questionnaire. Across both groups, we found a significant linear increase in mu suppression across the conditions involving greater levels of social engagement and interaction, but no significant group or interaction effects. Patients self-reported diminished empathic concern and perspective taking, which showed some moderate relations to mu suppression levels. Thus, the schizophrenia group showed generally intact modulation of MNS functioning at the electrophysiological level, despite self-reporting empathic disturbances. The disturbances commonly seen on self-report, performance, and neuroimaging measures of mentalizing in schizophrenia may largely reflect difficulties with higher-level inferential processes about others' emotions, rather than a basic incapacity to share in these experiences. C1 [Horan, William P.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Pineda, Jaime A.] Univ Calif San Diego, San Diego, CA 92103 USA. [Iacoboni, Marco] Univ Calif Los Angeles, Los Angeles, CA USA. RP Horan, W (reprint author), Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM horan@ucla.edu OI Wynn, Jonathan/0000-0002-1763-8540 FU Abbott Laboratories; Amgen; Cypress; Lundbeck; Teva; Otsuka; Sunovion; VA Career Development Award; NIMH [MH065707, MH43292] FX M.F.G. reports having received consulting fees from Abbott Laboratories, Amgen, Cypress, Lundbeck, and Teva. He has received speaking fees from Otsuka and Sunovion. The rest of the authors report no biomedical financial interests or potential conflicts of interest. Support for this study came from a VA Career Development Award (to W. P. H.) and from NIMH Grant Nos. MH065707 and MH43292 (M. F. G.). The authors thank Amanda Bender, Michelle Dolinsky, Crystal Gibson, Cory Tripp, and Katherine Weiner for assistance in the data collection. NR 68 TC 14 Z9 15 U1 4 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 EI 1531-135X J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD SEP PY 2014 VL 14 IS 3 BP 1049 EP 1060 DI 10.3758/s13415-013-0245-8 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AN3FT UT WOS:000340471500013 PM 24415272 ER PT J AU Chen, SS Seliger, SL Fried, LF AF Chen, Shan Shan Seliger, Stephen L. Fried, Linda F. TI Complete inhibition of the renin-angiotensin-aldosterone system; where do we stand? SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE angiotensin receptor blocker; angiotensin-converting enzyme; cardiovascular disease; diabetic nephropathy; mineralocorticoid receptor blocker ID CONVERTING-ENZYME-INHIBITOR; CHRONIC HEART-FAILURE; LEFT-VENTRICULAR DYSFUNCTION; PRESERVED EJECTION FRACTION; RANDOMIZED CONTROLLED-TRIAL; CHRONIC RENAL-INSUFFICIENCY; TYPE-2 DIABETIC-PATIENTS; MYOCARDIAL-INFARCTION; ADDING SPIRONOLACTONE; RECEPTOR BLOCKER AB Purpose of review This review presents the role of combination therapy of renin-angiotensin-aldosterone system blockade on cardiovascular and kidney disease. Recent findings Three large randomized controlled trials comparing combination therapy of renin-angiotensin-aldosterone system blockade to monotherapy in individuals with increased cardiovascular risk, chronic kidney disease, or diabetic nephropathy have been reported. These trials - ONTARGET, ALTITUDE, and VA NEPHRON-D - demonstrated an excess risk of adverse effects [ especially acute kidney injury (AKI) and hyperkalemia] with combination therapy, without significant benefit in reducing cardiovascular and renal morbidity. Summary Current evidence supports avoiding dual renin-angiotensin-aldosterone system blockade in patients with chronic kidney disease. Subsequent studies of dual renin-angiotensin-aldosterone system blockade should examine adverse event risks and renal progression endpoints. C1 [Chen, Shan Shan; Fried, Linda F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Seliger, Stephen L.] VA Maryland Healthcare Syst, Baltimore, MD USA. [Seliger, Stephen L.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Chen, SS (reprint author), Univ Pittsburgh, Sch Med, Presbyterian Univ Hosp C1100, Renal Electrolyte Div, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM Chens4@upmc.edu NR 61 TC 3 Z9 3 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 EI 1473-6543 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 2014 VL 23 IS 5 BP 449 EP 455 DI 10.1097/MNH.0000000000000043 PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA AN4OG UT WOS:000340566800003 PM 25014549 ER PT J AU de Guillory, CD Schoolfield, JD Johnson, D Yeh, CK Chen, S Cappelli, DP Bober-Moken, IG Dang, H AF de Guillory, Carolina Diaz Schoolfield, John D. Johnson, Dorthea Yeh, Chih-Ko Chen, Shuo Cappelli, David P. Bober-Moken, Irene G. Dang, Howard TI Co-Relationships between glandular salivary flow rates and dental caries SO GERODONTOLOGY LA English DT Article DE caries; saliva; ageing; ethnicity ID DIFFERENT AGE-GROUPS; ROOT CARIES; HEALTH; IMPACT AB Objective: This study was designed to evaluate the relationship of age, gender, ethnicity and salivary flow rates on dental caries in an adult population using data collected from the Oral Health San Antonio Longitudinal Study of Aging (OH: SALSA). Background: Saliva is essential to maintain a healthy oral environment and diminished output can result in dental caries. Although gender and age play a role in the quantity of saliva, little is known about the interaction of age, gender and ethnicity on dental caries and salivary flow rates. Materials and methods: Data from the 1147 participants in the OH: SALSA were analysed. The dependent variables were the number of teeth with untreated coronal caries, number of teeth with root caries and the number of coronal and root surfaces with untreated caries. The independent variables were stimulated and unstimulated glandular salivary flow rates along with the age, sex and ethnicity (e. g. European or Mexican ancestry) of the participants. Results: Coronal caries experience was greater in younger participants while root surface caries experience was greater in the older participants. Coronal caries was lower in the older age groups while the root caries experience increased. Men had a statistically significant (p < 0.02) higher experience of root caries than women. Values for unstimulated and stimulated parotid salivary flow rates showed no age difference and remained constant with age, whereas the age differences in the unstimulated and stimulated submandibular/sublingual salivary flow rates were significant. The mean number of teeth with coronal and root caries was higher in Mexican-Americans than in European-Americans. Conclusions: Over one-fourth of the adults between the ages of 60 and 79 have untreated root caries over one-third having untreated coronal caries. Lower salivary flow rates play a significant role in both the number of teeth and the number of surfaces developing caries in these adults. Women and individuals of European-American ancestry experience less caries. C1 [de Guillory, Carolina Diaz; Yeh, Chih-Ko; Cappelli, David P.; Bober-Moken, Irene G.; Dang, Howard] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Schoolfield, John D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Johnson, Dorthea] Univ Texas Hlth Sci Ctr San Antonio, Dept Community Dent, San Antonio, TX 78229 USA. [Chen, Shuo] Univ Texas Hlth Sci Ctr San Antonio, Dept Dev Dent, San Antonio, TX 78229 USA. [Yeh, Chih-Ko] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Dang, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM dang@uthscsa.edu FU HRSA [D13HP30016]; NIH [DE019892] FX This work was supported by grants from HRSA (D13HP30016 to DPC) and NIH (DE019892 to SC). NR 29 TC 2 Z9 2 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0734-0664 EI 1741-2358 J9 GERODONTOLOGY JI Gerodontology PD SEP PY 2014 VL 31 IS 3 BP 210 EP 219 DI 10.1111/ger.12028 PG 10 WC Dentistry, Oral Surgery & Medicine; Geriatrics & Gerontology SC Dentistry, Oral Surgery & Medicine; Geriatrics & Gerontology GA AN3ZP UT WOS:000340527700007 ER PT J AU Park, LG Howie-Esquivel, J Dracup, K AF Park, Linda G. Howie-Esquivel, Jill Dracup, Kathleen TI A quantitative systematic review of the efficacy of mobile phone interventions to improve medication adherence SO JOURNAL OF ADVANCED NURSING LA English DT Review DE medication adherence; mobile phone; nursing; short message service (SMS); text messaging ID RANDOMIZED-CONTROLLED-TRIAL; SHORT-MESSAGE SERVICE; ANTIRETROVIRAL THERAPY; TEXT MESSAGES; PROGRAM; SMS; REMINDERS; SCHIZOPHRENIA; HIV/AIDS; MHEALTH AB Aims. To evaluate the characteristics and efficacy of mobile phone interventions to improve medication adherence. Secondary aims are to explore participants' acceptability and satisfaction with mobile phone interventions and to evaluate the selected studies in terms of study rigour, impact, cost and resource feasibility, generalizability and implications for nursing practice and research. Background. Medication non-adherence is a major global challenge. Mobile phones are the most commonly used form of technology worldwide and have the potential to promote medication adherence. Design. Guidelines from the Centre for Reviews and Dissemination were followed for this systematic review. Data Sources. A comprehensive search of databases (PubMed, Web of Science, CINAHL, PsycInfo, Google Chrome and Cochrane) and bibliographies from related articles was performed from January 2002-January 2013 to identify the included studies. Review Methods. A quantitative systematic review without meta-analysis was conducted and the selected studies were critically evaluated to extract and summarize pertinent characteristics and outcomes. Results. The literature search produced 29 quantitative research studies related to mobile phones and medication adherence. The studies were conducted for prevention purposes as well as management of acute and chronic illnesses. All of the studies used text messaging. Eighteen studies found significant improvement in medication adherence. Conclusion. While the majority of investigators found improvement in medication adherence, long-term studies characterized by rigorous research methodologies, appropriate statistical and economic analyses and the test of theory-based interventions are needed to determine the efficacy of mobile phones to influence medication adherence. C1 [Park, Linda G.] Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA USA. [Howie-Esquivel, Jill; Dracup, Kathleen] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. RP Park, LG (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA USA. EM linda.park@ucsf.edu RI Emchi, Karma/Q-1952-2016 NR 49 TC 21 Z9 21 U1 7 U2 47 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-2402 EI 1365-2648 J9 J ADV NURS JI J. Adv. Nurs. PD SEP PY 2014 VL 70 IS 9 BP 1932 EP 1953 DI 10.1111/jan.12400 PG 22 WC Nursing SC Nursing GA AN2CJ UT WOS:000340390700002 PM 24689978 ER PT J AU Adams, ZW Sumner, JA Danielson, CK McCauley, JL Resnick, HS Gros, K Paul, LA Welsh, KE Ruggiero, KJ AF Adams, Zachary W. Sumner, Jennifer A. Danielson, Carla Kmett McCauley, Jenna L. Resnick, Heidi S. Groes, Kirstin Paul, Lisa A. Welsh, Kyleen E. Ruggiero, Kenneth J. TI Prevalence and predictors of PTSD and depression among adolescent victims of the Spring 2011 tornado outbreak SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Disaster; adolescents; PTSD; depression; tornadoes ID POSTTRAUMATIC STRESS SYMPTOMS; MENTAL-HEALTH RESEARCH; NEW-YORK-CITY; NATURAL DISASTER; NATIONAL SAMPLE; RISK-FACTORS; COMORBIDITY; CHILDREN; ATTACKS AB Background: Relatively few studies have examined prevalence and predictors of posttraumatic stress disorder (PTSD) or major depressive episode (MDE) in disaster-affected adolescents. Fewer still have administered diagnostic measures or studied samples exposed to tornadoes, a common type of disaster. Further, methodologic problems limit the generalizability of previous findings. This study addressed prevalence estimates and risk factors for PTSD and MDE among adolescents exposed to the Spring 2011 tornado outbreak in Alabama and Joplin, Missouri. Methods: A large (N = 2000), population-based sample of adolescents and caregivers, recruited randomly from tornado-affected communities, participated in structured telephone interviews. PTSD and MDE prevalence were estimated for the overall sample, by gender, and by age. Hierarchical logistic regression was used to identify risk factors for PTSD and MDE. Results: Overall, 6.7% of adolescents met diagnostic criteria for PTSD and 7.5% of adolescents met diagnostic criteria for MDE since the tornado. Girls were significantly more likely than boys to meet diagnostic criteria for MDE, and older adolescents were more likely than younger adolescents to report MDE since the tornado. Female gender, prior trauma exposure, and an injured family member were associated with greater risk for PTSD and MDE. Specific incident characteristics (loss of services, concern about others' safety) were associated with greater PTSD risk; prior disaster exposure was associated with lower MDE risk. Conclusions: However, most adolescents were resilient following tornado exposure, roughly 1 in 15 developed PTSD, 1 in 13 developed MDE, and many more endorsed subclinical mental health problems. Information regarding specific risk factors can guide early screening, prevention, and intervention efforts in disaster-affected communities. C1 [Adams, Zachary W.; Sumner, Jennifer A.; Danielson, Carla Kmett; McCauley, Jenna L.; Resnick, Heidi S.; Groes, Kirstin; Welsh, Kyleen E.; Ruggiero, Kenneth J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Groes, Kirstin; Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Paul, Lisa A.] No Illinois Univ, Dept Psychol, De Kalb, IL 60115 USA. RP Adams, ZW (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA. EM adamsz@musc.edu FU National Institutes of Health [R01-MH081056]; [R21-MH086313]; [R01-DA031285]; [K12-DA031794]; [T32-MH018869] FX The National Institutes of Health (Grants R01-MH081056 to KJR) supported this study and the team of collaborators (R21-MH086313 and R01-DA031285 to C. K. D, K12-DA031794 sponsoring J.L.M, and T32-MH018869 sponsoring Z.W.A and J.A.S). All the authors declare that they have no potential or competing conflicts of interest. The authors thank the families for participating in this study. NR 33 TC 18 Z9 18 U1 9 U2 37 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD SEP PY 2014 VL 55 IS 9 BP 1047 EP 1055 DI 10.1111/jcpp.12220 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AN2JD UT WOS:000340410000012 PM 24580551 ER PT J AU Benedek, G Zhu, WB Libal, N Casper, A Yu, XL Meza-Romero, R Vandenbark, AA Alkayed, NJ Offner, H AF Benedek, Gil Zhu, Wenbin Libal, Nicole Casper, Amanda Yu, Xiaolin Meza-Romero, Roberto Vandenbark, Arthur A. Alkayed, Nabil J. Offner, Halina TI A novel HLA-DR alpha 1-MOG-35-55 construct treats experimental stroke (vol 29, pg 37, 2014) SO METABOLIC BRAIN DISEASE LA English DT Correction C1 [Benedek, Gil; Yu, Xiaolin; Meza-Romero, Roberto; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. [Zhu, Wenbin; Libal, Nicole; Casper, Amanda; Alkayed, Nabil J.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Benedek, Gil; Yu, Xiaolin; Meza-Romero, Roberto; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu NR 1 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 EI 1573-7365 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD SEP PY 2014 VL 29 IS 3 BP 885 EP 885 DI 10.1007/s11011-014-9518-3 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AN3MP UT WOS:000340492600036 ER PT J AU Wang, CC Maciejewski, ML Rao, JK Sheitman, BB Sleath, BL Farley, JF AF Wang, Chi-Chuan Maciejewski, Matthew L. Rao, Jaya K. Sheitman, Brian B. Sleath, Betsy L. Farley, Joel F. TI Examining the Relationship Between Adjunctive Psychotherapy Use and Antipsychotic Persistence and Hospitalization SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Medicaid; Schizophrenia; Adjunctive psychotherapy; Adherence; Hospitalization ID IMPROVE MEDICATION ADHERENCE; RESEARCH-TEAM PORT; OUTCOMES-RESEARCH; TREATMENT RECOMMENDATIONS; PSYCHOSOCIAL TREATMENTS; NATIONAL TRENDS; CLAIMS DATA; FOLLOW-UP; SCHIZOPHRENIA; PATTERNS AB This study assessed whether the addition of adjunctive psychotherapy to antipsychotic pharmacotherapy improved antipsychotic persistence and reduced the risk of hospitalization among patients with schizophrenia using 2001-2003 Medicaid claims data from four states: Illinois, Kansas, Minnesota, and North Carolina. New antipsychotic users aged 18 or older were included. Our study showed that adjunctive psychotherapy use was associated with increased antipsychotic persistence during the first two months of treatment but was not associated with risk of hospitalization. Further research is needed to understand how to optimize the benefits of psychotherapy in terms of frequency of appointments, duration, and type. C1 [Wang, Chi-Chuan] Natl Taiwan Univ, Sch Pharm, Taipei 10051, Taiwan. [Maciejewski, Matthew L.] US Dept Vet Affairs, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. [Rao, Jaya K.; Sleath, Betsy L.; Farley, Joel F.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmaceut Outcomes & Policy, Chapel Hill, NC USA. [Sheitman, Brian B.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. RP Wang, CC (reprint author), Natl Taiwan Univ, Sch Pharm, 1 Jen Ai Rd,Sect 1, Taipei 10051, Taiwan. EM chicwang@ntu.edu.tw; matthew.maciejewski@va.gov; jayarao@unc.edu; brian_sheitman@med.unc.edu; betsy_sleath@unc.edu; jffarley@unc.edu NR 48 TC 1 Z9 1 U1 3 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD SEP PY 2014 VL 41 IS 5 BP 598 EP 607 DI 10.1007/s10488-013-0503-7 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AM6IC UT WOS:000339966800004 PM 23733044 ER PT J AU Singh, H Meyer, AND Thomas, EJ AF Singh, Hardeep Meyer, Ashley N. D. Thomas, Eric J. TI The frequency of diagnostic errors in outpatient care: estimations from three large observational studies involving US adult populations SO BMJ QUALITY & SAFETY LA English DT Article ID CANCER DIAGNOSIS; ADVERSE EVENTS; MISSED OPPORTUNITIES; MALPRACTICE CLAIMS; UNITED-STATES; FOLLOW-UP; NEGLIGENT AB Background The frequency of outpatient diagnostic errors is challenging to determine due to varying error definitions and the need to review data across multiple providers and care settings over time. We estimated the frequency of diagnostic errors in the US adult population by synthesising data from three previous studies of clinic-based populations that used conceptually similar definitions of diagnostic error. Methods Data sources included two previous studies that used electronic triggers, or algorithms, to detect unusual patterns of return visits after an initial primary care visit or lack of follow-up of abnormal clinical findings related to colorectal cancer, both suggestive of diagnostic errors. A third study examined consecutive cases of lung cancer. In all three studies, diagnostic errors were confirmed through chart review and defined as missed opportunities to make a timely or correct diagnosis based on available evidence. We extrapolated the frequency of diagnostic error obtained from our studies to the US adult population, using the primary care study to estimate rates of diagnostic error for acute conditions (and exacerbations of existing conditions) and the two cancer studies to conservatively estimate rates of missed diagnosis of colorectal and lung cancer (as proxies for other serious chronic conditions). Results Combining estimates from the three studies yielded a rate of outpatient diagnostic errors of 5.08%, or approximately 12 million US adults every year. Based upon previous work, we estimate that about half of these errors could potentially be harmful. Conclusions Our population-based estimate suggests that diagnostic errors affect at least 1 in 20 US adults. This foundational evidence should encourage policymakers, healthcare organisations and researchers to start measuring and reducing diagnostic errors. C1 [Singh, Hardeep; Meyer, Ashley N. D.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Vet Affairs Ctr Innovat Qual Effectivenes, Houston, TX 77030 USA. [Singh, Hardeep; Meyer, Ashley N. D.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Thomas, Eric J.] Univ Texas Med Sch Houston, Div Gen Med, Dept Med, Univ Texas Houston,Mem Hermann Ctr Healthcare Qua, Houston, TX USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd,VAMC 152, Houston, TX 77030 USA. EM hardeeps@bcm.edu OI Meyer, Ashley/0000-0001-7993-8584 FU NIH K23 Career Development Award [K23CA125585]; VA National Center of Patient Safety; Agency for Healthcare Research and Quality [R18HS017820, R18HS17244-02]; Houston VA Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX Studies mentioned in this paper were supported by an NIH K23 Career Development Award (K23CA125585), the VA National Center of Patient Safety, and Agency for Healthcare Research and Quality (R18HS017820 and R18HS17244-02). HS and ANDM were supported in part by the Houston VA Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). NR 28 TC 38 Z9 38 U1 1 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD SEP PY 2014 VL 23 IS 9 BP 727 EP 731 DI 10.1136/bmjqs-2013-002627 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AN0AR UT WOS:000340244000006 PM 24742777 ER PT J AU Long, TJ Sprenger, CC Plymate, SR Ratner, BD AF Long, Thomas J. Sprenger, Cynthia C. Plymate, Stephen R. Ratner, Buddy D. TI Prostate cancer xenografts engineered from 3D precision-porous poly(2-hydroxyethyl methacrylate) hydrogels as models for tumorigenesis and dormancy escape SO BIOMATERIALS LA English DT Article DE PolyHEMA; Scaffold; Xenograft; Prostate cancer; Dormancy; Tumor microenvironment ID PROTEIN-RELATED PROTEIN-1; MAMMARY EPITHELIAL-CELLS; IN-VITRO EVALUATION; TUMOR DORMANCY; GROWTH; PROGRESSION; CULTURE; EXPRESSION; METASTASIS; BIOLOGY AB Synthetic biomaterial scaffolds show promise for in vitro and in vivo 3D cancer models. Tumors engineered in biomaterial scaffolds have shown evidence of being more physiologically relevant than some traditional preclinical model systems, and synthetic biomaterials provide the added benefit of defined and consistent microenvironmental control. Here, we examine sphere-templated poly(2-hydroxyethyl methacrylate) (pHEMA) scaffolds as the basis for engineering xenografts from multiple human prostate cancer cell lines. pHEMA scaffolds seeded and pre-cultured with tumorigenic M12 cells prior to implantation generated tumors in athymic nude mice, demonstrating the ability of the scaffolds to be used as a synthetic vehicle for xenograft generation. pHEMA scaffolds seeded with LNCaP C4-2 cells, which require Matrigel or stromal cell support for tumor formation, were poorly tumorigenic up to 12 weeks after implantation even when Matrigel was infused into the scaffold, demonstrating a lack of necessary pro-tumorigenic signaling within the scaffolds. Finally, M12mac25 cells, which are ordinarily rendered non-tumorigenic through the expression of the tumor suppressor insulin-like growth factor binding protein 7 (IGFBP7), displayed a tumorigenic response when implanted within porous pHEMA scaffolds. These M12mac25 tumors showed significant macrophage infiltration within the scaffolds driven by the foreign body response to the materials. These findings show the potential for this biomaterials-based model system to be used in the study of prostate cancer tumorigenesis and dormancy escape. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Long, Thomas J.; Ratner, Buddy D.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Sprenger, Cynthia C.; Plymate, Stephen R.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Plymate, Stephen R.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Ratner, BD (reprint author), Univ Washington, Dept Bioengn, Box 355061,3720 15th Ave NE, Seattle, WA 98195 USA. EM ratner@uweb.engr.washington.edu FU Nanotechnology and Physical Science in Cancer Research Training Program NIH [T32CA138312]; TMEN [U54-CAl26540, P01 CA085859]; Veterans Affairs Research Service FX The authors would like to thank Shihua Sun, Colleen Irvin, Kathryn Soriano, and Gerry Hammer for technical assistance. This work was supported by the Nanotechnology and Physical Science in Cancer Research Training Program NIH T32CA138312 (TJL and BDR), TMEN U54-CAl26540 (SRP), P01 CA085859 (SRP), and the Veterans Affairs Research Service (SRP). NR 56 TC 8 Z9 8 U1 1 U2 50 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2014 VL 35 IS 28 BP 8164 EP 8174 DI 10.1016/j.biomaterials.2014.04.090 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA AM3TC UT WOS:000339774700011 PM 24942815 ER PT J AU Yokoyama, JS Evans, DS Coppola, G Kramer, JH Tranah, GJ Yaffe, K AF Yokoyama, Jennifer S. Evans, Daniel S. Coppola, Giovanni Kramer, Joel H. Tranah, Gregory J. Yaffe, Kristine TI Genetic Modifiers of Cognitive Maintenance Among Older Adults SO HUMAN BRAIN MAPPING LA English DT Article DE genetics; genomics; aging; cognition; genome wide association study; neuroimaging ID GENOME-WIDE ASSOCIATION; MINI-MENTAL STATE; ALZHEIMERS-DISEASE; METABOLIC SYNDROME; OSTEOPOROTIC FRACTURES; SUSCEPTIBILITY LOCI; DECLINE; BRAIN; RISK; METAANALYSIS AB Objective: Identify genetic factors associated with cognitive maintenance in late life and assess their association with gray matter (GM) volume in brain networks affected in aging. Methods: We conducted a genome-wide association study of similar to 2.4 M markers to identify modifiers of cognitive trajectories in Caucasian participants (N=7,328) from two population-based cohorts of non-demented elderly. Standardized measures of global cognitive function (z-scores) over 10 and 6 years were calculated among participants and mixed model regression was used to determine subject-specific cognitive slopes. "Cognitive maintenance" was defined as a change in slope of >= 0 and was compared with all cognitive decliners (slope <0). In an independent cohort of cognitively normal older Caucasians adults (N=122), top association findings were then used to create genetic scores to assess whether carrying more cognitive maintenance alleles was associated with greater GM volume in specific brain networks using voxel-based morphometry. Results: The most significant association was on chromosome 11 (rs7109806, P=7.8 x 10(-8)) near RIC3. RIC3 modulates activity of alpha 7 nicotinic acetylcholine receptors, which have been implicated in synaptic plasticity and beta-amyloid binding. In the neuroimaging cohort, carrying more cognitive maintenance alleles was associated with greater volume in the right executive control network (RECN; P-FWE=0.01). Conclusions: These findings suggest that there may be genetic loci that promote healthy cognitive aging and that they may do so by conferring robustness to GM in the RECN. Future work is required to validate top candidate genes such as RIC3 for involvement in cognitive maintenance. Hum Brain Mapp 35:4556-4565, 2014. (C) 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc. C1 [Yokoyama, Jennifer S.; Kramer, Joel H.; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Evans, Daniel S.; Tranah, Gregory J.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Yokoyama, JS (reprint author), UCSF Memory & Aging Ctr, 675 Nelson Rising Ln,Suite 190, San Francisco, CA 94158 USA. EM jyokoyama@memory.ucsf.edu FU Larry L. Hillblom Foundation [2012-A-015-FEL]; National Institute on Aging (NIA) [P50-AG023501-08S1, R01 AG032289, R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, RC1 AG035610]; National Institutes of Health (NIH) [K24 AG031155]; NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (GWAS in MrOS and SOF) [RC2AR058973]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center for Research Resources (NCRR) [2007/2I] FX Contract grant sponsor: Larry L. Hillblom Foundation; Contract grant number: 2012-A-015-FEL; Contract grant sponsor: National Institute on Aging (NIA); Contract grant number: P50-AG023501-08S1; Contract grant sponsor: National Institutes of Health (NIH); Contract grant number: K24 AG031155; Contract grant sponsor: National Institute on Aging (NIA); Contract grant numbers: R01 AG032289, R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, and RC1 AG035610; Contract grant sponsor: NIH Roadmap for Medical Research; Contract grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140; Contract grant sponsor: The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (GWAS in MrOS and SOF); Contract grant number: RC2AR058973; Contract grant sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the National Center for Research Resources (NCRR); Contract grant number: 2007/2I NR 61 TC 4 Z9 4 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2014 VL 35 IS 9 BP 4556 EP 4565 DI 10.1002/hbm.22494 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AM0VZ UT WOS:000339567000022 PM 24616004 ER PT J AU Lee, J Cohen, MS Engel, SA Glahn, D Nuechterlein, KH Wynn, JK Green, MF AF Lee, Junghee Cohen, Mark S. Engel, Stephen A. Glahn, David Nuechterlein, Keith H. Wynn, Jonathan K. Green, Michael F. TI Neural Substrates of Visual Masking by Object Substitution in Schizophrenia SO HUMAN BRAIN MAPPING LA English DT Article DE object substitution masking; schizophrenia; visual backward masking; fMRI ID FUNCTIONAL MRI; SEPARATING PROCESSES; OCCIPITAL CORTEX; BACKWARD-MASKING; AWARENESS; ATTENTION; FMRI; REPRESENTATION; CONSCIOUSNESS; OPTIMIZATION AB Despite a well-known behavioral finding of visual backward masking impairment in schizophrenia, its underlying neural mechanism remains obscure. This study examined neural correlates of a distinct type of visual backward masking, object substitution masking (OSM), in schizophrenia. Twenty schizophrenia patients and 26 healthy controls completed a 4-Dot OSM task and three functional localizer tasks for the lateral occipital (LO), human motion-sensitive (hMT+), and retinotopic areas in the scanner. In 4-dot masking, subjects detected a target that was followed by a mask consisting of 4 dots that surrounded a target. Stimulus-onset asynchrony (SOA) between target and mask was varied to examine the modulation of masking: (1) within three visual processing areas regions of interest (ROI) (i.e., ROI analysis) and (2) in brain regions outside the three visual processing areas (i.e., whole brain analysis). In the ROI analyses, LO and retinotopic areas showed increased peak amplitude when SOA become longer in both patients and controls. There was also an effect of ROI in that both groups showed higher activation in LO and hMT+ compared with the retinotopic areas. The whole brain analyses revealed a significantly activated area for longer SOAs vs. a short SOA in the occipital cortex in controls only, but the group contrast was not significant. Overall, this study did not find strong evidence for neural abnormalities of OSM in schizophrenia, suggesting that neural substrates of OSM in schizophrenia are not as compromised as those involved in the more common masking methods that rely on disruption of object formation. (C) 2014 Wiley Periodicals, Inc. C1 [Lee, Junghee; Cohen, Mark S.; Nuechterlein, Keith H.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Lee, Junghee; Wynn, Jonathan K.; Green, Michael F.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Engel, Stephen A.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Glahn, David] Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT USA. [Glahn, David; Nuechterlein, Keith H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Lee, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza 77-361, Los Angeles, CA 90024 USA. EM jungheelee@ucla.edu RI Lee, Junghee/C-5226-2014; Wynn, Jonathan/H-3749-2014 OI Lee, Junghee/0000-0001-9567-8700; Wynn, Jonathan/0000-0002-1763-8540 FU National Institute of Mental Health [MH43292, MH065707]; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Tamkin Foundation; Jennifer Jones-Simon Foundation; Capital Group Companies Charitable Foundation; Robson Family; Northstar Fund FX Contract grant sponsor: National Institute of Mental Health; Contract grant number: MH43292, MH065707; Contract grant sponsors: Brain Mapping Medical Research Organization, the Brain Mapping Support Foundation, the Pierson-Lovelace Foundation, the Tamkin Foundation, the Jennifer Jones-Simon Foundation, the Capital Group Companies Charitable Foundation, the Robson Family, the Northstar Fund. NR 38 TC 2 Z9 2 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2014 VL 35 IS 9 BP 4654 EP 4662 DI 10.1002/hbm.22501 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AM0VZ UT WOS:000339567000029 PM 24677632 ER PT J AU Cash, TV Konig, A Eonta, AM Vrana, SR AF Cash, Therese V. Konig, Andrea Eonta, Alison M. Vrana, Scott R. TI RESPIRATORY SINUS ARRYTHMIA PREDICTS MENTAL HEALTH OUTCOMES IN AN EXPRESSIVE WRITING TASK SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE respiratory sinus arrhythmia; expressive writing C1 [Cash, Therese V.; Konig, Andrea; Vrana, Scott R.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Eonta, Alison M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 3-49 BP S55 EP S55 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500303 ER PT J AU Jahshan, C Wynn, JK Mathis, KI Green, MF AF Jahshan, Carol Wynn, Jonathan K. Mathis, Kristopher I. Green, Michael F. TI THE NEUROPHYSIOLOGY OF BIOLOGICAL MOTION PERCEPTION IN SCHIZOPHRENIA SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE biological motion; electroencephalography; schizophrenia C1 VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 3-17 BP S49 EP S49 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500271 ER PT J AU Wangelin, BC Tuerk, PW AF Wangelin, Bethany C. Tuerk, Peter W. TI TAKING THE PULSE OF PROLONGED EXPOSURE THERAPY: CHANGES IN TRAUMA-RELATED PHYSIOLOGICAL AROUSAL ACROSS THE COURSE OF PTSD TREATMENT SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE PTSD; anxiety; emotion C1 [Wangelin, Bethany C.; Tuerk, Peter W.] Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 4-81 BP S77 EP S77 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500426 ER PT J AU Wynn, JK Roach, BJ Lee, J Horan, WP Ford, JM Jimenez, AM Weiner, K Ghermezi, L Green, MF AF Wynn, Jonathan K. Roach, Brian J. Lee, Junghee Horan, William P. Ford, Judith M. Jimenez, Amy M. Weiner, Katherine Ghermezi, Livon Green, Michael F. TI EEG FINDINGS OF REDUCED NEURAL SYNCHRONIZATION DURING VISUAL INTEGRATION IN SCHIZOPHRENIA SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE schizophrenia; event-related potentials; visual integration C1 [Wynn, Jonathan K.; Horan, William P.; Jimenez, Amy M.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Wynn, Jonathan K.; Lee, Junghee; Horan, William P.; Weiner, Katherine; Ghermezi, Livon; Green, Michael F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Roach, Brian J.] Vet Affairs San Francisco Med Ctr, San Francisco, CA USA. [Ford, Judith M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 3-16 BP S49 EP S49 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500270 ER PT J AU Sher, L Grunebaum, MF Sullivan, GM Burke, AK Cooper, TB Mann, JJ Oquendo, MA AF Sher, Leo Grunebaum, Michael F. Sullivan, Gregory M. Burke, Ainsley K. Cooper, Thomas B. Mann, J. John Oquendo, Maria A. TI Association of testosterone levels and future suicide attempts in females with bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar; Female; Testosterone; Suicide ID HUMAN-AGGRESSION; GONADAL AXIS; WOMEN; DEPRESSION; BEHAVIOR; ANDROGENS; SCALE; RISK; METAANALYSIS; METABOLITES AB Background: Considerable evidence suggests that testosterone may play a role in the pathophysiology of mood disorders in females. This is the first prospective study to examine whether blood testosterone levels predict suicide attempts in females with bipolar disorder. Methods: Females with a DSM-PI diagnosis of a bipolar disorder in a depressive or mixed episode with at least one past suicide attempt were enrolled. Demographic and clinical parameters were assessed and recorded. Plasma testosterone was assayed using a double antibody radioimmunoassay procedure. Patients were followed up prospectively for up to 2.5 years. Results: At baseline, testosterone levels positively correlated with the number of previous major depressive episodes and suicide attempts. Cox proportional hazards regression analysis found that higher baseline testosterone levels predicted suicide attempts during the follow-up period. Limitations: A limitation of the study is that the sample size is modest. Another limitation is that we did not have a bipolar nonattempter or healthy volunteer control group for comparison. Conclusion: Testosterone levels may predict suicidal behavior in women with bipolar disorder. Published by Elsevier B.V. C1 [Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY 10468 USA. [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 West Kingsbridge Rd, New York, NY 10468 USA. EM Leo.Sher@mssm.edu FU NIH [R01 MH59710, P50 MH62185, R01 MH48514] FX This study was supported by grants R01 MH59710, P50 MH62185, and R01 MH48514 from the NIH. The funding source had no role in study design; data collection, analysis, or interpretation; or in writing of the manuscript and submission process. NR 54 TC 5 Z9 5 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 2014 VL 166 BP 98 EP 102 DI 10.1016/j.jad.2014.04.068 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AK8UV UT WOS:000338705000014 PM 25012416 ER PT J AU Hebenstreit, C Madden, E Maguen, S AF Hebenstreit, Claire Madden, Erin Maguen, Shira TI Latent classes of PTSD symptoms in Iraq and Afghanistan female veterans SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Posttraumatic stress disorder; Women's health services; Veterans/psychology; Female ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSES; MENTAL-HEALTH DIAGNOSES; DISSOCIATIVE SUBTYPE; CARE; BARRIERS; VA; ETHNICITY; CONFLICTS; SERVICES AB Background: Recent studies have used latent class analysis (LCA) to identify subgroups of individuals who slut e similar patterns of PTSD symptom endorsement; however, further study is needed among Female veterans, whose PTSD symptom expression may vary from that of their male counterparts. The current study examined latent PTSD symptom classes in female veterans who returned from recent military service in Iraq and Afghanistan, and explored military and demographic variables associated with distinct PTSD symptom presentations. Methods: A retrospective analysis was conducted using existing medical records from female Iraq and Afghanistan veterans who were new users of VA mental health outpatient (MHO) care, had received a PTSD diagnosis anytime during the post-deployment period, and completed the PTSD checklist within 30 days of their first MHO visit (N=2425). Results: The LCA results identified four latent classes of PTSD symptom profiles in the sample: High Symptom, Intermediate Symptom, Intermediate Symptom with High Emotional Numbing (EN), and Low Symptom. Race/ethnicity, age, Lime since last deployment, and distance from a VA facility emerged as predictors of PTSD symptom presentation. Limitations: The current study was cross-sectional and utilized administrative data. The results may not be generalizable to female veterans from other service eras. Conclusions: Longer times between end of last deployment and initiation of MHO services were associated with more symptomatic classes. Exploration of PTSD symptom presentation may enhance our understanding of the service needs of female veterans with PTSD, and suggests potential benefits to engaging veterans in MHO soon after last deployment. Published by Elsevier B.V. C1 [Hebenstreit, Claire; Madden, Erin; Maguen, Shira] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Hebenstreit, Claire; Maguen, Shira] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Hebenstreit, C (reprint author), San Francisco VA Med Ctr, PTSD Program 116P, 4150 Clement St, San Francisco, CA 94121 USA. EM Claire.Hebenstreit@va.gov OI Hebenstreit, Claire/0000-0001-5970-2195 FU Department of Defense Award Grant [W81XWH-11-2-0189] FX This research was supported by Department of Defense Award Grant (W81XWH-11-2-0189). NR 52 TC 7 Z9 7 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 2014 VL 166 BP 132 EP 138 DI 10.1016/j.jad.2014.04.061 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AK8UV UT WOS:000338705000019 PM 25012421 ER PT J AU Jasinska, AJ Zorick, T Brody, AL Stein, EA AF Jasinska, Agnes J. Zorick, Todd Brody, Arthur L. Stein, Elliot A. TI Dual role of nicotine in addiction and cognition: A review of neuroimaging studies in humans SO NEUROPHARMACOLOGY LA English DT Review DE Nicotine; Tobacco; Smoking; Dopamine; PET; SPECT; fMRI; Addiction; Cognition ID CEREBRAL-BLOOD-FLOW; STRIATAL DOPAMINE RELEASE; ACETYLCHOLINE-RECEPTOR OCCUPANCY; STATE FUNCTIONAL CONNECTIVITY; POSITRON-EMISSION-TOMOGRAPHY; WORKING-MEMORY TASK; HUMAN-BRAIN; SMOKING-CESSATION; CIGARETTE-SMOKING; TOBACCO SMOKERS AB Substantial evidence demonstrates both nicotine's addiction liability and its cognition-enhancing effects. However, the neurobiological mechanisms underlying nicotine's impact on brain function and behavior remain incompletely understood. Elucidation of these mechanisms is of high clinical importance and may lead to improved therapeutics for smoking cessation as well as for a number of cognitive disorders such as schizophrenia. Neuroimaging techniques such as positron emission tomography (PET), single photon emission computed tomography (SPEC), and functional magnetic resonance imaging (fMRI), which make it possible to study the actions of nicotine in the human brain in vivo, play an increasingly important role in identifying these dual mechanisms of action. In this review, we summarize the current state of knowledge and discuss outstanding questions and future directions in human neuroimaging research on nicotine and tobacco. This research spans from receptor-level PET and SPECT studies demonstrating nicotine occupancy at nicotinic acetylcholine receptors (nAChRs) and upregulation of nAChRs induced by chronic smoking; through nicotine's interactions with the mesocorticolimbic dopamine system believed to mediate nicotine's reinforcing effects leading to dependence; to functional activity and connectivity fMRI studies documenting nicotine's complex behavioral and cognitive effects manifest by its actions on large-scale brain networks engaged both during task performance and at rest. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Published by Elsevier Ltd. C1 [Jasinska, Agnes J.; Stein, Elliot A.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA. [Zorick, Todd; Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Zorick, Todd; Brody, Arthur L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Jasinska, AJ (reprint author), NIDA, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM jasinskaaj@mail.nih.gov; abrody@ucla.edu; EStein@intra.nida.nih.gov FU Intramural Research Program of NIDA; National Institute on Drug Abuse [R01 DA20872]; Tobacco-Related Disease Research Program [19XT-0135]; Merit Review Award from the Department of Veterans Affairs, Office of Research and Development FX Supported by the Intramural Research Program of NIDA (E.A.S., NJ.) and grants R01 DA20872 from the National Institute on Drug Abuse (A.L.B.), 19XT-0135 from the Tobacco-Related Disease Research Program (A.L.B.), and a Merit Review Award from the Department of Veterans Affairs, Office of Research and Development (A.L.B.). NR 156 TC 24 Z9 27 U1 3 U2 55 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2014 VL 84 SI SI BP 111 EP 122 DI 10.1016/j.neuropharm.2013.02.015 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AK7OC UT WOS:000338616600012 PM 23474015 ER PT J AU Koppel, J Acker, C Davies, P Lopez, OL Jimenez, H Azose, M Greenwald, BS Murray, PS Kirkwood, CM Kofler, J Sweet, RA AF Koppel, Jeremy Acker, Chris Davies, Peter Lopez, Oscar L. Jimenez, Heidy Azose, Miriam Greenwald, Blaine S. Murray, Patrick S. Kirkwood, Caitlin M. Kofler, Julia Sweet, Robert A. TI Psychotic Alzheimer's disease is associated with gender-specific tau phosphorylation abnormalities SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Psychosis; Tau; Dementia with Lewy bodies; Alpha-synuclein; Neurofibrillary tangles ID INCREASED FAMILIAL RISK; NEUROFIBRILLARY TANGLES; ATYPICAL ANTIPSYCHOTICS; LEWY BODY; DEMENTIA; DELUSIONS; HALLUCINATIONS; CONSORTIUM; EPIDEMIOLOGY; TRAJECTORIES AB Converging evidence suggests that psychotic Alzheimer's disease (AD + P) is associated with an acceleration of frontal degeneration, with tau pathology playing a primary role. Previous histopathologic and biomarker studies have specifically implicated tau pathology in this condition. To precisely quantify tau abnormalities in the frontal cortex in AD + P, we used a sensitive biochemical assay of total tau and 4 epitopes of phospho-tau relevant in AD pathology in a postmortem sample of AD + P and AD - P. Samples of superior frontal gyrus from 26 AD subjects without psychosis and 45 AD + P subjects with psychosis were analyzed. Results of enzyme-linked immunosorbent assay demonstrate that AD + P females, but not males, had significantly higher levels of phosphorylated tau in the frontal cortex. In males, but not females, AD + P was associated with the presence of alpha-synuclein pathology. These results support a gender dissociation of pathology in AD + P. The design of future studies aimed at the elucidation of cognitive and/or functional outcomes; regional brain metabolic deficits; or genetic correlates of AD + P should take gender into consideration. (C) 2014 Elsevier Inc. All rights reserved. C1 [Koppel, Jeremy; Acker, Chris; Davies, Peter; Jimenez, Heidy; Sweet, Robert A.] Feinstein Inst Med Res, Litwin Zucker Res Ctr Study Alzheimers Dis, Manhasset, NY USA. [Koppel, Jeremy; Greenwald, Blaine S.] North Shore LIJ Hlth Syst, Zucker Hillside Hosp, Glen Oaks, NY USA. [Lopez, Oscar L.; Murray, Patrick S.; Kirkwood, Caitlin M.; Kofler, Julia; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Lopez, Oscar L.; Murray, Patrick S.; Kirkwood, Caitlin M.; Kofler, Julia; Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Azose, Miriam] Touro Coll, Brooklyn, NY USA. VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC Q2, Pittsburgh, PA USA. RP Koppel, J (reprint author), Zucker Hillside Hosp, Litwin Zucker Res Ctr Study Alzheimers Dis, 350 Community Dr, Manhasset, NY 11030 USA. EM jkoppel@nshs.edu OI Murray, Patrick/0000-0002-6525-2888 FU Veterans Health Administration [BX000452]; National Institute on Aging [AG005133, AG027224] FX This work was supported by the Veterans Health Administration (BX000452 to Robert A. Sweet) and the National Institute on Aging (AG005133 to Oscar L. Lopez, AG027224 to Robert A. Sweet). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, the National Institutes of Health, or the United States Government. NR 52 TC 10 Z9 10 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2014 VL 35 IS 9 BP 2021 EP 2028 DI 10.1016/j.neurobiolaging.2014.03.003 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AK1SB UT WOS:000338195100011 PM 24731519 ER PT J AU Liang, S Salas, T Gencaslan, E Li, BJ Habib, SL AF Liang, Sitai Salas, Tiffanie Gencaslan, Emre Li, Baojie Habib, Samy L. TI Tuberin-deficiency downregulates N-cadherin and upregulates vimentin in kidney tumor of TSC patients SO ONCOTARGET LA English DT Article DE N-cadherin; vimentin; Akt; tuberin; mTOR and angiomyolipomas ID REPAIR ENZYME OGG1; SCLEROSIS COMPLEX; MESENCHYMAL-TRANSITION; 3-KINASE/AKT PATHWAY; GAP ACTIVITY; EXPRESSION; GENE; ANGIOMYOLIPOMAS; DISEASE; TISSUES AB Angiomyolipomas (AMLs) are associated with cell fibrosis in kidney of Tuberous Sclerosis Complex patients. The mechanism by which the fibrotic proteins accumulated in AMLs has not been explored. In the present study, we investigated the role of Akt/tuberin/mTOR pathway in the regulation cell fibrosis proteins. AML cells that expressed low levels of tuberin showed less expression of N-cadherin and higher of vimentin proteins compared to HEK293 cells. AML cells infected with Ad-tuberin showed a significant decrease in vimentin and an increase in N-cadherin protein expression. In addition, cells treated with rapamycin showed a significant increase in p-Akt and a decrease in p-p70S6K that was associated with a decrease expression of vimentin and a slight increase expression in N-cadherin. On the other hand, cells treated with Akt inhibitor revealed a significant decrease in p-Akt and p-p70S6K that was associated with a significant decrease in vimentin and an increase in N-cadherin expression. In addition, cells transfected with DN-Akt or DN-S6K show significant increase expression in N-cadherin and a decrease in vimentin. Moreover, cells transfected with siRNA against rictor or siRNA against raptor resulted in a decrease in vimentin and an increase N-cadherin expression. Kidney tumors from TSC patients showed significant decrease in N-cadherin and significant increased in vimentin protein expression compared to control kidney tissues. These data comprise the first report to provide the role of Akt/tuberin/mTORC1/2 in the regulation of N-cadherin and vimentin that are involved in the progression of fibrosis in kidney tumor of TSC patients. C1 [Liang, Sitai; Salas, Tiffanie; Habib, Samy L.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Gencaslan, Emre] Akdeniz Univ, Sch Med, TR-07058 Antalya, Turkey. [Li, Baojie] Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiatr Disorders, BioX Inst, Shanghai 200030, Peoples R China. [Habib, Samy L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Habib, SL (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM habib@uthscsa.edu FU American Heart Association; Merit Review Award from South Texas Veterans Healthcare System FX This work was supported in part by grants from the American Heart Association, and Merit Review Award from South Texas Veterans Healthcare System (to S.L.H.). NR 39 TC 3 Z9 4 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG 30 PY 2014 VL 5 IS 16 BP 6936 EP 6946 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AZ0EX UT WOS:000347920100034 PM 25149531 ER PT J AU Shanmugasundaram, K Nayak, B Shim, EH Livi, CB Block, K Sudarshan, S AF Shanmugasundaram, Karthigayan Nayak, Bijaya Shim, Eun-Hee Livi, Carolina B. Block, Karen Sudarshan, Sunil TI The Oncometabolite Fumarate Promotes Pseudohypoxia Through Noncanonical Activation of NF-kappa B Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cancer Biology; Cell Metabolism; Hypoxia-inducible Factor (HIF); NF-B (NF-KB); Small Molecule; Small ID RENAL-CELL CANCER; PROLINE HYDROXYLATION; PROLYL HYDROXYLATION; KIDNEY CANCER; HIF-ALPHA; HYPOXIA; HYDRATASE; HEREDITARY; KINASES; TBK1 AB Background: We examined alternative mechanisms by which fumarate levels contribute to hypoxia inducible factor (HIF)-1 accumulation and fumarate hydratase (FH)-deficient renal carcinogenesis. Results: Fumarate promotes HIF-1 transcription through Tank binding kinase 1 (TBK1)-dependent noncannonical activation of NF-B signaling. Conclusion: Fumarate-mediated, TBK-dependent accumulation of HIF-1 mediates cell invasion in FH-deficient RCC. Significance: TBK is a novel putative therapeutic target for the treatment of aggressive fumarate-driven tumors. Inactivating mutations of the gene encoding the tricarboxylic acid cycle enzyme fumarate hydratase (FH) have been linked to an aggressive variant of hereditary kidney cancer (hereditary leiomyomatosis and renal cell cancer). These tumors accumulate markedly elevated levels of fumarate. Fumarate is among a growing list of oncometabolites identified in cancers with mutations of genes involved in intermediary metabolism. FH-deficient tumors are notable for their pronounced accumulation of the transcription factor hypoxia inducible factor-1 (HIF-1) and aggressive behavior. To date, HIF-1 accumulation in hereditary leiomyomatosis and renal cell cancer tumors is thought to result from fumarate-dependent inhibition of prolyl hydroxylases and subsequent evasion from von Hippel-Lindau-dependent degradation. Here, we demonstrate a novel mechanism by which fumarate promotes HIF-1 mRNA and protein accumulation independent of the von Hippel-Lindau pathway. Here we demonstrate that fumarate promotes p65 phosphorylation and p65 accumulation at the HIF-1 promoter through non-canonical signaling via the upstream Tank binding kinase 1 (TBK1). Consistent with these data, inhibition of the TBK1/p65 axis blocks HIF-1 accumulation in cellular models of FH loss and markedly reduces cell invasion of FH-deficient RCC cancer cells. Collectively, our data demonstrate a novel mechanism by which pseudohypoxia is promoted in FH-deficient tumors and identifies TBK1 as a novel putative therapeutic target for the treatment of aggressive fumarate-driven tumors. C1 [Shanmugasundaram, Karthigayan; Nayak, Bijaya; Block, Karen] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Livi, Carolina B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Shim, Eun-Hee; Sudarshan, Sunil] Univ Alabama Birmingham, Dept Urol, Birmingham, AL 35294 USA. [Block, Karen] South Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX 78229 USA. RP Block, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM block@uthscsa.edu; sudarshan@uab.edu FU National Institutes of Health [K08 CA138774]; Urology Care Foundation; Astellas Pharma Rising Star Award; America Cancer Society [RSG-12-127-01 CNE]; Veterans Affairs Merit Grants [CPRIT RP120190, P30CA054174] FX This work was supported, in whole or in part, by National Institutes of Health Grant K08 CA138774 (to S. S.), Urology Care Foundation and Astellas Pharma Rising Star Award, and America Cancer Society RSG-12-127-01 CNE (to S. S.) and Veterans Affairs Merit Grants CPRIT RP120190 and P30CA054174 (to K. B). NR 35 TC 8 Z9 9 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 29 PY 2014 VL 289 IS 35 BP 24691 EP 24699 DI 10.1074/jbc.M114.568162 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO7AY UT WOS:000341505600058 PM 25028521 ER PT J AU Zhang, H Singh, KK AF Zhang, Hengshan Singh, Keshav K. TI Global Genetic Determinants of Mitochondrial DNA Copy Number SO PLOS ONE LA English DT Article ID CONGENITAL MUSCULAR-DYSTROPHY; RENAL-CELL CARCINOMA; SACCHAROMYCES-CEREVISIAE; THYMIDINE KINASE; GASTRIC-CANCER; LARGE SUBUNIT; HUMAN-DISEASE; MUTATIONS; DEPLETION; EXPRESSION AB Many human diseases including development of cancer is associated with depletion of mitochondrial DNA (mtDNA) content. These diseases are collectively described as mitochondrial DNA depletion syndrome (MDS). High similarity between yeast and human mitochondria allows genomic study of the budding yeast to be used to identify human disease genes. In this study, we systematically screened the pre-existing respiratory-deficient Saccharomyces cerevisiae yeast strains using fluorescent microscopy and identified 102 nuclear genes whose deletions result in a complete mtDNA loss, of which 52 are not reported previously. Strikingly, these genes mainly encode protein products involved in mitochondrial protein biosynthesis process (54.9%). The rest of these genes either encode protein products associated with nucleic acid metabolism (14.7%), oxidative phosphorylation (3.9%), or other protein products (13.7%) responsible for bud-site selection, mitochondrial intermembrane space protein import, assembly of cytochrome-c oxidase, vacuolar protein sorting, protein-nucleus import, calcium-mediated signaling, heme biosynthesis and iron homeostasis. Thirteen (12.7%) of the genes encode proteins of unknown function. We identified human orthologs of these genes, conducted the interaction between the gene products and linked them to human mitochondrial disorders and other pathologies. In addition, we screened for genes whose defects affect the nuclear genome integrity. Our data provide a systematic view of the nuclear genes involved in maintenance of mitochondrial DNA. Together, our studies i) provide a global view of the genes regulating mtDNA content; ii) provide compelling new evidence toward understanding novel mechanism involved in mitochondrial genome maintenance and iii) provide useful clues in understanding human diseases in which mitochondrial defect and in particular depletion of mitochondrial genome plays a critical role. C1 [Zhang, Hengshan] Fujian Med Univ, Affiliated Hosp 1, Dept Cent Lab, Fuzhou, Peoples R China. [Singh, Keshav K.] Univ Alabama Birmingham, Dept Genet, Ctr Free Radical Biol, Ctr Aging, Birmingham, AL 35294 USA. [Singh, Keshav K.] Univ Alabama Birmingham, UAB Comprehens Canc Ctr, Birmingham, AL USA. [Singh, Keshav K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Singh, KK (reprint author), Univ Alabama Birmingham, Dept Genet, Ctr Free Radical Biol, Ctr Aging, Birmingham, AL 35294 USA. EM kksingh@uab.edu FU Veterans Administration [1I01BX001716]; National Institutes of Health (NIH) [R01CA121904] FX Studies reported in this manuscript were supported in part by Veterans Administration grant 1I01BX001716 and National Institutes of Health (NIH) R01CA121904 (to KKS). Funding agencies has no role in design or data collection. NR 51 TC 3 Z9 3 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 29 PY 2014 VL 9 IS 8 AR e105242 DI 10.1371/journal.pone.0105242 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO2EE UT WOS:000341127500037 PM 25170845 ER PT J AU Pevnick, JM Li, N Asch, SM Jackevicius, CA Bell, DS AF Pevnick, Joshua M. Li, Ning Asch, Steven M. Jackevicius, Cynthia A. Bell, Douglas S. TI Effect of electronic prescribing with formulary decision support on medication tier, copayments, and adherence SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE Clinical decision support; Electronic prescribing; Medication adherence ID DRUG-THERAPY; HEALTH; IMPACT; CARE; INTERVENTIONS; PERSISTENCE; ADOPTION; RECORDS; ASTHMA; COST AB Background: Medication non-adherence is prevalent. We assessed the effect of electronic prescribing (e-prescribing) with formulary decision support on preferred formulary tier usage, copayment, and concomitant adherence. Methods: We retrospectively analyzed 14,682 initial pharmaceutical claims for angiotensin receptor blocker and inhaled steroid medications among 14,410 patients of 2189 primary care physicians (PCPs) who were offered e-prescribing with formulary decision support, including 297 PCPs who adopted it. Formulary decision support was initially non-interruptive, such that formulary tier symbols were displayed adjacent to medication names. Subsequently, interruptive formulary decision support alerts also interrupted e-prescribing when preferred-tier alternatives were available. A difference in differences design was used to compare the pre-post differences in medication tier for each new prescription attributed to non-adopters, low user (<30% usage rate), and high user PCPs (>30% usage rate). Second, we modeled the effect of formulary tier on prescription copayment. Last, we modeled the effect of copayment on adherence (proportion of days covered) to each new medication. Results: Compared with non-adopters, high users of e-prescribing were more likely to prescribe preferred-tier medications (vs. non-preferred tier) when both non-interruptive and interruptive formulary decision support were in place (OR 1.9 [95% CI 1.0-3.4], p = 0.04), but no more likely to prescribe preferred-tier when only non-interruptive formulary decision support was in place (p = 0.90). Preferred-tier claims had only slightly lower mean monthly copayments than non-preferred tier claims (angiotensin receptor blocker: $ 10.60 versus $ 11.81, inhaled steroid: $ 14.86 versus $ 16.42, p < 0.0001). Medication possession ratio was 8% lower for each $ 1.00 increase in monthly copayment to the one quarter power (p < 0.0001). However, we detected no significant direct association between formulary decision support usage and adherence. Conclusion: Interruptive formulary decision support shifted prescribing toward preferred tiers, but these medications were only minimally less expensive in the studied patient population. In this context, formulary decision support did not significantly increase adherence. To impact cost-related non-adherence, formulary decision support will likely need to be paired with complementary drug benefit design. Formulary decision support should be studied further, with particular attention to its effect on adherence in the setting of different benefit designs. C1 [Pevnick, Joshua M.] Cedars Sinai Hlth Syst, Dept Med, Div Gen Internal Med, Los Angeles, CA 90048 USA. [Pevnick, Joshua M.; Bell, Douglas S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Li, Ning] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Asch, Steven M.] Stanford Sch Med, Palo Alto, CA USA. [Asch, Steven M.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA USA. [Bell, Douglas S.] RAND Hlth, Santa Monica, CA USA. RP Pevnick, JM (reprint author), Cedars Sinai Hlth Syst, Dept Med, Div Gen Internal Med, 8700 Beverly Blvd,PACT 400-8G, Los Angeles, CA 90048 USA. EM jpevnick@gmail.com FU Agency for Healthcare Research and Quality [1U18HS016391-01]; Burns and Allen Research Institute at Cedars-Sinai Medical Center; National Center for Advancing Translational Science [UL1TR000124] FX This data was initially gathered during work on grant 1U18HS016391-01 funded by the Agency for Healthcare Research and Quality as part of a larger set of e-prescribing pilot studies (Dr. Bell). This work was also supported by a Clinical Scholars Research Grant from the Burns and Allen Research Institute at Cedars-Sinai Medical Center (Dr. Pevnick), and by the National Center for Advancing Translational Science, Grant UL1TR000124 (Drs. Bell and Pevnick). The authors have no conflicts of interest to disclose. NR 30 TC 2 Z9 2 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD AUG 28 PY 2014 VL 14 AR 79 DI 10.1186/1472-6947-14-79 PG 12 WC Medical Informatics SC Medical Informatics GA AS2KJ UT WOS:000344108600001 PM 25167807 ER PT J AU Papay, K Xie, SX Stern, M Hurtig, H Siderowf, A Duda, JE Minger, J Weintraub, D AF Papay, Kimberly Xie, Sharon X. Stern, Matthew Hurtig, Howard Siderowf, Andrew Duda, John E. Minger, James Weintraub, Daniel TI Naltrexone for impulse control disorders in Parkinson disease A placebo-controlled study SO NEUROLOGY LA English DT Article ID ALZHEIMER-DISEASE; LONGITUDINAL DATA; DEPRESSION; BEHAVIORS; TRIAL; ANTAGONIST; AMANTADINE; DEPENDENCE; SYMPTOMS; MODELS AB Objective: Impulse control disorders (ICDs) in Parkinson disease (PD) are common and can be difficult to manage. The objective of this study was to determine the efficacy and tolerability of naltrexone, an opioid antagonist, for the treatment of ICDs in PD. Methods: Patients with PD (n = 50) and an ICD were enrolled in an 8-week, randomized (1: 1), double-blind, placebo-controlled study of naltrexone 50-100 mg/d (flexible dosing). The primary outcome measure was response based on the Clinical Global Impression-Change score, and the secondary outcome measure was change in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) ICD score. Results: Forty-five patients (90%) completed the study. The Clinical Global Impression-Change response rate difference favoring naltrexone in completers was 19.8%(95% confidence interval [CI] -8.7% to 44.2%). While this difference was not significant (odds ratio = 1.6, 95% CI 0.5-5.2, Wald x(2) [df] = 0.5 [1], p = 0.5), naltrexone treatment led to a significantly greater decrease in QUIP-RS ICD score over time compared with placebo (regression coefficient for interaction term in linear mixed-effects model = 27.37, F[df] = 4.3 [1, 49], p = 0.04). The estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points (95% CI 9.9-19.9) for naltrexone and 7.5 points (95% CI 2.5-12.6) for placebo. Conclusions: Naltrexone treatment was not efficacious for the treatment of ICDs in PD using a global assessment of response, but findings using a PD-specific ICD rating scale support further evaluation of opioid antagonists for the treatment of ICD symptoms in PD. Classification of evidence: This study provides Class I evidence that in patients with PD and an ICD, naltrexone does not significantly increase the probability of achieving response. However, the study lacked the precision to exclude an important difference in response rates. C1 [Papay, Kimberly; Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Xie, Sharon X.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Stern, Matthew; Hurtig, Howard; Duda, John E.; Minger, James] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Siderowf, Andrew] Avid Radiopharmaceut, Philadelphia, PA USA. [Duda, John E.; Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU Clinical Intervention Award from the Michael J. Fox Foundation for Parkinson's Research [NCT1052831] FX This study was funded by a Clinical Intervention Award from the Michael J. Fox Foundation for Parkinson's Research (D.W., NCT1052831). NR 39 TC 14 Z9 15 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 26 PY 2014 VL 83 IS 9 BP 826 EP 833 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AO1SY UT WOS:000341096100012 PM 25037206 ER PT J AU Stefan, M Wei, CG Lombardi, A Li, CW Concepcion, ES Inabnet, WB Owen, R Zhang, WJ Tomer, Y AF Stefan, Mihaela Wei, Chengguo Lombardi, Angela Li, Cheuk Wun Concepcion, Erlinda S. Inabnet, William B., III Owen, Randall Zhang, Weijia Tomer, Yaron TI Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE histone modifications; interferon; thyroiditis ID INTERFERON-INDUCED THYROIDITIS; GRAVES-DISEASE; CHROMATIN-STRUCTURE; ALPHA; TRANSCRIPTION; ASSOCIATION; BINDING; CELLS; SUSCEPTIBILITY; TOLERANCE AB Graves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that epigenetic modifications induced by microenvironmental influences of cytokines can reveal the functionality of GD-associated SNPs. We analyzed genome-wide histone H3 lysine 4 methylation and gene expression in thyroid cells induced by IFN alpha, a key cytokine secreted during viral infections, and overlapped them with known GD-associated SNPs. We mapped an open chromatin region overlapping two adjacent GD-associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid stimulating hormone receptor (TSHR) gene. We then demonstrated that this region functions as a regulatory element through binding of the transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261 site. Repression by PLZF depended on the rs12101261 disease susceptibility allele and was increased by IFNa. Intrathymic TSHR expression was decreased in individuals homozygous for the rs12101261 disease-associated genotype compared with carriers of the disease-protective allele. Our studies discovered a genetic-epigenetic interaction involving a noncoding SNP in the TSHR gene that regulates thymic TSHR gene expression and facilitates C1 [Stefan, Mihaela; Lombardi, Angela; Li, Cheuk Wun; Concepcion, Erlinda S.; Tomer, Yaron] Icahn Sch Med Mt Sinai, Div Endocrinol, New York, NY 10029 USA. [Stefan, Mihaela; Tomer, Yaron] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. [Wei, Chengguo; Zhang, Weijia] Icahn Sch Med Mt Sinai, Dept Med Bioinformat Core, New York, NY 10029 USA. [Inabnet, William B., III; Owen, Randall] Icahn Sch Med Mt Sinai, Dept Surg, New York, NY 10029 USA. RP Tomer, Y (reprint author), Icahn Sch Med Mt Sinai, Div Endocrinol, New York, NY 10029 USA. EM yaron.tomer@mssm.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK061659, DK067555, DK073681]; Department of Veterans Affairs (VA), Office of Research and Development; VA Biomedical Laboratory Research and Development Merit Award [1I01BX002031] FX We thank Dr. Rauf Latif for helpful advice. This work was supported in part by Grants DK061659, DK067555, and DK073681 from the National Institute of Diabetes and Digestive and Kidney Diseases (to Y.T.). In addition, this material is based upon work supported in part by the Department of Veterans Affairs (VA), Office of Research and Development, and by VA Biomedical Laboratory Research and Development Merit Award 1I01BX002031 (to Y.T.). NR 36 TC 18 Z9 21 U1 1 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 26 PY 2014 VL 111 IS 34 BP 12562 EP 12567 DI 10.1073/pnas.1408821111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN7LA UT WOS:000340780300065 PM 25122677 ER PT J AU Marshall, KM He, SQ Zhong, Z Atkinson, C Tomlinson, S AF Marshall, Keely M. He, Songqing Zhong, Zhi Atkinson, Carl Tomlinson, Stephen TI Dissecting the complement pathway in hepatic injury and regeneration with a novel protective strategy SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MEMBRANE ATTACK COMPLEX; ISCHEMIA-REPERFUSION INJURY; C5A RECEPTOR ANTAGONIST; LIVER-REGENERATION; ISCHEMIA/REPERFUSION INJURY; MONOCLONAL-ANTIBODY; PARTIAL-HEPATECTOMY; NLRP3 INFLAMMASOME; KUPFFER CELLS; MICE AB Liver resection is commonly performed under ischemic conditions, resulting in two types of insult to the remnant liver: ischemia reperfusion injury (IRI) and loss of liver mass. Complement inhibition is recognized as a potential therapeutic modality for IRI, but early complement activation products are also essential for liver regeneration. We describe a novel site-targeted murine complement inhibitor, CR2-CD59, which specifically inhibits the terminal membrane attack complex (MAC), and we use this protein to investigate the complement-dependent balance between liver injury and regeneration in a clinical setting of pharmacological inhibition. CR2-CD59 did not impact in vivo generation of C3 and C5 activation products but was as effective as the C3 activation inhibitor CR2-Crry at ameliorating hepatic IRI, indicating that the MAC is the principle mediator of hepatic IRI. Furthermore, unlike C3 or C5 inhibition, CR2-CD59 was not only protective but significantly enhanced hepatocyte proliferation after partial hepatectomy, including when combined with ischemia and reperfusion. Remarkably, CR2-CD59 also enhanced regeneration after 90% hepatectomy and improved long-term survival from 0 to 70%. CR2-CD59 functioned by increasing hepatic TNF and IL-6 levels with associated STAT3 and Akt activation, and by preventing mitochondrial depolarization and allowing recovery of ATP stores. C1 [Marshall, Keely M.; He, Songqing; Atkinson, Carl; Tomlinson, Stephen] Med Univ S Carolina, Darby Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Zhong, Zhi] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [He, Songqing] Guilin Med Univ, Affiliated Hosp, Dept Hepatobiliary Surg, Guilin 541001, Guangxi, Peoples R China. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Darby Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU National Institutes of Health [R56 AI095657, R01 HL86576, R01 HL082485]; National Natural Science Foundation of China [81160066, 31370917]; Guangxi Natural Science Foundation [2013GXNSFCA019012]; Science & Technology Planning Project of Guangxi Province [1140003-79]; Science & Technology Planning Project of Guilin City [20110119-1-8] FX This work was supported by grants from the National Institutes of Health (R56 AI095657, R01 HL86576, and R01 HL082485), the National Natural Science Foundation of China (81160066 and 31370917), Guangxi Natural Science Foundation (2013GXNSFCA019012), the Science & Technology Planning Project of Guangxi Province (1140003-79), and the Science & Technology Planning Project of Guilin City (20110119-1-8). NR 55 TC 11 Z9 13 U1 3 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD AUG 25 PY 2014 VL 211 IS 9 BP 1793 EP 1805 DI 10.1084/jem.20131902 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AQ4EA UT WOS:000342744500010 PM 25113972 ER PT J AU Simmons, DA Knowles, JK Belichenko, NP Banerjee, G Finkle, C Massa, SM Longo, FM AF Simmons, Danielle A. Knowles, Juliet K. Belichenko, Nadia P. Banerjee, Gargi Finkle, Carly Massa, Stephen M. Longo, Frank M. TI A Small Molecule p75(NTR) Ligand, LM11A-31, Reverses Cholinergic Neurite Dystrophy in Alzheimer's Disease Mouse Models with Mid- to Late-Stage Disease Progression SO PLOS ONE LA English DT Article ID P75 NEUROTROPHIN RECEPTOR; NERVE GROWTH-FACTOR; AMYLOID PRECURSOR PROTEIN; BASAL FOREBRAIN NEURONS; TRANSGENIC MICE; COGNITIVE IMPAIRMENT; BETA PROTEIN; EXPRESSION; BRAIN; DEFICITS AB Degeneration of basal forebrain cholinergic neurons contributes significantly to the cognitive deficits associated with Alzheimer's disease (AD) and has been attributed to aberrant signaling through the neurotrophin receptor p75 (p75(NTR)). Thus, modulating p75(NTR) signaling is considered a promising therapeutic strategy for AD. Accordingly, our laboratory has developed small molecule p75(NTR) ligands that increase survival signaling and inhibit amyloid-beta-induced degenerative signaling in in vitro studies. Previous work found that a lead p75(NTR) ligand, LM11A-31, prevents degeneration of cholinergic neurites when given to an AD mouse model in the early stages of disease pathology. To extend its potential clinical applications, we sought to determine whether LM11A-31 could reverse cholinergic neurite atrophy when treatment begins in AD mouse models having mid-to late stages of pathology. Reversing pathology may have particular clinical relevance as most AD studies involve patients that are at an advanced pathological stage. In this study, LM11A-31 (50 or 75 mg/kg) was administered orally to two AD mouse models, Thy-1 hAPP(Lond/Swe) (APP(L/S)) and Tg2576, at age ranges during which marked AD-like pathology manifests. In mid-stage male APP(L/S) mice, LM11A-31 administered for 3 months starting at 6-8 months of age prevented and/or reversed atrophy of basal forebrain cholinergic neurites and cortical dystrophic neurites. Importantly, a 1 month LM11A-31 treatment given to male APP(L/S) mice (12-13 months old) with late-stage pathology reversed the degeneration of cholinergic neurites in basal forebrain, ameliorated cortical dystrophic neurites, and normalized increased basal forebrain levels of p75(NTR). Similar results were seen in female Tg2576 mice. These findings suggest that LM11A-31 can reduce and/or reverse fundamental AD pathologies in late-stage AD mice. Thus, targeting p75(NTR) is a promising approach to reducing AD-related degenerative processes that have progressed beyond early stages. C1 [Simmons, Danielle A.; Knowles, Juliet K.; Belichenko, Nadia P.; Banerjee, Gargi; Finkle, Carly; Longo, Frank M.] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Knowles, Juliet K.; Longo, Frank M.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Massa, Stephen M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Massa, Stephen M.] Univ Calif San Francisco, Lab Computat Neurochem & Drug Discovery, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Longo, FM (reprint author), Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. EM longo@stanford.edu FU Veteran's Administration; [NIA UO1 AG032225]; [NINDS F30 NA051971] FX This work was supported by grants NIA UO1 AG032225 (FML), NINDS F30 NA051971 (JKK) and the Veteran's Administration (SMM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 10 Z9 10 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 25 PY 2014 VL 9 IS 8 AR e102136 DI 10.1371/journal.pone.0102136 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN9TR UT WOS:000340952200004 PM 25153701 ER PT J AU Gallun, FJ Diedesch, AC Kampel, SD Jakien, KM AF Gallun, Frederick J. Diedesch, Anna C. Kampel, Sean D. Jakien, Kasey M. TI Independent impacts of age and hearing loss on spatial release in a complex auditory environment (vol 8, pg 264, 2014) SO FRONTIERS IN NEUROSCIENCE LA English DT Correction DE spatial hearing; aging; hearing loss; virtual spatial array; sensation level C1 [Gallun, Frederick J.; Kampel, Sean D.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, Portland, OR 97239 USA. [Gallun, Frederick J.; Jakien, Kasey M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Diedesch, Anna C.] Vanderbilt Univ, Nashville, TN 37235 USA. RP Gallun, FJ (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, Portland, OR 97239 USA. EM frederick.gallun@va.gov NR 2 TC 0 Z9 0 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD AUG 22 PY 2014 VL 8 AR 264 DI 10.3389/fnins.2014.00264 PG 1 WC Neurosciences SC Neurosciences & Neurology GA AW8KY UT WOS:000346511900001 ER PT J AU Shen, KZ Yakhnitsa, V Munhall, AC Johnson, SW AF Shen, K. -Z. Yakhnitsa, V. Munhall, A. C. Johnson, S. W. TI AMP KINASE REGULATES K-ATP CURRENTS EVOKED BY NMDA RECEPTOR STIMULATION IN RAT SUBTHALAMIC NUCLEUS NEURONS SO NEUROSCIENCE LA English DT Article DE AMP kinase; NMDA; Subthalamic nucleus; Brain slice; K-ATP; Patch-clamp ID ACTIVATED PROTEIN-KINASE; SENSITIVE POTASSIUM CHANNELS; CENTRAL-NERVOUS-SYSTEM; INSULIN-SECRETION; IN-VITRO; GLOBUS-PALLIDUS; CELLULAR-ENERGY; ARCUATE NUCLEUS; NEUROPEPTIDE-Y; BASAL GANGLIA AB Our lab recently showed that N-methyl-D-aspartate (NMDA) evokes ATP-sensitive K+ (K-ATP) currents in subthalamic nucleus (STN) neurons in slices of the rat brain. Both K-ATP channels and 5'-adenosine monophosphate-activated protein kinase (AMPK) are considered cellular energy sensors because their activities are influenced by the phosphorylation state of adenosine nucleotides. Moreover, AMPK has been shown to regulate K-ATP function in a variety of tissues including pancreas, cardiac myocytes, and hypothalamus. We used whole-cell patch clamp recordings to study the effect of AMPK activation on K-ATP channel function in STN neurons in slices of the rat brain. We found that bath or intracellular application of the AMPK activators A769662 and PT1 augmented tolbutamide-sensitive K-ATP currents evoked by NMDA receptor stimulation. The effect of AMPK activators was blocked by the AMPK inhibitor dorsomorphin (compound C), and by STO609, an inhibitor of the upstream AMPK activator CaMKK beta. AMPK augmentation of NMDA-induced K-ATP current was also blocked by intracellular BAPTA and by inhibitors of nitric oxide synthase and guanylyl cyclase. However, A769662 did not augment currents evoked by the K-ATP channel opener diazoxide. In the presence of NMDA, A769662 inhibited depolarizing plateau potentials and burst firing, both of which could be antagonized by tolbutamide or dorsomorphin. These studies show that AMPK augments NMDA-induced K-ATP currents by a Ca2+-dependent process that involves nitric oxide and cGMP. By augmenting K-ATP currents, AMPK activation would be expected to dampen the excitatory effect of glutamate-mediated transmission in the STN. Published by Elsevier Ltd. on behalf of IBRO. C1 [Shen, K. -Z.; Yakhnitsa, V.; Munhall, A. C.; Johnson, S. W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, S. W.] Portland VA Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, Portland, OR 97207 USA. EM johnsost@ohsu.edu FU NIH [NS038715]; Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center FX This work was supported by NIH grant NS038715 and by the Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center. NR 59 TC 5 Z9 5 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD AUG 22 PY 2014 VL 274 BP 138 EP 152 DI 10.1016/j.neuroscience.2014.05.031 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AK8XO UT WOS:000338712300014 PM 24875176 ER PT J AU Woo, JH Wang, SM Melhem, ER Gee, JC Cucchiara, A McCluskey, L Elman, L AF Woo, John H. Wang, Sumei Melhem, Elias R. Gee, James C. Cucchiara, Andrew McCluskey, Leo Elman, Lauren TI Linear Associations between Clinically Assessed Upper Motor Neuron Disease and Diffusion Tensor Imaging Metrics in Amyotrophic Lateral Sclerosis SO PLOS ONE LA English DT Article ID CORTICOSPINAL TRACT; WHITE-MATTER; MRI; ALS; REGISTRATION; TRACTOGRAPHY; INVOLVEMENT; ATLAS; TOOL AB Objective: To assess the relationship between clinically assessed Upper Motor Neuron (UMN) disease in Amyotrophic Lateral Sclerosis (ALS) and local diffusion alterations measured in the brain corticospinal tract (CST) by a tractography-driven template-space region-of-interest (ROI) analysis of Diffusion Tensor Imaging (DTI). Methods: This cross-sectional study included 34 patients with ALS, on whom DTI was performed. Clinical measures were separately obtained including the Penn UMN Score, a summary metric based upon standard clinical methods. After normalizing all DTI data to a population-specific template, tractography was performed to determine a region-of-interest (ROI) outlining the CST, in which average Mean Diffusivity (MD) and Fractional Anisotropy (FA) were estimated. Linear regression analyses were used to investigate associations of DTI metrics (MD, FA) with clinical measures (Penn UMN Score, ALSFRS-R, duration-of-disease), along with age, sex, handedness, and El Escorial category as covariates. Results: For MD, the regression model was significant (p = 0.02), and the only significant predictors were the Penn UMN Score (p = 0.005) and age (p = 0.03). The FA regression model was also significant (p = 0.02); the only significant predictor was the Penn UMN Score (p = 0.003). Conclusions: Measured by the template-space ROI method, both MD and FA were linearly associated with the Penn UMN Score, supporting the hypothesis that DTI alterations reflect UMN pathology as assessed by the clinical examination. C1 [Woo, John H.; Wang, Sumei; Gee, James C.] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cucchiara, Andrew] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [McCluskey, Leo; Elman, Lauren] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Woo, John H.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Melhem, Elias R.] Univ Maryland, Dept Radiol, Baltimore, MD 21201 USA. RP Woo, JH (reprint author), Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. EM john.woo@uphs.upenn.edu FU National Institutes of Health [NS063111, NS065347, DA022807, NS045839, AG032953]; Greater Philadelphia Chapter of the ALS Association; Philadelphia Veterans Affairs Medical Center; National Center for Advancing Translational Sciences (NCATS) of the NIH [UL1TR000003] FX The authors acknowledge the financial support of the following institutions: National Institutes of Health (NS063111, NS065347, DA022807, NS045839, AG032953), the Greater Philadelphia Chapter of the ALS Association, and the Philadelphia Veterans Affairs Medical Center. This project was also supported by Grant Number UL1TR000003 from the National Center for Advancing Translational Sciences (NCATS) of the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official view of NCATS or the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 3 Z9 3 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 21 PY 2014 VL 9 IS 8 AR e105753 DI 10.1371/journal.pone.0105753 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO1WL UT WOS:000341106100118 PM 25144708 ER PT J AU McDougal, SJ Alexander, J Dhanireddy, S Harrington, RD Stekler, JD AF McDougal, Sarah J. Alexander, Jeremiah Dhanireddy, Shireesha Harrington, Robert D. Stekler, Joanne D. TI Non-Occupational Post-Exposure Prophylaxis for HIV: 10-Year Retrospective Analysis in Seattle, Washington SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTION-DRUG EXPOSURE; SEXUAL EXPOSURE; COST-EFFECTIVENESS; ZIDOVUDINE TREATMENT; UNITED-STATES; INFECTION; RISK; MEN; TRANSMISSION AB Despite treatment guidelines in place since 2005, non-occupational post-exposure HIV prophylaxis (nPEP) remains an underutilized prevention strategy. We conducted a retrospective chart review of patients presenting to a publicly-funded HIV clinic in Seattle, Washington for nPEP between 2000 and 2010 (N = 360). nPEP prescriptions were provided for 324 (90%) patients; 83% of prescription decisions were appropriate according to Centers for Disease Control and Prevention guidelines, but only 31% (N = 111/360) of patients were considered "high risk.'' In order to use limited resources most efficiently, public health agencies should target messaging for this high-cost intervention to individuals with high-risk HIV exposures. C1 [McDougal, Sarah J.; Alexander, Jeremiah; Dhanireddy, Shireesha; Harrington, Robert D.; Stekler, Joanne D.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Stekler, Joanne D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Alexander, Jeremiah] Vet Affairs Puget Sound, Gen Med Serv, Seattle, WA USA. RP McDougal, SJ (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM sjmcd13@uw.edu NR 36 TC 4 Z9 4 U1 3 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 20 PY 2014 VL 9 IS 8 AR e105030 DI 10.1371/journal.pone.0105030 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AQ3JB UT WOS:000342687200048 PM 25140868 ER PT J AU Tsai, J Elhai, JD Pietrzak, RH Hoff, RA Harpaz-Rotem, I AF Tsai, Jack Elhai, Jon D. Pietrzak, Robert H. Hoff, Rani A. Harpaz-Rotem, Ilan TI Comparing four competing models of depressive symptomatology: A confirmatory factor analytic study of 986,647 US veterans SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Depression; Veterans; Confirmatory factor analyses ID SPINAL-CORD-INJURY; PATIENT HEALTH QUESTIONNAIRE-9; NATIONAL-COMORBIDITY-SURVEY; OF-FIT INDEXES; MAJOR DEPRESSION; PRIMARY-CARE; SYMPTOMS; EPIDEMIOLOGY; ANXIETY; INVARIANCE AB Background: Few rigorous studies have examined the factor structure of major depression symptoms as assessed by current diagnostic systems. This study evaluated four competing models of depressive symptomatology among a large, heterogeneous sample of U.S. veterans. Methods: To determine the best fitting model of major depressive symptoms among four competing models, this study conducted a series of confirmatory factor analyses on a national sample of 986,647 U.S. veterans. Results: A two-factor model first reported by Krause, Reed, and McArdle (2010) provided superior fit to symptom-level data compared to three other models. The optimal model consists of a somatic factor including anhedonia, sleep difficulties, fatigue, appetite changes, concentration difficulties, and psychomotor agitation; and a non-somatic factor including depressed mood, feelings of worthlessness, and thoughts of death. Factorial invariance testing found this model to be invariant by gender and major depression diagnosis. Limitations: A widely used self-report measure of depression was used and the sample consisted solely of veterans so further study is needed with clinician-administered measures and non-veteran samples. Conclusions: Together, these findings support separating symptoms of major depression into somatic and non-somatic factors which may have clinical relevance, and help clarify debates about the factor structure of depressive symptoms. Published by Elsevier B.V. C1 [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT 06516 USA. [Tsai, Jack; Pietrzak, Robert H.; Hoff, Rani A.; Harpaz-Rotem, Ilan] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. [Elhai, Jon D.] Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. [Elhai, Jon D.] Univ Toledo, Dept Psychiat, Toledo, OH 43606 USA. [Pietrzak, Robert H.; Harpaz-Rotem, Ilan] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT 06516 USA. [Hoff, Rani A.] Vet Affairs Northeast Program Evaluat Ctr, West Haven, CT 06516 USA. RP Tsai, J (reprint author), US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM Jack.Tsai@yale.edu OI Tsai, Jack/0000-0002-0329-648X FU Bristol Meyers Squibb Foundation; United States Department of Veterans Affairs, Office of Research and Development FX None of the authors report any conflicts of interest related to this work. Dr. Tsai has received funding from the Bristol Meyers Squibb Foundation, which had no influence on this work. This work was supported by the United States Department of Veterans Affairs, Office of Research and Development. The views presented here are those of the authors alone and do not represent the position of any federal agency or of the United States Government. NR 24 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD AUG 20 PY 2014 VL 165 BP 166 EP 169 DI 10.1016/j.jad.2014.04.075 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AJ7FF UT WOS:000337861900026 PM 24882195 ER PT J AU Kansagara, D Papak, J Pasha, AS O'Neil, M Freeman, M Relevo, R Quinones, A Motu'apuaka, M Jou, JH AF Kansagara, Devan Papak, Joel Pasha, Amirala S. O'Neil, Maya Freeman, Michele Relevo, Rose Quinones, Ana Motu'apuaka, Makalapua Jou, Janice H. TI Screening for Hepatocellular Carcinoma in Chronic Liver Disease A Systematic Review SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC VIRAL-HEPATITIS; CIRRHOTIC-PATIENTS; PATIENT SURVIVAL; NATURAL-HISTORY; SURVEILLANCE PROGRAM; COST-EFFECTIVENESS; CLINICAL-PRACTICE; CANCER INCIDENCE; EARLY-DIAGNOSIS AB Background: Guidelines recommend routine screening for hepatocellular carcinoma (HCC) in high-risk patients, but the strength of evidence supporting these recommendations is unclear. Purpose: To review the benefits and harms of HCC screening in patients with chronic liver disease. Data Sources: MEDLINE, PsycINFO, and ClinicalTrials.gov from inception to April 2014; Cochrane databases to June 2013; reference lists; and technical advisors. Study Selection: English-language trials and observational studies comparing screening versus no screening, studies of harms, and trials comparing different screening intervals. Data Extraction: Mortality and adverse events were the outcomes of interest. Individual-study quality and the overall strength of evidence were dual-reviewed using published criteria. Data Synthesis: Of 13 801 citations, 22 studies met inclusion criteria. The overall strength of evidence on the effects of screening was very low. One large trial of patients with hepatitis B found decreased HCC mortality with periodic ultrasonographic screening (rate ratio, 0.63 [95% CI, 0.41 to 0.98]), but the study was limited by methodological flaws. Another trial in patients with hepatitis B found no survival benefit with periodic alpha-fetoprotein screening. In 18 observational studies, screened patients had earlier-stage HCC than clinically diagnosed patients, but lead- and length-time biases confounded the effects on mortality. Two trials found no survival differences between shorter (3- to 4-month) and longer (6- to 12-month) screening intervals. Harms of screening were not well-studied. Limitations: Only English-language studies were included. The evidence base is limited by methodological issues and a paucity of trials. Conclusion: There is very-low-strength evidence about the effects of HCC screening on mortality in patients with chronic liver disease. Screening tests can identify early-stage HCC, but whether systematic screening leads to a survival advantage over clinical diagnosis is uncertain. C1 [Kansagara, Devan; O'Neil, Maya; Freeman, Michele; Relevo, Rose] Portland VA Med Ctr, Portland, OR 97239 USA. [Papak, Joel; Jou, Janice H.] Portland VA Med Ctr, Dept Med, Portland, OR 97239 USA. [Pasha, Amirala S.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Quinones, Ana] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Motu'apuaka, Makalapua] Oregon Evidence Based Practice Ctr, Portland, OR 97233 USA. RP Kansagara, D (reprint author), Portland VA Med Ctr, RD71,3710 SW US Veterans Hosp Rd, Portland, OR 97239 USA. EM kansagar@ohsu.edu FU U.S. Department of Veterans Affairs Quality Enhancement Research Initiative FX U.S. Department of Veterans Affairs Quality Enhancement Research Initiative. NR 56 TC 38 Z9 39 U1 2 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 19 PY 2014 VL 161 IS 4 BP 261 EP + DI 10.7326/M14-0558 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AP8RU UT WOS:000342347300016 PM 24934699 ER PT J AU Zipkin, DA Umscheid, CA Keating, NL Allen, E Aung, K Beyth, R Kaatz, S Mann, DM Sussman, JB Korenstein, D Schardt, C Nagi, A Sloane, R Feldstein, DA AF Zipkin, Daniella A. Umscheid, Craig A. Keating, Nancy L. Allen, Elizabeth Aung, Koko Beyth, Rebecca Kaatz, Scott Mann, Devin M. Sussman, Jeremy B. Korenstein, Deborah Schardt, Connie Nagi, Avishek Sloane, Richard Feldstein, David A. TI Evidence-Based Risk Communication A Systematic Review SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER RISKS; DECISION-MAKING; PRESENTING RISK; DIFFERENT FORMATS; RELATIVE RISK; QUANTITATIVE INFORMATION; FRAMING INFORMATION; INFORMING PATIENTS; TREATMENT CHOICES AB Background: Effective communication of risks and benefits to patients is critical for shared decision making. Purpose: To review the comparative effectiveness of methods of communicating probabilistic information to patients that maximize their cognitive and behavioral outcomes. Data Sources: PubMed (1966 to March 2014) and CINAHL, EMBASE, and the Cochrane Central Register of Controlled Trials (1966 to December 2011) using several keywords and structured terms. Study Selection: Prospective or cross-sectional studies that recruited patients or healthy volunteers and compared any method of communicating probabilistic information with another method. Data Extraction: Two independent reviewers extracted study characteristics and assessed risk of bias. Data Synthesis: Eighty-four articles, representing 91 unique studies, evaluated various methods of numerical and visual risk display across several risk scenarios and with diverse outcome measures. Studies showed that visual aids (icon arrays and bar graphs) improved patients' understanding and satisfaction. Presentations including absolute risk reductions were better than those including relative risk reductions for maximizing accuracy and seemed less likely than presentations with relative risk reductions to influence decisions to accept therapy. The presentation of numbers needed to treat reduced understanding. Comparative effects of presentations of frequencies (such as 1 in 5) versus event rates (percentages, such as 20%) were inconclusive. Limitation: Most studies were small and highly variable in terms of setting, context, and methods of administering interventions. Conclusion: Visual aids and absolute risk formats can improve patients' understanding of probabilistic information, whereas numbers needed to treat can lessen their understanding. Due to study heterogeneity, the superiority of any single method for conveying probabilistic information is not established, but there are several good options to help clinicians communicate with patients. C1 [Zipkin, Daniella A.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Umscheid, Craig A.] Univ Penn, Ctr Evidence Based Practice, Philadelphia, PA 19104 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Allen, Elizabeth] Portland VA Med Ctr, Portland, OR 97207 USA. [Aung, Koko] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Beyth, Rebecca] North Florida South Georgia Vet Hlth Syst, Geriatric Res Educ & Clin Ctr T2 182, Gainesville, FL 32608 USA. [Kaatz, Scott] Hurley Med Ctr, Flint, MI 48503 USA. [Mann, Devin M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Sussman, Jeremy B.] Ctr Clin Management Res, Ann Arbor, MI 48109 USA. [Korenstein, Deborah] Amer Coll Physicians, Philadelphia, PA 19106 USA. [Schardt, Connie] Univ N Carolina, Sch Lib & Informat Sci, Chapel Hill, NC 27599 USA. [Nagi, Avishek] Vet Affairs Med Ctr, Durham, NC 27705 USA. [Sloane, Richard] Duke Univ, Med Ctr, Ctr Study Aging, Durham, NC 27710 USA. [Feldstein, David A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53705 USA. RP Zipkin, DA (reprint author), Duke Univ, Med Ctr, Box 2992, Durham, NC 27710 USA. EM daniella.zipkin@duke.edu OI Mann, Devin/0000-0002-2099-0852 NR 103 TC 41 Z9 41 U1 6 U2 32 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 19 PY 2014 VL 161 IS 4 BP 270 EP + DI 10.7326/M14-0295 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AP8RU UT WOS:000342347300017 PM 25133362 ER PT J AU Liu, J Wang, PP Zou, LY Qu, J Litovsky, S Umeda, P Zhou, LF Chatham, J Marsh, SA Dell'Italia, LJ Lloyd, SG AF Liu, Jian Wang, Peipei Zou, Luyun Qu, Jing Litovsky, Silvio Umeda, Patrick Zhou, Lufang Chatham, John Marsh, Susan A. Dell'Italia, Louis J. Lloyd, Steven G. TI High-fat, low-carbohydrate diet promotes arrhythmic death and increases myocardial ischemia-reperfusion injury in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE diet; myocardial ischemia; reperfusion injury; mitochondria; arrhythmia ID ACID OXIDATION; CARDIAC-FUNCTION; GENE-EXPRESSION; VENTRICULAR-FIBRILLATION; MITOCHONDRIAL DYNAMICS; LIPID-ACCUMULATION; HEART-DISEASE; HIGH-PROTEIN; DYSFUNCTION; ARRHYTHMOGENESIS AB High-fat, low-carbohydrate diets (HFLCD) are often eaten by humans for a variety of reasons, but the effects of such diets on the heart are incompletely understood. We evaluated the impact of HFLCD on myocardial ischemia/reperfusion (I/R) using an in vivo model of left anterior descending coronary artery ligation. Sprague-Dawley rats (300 g) were fed HFLCD (60% calories fat, 30% protein, 10% carbohydrate) or control (CONT; 16% fat, 19% protein, 65% carbohydrate) diet for 2 wk and then underwent open chest I/R. At baseline (preischemia), diet did not affect left ventricular (LV) systolic and diastolic function. Oil red O staining revealed presence of lipid in the heart with HFLCD but not in CONT. Following I/R, recovery of LV function was decreased in HFLCD. HFLCD hearts exhibited decreased ATP synthase and increased uncoupling protein-3 gene and protein expression. HFLCD downregulated mitochondrial fusion proteins and upregulated fission proteins and store-operated Ca2+ channel proteins. HFLCD led to increased death during I/R; 6 of 22 CONT rats and 16 of 26 HFLCD rats died due to ventricular arrhythmias and hemodynamic shock. In surviving rats, HFLCD led to larger infarct size. We concluded that in vivo HFLCD does not affect nonischemic LV function but leads to greater myocardial injury during I/R, with increased risk of death by pump failure and ventricular arrhythmias, which might be associated with altered cardiac energetics, mitochondrial fission/fusion dynamics, and store-operated Ca2+ channel expression. C1 [Liu, Jian; Qu, Jing; Umeda, Patrick; Zhou, Lufang; Dell'Italia, Louis J.; Lloyd, Steven G.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Zou, Luyun; Litovsky, Silvio; Chatham, John] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Wang, Peipei] Natl Univ Singapore, Natl Univ Hlth Syst, Cardiovasc Res Inst, Singapore 117548, Singapore. [Marsh, Susan A.] Washington State Univ, Dept Clin Pharmacol, Pullman, WA 99164 USA. [Dell'Italia, Louis J.; Lloyd, Steven G.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Lloyd, SG (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, D-101 Cardiac MRI,1808 7th Ave South, Birmingham, AL 35294 USA. EM sglloyd@uab.edu RI Marsh, Sue/J-3711-2014 OI Marsh, Sue/0000-0002-7530-0417 FU American Heart Association (Scientist Development Grant) [0735212N]; National Institutes of Health [P30DK056336] FX This work was supported in part by the American Heart Association (Scientist Development Grant 0735212N) and by the National Institutes of Health (P30DK056336). NR 65 TC 3 Z9 3 U1 1 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG 15 PY 2014 VL 307 IS 4 BP H598 EP H608 DI 10.1152/ajpheart.00058.2014 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA AN8FZ UT WOS:000340840200013 PM 24929857 ER PT J AU Smith, JA Stallons, LJ Schnellmann, RG AF Smith, Joshua A. Stallons, L. Jay Schnellmann, Rick G. TI Renal cortical hexokinase and pentose phosphate pathway activation through the EGFR/Akt signaling pathway in endotoxin-induced acute kidney injury SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE lipopolysaccharide; acute kidney injury; hexokinase; EGFR; pentose phosphate pathway ID GROWTH-FACTOR RECEPTOR; GLYCOGEN-SYNTHESIS PATHWAY; OXIDATIVE STRESS; IN-VIVO; MITOCHONDRIAL HEXOKINASE; OXYGEN-CONSUMPTION; AKT INHIBITOR; FAILURE; METABOLISM; CELLS AB While disruption of energy production is an important contributor to renal injury, metabolic alterations in sepsis-induced AKI remain understudied. We assessed changes in renal cortical glycolytic metabolism in a mouse model of sepsis-induced AKI. A specific and rapid increase in hexokinase (HK) activity (similar to 2-fold) was observed 3 h after LPS exposure and maintained up to 18 h, in association with a decline in renal function as measured by blood urea nitrogen (BUN). LPS-induced HK activation occurred independently of HK isoform expression or mitochondrial localization. No other changes in glycolytic enzymes were observed. LPS-mediated HK activation was not sufficient to increase glycolytic flux as indicated by reduced or unchanged pyruvate and lactate levels in the renal cortex. LPS-induced HK activation was associated with increased glucose-6-phosphate dehydrogenase activity but not glycogen production. Mechanistically, LPS-induced HK activation was attenuated by pharmacological inhibitors of the EGF receptor (EGFR) and Akt, indicating that EGFR/phosphatidylinositol 3-kinase/Akt signaling is responsible. Our findings reveal LPS rapidly increases renal cortical HK activity in an EGFR-and Akt-dependent manner and that HK activation is linked to increased pentose phosphate pathway activity. C1 [Smith, Joshua A.; Stallons, L. Jay; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institute of General Medical Sciences [GM084147, P20GM103542-02]; National Center for Research Resources [UL1-RR029882, C06-RR015455]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [5I01 BX-000851]; South Carolina Clinical and Translational Research Institute at the Medical University of South Carolina FX This material is based on work supported in part by National Institute of General Medical Sciences Grants GM084147 (to R. G. Schnellmann) and P20GM103542-02 (to South Carolina COBRE in Oxidants, Redox Balance, and Stress Signaling); National Center for Research Resources Grant UL1-RR029882; the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [Grant 5I01 BX-000851 (to R. G. Schnellmann)], and the South Carolina Clinical and Translational Research Institute at the Medical University of South Carolina. Animal facilities were funded by National Center for Research Resources Grant C06-RR015455. NR 75 TC 4 Z9 4 U1 1 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG 15 PY 2014 VL 307 IS 4 BP F435 EP F444 DI 10.1152/ajprenal.00271.2014 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AO1PN UT WOS:000341085600008 PM 24990892 ER PT J AU Moser, R Xu, C Kao, M Annis, J Lerma, LA Schaupp, CM Gurley, KE Jang, IS Biktasova, A Yarbrough, WG Margolin, AA Grandori, C Kemp, CJ Mendez, E AF Moser, Russell Xu, Chang Kao, Michael Annis, James Lerma, Luisa Angelica Schaupp, Christopher M. Gurley, Kay E. Jang, In Sock Biktasova, Asel Yarbrough, Wendell G. Margolin, Adam A. Grandori, Carla Kemp, Christopher J. Mendez, Eduardo TI Functional Kinomics Identifies Candidate Therapeutic Targets in Head and Neck Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; FOCAL-ADHESION KINASE; LOCALLY ADVANCED HEAD; DNA-DAMAGING AGENTS; SRC FAMILY KINASES; MALIGNANT PROGRESSION; TYROSINE KINASE; TUMOR-CELLS; WEE1 KINASE AB Purpose: To identify novel therapeutic drug targets for p53-mutant head and neck squamous cell carcinoma (HNSCC). Experimental Design: RNAi kinome viability screens were performed on HNSCC cells, including autologous pairs from primary tumor and recurrent/metastatic lesions, and in parallel on murine squamous cell carcinoma (MSCC) cells derived from tumors of inbred mice bearing germline mutations in Trp53, and p53 regulatory genes: Atm, Prkdc, and p19(Arf). Cross-species analysis of cell lines stratified by p53 mutational status and metastatic phenotype was used to select 38 kinase targets. Both primary and secondary RNAi validation assays were performed on additional HNSCC cell lines to credential these kinase targets using multiple phenotypic endpoints. Kinase targets were also examined via chemical inhibition using a panel of kinase inhibitors. A preclinical study was conducted on the WEE1 kinase inhibitor, MK-1775. Results: Our functional kinomics approach identified novel survival kinases in HNSCC involved in G(2)-M cell-cycle checkpoint, SFK, PI3K, and FAK pathways. RNAi-mediated knockdown and chemical inhibition of the WEE1 kinase with a specific inhibitor, MK-1775, had a significant effect on both viability and apoptosis. Sensitivity to the MK-1775 kinase inhibitor is in part determined by p53 mutational status, and due to unscheduled mitotic entry. MK-1775 displays single-agent activity and potentiates the efficacy of cisplatin in a p53-mutant HNSCC xenograft model. Conclusions: WEE1 kinase is a potential therapeutic drug target for HNSCC. This study supports the application of a functional kinomics strategy to identify novel therapeutic targets for cancer. (C) 2014 AACR. C1 [Moser, Russell; Gurley, Kay E.; Grandori, Carla; Kemp, Christopher J.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. [Xu, Chang; Kao, Michael; Lerma, Luisa Angelica; Mendez, Eduardo] Univ Washington, Med Ctr, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Xu, Chang; Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Annis, James; Grandori, Carla] Univ Washington Med Res, Inst Stem Cell & Regenerat Med, Quellos High Throughput Facil, Seattle, WA USA. [Schaupp, Christopher M.] Univ Washington, Dept Environm & Occupat Hlth Sci, Toxicol Program, Seattle, WA 98195 USA. [Jang, In Sock; Margolin, Adam A.] Sage Bionetworks, Seattle, WA USA. [Biktasova, Asel; Yarbrough, Wendell G.] Yale Univ, Sch Med, Dept Surg Otolaryngol Head & Neck Surg, New Haven, CT USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. RP Mendez, E (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North, Seattle, WA 98109 USA. EM cjkemp@fhcrc.org; edmendez@u.washington.edu FU FHCRC/UW Cancer Consortium Pilot grants from the NIH [P30CA015704]; National Center for Research Resources [5KL2RR025015]; Howard Hughes Medical Institute Early Physician-Scientist Career Development Award; American Cancer Society [RSG TBG-123653]; Mouse Models of Human Cancer Consortium [U01 CA141550]; National Institute of Environmental Health Science [ES020116]; Integrated Cancer Biology Program [54CA149237]; National Cancer Institute [U01 CA176303]; Department of Otolaryngology/Head and Neck Surgery at the University of Washington; VA Puget Sound Health Care System FX This work was supported by two FHCRC/UW Cancer Consortium Pilot grants from the NIH (P30CA015704); the National Center for Research Resources (5KL2RR025015); the Howard Hughes Medical Institute Early Physician-Scientist Career Development Award; American Cancer Society grant (RSG TBG-123653); the Mouse Models of Human Cancer Consortium (U01 CA141550); the National Institute of Environmental Health Science (ES020116); the Integrated Cancer Biology Program (54CA149237); National Cancer Institute grant (U01 CA176303); and center funds from the Department of Otolaryngology/Head and Neck Surgery at the University of Washington and VA Puget Sound Health Care System NR 50 TC 14 Z9 14 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2014 VL 20 IS 16 BP 4274 EP 4288 DI 10.1158/1078-0432.CCR-13-2858 PG 15 WC Oncology SC Oncology GA AO2WB UT WOS:000341186100012 PM 25125259 ER PT J AU Singhi, AD Nikiforova, MN Fasanella, KE McGrath, KM Pai, RK Ohori, NP Bartholow, TL Brand, RE Chennat, JS Lu, X Papachristou, GI Slivka, A Zeh, HJ Zureikat, AH Lee, KK Tsung, A Mantha, GS Khalid, A AF Singhi, Aatur D. Nikiforova, Marina N. Fasanella, Kenneth E. McGrath, Kevin M. Pai, Reetesh K. Ohori, N. Paul Bartholow, Tanner L. Brand, Randall E. Chennat, Jennifer S. Lu, Xuong Papachristou, Georgios I. Slivka, Adam Zeh, Herbert J. Zureikat, Amer H. Lee, Kenneth K. Tsung, Allan Mantha, Geeta S. Khalid, Asif TI Preoperative GNAS and KRAS Testing in the Diagnosis of Pancreatic Mucinous Cysts SO CLINICAL CANCER RESEARCH LA English DT Article ID INTERNATIONAL CONSENSUS GUIDELINES; FINE-NEEDLE-ASPIRATION; DNA ANALYSIS; MUTATIONS; MANAGEMENT; LESIONS; NEOPLASMS; CANCER; PRECURSORS; CYTOLOGY AB Purpose: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear. Experimental Design: GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst. Results: Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92). Conclusions: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms. (C)2014 AACR. C1 [Singhi, Aatur D.; Nikiforova, Marina N.; Pai, Reetesh K.; Ohori, N. Paul; Bartholow, Tanner L.; Mantha, Geeta S.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15213 USA. [Fasanella, Kenneth E.; McGrath, Kevin M.; Brand, Randall E.; Chennat, Jennifer S.; Lu, Xuong; Papachristou, Georgios I.; Slivka, Adam; Khalid, Asif] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15213 USA. [Zeh, Herbert J.; Zureikat, Amer H.; Lee, Kenneth K.; Tsung, Allan] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA 15213 USA. [Papachristou, Georgios I.; Khalid, Asif] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Singhi, AD (reprint author), Univ Pittsburgh, Med Ctr, Presbyterian Hosp, Scaife Hall,Room 616-2,200 Lothrop St, Pittsburgh, PA 15213 USA. EM singhiad@upmc.edu FU National Pancreas Foundation, Western Pennsylvania Chapter FX This study was supported in part by a grant from the National Pancreas Foundation, Western Pennsylvania Chapter (to A.D. Singhi). NR 26 TC 27 Z9 27 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2014 VL 20 IS 16 BP 4381 EP 4389 DI 10.1158/1078-0432.CCR-14-0513 PG 9 WC Oncology SC Oncology GA AO2WB UT WOS:000341186100021 PM 24938521 ER PT J AU Xiong, GX Elkind, JA Kundu, S Smith, CJ Antunes, MB Tamashiro, E Kofonow, JM Mitala, CM Stein, SC Grady, MS Einhorn, E Cohen, NA Cohen, AS AF Xiong, Guoxiang Elkind, Jaclynn A. Kundu, Suhali Smith, Colin J. Antunes, Marcelo B. Tamashiro, Edwin Kofonow, Jennifer M. Mitala, Christina. M. Stein, Sherman C. Grady, M. Sean Einhorn, Eugene Cohen, Noam A. Cohen, Akiva S. TI Traumatic Brain Injury-Induced Ependymal Ciliary Loss Decreases Cerebral Spinal Fluid Flow SO JOURNAL OF NEUROTRAUMA LA English DT Article DE beta-tubulin; basal body; hydrocephalus; lateral fluid percussion; particle tracking ID POSTTRAUMATIC HYDROCEPHALUS; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; BEAT FREQUENCY; CHOROID-PLEXUS; MICE; DYSFUNCTION; DYSKINESIA; MOTILITY; SLEEP AB Traumatic brain injury (TBI) afflicts up to 2 million people annually in the United States and is the primary cause of death and disability in young adults and children. Previous TBI studies have focused predominantly on the morphological, biochemical, and functional alterations of gray matter structures, such as the hippocampus. However, little attention has been given to the brain ventricular system, despite the fact that altered ventricular function is known to occur in brain pathologies. In the present study, we investigated anatomical and functional alterations to mouse ventricular cilia that result from mild TBI. We demonstrate that TBI causes a dramatic decrease in cilia. Further, using a particle tracking technique, we demonstrate that cerebrospinal fluid flow is diminished, thus potentially negatively affecting waste and nutrient exchange. Interestingly, injury-induced ventricular system pathology resolves completely by 30 days after injury as ependymal cell ciliogenesis restores cilia density to uninjured levels in the affected lateral ventricle. C1 [Xiong, Guoxiang; Elkind, Jaclynn A.; Kundu, Suhali; Smith, Colin J.; Mitala, Christina. M.; Cohen, Akiva S.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Antunes, Marcelo B.; Tamashiro, Edwin; Kofonow, Jennifer M.; Cohen, Noam A.] Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Stein, Sherman C.; Grady, M. Sean] Univ Penn, Perelman Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. [Cohen, Akiva S.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Einhorn, Eugene; Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Cohen, AS (reprint author), Univ Penn, Perelman Sch Med, Dept Pediat, 3615 Civ Ctr Blvd,816-H ARC, Philadelphia, PA 19104 USA. EM cohena@email.chop.edu RI Tamashiro, Edwin/C-5062-2012 OI Tamashiro, Edwin/0000-0002-3153-6292 FU National Institutes of Health [R01HD059288, R01NS069629] FX The authors thank Michael Schell for critiquing an earlier draft of the manuscript and Kathleen Joy Propert for statistical guidance. This study was supported in part by National Institutes of Health grants (R01HD059288 and R01NS069629; to A.S.C.). NR 59 TC 5 Z9 5 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG 15 PY 2014 VL 31 IS 16 BP 1396 EP 1404 DI 10.1089/neu.2013.3110 PG 9 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA AN4DB UT WOS:000340536700003 PM 24749541 ER PT J AU Bodhankar, S Chen, YX Lapato, A Vandenbark, AA Murphy, SJ Offner, H AF Bodhankar, Sheetal Chen, Yingxin Lapato, Andrew Vandenbark, Arthur A. Murphy, Stephaine J. Offner, Halina TI Targeting immune co-stimulatory effects of PD-L1 and PD-L2 might represent an effective therapeutic strategy n stroke SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE MCAO; co-stimulatory pathway; programmed death ligand-1 and 2; T-cells; regulatory B cells ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROGRAMMED DEATH-1 PD-1; T-CELL PROLIFERATION; ISCHEMIC-STROKE; INFARCT SIZE; IMMUNOLOGICAL-TOLERANCE; CEREBRAL-ISCHEMIA; CNS INFLAMMATION; DEFICIENT MICE; REGULATORY T AB Stroke outcome is worsened by the infiltration of inflammatory immune cells into ischemic brains. Our recent study demonstrated that PD-L1- and to a lesser extent PD-L2-deficient mice had smaller brain infarcts and fewer brain-infiltrating cells vs. wild-type (WI) mice, suggesting a pathogenic role for PD-ligands in experimental stroke. We sought to ascertain PD-L1 and PD-L2-expressing cell types that affect T-cell activation, post-stroke in the context of other known co-stimulatory molecules. Thus, cells from male WT and PD-1, deficient mice undergoing 60 min of middle cerebral artery occlusion (MCAO) followed by 96 h of reperfusion were treated with neutralizing antibodies to study co-stimulatory and co-inhibitory interactions between CD80, cytotoxic T-lymphocyte antigen-4 (CTLA-4), PD-1, and PD-Ls that regulate CD8+ and CD4+ T-cell activation. We found that antibody neutralization of PD-1 and CTLA-4 signaling post-MCAO resulted in higher proliferation in WT CD8+ and CD4+ T-cells, confirming an inhibitory role of PD-1 and CTLA-4 on Tcell activation. Also, CD80/CD28 interactions played a prominent regulatory role for the CD8+ T-cells and the PD-1/PD-L2 interactions were dominant in controlling the CD4+ T-cell responses in WT mice after stroke. A suppressive phenotype in PD-L1-deficient mice was attributed to CD80/CTLA-4 and PD-1/PD-L2 interactions. PD-L2 was crucial in modulating CD4+T-cell responses, whereas PD-L1 regulated both CD8+ and CD4+ T-cells. To establish the contribution of PD-L1 and PD-L2 on regulatory B-cells (Bregs), infarct volumes were evaluated in male PD-L1- and PD-L2-deficient mice receiving IL-10+ B-cells 4h post-MCAO. PD-L2- but not PD-L1-deficient recipients of IL-10+ B-cells had markedly reduced infarct volumes, indicating a regulatory role of PD-L2 on Bregs. These results imply that PDL1 and PD-L2 differentially control induction of T- and Breg-cell responses after MCAO, thus suggesting that selective targeting of PD-L1 and PD-L2 might represent a valuable therapeutic strategy in stroke. C1 [Bodhankar, Sheetal; Lapato, Andrew; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. [Bodhankar, Sheetal; Lapato, Andrew; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. [Chen, Yingxin; Murphy, Stephaine J.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D-31,3710 SW,US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIH/NINDS [1R01 NS075887]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; Biomedical Laboratory Research and Development FX The authors wish to thank Gail Kent for assistance in manuscript submission. This work was supported by NIH/NINDS 1R01 NS075887. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 69 TC 1 Z9 1 U1 1 U2 12 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD AUG 11 PY 2014 VL 8 AR 228 DI 10.3389/fncel.2014.00228 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AM7EH UT WOS:000340027000001 PM 25157219 ER PT J AU Abad, CL Moseley, RH Crnich, CJ Saint, S Safdar, N AF Abad, Cybele L. Moseley, Richard H. Crnich, Christopher J. Saint, Sanjay Safdar, Nasia TI A Gut Instinct SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TUBERCULOSIS INFECTION; ABDOMINAL-PAIN C1 [Abad, Cybele L.; Crnich, Christopher J.; Safdar, Nasia] Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53706 USA. [Crnich, Christopher J.; Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Moseley, Richard H.; Saint, Sanjay] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Moseley, Richard H.; Saint, Sanjay] Ann Arbor Healthcare Syst & Hlth Serv Res & Dev C, Dept Vet Affairs, Ann Arbor, MI USA. RP Safdar, N (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu FU Covance; Doximity; Jvion FX Dr. Moseley reports providing expert testimony in a case related to chronic hepatitis B virus infection; Dr. Crnich, receiving fees for serving on a data and safety monitoring board from Covance; and Dr. Saint, receiving fees for board membership from Doximity and Jvion. No other potential conflict of interest relevant to this article was reported. NR 12 TC 1 Z9 1 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 7 PY 2014 VL 371 IS 6 BP 560 EP 564 DI 10.1056/NEJMcps1202137 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AM5LE UT WOS:000339899100012 PM 25099581 ER PT J AU Elvington, M Scheiber, M Yang, XF Lyons, K Jacqmin, D Wadsworth, C Marshall, D Vanek, K Tomlinson, S AF Elvington, Michelle Scheiber, Melissa Yang, Xiaofeng Lyons, Katherine Jacqmin, Dustin Wadsworth, Casey Marshall, David Vanek, Kenneth Tomlinson, Stephen TI Complement-Dependent Modulation of Antitumor Immunity following Radiation Therapy SO CELL REPORTS LA English DT Article ID CD8(+) T-CELLS; APOPTOTIC CELLS; NEUTROPHIL RECRUITMENT; DOSE RADIOTHERAPY; MURINE MODEL; TUMOR-GROWTH; CANCER; INHIBITION; INTERLEUKIN-10; MELANOMA AB Complement is traditionally thought of as a proinflammatory effector mechanism of antitumor immunity. However, complement is also important for effective clearance of apoptotic cells, which can be an anti-inflammatory and tolerogenic process. We show that localized fractionated radiation therapy (RT) of subcutaneous murine lymphoma results in tumor cell apoptosis and local complement activation. Cotreatment of mice with tumor-targeted complement inhibition markedly improved therapeutic outcome of RT, an effect linked to early increases in apoptotic cell numbers and increased inflammation. Improved outcome was dependent on an early neutrophil influx and was characterized by increased numbers of mature dendritic cells and the subsequent modulation of T cell immunity. Appropriate complement inhibition may be a promising strategy to enhance a mainstay of treatment for cancer. C1 [Elvington, Michelle; Scheiber, Melissa; Yang, Xiaofeng; Wadsworth, Casey; Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Lyons, Katherine; Jacqmin, Dustin; Marshall, David; Vanek, Kenneth] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU NIH [RO1CA158179] FX This work was supported by a grant from the NIH (RO1CA158179). We thank Ms. Emily Paulling for expert technical assistance. S.T. holds licensed patents for CR2-targeted complement inhibitors. NR 44 TC 7 Z9 7 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD AUG 7 PY 2014 VL 8 IS 3 BP 818 EP 830 DI 10.1016/j.celrep.2014.06.051 PG 13 WC Cell Biology SC Cell Biology GA AO7ZR UT WOS:000341572200018 PM 25066124 ER PT J AU Bakaeen, FG Blaustein, A Kibbe, MR AF Bakaeen, Faisal G. Blaustein, Alvin Kibbe, Melina R. TI Health Care at the VA Recommendations for Change SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Bakaeen, Faisal G.] Texas Heart Inst, Div Cardiovasc Surg, Michael E DeBakey Vet Affairs Med Ctr, Dept Cardiovasc Surg, Houston, TX 77025 USA. [Bakaeen, Faisal G.] Baylor Coll Med, Div Cardiothorac Surg, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Blaustein, Alvin] Michael E DeBakey VA Med Ctr, Div Cardiol, Houston, TX 77030 USA. [Blaustein, Alvin] Baylor Coll Med, Dept Med, Div Cardiol, Houston, TX 77030 USA. [Kibbe, Melina R.] Jesse Brown Vet Affairs Med Ctr, Surg Serv, Chicago, IL USA. [Kibbe, Melina R.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. RP Bakaeen, FG (reprint author), Michael E DeBakey VA Med Ctr, OCL 112,2002 Holcombe Blvd, Houston, TX 77030 USA. EM fbakaeen@bcm.edu NR 6 TC 5 Z9 5 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 6 PY 2014 VL 312 IS 5 BP 481 EP 482 DI 10.1001/jama.2014.8054 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AM4FL UT WOS:000339808600012 PM 24945974 ER PT J AU Anderson, TS Good, CB Gellad, WF AF Anderson, Timothy S. Good, Chester B. Gellad, Walid F. TI Potential Conflicts of Interest for Academic Medical Center Leaders Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Anderson, Timothy S.] Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA USA. [Good, Chester B.; Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. RP Gellad, WF (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, 151C Univ Dr, Pittsburgh, PA 15240 USA. EM wfg3@pitt.edu NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 6 PY 2014 VL 312 IS 5 BP 558 EP 559 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AM4FL UT WOS:000339808600031 PM 25096702 ER PT J AU Han, S Mallampalli, RK AF Han, SeungHye Mallampalli, Rama K. TI Sizing up Surfactant Synthesis SO CELL METABOLISM LA English DT Editorial Material ID LYSOPHOSPHATIDYLCHOLINE ACYLTRANSFERASE; II CELLS; PHOSPHOLIPIDS; LPCAT1 AB Phosphatidylcholine is generated through de novo synthesis and remodeling involving a lysophospholipid. In this issue of Cell Metabolism, research from the Shimizu lab (Harayama et al., 2014) demonstrates the highly selective enzymatic behavior of lysophospholipid acyltransferases. The authors present an enzymatic model for phosphatidylcholine molecular species diversification that impacts surfactant formation. C1 [Han, SeungHye; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, 930 Scaife Hall, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU BLRD VA [I01 BX002200]; NHLBI NIH HHS [R01 HL098174, R01 HL096376, R01 HL081784, UH2 HL123502, P01 HL114453, R01 HL097376] NR 11 TC 0 Z9 0 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD AUG 5 PY 2014 VL 20 IS 2 BP 195 EP 196 DI 10.1016/j.cmet.2014.07.015 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA AO5RJ UT WOS:000341402500002 PM 25100056 ER PT J AU Wong, CA Asch, DA Vinoya, CM Ford, CA Baker, T Town, R Merchant, RM AF Wong, Charlene A. Asch, David A. Vinoya, Cjloe M. Ford, Carol A. Baker, Tom Town, Robert Merchant, Raina M. TI The Experience of Young Adults on HealthCare.gov: Suggestions for Improvement SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Wong, Charlene A.; Vinoya, Cjloe M.; Ford, Carol A.; Merchant, Raina M.] Univ Penn, Philadelphia, PA 19104 USA. [Wong, Charlene A.; Ford, Carol A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Asch, David A.; Town, Robert] Univ Penn, Wharton Sch, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Baker, Tom] Univ Penn, Sch Law, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Wong, CA (reprint author), Univ Penn, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [K23 HL109083] NR 5 TC 10 Z9 10 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 5 PY 2014 VL 161 IS 3 BP 231 EP U107 DI 10.7326/L14-0287 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AN3KH UT WOS:000340486000013 PM 25004086 ER PT J AU Boekholdt, SM Hovingh, GK Mora, S Arsenault, BJ Amarenco, P Pedersen, TR LaRosa, JC Waters, DD DeMicco, DA Simes, RJ Keech, AC Colquhoun, D Hitman, GA Betteridge, J Clearfield, MB Downs, JR Colhoun, HM Gotto, AM Ridker, PM Grundy, SM Kastelein, JJP AF Boekholdt, S. Matthijs Hovingh, G. Kees Mora, Samia Arsenault, Benoit J. Amarenco, Pierre Pedersen, Terje R. LaRosa, John C. Waters, David D. DeMicco, David A. Simes, R. John Keech, Antony C. Colquhoun, David Hitman, Graham A. Betteridge, John Clearfield, Michael B. Downs, John R. Colhoun, Helen M. Gotto, Antonio M., Jr. Ridker, Paul M. Grundy, Scott M. Kastelein, John J. P. TI Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events A Meta-Analysis of Statin Trials SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE apolipoprotein B; LDL-cholesterol; meta-analysis; non-HDL-cholesterol ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; SCANDINAVIAN SIMVASTATIN SURVIVAL; HIGH-DOSE ATORVASTATIN; CHOLESTEROL REDUCTION; PRIMARY PREVENTION; LDL CHOLESTEROL; LIPID TRIAL; TARGETS TNT; THERAPY AB BACKGROUND Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented. OBJECTIVES The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk. METHODS This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. RESULTS Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target < 70 mg/dl. Compared with patients who achieved an LDL-C > 175 mg/dl, those who reached an LDL-C 75 to < 100 mg/dl, 50 to < 75 mg/dl, and < 50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB. CONCLUSIONS The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, > 40% did not reach an LDL-C target < 70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels. (C) 2014 by the American College of Cardiology Foundation. C1 [Boekholdt, S. Matthijs] Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands. [Hovingh, G. Kees; Arsenault, Benoit J.; Gotto, Antonio M., Jr.] Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Mora, Samia] Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. [Amarenco, Pierre] Hop Xavier Bichat, Dept Neurol & Stroke Ctr, Paris, France. [Pedersen, Terje R.] Ulleval & Univ Oslo, Oslo Univ Hosp, Ctr Prevent Med, Oslo, Norway. [LaRosa, John C.] State Univ New York, Hlth Sci Ctr, Brooklyn, NY USA. [Waters, David D.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94143 USA. [DeMicco, David A.] Pfizer Inc, New York, NY USA. [Simes, R. John; Keech, Antony C.] Univ Sydney, NHMRC, Clin Trials Ctr, Sydney, NSW 2006, Australia. [Simes, R. John; Keech, Antony C.] Wesley Hosp, Brisbane, Qld, Australia. [Hitman, Graham A.] Univ London Queen Mary, Barts & London Sch Med & Dent, Ctr Diabet, London, England. [Betteridge, John] Univ Coll London Hosp, Dept Endocrinol & Diabet, London, England. [Clearfield, Michael B.] Touro Univ, Mare Island, CA USA. [Downs, John R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Downs, John R.] South Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX USA. [Colhoun, Helen M.] Univ Dundee, Inst Med Res, Dundee, Scotland. [Gotto, Antonio M., Jr.] Weill Cornell Med Coll, New York, NY USA. [Grundy, Scott M.] Univ Texas Dallas, Ctr Human Nutr, SW Med Ctr, Dallas, TX 75230 USA. RP Kastelein, JJP (reprint author), Acad Med Ctr, Dept Vasc Med, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM j.j.kastelein@amc.uva.nl RI Simes, Robert/P-1497-2014; Colquhoun, David/F-9078-2013; Boekholdt, Matthijs/G-7562-2014 OI Colhoun, Helen/0000-0002-8345-3288 FU Netherlands Organisation for Scientific Research [91612122]; Pfizer Inc.; Atherotech Diagnostics; AstraZeneca Pharma U.S., Inc.; National Heart, Lung, and Blood Institute [HL117861]; Cerenis Therapeutics; Genzyme Corporation; Quest Diagnostics Inc.; AstraZeneca France; Bayer S.A.S.; Boehringer France S.A.S.; Boston Scientific-France; Bristol-Myers Squibb Agen; Daiichi Sankyo France S.A.S.; Edwards Lifesciences S.A.S.; Kowa Europe GmbH; H. Lundbeck A/S; Merck KGaA; Amgen Inc.; Merck Sharp & Dohme Corporation; Roche Therapeutics Inc.; Anthera Pharmaceuticals Inc.; Genentech U.S.A., Inc.; Laboratoires Servier; Aegerion Pharmaceuticals, Inc.; BioSante Pharmaceuticals, Inc.; Merck Co., Inc.; Sanofi-Aventis; Abbott Australasia Pty. Ltd.; AstraZeneca Australia; Bristol-Myers Squibb Australia; Eli Lilly Australia; Novartis A.G.; Roche Products Pty. Ltd.; Solvay Interox Pty.; AstraZeneca; Eli Lilly and Co. Ltd.; GlaxoSmithKline plc.; Merck Sharp Dohme Ltd.; Novo Nordisk Ltd.; OSI Pharmaceuticals Ltd.; Takeda U.K. Ltd.; Parke-Davis; Eli Lilly and Co., Ltd.; E.U. Innovative Medicines Initiative from AstraZeneca; Boehringer Ingelheim Ltd. U.K.; JRDF; Roche Products Ltd.; Novartis Pharmaceuticals U.K. Ltd.; Janssen Pharmaceuticals, Inc.; Kowa Pharmaceuticals America, Inc.; Abbott Laboratories; Boehringer-Ingelheim Pharmaceuticals; Isis Pharmaceuticals, Inc.; Vascular Biogenics Ltd. FX This meta-analysis was not supported by any funding. The contributing trials were funded by their respective sponsors and provided the requested data. They did not play any role in the statistical analysis, interpretation of the data, writing of the manuscript, or the decision to submit the manuscript. Dr. Hovingh is funded by a Veni grant (project number 91612122) from the Netherlands Organisation for Scientific Research. Drs. Boekholdt, Hovingh, and Arsenault have received consulting fees from Pfizer Inc. Dr. Hovingh has served on the speakers' bureaus of Amgen Europe B.V., Genzyme Netherlands, Merck Sharp & Dohme Corporation, Pfizer B.V., Roche Nederland B.V., and Sanofi-Aventis Netherlands B.V. Dr. Mora has received honoraria grants through her institution from Atherotech Diagnostics, AstraZeneca Pharma U.S., Inc., and the National Heart, Lung, and Blood Institute (HL117861); consulting fees from Cerenis Therapeutics, Genzyme Corporation, Pfizer Inc., and Quest Diagnostics Inc.; and travel accommodations/meeting expenses from Pfizer Inc.; and has served on the speakers' bureaus of Abbott Laboratories and AstraZeneca Pharma U.S., Inc. Dr. Amarenco has served on the speakers' bureaus of AstraZeneca France, Boehringer Ingelheim France S.A.S., Merck KGaA, Pfizer Inc., Sanofi-Aventis, and the government of France; and has received consulting fees from AstraZeneca France, Bayer S.A.S., Boehringer France S.A.S., Boston Scientific-France, Bristol-Myers Squibb Agen, Daiichi Sankyo France S.A.S., Edwards Lifesciences S.A.S., Kowa Europe GmbH, H. Lundbeck A/S, Merck KGaA, and Pfizer Inc. Dr. LaRosa has received consulting fees from Amgen Inc. and Pfizer Inc.; and travel expenses from Pfizer Inc. Dr. Pedersen has received honoraria grants and/or served on the speakers' bureaus of AstraZeneca Pharma U.S., Inc., Merck Sharp & Dohme Corporation, Pfizer Inc., and Roche Therapeutics Inc. Dr. Waters has received consulting fees from Anthera Pharmaceuticals Inc., Genentech U.S.A., Inc., Pfizer Inc., Roche Therapeutics Inc., and Laboratoires Servier; has served on the speakers' bureaus of Pfizer Inc. and Zydus Cadila Healthcare Ltd. (Medica); and has participated in committees of clinical trials sponsored by Aegerion Pharmaceuticals, Inc., BioSante Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., and Sanofi-Aventis. Dr. DeMicco is an employee of, and holds stock options in, Pfizer Inc. Prof. Keech has received honoraria grants from and/or served on the speakers' bureaus and/or advisory boards of Abbott Australasia Pty. Ltd., AstraZeneca Australia, Bristol-Myers Squibb Australia, Eli Lilly Australia, Merck KGaA, Novartis A.G., Pfizer Inc., Roche Products Pty. Ltd., and Solvay Interox Pty. Ltd. Dr. Hitman has received consulting fees from and/or served on the speakers' bureaus of AstraZeneca, Eli Lilly and Co. Ltd., GlaxoSmithKline plc., Merck Sharp & Dohme Ltd., Novo Nordisk Ltd., OSI Pharmaceuticals Ltd., Pfizer Inc., and Takeda U.K. Ltd.; and has received honoraria grants from Parke-Davis and Eli Lilly and Co., Ltd. Dr. Betteridge has served on the speakers' bureaus and/or advisory boards for Aegerion Pharmaceuticals, Inc., Amgen Europe B.V., AstraZeneca, Janssen Ltd., Kowa Europe GmbH, Merck Sharp & Dohme Ltd., Pfizer Inc., Roche Products Ltd., Sanofi-Synthelabo Ltd., and Takeda U.K. Ltd. Dr. Clearfield has received honoraria for consulting on the advisory boards for AstraZeneca Pharma U.S., Inc., and Merck Sharp & Dohme Corporation. Dr. Colhoun has received honoraria grants through the E.U.; Innovative Medicines Initiative from AstraZeneca, Boehringer Ingelheim Ltd. U.K., Eli Lilly and Co., Ltd., JRDF, Pfizer Inc., Roche Products Ltd., and Sanofi-Aventis; consulting fees from Eli Lilly and Co., Ltd., Novartis Pharmaceuticals U.K. Ltd., Pfizer Inc., and Sanofi-Aventis; has served on the speakers' bureaus of, and received travel expenses from, Pfizer Inc.; served on the advisory boards of Eli Lilly and Co., Ltd., Novartis Pharmaceuticals U.K. Ltd., Pfizer Inc., and Sanofi-Aventis; holds stock options in Roche Products Ltd.; and has participated in committees of clinical trials sponsored by Eli Lilly and Co., Ltd., JDRF, Novartis Pharmaceuticals U.K. Ltd., and Sanofi-Aventis. Dr. Gotto has received consulting fees from Roche Products Ltd., Janssen Pharmaceuticals, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., and Roche Therapeutics Inc.; has been a member of the boards of directors for Aegerion Pharmaceuticals, Inc. and Arisaph Pharmaceuticals, Inc.; and has been a member of the scientific advisory boards for DuPont, Haptocure Ltd., vascuVis Inc., and Vatera Healthcare Partners. Dr. Ridker has received honoraria grants from AstraZeneca Pharma U.S., Inc., Novartis A.G., and Pfizer Inc.; consulting fees from Abbott Laboratories, Boehringer-Ingelheim Pharmaceuticals, Isis Pharmaceuticals, Inc., Merck Sharp & Dohme Corporation, and Vascular Biogenics Ltd.; has been a member of the scientific advisory board for Boston Heart Diagnostics Corporation, Janssen Pharmaceuticals, Inc., Isis Pharmaceuticals, Inc., Merck Sharp & Dohme Corporation, and Pfizer Inc.; has received honoraria grants to his institution from Amgen Inc.; and is listed as a co-inventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes and that have been licensed to AstraZeneca Pharma U.S., Inc. and Siemens Corporation. Dr. Kastelein has received honoraria for serving on the speakers' bureaus of AstraZeneca, Genzyme Australia, Labortoires Isispharma, Kowa Australia Pty. Ltd., Merck Sharp & Dohme Pty. Ltd., Novartis Pharmaceuticals Australia Pty. Ltd., Pfizer Inc., and Roche Products Pty. Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 34 TC 121 Z9 127 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 5 PY 2014 VL 64 IS 5 BP 485 EP 494 DI 10.1016/j.jacc.2014.02.615 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AM9ZR UT WOS:000340241100011 PM 25082583 ER PT J AU Wong, ES Maciejewski, ML Hebert, PL Bryson, CL Liu, CF AF Wong, Edwin S. Maciejewski, Matthew L. Hebert, Paul L. Bryson, Christopher L. Liu, Chuan-Fen TI Massachusetts Health Reform and Veterans Affairs Health System Enrollment SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID AFFORDABLE CARE ACT; MEDICARE; COVERAGE; IMPACTS; ACCESS; RATES AB Objectives Veterans Health Administration (VA) operates the largest integrated health system in the nation. The Affordable Care Act (ACA) does not require any changes to VA, but the individual mandate and expanded health insurance options may change veterans' preferences for coverage. We examined the impact of healthcare reform in Massachusetts, which also included these policy changes, on veterans' enrollment in VA, private insurance, and Medicaid. Study Design Massachusetts' healthcare reform in June 2006 served as a natural experiment. Using data from the 2004-2013 Current Population Surveys, we examined enrollment in VA, private insurance, and Medicaid, comparing veterans residing in Massachusetts with veterans residing in neighboring New England states that did not undergo health reform. Methods We estimated the probability of being enrolled in VA, private insurance, and Medicaid before and after healthcare reform, using multivariate probit models while adjusting for individual characteristics. Using a difference-in-difference approach, we compared pre-post changes in enrollment probability among Massachusetts and non-Massachusetts veterans, respectively. Results Compared with other New England veterans, Massachusetts veterans decreased their enrollment in VA and private insurance by 0.2 (P =.857) and 0.9 (P = .666) percentage points, respectively, following health reform. In contrast, Medicaid enrollment increased by 2.5 percentage points (P = .038). Conclusions Healthcare reform in Massachusetts was associated with greater Medicaid enrollment, but was not significantly associated with VA and private insurance enrollment. Our results are significant for informing VA fiscal planning in the post ACA era. C1 [Wong, Edwin S.; Hebert, Paul L.; Bryson, Christopher L.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Seattle, WA USA. [Wong, Edwin S.; Hebert, Paul L.; Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Dept Med, Div Gen Internal Med, Durham, NC USA. [Bryson, Christopher L.] Univ Washington, Dept Med, Seattle, WA USA. RP Wong, ES (reprint author), Ctr Innovat Vet Ctr & Value Driven Care, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM edwin.wong@va.gov FU VA Health Services Research and Development Career Development Award [CDA 13-024] FX Dr Wong is supported by a VA Health Services Research and Development Career Development Award (CDA 13-024). Dr Maciejewski is a VA Research Career Scientist (RCS 10-391). The views expressed are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs, the University of Washington, and Duke University. NR 25 TC 1 Z9 1 U1 0 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD AUG PY 2014 VL 20 IS 8 BP 629 EP 636 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD3PK UT WOS:000350990800011 PM 25295677 ER PT J AU Kimbro, LB Li, JN Turk, N Ettner, SL Moin, T Mangione, CM Duru, OK AF Kimbro, Lindsay B. Li, Jinnan Turk, Norman Ettner, Susan L. Moin, Tannaz Mangione, Carol M. Duru, O. Kenrik TI Optimizing Enrollment in Employer Health Programs: A Comparison of Enrollment Strategies in the Diabetes Health Plan SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID MEXICAN-AMERICANS; MEDICAL-CARE; INSURANCE; ACCULTURATION; ADHERENCE; SERVICES; ACCESS AB Background Many health programs struggle with low enrollment rates. Objectives To compare the characteristics of populations enrolled in a new health plan when employer groups implement voluntary versus automatic enrollment approaches. Study Design We analyzed enrollment rates resulting from 2 different strategies: voluntary and automatic enrollment. We used regression modeling to estimate the associations of patient characteristics with the probability of enrolling within each strategy. The subjects were 5014 eligible employees from 11 self-insured employers who had purchased the Diabetes Health Plan (DHP), which offers free or discounted copayments for diabetes related medications, testing supplies, and physician visits. Six employers used voluntary enrollment while five5 used automatic enrollment. The main outcome of interest was enrollment into the DHP. Predictors were gender, age, race/ethnicity, dependent status, household income, education level, number of comorbidities, and employer group. Results Overall, the proportion of eligible members who were enrolled within the automatic enrollment strategy was 91%, compared with 35% for voluntary enrollment. Income was a significant predictor for voluntary enrollment but not for automatic enrollment. Within automatic enrollment, covered dependents, Hispanics, and persons with 1 nondiabetes comorbidity were more likely to enroll than other subgroups. Employer group was also a significant correlate of enrollment. Notably, all demographic groups had higher DHP enrollment rates under automatic enrollment than under voluntary enrollment. Conclusions For employer-based programs that struggle with low enrollment rates, especially among certain employee subgroups, an automatic enrollment strategy may not only increase the total number of enrollees but may also decrease some enrollment disparities. C1 [Kimbro, Lindsay B.; Li, Jinnan; Turk, Norman; Ettner, Susan L.; Mangione, Carol M.; Duru, O. Kenrik] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Ettner, Susan L.; Mangione, Carol M.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Moin, Tannaz] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Moin, Tannaz] Vet Affairs Greater Los Angeles Healthcare Syst, HSR&D Ctr Excellence Study Healthcare Provider Be, Los Angeles, CA USA. RP Kimbro, LB (reprint author), 10940 Wilshire Blvd,Ste 700, Los Angeles, CA 90095 USA. EM lkimbro@mednet.ucla.edu FU Centers for Disease Control and Prevention; National Institute of Diabetes and Digestive and Kidney Diseases as part of the Natural Experiments for the Translation of Diabetes (NEXT-D) Study [DP002722]; VA Office of Academic Affiliations, Health Services Research and Development through the Health Services Fellowship Training Program [TPM65-010]; VA Greater Los Angeles Healthcare System; University of California, Los Angeles; Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly (RCMAR/CHIME) under NIH/NIA [P30-AG021684]; [K08 AG033630] FX Funding received from the Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases as part of the Natural Experiments for the Translation of Diabetes (NEXT-D) Study (Grant number DP002722). Dr Moin is supported by VA Office of Academic Affiliations, Health Services Research and Development, through the Health Services Fellowship Training Program (TPM65-010), VA Greater Los Angeles Healthcare System. Dr Mangione and Dr Duru are supported in part by the University of California, Los Angeles, Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly (RCMAR/CHIME) under NIH/NIA Grant P30-AG021684. Dr Duru is supported in part by the Career Development award K08 AG033630. NR 19 TC 1 Z9 1 U1 0 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD AUG PY 2014 VL 20 IS 8 BP E311 EP E319 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD3PK UT WOS:000350990800004 PM 25295794 ER PT J AU Conner, JD Wolden-Hanson, T Quinn, LS AF Conner, Jennifer D. Wolden-Hanson, Tami Quinn, LeBris S. TI Assessment of Murine Exercise Endurance Without the Use of a Shock Grid: An Alternative to Forced Exercise SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Behavior; Issue 90; Exercise; Mouse; Treadmill; Endurance; Refinement ID PHYSICAL-ACTIVITY; MICE; PGC-1-ALPHA; RECEPTOR; OBESITY; INFLAMMATION; PERFORMANCE; METABOLISM; EXPRESSION; SPEED AB Using laboratory mouse models, the molecular pathways responsible for the metabolic benefits of endurance exercise are beginning to be defined. The most common method for assessing exercise endurance in mice utilizes forced running on a motorized treadmill equipped with a shock grid. Animals who quit running are pushed by the moving treadmill belt onto a grid that delivers an electric foot shock; to escape the negative stimulus, the mice return to running on the belt. However, avoidance behavior and psychological stress due to use of a shock apparatus can interfere with quantitation of running endurance, as well as confound measurements of postexercise serum hormone and cytokine levels. Here, we demonstrate and validate a refined method to measure running endurance in naive C57BL/6 laboratory mice on a motorized treadmill without utilizing a shock grid. When mice are preacclimated to the treadmill, they run voluntarily with gait speeds specific to each mouse. Use of the shock grid is replaced by gentle encouragement by a human operator using a tongue depressor, coupled with sensitivity to the voluntary willingness to run on the part of the mouse. Clear endpoints for quantifying running time-to-exhaustion for each mouse are defined and reflected in behavioral signs of exhaustion such as splayed posture and labored breathing. This method is a humane refinement which also decreases the confounding effects of stress on experimental parameters. C1 [Conner, Jennifer D.; Wolden-Hanson, Tami; Quinn, LeBris S.] VA Puget Sound Hlth Care Syst, Res Serv, Seattle, WA 98108 USA. [Conner, Jennifer D.] Seattle Inst Biomed & Clin Res, Seattle, WA USA. [Quinn, LeBris S.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Quinn, LeBris S.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Quinn, LS (reprint author), VA Puget Sound Hlth Care Syst, Res Serv, Seattle, WA 98108 USA. EM quinnL@uw.edu FU Department of Veterans Affairs [BX001026]; NIA [5P30AG-013280]; University of Washington Diabetes Endocrinology Research Center (NIH) [P30 DK-17047] FX Supported by Merit Review #BX001026 from the Department of Veterans Affairs (LSQ), and use of resources and facilities at VA Puget Sound Health Care System, the Transgenic Resource Core at the University of Washington Nathan Shock Center of Excellence in the Basic Biology of Aging (NIA #5P30AG-013280), and the University of Washington Diabetes Endocrinology Research Center (NIH #P30 DK-17047). We thank Cynthia Pekow DVM and Kari L. Koszdin DVM, VA Puget Sound, provided helpful comments on the manuscript. NR 25 TC 0 Z9 0 U1 2 U2 6 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD AUG PY 2014 IS 90 AR e51846 DI 10.3791/51846 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CB0EV UT WOS:000349299200068 PM 25145813 ER PT J AU Wood, KH Hoef, LWV Knight, DC AF Wood, Kimberly H. Hoef, Lawrence W. Ver Knight, David C. TI The Amygdala Mediates the Emotional Modulation of Threat-Elicited Skin Conductance Response SO EMOTION LA English DT Article DE fMRI; emotion; threat; amygdala; skin conductance ID FEAR-POTENTIATED STARTLE; FACIAL EXPRESSIONS; INDIVIDUAL-DIFFERENCES; TRAIT ANXIETY; CONDITIONED DIMINUTION; NEURAL RESPONSES; VIETNAM VETERANS; FUNCTIONAL MRI; LONG-TERM; ACTIVATION AB The ability to respond adaptively to threats in a changing environment is an important emotional function. The amygdala is a critical component of the neural circuit that mediates many emotion-related processes, and thus likely plays an important role in modulating the peripheral emotional response to threat. However, prior research has largely focused on the amygdala's response to stimuli that signal impending threat, giving less attention to the amygdala's response to the threat itself. From a functional perspective, however, it is the response to the threat itself that is most biologically relevant. Thus, understanding the factors that influence the amygdala's response to threat is critical for a complete understanding of adaptive emotional processes. Therefore, we used functional MRI to investigate factors (i.e., valence and arousal of co-occurring visual stimuli) that influence the amygdala's response to threat (loud white noise). We also assessed whether changes in amygdala activity varied with the peripheral expression of emotion (indexed via skin conductance response; SCR). The results showed that threat-elicited amygdala activation varied with the arousal, not valence, of emotional images. More specifically, threat-elicited amygdala activation was larger to the threat when presented during high-arousal (i.e., negative and positive) versus low-arousal (i.e., neutral) images. Further, the threat-elicited amygdala response was positively correlated with threat-elicited SCR. These findings indicate the amygdala's response to threat is modified by the nature (e.g., arousal) of other stimuli in the environment. In turn, the amygdala appears to mediate important aspects of the peripheral emotional response to threat. C1 [Wood, Kimberly H.; Knight, David C.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35233 USA. [Hoef, Lawrence W. Ver] Univ Alabama Birmingham, Sch Med, Dept Neurol, Birmingham, AL 35233 USA. [Hoef, Lawrence W. Ver] Birmingham VA Med Ctr, Dept Neurol, Birmingham, AL USA. RP Knight, DC (reprint author), Univ Alabama Birmingham, CIRC 235H,1720 2nd Ave South, Birmingham, AL 35233 USA. EM knightdc@uab.edu FU NIMH NIH HHS [R01 MH098348, MH098348] NR 68 TC 9 Z9 9 U1 5 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 EI 1931-1516 J9 EMOTION JI Emotion PD AUG PY 2014 VL 14 IS 4 BP 693 EP 700 DI 10.1037/a0036636 PG 8 WC Psychology, Experimental SC Psychology GA CA9CS UT WOS:000349218600006 PM 24866521 ER PT J AU Sarver, NW Gros, DF AF Sarver, Nina Wong Gros, Daniel F. TI A Modern Behavioral Treatment to Address Fetishism and Associated Functional Impairment SO CLINICAL CASE STUDIES LA English DT Article DE behavioral treatment; behavioral activation; sensate focused therapy; fetishism; paraphilias ID TERM PSYCHODYNAMIC PSYCHOTHERAPY; ACTIVATION TREATMENTS; SEXUAL DYSFUNCTION; DSM-IV; METAANALYSIS; THERAPY; AVERSION; INTERVENTIONS; SENSITIZATION; PARAPHILIAS AB The clinical research and treatment options for sexual paraphilias are scant and have generally been limited to psychodynamic and early behavioral approaches. This article highlights the application of two existing evidence-based modern behavioral interventions, specifically behavioral activation and sensate focused therapy, to treat foot fetishism/sexual impulses and co-occurring mood/anxiety symptoms in a 57-year-old male Vietnam War veteran. This brief 6-week treatment addressed the patient's complicating psychosocial factors and medical conditions, and focused on targeting behavioral avoidance symptoms associated with fetishism and depression (e.g., increasing socially and sexually appropriate and positive reinforcing behaviors in his environment). The patient no longer met diagnostic criteria for fetishism and endorsed significant reductions in depressed mood, anxiety, and stress at post-treatment and 1-month follow-up. This case illustrated how current behavioral treatments may be used to successfully treat patients with rare symptom presentations who may otherwise be neglected within a medical system. C1 [Sarver, Nina Wong] Boston Univ, Boston, MA 02215 USA. [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Gros, Daniel F.] Med Univ S Carolina, Charleston, SC USA. RP Gros, DF (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu NR 64 TC 0 Z9 0 U1 2 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-6501 EI 1552-3802 J9 CLIN CASE STUD JI Clin. Case Stud. PD AUG PY 2014 VL 13 IS 4 BP 336 EP 351 DI 10.1177/1534650113512020 PG 16 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AW9PK UT WOS:000346589300004 ER PT J AU Walters, PR Zuckerbraun, BS AF Walters, Pamela R. Zuckerbraun, Brian S. TI Clostridium difficile Infection Clinical Challenges and Management Strategies SO CRITICAL CARE NURSE LA English DT Article ID POLYMERASE-CHAIN-REACTION; HEALTH-CARE SETTINGS; HOSPITALIZED-PATIENTS; SURGICAL-MANAGEMENT; DISEASE; DIARRHEA; COLITIS; EPIDEMIOLOGY; COLECTOMY; VANCOMYCIN AB Clostridium difficile has become the leading cause of nosocomial diarrhea in adults. A substantial increase has occurred in morbidity and mortality associated with disease caused by C difficile and in the identification of new hypervirulent strains, warranting a high clinical index of suspicion for infections due to this organism. Prevention of infection requires a multidisciplinary approach, including early recognition of disease, effective contact isolation precautions, adherence to disinfectant policies, and judicious use of antibiotics. Current treatment approaches are based on the severity of illness. As hypervirulent strains evolve, unsuccessful treatments are more common. Complicated colitis caused by C difficile may benefit from surgical intervention. Subtotal colectomy and end ileostomy have been the procedures of choice, but are associated with a high mortality rate because of late surgical consultation and use of surgery as a salvage therapy. A promising surgical alternative is creation of a diverting loop ileostomy with colonic lavage. C1 [Walters, Pamela R.] Univ Pittsburgh, Ctr Sports Med, Pittsburgh, PA 15213 USA. [Zuckerbraun, Brian S.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Walters, PR (reprint author), Univ Pittsburgh, Med Ctr, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM pamelarwalters@gmail.com NR 58 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 0279-5442 EI 1940-8250 J9 CRIT CARE NURSE JI Crit. Care Nurse PD AUG PY 2014 VL 34 IS 4 BP 24 EP 33 DI 10.4037/ccn2014822 PG 10 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA AW8WF UT WOS:000346538700003 PM 25086091 ER PT J AU Williams, NR Taylor, JJ Kerns, S Short, EB Kantor, EM George, MS AF Williams, Nolan R. Taylor, Joseph J. Kerns, Suzanne Short, E. Baron Kantor, Edward M. George, Mark S. TI Interventional Psychiatry: Why Now? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter ID DEEP BRAIN-STIMULATION; OBSESSIVE-COMPULSIVE DISORDER; TRANSCRANIAL MAGNETIC STIMULATION; TREATMENT-RESISTANT DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; ELECTROCONVULSIVE-THERAPY; CLINICAL NEUROSCIENCE; MAJOR DEPRESSION; NEURAL CIRCUITS; EFFICACY C1 [Williams, Nolan R.; Taylor, Joseph J.; Kerns, Suzanne; Short, E. Baron; Kantor, Edward M.; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Williams, Nolan R.; Taylor, Joseph J.; George, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Williams, NR (reprint author), Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. EM willianr@musc.edu OI Williams, Nolan/0000-0003-4368-3203 FU NIDA NIH HHS [R25 DA020537, F30 DA033748] NR 57 TC 2 Z9 2 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2014 VL 75 IS 8 BP 895 EP 897 DI 10.4088/JCP.13l08745 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AU3RC UT WOS:000345530300019 PM 25191910 ER PT J AU Charles, R Sakurai, T Takahashi, N Elder, GA Sosa, MAG Young, LJ Buxbaum, JD AF Charles, Rhonda Sakurai, Takeshi Takahashi, Nagahide Elder, Gregory A. Sosa, Miguel A. Gama Young, Larry J. Buxbaum, Joseph D. TI Introduction of the human AVPR1A gene substantially alters brain receptor expression patterns and enhances aspects of social behavior in transgenic mice SO DISEASE MODELS & MECHANISMS LA English DT Article DE AVPR1A; Humanized mouse; Social behavior; Species-specific; Microsatellite; Autism ID ANXIETY-RELATED BEHAVIOR; VASOPRESSIN RECEPTOR; KNOCKOUT MICE; PREPULSE INHIBITION; PROMOTER REGION; PSYCHIATRIC-DISORDERS; MONOGAMOUS VOLE; BINDING-SITES; MESSENGER-RNA; V-1A RECEPTOR AB Central arginine vasopressin receptor 1A(AVPR1A) modulates a wide range of behaviors, including stress management and territorial aggression, as well as social bonding and recognition. Inter- and intra-species variations in the expression pattern of AVPR1A in the brain and downstream differential behavioral phenotypes have been attributed to differences in the non-coding regions of the AVPR1A gene, including polymorphic elements within upstream regulatory areas. Gene association studies have suggested a link between AVPR1A polymorphisms and autism, and AVPR1A has emerged as a potential pharmacological target for treatment of social cognitive impairments and mood and anxiety disorders. To further investigate the genetic mechanism giving rise to species differences in AVPR1A expression patterns and associated social behaviors, and to create a preclinical mouse model useful for screening drugs targeting AVPR1A, we engineered and extensively characterized bacterial artificial chromosome(BAC) transgenic mice harboring the entire human AVPR1A locus with the surrounding regulatory elements. Compared with wild-type animals, the humanized mice displayed a more widely distributed ligand-AVPR1A binding pattern, which overlapped with that of primates. Furthermore, humanized AVPR1A mice displayed increased reciprocal social interactions compared with wild-type animals, but no differences in social approach and preference for social novelty were observed. Aspects of learning and memory, specifically novel object recognition and spatial relocation recognition, were unaffected. The biological alterations in humanized AVPR1A mice resulted in the rescue of the prepulse inhibition impairments that were observed in knockout mice, indicating conserved functionality. Although further behavioral paradigms and additional cohorts need to be examined in humanized AVPR1A mice, the results demonstrate that species-specific variations in the genomic content of regulatory regions surrounding the AVPR1A locus are responsible for differential receptor protein expression patterns across species and that they are likely to contribute to species-specific behavioral variation. The humanized AVPR1A mouse is a potential preclinical model for further understanding the regulation of receptor gene expression and the impact of variation in receptor expression on behaviors, and should be useful for screening drugs targeting human AVPR1A, taking advantage of the expression of human AVPR1A in human-relevant brain regions. C1 [Charles, Rhonda; Sakurai, Takeshi; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Charles, Rhonda; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Sakurai, Takeshi; Takahashi, Nagahide; Elder, Gregory A.; Sosa, Miguel A. Gama; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Elder, Gregory A.] James J Peters VA Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [Sosa, Miguel A. Gama] James J Peters VA Med Ctr, Res & Dev Serv, Bronx, NY 10468 USA. [Young, Larry J.] Emory Univ, Yerkes Natl Primate Res Ctr, Dept Psychiat & Behav Sci, Ctr Translat Social Neurosci, Atlanta, GA 30329 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu OI Buxbaum, Joseph/0000-0001-8898-8313 FU Seaver Foundation; Autism Science Foundation; National Institutes of Health [MH056897, MH064692, P51OD11132] FX This work was supported by the Seaver Foundation and a predoctoral fellowship from the Autism Science Foundation to R. C. Additional support was provided by National Institutes of Health grants [MH056897 and MH064692 to L.J.Y. and P51OD11132 to Yerkes National Primate Research Center]. NR 55 TC 3 Z9 3 U1 0 U2 15 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD AUG PY 2014 VL 7 IS 8 BP 1013 EP 1022 DI 10.1242/dmm.017053 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA AT5TF UT WOS:000345004200009 PM 24924430 ER PT J AU Sher, L Landers, S AF Sher, Leo Landers, Sean TI Bipolar disorder, testosterone administration, and homicide: A case report SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE LA English DT Article DE Bipolar disorder; testosterone; homicide ID STEROID USE; OFFENDERS AB Objective. Homicide is a major public health and social concern in the United States. Studies have found higher rates of psychiatric disorders in homicide off enders than in the general population. The aim of this article is to report and to discuss a case of a patient with bipolar disorder and hypogonadism who murdered his wife shortly aft er a testosterone injection. Methods. A case study and a review of the relevant literature. Results. Our case study as well as several case reports in the literature suggests that testosterone administration or high testosterone levels may be associated with homicidal behavior. Conclusion. Further studies of the role of testosterone in the neurobiology of violent and homicidal behavior may lead to improvements in the prevention of homicides. C1 [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. [Landers, Sean] Ninth Judicial Circuit, Orlando, FL USA. RP Sher, L (reprint author), James J Peters Vet Adm, Icahn Sch Med Mt Sinai, Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM DrLeoSher@gmail.com NR 13 TC 1 Z9 1 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1365-1501 EI 1471-1788 J9 INT J PSYCHIAT CLIN JI Int. J. Psychiat. Clin. PD AUG PY 2014 VL 18 IS 3 BP 215 EP 216 DI 10.3109/13651501.2014.894075 PG 2 WC Psychiatry SC Psychiatry GA AS8AO UT WOS:000344473100011 PM 24527885 ER PT J AU Lytle, MC De Luca, SM Blosnich, JR AF Lytle, Megan C. De Luca, Susan M. Blosnich, John R. TI The Influence of Intersecting Identities on Self-Harm, Suicidal Behaviors, and Depression among Lesbian, Gay, and Bisexual Individuals SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID SEXUAL ORIENTATION; RISK-FACTORS; DISORDERS; IDEATION; ADULTS; LATINO AB Individuals with lesbian, gay, and bisexual (LGB) identities have higher prevalence of self-directed violence, but very little is known about racial/ethnic differences between LGB populations. This study aimed to examine racial/ethnic differences in self-harm, suicidal ideation, suicide attempt, and depression among LGB and heterosexual emerging adults. Data are compiled from the Fall 2008 and Spring 2009 National College Health Assessment and limited to respondents within emerging adulthood (ages 18-24) who indicated their sexual orientation and racial/ethnic identities (n = 89,199). Within each racial/ethnic group, LGB individuals were significantly more likely to report self-harm, suicidal ideation, suicide attempt, and depression than non-LGB individuals. C1 [Lytle, Megan C.] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. [De Luca, Susan M.] Univ Texas Austin, Sch Social Work, Austin, TX 78712 USA. [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Lytle, MC (reprint author), Univ Rochester, Med Ctr, Dept Psychiat, 300 Crittenden Blvd, Rochester, NY 14642 USA. EM megan_lytle@urmc.rochester.edu FU NCATS NIH HHS [KL2 TR000095]; NIMH NIH HHS [T32 MH020061] NR 22 TC 5 Z9 5 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD AUG PY 2014 VL 44 IS 4 BP 384 EP 391 DI 10.1111/sltb.12083 PG 8 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AS3LI UT WOS:000344178900004 PM 25250405 ER PT J AU Walter, KH Varkovitzky, RL Owens, GP Lewis, J Chard, KM AF Walter, Kristen H. Varkovitzky, Ruth L. Owens, Gina P. Lewis, Jennifer Chard, Kathleen M. TI Cognitive Processing Therapy for Veterans With Posttraumatic Stress Disorder: A Comparison Between Outpatient and Residential Treatment SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE posttraumatic stress disorder; cognitive processing therapy; outpatient treatment; residential treatment; veterans ID ADMINISTERED PTSD SCALE; PSYCHOMETRIC PROPERTIES; BEHAVIORAL THERAPY; PROLONGED EXPOSURE; AFGHANISTAN; IRAQ; PROGRAM; TRIAL; CARE AB Objective: Across the Veterans Affairs (VA) Healthcare System, outpatient and residential posttraumatic stress disorder (PTSD) treatment programs are available to veterans of all ages and both genders; however, no research to date has compared these treatment options. This study compared veterans who received outpatient (n = 514) to those who received residential treatment (n = 478) within a VA specialty clinic on demographic and pretreatment symptom variables. Further, the study examined pre- to posttreatment symptom trajectories across the treatment programs. Method: All 992 veterans met diagnostic criteria for PTSD and attended at least 1 session of cognitive processing therapy (CPT) in either the outpatient or residential program. Bivariate analyses were utilized to investigate differences between samples on demographic variables and severity of pretreatment symptoms. Multilevel modeling (MLM) was used to investigate the change in symptomatology between the 2 samples from pre- to posttreatment. Results: Analyses indicated that the samples differed on all demographic and pretreatment symptom variables, with residential patients reporting higher scores on all assessment measures. MLM results demonstrated that symptom scores improved for all veterans across time, with outpatients consistently reporting fewer symptoms at both time points. The time by program interaction was significant for PTSD-related symptom trajectories, but not for the depression-related symptom trajectory. Conclusion: This is the 1st study to compare pretreatment characteristics and treatment outcome between veterans receiving outpatient and residential PTSD treatment. Findings may help clinicians select appropriate care for their patients by identifying relevant pretreatment characteristics and generally informing expectations of treatment outcome. C1 [Walter, Kristen H.] Vet Med Res Fdn, San Diego, CA 92161 USA. [Walter, Kristen H.] Vet Affairs San Diego Healthcare Syst, Res Serv, San Diego, CA USA. [Varkovitzky, Ruth L.] Vet Affairs Puget Sound Healthcare Syst, Amer Lake Div, PTSD Outpatient Clin, Tacoma, WA USA. [Owens, Gina P.] Univ Tennessee, Dept Psychol, Knoxville, TN 37996 USA. [Lewis, Jennifer; Chard, Kathleen M.] Cincinnati Vet Affairs Med Ctr, Trauma Recovery Ctr, Cincinnati, OH USA. [Chard, Kathleen M.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45221 USA. RP Walter, KH (reprint author), Vet Med Res Fdn, 3350 La Jolla Village Dr,111N-1,Bldg 13, San Diego, CA 92161 USA. EM Kristen.Walter@va.gov NR 37 TC 3 Z9 3 U1 3 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2014 VL 82 IS 4 BP 551 EP 561 DI 10.1037/a0037075 PG 11 WC Psychology, Clinical SC Psychology GA AS3FY UT WOS:000344164000001 PM 24911422 ER PT J AU Shah, A Carreno, FR Frazer, A AF Shah, Aparna Carreno, Flavia Regina Frazer, Alan TI Therapeutic Modalities for Treatment Resistant Depression: Focus on Vagal Nerve Stimulation and Ketamine SO CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE LA English DT Review DE Depression; Vagal nerve stimulation; Ketamine; TrkB ID D-ASPARTATE ANTAGONIST; PHARMACOLOGICALLY DIVERSE ANTIDEPRESSANTS; TRANSCRANIAL MAGNETIC STIMULATION; COGNITIVE-BEHAVIORAL THERAPY; NEUROTROPHIC FACTOR-RECEPTOR; DELTA-FOSB IMMUNOREACTIVITY; RANDOMIZED CONTROLLED-TRIAL; VAGUS NERVE; MAJOR DEPRESSION; RAT-BRAIN AB Treatment resistant depression (TRD) is a global health concern affecting a large proportion of depressed patients who then require novel therapeutic options. One such treatment option that has received some attention in the past several years. is vagal nerve stimulation (VNS). The present review briefly describes the relevance of this treatment in the light of other existing pharmacological and non-pharmacological options, It then summarizes clinical findings with respect to the efficacy of VNS. The anatomical rationale for its efficacy and other potential mechanisms of its antidepressant effects as compared to those employed by classical antidepressant drugs are discussed. VNS has been approved in some countries and has been used for patients with TRD for quite some time, A newer, fast-acting, non-invasive pharmacological option called ketamine is currently in the limelight with reference to TRD. This drug is currently in the investigational phase but shows promise. The clinical and preclinical findings related to ketamine have also been summarized and compared with those for VNS. The role of neurotrophin factors, specifically brain derived neurotrophic factor and its receptor, in the beneficial effects of both VNS and ketamine have been highlighted. It can be concluded that both these therapeutic modalities, while effective, need further research that can reveal specific targets for intervention by novel drugs and address concerns related to side-effects, especially those seen with ketamine. C1 [Shah, Aparna; Carreno, Flavia Regina; Frazer, Alan] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Shah, Aparna; Carreno, Flavia Regina; Frazer, Alan] Univ Texas Hlth Sci Ctr San Antonio, Ctr Biomed Neurosci, San Antonio, TX 78229 USA. [Frazer, Alan] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Shah, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr,Mail Code 7764, San Antonio, TX 78229 USA. EM shahap@uthscsa.edu FU Lundbeck; Takeda Pharmaceuticals International, Inc.; Eli Lilly and Co. FX Dr. Frazer has served on advisory boards for Lundbeck and for Takeda Pharmaceuticals International, Inc. and Eli Lilly and Co. Previously, Dr. Frazer had received financial compensation as a consultant for Cyberonics Inc. and had also obtained grant support from them for a preclinical study. NR 126 TC 9 Z9 9 U1 1 U2 10 PU KOREAN COLL NEUROPSYCHOPHARMACOLOGY PI SEOUL PA RN 1003 OFFICETEL 40, 63-RO YEONGDEUNGPO-GU, SEOUL, 150-731, SOUTH KOREA SN 1738-1088 EI 2093-4327 J9 CLIN PSYCHOPHARM NEU JI Clin. Psychopharmacol. Neurosci. PD AUG PY 2014 VL 12 IS 2 BP 83 EP 93 DI 10.9758/cpn.2014.12.2.83 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AQ5NK UT WOS:000342855700002 PM 25191499 ER PT J AU Shalaby, AA Brumberg, GE Pointer, L Bekelman, DB Rumsfeld, JS Yang, YF Pellegrini, CN Heidenreich, PA Keung, E Massie, BM Varosy, PD AF Shalaby, Alaa A. Brumberg, Genevieve E. Pointer, Lauren Bekelman, David B. Rumsfeld, John S. Yang, Yanfei Pellegrini, Cara N. Heidenreich, Paul A. Keung, Edmund Massie, Barry M. Varosy, Paul D. TI Depression and Outcome among Veterans with Implantable Cardioverter Defibrillators with or without Cardiac Resynchronization Therapy Capability SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE depression; implantable cardiac defibrillator; mortality; heart failure ID CHRONIC HEART-FAILURE; MYOCARDIAL-INFARCTION; COLLABORATIVE CARE; SYMPTOMS; RISK; MORTALITY; PREVALENCE; LIFE AB Background: The impact of depression on outcome in implantable cardioverter defibrillator (ICD) recipients has not been fully appreciated. We assessed the prevalence of depression and its association with heart failure (HF) outcome among veterans with ICDs. Methods and Results: Patients enrolled between January 2005 and January 2010 in the Outcomes among Veterans with Implantable Defibrillators Registry were studied. We examined the cross-sectional association of depression with severity of HF functional class as well as the association of depression with the composite outcome of mortality or HF hospitalization over a mean follow-up time of 2.7 years. There were 3,862 patients enrolled. Patients with depression (1,162, 43%) were younger (63.1 +/- 9.4 years vs 66.6 +/- 9.9 years, P<0.001), more likely to have a history of tobacco or alcohol abuse (P<0.0001) or atrial fibrillation (P=0.05) while having a higher ejection fraction (28.3% vs 27.4%, P=0.03). Depression was associated with advanced HF class at time of implant; odds ratio (OR; vs class I) for class III: 1.65 (confidence interval [CI] 1.17-2.33), class IV: 1.73 (95% CI 1.08-2.76). Death or HF hospitalization was more likely to occur in patients with depression (35.2% vs 32.0%, HR: 1.15 [95% CI 0.99-1.33]). The predictive value of depression was stronger after multivariable adjustment; HR: 1.25 (95% CI 1.05-1.49). Conclusion: Depression was prevalent among veterans with ICDs. Depression was associated with severity of HF. The predictive value of associated depression was significant after multivariable adjustment. C1 [Shalaby, Alaa A.; Brumberg, Genevieve E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15240 USA. [Shalaby, Alaa A.; Brumberg, Genevieve E.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Pointer, Lauren; Bekelman, David B.; Rumsfeld, John S.; Varosy, Paul D.] Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA. [Pointer, Lauren; Bekelman, David B.; Rumsfeld, John S.; Varosy, Paul D.] Univ Colorado, Colorado Cardiovasc Outcomes Res, Denver, CO 80202 USA. [Yang, Yanfei; Heidenreich, Paul A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Yang, Yanfei; Heidenreich, Paul A.] Stanford Univ, Palo Alto, CA 94304 USA. [Pellegrini, Cara N.; Keung, Edmund; Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Pellegrini, Cara N.; Keung, Edmund; Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Shalaby, AA (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Div Cardiol, 111 C Univ Dr, Pittsburgh, PA 15240 USA. EM Alaa.Shalaby@va.gov OI Heidenreich, Paul/0000-0001-7730-8490 NR 37 TC 2 Z9 2 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 EI 1540-8159 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD AUG PY 2014 VL 37 IS 8 BP 994 EP 1001 DI 10.1111/pace.12361 PG 8 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA AQ5FL UT WOS:000342831900011 PM 24520992 ER PT J AU Deyo, RA Dworkin, SF Amtmann, D Andersson, G Borenstein, D Carragee, E Carrino, J Chou, R Cook, K DeLitto, A Goertz, C Khalsa, P Loeser, J Mackey, S Panagis, J Rainville, J Tosteson, T Turk, D Von Korff, M Weiner, DK AF Deyo, Richard A. Dworkin, Samuel F. Amtmann, Dagmar Andersson, Gunnar Borenstein, David Carragee, Eugene Carrino, John Chou, Roger Cook, Karon DeLitto, Anthony Goertz, Christine Khalsa, Partap Loeser, John Mackey, Sean Panagis, James Rainville, James Tosteson, Tor Turk, Dennis Von Korff, Michael Weiner, Debra K. TI Report of the NIH Task Force on Research Standards for Chronic Low Back Pain SO PAIN MEDICINE LA English DT Article DE Low Back Pain; Chronic Low Back Pain; Research Standards; Minimum Dataset; NIH Task Force ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM PROMIS; FUNCTION ITEM BANK; QUALITY-OF-LIFE; PRIMARY-CARE; PROGNOSTIC APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES AB Objective. Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific, and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Design. Expert panel and preliminary evaluation of key recommendations. Methods. The NIH Pain Consortium charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. Results. The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimal data set to describe research subjects (drawing heavily on the PROMIS methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. Conclusion. The RTF believes these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect the RTF recommendations will be come a dynamic document, and undergo continual improvement. Perspective. A task force was convened by the NIH Pain Consortium with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimum dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. C1 [Deyo, Richard A.; Chou, Roger] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Dworkin, Samuel F.; Amtmann, Dagmar; Loeser, John; Turk, Dennis] Univ Washington, Seattle, WA 98195 USA. [Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. [Andersson, Gunnar] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Cook, Karon; Weiner, Debra K.] Northwestern Univ, Evanston, IL USA. [Borenstein, David] George Washington Univ, Washington, DC USA. [Carragee, Eugene; Mackey, Sean] Stanford Univ, Stanford, CA 94305 USA. [Carrino, John] Johns Hopkins Univ, Baltimore, MD USA. [Khalsa, Partap] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Panagis, James] NIAMSD, Bethesda, MD 20892 USA. [DeLitto, Anthony] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [DeLitto, Anthony] Univ Pittsburgh, Pittsburgh, PA USA. [Goertz, Christine] Palmer Coll Chiropract, Davenport, IA USA. [Rainville, James] New England Baptist Hosp, Roxbury Crossing, MA USA. [Tosteson, Tor] Dartmouth Coll, Hanover, NH USA. RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code FM, Portland, OR 97239 USA. EM deyor@ohsu.edu FU National Center for Complementary and Alternative Medicine; National Institute for Arthritis, Musculoskeletal, and Skin Diseases FX This study was supported by the National Center for Complementary and Alternative Medicine and the National Institute for Arthritis, Musculoskeletal, and Skin Diseases. NR 126 TC 12 Z9 13 U1 8 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD AUG PY 2014 VL 15 IS 8 BP 1249 EP 1267 DI 10.1111/pme.12538 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA AQ2PW UT WOS:000342630800004 PM 25132307 ER PT J AU Allen, JL Kautz, SA Neptune, RR AF Allen, Jessica L. Kautz, Steven A. Neptune, Richard R. TI Forward propulsion asymmetry is indicative of changes in plantarflexor coordination during walking in individuals with post-stroke hemiparesis SO CLINICAL BIOMECHANICS LA English DT Article DE Forward dynamic simulations; Gait; Post-stroke hemiparesis; Rehabilitation ID GROUND REACTION FORCES; BODY-WEIGHT SUPPORT; MECHANICAL-PROPERTIES; STROKE SURVIVORS; GAIT ANALYSIS; PARETIC LEG; ENERGY-COST; MUSCLE; SPEED; PROGRESSION AB Background: A common measure of rehabilitation effectiveness post-stroke is self-selected walking speed, yet individuals may achieve the same speed using different coordination strategies. Asymmetry in the propulsion generated by each leg can provide insight into paretic leg coordination due to its relatively strong correlation with hemiparetic severity. Subjects walking at the same speed can exhibit different propulsion asymmetries, with some subjects relying more on the paretic leg and others on the nonparetic leg. The goal of this study was to assess whether analyzing propulsion asymmetry can help distinguish between improved paretic leg coordination versus nonparetic leg compensation. Methods: Three-dimensional forward dynamics simulations were developed for two post-stroke hemiparetic subjects walking at identical speeds before/after rehabilitation with opposite changes in propulsion asymmetry. Changes in the individual muscle contributions to forward propulsion were examined. Findings: The major source of increased forward propulsion in both subjects was from the ankle plantarflexors. How they were utilized differed and appears related to changes in propulsion asymmetry. Subject A increased propulsion generated from the paretic plantarflexors, while Subject B increased propulsion generated from the nonparetic plantarflexors. Each subject's strategy to increase speed also included differences in other muscle groups (e.g., hamstrings) that did not appear to be related to propulsion asymmetry. Interpretation: The results of this study highlight how speed cannot be used to elucidate underlying muscle coordination changes following rehabilitation. In contrast, propulsion asymmetry appears to provide insight into changes in plantarflexor output affecting propulsion generation and may be useful in monitoring rehabilitation outcomes. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Allen, Jessica L.; Neptune, Richard R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Neptune, RR (reprint author), Univ Texas Austin, Dept Mech Engn, 1 Univ Stn C2200, Austin, TX 78712 USA. EM rneptune@mail.utexas.edu FU NIH [R01 NS55380]; Rehabilitation Research & Development Service of the VA; NSF Graduate Research Fellowship Program FX The authors would like to thank Dr. Mark Bowden and the intervention research team for their contributions to the data collection and processing. This project was supported by NIH grant R01 NS55380, the Rehabilitation Research & Development Service of the VA, and the NSF Graduate Research Fellowship Program. The comments are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NICHD, VA or NSF. NR 42 TC 6 Z9 6 U1 3 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 EI 1879-1271 J9 CLIN BIOMECH JI Clin. Biomech. PD AUG PY 2014 VL 29 IS 7 BP 780 EP 786 DI 10.1016/j.clinbiomech.2014.06.001 PG 7 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA AQ1GY UT WOS:000342531100010 PM 24973825 ER PT J AU Ho, JM Anekonda, VT Thompson, BW Zhu, MY Curry, RW Hwang, BH Morton, GJ Schwartz, MW Baskin, DG Appleyard, SM Blevins, JE AF Ho, Jacqueline M. Anekonda, Vishwanath T. Thompson, Benjamin W. Zhu, Mingyan Curry, Robert W. Hwang, Bang H. Morton, Gregory J. Schwartz, Michael W. Baskin, Denis G. Appleyard, Suzanne M. Blevins, James E. TI Hindbrain Oxytocin Receptors Contribute to the Effects of Circulating Oxytocin on Food Intake in Male Rats SO ENDOCRINOLOGY LA English DT Article ID BRAIN-STEM NUCLEI; C-FOS EXPRESSION; HUMAN GASTROINTESTINAL-TRACT; PROLACTIN-RELEASING PEPTIDE; DORSAL VAGAL COMPLEX; PARAVENTRICULAR NUCLEUS; MESSENGER-RNA; CATECHOLAMINERGIC NEURONS; ADMINISTERED OXYTOCIN; GASTRIC-MOTILITY AB Oxytocin (OT)-elicited hypophagia has been linked to neural activity in the nucleus of the solitary tract (NTS). Because plasma OT levels increase after a meal, we hypothesized that circulating OT acts at both peripheral and hindbrain OT receptors (OTRs) to limit food intake. To initially determine whether circulating OT inhibits food intake by acting at hindbrain OTRs, we pretreated rats with an OTR antagonist administered into the fourth ventricle (4V) followed by either central or systemic OT administration. Administration of the OTR antagonist into the 4V blocked anorexia induced by either 4V or ip injection of OT. However, blockade of peripheral OTRs also weakened the anorectic response to ip OT. Our data suggest a predominant role for hindbrain OTRs in the hypophagic response to peripheral OT administration. To elucidate central mechanisms of OT hypophagia, we tested whether OT activates NTS catecholaminergic neurons. OT (ip) increased the number of NTS cells expressing c-Fos, of which 10%-15% were catecholaminergic. Furthermore, electrophysiological studies in mice revealed that OT stimulated 47% (8 of 17) of NTS catecholamine neurons through a presynaptic mechanism. However, OT-elicited hypophagia did not appear to require activation of alpha(1)-adrenoceptors, and blockade of glucagon-like peptide-1 receptors similarly did not attenuate anorexia induced by OT. These findings demonstrate that OT elicits satiety through both central and peripheral OTRs and that although catecholamine neurons are a downstream target of OT signaling in the NTS, the hypophagic effect is mediated independently of alpha(1)-adrenoceptor signaling. C1 [Ho, Jacqueline M.; Anekonda, Vishwanath T.; Thompson, Benjamin W.; Curry, Robert W.; Hwang, Bang H.; Baskin, Denis G.; Blevins, James E.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA 98108 USA. [Ho, Jacqueline M.; Morton, Gregory J.; Schwartz, Michael W.; Baskin, Denis G.; Blevins, James E.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Morton, Gregory J.; Schwartz, Michael W.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Morton, Gregory J.; Schwartz, Michael W.] Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA. [Zhu, Mingyan; Appleyard, Suzanne M.] Washington State Univ, Dept Integrat Physiol & Neurosci, Program Neurosci, Pullman, WA 99164 USA. RP Blevins, JE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res 151,1660 South Columbian Way, Seattle, WA 98108 USA. EM jeblevin@u.washington.edu FU Research and Development Service of the Department of Veterans Affairs; Cellular and Molecular Imaging Core of the Diabetes Research Center at the University of Washington; National Institutes of Health [P30DK017047, P30DK017047-31689, DK083452]; Department of Veterans Affairs Merit Review Research Program; Diabetes, Obesity, and Metabolism Training Grant [2T32DK007247]; Veterans Affairs Senior Research Career Scientist award FX This work was supported by the Research and Development Service of the Department of Veterans Affairs and the Cellular and Molecular Imaging Core of the Diabetes Research Center at the University of Washington and supported by National Institutes of Health Grant P30DK017047. The research in our laboratory has been supported by the Department of Veterans Affairs Merit Review Research Program as well as National Institutes of Health Grants P30DK017047-31689, DK083452 (to S.M.A.), and Diabetes, Obesity, and Metabolism Training Grant 2T32DK007247. D.G.B. is the recipient of a Veterans Affairs Senior Research Career Scientist award. NR 70 TC 10 Z9 10 U1 0 U2 8 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2014 VL 155 IS 8 BP 2845 EP 2857 DI 10.1210/en.2014-1148 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8QL UT WOS:000342343800011 PM 24877632 ER PT J AU McMillan, KK Pugh, MJ Hamid, H Salinsky, M Pugh, J Noel, PH Finley, EP Leykum, LK Lanham, HJ LaFrance, WC AF McMillan, Katharine K. Pugh, Mary Jo Hamid, Hamada Salinsky, Martin Pugh, Jacqueline Noel, Polly H. Finley, Erin P. Leykum, Luci K. Lanham, Holly J. LaFrance, W. Curt, Jr. TI Providers' perspectives on treating psychogenic nonepileptic seizures: Frustration and hope SO EPILEPSY & BEHAVIOR LA English DT Article DE Nonepileptic seizures; Diagnosis; Treatment; Veterans; Practitioners; Cognitive behavioral therapy ID GROUP PSYCHOEDUCATION; EPILEPSY CENTER; CARE; DIAGNOSIS; VETERANS; PSYCHIATRISTS; PERCEPTIONS; MANAGEMENT; SYMPTOMS; OUTCOMES AB Recent diagnostic and treatment advances in psychogenic nonepileptic seizures (PNES) have the potential to improve care for patients, but little is known about the current state of PNES care delivery in the Veterans Health Administration (VA). We conducted semistructured interviews with 74 health-care clinicians and workers in the VA, eliciting provider perceptions of PNES care. Data were analyzed according to principles of Grounded Theory. The results revealed variation in care and two emergent domain themes of frustration and hope. Frustration was manifest in subthemes including Complexity, Patient Acceptance, Uncertainty About Treatment, Need for Evidence-based Treatment, and Failure of Cross-Disciplinary Collaboration between neurologists and mental health providers. Hope encompassed subthemes of Positive Attitudes, Developing Cross-Disciplinary Treatment, and Specific PNES Care. Increased resources for diagnosing, treating, and researching PNES have improved awareness of the disorder. More research is needed to understand patients' and caregivers' perceptions of PNES care. (C) 2014 Elsevier Inc. All rights reserved. C1 [McMillan, Katharine K.; Pugh, Mary Jo; Noel, Polly H.; Finley, Erin P.; Leykum, Luci K.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [McMillan, Katharine K.; Pugh, Mary Jo; Pugh, Jacqueline; Noel, Polly H.; Finley, Erin P.; Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Pugh, Mary Jo; Hamid, Hamada] VA Epilepsy Ctr Excellence, San Antonio, TX USA. [Hamid, Hamada] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Hamid, Hamada] Yale Univ, New Haven, CT USA. [Salinsky, Martin] Portland VA Med Ctr, Portland, OR USA. [Salinsky, Martin] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lanham, Holly J.] Univ Texas Austin, McCombs Sch Business, Austin, TX 78712 USA. [LaFrance, W. Curt, Jr.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence Vet Affairs Med Ctr, Providence, RI 02903 USA. [LaFrance, W. Curt, Jr.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Neuropsychiat & Behav Neurol Div, Providence, RI 02903 USA. [Finley, Erin P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Finley, Erin P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. RP McMillan, KK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, MSC 7933, San Antonio, TX 78229 USA. EM mcmillank@uthscsa.edu OI LaFrance, Jr., W Curt/0000-0002-4901-3852; Pugh, Jacqueline/0000-0003-4933-141X; Pugh, Mary Jo/0000-0003-4196-7763; Finley, Erin/0000-0003-4497-7721 FU VA Health Services Research and Development [IIR-067-11-2]; Implementation Research Institute (IRI) at the George Warren Brown School of Social Work, Washington University in St. Louis, through an award from the National Institute of Mental Health [R25 MH080916-01A2] FX VA Health Services Research and Development (IIR-067-11-2; Dr. MJ Pugh PI) funded this study. Dr. Finley is an investigator with the Implementation Research Institute (IRI) at the George Warren Brown School of Social Work, Washington University in St. Louis, through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI). The content of this article is solely the responsibility of the authors and does not necessarily reflect the official views of the Veterans' Health Administration. The funding organizations had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. NR 42 TC 13 Z9 13 U1 4 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD AUG PY 2014 VL 37 BP 276 EP 281 DI 10.1016/j.yebeh.2014.07.001 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA AP7MJ UT WOS:000342261100048 PM 25128685 ER PT J AU Swanson, CM Nielson, CM Shrestha, S Lee, CG Barrett-Connor, E Jans, I Cauley, JA Boonen, S Bouillon, R Vanderschueren, D Orwoll, ES AF Swanson, Christine M. Nielson, Carrie M. Shrestha, Smriti Lee, Christine G. Barrett-Connor, Elizabeth Jans, Ivo Cauley, Jane A. Boonen, Steven Bouillon, Roger Vanderschueren, Dirk Orwoll, Eric S. CA Osteoporotic Fractures Men MrOS St TI Higher 25(OH)D-2 Is Associated With Lower 25(OH)D-3 and 1,25(OH)(2)D-3 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID VITAMIN-D DEFICIENCY; SERUM 25-HYDROXYVITAMIN D; OLDER MEN; OSTEOPOROTIC FRACTURES; D 25-HYDROXYLASE; D-2; SUPPLEMENTATION; CHOLECALCIFEROL; ERGOCALCIFEROL; CYP2R1 AB Context: Despite common use of supplemental vitamin D-2 in clinical practice, the associations of serum vitamin D-2 concentrations with other vitaminDmetabolites and total vitamin D are unclear. Objective: The aim of the study was to measure vitamin D-2 and D-3 levels and examine their associations with each other and with total vitamin D. Design: We performed a cross-sectional analysis of 679 randomly selected participants from the Osteoporotic Fractures in Men Study. 25-Hydroxyvitamin D-2 [ 25(OH)D-2], 25(OH)D-3, 1,25-dihydroxyvitamin D-2 [1,25(OH)(2)D-2], and 1,25(OH)(2)D-3 were measured using liquid chromatography-tandem mass spectrometry and were summed to obtain total 25(OH)D and 1,25(OH)(2)D. Associations between all metabolites (D-2, D-3, and total levels) were examined using Wilcoxon rank-sum tests and Spearman correlations. Results: 25(OH)D-2 and 1,25(OH)(2)D-2 were detectable in 189 (27.8%) and 178 (26.2%) of the men, respectively. Higher 25(OH)D-2 levels did not correlate with higher total 25(OH) D (r = 0.10; P = .17), although median total 25(OH)D was slightly higher in those with detectable vs undetectable 25(OH)D-2 (25.8 vs 24.3 ng/mL; P < .001). 25(OH)D-2 was not positively associated with total 1,25(OH)(2)D levels (r = -0.11; P = .13), and median 1,25(OH)(2)D level was not higher in those with detectable vs undetectable 25(OH)D-2. Higher 25(OH)D-2 was associated with lower 25(OH)D-3 (r = -0.35; P < .001) and 1,25(OH)(2)D-3 (r = -0.32; P < .001), with median levels of both D-3 metabolites 18-35% higher when D-2 metabolites were undetectable. Conclusions: In a cohort of older men, 25(OH)D-2 is associated with lower levels of 25(OH)D-3 and 1,25(OH)(2)D-3, suggesting that vitamin D-2 may decrease the availability of D-3 and may not increase calcitriol levels. C1 [Swanson, Christine M.; Lee, Christine G.; Orwoll, Eric S.] Oregon Hlth & Sci Univ, Div Endocrinol, Portland, OR 97239 USA. [Swanson, Christine M.; Nielson, Carrie M.; Shrestha, Smriti; Lee, Christine G.; Orwoll, Eric S.] Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland, OR 97239 USA. [Nielson, Carrie M.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Lee, Christine G.] Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, Div Epidemiol, La Jolla, CA 92093 USA. [Jans, Ivo; Vanderschueren, Dirk] Univ Leuven, KU Leuven, Lab Diagnost Med, B-3000 Leuven, Belgium. [Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Boonen, Steven] Univ Leuven, KU Leuven, Div Geriatr Med, B-3000 Leuven, Belgium. [Boonen, Steven] Univ Leuven, KU Leuven, Ctr Metab Bone Dis, B-3000 Leuven, Belgium. [Bouillon, Roger; Vanderschueren, Dirk] Univ Leuven, KU Leuven, Lab Clin & Expt Endocrinol, B-3000 Leuven, Belgium. RP Orwoll, ES (reprint author), 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM Orwoll@ohsu.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU National Institutes of Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute on Aging; National Center for Research Resources; NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01 AG027810, UL1 TR000128]; Merck Co, Inc. [SRA-12-009]; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007674-20]; University Hospital in Leuven FX The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging, the National Center for Research Resources, and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01 AG027810, and UL1 TR000128.; This work was supported in part by an independent investigator grant (SRA-12-009) (to E.S.O.) from Merck & Co, Inc. C.M.S. is supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant T32DK007674-20. D.V. is a senior clinical investigator supported by the University Hospital in Leuven. NR 30 TC 9 Z9 9 U1 1 U2 7 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2014 VL 99 IS 8 BP 2736 EP 2744 DI 10.1210/jc.2014-1069 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PO UT WOS:000342341200046 PM 24828488 ER PT J AU Calvert, JK Holt, SK Mossanen, M James, AC Wright, JL Porter, MP Gore, JL AF Calvert, Joshua K. Holt, Sarah K. Mossanen, Matthew James, Andrew C. Wright, Jonathan L. Porter, Michael P. Gore, John L. TI Use and Outcomes of Extended Antibiotic Prophylaxis in Urological Cancer Surgery SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; kidney neoplasms; urinary bladder neoplasms; antibiotic prophylaxis; cross infection ID CLOSTRIDIUM-DIFFICILE INFECTION; PROSTATE-CANCER; ANTIMICROBIAL-PROPHYLAXIS; BLADDER-CANCER; KIDNEY CANCER; RISK; METAANALYSIS; CARE; CYSTECTOMY; THERAPY AB Purpose: Although perioperative antibiotic prophylaxis prevents postoperative infectious complications, national guidelines recommend cessation of antibiotics within 24 hours after the procedure. Extended antibiotic prophylaxis beyond 24 hours may contribute to hospital acquired infections such as Clostridium difficile colitis. We evaluated practice patterns of antibiotic prophylaxis in genitourinary cancer surgery and assessed the impact of antibiotic prophylaxis on hospital acquired C. difficile infections. Materials and Methods: We identified 59,184 patients treated with radical prostatectomy, 27,921 who underwent partial or radical nephrectomy, and 5,425 treated with radical cystectomy for prostate, kidney and bladder cancers, respectively, from the Premier Perspective Database (Premier Inc., Charlotte, North Carolina) from 2007 to 2012. We constructed hierarchical linear regression models to identify patient and hospital factors associated with extended antibiotic prophylaxis. We evaluated the association between extended antibiotic prophylaxis and C. difficile infections for patients who underwent partial or radical nephrectomy and radical cystectomy with multivariate logistic regression. Results: Surgery specific models demonstrated that hospital identity was associated with a substantial proportion of the variation in extended antibiotic prophylaxis (20% to 35% for radical prostatectomy, partial or radical nephrectomy, and radical cystectomy). Postoperative C. difficile colitis occurred in 0.02% of patients treated with radical prostatectomy, 0.23% of those treated with partial or radical nephrectomy and 1.7% of those treated with radical cystectomy. On multivariate analysis extended antibiotic prophylaxis was associated with higher odds of C. difficile infection after partial or radical nephrectomy (OR 3.79, 95% CI 2.46-5.84) and radical cystectomy (OR 1.64, 95% CI 1.12-2.39). Conclusions: Antibiotics may be overused after genitourinary cancer surgery and this overuse is associated with hospital acquired C. difficile colitis. Efforts are needed to encourage greater compliance with evidence-based approaches to postoperative care. C1 [Calvert, Joshua K.; Holt, Sarah K.; Mossanen, Matthew; James, Andrew C.; Wright, Jonathan L.; Porter, Michael P.; Gore, John L.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Wright, Jonathan L.; Porter, Michael P.] VA Puget Sound Hlth Care Syst, Div Urol, Seattle, WA 98195 USA. RP Gore, JL (reprint author), 1959 NE Pacific St,Box 356510, Seattle, WA 98195 USA. EM jlgore@u.washington.edu NR 27 TC 17 Z9 18 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD AUG PY 2014 VL 192 IS 2 BP 425 EP 429 DI 10.1016/j.juro.2014.02.096 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA AP5BT UT WOS:000342095400038 PM 24603103 ER PT J AU Ripley, D Wierman, M Gerber, D Weintraub, A Newman, J AF Ripley, David Wierman, Margaret Gerber, Don Weintraub, Alan Newman, Jody TI Comment on The Decision to Provide Testosterone Supplementation to Patients With Traumatic Brain Injury SO PM&R LA English DT Letter C1 [Ripley, David] Rehabil Inst Chicago, Chicago, IL 60611 USA. [Wierman, Margaret] Univ Colorado, Sch Med, Aurora, CO USA. [Wierman, Margaret] Denver VA Med Ctr, Denver, CO USA. [Gerber, Don] Craig Hosp, Brain Injury Program, Englewood, CO USA. [Weintraub, Alan; Newman, Jody] Craig Hosp, Englewood, CO USA. RP Ripley, D (reprint author), Rehabil Inst Chicago, Chicago, IL 60611 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD AUG PY 2014 VL 6 IS 8 BP 761 EP 761 DI 10.1016/j.pmrj.2014.03.008 PG 1 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AO8PN UT WOS:000341616800017 PM 25169710 ER PT J AU Ross, RJ AF Ross, Richard J. TI The Changing REM Sleep Signature of Posttraumatic Stress Disorder SO SLEEP LA English DT Editorial Material ID DEPENDENT PLASTICITY; COMBAT VETERANS; DISTURBANCE; PRAZOSIN; NIGHTMARES; MECHANISM; PTSD C1 [Ross, Richard J.] Philadelphia VA Med Ctr, Behav Hlth Serv, Philadelphia, PA 19104 USA. [Ross, Richard J.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Ross, RJ (reprint author), Philadelphia VA Med Ctr, Behav Hlth Serv, 116 MHC,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM rossri@mail.med.upenn.edu FU NIMHD NIH HHS [1P20MD006899-01] NR 22 TC 4 Z9 4 U1 6 U2 12 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD AUG 1 PY 2014 VL 37 IS 8 BP 1281 EP 1282 DI 10.5665/sleep.3912 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AO7DL UT WOS:000341512100004 PM 25083007 ER PT J AU Pellegrino, R Kavakli, IH Goel, N Cardinale, CJ Dinges, DF Kuna, ST Maislin, G Van Dongen, HPA Tufik, S Hogenesch, JB Hakonarson, H Pack, AI AF Pellegrino, Renata Kavakli, Ibrahim Halil Goel, Namni Cardinale, Christopher J. Dinges, David F. Kuna, Samuel T. Maislin, Greg Van Dongen, Hans P. A. Tufik, Sergio Hogenesch, John B. Hakonarson, Hakon Pack, Allan I. TI A Novel BHLHE41 Variant is Associated with Short Sleep and Resistance to Sleep Deprivation in Humans SO SLEEP LA English DT Article DE BHLHE41; delta power; genetics; sleep; sleep deprivation; sleep loss ID SLOW-WAVE ACTIVITY; VIGILANCE TEST PVT; E-BOX ELEMENTS; TRANSCRIPTION FACTOR; INTERINDIVIDUAL DIFFERENCES; GENE-EXPRESSION; 2-PROCESS MODEL; MOLECULAR CLOCK; LONG SLEEPERS; DEC2 AB Study Objectives: Earlier work described a mutation in DEC2 also known as BHLHE41 (basic helix-loop-helix family member e41) as causal in a family of short sleepers, who needed just 6 h sleep per night. We evaluated whether there were other variants of this gene in two well-phenotyped cohorts. Design: Sequencing of the BHLHE41 gene, electroencephalographic data, and delta power analysis and functional studies using cell-based luciferase. Results: We identified new variants of the BHLHE41 gene in two cohorts who had either acute sleep deprivation (n = 200) or chronic partial sleep deprivation (n = 217). One variant, Y362H, at another location in the same exon occurred in one twin in a dizygotic twin pair and was associated with reduced sleep duration, less recovery sleep following sleep deprivation, and fewer performance lapses during sleep deprivation than the homozygous twin. Both twins had almost identical amounts of non rapid eye movement (NREM) sleep. This variant reduced the ability of BHLHE41 to suppress CLOCK/BMAL1 and NPAS2/BMAL1 transactivation in vitro. Another variant in the same exome had no effect on sleep or response to sleep deprivation and no effect on CLOCK/BMAL1 transactivation. Random mutagenesis identified a number of other variants of BHLHE41 that affect its function. Conclusions: There are a number of mutations of BHLHE41. Mutations reduce total sleep while maintaining NREM sleep and provide resistance to the effects of sleep loss. Mutations that affect sleep also modify the normal inhibition of BHLHE41 of CLOCK/BMAL1 transactivation. Thus, clock mechanisms are likely involved in setting sleep length and the magnitude of sleep homeostasis. C1 [Pellegrino, Renata; Cardinale, Christopher J.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Pellegrino, Renata; Goel, Namni; Dinges, David F.; Kuna, Samuel T.; Maislin, Greg; Pack, Allan I.] Univ Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Pellegrino, Renata; Tufik, Sergio] Univ Fed Sao Paulo, UNIFESP, Dept Psicobiol, Sao Paulo, Brazil. [Kavakli, Ibrahim Halil] Koc Univ, Dept Chem & Biol Engn, Sariyer, Turkey. [Kavakli, Ibrahim Halil] Koc Univ, Dept Mol Biol & Genet, Sariyer, Turkey. [Goel, Namni; Dinges, David F.] Univ Penn, Dept Psychiat, Perelman Sch Med, Div Sleep & Chronobiol, Philadelphia, PA 19104 USA. [Kuna, Samuel T.; Maislin, Greg; Pack, Allan I.] Univ Penn, Perelman Sch Med, Div Sleep Med, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. [Van Dongen, Hans P. A.] Washington State Univ, Sleep & Performance Res Ctr, Pullman, WA 99164 USA. [Hakonarson, Hakon] Univ Penn, Dept Pharmacol, Perelman Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. RP Pellegrino, R (reprint author), Childrens Hosp Philadelphia, Ctr Appl Genom, Abramson Res Ctr, 3615 Civ Ctr Blvd,Suite 1014, Philadelphia, PA 19104 USA. EM renata.pellegrino@gmail.com RI Cardinale, Christopher/G-3351-2013 OI Cardinale, Christopher/0000-0001-7513-8977 FU NIH [P01 HL094307, NR004281]; Institutional Development Fund from the Center for Applied Genomics at The Children's Hospital of Philadelphia; National Space Biomedical Research Institute through NASA [NCC 9-58]; CTRC [UL1RR024134]; Department of the Navy, Office of Naval Research [N00014-11-1-0361]; Pulsar Informatics; Boeing Company; Battelle Center for Human Performance Safety; Institutes for Behavior Resources; FedEx Express FX This was not an industry supported study. This work was supported in part by NIH grant P01 HL094307 and Institutional Development Fund from the Center for Applied Genomics at The Children's Hospital of Philadelphia. Data analyzed from experiments on chronic partial sleep deprivation were supported by the National Space Biomedical Research Institute through NASA NCC 9-58, NIH NR004281, CTRC UL1RR024134 and the Department of the Navy, Office of Naval Research Award No. N00014-11-1-0361. Drs Pellegrino and Kavakli are co-first authors. Dr. Dinges is Editor-in-Chief of SLEEP. Dr. Van Dongen has received grant funding from Pulsar Informatics, Boeing Company, Battelle Center for Human Performance & Safety, and Institutes for Behavior Resources; has received consulting fees from Pulsar Informatics and FedEx Express; and has participated in a paid speaking engagement with the Ohio Sleep Medicine Institute. The other authors have indicated no financial conflicts of interest. NR 47 TC 13 Z9 13 U1 2 U2 26 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD AUG 1 PY 2014 VL 37 IS 8 BP 1327 EP U127 DI 10.5665/sleep.3924 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AO7DL UT WOS:000341512100010 PM 25083013 ER PT J AU Manzo, CE Merrigan, MM Johnson, S Gerding, DN Riley, TV Silva, J Brazier, JS AF Manzo, Carl E. Merrigan, Michelle M. Johnson, Stuart Gerding, Dale N. Riley, Thomas V. Silva, Joseph, Jr. Brazier, Jon S. CA Int Clostridium Difficile Study Gr TI International typing study of Clostridium difficile SO ANAEROBE LA English DT Article DE Clostridium difficile; Genotypic typing; Phenotypic typing; PCR ribotyping; REA typing ID SYSTEMS; SCHEME; STRAIN AB We report the results of an international Clostridium difficile typing study to cross reference strain designations for seven typing methodologies and facilitate inter-laboratory communication. Four genotypic and three phenotypic methods were used to type 100 isolates and compare the results to 39 PCR ribotypes identified among the collection. Published by Elsevier Ltd. C1 [Manzo, Carl E.; Johnson, Stuart; Gerding, Dale N.] Loyola Univ, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Merrigan, Michelle M.; Johnson, Stuart; Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Riley, Thomas V.] Univ Western Australia, Perth, WA 6009, Australia. [Riley, Thomas V.] Queen Elizabeth II Med Ctr, Perth, WA, Australia. [Silva, Joseph, Jr.] Univ Calif Davis, Sacramento, CA 95817 USA. [Brazier, Jon S.] Univ Wales Hosp, Publ Hlth Lab, Anaerobe Reference Unit, Cardiff CF4 4XW, S Glam, Wales. RP Johnson, S (reprint author), Edward Hines Jr VA Hosp, Res Serv, 5000 S 5th St, Hines, IL 60141 USA. EM stuart.johnson2@va.gov; dale.gerding2@va.gov FU US Department of Veterans Affairs Research Service FX This work was supported in part by the US Department of Veterans Affairs Research Service Merit Review grants to DNG and SJ. NR 14 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1075-9964 EI 1095-8274 J9 ANAEROBE JI Anaerobe PD AUG PY 2014 VL 28 BP 4 EP 7 DI 10.1016/j.anaerobe.2014.04.005 PG 4 WC Microbiology SC Microbiology GA AO4YT UT WOS:000341348000002 PM 24768986 ER PT J AU Kowalkowski, MA Mims, MA Day, RS Du, XL Chan, W Chiao, EY AF Kowalkowski, M. A. Mims, M. A. Day, R. S. Du, X. L. Chan, W. Chiao, E. Y. TI Longer duration of combination antiretroviral therapy reduces the risk of Hodgkin lymphoma: A cohort study of HIV-infected male veterans SO CANCER EPIDEMIOLOGY LA English DT Article DE Hodgkin lymphoma; HIV; Non-AIDS defining cancer; Epidemiology; Combined antiretroviral therapy ID UNITED-STATES; IN-VITRO; IMMUNE RECONSTITUTION; PROTEASE INHIBITOR; CARCINOMA-CELLS; AIDS; CANCER; NELFINAVIR; DISEASE; VIVO AB Background: Hodgkin lymphoma (HL) incidence has increased since combined antiretroviral therapy (cART) introduction. It is unclear how different cART classes (e.g., protease inhibitors (PI), non-nucleoside reverse transcription inhibitors (NNRTI)) influence HL. This study aimed to determine the effects of cART duration on HL incidence among HIV-infected veterans. Methods: We performed a retrospective cohort study utilizing the Veterans Affairs HIV Clinical Case Registry (1985-2010). HL cases were identified using ICD-9 codes (201.4-9). cART, PI, and NNRTI duration was the aggregate number of treatment days delivered. Incidence rates (IR) and rate ratios (IRR) were calculated from Poisson regression models to examine the effects of cART duration on HL. Results: 31,576 cART users contributed 288,736 person-years (PY) and 211 HL cases (IR = 7.3/10,000 person-years). HL incidence decreased from 25.1/10,000 PY (95%CI = 18.9-33.4) within the first year of cART to 0.6/10,000 PY (95%CI = 0.3-1.6) after >= 10 years. In multivariable models, each additional year of cART was associated with decreased HL incidence (IRR = 0.80; 95%CI = 0.75-0.86); similar effects were observed in models assessing HL incidence by PI and NNRTI. Conclusion: Our findings indicate long-term cART of any class is associated with decreased HL risk. High HL incidence directly following cART initiation supports a potential immune reconstitution mechanism in HIV-related HL. Further research is needed to evaluate the interaction between early cART, immune reconstitution, and HL. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Kowalkowski, M. A.] Levine Canc Inst, Carolinas HealthCare Syst, Charlotte, NC 28204 USA. [Kowalkowski, M. A.; Mims, M. A.; Chiao, E. Y.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Kowalkowski, M. A.; Chiao, E. Y.] Houston Hlth Serv Res & Dev Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Day, R. S.; Du, X. L.] Univ Texas Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Chan, W.] Univ Texas Houston, Sch Publ Hlth, Dept Biostat, Houston, TX USA. RP Kowalkowski, MA (reprint author), Levine Canc Inst, Carolinas HealthCare Syst, Charlotte, NC 28204 USA. EM marc.kowalkowski@carolinashealthcare.org FU Houston Health Services Research and Development Center of Innovation [HFP90-020]; Michael E. DeBakey Veterans Affairs Medical Center; Baylor College of Medicine Dan L. Duncan Cancer Center [P30CA125123-04S1]; Baylor-UTHouston Center for AIDS Research (CFAR); NIH [AI036211]; NCI [R01CA163103] FX This work was supported in part by resources and the use of facilities at the Houston Health Services Research and Development Center of Innovation (HFP90-020), Michael E. DeBakey Veterans Affairs Medical Center and the Baylor College of Medicine Dan L. Duncan Cancer Center (P30CA125123-04S1). This research was also supported by the Baylor-UTHouston Center for AIDS Research (CFAR), an NIH-funded program (AI036211). EYC (R01CA163103) also received support from the NCI. The funders had no role in study design, data collection and analysis, or preparation of this report. NR 33 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 EI 1877-783X J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD AUG PY 2014 VL 38 IS 4 BP 386 EP 392 DI 10.1016/j.canep.2014.05.009 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AO5AI UT WOS:000341352100010 PM 24947588 ER PT J AU Liclican, EL Walser, TC Hazra, S Krysan, K Park, SJ Pagano, PC Gardner, BK Larsen, JE Minna, JD Dubinett, SM AF Liclican, Elvira L. Walser, Tonya C. Hazra, Saswati Krysan, Kostyantyn Park, Stacy J. Pagano, Paul C. Gardner, Brian K. Larsen, Jill E. Minna, John D. Dubinett, Steven M. TI Loss of miR125a Expression in a Model of K-ras-Dependent Pulmonary Premalignancy SO CANCER PREVENTION RESEARCH LA English DT Article ID CELL LUNG-CANCER; ACTIVATED RECEPTOR-GAMMA; MICRORNA EXPRESSION; EPITHELIAL-CELLS; CIGARETTE-SMOKE; DOWN-REGULATION; CHEMOPREVENTION; PIOGLITAZONE; ROSIGLITAZONE; ANGIOGENESIS AB Understanding the molecular pathogenesis of lung cancer is necessary to identify biomarkers/targets specific to individual airway molecular profiles and to identify options for targeted chemoprevention. Herein, we identify mechanisms by which loss of microRNA (miRNA) 125a-3p (miR125a) contributes to the malignant potential of human bronchial epithelial cells (HBEC) harboring an activating point mutation of the K-ras proto-oncogene (HBEC K-ras). Among other miRNAs, we identified significant miR125a loss in HBEC K-ras lines and determined that miR125a is regulated by the PEA3 transcription factor. PEA3 is upregulated in HBEC K-ras cells, and genetic knockdown of PEA3 restores miR125a expression. From a panel of inflammatory/angiogenic factors, we identified increased CXCL1 and vascular endothelial growth factor (VEGF) production by HBEC K-ras cells and determined that miR125a overexpression significantly reduces K-ras-mediated production of these tumorigenic factors. miR125a overexpression also abrogates increased proliferation of HBEC K-ras cells and suppresses anchorage-independent growth (AIG) of HBEC K-ras/P53 cells, the latter of which is CXCL1-dependent. Finally, pioglitazone increases levels of miR125a in HBEC K-ras cells via PEA3 downregulation. In addition, pioglitazone and miR125a overexpression elicit similar phenotypic responses, including suppression of both proliferation and VEGF production. Our findings implicate miR125a loss in lung carcinogenesis and lay the groundwork for future studies to determine whether miR125a is a possible biomarker for lung carcinogenesis and/or a chemoprevention target. Moreover, our studies illustrate that pharmacologic augmentation of miR125a in K-ras-mutated pulmonary epithelium effectively abrogates several deleterious downstream events associated with the mutation. (C)2014 AACR. C1 [Liclican, Elvira L.; Walser, Tonya C.; Hazra, Saswati; Krysan, Kostyantyn; Park, Stacy J.; Gardner, Brian K.; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Dept Med, Los Angeles, CA 90095 USA. [Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Pagano, Paul C.; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Liclican, Elvira L.; Walser, Tonya C.; Hazra, Saswati; Krysan, Kostyantyn; Park, Stacy J.; Gardner, Brian K.; Dubinett, Steven M.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Dubinett, Steven M.] VA Greater Los Angeles Hlth Care Ctr, Los Angeles, CA USA. [Larsen, Jill E.; Minna, John D.] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA. [Larsen, Jill E.; Minna, John D.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Ctr Hlth Sci 37 131, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu RI Larsen, Jill/G-3787-2010 OI Larsen, Jill/0000-0001-7806-3931 FU NIH/NHLBI [T32HL072752]; NCI [U01CA152751]; NIH/NCATS UCLA CTSI [UL1TR000124]; Department of Veteran Affairs [5I01BX000359]; NCI Lung Cancer SPORE [P50CA70907]; Cancer Prevention & Research Institute of Texas [RP120732] FX These studies were supported by funding from the following sources: NIH/NHLBI #T32HL072752 (to S.M. Dubinett, E.L. Liclican, T.C. Walser, S.J. Park), NCI #U01CA152751 (to S.M. Dubinett, T.C. Walser, K. Krysan, B.K. Gardner), NIH/NCATS UCLA CTSI #UL1TR000124 (to S.M. Dubinett), Department of Veteran Affairs #5I01BX000359 (S. M. Dubinett), NCI Lung Cancer SPORE #P50CA70907 (to J.D. Minna, J.E. Larsen), and Cancer Prevention & Research Institute of Texas #RP120732 (to J.D. Minna). NR 47 TC 1 Z9 1 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD AUG PY 2014 VL 7 IS 8 BP 845 EP 855 DI 10.1158/1940-6207.CAPR-14-0063 PG 11 WC Oncology SC Oncology GA AO9TU UT WOS:000341701200009 PM 24913817 ER PT J AU Bekelman, JE Epstein, AJ Emanuel, EJ AF Bekelman, Justin E. Epstein, Andrew J. Emanuel, Ezekiel J. TI Getting the Next Version of Payment Policy "Right" on the Road Toward Accountable Cancer Care SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID CLUSTER RANDOMIZED-TRIALS; HEALTH-CARE; QUALITY; PROVIDERS; BEHAVIOR C1 [Bekelman, Justin E.] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Bekelman, Justin E.] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Bekelman, Justin E.; Emanuel, Ezekiel J.] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Univ Penn, Perelman Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Emanuel, Ezekiel J.] Univ Penn, Wharton Sch Business, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Dept Vet Affairs, Philadelphia, PA USA. RP Bekelman, JE (reprint author), Univ Penn, Abramson Canc Ctr, Perelman Ctr Adv Med, Perelman Sch Med, 4 West,3400 Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM bekelman@uphs.upenn.edu FU NCI NIH HHS [K07-CA163616, K07 CA163616] NR 19 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2014 VL 89 IS 5 BP 954 EP 957 DI 10.1016/j.ijrobp.2014.04.022 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AO6IK UT WOS:000341453600005 PM 25035198 ER PT J AU Kerlikowske, K Hubbard, R Tosteson, ANA AF Kerlikowske, Karla Hubbard, Rebecca Tosteson, Anna N. A. TI Higher Mammography Screening Costs Without Appreciable Clinical Benefit: The Case of Digital Mammography SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; COMMUNITY PRACTICE; STAGE; WOMEN; RISK; AGE C1 [Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Vet Affairs, Gen Internal Med Sect, San Francisco, CA 94143 USA. [Hubbard, Rebecca] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Tosteson, Anna N. A.] Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Lebanon, NH USA. RP Kerlikowske, K (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM Karla.Kerlikowske@ucsf.edu NR 19 TC 2 Z9 2 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD AUG PY 2014 VL 106 IS 8 AR dju191 DI 10.1093/jnci/dju191 PG 2 WC Oncology SC Oncology GA AO8XB UT WOS:000341637800025 ER PT J AU Mulligan, JK Nagel, W O'Connell, BP Wentzel, J Atkinson, C Schlosser, RJ AF Mulligan, Jennifer K. Nagel, Whitney O'Connell, Brendan P. Wentzel, Jennifer Atkinson, Carl Schlosser, Rodney J. TI Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Vitamin D; secondhand smoke; sinusitis; epithelial cell ID ALLERGIC FUNGAL RHINOSINUSITIS; PRO-INFLAMMATORY CYTOKINE; REGULATORY T-CELLS; DENDRITIC CELLS; EPITHELIAL-CELLS; 2ND-HAND SMOKE; NASAL POLYPS; LIQUID-CHROMATOGRAPHY; 25-HYDROXYVITAMIN D; CHILDHOOD ASTHMA AB Background: Cigarette smoke (CS) plays a role in the exacerbation of chronic rhinosinusitis (CRS); however, the mechanism for this is unknown. We hypothesize that CS impairs human sinonasal epithelial cell (HSNEC) conversion of 25(OH) D3 (25VD3) to 1,25-dihydroxyvitamin D3 (1,25VD3) and, furthermore, that supplementation with 1,25VD3 will reverse smoke-induced inflammatory responses by HSNECs. Objective: We sought to determine the effect of CS on vitamin D3 (VD3) levels, conversion, and regulation of CS-induced inflammation in control subjects and patients with CRS. Methods: Blood and sinus tissue explants were collected at the time of surgery from control subjects, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic sinusitis with nasal polyps (CRSwNP). Expression of VD3 metabolizing enzymes were measured by using RT-PCR. Primary HSNECs were cultured from tissue explants. 25VD3 with and without cigarette smoke extract (CSE) was used to examine conversion of 25VD3 to 1,25VD3, as well as HSNEC production of proinflammatory cytokines. Results: CS exposure was associated with reduced circulating and sinonasal 25VD3 levels in all groups compared with those seen in CS-naive, disease-matched counterparts. CS exposure decreased expression of CYP27B1 and was especially pronounced in patients with CRSwNP. CSE impairs control HSNEC conversion of 25VD3. HSNECs from patients with CRSwNP also demonstrate an intrinsic reduction in conversion of 25VD3 to 1,25VD3. Exogenous 1,25VD3 reduces CSE-induced cytokine production by HSNECs. Conclusions: Exposure to CS is associated with reduced 25VD3 levels and an impaired ability of HSNECs to convert 25VD3 to 1,25VD3. Addition of 1,25VD3 reduces the proinflammatory effects of CS on HSNECs. Impaired VD3 conversion by CS exposure represents a novel mechanism through which CS induces its proinflammatory effects. C1 [Mulligan, Jennifer K.; Nagel, Whitney; O'Connell, Brendan P.; Wentzel, Jennifer; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC USA. [Atkinson, Carl] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC USA. [Mulligan, Jennifer K.; Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Mulligan, JK (reprint author), 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM konopa@musc.edu FU Flight Attendant Medical Research Institute [092401, 113039]; National Institutes of Health [R01HL091944]; Department of Veterans Affairs FX Supported by grants from the Flight Attendant Medical Research Institute (092401 to J.K.M. and 113039 to R.J.S.), the National Institutes of Health (R01HL091944 to C. A.), and a grant from the Department of Veterans Affairs. NR 55 TC 18 Z9 18 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2014 VL 134 IS 2 BP 342 EP + DI 10.1016/j.jaci.2014.01.039 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA AO5GB UT WOS:000341370800013 PM 24698317 ER PT J AU Harrell, KM Wilkins, SS Connor, MK Chodosh, J AF Harrell, Kathryn M. Wilkins, Stacy S. Connor, Megan K. Chodosh, Joshua TI Telemedicine and the Evaluation of Cognitive Impairment: The Additive Value of Neuropsychological Assessment SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Telemedicine; telehealth; neuropsychology; dementia; cognitive assessment ID TELEMENTAL HEALTH-SERVICES; MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; SCREENING TOOL; PRIMARY-CARE; IN-PERSON; DEMENTIA; TELEHEALTH; RELIABILITY; DIAGNOSIS AB Introduction: The number of people in the United States living with dementia is projected to rise to over 7.1 million in the next 12 years, representing a 40% increase from current levels. This anticipated "dementia tsunami" has led to a recent state and national policy emphasis on early detection, improved care quality, reduced caregiver burden, and increased access to care. The ability to achieve these objectives is limited by few dementia specialists in rural and small communities and the challenges of travel to and within congested urban regions for dementia patients and their caregivers. Telemedicine is one such means for responding to this lack of access to subspecialty assessment and care. We describe our early experiences with this technology applied to neuropsychological assessments, with data from 31 patients. Methods: As part of an interdisciplinary dementia care demonstration project, clinical video teleconferencing provides real-time high resolution video interactions between dementia subspecialists in a major metropolitan medical center and patients in 3 outlying clinics located 180, 150, and 100 miles away. Comprehensive neuropsychological assessments, designed to address referral questions related to neurocognitive disorders via clinical video teleconferencing, are conducted as one component of interdisciplinary care. Outcomes: Eighty-seven percent of patients referred for neuropsychological assessment had an inaccurate neurocognitive diagnosis at the time of referral. Unmet and unrecognized mental health treatment needs were identified in over 77% of patients. In addition, acceptance was good for patients, caregivers, and clinicians. Discussion: Teleneuropsychology is proving to be an excellent resource for clarifying cognitive and psychiatric diagnoses, and integrating individual strengths, weaknesses, and preferences into treatment and care plans used by other health care providers, patients, and caregivers. Published by Elsevier Inc. on behalf of AMDA - The Society for Post-Acute and Long-Term Care Medicine. C1 [Harrell, Kathryn M.; Wilkins, Stacy S.; Connor, Megan K.; Chodosh, Joshua] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Wilkins, Stacy S.; Chodosh, Joshua] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Harrell, KM (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 11G, Los Angeles, CA 90073 USA. EM kathryn.harrell@va.gov OI Chodosh, Joshua/0000-0001-7784-4306 FU US Department of Veterans Affairs, Office of Rural Health (ORH) [N22-FY13Q1-S1-P00555] FX Funding for this clinical demonstration project was provided by the US Department of Veterans Affairs, Office of Rural Health (ORH Project ID Number: N22-FY13Q1-S1-P00555). NR 51 TC 11 Z9 11 U1 2 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 EI 1538-9375 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD AUG PY 2014 VL 15 IS 8 BP 600 EP 606 DI 10.1016/j.jamda.2014.04.015 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AO2PL UT WOS:000341167400014 PM 24913209 ER PT J AU Dransfield, MT Feldman, G Korenblat, P LaForce, CF Locantore, N Pistolesi, M Watkins, ML Crim, C Martinez, FJ AF Dransfield, Mark T. Feldman, Gregory Korenblat, Phillip LaForce, Craig F. Locantore, Nicholas Pistolesi, Massimo Watkins, Michael L. Crim, Courtney Martinez, Fernando J. TI Efficacy and safety of once-daily fluticasone furoate/vilanterol (100/25 mcg) versus twice-daily fluticasone propionate/salmeterol (250/50 mcg) in COPD patients SO RESPIRATORY MEDICINE LA English DT Article DE Chronic obstructive pulmonary disease; Head-to-head; Inhaled corticosteroid; Long-acting beta(2)-agonist; Lung function ID MU-G; RANDOMIZED-TRIAL; PERSISTENT ASTHMA; LUNG-FUNCTION; FUROATE; EXACERBATIONS; SALMETEROL; VILANTEROL; AGONIST AB Background: Fluticasone furoate/vilanterol (FF/VI) is an inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA), recently approved as once-daily maintenance therapy for COPD. We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol (FP/SAL). Methods: Three 12 week studies comparing FF/VI and FP/SAL were conducted. Patients aged >= 40 years with moderate-to-very severe COPD were randomized to receive double-blind, double-dummy FF/VI 100/25 mcg once-daily, or FP/SAL 250/50 nncg twice-daily for 12 weeks following a 2 week placebo run-in period. The primary endpoint of each study was change from baseline trough in 0-24 h weighted mean FEV1 (wmFEV(1)) on Day 84. Safety was also assessed. Results: In Study 1 (HZC113109) (intent-to-treat n: FF/VI = 260; FP/SAL = 259), the increase from baseline in 0-24 h wmFEVi was significantly greater with FF/VI than FP/SAL (A80 mL, P < 0.001). In Study 2 (HZC112352) (intent-to-treat n: FF/VI = 259; FP/SAL = 252) and Study 3 (RLV116974) (intent-to-treat n: FF/VI = 412; FP/SAL = 416), the increase from baseline in 0 24 h wmFEVi was not significantly greater with FF/VI than FP/SAL (A29 mL, P = 0.267; A25 mL, P = 0.137). The treatment difference was statistically but not clinically significant in a pooled analysis (6,41 mL, P < 0.001). Pooled adverse events (FF/VI 27%; FP/SAL 28%) and serious adverse events (FF/VI 2%; FP/SAL 3%) were similar between treatments. Conclusions: Our data suggest that once-daily FF/VI 100/25 mcg provides FEV, improvement in COPD that is at least comparable with that conferred by twice-daily FP/SAL 250/50 mcg, although interpretation is limited by differences in individual study outcomes. The safety profiles of FF/VI 100/25 mcg and FP/SAL 250/50 mcg are similar. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Dransfield, Mark T.] Univ Alabama Birmingham, UAB Lung Hlth Ctr, Birmingham, AL 35294 USA. [Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Feldman, Gregory] S Carolina Pharmaceut Res, Spartanburg, SC 29303 USA. [Korenblat, Phillip] Clin Res Ctr LLB, St Louis, MO 63141 USA. [LaForce, Craig F.] North Carolina Clin Res, Raleigh, NC 27607 USA. [Locantore, Nicholas; Watkins, Michael L.; Crim, Courtney] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. [Pistolesi, Massimo] Univ Florence, I-50121 Florence, Italy. [Martinez, Fernando J.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Dransfield, MT (reprint author), Univ Alabama Birmingham, UAB Lung Hlth Ctr, Div Pulm Allergy & Crit Care Med, 1900 Univ Blvd,THT-422, Birmingham, AL 35294 USA. EM mdrans99@uab.edu FU GlaxoSmithKline (GSK) [HZC113109, HZC112352, RLV116974]; GlaxoSmithKline FX This study was funded by GlaxoSmithKline (GSK study numbers HZC113109, HZC112352, RLV116974). NL, an employee of the sponsor (GlaxoSmithKline), performed the statistical analysis; all authors (MTD, GE, PK, CFL, NL, MP, MLW, CC, FJM) contributed to the study design, interpreted the data and developed the manuscript. All authors had full access to the data and were responsible for the decision to publish the paper. The authors acknowledge the contribution of Anna Ellsworth, who performed the statistical analysis of Study 3 and of the pooled analysis, and thank all patients and investigators involved in the study. Editorial support, in the form of development of a draft outline in consultation with the authors, development of a manuscript first draft in consultation with the authors, editorial suggestions to draft versions of this paper, assembling tables and figures, collating author comments, copyediting, fact checking, referencing and graphic services, was provided by Geoff Weller, PhD, and Ian Grieve, PhD, at Gardiner-Caldwell Communications (Macclesfield, UK) and was funded by GlaxoSmithKline. NR 25 TC 18 Z9 19 U1 2 U2 9 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 EI 1532-3064 J9 RESP MED JI Respir. Med. PD AUG PY 2014 VL 108 IS 8 BP 1171 EP 1179 DI 10.1016/j.rmed.2014.05.008 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA AO4YU UT WOS:000341348100012 PM 24998880 ER PT J AU Minzenberg, MJ Lesh, TA Niendam, TA Yoon, JH Rhoades, RN Carter, CS AF Minzenberg, Michael J. Lesh, Tyler A. Niendam, Tara A. Yoon, Jong H. Rhoades, Remy N. Carter, Cameron S. TI Frontal cortex control dysfunction related to long-term suicide risk in recent-onset schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Suicide; Cognitive control; fMRI; Frontal cortex ID COGNITIVE CONTROL; PREFRONTAL CORTEX; 1ST EPISODE; PREMOTOR AREAS; WORST-POINT; BEHAVIOR; PSYCHOSIS; MOTOR; PREVENTION; VOLUME AB Objective: Suicide is highly-prevalent and the most serious outcome in schizophrenia, yet the disturbances in neural system functions that confer suicide risk remain obscure. Circuits operated by the prefrontal cortex (PFC) are altered in psychotic disorders, and various PFC changes are observed in post-mortem studies of completed suicide. We tested whether PFC activity during goal-representation (an important component of cognitive control) relates to long-term suicide risk in recent-onset schizophrenia. Method: 35 patients with recent-onset of DSM-IV-TR-defined schizophrenia (SZ) were evaluated for long-term suicide risk (using the Columbia Suicide Severity Rating Scale) and functional MRI during cognitive control task performance. Group-level regression models associating control-related brain activation with suicide risk controlled for depression, psychosis and impulsivity. Results: Within this group, past suicidal ideation was associated with lower activation with goal-representation demands in multiple PFC sectors. Among those with past suicidal ideation (n = 18), reported suicidal behavior was associated with lower control-related activation in premotor cortex ipsilateral to the active primary motor cortex. Conclusions: This study provides unique evidence that suicide risk directly relates to PFC-based circuit dysfunction during goal-representation, in a major mental illness with significant suicide rates. Among those with suicidal ideation, the overt expression in suicidal behavior may stem from impairments in premotor cortex support of action-planning as an expression of control. Furtherwork should address how PFC-based control function changes with risk over time, whether this brain-behavior relationship is specific to schizophrenia, and address its potential utility as a biomarker for interventions to mitigate suicide risk. Published by Elsevier B.V. C1 [Minzenberg, Michael J.; Rhoades, Remy N.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Minzenberg, Michael J.; Rhoades, Remy N.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Lesh, Tyler A.; Niendam, Tara A.; Carter, Cameron S.] Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA. [Carter, Cameron S.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. [Yoon, Jong H.] Stanford Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA USA. [Yoon, Jong H.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Minzenberg, MJ (reprint author), San Francisco VA Med Ctr, 116C,4150 Clement St, San Francisco, CA 94121 USA. EM Michael.minzenberg@ucsf.edu RI Niendam, Tara/K-8475-2015 OI Niendam, Tara/0000-0003-2285-5002 FU American Foundation for Suicide Prevention Young Investigator Award; Doris Duke Charitable Foundation Grant [2009045, MH059883] FX This work was supported by an American Foundation for Suicide Prevention Young Investigator Award, and the Doris Duke Charitable Foundation Grant # 2009045, both to MJM, and MH059883 to CSC. NR 41 TC 10 Z9 12 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2014 VL 157 IS 1-3 BP 19 EP 25 DI 10.1016/j.schres.2014.05.039 PG 7 WC Psychiatry SC Psychiatry GA AO4MR UT WOS:000341314100004 PM 24972755 ER PT J AU McCleery, A Ventura, J Kern, RS Subotnik, KL Gretchen-Doorly, D Green, MF Hellemann, GS Nuechterlein, KH AF McCleery, A. Ventura, J. Kern, R. S. Subotnik, K. L. Gretchen-Doorly, D. Green, M. F. Hellemann, G. S. Nuechterlein, K. H. TI Cognitive functioning in first-episode schizophrenia: MATRICS Consensus Cognitive Battery (MCCB) Profile of Impairment SO SCHIZOPHRENIA RESEARCH LA English DT Article DE MCCB; First-episode schizophrenia; Cognition; Profile analysis; First episode schizophrenia ID FIRST-EPISODE SCHIZOPHRENIA; FACIAL AFFECT RECOGNITION; 1ST EPISODE; ONSET SCHIZOPHRENIA; WORKING-MEMORY; PSYCHOSIS; DEFICITS; DISORDERS; DETERIORATION; RELIABILITY AB Background: Although many studies have assessed cognitive functioning in first-episode schizophrenia (FESz), the pattern and severity of impairment across cognitive domains remain unclear. Moreover, few studies have directly compared the pattern of cognitive performance between FESz and chronic schizophrenia (CSz). In this study we examined the cognitive impairment profile in FESz using a standardized neurocognitive battery (MATRICS Consensus Cognitive Battery; MCCB). Methods: MCCB data were compared from 105 FESz patients, 176 CSz patients and 300 non-psychiatric (NP) participants. Mixed model analysis evaluated group differences in MCCB profiles and relative strengths and weaknesses in the MCCB profiles of patients. Clinical implications of MCCB performance were also examined; we compared the proportion of participants from each group who exhibited clinically-significant global cognitive impairment based on the MCCB Overall Composite score. Results: FESz and CSz showed impaired performance across all MCCB domains relative to NP. With the exception of relative preservation of working memory and social cognition in FESz, the MCCB domain scores were similar in FESz and CSz. The distribution of impairment on the Overall Composite score did not significantly differ between FESz and CSz; compared to NP, both patient groups were over represented in moderate and severe impairment categories. Conclusion: The pattern, magnitude, and distribution of severity of impairment in FESz were similar to that observed in CSz. However, early in the illness, there may be relative sparing of working memory and social cognition. (C) 2014 Elsevier B.V. All rights reserved. C1 [McCleery, A.; Ventura, J.; Kern, R. S.; Subotnik, K. L.; Gretchen-Doorly, D.; Green, M. F.; Hellemann, G. S.; Nuechterlein, K. H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Kern, R. S.; Green, M. F.] Greater Los Angeles VA Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 22, Los Angeles, CA USA. [Nuechterlein, K. H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. RP McCleery, A (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat, 300 Med Plaza,Room 2213, Los Angeles, CA 90095 USA. EM amccleery@mednet.ucla.edu RI McCleery, Amanda/D-5471-2016 OI McCleery, Amanda/0000-0003-2714-6897 FU MATRICS Assessment, Inc.; Janssen Scientific Affairs [R092670SCH4005, RIS-NAP-4009]; Genentech [ML28264]; Posit Science [BPI-1000-11]; Genentech, Inc. [C4-150335]; Janssen Scientific Affairs, LLC; Genentech, Inc.; Amgen Foundation [20130132] FX M.F. Green and K.H. Nuechterlein are officers within MATRICS Assessment, Inc., the publisher of the MCCB, but do not receive any financial remuneration for their respective roles. R.S. Kern is an officer for MATRICS Assessment, Inc. and receives financial compensation for his role within the non-profit organization. K. H. Nuechterlein has received unrelated research grants from Janssen Scientific Affairs (R092670SCH4005; RIS-NAP-4009), Genentech (ML28264), and Posit Science (BPI-1000-11) and has been a consultant to Otsuka and Genentech. J. Ventura has received funding from Genentech, Inc. (C4-150335). He has served as a consultant to Brain Plasticity, Inc., and Boehringer-Ingelheim GmbH. K.L. Subotnik and D. Gretchen-Doorly have received research funding from Janssen Scientific Affairs, LLC, and Genentech, Inc., through grants to K. H. Nuechterlein and J. Ventura. K. L. Subotnik is a consultant to Otsuka America Pharmaceutical, Inc. M. F. Green has been a consultant to AbbVie, Biogen, DSP, FORUM Pharmaceuticals, and Roche, and he is on the scientific advisory board of Mnemosyne. He has received research funds from Amgen Foundation (20130132). All other authors declare they have no conflicts of interest. NR 60 TC 14 Z9 15 U1 7 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2014 VL 157 IS 1-3 BP 33 EP 39 DI 10.1016/j.schres.2014.04.039 PG 7 WC Psychiatry SC Psychiatry GA AO4MR UT WOS:000341314100006 PM 24888526 ER PT J AU Walsh-Messinger, J Ramirez, PM Wong, P Antonius, D Aujero, N McMahon, K Opler, LA Malaspina, D AF Walsh-Messinger, Julie Ramirez, Paul Michael Wong, Philip Antonius, Daniel Aujero, Nicole McMahon, Kevin Opler, Lewis A. Malaspina, Dolores TI Impairment in emotional modulation of attention and memory in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Emotion; Cognition; Negative symptoms ID SERIAL VISUAL PRESENTATION; AFFECTIVE-PICTURE-SYSTEM; HUMAN AMYGDALA; BLINK; WORDS; PERCEPTION; BEHAVIOR; STIMULI; AROUSAL; INFORMATION AB Emotion plays a critical role in cognition and goal-directed behavior via complex interconnections between the emotional and motivational systems. It has been hypothesized that the impairment in goal-directed behavior widely noted in schizophrenia may result from defects in the interaction between the neural (ventral) emotional system and (rostral) cortical processes. The present study examined the impact of emotion on attention and memory in schizophrenia. Twenty-five individuals with schizophrenia related psychosis and 25 healthy control subjects were administered a computerized task in which they were asked to search for target images during a Rapid Serial Visual Presentation of pictures. Target stimuli were either positive or negative, or neutral images presented at either 200 ms or 700 ms lag. Additionally, a visual hedonic task was used to assess differences between the schizophrenia group and controls on ratings of valence and arousal from the picture stimuli. Compared to controls, individuals with schizophrenia detected fewer emotional images under both the 200 ms and 700 ms lag conditions. Multivariate analyses showed that the schizophrenia group also detected fewer positive images under the 700 ms lag condition and fewer negative images under the 200 ms lag condition. Individuals with schizophrenia reported higher pleasantness and unpleasantness ratings than controls in response to neutral stimuli, while controls reported higher arousal ratings for neutral and positive stimuli compared to the schizophrenia group. These results highlight dysfunction in the neural modulation of emotion, attention, and cortical processing in schizophrenia, adding to the growing but mixed body of literature on emotion processing in the disorder. Published by Elsevier B.V. C1 [Walsh-Messinger, Julie; Ramirez, Paul Michael; Wong, Philip] Long Isl Univ, Dept Psychol, Brooklyn, NY USA. [Walsh-Messinger, Julie; Antonius, Daniel; Aujero, Nicole; McMahon, Kevin; Malaspina, Dolores] NYU, Sch Med, Dept Psychiat, InSPIRES, New York, NY USA. [Antonius, Daniel] SUNY Buffalo, Buffalo, NY 14260 USA. [Antonius, Daniel] Erie Cty Forens Mental Hlth Serv, Buffalo, NY USA. [Opler, Lewis A.] Columbia Univ, Dept Psychiat, New York, NY USA. [Malaspina, Dolores] NY State Off Mental Hlth, Creedmoor Psychiat Ctr, Queens, NY USA. RP Walsh-Messinger, J (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC, 130 West Kingsbridge Rd,6th Floor,Suite 6A-41C, Bronx, NY 10468 USA. EM julie.walshmessinger@mssm.edu FU National Institute of Mental Health [RC1MH088843, 2K24MH00169] FX This work was supported by the National Institute of Mental Health grants RC1MH088843 (DM) and 2K24MH00169 (DM). NR 58 TC 4 Z9 4 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2014 VL 157 IS 1-3 BP 63 EP 69 DI 10.1016/j.schres.2014.05.014 PG 7 WC Psychiatry SC Psychiatry GA AO4MR UT WOS:000341314100011 PM 24910446 ER PT J AU Tabak, NT Granholm, E AF Tabak, Naomi T. Granholm, Eric TI Mindful cognitive enhancement training for psychosis: A pilot study SO SCHIZOPHRENIA RESEARCH LA English DT Letter ID MEDITATION; ATTENTION C1 [Tabak, Naomi T.; Granholm, Eric] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Granholm, Eric] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. RP Tabak, NT (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, MIRECC, Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ntabak@ucla.edu RI Granholm, Eric/P-7680-2014 FU NIMH NIH HHS [T32 MH096682, T32MH09668] NR 10 TC 2 Z9 2 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2014 VL 157 IS 1-3 BP 312 EP 313 DI 10.1016/j.schres.2014.06.002 PG 2 WC Psychiatry SC Psychiatry GA AO4MR UT WOS:000341314100049 PM 24968738 ER PT J AU Deyo, RA Dworkin, SF Amtmann, D Andersson, G Borenstein, D Carragee, E Carrino, J Chou, R Cook, K DeLitto, A Goertz, C Khalsa, P Loeser, J Mackey, S Panagis, J Rainville, J Tosteson, T Turk, D Von Korff, M Weiner, DK AF Deyo, Richard A. Dworkin, Samuel F. Amtmann, Dagmar Andersson, Gunnar Borenstein, David Carragee, Eugene Carrino, John Chou, Roger Cook, Karon DeLitto, Anthony Goertz, Christine Khalsa, Partap Loeser, John Mackey, Sean Panagis, James Rainville, James Tosteson, Tor Turk, Dennis Von Korff, Michael Weiner, Debra K. TI Report of the NIH Task Force on Research Standards for Chronic Low Back Pain SO SPINE JOURNAL LA English DT Article DE Low back pain; chronic low back pain; research standards; minimum dataset; NIH Task Force ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM PROMIS; FUNCTION ITEM BANK; QUALITY-OF-LIFE; PRIMARY-CARE; PROGNOSTIC APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES AB Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Therefore, NIH Pain Consortium charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimum dataset to describe research participants (drawing heavily on the PROMIS methodology); reporting "responder analyses'' in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. We expect that the RTF recommendations will become a dynamic document and undergo continual improvement. PERSPECTIVE: A task force was convened by the NIH Pain Consortium with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimum dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. This guideline article was first reported in the The Journal of Pain. (C) 2014 by the American Pain Society. C1 [Deyo, Richard A.; Chou, Roger] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Dworkin, Samuel F.; Amtmann, Dagmar; Loeser, John; Turk, Dennis] Univ Washington, Seattle, WA 98195 USA. [Andersson, Gunnar] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Borenstein, David] George Washington Univ, Washington, DC USA. [Carragee, Eugene; Mackey, Sean] Stanford Univ, Stanford, CA 94305 USA. [Carrino, John; Weiner, Debra K.] Johns Hopkins Univ, Baltimore, MD USA. [Cook, Karon] Northwestern Univ, Evanston, IL USA. [DeLitto, Anthony] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [DeLitto, Anthony] Univ Pittsburgh, Pittsburgh, PA USA. [Goertz, Christine] Palmer Coll Chiropract, Davenport, IA USA. [Khalsa, Partap] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Panagis, James] Natl Inst Arthritis Musculoskeletal & Skin Dis, Bethesda, MD USA. [Rainville, James] New England Baptist Hosp, Roxbury Crossing, MA USA. [Tosteson, Tor] Dartmouth Coll, Hanover, NH USA. [Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code FM, Portland, OR 97239 USA. EM deyor@ohsu.edu FU National Center for Complementary and Alternative Medicine; National Institute for Arthritis, Musculoskeletal, and Skin Diseases FX This study was supported by the National Center for Complementary and Alternative Medicine and the National Institute for Arthritis, Musculoskeletal, and Skin Diseases. NR 124 TC 6 Z9 6 U1 8 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD AUG PY 2014 VL 14 IS 8 BP 1375 EP 1391 DI 10.1016/j.spinee.2014.05.002 PG 17 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AO4JT UT WOS:000341304300002 PM 24950669 ER PT J AU Yokoe, DS Anderson, DJ Berenholtz, SM Calfee, DP Dubberke, ER Ellingson, KD Gerding, DN Haas, JP Kaye, KS Klompas, M Lo, E Marschall, J Mermel, LA Nicolle, LE Salgado, CD Bryant, K Classen, D Crist, K Deloney, VM Fishman, NO Foster, N Goldmann, DA Humphreys, E Jernigan, JA Padberg, J Perl, TM Podgorny, K Septimus, EJ VanAmringe, M Weaver, T Weinstein, RA Wise, R Maragakis, LL AF Yokoe, Deborah S. Anderson, Deverick J. Berenholtz, Sean M. Calfee, David P. Dubberke, Erik R. Ellingson, Katherine D. Gerding, Dale N. Haas, Janet P. Kaye, Keith S. Klompas, Michael Lo, Evelyn Marschall, Jonas Mermel, Leonard A. Nicolle, Lindsay E. Salgado, Cassandra D. Bryant, Kristina Classen, David Crist, Katrina Deloney, Valerie M. Fishman, Neil O. Foster, Nancy Goldmann, Donald A. Humphreys, Eve Jernigan, John A. Padberg, Jennifer Perl, Trish M. Podgorny, Kelly Septimus, Edward J. VanAmringe, Margaret Weaver, Tom Weinstein, Robert A. Wise, Robert Maragakis, Lisa L. TI A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2014 Updates SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID CLOSTRIDIUM-DIFFICILE INFECTIONS; RESISTANT STAPHYLOCOCCUS-AUREUS; SURGICAL SITE INFECTIONS; BLOOD-STREAM INFECTIONS; TRANSMISSION AB Since the publication of "A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals" in 2008, prevention of healthcare-associated infections (HAIs) has become a national priority. Despite improvements, preventable HAIs continue to occur. The 2014 updates to the Compendium were created to provide acute care hospitals with up-to-date, practical, expert guidance to assist in prioritizing and implementing their HAI prevention efforts. They are the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Institute for Healthcare Improvement (IHI), the Pediatric Infectious Diseases Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), and the Surgical Infection Society (SIS). C1 [Yokoe, Deborah S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yokoe, Deborah S.; Goldmann, Donald A.] Harvard Univ, Sch Med, Boston, MA USA. [Anderson, Deverick J.] Duke Univ, Med Ctr, Durham, NC USA. [Berenholtz, Sean M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Berenholtz, Sean M.; Perl, Trish M.; Maragakis, Lisa L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Calfee, David P.] Weill Cornell Med Coll, New York, NY USA. [Dubberke, Erik R.] Washington Univ, Sch Med, St Louis, MO USA. [Ellingson, Katherine D.; Jernigan, John A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Gerding, Dale N.] Loyola Univ Chicago, Stritch Sch Med, Chicago, IL USA. [Haas, Janet P.] Westchester Med Ctr, Valhalla, NY USA. [Haas, Janet P.] New York Med Coll, Valhalla, NY 10595 USA. [Kaye, Keith S.] Detroit Med Ctr, Detroit, MI USA. [Kaye, Keith S.] Wayne State Univ, Detroit, MI USA. [Klompas, Michael] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Lo, Evelyn] St Boniface Gen Hosp, Winnipeg, MB R2H 2A6, Canada. [Lo, Evelyn; Nicolle, Lindsay E.] Univ Manitoba, Winnipeg, MB, Canada. [Marschall, Jonas] Univ Hosp Bern, CH-3010 Bern, Switzerland. [Marschall, Jonas] Univ Bern, Bern, Switzerland. [Mermel, Leonard A.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Mermel, Leonard A.] Rhode Isl Hosp, Providence, RI USA. [Nicolle, Lindsay E.] Hlth Sci Ctr, Winnipeg, MB, Canada. [Salgado, Cassandra D.] Med Univ S Carolina, Charleston, SC 29425 USA. [Bryant, Kristina] Univ Louisville, Louisville, KY 40292 USA. [Classen, David] Univ Utah, Sch Med, Salt Lake City, UT USA. [Crist, Katrina; Weaver, Tom] Assoc Profess Infect Control & Epidemiol, Washington, DC USA. [Deloney, Valerie M.; Humphreys, Eve] Soc Healthcare Epidemiol Amer, Arlington, VA USA. [Fishman, Neil O.] Univ Penn Hlth Syst, Philadelphia, PA USA. [Foster, Nancy] Amer Hosp Assoc, Washington, DC USA. [Goldmann, Donald A.] Inst Healthcare Improvement, Cambridge, MA USA. [Goldmann, Donald A.] Boston Childrens Hosp, Boston, MA USA. [Jernigan, John A.] Emory Univ, Sch Med, Atlanta, GA USA. [Padberg, Jennifer] Infect Dis Soc Amer, Arlington, VA USA. [Podgorny, Kelly; VanAmringe, Margaret; Wise, Robert] Joint Commiss, Oak Brook Terrace, IL USA. [Septimus, Edward J.] Texas A&M Hlth Sci Ctr, Coll Med, Houston, TX USA. [Septimus, Edward J.] Hosp Corp Amer, Nashville, TN USA. [Weinstein, Robert A.] Stroger Hosp, Chicago, IL USA. [Weinstein, Robert A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Yokoe, DS (reprint author), 181 Longwood Ave, Boston, MA 02115 USA. EM dyokoe@partners.org FU Society for Healthcare Epidemiology of America FX Support for this Compendium was provided by the Society for Healthcare Epidemiology of America. NR 21 TC 0 Z9 0 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD AUG PY 2014 VL 35 IS 8 BP 967 EP 977 DI 10.1086/677216 PG 11 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AL3RQ UT WOS:000339046900005 ER PT J AU Batki, SL Pennington, DL Lasher, B Neylan, TC Metzler, T Waldrop, A Delucchi, K Herbst, E AF Batki, Steven L. Pennington, David L. Lasher, Brooke Neylan, Thomas C. Metzler, Thomas Waldrop, Angela Delucchi, Kevin Herbst, Ellen TI Topiramate Treatment of Alcohol Use Disorder in Veterans with Posttraumatic Stress Disorder: A Randomized Controlled Pilot Trial SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Topiramate; Clinical Trial; Alcohol Use Disorder; Posttraumatic Stress Disorder; Cognition ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; COGNITIVE FUNCTION; DEPENDENT PATIENTS; OPEN-LABEL; ADD-ON; EFFICACY; PTSD; NALTREXONE; THERAPY AB Background: The course of posttraumatic stress disorder (PTSD) is frequently and severely complicated by co-occurring alcohol use disorder (AUD), yet there are few reports of pharmacologic treatments for these comorbid conditions. The objective of this pilot study was to obtain a preliminary assessment of the efficacy and safety of topiramate in reducing alcohol use and PTSD symptoms in veterans with both disorders. Methods: This was a prospective 12-week, randomized, double-blind, placebo-controlled pilot trial of flexible-dose topiramate up to 300 mg/d in 30 veterans with PTSD and AUD. The primary outcome measure was frequency of drinking. Secondary outcomes consisted of other measures of alcohol use and PTSD symptom severity. Results: Within-group analyses showed that topiramate treatment was associated with significant reductions in frequency and amount of alcohol use and alcohol craving from baseline through week 12. Between-group analyses showed that topiramate reduced frequency of alcohol use and alcohol craving significantly more than placebo and tended to reduce drinking amount. Topiramate treatment was also associated with decreased PTSD symptom severity and tended to reduce hyperarousal symptoms compared with placebo. Topiramate transiently impaired learning and memory, with significant recovery by the end of treatment. Conclusions: These preliminary results indicate that in veterans with co-occurring PTSD and AUD, topiramate may be effective in reducing alcohol consumption, alcohol craving, and PTSD symptom severity-particularly hyperarousal symptoms. Topiramate was associated with transient cognitive impairment but was otherwise well tolerated. C1 [Batki, Steven L.; Pennington, David L.; Lasher, Brooke; Neylan, Thomas C.; Metzler, Thomas; Waldrop, Angela; Herbst, Ellen] San Francisco VA Med Ctr, San Francisco, CA USA. [Batki, Steven L.; Pennington, David L.; Lasher, Brooke; Neylan, Thomas C.; Metzler, Thomas; Waldrop, Angela; Herbst, Ellen] NCIRE, Addict Res Program, San Francisco, CA USA. [Batki, Steven L.; Neylan, Thomas C.; Metzler, Thomas; Waldrop, Angela; Delucchi, Kevin; Herbst, Ellen] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Batki, SL (reprint author), San Francisco VA Med Ctr 116E, Dept Psychiat, Subst Abuse Programs, 4150 Clement St, San Francisco, CA 94121 USA. EM steven.batki@ucsf.edu FU Department of Defense [W81XWH-05-2-0094, W81XWH-12-2-0137, W81XWH-11-2-0245]; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health UCSF-CTSI [UL1 RR024131] FX This work was supported by grants from the Department of Defense W81XWH-05-2-0094, W81XWH-12-2-0137, and W81XWH-11-2-0245 (SLB), National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health UCSF-CTSI UL1 RR024131, which were administered by the Northern California Institute for Research and Education, and with resources of the Veterans Affairs Medical Center, San Francisco, California. NR 43 TC 15 Z9 16 U1 9 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2014 VL 38 IS 8 BP 2169 EP 2177 DI 10.1111/acer.12496 PG 9 WC Substance Abuse SC Substance Abuse GA AO2UQ UT WOS:000341181900005 PM 25092377 ER PT J AU Hill, JN Hogan, TP Cameron, KA Guihan, M Goldstein, B Evans, ME Evans, CT AF Hill, Jennifer N. Hogan, Timothy P. Cameron, Kenzie A. Guihan, Marylou Goldstein, Barry Evans, Martin E. Evans, Charlesnika T. TI Perceptions of methicillin-resistant Staphylococcus aureus and hand hygiene provider training and patient education: Results of a mixed method study of health care providers in Department of Veterans Affairs spinal cord injury and disorder units SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Provider training; Patient education; Methicillin-resistant Staphylococcus aureus; Spinal cord injury and disorders ID INFECTIONS; KNOWLEDGE; PREVENTION; BELIEFS; ATTITUDES; AWARENESS; STAFF; MRSA AB Background: The goal of this study was to assess current practices for training of spinal cord injury and disorder (SCI/D) health care workers and education of veterans with SCI/D in Department of Veterans Affairs (VA) spinal cord injury (SCI) centers on methicillin-resistant Staphylococcus aureus (MRSA) prevention. Methods: Mixed methods. A Web-based survey was distributed to 673 VA SCI/D providers across 24 SCI centers; 21 acute care and 1 long-term care facility participated. There were 295 that responded, 228 had complete data and were included in this analysis. Semistructured interviews were conducted with 30 SCI/D providers across 9 SCI centers. Results: Nurses, physicians, and therapists represent most respondents (92.1%, n = 210); over half (56.6%, n = 129) were nurses. Of providers, 75.9% (n = 173) reported receiving excellent or good training on how to educate patients about MRSA. However, nurses were more likely to report having excellent or good training for how to educate patients about MRSA (P = .005). Despite this, only 63.6% (n = 82) of nurses perceived the education they provide patients on how MRSA is transmitted as excellent or good. Conclusion: Despite health care workers reporting receiving excellent or good training on MRSA-related topics, this did not translate to excellent or good education for patients, suggesting that health care workers need additional training for educating patients. Population-specific MRSA prevention educational materials may also assist providers in educating patients about MRSA prevention for individuals with SCI/D. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Hill, Jennifer N.; Guihan, Marylou; Evans, Charlesnika T.] Edward Hines Jr VA Hosp, Vet Hlth Adm, Dept Vet Affairs, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL 60141 USA. [Hill, Jennifer N.; Guihan, Marylou; Evans, Charlesnika T.] Edward Hines Jr VA Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL 60141 USA. [Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, US Dept Vet Affairs, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, US Dept Vet Affairs, Natl EHlth Qual Enhancement Res Initiat Coordinat, EHlth Qual Enhancement Res Initiat, Bedford, MA USA. [Hogan, Timothy P.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Hlth Informat & Implementat Sci, Worcester, MA USA. [Hogan, Timothy P.] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Gen Internal Med & Geriatr, Chicago, IL 60611 USA. [Cameron, Kenzie A.; Evans, Charlesnika T.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. [Cameron, Kenzie A.; Evans, Charlesnika T.] Northwestern Univ, Feinberg Sch Med, Ctr Healthcare Studies, Chicago, IL USA. [Goldstein, Barry] Dept Vet Affairs, Patient Care Serv, Spinal Cord Injury Disorders Serv, Seattle, WA USA. [Goldstein, Barry] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Evans, Martin E.] Dept Vet Affairs, Vet Hlth Adm Methicillin Resistant Staphylococcus, Natl Infect Dis Serv, Cent Off, Lexington, KY USA. [Evans, Martin E.] Lexington VA Med Ctr, Lexington, KY USA. [Evans, Martin E.] Univ Kentucky, Sch Med, Dept Internal Med, Div Infect Dis, Lexington, KY 40536 USA. RP Hill, JN (reprint author), Edward Hines Jr VA Hosp, Vet Hlth Adm, Dept Vet Affairs, 5000 S 5th Ave 151H, Hines, IL 60141 USA. EM jennifer.hill3@va.gov OI Cameron, Kenzie/0000-0002-3535-6459 FU United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service, and Quality Enhancement Research Initiative [RRP09-163] FX This study was supported by the United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service, and Quality Enhancement Research Initiative (Grant: RRP09-163). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 25 TC 2 Z9 2 U1 2 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD AUG PY 2014 VL 42 IS 8 BP 834 EP 840 DI 10.1016/j.ajic.2014.04.026 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AO4KN UT WOS:000341306700004 PM 24950922 ER PT J AU Pang, CE Shah, VP Sarraf, D Freund, KB AF Pang, Claudine E. Shah, Vinnie P. Sarraf, David Freund, K. Bailey TI Ultra-Widefield Imaging With Autofluorescence and Indocyanine Green Angiography in Central Serous Chorioretinopathy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID UVEAL EFFUSION SYNDROME; FUNDUS AUTOFLUORESCENCE; SURGICAL-TREATMENT; CLINICAL-FEATURES; PATHOGENESIS; HYPOTHESIS AB PURPOSE: To describe the spectrum of ultra-widefield autofluorescence (AF) and indocyanine green (ICG) angiographic findings in central serous chorioretinopathy (CSC). DESIGN: Retrospective observational case series. METHODS: In 37 patients, 65 eyes with CSC from 2 vitreoretinal clinical practices were imaged using ultra-widefield AF and 24 of these eyes with ultra-widefield ICG angiography. Images were correlated with clinical findings and spectral-domain optical coherence tomography (OCT). RESULTS: In 37 (57%) eyes, a variety of altered AF patterns, including gravitational tracts, extended beyond the posterior 50 degrees of retina. Hyper-AF corresponded to areas of subretinal fluid (SRF) on spectral-domain OCT and was found to persist in 44 (70%) eyes for up to 8 years despite resolution of SRF. These areas corresponded to outer retinal atrophy with viable retinal pigment epithelium (RPE) on spectral-domain OCT and may be explained by the unmasking of normal background RPE AF. Ultra-widefield ICG angiography revealed dilated choroidal vessels and choroidal hyperpermeability in areas corresponding to altered AF on ultra-widefield AF in all 24 eyes. In 20 (83.3%) eyes, dilated vessels were observed in association with 1 or more congested vortex veins ampullas, suggesting that outflow congestion may be a contributing factor to the pathogenesis of CSC. CONCLUSIONS: Ultra-widefield AF and ICG angiography in CSC revealed more widespread disease in a single image than with standard field imaging and may be useful for identifying peripheral areas of previous or ongoing SRF and choroidal hyperpermeability that can assist in the diagnosis of CSC, surveillance of recurrent disease and treatment of active disease. (C) 2014 by Elsevier Inc. All rights reserved. C1 [Pang, Claudine E.; Shah, Vinnie P.; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY 10022 USA. [Pang, Claudine E.; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA. [Shah, Vinnie P.; Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY 10003 USA. [Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90024 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. RP Freund, KB (reprint author), Vitreous Retina Macula Consultants New York, 460 Pk Ave,Fifth Floor, New York, NY 10022 USA. EM kbfnyf@aol.com OI Shah, Vinnie/0000-0003-1325-7019; Freund, K. Bailey/0000-0002-7888-9773 FU Macula Foundation, Inc., New York, NY, USA; Regeneron; Heidelberg FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST, and the following were reported. Financial support was received from the Macula Foundation, Inc., New York, NY, USA. The funding organization had no role in the design or conduct of this research. Dr Freund is a consultant to Genentech, Regeneron, Optos, Heidelberg Engineering, and Bayer. Dr Sarraf received research support from Regeneron and financial support from Heidelberg. Dr Pang and Dr Shah have no financial disclosures. Design and conduct of study (C.E.P., V.P.S., K.B.F., D.S.); Collection, management, analysis, and interpretation of data (C.E.P., V.P.S., K.B.F., D.S.); and Preparation, review, or approval of the manuscript (C.E.P., V.P.S., K.B.F., D.S.). NR 36 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 2014 VL 158 IS 2 BP 362 EP 371 DI 10.1016/j.ajo.2014.04.021 PG 10 WC Ophthalmology SC Ophthalmology GA AN6EB UT WOS:000340686600021 PM 24794091 ER PT J AU Ioannou, GN Beste, LA Green, PK AF Ioannou, George N. Beste, Lauren A. Green, Pamela K. TI Similar Effectiveness of Boceprevir and Telaprevir Treatment Regimens for Hepatitis C Virus Infection on the Basis of a Nationwide Study of Veterans SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE DAA; Antiviral Therapy; Population; APRI; Outcome; LDL ID HEPATOCELLULAR-CARCINOMA; CIRRHOSIS; PREDICTORS; PREVALENCE; FIBROSIS AB BACKGROUND & AIMS: We investigated the real-world effectiveness of triple therapy regimens against hepatitis C virus (HCV) and compared rates of sustained virologic response (SVR) between telaprevir-based and boceprevir-based regimens in a population-based study. METHODS: We analyzed data on all patients in the Veterans Administration healthcare system who were infected with HCV genotype 1 and began treatment with pegylated interferon, ribavirin, and either boceprevir (n = 3696,83%) or telaprevir (n = 759,17%) from June 2011 to February 2013. RESULTS: Patients treated with telaprevir were more likely to have baseline characteristics associated with not achieving SVR than patients treated with boceprevir. Fewer than half of patients eligible for short-duration regimens (28 weeks for boceprevir, 24 weeks for telaprevir) successfully completed treatment (37% for boceprevir, 27.5% for telaprevir); similar to 25% discontinued early, and the remaining patients were treated for longer durations. Of the patients who were supposed to complete 48-week regimens, only 35% of boceprevir-treated and 34% of telaprevir-treated patients completed >44 weeks. The rate of SVR was 51.5% overall, 42.7% among patients with cirrhosis, 56.8% among treatment-naive patients, 64.2% among prior relapsers, 31.7% among prior partial responders, and 29.8% among prior null responders. There were no significant differences in rate of SVR between patients given boceprevir or telaprevir in the entire population or among subgroups. The most important predictors of failure to achieve SVR were IL28B genotype, high viral load, black race, diabetes, high aspartate aminotransferase to platelet ratio index or FIB-4 scores, low platelet counts, or low levels of low-density lipoprotein cholesterol. Erythropoietin use was not associated with SVR. CONCLUSIONS: In a nationwide analysis of veterans with HCV genotype 1 infection, rates of SVR were similar for those treated with boceprevir vs telaprevir. However, rates of treatment completion and SVR in real clinical practice were substantially lower than those in clinical trials. C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA 98108 USA. [Ioannou, George N.; Green, Pamela K.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Beste, Lauren A.] Vet Affairs Puget Sound Hlth Care Syst, Div Internal Med, Seattle, WA 98108 USA. [Ioannou, George N.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Beste, Lauren A.] Univ Washington, Div Internal Med, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, S 111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU Merit Review grant, Clinical Science Research and Development, Office of Research and Development, Veterans Affairs [I01CX000320] FX Supported by a Merit Review grant (I01CX000320), Clinical Science Research and Development, Office of Research and Development, Veterans Affairs (G.N.I.). NR 15 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD AUG PY 2014 VL 12 IS 8 BP 1371 EP 1380 DI 10.1016/j.cgh.2013.12.011 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO2BG UT WOS:000341119700027 PM 24361415 ER PT J AU May, FP Bromley, EG Reid, MW Baek, M Yoon, J Cohen, E Lee, A van Oijen, MGH Spiegel, BMR AF May, Folasade P. Bromley, Erica G. Reid, Mark W. Baek, Michael Yoon, Jessica Cohen, Erica Lee, Aaron van Oijen, Martijn G. H. Spiegel, Brennan M. R. TI Low uptake of colorectal cancer screening among African Americans in an integrated Veterans Affairs health care network SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COLON-CANCER; MEDICARE BENEFICIARIES; DISPARITIES; POPULATION; PREDICTORS; PATTERNS; COVERAGE; WOMEN AB Background: African Americans have the highest incidence and mortality from colorectal cancer (CRC). Despite guidelines to initiate screening with colonoscopy at age 45 in African Americans, the CRC incidence remains high in this group. Objective: To examine the rates and predictors of CRC screening uptake as well as time to screening in a population of African Americans and non-African Americans in a health care system that minimizes variations in insurance and access. Design: Retrospective cohort study. Setting: Greater Los Angeles Veterans Affairs (VA) Healthcare System. Patients: Random sample (N = 357) of patients eligible for initial CRC screening. Main Outcome Measurements: Uptake of any screening method; uptake of colonoscopy, in particular; predictors of screening; and time to screening in African Americans and non-African Americans. Results: The overall screening rate by any method was 50%. Adjusted rates for any screening were lower among African Americans than non-African Americans (42% vs 58%; odds ratio [OR] 0.49; 95% confidence interval [CI], 0.31-0.77). Colonoscopic screening was also lower in African Americans (11% vs 23%; adjusted OR 0.43; 95% CI, 0.24-0.77). In addition to race, homelessness, lower service connectedness, taking more prescription drugs, and not seeing a primary care provider within 2 years of screening eligibility predicted lower uptake of screening. Time to screening colonoscopy was longer in African Americans (adjusted hazard ratio 0.43; 95% CI, 0.25-0.75). Limitations: The sample may not be generalizable. Conclusions: We found marked disparities in CRC screening despite similar access to care across races. Despite current guidelines aimed at increasing CRC screening in African Americans, participation in screening remained low, and use of colonoscopy was infrequent. C1 [May, Folasade P.; Bromley, Erica G.; Baek, Michael; Yoon, Jessica; Cohen, Erica; Lee, Aaron; Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Dept Med, Div Gastroenterol, Los Angeles, CA USA. [May, Folasade P.; van Oijen, Martijn G. H.; Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. [May, Folasade P.; Spiegel, Brennan M. R.] UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [May, Folasade P.; Reid, Mark W.; Spiegel, Brennan M. R.] UCLA VA Ctr Outcomes Res & Educ CORE, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, UCLA VA Ctr Outcomes Res & Educ CORE, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. FU NIH [T32DK07180-34] FX All authors disclosed no financial relationships relevant to this publication. This research was supported by NIH training grant T32DK07180-34 to Dr May. NR 26 TC 9 Z9 9 U1 2 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD AUG PY 2014 VL 80 IS 2 BP 291 EP 298 DI 10.1016/j.gie.2014.01.045 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO2KX UT WOS:000341151700012 PM 24674351 ER PT J AU Yaghoobi, M AF Yaghoobi, Mohammad TI Treatment of patients with new diagnosis of achalasia: laparoscopic Heller's myotomy may be more effective than pneumatic dilation SO GASTROINTESTINAL ENDOSCOPY LA English DT Letter C1 Med Univ S Carolina, Div Gastroenterol & Hepatol, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Yaghoobi, M (reprint author), Med Univ S Carolina, Div Gastroenterol & Hepatol, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD AUG PY 2014 VL 80 IS 2 BP 360 EP 360 DI 10.1016/j.gie.2014.02.029 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO2KX UT WOS:000341151700035 PM 25034845 ER PT J AU Nelson, KM Helfrich, C Sun, HL Hebert, PL Liu, CF Dolan, E Taylor, L Wong, E Maynard, C Hernandez, SE Sanders, W Randall, I Curtis, I Schectman, G Stark, R Fihn, SD AF Nelson, Karin M. Helfrich, Christian Sun, Haili Hebert, Paul L. Liu, Chuan-Fen Dolan, Emily Taylor, Leslie Wong, Edwin Maynard, Charles Hernandez, Susan E. Sanders, William Randall, Ian Curtis, Idamay Schectman, Gordon Stark, Richard Fihn, Stephan D. TI Implementation of the Patient-Centered Medical Home in the Veterans Health Administration Associations With Patient Satisfaction, Quality of Care, Staff Burnout, and Hospital and Emergency Department Use SO JAMA INTERNAL MEDICINE LA English DT Article ID RECEIVING PRIMARY-CARE; CLINICS; TRANSFORMATION; PHYSICIANS; INVENTORY; SYSTEM AB IMPORTANCE In 2010, the Veterans Health Administration (VHA) began implementing the patient-centered medical home (PCMH) model. The Patient Aligned Care Team (PACT) initiative aims to improve health outcomes through team-based care, improved access, and care management. To track progress and evaluate outcomes at all VHA primary care clinics, we developed and validated a method to assess PCMH implementation. OBJECTIVES To create an index that measures the extent of PCMH implementation, describe variation in implementation, and examine the association between the implementation index and key outcomes. DESIGN, SETTING, AND PARTICIPANTS We conducted an observational study using data on more than 5.6 million veterans who received care at 913 VHA hospital-based and community-based primary care clinics and 5404 primary care staff from (1) VHA clinical and administrative databases, (2) a national patient survey administered to a weighted random sample of veterans who received outpatient care from June 1 to December 31, 2012, and (3) a survey of all VHA primary care staff in June 2012. Composite scores were constructed for 8 core domains of PACT: access, continuity, care coordination, comprehensiveness, self-management support, patient-centered care and communication, shared decision making, and team-based care. MAIN OUTCOMES AND MEASURES Patient satisfaction, rates of hospitalization and emergency department use, quality of care, and staff burnout. RESULTS Fifty-three items were included in the PACT Implementation Progress Index (Pi(2)). Compared with the 87 clinics in the lowest decile of the Pi(2), the 77 sites in the top decile exhibited significantly higher patient satisfaction (9.33 vs 7.53; P < .001), higher performance on 41 of 48 measures of clinical quality, lower staff burnout (Maslach Burnout Inventory emotional exhaustion subscale, 2.29 vs 2.80; P = .02), lower hospitalization rates for ambulatory care-sensitive conditions (4.42 vs 3.68 quarterly admissions for veterans 65 years or older per 1000 patients; P < .001), and lower emergency department use (188 vs 245 visits per 1000 patients; P < .001). CONCLUSIONS AND RELEVANCE The extent of PCMH implementation, as measured by the Pi2, was highly associated with important outcomes for both patients and providers. This measure will be used to track the effectiveness of implementing PACT over time and to elucidate the correlates of desired health outcomes. C1 [Nelson, Karin M.; Helfrich, Christian; Sun, Haili; Hebert, Paul L.; Liu, Chuan-Fen; Dolan, Emily; Taylor, Leslie; Maynard, Charles; Hernandez, Susan E.; Randall, Ian] VA Puget Sound Hlth Care Syst, Seattle Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA 98108 USA. [Nelson, Karin M.; Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, Gen Internal Med Serv, Seattle, WA 98108 USA. [Nelson, Karin M.; Fihn, Stephan D.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Helfrich, Christian; Sun, Haili; Hebert, Paul L.; Liu, Chuan-Fen; Wong, Edwin; Maynard, Charles; Hernandez, Susan E.; Randall, Ian] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Sanders, William; Curtis, Idamay; Fihn, Stephan D.] Vet Hlth Adm, Off Analyt & Business Intelligence, Washington, DC USA. [Schectman, Gordon] US Dept Vet Affairs, Off Patient Care Serv, Washington, DC USA. [Stark, Richard] US Dept Vet Affairs, Off Clin Operat, Washington, DC USA. RP Nelson, KM (reprint author), VA Puget Sound Hlth Care Syst, Seattle Ctr Innovat Vet Ctr & Value Driven Care, 1100 Olive Way,Ste 1400, Seattle, WA 98108 USA. EM karin.nelson@va.gov RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU VHA Office of Patient Care Service FX This work was supported by the VHA Office of Patient Care Service. NR 43 TC 40 Z9 40 U1 11 U2 39 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD AUG PY 2014 VL 174 IS 8 BP 1350 EP 1358 DI 10.1001/jamainternmed.2014.2488 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AN2WP UT WOS:000340447000031 PM 25055197 ER PT J AU Wiener, RS Slatore, CG AF Wiener, Renda Soylemez Slatore, Christopher G. TI Real-World Evidence About Potential Psychosocial Harms of Lung Cancer Screening SO JAMA INTERNAL MEDICINE LA English DT Letter ID PULMONARY NODULES C1 [Wiener, Renda Soylemez] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Wiener, Renda Soylemez] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Slatore, Christopher G.] Portland VA Med Ctr, Hlth Serv Res & Dev, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. RP Wiener, RS (reprint author), Boston Univ, Sch Med, Ctr Pulm, 72 E Concord St,R-304, Boston, MA 02118 USA. EM rwiener@bu.edu OI Wiener, Renda/0000-0001-7712-2135 NR 4 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD AUG PY 2014 VL 174 IS 8 BP 1416 EP 1416 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AN2WP UT WOS:000340447000055 PM 25090181 ER PT J AU Sacks, GD Dawes, AJ Russell, MM Lin, AY Maggard-Gibbons, M Winograd, D Chung, HR Tomlinson, J Tillou, A Shew, SB Hiyama, DT Cryer, HG Brunicardi, FC Hiatt, JR Ko, C AF Sacks, Greg D. Dawes, Aaron J. Russell, Marcia M. Lin, Anne Y. Maggard-Gibbons, Melinda Winograd, Deborah Chung, Hallie R. Tomlinson, James Tillou, Areti Shew, Stephen B. Hiyama, Darryl T. Cryer, H. Gill Brunicardi, F. Charles Hiatt, Jonathan R. Ko, Clifford TI Evaluation of Hospital Readmissions in Surgical Patients Do Administrative Data Tell the Real Story? SO JAMA SURGERY LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; POSTOPERATIVE ADVERSE EVENTS; DATA SETS; COMPLICATIONS; RATES AB IMPORTANCE The Centers for Medicare & Medicaid Services has developed an all-cause readmission measure that uses administrative data to measure readmission rates and financially penalize hospitals with higher-than-expected readmission rates. OBJECTIVES To examine the accuracy of administrative codes in determining the cause of readmission as determined by medical record review, to evaluate the readmission measure's ability to accurately identify a readmission as planned, and to document the frequency of readmissions for reasons clinically unrelated to the original hospital stay. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of all consecutive patients discharged from general surgery services at a tertiary care, university-affiliated teaching hospital during 8 consecutive quarters (quarter 4 [October through December] of 2009 through quarter 3 [July through September] of 2011). Clinical readmission diagnosis determined from direct medical record review was compared with the administrative diagnosis recorded in a claims database. The number of planned hospital readmissions defined by the readmission measure was compared with the number identified using clinical data. Readmissions unrelated to the original hospital stay were identified using clinical data. MAIN OUTCOMES AND MEASURES Discordance rate between administrative and clinical diagnoses for all hospital readmissions, discrepancy between planned readmissions defined by the readmission measure and identified by clinical medical record review, and fraction of hospital readmissions unrelated to the original hospital stay. RESULTS Of the 315 hospital readmissions, the readmission diagnosis listed in the administrative claims data differed from the clinical diagnosis in 97 readmissions (30.8%). The readmission measure identified 15 readmissions (4.8%) as planned, whereas clinical data identified 43 readmissions (13.7%) as planned. Unrelated readmissions comprised 70 of the 258 unplanned readmissions (27.1%). CONCLUSIONS AND RELEVANCE Administrative billing data, as used by the readmission measure, do not reliably describe the reason for readmission. The readmission measure accounts for less than half of the planned readmissions and does not account for the nearly one-third of readmissions unrelated to the original hospital stay. Implementation of this readmission measure may result in unwarranted financial penalties for hospitals. C1 [Sacks, Greg D.; Dawes, Aaron J.; Russell, Marcia M.; Lin, Anne Y.; Maggard-Gibbons, Melinda; Winograd, Deborah; Chung, Hallie R.; Tomlinson, James; Tillou, Areti; Shew, Stephen B.; Hiyama, Darryl T.; Cryer, H. Gill; Brunicardi, F. Charles; Hiatt, Jonathan R.; Ko, Clifford] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Russell, Marcia M.; Maggard-Gibbons, Melinda; Tomlinson, James; Ko, Clifford] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Sacks, GD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM gsacks@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 NR 20 TC 33 Z9 33 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD AUG PY 2014 VL 149 IS 8 BP 759 EP 764 DI 10.1001/jamasurg.2014.18 PG 6 WC Surgery SC Surgery GA AN8DZ UT WOS:000340834300002 PM 24920156 ER PT J AU McCann, RA Armstrong, CM Skopp, NA Edwards-Stewart, A Smolenski, DJ June, JD Metzger-Abamukong, M Reger, GM AF McCann, Russell A. Armstrong, Christina M. Skopp, Nancy A. Edwards-Stewart, Amanda Smolenski, Derek J. June, Jennifer D. Metzger-Abamukong, Melinda Reger, Greg M. TI Virtual reality exposure therapy for the treatment of anxiety disorders: An evaluation of research quality SO JOURNAL OF ANXIETY DISORDERS LA English DT Review DE Randomized controlled trials; Effectiveness; Adherence ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIALS; PUBLIC SPEAKING ANXIETY; IN-VIVO EXPOSURE; CLINICAL-TRIAL; PANIC DISORDER; CONSORT STATEMENT; GRADED EXPOSURE; SPIDER PHOBIA AB Randomized controlled trials (RCTs) support the effectiveness of virtual reality exposure therapy (VRET) for anxiety disorders; however, the overall quality of the VRET RCT literature base has yet to be evaluated. This study reviewed 27 VRET RCTs and the degree of adherence to 8 RCT research design criteria derived from existing standards. Adherence to the study quality criteria was generally low as the articles met an average 2.85 criteria (SD = 1.56). None of the studies met more than six quality criteria. Study quality did not predict effect size; however, a reduction in effect size magnitude was observed for studies with larger sample sizes when comparing VRET to non-active control groups. VRET may be an effective method of treatment but caution should be exercised in interpreting the existing body of literature supporting VRET relative to existing standards of care. The need for well-designed VRET research is discussed. (C) 2014 Published by Elsevier Ltd. C1 [McCann, Russell A.; Armstrong, Christina M.; Skopp, Nancy A.; Edwards-Stewart, Amanda; Smolenski, Derek J.; June, Jennifer D.; Metzger-Abamukong, Melinda; Reger, Greg M.] Madigan Army Med Ctr, Natl Ctr Telehlth & Technol, Tacoma, WA 98431 USA. RP Reger, GM (reprint author), VA Puget Sound, 9600 Vet Dr, Tacoma, WA 98493 USA. EM Greg.reger2@gmail.com NR 58 TC 13 Z9 13 U1 8 U2 47 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD AUG PY 2014 VL 28 IS 6 BP 625 EP 631 DI 10.1016/j.janxdis.2014.05.010 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AN8OW UT WOS:000340864500015 PM 25093964 ER PT J AU Vagin, O Tokhtaeva, E Garay, PE Souda, P Bassilian, S Whitelegge, JP Lewis, R Sachs, G Wheeler, L Aoki, R Fernandez-Salas, E AF Vagin, Olga Tokhtaeva, Elmira Garay, Patton E. Souda, Puneet Bassilian, Sara Whitelegge, Julian P. Lewis, Ramilla Sachs, George Wheeler, Larry Aoki, Roger Fernandez-Salas, Ester TI Recruitment of septin cytoskeletal proteins by botulinum toxin A protease determines its remarkable stability SO JOURNAL OF CELL SCIENCE LA English DT Article DE Septin; Botulinum toxin A protease; Protein stability; Degradation; Ubiquitylation ID NEUROTRANSMITTER RELEASE; MAMMALIAN SEPTINS; BETA(1) SUBUNITS; NEUROTOXIN; FORCHLORFENURON; RECOGNITION; SIGNALS; COMPLEX; AP-3; LOCALIZATION AB Proteolytic cleavage of synaptosomal-associated protein 25 by the light chain of botulinum neurotoxin type A (LCA) results in a blockade of neurotransmitter release that persists for several months in motor neurons. The L428A/L429A mutation in LCA is known to significantly shorten both the proteolytic and neuroparalytic effects of the neurotoxin in mice. To elucidate the cellular mechanism for LCA longevity, we studied the effects of L428A/L429A mutation on the interactome, localization and stability of LCA expressed in cultured neuronal cells. Mass spectrometry analysis of the LCA interactome showed that the mutation prevented the interaction of LCA with septins. The wild-type LCA was concentrated in plasma-membrane-associated clusters, colocalizing with septins-2 and septin-7, which accumulated in these clusters only in the presence of LCA. The L428A/L429A mutation decreased co-clustering of LCA and septins and accelerated proteasomal and non-proteasomal degradation of LCA. Similarly, the impairment of septin oligomerization by forchlorfenuron or silencing of septin-2 prevented LCA interaction and clustering with septins and increased LCA degradation. Therefore, the dileucine-mediated LCA-septin co-clustering is crucial for the long-lasting stabilization of LCA-related proteolytic and presumably neuroparalytic activity. C1 [Vagin, Olga; Tokhtaeva, Elmira; Bassilian, Sara; Sachs, George] UCLA, Sch Med, Dept Physiol, Los Angeles, CA 91343 USA. [Vagin, Olga; Tokhtaeva, Elmira; Bassilian, Sara; Sachs, George] Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA 91343 USA. [Garay, Patton E.; Lewis, Ramilla; Wheeler, Larry; Aoki, Roger; Fernandez-Salas, Ester] Allergan Pharmaceut Inc, Dept Biol Sci, Irvine, CA 92612 USA. [Souda, Puneet; Whitelegge, Julian P.] Univ Calif Los Angeles, Semel Inst, NPI, Pasarow Mass Spectrometry Lab, Los Angeles, CA 90095 USA. RP Vagin, O (reprint author), UCLA, Sch Med, Dept Physiol, Los Angeles, CA 91343 USA. EM olgav@ucla.edu FU Allergan, Inc. FX This work was supported by a grant from Allergan, Inc. to O.V. NR 56 TC 6 Z9 6 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD AUG 1 PY 2014 VL 127 IS 15 BP 3294 EP 3308 DI 10.1242/jcs.146324 PG 15 WC Cell Biology SC Cell Biology GA AO2SS UT WOS:000341176800010 PM 24928902 ER PT J AU Pierre, JF Barlow-Anacker, AJ Erickson, CS Heneghan, AF Leverson, GE Dowd, SE Epstein, ML Kudsk, KA Gosain, A AF Pierre, Joseph F. Barlow-Anacker, Amanda J. Erickson, Christopher S. Heneghan, Aaron F. Leverson, Glen E. Dowd, Scot E. Epstein, Miles L. Kudsk, Kenneth A. Gosain, Ankush TI Intestinal dysbiosis and bacterial enteroinvasion in a murine model of Hirschsprung's disease SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Hirschsprung's disease; Hirschsprung's-associated enterocolitis; Microbiome; Secretory phospholipase A2; Dysbiosis; Mucosal immunity ID AMPLICON PYROSEQUENCING BTEFAP; INFLAMMATORY-BOWEL-DISEASE; ALPHA-DEFENSIN EXPRESSION; ENTERIC NERVOUS-SYSTEM; ILEAL CROHNS-DISEASE; KINASE RECEPTOR RET; NECROTIZING ENTEROCOLITIS; PHOSPHOLIPASE A(2); ESCHERICHIA-COLI; NEURAL CREST AB Background/purpose: Hirschsprung's disease (HSCR), characterized by the absence of ganglia in the distal colon, results in functional obstruction. Despite surgical resection of the aganglionic segment, around 40% of patients suffer recurrent life threatening Hirschsprung's-associated enterocolitis (HAEC). The aim of this study was to investigate whether gut microbiota and intestinal immunity changes contribute to the HAEC risk in an HSCR model. Methods: Mice with neural crest conditional deletion of Endothelin receptor B (EdnrB) and their littermate controls were used (EdnrB-null and EdnrB-het). Bacterial DNA was prepared from cecal contents of P16-18 and P21-24 animals and pyrosequencing employed for microbiome analysis. Ileal tissue was isolated and secretory phospholipase A(2) (sPLA(2)) expression and activity determined. Enteroinvasion of Escherichia coli into ileal explants was measured using an ex vivo organ culture system. Results: EdnrB-het and EdnrB-nulls displayed similar flora, sPLA(2) expression and activity at P16-18. However, by P21-24, EdnrB-hets demonstrated increased Lactobacillus and decreased Bacteroides and Clostridium, while EdnrB-nulls exhibited reciprocal changes. EdnrB-nulls also showed reduced sPLA(2) expression and luminal activity at this stage. Functionally, EdnrB-nulls were more susceptible to enteroinvasion with E. coli ex vivo and released less sPLA(2) than EdnrB-hets. Conclusions: Initially, EdnrB-het and EdnrB-nulls contain similar cecal flora but then undergo reciprocal changes. EdnrB-nulls display dysbiosis, demonstrate impaired mucosal defense, decreased luminal sPLA(2) and increased enteroinvasion of E. coli just prior to robust colonic inflammation and death. These findings suggest a role for the intestinal microbiome in the development of HAEC. (C) 2014 Elsevier Inc. All rights reserved. C1 [Pierre, Joseph F.; Barlow-Anacker, Amanda J.; Erickson, Christopher S.; Heneghan, Aaron F.; Leverson, Glen E.; Kudsk, Kenneth A.; Gosain, Ankush] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Epstein, Miles L.; Gosain, Ankush] Univ Wisconsin, Dept Neurosci, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Dowd, Scot E.] Res & Testing Lab, Lubbock, TX USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Gosain, A (reprint author), Univ Wisconsin, Dept Surg, Clin Sci Ctr H4 750, 600 Highland Ave, Madison, WI 53792 USA. EM gosain@surgery.wisc.edu OI Gosain, Ankush/0000-0002-0428-1503 FU National Institutes of Health [NIDDK RO1DK081634]; Veteran's Affairs Office of Research and Development (Biomedical Laboratory Research & Development Award) [I01BX001672]; Central Surgical Association Foundation Turcotte Award; American Pediatric Surgery Association Foundation Award FX This work was supported by the National Institutes of Health (NIDDK RO1DK081634) to MLE, the Veteran's Affairs Office of Research and Development (Biomedical Laboratory Research & Development Award I01BX001672) to KAK, the Central Surgical Association Foundation Turcotte Award to AG, and the American Pediatric Surgery Association Foundation Award to AG. The contents of this article do not represent the views of the Veterans Affairs or the United States Government (KAK). NR 60 TC 12 Z9 14 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 EI 1531-5037 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD AUG PY 2014 VL 49 IS 8 BP 1242 EP 1251 DI 10.1016/j.jpedsurg.2014.01.060 PG 10 WC Pediatrics; Surgery SC Pediatrics; Surgery GA AN0EM UT WOS:000340256200011 PM 25092084 ER PT J AU Mishra, RK Beatty, AL Jaganath, R Regan, M Wu, AHB Whooley, MA AF Mishra, Rakesh K. Beatty, Alexis L. Jaganath, Rajesh Regan, Mathilda Wu, Alan H. B. Whooley, Mary A. TI B-type Natriuretic Peptides for the Prediction of Cardiovascular Events in Patients With Stable Coronary Heart Disease: The Heart and Soul Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE adverse cardiovascular outcomes; BNP; NT-proBNP; risk assessment; stable coronary heart disease ID TERMINAL PRO-BNP; ARTERY-DISEASE; PROGNOSTIC VALUE; NT-PROBNP; BIOMARKERS; FAILURE; MORTALITY; PREVENTION; SECRETION; TRIAL AB Background-Brain-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are known predictors of cardiovascular outcomes in patients with coronary heart disease; however, the relative prognostic value of these 2 biomarkers for secondary events remains unclear. Methods and Results-In 983 participants with stable coronary heart disease, we evaluated the association of BNP and NT-proBNP with time to hospitalization for heart failure, nonfatal myocardial infarction, stroke or transient ischemic attack, cardiovascular death, and combined major adverse cardiovascular events (MACE). During an average follow-up of 6.5 +/- 3.3 years, both BNP and NT-proBNP were associated with increased risk of MACE in a multivariable-adjusted model (hazard ratio per standard deviation of log BNP: 1.58; 95% Cl: 1.32 to 1.89; hazard ratio per standard deviation of log NT-proBNP: 1.84; 95% Cl: 1.52 to 2.24). When added to traditional risk factors, NT-proBNP predicted MACE better than BNP (C statistic: 0.76 versus 0.72, P<0.001). Similarly, the addition of NT-proBNP resulted in a greater net reclassification improvement for predicting MACE than the addition of BNP (65% for NT-proBNP, 56% for BNP). Conclusions-Both BNP and NT-proBNP were significant predictors of MACE in stable coronary heart disease; however, NT-proBNP was superior to BNP for net risk reclassification for MACE. C1 [Mishra, Rakesh K.; Beatty, Alexis L.; Jaganath, Rajesh; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Wu, Alan H. B.] Univ Calif San Francisco, Dept Pathol & Lab Med, San Francisco, CA 94121 USA. [Mishra, Rakesh K.; Regan, Mathilda; Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Mishra, RK (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. EM rakesh.mishra@ucsf.edu FU Department of Veterans Affairs (Washington, DC); National Heart, Lung, and Blood Institute [R01 HL079235]; American Federation for Aging Research; Robert Wood Johnson Foundation; Nancy Kirwan Heart Research Fund, San Francisco, California; Ischemia Research and Education Foundation; Roche Diagnostics Corporation; Alere Inc. FX The Heart and Soul Study was funded by the Department of Veterans Affairs (Washington, DC); the National Heart, Lung, and Blood Institute (grant R01 HL079235); the American Federation for Aging Research (Paul Beeson Scholars Program); the Robert Wood Johnson Foundation (Faculty Scholars Program); the Nancy Kirwan Heart Research Fund, San Francisco, California; and the Ischemia Research and Education Foundation. The NT-proBNP assays were funded by Roche Diagnostics Corporation. The BNP assays were funded by Alere Inc. NR 32 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2014 VL 3 IS 4 AR e000907 DI 10.1161/JAHA.114.000907 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO4HD UT WOS:000341296600024 ER PT J AU Alosco, ML Gunstad, J Xu, X Clark, US Labbe, DR Riskin-Jones, HH Terrero, G Schwarz, NF Walsh, EG Poppas, A Cohen, RA Sweet, LH AF Alosco, Michael L. Gunstad, John Xu, Xiaomeng Clark, Uraina S. Labbe, Donald R. Riskin-Jones, Hannah H. Terrero, Gretel Schwarz, Nicolette F. Walsh, Edward G. Poppas, Athena Cohen, Ronald A. Sweet, Lawrence H. TI The impact of hypertension on cerebral perfusion and cortical thickness in older adults SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Article DE Arterial spin labeling; Blood pressure; brain structure; cerebral blood flow ID SURFACE-BASED ANALYSIS; BLOOD-PRESSURE LEVELS; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; ANTIHYPERTENSIVE THERAPY; CEREBROVASCULAR-DISEASE; LONGITUDINAL CHANGES; BRAIN MORPHOLOGY; APOLIPOPROTEIN-E; FLOW-VELOCITY AB Hypertension may increase risk for dementia possibly because of its association with decreased cortical thickness. Disturbed cerebral autoregulation is one plausible mechanism by which hypertension impacts the cerebral structure, but the associations among hypertension, brain perfusion, and cortical thickness are poorly understood. The current sample consisted of 58 older adults with varying levels of vascular disease. Diagnostic history of hypertension and antihypertensive medication status was ascertained through self-report, and when available, confirmed by medical record review. All participants underwent arterial spin labeling and T1-weighted magnetic resonance imaging to quantify total and regional cortical perfusion and thickness. Analysis of covariance adjusting for medical variables showed that participants with hypertension exhibited reduced temporal and occipital brain perfusion and total and regional cortical thickness relative to those without hypertension. The effects of hypertension on total brain perfusion remained unchanged even after adjustment for age, although no such pattern emerged for cortical thickness. Decreased total brain perfusion predicted reduced thickness of the total brain and of the frontal, temporal, and parietal lobe cortices. Antihypertensive treatment was not associated with total cerebral perfusion or cortical thickness. This study provides initial evidence for the adverse effects of a diagnostic history of hypertension on brain hypoperfusion and reduced cortical thickness. Longitudinal studies are needed to investigate the role of hypertension and its interaction with other contributing factors (eg, age) in the manifestation of cerebral hypoperfusion and reduced cortical thickness. (C) 2014 American Society of Hypertension. All rights reserved. C1 [Alosco, Michael L.; Gunstad, John] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. [Xu, Xiaomeng] Idaho State Univ, Dept Psychol, Pocatello, ID 83209 USA. [Clark, Uraina S.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Labbe, Donald R.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Riskin-Jones, Hannah H.] VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, Los Angeles, CA USA. [Terrero, Gretel] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Schwarz, Nicolette F.; Sweet, Lawrence H.] Univ Georgia, Dept Psychol, Athens, GA 30602 USA. [Walsh, Edward G.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Walsh, Edward G.] Brown Univ, Dept Diagnost Imaging, Providence, RI 02912 USA. [Poppas, Athena] Brown Univ, Dept Med, Alpert Med Sch, Providence, RI 02912 USA. [Cohen, Ronald A.] Univ Florida, Inst Aging, Clin Translat Res Program, Cognit Aging & Memory Program, Gainesville, FL USA. RP Alosco, ML (reprint author), Kent State Univ, Dept Psychol, Kent, OH 44242 USA. EM Malosco@kent.edu OI Clark, Uraina/0000-0002-2683-6696 FU National Institutes of Health Grant [R01HL084178] FX Support for this work was provided by National Institutes of Health Grant R01HL084178. NR 69 TC 11 Z9 11 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-1711 EI 1878-7436 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD AUG PY 2014 VL 8 IS 8 BP 561 EP 570 DI 10.1016/j.jash.2014.04.002 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AO3JT UT WOS:000341226200006 PM 25151318 ER PT J AU Tipps, ME Raybuck, JD Buck, KJ Lattal, KM AF Tipps, Megan E. Raybuck, Jonathan D. Buck, Kari J. Lattal, K. Matthew TI Delay and trace fear conditioning in C57BL/6 and DBA/2 mice: issues of measurement and performance SO LEARNING & MEMORY LA English DT Article ID INBRED MOUSE STRAINS; PROTEIN-KINASE-C; HIPPOCAMPUS-DEPENDENT MEMORY; F-1 HYBRIDS IMPLICATIONS; TRAIT LOCUS ANALYSIS; CONTEXTUAL FEAR; PREPULSE INHIBITION; GENETIC-DIFFERENCES; DORSAL HIPPOCAMPUS; SINGLE-GENE AB Strain comparison studies have been critical to the identification of novel genetic and molecular mechanisms in learning and memory. However, even within a single learning paradigm, the behavioral data for the same strain can vary greatly, making it difficult to form meaningful conclusions at both the behavioral and cellular level. In fear conditioning, there is a high level of variability across reports, especially regarding responses to the conditioned stimulus ( CS). Here, we compare C57BL/6 and DBA/2 mice using delay fear conditioning, trace fear conditioning, and a nonassociative condition. Our data highlight both the significant strain differences apparent in these fear conditioning paradigms and the significant differences in conditioning type within each strain. We then compare our data to an extensive literature review of delay and trace fear conditioning in these two strains. Finally, we apply a number of commonly used baseline normalization approaches to compare how they alter the reported differences. Our findings highlight three major sources of variability in the fear conditioning literature: CS duration, number of CS presentations, and data normalization to baseline measures. C1 [Tipps, Megan E.; Raybuck, Jonathan D.; Buck, Kari J.; Lattal, K. Matthew] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Buck, Kari J.] Portland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR 97239 USA. RP Tipps, ME (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. EM metipps@gmail.com FU National Institutes of Health [1F32 AA022011, F32DA031537, R01 DA005228, P60 AA10760, R01 AA011114, R24 AA020245, DA02592, T32 DA07262, T32 AA07468]; US Department of the Army/DOD-TATRC [W81XWH-12-2-0048]; Portland VA Medical Center FX This work was funded by National Institutes of Health 1F32 AA022011 (to M.E.T.); National Institutes of Health F32DA031537 (to J.D.R.); National Institutes of Health R01 DA005228, P60 AA10760, R01 AA011114, and R24 AA020245 (to K.J.B.); National Institutes of Health DA02592 and US Department of the Army/DOD-TATRC:W81XWH-12-2-0048 (to K.M.L.); and National Institutes of Health T32 DA07262 and T32 AA07468 and the Portland VA Medical Center. NR 76 TC 4 Z9 5 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1072-0502 EI 1549-5485 J9 LEARN MEMORY JI Learn. Mem. PD AUG PY 2014 VL 21 IS 8 BP 380 EP 393 DI 10.1101/lm.035261.114 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AO4IO UT WOS:000341300900003 PM 25031364 ER PT J AU Goldman, SM Kamel, F Ross, GW Jewell, SA Marras, C Hoppin, JA Umbach, DM Bhudhikanok, GS Meng, C Korell, M Comyns, K Hauser, RA Jankovic, J Factor, SA Bressman, S Lyons, KE Sandler, DP Langston, JW Tanner, CM AF Goldman, Samuel M. Kamel, Freya Ross, G. Webster Jewell, Sarah A. Marras, Connie Hoppin, Jane A. Umbach, David M. Bhudhikanok, Grace S. Meng, Cheryl Korell, Monica Comyns, Kathleen Hauser, Robert A. Jankovic, Joseph Factor, Stewart A. Bressman, Susan Lyons, Kelly E. Sandler, Dale P. Langston, J. William Tanner, Caroline M. TI Peptidoglycan Recognition Protein Genes and Risk of Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; peptidoglycan; PGLYRP; microbiome; gut ID ALPHA-SYNUCLEIN; IMMUNE-RESPONSES; GUT MICROBIOTA; ASSOCIATION; INFLAMMATION; PATHOLOGY; SYSTEM; BRAIN; NEUROINFLAMMATION; NEURODEGENERATION AB Increased gut permeability, inflammation, and colonic alpha-synuclein pathology are present in early Parkinson's disease (PD) and have been proposed to contribute to PD pathogenesis. Peptidoglycan is a structural component of the bacterial cell wall. Peptidoglycan recognition proteins (PGRPs) maintain healthy gut microbial flora by regulating the immune response to both commensal and harmful bacteria. We tested the hypothesis that variants in genes that encode PGRPs are associated with PD risk. Participants in two independent case-control studies were genotyped for 30 single-nucleotide polymorphisms (SNPs) in the four PGLYRP genes. Using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounding variables, we conducted analyses in each study, separately and pooled. One SNP failed the assay, and three had little to no variation. The ORs were similar in both study populations. In pooled analyses, three of seven PGLYRP2 SNPs (rs3813135, rs733731, rs892145), one of five PGLYRP3 SNPs (rs2987763), and six of nine PGLYRP4 SNPs (rs10888557, rs12063091, rs3006440, rs3006448, rs3006458, and rs3014864) were significantly associated with PD risk. Association was strongest for PGLYRP4 5' untranslated region (UTR) SNP rs10888557 (GG reference, CG OR 0.6 [95% CI 0.4-0.9], CC OR 0.15 [95% CI 0.04-0.6]; log-additive P-trend, 0.0004). Common variants in PGLYRP genes are associated with PD risk in two independent studies. These results require replication, but they are consistent with hypotheses of a causative role for the gut microbiota and gastrointestinal immune response in PD. (C) 2014 International Parkinson and Movement Disorder Society C1 [Goldman, Samuel M.; Tanner, Caroline M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Goldman, Samuel M.; Tanner, Caroline M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goldman, Samuel M.; Bhudhikanok, Grace S.; Meng, Cheryl; Korell, Monica; Comyns, Kathleen; Langston, J. William] Parkinsons Inst, Sunnyvale, CA USA. [Kamel, Freya; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA. [Jewell, Sarah A.] German Ctr Neurodegenerat Dis, DZNE, Bonn, Germany. [Marras, Connie] Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Hoppin, Jane A.] N Carolina State Univ, Raleigh, NC 27695 USA. [Umbach, David M.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Hauser, Robert A.] Univ S Florida, Tampa, FL USA. [Jankovic, Joseph] Baylor Coll Med, Houston, TX 77030 USA. [Factor, Stewart A.] Emory Univ, Sch Med, Atlanta, GA USA. [Bressman, Susan] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Lyons, Kelly E.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. RP Goldman, SM (reprint author), San Francisco VA Med Ctr, 4150 Clement St,PADRECC 127P, San Francisco, CA 94121 USA. EM samuel.goldman@ucsf.edu OI Jewell, Sarah/0000-0002-9877-2599; Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 FU NIH; National Institute of Environmental Health Sciences; NIEHS [Z01-ES044007, Z01-ES049030, R01-ES10803, U54 ES012077]; NCI [Z01-CP010119]; Michael J. Fox Foundation; Parkinson's Unity Walk FX This study was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, NIEHS (grants Z01-ES044007 and Z01-ES049030), NCI (grant Z01-CP010119), NIEHS grants R01-ES10803 and U54 ES012077, the Michael J. Fox Foundation, Parkinson's Unity Walk, and James and Sharron Clark. SEARCH was supported by an unrestricted grant from a group of current and former manufacturers of welding consumables awarded to The Parkinson's Institute. NR 59 TC 8 Z9 9 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD AUG PY 2014 VL 29 IS 9 BP 1171 EP 1180 DI 10.1002/mds.25895 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AN4BJ UT WOS:000340532300015 PM 24838182 ER PT J AU Rodriguez-Violante, M Gonzalez-Latapi, P Cervantes-Arriaga, A Camacho-Ordonez, A Weintraub, D AF Rodriguez-Violante, Mayela Gonzalez-Latapi, Paulina Cervantes-Arriaga, Amin Camacho-Ordonez, Azyadeh Weintraub, Daniel TI Impulse control and related disorders in Mexican Parkinson's disease patients SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Impulse control disorder; Parkinson's disease; Mexico; QUIP-RS ID COMPULSIVE DISORDERS; DOPAMINE AGONIST; RATING-SCALE; PREVALENCE; BEHAVIORS; QUESTIONNAIRE; VALIDATION; SYMPTOMS; DRUGS AB Background: Impulse control disorders (ICDs) are a relatively recent addition to the behavioral spectrum of PD-related non-motor symptoms. Social and economic factors may play a role on the ICD phenotype of PD patients. Objective: The aim of this study is to determine the prevalence and characterize the clinical profile of ICDs in a sample of low-income, low-education PD patients with no social security benefits from a Latin American country. Methods: We included 300 consecutive PD patients and 150 control subjects. The presence of ICD and related disorders was assessed using a structured interview. After the interview and neurological evaluation were concluded, all subjects completed the Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS). Results: Regarding ICDs and related disorders (hobbyism-punding), 25.6% (n = 77) of patients in the PD group and 16.6% (n = 25) in the control group fulfilled criteria for at least one ICD or related disorder (p = 0.032). There was a statistically significant difference in the QUIP-RS mean score between PD and control subjects (5.6 +/- 9.7 and 2.7 +/- 4.21, p = 0.001). The most common ICD was compulsive eating for both PD (8.6%) and control (2.6%) groups. Conclusions: The results of this study confirm that for this population, symptoms of an ICD are significantly more frequent in PD subjects than in control subjects. Nevertheless, socioeconomic differences may contribute to a lower overall frequency and distinct pattern of ICDs in PD patients compared with what has been reported in other countries. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Rodriguez-Violante, Mayela; Gonzalez-Latapi, Paulina; Cervantes-Arriaga, Amin; Camacho-Ordonez, Azyadeh] Natl Inst Neurol & Neurosurg, Clin Lab Neurodegenerat Dis, Mexico City 14269, DF, Mexico. [Rodriguez-Violante, Mayela] Natl Inst Neurol & Neurosurg, Movement Disorders Clin, Mexico City 14269, DF, Mexico. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. RP Rodriguez-Violante, M (reprint author), Natl Inst Neurol & Neurosurg, Clin Lab Neurodegenerat Dis, Insurgentes 3877, Mexico City 14269, DF, Mexico. EM mrodriguez@innn.edu.mx RI Rodriguez-Violante, Mayela/G-7056-2015 OI Rodriguez-Violante, Mayela/0000-0002-6041-9941; Cervantes-Arriaga, Amin/0000-0002-3935-9278 NR 28 TC 9 Z9 10 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD AUG PY 2014 VL 20 IS 8 BP 907 EP 910 DI 10.1016/j.parkreldis.2014.05.014 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AO0DF UT WOS:000340978600021 PM 24935236 ER PT J AU Hu, XM Liou, AKF Leak, RK Xu, MY An, CR Suenaga, J Shi, YJ Gao, YQ Zheng, P Chen, J AF Hu, Xiaoming Liou, Anthony K. F. Leak, Rehana K. Xu, Mingyue An, Chengrui Suenaga, Jun Shi, Yejie Gao, Yanqin Zheng, Ping Chen, Jun TI Neurobiology of microglial action in CNS injuries: Receptor-mediated signaling mechanisms and functional roles SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Microglia; Receptor; Central nervous system injuries ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; FC-GAMMA-RECEPTOR; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; ADVANCED GLYCATION ENDPRODUCTS; TOLL-LIKE RECEPTORS; NF-KAPPA-B; AMYLOID-BETA-PEPTIDE; MAST-CELL ACTIVATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AB Microglia are the first line of immune defense against central nervous system (CNS) injuries and disorders. These highly plastic cells play dualistic roles in neuronal injury and recovery and are known for their ability to assume diverse phenotypes. A broad range of surface receptors are expressed on microglia and mediate microglial 'On' or 'Off' responses to signals from other host cells as well as invading microorganisms. The integrated actions of these receptors result in tightly regulated biological functions, including cell mobility, phagocytosis, the induction of acquired immunity, and trophic factor/inflammatory mediator release. Over the last few years, significant advances have been made toward deciphering the signaling mechanisms related to these receptors and their specific cellular functions. In this review, we describe the current state of knowledge of the surface receptors involved in microglial activation, with an emphasis on their engagement of distinct functional programs and their roles in CNS injuries. It will become evident from this review that microglial homeostasis is carefully maintained by multiple counterbalanced strategies, including, but not limited to, 'On' and 'Off' receptor signaling. Specific regulation of theses microglial receptors may be a promising therapeutic strategy against CNS injuries. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Hu, Xiaoming; Liou, Anthony K. F.; Suenaga, Jun; Shi, Yejie; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Hu, Xiaoming; Xu, Mingyue; An, Chengrui; Gao, Yanqin; Zheng, Ping; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Hu, Xiaoming; Xu, Mingyue; An, Chengrui; Gao, Yanqin; Zheng, Ping; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China. [Hu, Xiaoming; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15240 USA. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. RP Hu, XM (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. EM hux2@upmc.edu; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417; Shi, Yejie/0000-0001-7502-9201 FU American Heart Association [13SDG14570025]; Ethyl Vincent pilot grant in multiple sclerosis from Department of Neurology, University of Pittsburgh; Commonwealth Universal Research Enhancement (C.U.R.E.) Award from the Department of Health; Michael J. Fox Foundation Innovation Award; Chinese Natural Science Foundation grants [81171149, 81371306]; National Institutes of Health Grants [NS45048, NS62157, NS59806, NS36736]; Chinese Natural Science Foundation [81228008]; VA Merit Review FX Dr. Xiaoming Hu is supported by the American Heart Association (13SDG14570025) and the Ethyl Vincent pilot grant in multiple sclerosis from Department of Neurology, University of Pittsburgh. Dr. Rehana K. Leak is supported by a Commonwealth Universal Research Enhancement (C.U.R.E.) Award from the Department of Health and a Michael J. Fox Foundation Innovation Award. Dr. Yanqin Gao is supported by the Chinese Natural Science Foundation grants (81171149 and 81371306). Dr. Jun Chen is supported by the National Institutes of Health Grants (NS45048, NS62157, NS59806, and NS36736), Chinese Natural Science Foundation grants (81228008) and a VA Merit Review. NR 353 TC 28 Z9 29 U1 2 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD AUG-SEP PY 2014 VL 119 BP 60 EP 84 DI 10.1016/j.pneurobio.2014.06.002 PG 25 WC Neurosciences SC Neurosciences & Neurology GA AO0GI UT WOS:000340986700004 PM 24923657 ER PT J AU Costa, DK Barg, FK Asch, DA Kahn, JM AF Costa, Deena Kelly Barg, Frances K. Asch, David A. Kahn, Jeremy M. TI Facilitators of an Interprofessional Approach to Care in Medical and Mixed Medical/Surgical ICUs: A Multicenter Qualitative Study SO RESEARCH IN NURSING & HEALTH LA English DT Article DE critical care; collaboration; communication; hospital/institutional environment; interprofessional care; health care delivery ID INTENSIVE-CARE; HEALTH-CARE; MECHANICAL VENTILATION; UNIT; COLLABORATION; MULTIDISCIPLINARY; MORTALITY; TEAMWORK; OUTCOMES; ASSOCIATION AB The purpose of this study was to describe clinicians' perceptions of interprofessional collaboration in the intensive care unit and identify factors associated with interprofessional collaboration. We performed 64 semi-structured interviews in seven hospitals with ICU nurses, physicians, respiratory therapists, nurse managers, clinical pharmacists, and dieticians. ICU clinicians perceived two distinct types of facilitators to interprofessional collaboration in critical care: cultural and structural. In the critical care setting, cultural and structural facilitators worked independently as well as in concert to create effective interprofessional collaboration. Initiatives aimed at creating and facilitating interprofessional collaboration should focus attention on cultural and structural facilitators to improve patient care and team effectiveness. (C) 2014 Wiley Periodicals, Inc. C1 [Costa, Deena Kelly] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15221 USA. [Barg, Frances K.] Univ Penn, Dept Family Med & Community Hlth, Perelman Sch Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Perelman Sch Med, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Wharton Sch, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Ctr Hlth Care Innovat, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Kahn, Jeremy M.] Univ Pittsburgh, Dept Crit Care Med, Grad Sch Publ Hlth, Pittsburgh, PA 15221 USA. RP Costa, DK (reprint author), Univ Pittsburgh, Dept Crit Care Med, Scaife Hall Room 607 3550 Terrace Sreet, Pittsburgh, PA 15221 USA. EM kellydm2@upmc.edu FU National Institutes of Health [K23HL082650, T32HL007820] FX This work was supported by a career development award (K23HL082650) and an institutional training grant (T32HL007820) from the National Institutes of Health. We would like to acknowledge Eve Weiss at the University of Pennsylvania for thoughtful input and feedback on the manuscript. NR 45 TC 5 Z9 5 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-6891 EI 1098-240X J9 RES NURS HEALTH JI Res. Nurs. Health PD AUG PY 2014 VL 37 IS 4 BP 326 EP 335 DI 10.1002/nur.21607 PG 10 WC Nursing SC Nursing GA AN5XL UT WOS:000340665400008 PM 24995554 ER PT J AU Mehta, NN Miyasaki, SH Hirsch, J Fidler, RL AF Mehta, Niyati N. Miyasaki, Shelley H. Hirsch, Jan Fidler, Richard L. TI Easy-to-Implement Oral Cavity Modification to Expand Simulation-based Training in Airway Management SO SIMULATION IN HEALTHCARE-JOURNAL OF THE SOCIETY FOR SIMULATION IN HEALTHCARE LA English DT Article DE Emergency airway management; Dental trauma ID DENTAL INJURIES; INTUBATION AB Introduction: Injuries to the oral cavity and teeth can occur during routine intubation and general anesthesia but often occur in emergency situations when the priority of securing the airway supersedes preanesthetic evaluation. This study demonstrates the feasibility of modifying the oral cavity to increase the dental fidelity during emergency airway management. Methods: A Laerdal Manikin was used to manipulate the preexisting Polyester (hard) and the Vinyl (flexible) dentition sets that are interchangeable among the Laerdal family of manikins. Items easily available in a dental laboratory such as dental acrylic and dental impression material were used to create modifications. Results: Laerdal dentition sets were altered to simulate common dental (tooth-related) trauma encountered during intubation such as a fracture, luxation, or avulsion injuries. Anatomic variations such as carious (decayed) teeth, loose teeth, and class II malocclusion (overbite) were also fabricated. Tooth luxation was engineered to occur with pressure by a laryngoscope, and bleeding teeth were also created to demonstrate excessive pressure applied during direct laryngoscopy. It is feasible to improve the realism of the Laerdal family of manikins with simple modifications. Conclusions: This project proves the concept of feasibly fabricating anatomic variations to increase the fidelity of existing simulation manikins. Other anatomic variations present challenges to airway management, and future research will aim at creating additional modifications. In addition, future research will seek to quantify the improvement in airway management skills by anesthesia and emergency medicine providers by training on manikins with variable oral cavity anatomy. C1 [Mehta, Niyati N.; Miyasaki, Shelley H.; Hirsch, Jan; Fidler, Richard L.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Clin Simulat Program, San Francisco, CA 94143 USA. RP Mehta, NN (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM niyati.n.mehta@gmail.com NR 6 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 EI 1559-713X J9 SIMUL HEALTHC JI Simul. Healthc. PD AUG PY 2014 VL 9 IS 4 BP 260 EP 263 DI 10.1097/SIH.0000000000000028 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AN7XG UT WOS:000340813700007 PM 24787560 ER PT J AU De Waele, JJ Rello, J Anzueto, A Moreno, R Lipman, J Sakr, Y Pickkers, P Leone, M Ferguson, A Oud, L Vincent, JL AF De Waele, Jan J. Rello, Jordi Anzueto, Antonio Moreno, Rui Lipman, Jeffrey Sakr, Yasser Pickkers, Peter Leone, Marc Ferguson, Andrew Oud, Lavi Vincent, Jean-Louis CA EPIC II Investigators TI Infections and Use of Antibiotics in Patients Admitted for Severe Acute Pancreatitis: Data from the EPIC II Study SO SURGICAL INFECTIONS LA English DT Article ID ACUTE NECROTIZING PANCREATITIS; DOUBLE-BLIND; FUNGAL-INFECTION; PREVALENCE; MANAGEMENT; TRIAL AB Background: Infectious complications are frequent in severe acute pancreatitis (SAP) but multinational epidemiologic data are lacking. The aim of the study was to analyze the characteristics of the infectious complications and antimicrobial use in this setting. Methods: One-day point prevalence study of infection in critically ill patients (Extended Prevalence of Infection in the ICU-II study), performed in 1,265 ICUs in 75 countries. Results: Of the 13,796 patients in the study, 159 were admitted with SAP. One-hundred sixteen (73%) had infections: 31% intra-abdominal, 16% extra-abdominal, and 26% both. Gram-negative bacteria were more prevalent than gram-positive organisms, anaerobes, or fungi. Therapeutically, penicillins and other beta-lactams were used most frequently. Prophylactic antibiotics were administered to 24% of the patients with SAP. Conclusions: Infections are frequent in patients admitted with SAP; most are intra-abdominal infections. Microbiology is diverse with gram-negative micro-organisms most frequently isolated. Most patients admitted to the ICU for SAP receive antibiotics at some point. C1 [De Waele, Jan J.] Ghent Med Sch & Univ Hosp, Dept Crit Care Med, Ghent, Belgium. [Rello, Jordi] Univ Autonoma Barcelona, Hosp Vall dHebron, Crit Care Dept, CIBERES, E-08193 Barcelona, Spain. [Anzueto, Antonio] Univ Texas Hlth Sci, Dept Pulm Crit Care, San Antonio, TX USA. [Anzueto, Antonio] Univ Texas Hlth Sci, Dept Internal Med, San Antonio, TX USA. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Moreno, Rui] Hosp Sao Jose, Ctr Hosp Lisboa Cent, UCINC, Lisbon, Portugal. [Lipman, Jeffrey] Univ Queensland, Sch Med, Discipline Anesthesiol & Crit Care, Herston, Qld, Australia. [Lipman, Jeffrey] Royal Brisbane & Womens Hosp, Dept Intens Care Med, Herston, Qld, Australia. [Sakr, Yasser] Univ Jena, Dept Anesthesiol & Intens Care, Jena, Germany. [Pickkers, Peter] Radboud Univ Nijmegen, Med Ctr, Dept Intens Care, NL-6525 ED Nijmegen, Netherlands. [Leone, Marc] Aix Marseille Univ, Hop Nord, AP HM,Dept Intens Care & Anesthesiol, Unite Rech Malad Infect & Transmissibles URMITE, Marseilles, France. [Ferguson, Andrew] Craigavon Area Hosp, Dept Intens Care Med, Portadown, North Ireland. [Oud, Lavi] Texas Tech Univ HSC, Div Pulm & Crit Care Med, Odessa, TX USA. [Vincent, Jean-Louis] Univ Libre Brussels, Erasme Hosp, Dept Intens Care, Brussels, Belgium. RP De Waele, JJ (reprint author), Ghent Univ Hosp, Dept Crit Care Med, De Pintelaan 185, B-9000 Ghent, Belgium. EM jan.dewaele@UGent.be RI Pickkers, R.P./H-8080-2014; Sakr, Yasser/D-9802-2013; Leone, Marc/P-4835-2016 OI Leone, Marc/0000-0002-3097-758X; Rello, Jordi/0000-0003-0676-6210 NR 21 TC 4 Z9 4 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-2964 EI 1557-8674 J9 SURG INFECT JI Surg. Infect. PD AUG PY 2014 VL 15 IS 4 BP 394 EP 398 DI 10.1089/sur.2012.228 PG 5 WC Infectious Diseases; Surgery SC Infectious Diseases; Surgery GA AO0PY UT WOS:000341014100007 PM 24819027 ER PT J AU Subak, LL Goode, PS Brubaker, L Kusek, JW Schembri, M Lukacz, ES Kraus, SR Chai, TC Norton, P Tennstedt, SL AF Subak, Leslee L. Goode, Patricia S. Brubaker, Linda Kusek, John W. Schembri, Michael Lukacz, Emily S. Kraus, Stephen R. Chai, Toby C. Norton, Peggy Tennstedt, Sharon L. CA Urinary Incontinence Treatment Net TI Urinary incontinence management costs are reduced following Burch or sling surgery for stress incontinence SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE costs; cost analysis; urinary incontinence; urinary incontinence costs ID QUALITY-OF-LIFE; WOMEN; TRIAL AB OBJECTIVE: The objective of the study was to estimate the effect of Burch and fascial sling surgery on out-of-pocket urinary incontinence (UI) management costs at 24 months postoperatively and identify predictors of change in cost among women enrolled in a randomized trial comparing these procedures. STUDY DESIGN: Resources used for UI management (supplies, laundry, dry cleaning) were self-reported by 491 women at baseline and 24 months after surgery, and total out-of-pocket costs for UI management (in 2012 US dollars) were estimated. Data from the 2 surgical groups were combined to examine the change in cost for UI management over 24 months. Univariate and bivariate changes in cost were analyzed using the Wilcoxon signed rank test. Predictors of change in cost were examined using multivariate mixed models. RESULTS: At baseline mean (+/- SD) age of participants was 53 +/- 10 years, and the frequency of weekly UI episodes was 23 +/- 21. Weekly UI episodes decreased by 86% at 24 months (P < .001). The mean weekly cost was $16.60 +/- $27.00 (median $9.39) at baseline and $4.57 +/- $15.00 (median $0.10) at 24 months (P < .001), a decrease of 72%. In multivariate analyses, cost decreased by $3.38 +/- $0.77 per week for each decrease of 1 UI episode per day (P < .001) and was strongly associated with greater improvement in Urogenital Distress Inventory and Incontinence Impact Questionnaire scores (P < .001) and decreased 24-hour pad weight (P < .02). CONCLUSION: Following Burch or fascial sling surgery, the UI management cost at 24 months decreased by 72% ($625 per woman per year) and was strongly associated with decreasing UI frequency. Reduced out-of-pocket expenses may be a benefit of these established urinary incontinence procedures. C1 [Subak, Leslee L.; Schembri, Michael] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94115 USA. [Subak, Leslee L.; Schembri, Michael] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94115 USA. [Subak, Leslee L.; Schembri, Michael] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94115 USA. [Subak, Leslee L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lukacz, Emily S.] Univ Calif San Diego, Sch Med, Dept Reprod Med, San Diego, CA 92103 USA. [Goode, Patricia S.] Birmingham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. [Goode, Patricia S.] Univ Alabama Birmingham, Birmingham, AL USA. [Brubaker, Linda] Loyola Univ, Chicago Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Brubaker, Linda] Loyola Univ, Chicago Sch Med, Dept Urol, Chicago, IL 60611 USA. [Kusek, John W.] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. [Chai, Toby C.] Univ Maryland, Sch Med, Dept Urol, Baltimore, MD 21201 USA. [Kraus, Stephen R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Norton, Peggy] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. [Tennstedt, Sharon L.] New England Res Inst, Watertown, MA 02172 USA. RP Subak, LL (reprint author), Univ Calif San Francisco, Mt Zion Womens Hlth Clin Res Ctr, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM subakl@obgyn.ucsf.edu OI Wadie, Bassem/0000-0002-6977-6849 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01 DK60395, U01 DK60397, U01 DK60401]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Office of Research in Women's Health, National Institutes of Health FX This study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01 DK60395, U01 DK60397, and U01 DK60401) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research in Women's Health, National Institutes of Health. NR 21 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2014 VL 211 IS 2 AR 171.e1 DI 10.1016/j.ajog.2014.03.012 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AN0FM UT WOS:000340259300025 PM 24631433 ER PT J AU Buie, JNJ Oates, JC AF Buie, Joy N. Jones Oates, Jim C. TI Role of Interferon Alpha in Endothelial Dysfunction: Insights Into Endothelial Nitric Oxide Synthase-Related Mechanisms SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Review DE Autoimmune disease; SLE: Systemic Lupus Erythematosus; Endothelial dysfunction; Type I interferons; Endothelial nitric oxide synthase; Lupus ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHRONIC HEPATITIS-C; ENOS-KNOCKOUT MICE; DEPENDENT PROTEIN-KINASE; NF-KAPPA-B; PROGENITOR CELLS; GROWTH-FACTOR; INSULIN-RESISTANCE; PROMOTER ACTIVITY; AP-1 ACTIVITY AB Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the production of autoantibodies against nuclear antigens such as double-stranded DNA. Lupus predominantly affects women (ratio, 9:1). Moreover, premenopausal women with SLE are 50 times more likely to have a myocardial infarction. Although specific risk factors for advanced cardiovascular complications have not been identified in this patient population, endothelial dysfunction is highly prevalent. Recent studies show that the type I interferon signature gene expression coincides with impaired brachial artery flow-mediated dilation and diminished endothelial progenitor cell circulation, both markers of impaired endothelial function. Although many factors promote the development of vascular endothelial dysfunction, all pathways converge on the diminished activity of endothelial nitric oxide synthase (eNOS) and loss of nitric oxide (NO) bioavailability. Studies examining the effects of type I interferons on eNOS and NO in SLE are missing. This literature review examines the current literature regarding the role of type I interferons in cardiovascular disease and its known effects on regulators of eNOS and NO bioavailability that are important for proper endothelial cell function. C1 [Buie, Joy N. Jones; Oates, Jim C.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Buie, Joy N. Jones; Oates, Jim C.] Med Univ S Carolina, Ralph H Johnson VAMC, Med Res Serv, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Buie, JNJ (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, Dept Microbiol & Immunol, 96 Jonathan Lucas St,Clin Sci Bldg Suite 816, Charleston, SC 29425 USA. EM jonejn@musc.edu FU Ralph H. Johnson VA Medical Center [5I01CX00021804]; National Institute of Arthritis and Musculoskeletal and Skin Diseases Veterans Affairs Research Enhancement Awards Program [5RO1AR04547613]; Initiative for Maximizing Student Diversity (IMSD); National Institute of General Medical Sciences National Arthritis Foundation [5R25GM07264308] FX Supported by Ralph H. Johnson VA Medical Center (5I01CX00021804), National Institute of Arthritis and Musculoskeletal and Skin Diseases Veterans Affairs Research Enhancement Awards Program (5RO1AR04547613), Initiative for Maximizing Student Diversity (IMSD), National Institute of General Medical Sciences National Arthritis Foundation (5R25GM07264308). NR 90 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD AUG PY 2014 VL 348 IS 2 BP 168 EP 175 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AN4LK UT WOS:000340559100015 ER PT J AU Allen, KD Golightly, YM Callahan, LF Helmick, CG Ibrahim, SA Kwoh, CK Renner, JB Jordan, JM AF Allen, Kelli D. Golightly, Yvonne M. Callahan, Leigh F. Helmick, Charles G. Ibrahim, Said A. Kwoh, C. Kent Renner, Jordan B. Jordan, Joanne M. TI Race and Sex Differences in Willingness to Undergo Total Joint Replacement: The Johnston County Osteoarthritis Project SO ARTHRITIS CARE & RESEARCH LA English DT Article ID TOTAL KNEE REPLACEMENT; TOTAL HIP-ARTHROPLASTY; PATIENT EXPECTATIONS; AFRICAN-AMERICANS; SOCIAL SUPPORT; UNITED-STATES; SURGERY; OUTCOMES; DISPARITIES; PREFERENCES AB Objective. Using data from the community-based Johnston County Osteoarthritis Project, we examined race and sex variations in willingness to undergo, and perceptions regarding, total joint replacement (TJR). Methods. Analyses were conducted for the total sample who participated in a followup measurement period from 2006-2010 (n = 1,522) and a subsample with symptomatic hip and/or knee osteoarthritis (sOA; n = 445). Participants indicated how willing they would be to have TJR (hip or knee) if their doctor recommended it; responses were categorized as "definitely" or "probably" willing versus "unsure," "probably not," or "definitely not" willing, or "don't know." Participants answered 7 questions regarding perceptions of TJR outcomes. Multivariable logistic regression models of willingness included participant characteristics (including socioeconomic status) and TJR perception variables that were associated with willingness at the P < 0.1 level in bivariate analyses. Results. African Americans had lower odds of willingness to undergo TJR than whites in the total sample (adjusted odds ratio [OR] 0.47 [95% confidence interval (95% CI) 0.31-0.72]) and the sOA subsample (adjusted OR 0.42 [95% CI 0.25-0.69]). There were no sex differences in willingness. African Americans expected poorer TJR outcomes than whites, but sex differences were minimal; perceptions of TJR outcomes were not significantly associated with willingness. Conclusion. In this community sample, race differences in TJR willingness and perceptions were substantial, but sex differences were small. Perceptions of TJR did not appear to affect willingness or explain race differences in willingness. C1 [Allen, Kelli D.] Durham VA Med Ctr, Durham, NC 27705 USA. [Allen, Kelli D.] Duke Univ, Med Ctr, Durham, NC USA. [Golightly, Yvonne M.; Callahan, Leigh F.; Renner, Jordan B.; Jordan, Joanne M.] Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC USA. [Helmick, Charles G.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Ibrahim, Said A.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Ibrahim, Said A.] Perelman Univ Penn, Sch Med, Philadelphia, PA USA. [Kwoh, C. Kent] Univ Arizona, Tucson, AZ USA. RP Allen, KD (reprint author), Durham VA Med Ctr, Hlth Serv Res & Dev Serv 152, 508 Fulton St, Durham, NC 27705 USA. EM kelli.allen@duke.edu FU CDC/Association of Schools of Public Health [S1734, S3486]; National Institute of Arthritis and Musculoskeletal and Skin Diseases Multipurpose Arthritis and Musculoskeletal Disease Center [5-P60-AR30701]; National Institute of Arthritis and Musculoskeletal and Skin Diseases Multidisciplinary Clinical Research Center [5-P60-AR49465-03]; Arthritis Foundation Postdoctoral Fellowship Award; K24 Award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases [1-K24-AR-055259-01]; Sci Metrika, LLC.; Pfizer FX Supported in part by the CDC/Association of Schools of Public Health (cooperative agreements S1734 and S3486), the National Institute of Arthritis and Musculoskeletal and Skin Diseases Multipurpose Arthritis and Musculoskeletal Disease Center (grant 5-P60-AR30701), the National Institute of Arthritis and Musculoskeletal and Skin Diseases Multidisciplinary Clinical Research Center (grant 5-P60-AR49465-03), and an Arthritis Foundation Postdoctoral Fellowship Award to Dr. Golightly. Dr. Ibrahim's work was supported by a K24 Award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant 1-K24-AR-055259-01).; Dr. Callahan has received consultancy fees, speaking fees, and/or honoraria (less than $10,000 each) from Sci Metrika, LLC. Dr. Kwoh has received consultancy fees, speaking fees, and/or honoraria (less than $10,000) from Pfizer. NR 39 TC 15 Z9 15 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD AUG PY 2014 VL 66 IS 8 BP 1193 EP 1202 DI 10.1002/acr.22295 PG 10 WC Rheumatology SC Rheumatology GA AN1PR UT WOS:000340356600008 PM 24470235 ER PT J AU George, M Pullman-Mooar, S Hussain, F Schumacher, HR AF George, Michael Pullman-Mooar, Sally Hussain, Fauzia Schumacher, H. Ralph TI Evaluating Appropriate Use of Prophylactic Colchicine for Gout Flare Prevention SO ARTHRITIS CARE & RESEARCH LA English DT Article ID SERUM URATE; ARTHRITIS; THERAPY; HYPERURICEMIA; ALLOPURINOL; FEBUXOSTAT; MANAGEMENT; PLACEBO; ATTACKS; TRIAL AB Objective. American College of Rheumatology and European League Against Rheumatism guidelines recommend colchicine to prevent gout flares in patients initiating and increasing uric acid-lowering therapy until serum uric acid is maintained at <= 6 mg/dl. We aimed to evaluate how well colchicine prescribing practices adhere to these guidelines and to examine factors associated with improved prescribing. Methods. Electronic medical records were reviewed for 126 patients with active colchicine prescriptions for prophylaxis of gout flares. Colchicine prescribing was defined as inappropriate if 1) no concurrent urate-lowering therapy was prescribed, 2) uric acid was not at goal and urate-lowering therapy had not been increased in the past 3 months, or 3) uric acid goals were met for >1 year and flares had resolved in the absence of tophi. Results. Colchicine use was considered inappropriate in 93 patients (73.8%). Thirty-four were prescribed no urate-lowering therapy, 50 were above the uric acid goal without urate-lowering therapy increase in the prior 3 months, and 9 were at the uric acid goal for >1 year without flares or tophi. Patients appropriately prescribed colchicine were younger and were more likely to have been seen by a rheumatologist. Allopurinol dose and allergy, uric acid level, and renal function were similar in the 2 groups. Conclusion. We found a high prevalence of what we considered inappropriate prophylactic colchicine use, driven largely by failure to prescribe concurrent urate-lowering therapies or adequately increase these medications. Rheumatology consultation was associated with improved colchicine prescribing. C1 [George, Michael] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Pullman-Mooar, Sally; Schumacher, H. Ralph] VA Med Ctr, Philadelphia, PA USA. [Pullman-Mooar, Sally; Schumacher, H. Ralph] Univ Penn, Philadelphia, PA 19104 USA. [Hussain, Fauzia] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP George, M (reprint author), Univ Penn, Div Rheumatol, 8th Floor,Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. EM michael.george@uphs.upenn.edu FU American College of Rheumatology Ephraim P. Engelman Endowed Resident Research Preceptorship Award; Ardea; Metabolex; Novartis; Pfizer; Regeneron; Takeda FX Supported by the American College of Rheumatology Ephraim P. Engelman Endowed Resident Research Preceptorship Award.; Dr. Schumacher has received consulting fees (less than $10,000 each) from Ardea, Metabolex, Novartis, Pfizer, Regeneron, and Takeda. NR 16 TC 3 Z9 3 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD AUG PY 2014 VL 66 IS 8 BP 1258 EP 1262 DI 10.1002/acr.22275 PG 5 WC Rheumatology SC Rheumatology GA AN1PR UT WOS:000340356600017 PM 24376081 ER PT J AU Halter, JB Musi, N Horne, FM Crandall, JP Goldberg, A Harkless, L Hazzard, WR Huang, ES Kirkman, MS Plutzky, J Schmader, KE Zieman, S High, KP AF Halter, Jeffrey B. Musi, Nicolas Horne, Frances McFarland Crandall, Jill P. Goldberg, Andrew Harkless, Lawrence Hazzard, William R. Huang, Elbert S. Kirkman, M. Sue Plutzky, Jorge Schmader, Kenneth E. Zieman, Susan High, Kevin P. TI Diabetes and Cardiovascular Disease in Older Adults: Current Status and Future Directions SO DIABETES LA English DT Article ID 10-YEAR FOLLOW-UP; A-BETA OLIGOMERS; WEIGHT-LOSS; INSULIN-RESISTANCE; RISK-FACTORS; SEVERE HYPOGLYCEMIA; ALZHEIMER-DISEASE; KIDNEY-DISEASE; HEART-FAILURE; UNITED-STATES AB The prevalence of diabetes increases with age, driven in part by an absolute increase in incidence among adults aged 65 years and older. Individuals with diabetes are at higher risk for cardiovascular disease, and age strongly predicts cardiovascular complications. Inflammation and oxidative stress appear to play some role in the mechanisms underlying aging, diabetes, cardiovascular disease, and other complications of diabetes. However, the mechanisms underlying the age-associated increase in risk for diabetes and diabetes-related cardiovascular disease remain poorly understood. Moreover, because of the heterogeneity of the older population, a lack of understanding of the biology of aging, and inadequate study of the effects of treatments on traditional complications and geriatric conditions associated with diabetes, no consensus exists on the optimal interventions for older diabetic adults. The Association of Specialty Professors, along with the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and the American Diabetes Association, held a workshop, summarized in this Perspective, to discuss current knowledge regarding diabetes and cardiovascular disease in older adults, identify gaps, and propose questions to guide future research. C1 [Halter, Jeffrey B.] Univ Michigan, Sch Med, Dept Internal Med, Div Geriatr & Palliat Med, Ann Arbor, MI 48109 USA. [Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Musi, Nicolas] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Horne, Frances McFarland] Assoc Specialty Prof, Alexandria, VA USA. [Crandall, Jill P.] Albert Einstein Coll Med, Div Endocrinol, Dept Med, Bronx, NY 10467 USA. [Goldberg, Andrew] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Goldberg, Andrew] Baltimore VA Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA. [Harkless, Lawrence] Western Univ Hlth Sci, Pomona, CA USA. [Hazzard, William R.] Univ Washington, Dept Med, Puget Sound VA Hlth Care Syst, Seattle, WA USA. [Huang, Elbert S.] Univ Chicago, Dept Med, Div Gen Internal Med, Chicago, IL 60637 USA. [Kirkman, M. Sue] Univ N Carolina, Dept Med, Div Endocrinol & Metab, Chapel Hill, NC USA. [Plutzky, Jorge] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Schmader, Kenneth E.] Duke Univ, Sch Med, Geriatr Res Educ & Clin Ctr, Durham, NC USA. [Schmader, Kenneth E.] Durham VA Med Ctr, Durham, NC USA. [Zieman, Susan] NIA, Bethesda, MD 20892 USA. [High, Kevin P.] Wake Forest Sch Med, Dept Internal Med, Infect Dis Sect, Winston Salem, NC USA. RP Halter, JB (reprint author), Univ Michigan, Sch Med, Dept Internal Med, Div Geriatr & Palliat Med, Ann Arbor, MI 48109 USA. EM jhalter@umich.edu; musi@uthscsa.edu FU National Institute on Aging [1-U13-AG-040938 01]; John A. Hartford Foundation; National Institutes of Health's National Institute on Aging; Alliance for Academic Internal Medicine; American Diabetes Association FX Funding. This workshop was supported by generous grants to Association of Specialty Professors from the National Institute on Aging (1-U13-AG-040938 01) and the John A. Hartford Foundation (J.B.H., K.E.S., K.P.H.). J.B.H. reports grants from the John A. Hartford Foundation, National Institutes of Health's National Institute on Aging, and Alliance for Academic Internal Medicine during the conduct of the project, and from the American Diabetes Association outside the submitted work. F.M.H. reports grants from the John A. Hartford Foundation during the conduct of the project. NR 54 TC 29 Z9 29 U1 2 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD AUG PY 2014 VL 63 IS 8 BP 2578 EP 2589 DI 10.2337/db14-0020 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN0GK UT WOS:000340262100004 PM 25060886 ER PT J AU Long, JA Wang, A Medvedeva, EL Eisen, SV Gordon, AJ Kreyenbuhl, J Marcus, SC AF Long, Judith A. Wang, Andrew Medvedeva, Elina L. Eisen, Susan V. Gordon, Adam J. Kreyenbuhl, Julie Marcus, Steven C. TI Glucose Control and Medication Adherence Among Veterans With Diabetes and Serious Mental Illness: Does Collocation of Primary Care and Mental Health Care Matter? SO DIABETES CARE LA English DT Article ID NEUROPSYCHOLOGICAL STATUS; REPEATABLE BATTERY; SCREENING-TEST; SCHIZOPHRENIA; DISORDERS; VALIDITY; RELIABILITY; PREVALENCE; MORTALITY; MELLITUS AB OBJECTIVE Persons with serious mental illness (SMI) may benefit from collocation of medical and mental health healthcare professionals and services in attending to their chronic comorbid medical conditions. We evaluated and compared glucose control and diabetes medication adherence among patients with SMI who received collocated care to those not receiving collocated care (which we call usual care). RESEARCH DESIGN AND METHODS We performed a cross-sectional, observational cohort study of 363 veteran patients with type 2 diabetes and SMI who received care from one of three Veterans Affairs medical facilities: two sites that provided both collocated and usual care and one site that provided only usual care. Through a survey, laboratory tests, and medical records, we assessed patient characteristics, glucose control as measured by a current HbA(1c), and adherence to diabetes medication as measured by the medication possession ration (MPR) and self-report. RESULTS In the sample, the mean HbA(1c) was 7.4% (57 mmol/mol), the mean MPR was 80%, and 51% reported perfect adherence to their diabetes medications. In both unadjusted and adjusted analyses, there were no differences in glucose control and medication adherence by collocation of care. Patients seen in collocated care tended to have better HbA(1c) levels (beta = 20.149; P = 0.393) and MPR values (beta = 0.34; P = 0.132) and worse self-reported adherence (odds ratio 0.71; P = 0.143), but these were not statistically significant. CONCLUSIONS In a population of veterans with comorbid diabetes and SMI, patients on average had good glucose control and medication adherence regardless of where they received primary care. C1 [Long, Judith A.; Wang, Andrew; Medvedeva, Elina L.; Marcus, Steven C.] Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. [Long, Judith A.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Eisen, Susan V.] Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA 01730 USA. [Eisen, Susan V.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kreyenbuhl, Julie] VA Capitol Hlth Care Network, Mental Illness Res Educ & Clin Ctr, Baltimore, MD USA. [Kreyenbuhl, Julie] Univ Maryland, Sch Med, Dept Psychiat, Div Res Serv, Baltimore, MD 21201 USA. [Marcus, Steven C.] Univ Penn, Penn Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Long, JA (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. EM jalong@mail.med.upenn.edu FU VA Health Services Research Development [IIR-07-124-3] FX This work was supported by VA Health Services Research & Development IIR-07-124-3. NR 30 TC 6 Z9 6 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2014 VL 37 IS 8 BP 2261 EP 2267 DI 10.2337/dc13-0051 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN3MI UT WOS:000340491800041 PM 24879839 ER PT J AU Dominitz, JA Robertson, DJ AF Dominitz, Jason A. Robertson, Douglas J. TI Tailoring Colonoscopic Screening to Individual Risk SO GASTROENTEROLOGY LA English DT Editorial Material ID SOCIETY-TASK-FORCE; COLORECTAL-CANCER; AMERICAN-COLLEGE; ADVANCED NEOPLASIA; GREATER-THAN-9 MM; SURVEILLANCE; POLYPS; SEX; COLONOGRAPHY; PREVALENCE C1 [Dominitz, Jason A.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Robertson, Douglas J.] Geisel Sch Med Dartmouth, White River Junct VA Med Ctr, Gastroenterol Sect, White River Jct, VT USA. RP Dominitz, JA (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way 111 Gastro, Seattle, WA 98108 USA. EM jason.dominitz@va.gov OI Dominitz, Jason/0000-0002-8070-7086 NR 24 TC 3 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2014 VL 147 IS 2 BP 264 EP 266 DI 10.1053/j.gastro.2014.06.018 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AN2WX UT WOS:000340447800008 PM 24976032 ER PT J AU Luo, YX Wong, CJ Kaz, AM Dzieciatkowski, S Carter, KT Morris, SM Wang, JP Willis, JE Makar, KW Ulrich, CM Lutterbaugh, JD Shrubsole, MJ Zheng, W Markowitz, SD Grady, WM AF Luo, Yanxin Wong, Chao-Jen Kaz, Andrew M. Dzieciatkowski, Slavomir Carter, Kelly T. Morris, Shelli M. Wang, Jianping Willis, Joseph E. Makar, Karen W. Ulrich, Cornelia M. Lutterbaugh, James D. Shrubsole, Martha J. Zheng, Wei Markowitz, Sanford D. Grady, William M. TI Differences in DNA Methylation Signatures Reveal Multiple Pathways of Progression From Adenoma to Colorectal Cancer SO GASTROENTEROLOGY LA English DT Article DE Epigenetic Modifications; Colon Cancer; Progression; Gene Regulation ID CPG ISLAND METHYLATION; HUMAN COLON; MICROSATELLITE INSTABILITY; SERRATED PATHWAY; BRAF MUTATION; PHENOTYPE; HYPERMETHYLATION; PATHOGENESIS; LESIONS; POLYPS AB BACKGROUND & AIMS: Genetic and epigenetic alterations contribute to the pathogenesis of colorectal cancer (CRC). There is considerable molecular heterogeneity among colorectal tumors, which appears to arise as polyps progress to cancer. This heterogeneity results in different pathways to tumorigenesis. Although epigenetic and genetic alterations have been detected in conventional tubular adenomas, little is known about how these affect progression to CRC. We compared methylomes of normal colon mucosa, tubular adenomas, and colorectal cancers to determine how epigenetic alterations might contribute to cancer formation. METHODS: We conducted genome-wide array-based studies and comprehensive data analyses of aberrantly methylated loci in 41 normal colon tissue, 42 colon adenomas, and 64 cancers using HumanMethylation450 arrays. RESULTS: We found genome-wide alterations in DNA methylation in the nontumor colon mucosa and cancers. Three classes of cancers and 2 classes of adenomas were identified based on their DNA methylation patterns. The adenomas separated into classes of high-frequency methylation and low-frequency methylation. Within the high-frequency methylation adenoma class a subset of adenomas had mutant KRAS. Additionally, the high-frequency methylation adenoma class had DNA methylation signatures similar to those of cancers with low or intermediate levels of methylation, and the low-frequency methylation adenoma class had methylation signatures similar to that of nontumor colon tissue. The CpG sites that were differentially methylated in these signatures are located in intragenic and intergenic regions. CONCLUSIONS: Genome-wide alterations in DNA methylation occur during early stages of progression of tubular adenomas to cancer. These findings reveal heterogeneity in the pathogenesis of colorectal cancer, even at the adenoma step of the process. C1 [Luo, Yanxin; Wang, Jianping] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Guangzhou 510655, Guangdong, Peoples R China. [Luo, Yanxin; Wong, Chao-Jen; Kaz, Andrew M.; Dzieciatkowski, Slavomir; Carter, Kelly T.; Morris, Shelli M.; Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Kaz, Andrew M.] VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. [Kaz, Andrew M.; Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Willis, Joseph E.] Case Comprehens Canc Ctr, Case Med Ctr, Dept Pathol, Cleveland, OH USA. [Willis, Joseph E.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Makar, Karen W.; Ulrich, Cornelia M.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. [Ulrich, Cornelia M.] Heidelberg Univ, Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Ulrich, Cornelia M.] Heidelberg Univ, German Canc Res Ctr DKFZ, Heidelberg, Germany. [Lutterbaugh, James D.; Markowitz, Sanford D.] Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA. [Lutterbaugh, James D.; Markowitz, Sanford D.] Case Western Reserve Univ, Ireland Canc Ctr, Sch Med, Cleveland, OH 44106 USA. [Lutterbaugh, James D.; Markowitz, Sanford D.] Case Med Ctr, Cleveland, OH USA. [Shrubsole, Martha J.; Zheng, Wei] Vanderbilt Univ, Sch Med, Dept Med, Vanderbilt Epidemiol Ctr,Div Epidemiol, Nashville, TN 37212 USA. RP Luo, YX (reprint author), Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Guangzhou 510655, Guangdong, Peoples R China. EM luoyx25@mail.sysu.edu.cn; wgrady@fhcrc.org RI Shrubsole, Martha/K-5052-2015 OI Shrubsole, Martha/0000-0002-5591-7575 FU National Cancer Institute of the National Institutes of Health [RO1CA115513, P30CA15704, UO1CA152756, U54CA143862, P01CA077852, P50CA95103, R01CA121060, P30CA68485, K07CA122451]; Burroughs Wellcome Fund; Program of Introducing Talents of Discipline to Universities of China [B12003]; International Science & Technology Cooperation Program of China [2011DFA32570]; National Natural Science Foundation of China [81201920]; [5P50CA150964] FX This research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number RO1CA115513, P30CA15704, UO1CA152756, U54CA143862, and P01CA077852 (WMG), P50CA95103 (ZW), R01CA121060, P30CA68485, K07CA122451 (MJS). The content is solely the responsibility of the authors, and does not necessarily represent the official views of the National Institutes of Health. Support for these studies was also provided by a Burroughs Wellcome Fund Translational Research Award for Clinician Scientist (WMG), Program of Introducing Talents of Discipline to Universities of China (B12003, JW) and International Science & Technology Cooperation Program of China (2011DFA32570, JW), National Natural Science Foundation of China (81201920, YL); and 5P50CA150964 (SDM). NR 52 TC 36 Z9 36 U1 1 U2 18 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2014 VL 147 IS 2 BP 418 EP + DI 10.1053/j.gastro.2014.04.039 PG 20 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AN2WX UT WOS:000340447800030 PM 24793120 ER PT J AU Redmann, M Dodson, M Boyer-Guittaut, M Darley-Usmar, V Zhang, JH AF Redmann, Matthew Dodson, Matthew Boyer-Guittaut, Michael Darley-Usmar, Victor Zhang, Jianhua TI Mitophagy mechanisms and role in human diseases SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Mitochondria; Parkinson's disease; Cancer; Mitophagy; Heart disease ID MITOCHONDRIAL QUALITY-CONTROL; OXIDATIVE STRESS; PARKINSONS-DISEASE; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; PINK1/PARKIN-MEDIATED MITOPHAGY; ADRENOCORTICAL TUMORS; DAMAGED MITOCHONDRIA; ATTENUATES MITOPHAGY; SELECTIVE AUTOPHAGY AB Mitophagy is a process of mitochondrial turnover through lysosomal mediated autophagy activities. This review will highlight recent studies that have identified mediators of mitophagy in response to starvation, loss of mitochondrial membrane potential or perturbation of mitochondrial integrity. Furthermore, we will review evidence of mitophagy dysfunction in various human diseases and discuss the potential for therapeutic interventions that target mitophagy processes. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Redmann, Matthew; Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Redmann, Matthew; Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL 35294 USA. [Boyer-Guittaut, Michael] Univ Franche Comte, Biochim Lab, EA3922, SFR IBCT FED4234, F-25030 Besancon, France. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, BMRII 534,901 19th St S, Birmingham, AL 35294 USA. EM zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU NIH [R01-NS064090]; VA FX This work was supported by NIH R01-NS064090 and a VA merit award (to JZ). NR 113 TC 33 Z9 34 U1 4 U2 26 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 EI 1878-5875 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD AUG PY 2014 VL 53 BP 127 EP 133 DI 10.1016/j.biocel.2014.05.010 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AN1KE UT WOS:000340340400016 PM 24842106 ER PT J AU Margolis, JM Chu, BC Wang, ZXJ Copher, R Cavazos, JE AF Margolis, Jay M. Chu, Bong-Chul Wang, Zhixiao J. Copher, Ronda Cavazos, Jose E. TI Effectiveness of Antiepileptic Drug Combination Therapy for Partial-Onset Seizures Based on Mechanisms of Action SO JAMA NEUROLOGY LA English DT Article ID TONIC CLONIC SEIZURES; CARBAMAZEPINE; EPILEPSY; ADULTS AB IMPORTANCE To our knowledge, the current study is the first to describe antiepileptic drug (AED) combination therapy patterns according to their mechanism of action (MOA) in a real-world setting and to evaluate the differences in outcomes comparing different-MOA combination therapy with same-MOA combination therapy for patients with partial-onset seizure. OBJECTIVE To compare treatment persistence and health care use with AED combinations categorized by MOA in patients with partial-onset seizures. DESIGN, SETTING, AND PARTICIPANTS Using the Truven Health MarketScan Commercial Claims Database containing 96 million covered lives from July 1, 2004, through March 31, 2011, adults with concomitant use of 2 different AEDs and a recent partial-onset seizure diagnosis were selected. Antiepileptic drugs were categorized by MOA: sodium channel blockers (SC), gamma-aminobutyric acid analogs (G), synaptic vesicle protein 2A binding (SV2), and multiple mechanisms (M). Patients were assigned a combination category based on their concomitant AED use. MAIN OUTCOMES AND MEASURES Treatment persistence was measured from the start of AED combination therapy until the end of the combination. Health care resource use was measured during the combination treatment duration. Multivariate analyses evaluated AED discontinuation risk and health care use according to MOA combinations. RESULTS Distribution of 8615 selected patients by combination was 3.3% for G+G, 7.5% for G+SV2, 8.6% for G+M, 13.9% for SC+SC, 19.0% for G+SC, 21.5% for SC+M, and 26.3% for SC+SV2. The same-MOA (G+G and SC+SC) combinations had the shortest persistence (mean [SD], 344 [345] days and 513 [530] days, respectively) and greater hazard of discontinuation compared with different-MOA combinations. Patients with different-MOA G combinations had a significantly lower risk for inpatient admission (odds ratio, 0.716; 95% CI, 0.539-0.952; P = .02) compared with G+G combinations. Patients with different-MOA SC combinations had significantly lower risks for emergency department visits (odds ratio, 0.853; 95% CI, 0.742-0.980; P = .03) compared with SC+SC combinations. CONCLUSIONS AND RELEVANCE The findings suggest that AED combinations with different MOAs have greater effectiveness as measured by treatment persistence and lower risks for hospitalization and emergency department visits. Further research is needed to more fully understand the role of the MOA in achieving optimal outcomes. C1 [Margolis, Jay M.] Truven Hlth Analyt, Bethesda, MD USA. [Chu, Bong-Chul] Truven Hlth Analyt, Santa Barbara, CA USA. [Wang, Zhixiao J.] Eisai Inc, Woodcliff Lake, NJ USA. [Copher, Ronda] Eisai Inc, Minneapolis, MN USA. [Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Cavazos, Jose E.] South Texas Vet Hlth Care Syst, San Antonio Epilepsy Ctr Excellence, San Antonio, TX USA. RP Margolis, JM (reprint author), Truven Hlth Analyt, 332 Bryn Mawr Ave, Bala Cynwyd, PA 19004 USA. EM jay.margolis@truvenhealth.com RI Cavazos, Jose/J-4122-2016 OI Cavazos, Jose/0000-0001-5777-2608 FU Eisai Inc, Woodcliff Lake, New Jersey FX This research was sponsored by Eisai Inc, Woodcliff Lake, New Jersey. NR 15 TC 21 Z9 21 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD AUG PY 2014 VL 71 IS 8 BP 985 EP 993 DI 10.1001/jamaneurol.2014.808 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AN3IW UT WOS:000340481800008 PM 24911669 ER PT J AU Makam, AN Auerbach, AD Steinman, MA AF Makam, Anil N. Auerbach, Andrew D. Steinman, Michael A. TI Blood culture use in the emergency department in patients hospitalized with respiratory symptoms due to a nonpneumonia illness SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; HOLD-UP; MANAGEMENT; SCRUTINY; NHAMCS; RULE AB BACKGROUND Guidelines and performance measures recommend obtaining blood cultures in selected patients hospitalized with community-acquired pneumonia (CAP). Due to inherent diagnostic uncertainty, there may be spillover effects of these recommendations on other conditions that resemble pneumonia. METHODS Using data from the 2002 to 2010 National Hospital Ambulatory Medical Care Survey, a nationally representative sample of emergency department (ED) visits in the United States, we analyzed trends in obtaining cultures in patients hospitalized with respiratory symptoms due to a nonpneumonia illness using linear regression. RESULTS The most common primary admission diagnoses for these visits included heart failure (16%), chronic obstructive pulmonary disease (13%), and chest pain (12%). The proportion of cultures collected in the ED during these visits increased from 10% (95% confidence interval [CI]: 7%-14%) in 2002 to 20% (95% CI: 16%-26%) in 2010 (P<0.001 for the trend). This represented a parallel increase compared to patients hospitalized with CAP (P=0.12 for the difference in trends). CONCLUSIONS The increase in collecting cultures in the ED in patients hospitalized with respiratory symptoms due to a nonpneumonia illness suggests an important potential unintended consequence of blood culture recommendations for CAP. More attention to the judicious use of blood cultures to reduce harm and costs is needed. Journal of Hospital Medicine 2014;9:521-524. (c) 2014 Society of Hospital Medicine C1 [Makam, Anil N.] Univ Texas SW Med Ctr Dallas, Div Gen Internal Med, Dallas, TX 75390 USA. [Auerbach, Andrew D.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Steinman, Michael A.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Steinman, Michael A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Makam, AN (reprint author), 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM anil.makam@utsouthwestern.edu OI Makam, Anil/0000-0001-7072-9946 FU NRSA [T32HP19025-07-00] FX Dr. Makam's work on this project was completed while he was a Primary Care Research Fellow at the University of California San Francisco, funded by an NRSA training grant (T32HP19025-07-00). The authors report no conflicts of interest. NR 17 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD AUG PY 2014 VL 9 IS 8 BP 521 EP 524 DI 10.1002/jhm.2205 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AN3YM UT WOS:000340524800007 PM 24753399 ER PT J AU Bailey, FA Williams, BR Goode, PS Woodby, LL Granstaff, US Echt, KV Redden, DT Kvale, E Burgio, KL AF Bailey, F. Amos Williams, Beverly R. Goode, Patricia S. Woodby, Lesa L. Granstaff, U. Shanette Echt, Katharina V. Redden, David T. Kvale, Elizabeth Burgio, Kathryn L. TI Impact of a Hospice Emergency Kit for Veterans and Their Caregivers: A Prospective Cohort Study SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID MANAGING MEDICATIONS; CARE; HOME; SUPPORT AB Background: Although hospice emergency kits (HEKs) are provided by many home hospice agencies, little is known about their use, side effects, and perceived impact. Objective: To evaluate HEK medication utilization, side effects, and impact as perceived by home hospice patients and their caregivers. Methods: We conducted a prospective longitudinal cohort study. Participants included 43 veterans and their family/caregivers referred to community home hospices with a Veterans Affairs (VA)-provided HEK. Measurements included patient/family reports based on weekly telephone interviews, electronic medical record (EMR) review, and after-death caregiver interviews. Results: The HEK was used by 27 of 43 patients/caregivers (62.8%). In 11 cases, they reported using the kit on more than one occasion. The most commonly used medications were morphine concentrate (30.2% of patients), lorazepam (20.9%), and levofloxacin (16.3%). In 15 cases (34.9%), the family thought the HEK may have helped the patient stay at home. Nineteen of the 43 patients made at least one visit to the emergency department (ED) and 22 were hospitalized. Most admissions through the ED were due to uncontrolled pain and/or gastrointestinal problems, such as nausea or bowel obstruction. In after-death interviews, opinions of the HEK were uniformly positive. Respondents described the HEK's usefulness and felt supported and empowered by its presence in the home. Minor side effects were reported in four cases. Conclusions: Findings provide promising evidence that HEKs are a feasible and well-tolerated method for achieving timely relief of emergent symptoms in home hospice patients and possibly avoiding unwanted ED visits and hospitalizations. C1 [Bailey, F. Amos; Williams, Beverly R.; Goode, Patricia S.; Woodby, Lesa L.; Granstaff, U. Shanette; Echt, Katharina V.; Redden, David T.; Kvale, Elizabeth; Burgio, Kathryn L.] Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Birmingham, AL USA. [Bailey, F. Amos; Williams, Beverly R.; Goode, Patricia S.; Woodby, Lesa L.; Granstaff, U. Shanette; Echt, Katharina V.; Redden, David T.; Kvale, Elizabeth; Burgio, Kathryn L.] Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Atlanta, GA USA. [Bailey, F. Amos; Williams, Beverly R.; Goode, Patricia S.; Woodby, Lesa L.; Granstaff, U. Shanette; Redden, David T.; Kvale, Elizabeth; Burgio, Kathryn L.] Univ Alabama Birmingham, Birmingham, AL USA. [Echt, Katharina V.] Emory Univ, Atlanta, GA 30322 USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, Geriatr Res Educ & Clin Ctr, 11G 700 South 19th St, Birmingham, AL 35233 USA. EM kburgio@uabmc.edu FU Birmingham/Atlanta Geriatric Research, Education, and Clinical Center (GRECC); Research Enhancement Award Program (REAP), Department of Veterans Affairs FX This research was supported by the Birmingham/Atlanta Geriatric Research, Education, and Clinical Center (GRECC) and Research Enhancement Award Program (REAP), Department of Veterans Affairs. NR 19 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD AUG PY 2014 VL 17 IS 8 BP 931 EP 938 DI 10.1089/jpm.2013.0395 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AN4BP UT WOS:000340532900013 PM 24927070 ER PT J AU Stey, AM Ko, CY Hall, BL Louie, R Lawson, EH Gibbons, MM Zingmond, DS Russell, MM AF Stey, Anne M. Ko, Clifford Y. Hall, Bruce Lee Louie, Rachel Lawson, Elise H. Gibbons, Melinda M. Zingmond, David S. Russell, Marcia M. TI Are Procedures Codes in Claims Data a Reliable Indicator of Intraoperative Splenic Injury Compared with Clinical Registry Data? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID OF-VETERANS-AFFAIRS; QUALITY IMPROVEMENT PROGRAM; SURGEONS NATIONAL DATABASES; BYPASS GRAFT-SURGERY; ADMINISTRATIVE DATA; SURGICAL QUALITY; ACS-NSQIP; COMPLICATION RATES; DECADES EXPERIENCE; ADVERSE EVENTS AB BACKGROUND: Identifying iatrogenic injuries using existing data sources is important for improved transparency in the occurrence of intraoperative events. There is evidence that procedure codes are reliably recorded in claims data. The objective of this study was to assess whether concurrent splenic procedure codes in patients undergoing colectomy procedures are reliably coded in claims data as compared with clinical registry data. STUDY DESIGN: Patients who underwent colectomy procedures in the absence of neoplastic diagnosis codes were identified from American College of Surgeons (ACS) NSQIP data linked with Medicare inpatient claims data file (2005 to 2008). A kappa statistic was used to assess coding concordance between ACS NSQIP and Medicare inpatient claims, with ACS NSQIP serving as the reference standard. RESULTS: A total of 11,367 colectomy patients were identified from 212 hospitals. There were 114 patients (1%) who had a concurrent splenic procedure code recorded in either ACS NSQIP or Medicare inpatient claims. There were 7 patients who had a splenic injury diagnosis code recorded in either data source. Agreement of splenic procedure codes between the data sources was substantial (kappa statistic 0.72; 95% CI, 0.64-0.79). Medicare inpatient claims identified 81% of the splenic procedure codes recorded in ACS NSQIP, and 99% of the patients without a splenic procedure code. CONCLUSIONS: It is feasible to use Medicare claims data to identify splenic injuries occurring during colectomy procedures, as claims data have moderate sensitivity and excellent specificity for capturing concurrent splenic procedure codes compared with ACS NSQIP. (C) 2014 by the American College of Surgeons C1 [Stey, Anne M.] Mt Sinai Med Ctr, Icahn Sch Med, New York, NY 10029 USA. [Stey, Anne M.; Ko, Clifford Y.; Louie, Rachel; Lawson, Elise H.; Gibbons, Melinda M.; Zingmond, David S.; Russell, Marcia M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Ko, Clifford Y.; Russell, Marcia M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ko, Clifford Y.; Hall, Bruce Lee] Amer Coll Surg, Chicago, IL USA. [Hall, Bruce Lee] Washington Univ, St Louis VA Med Ctr, Dept Surg, Olin Business Sch, St Louis, MO USA. [Hall, Bruce Lee] Washington Univ, St Louis VA Med Ctr, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce Lee] BJC Healthcare St Louis, St Louis, MO USA. RP Stey, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 10940 Wilshire Blvd,Suite 710, Los Angeles, CA 90024 USA. EM as013j@gmail.com FU Robert Wood Johnson Foundation; US Department of Veterans Affairs FX Dr Stey's time for this publication was supported by The Robert Wood Johnson Foundation Clinical Scholars program and the US Department of Veterans Affairs. NR 35 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2014 VL 219 IS 2 BP 237 EP U207 DI 10.1016/j.jamcollsurg.2014.02.029 PG 9 WC Surgery SC Surgery GA AN3LM UT WOS:000340489600013 PM 24891210 ER PT J AU Maggiore, RJ Dale, W Gross, CP Feng, T Tew, WP Mohile, SG Owusu, C Klepin, HD Lichtman, SM Gajra, A Ramani, R Katheria, V Zavala, L Hurria, A AF Maggiore, Ronald J. Dale, William Gross, Cary P. Feng, Tao Tew, William P. Mohile, Supriya G. Owusu, Cynthia Klepin, Heidi D. Lichtman, Stuart M. Gajra, Ajeet Ramani, Rupal Katheria, Vani Zavala, Laura Hurria, Arti CA Canc Aging Res Grp TI Polypharmacy and Potentially Inappropriate Medication Use in Older Adults with Cancer Undergoing Chemotherapy: Effect on Chemotherapy-Related Toxicity and Hospitalization During Treatment SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE polypharmacy; cancer; elderly; chemotherapy; toxicity ID ADVERSE DRUG-REACTIONS; ELDERLY-PATIENTS; BEERS CRITERIA; PREVALENCE; QUALITY; PEOPLE; APPROPRIATENESS; METAANALYSIS; POPULATION; MANAGEMENT AB OBJECTIVES: To evaluate the prevalence of polypharmacy and potentially inappropriate medication (PIM) use and the association between these and chemotherapy-related adverse events in older adults with cancer undergoing chemotherapy. DESIGN: Secondary analysis of prospectively collected data. SETTING: Outpatient oncology clinics in seven academic medical centers. PARTICIPANTS: Adults aged 65 and older with cancer undergoing chemotherapy. MEASUREMENTS: Measures included number of daily medications (polypharmacy); PIM use based on three indices (Beers, Zhan, and Drugs to Avoid in the Elderly criteria), and use of six "high risk" medication classes for adverse drug events (anticoagulants, antiplatelet agents, opioids, insulin, oral hypoglycemics, antiarrhythmics). Using multivariate logistic regression, the relations were evaluated between these criteria and Grade 3 to 5 chemotherapy-related toxicity and between these criteria and hospitalization during chemotherapy. RESULTS: Participants (N = 500; mean age 73, 61% Stage IV disease) took a mean of 5 +/- 4 daily medications (range 0-23). PIM use was common (up to 29% according to Beers criteria). No association was found between number of daily medications (reference 0-3 medications) and toxicity (4-9 medications, odds ratio (OR) = 1.34, 95% confidence interval (CI) = 0.92-1.97; >= 10 medications, OR = 0.82, 95% CI = 0.45-1.49) or hospitalization (>= 4 medications, OR = 1.34, 95% CI = 0.82-2.18, P = .24). There was also no association between PIM use and toxicity (P = .93) or hospitalization (P = .98). No medication class was associated with either outcome. CONCLUSIONS: Polypharmacy and PIM use were common but were not associated with chemotherapy-related toxicity or hospitalization in older adults with cancer. C1 [Maggiore, Ronald J.] Portland VA Med Ctr, Portland, OR USA. [Maggiore, Ronald J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Dale, William] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Gross, Cary P.] Yale Univ, Ctr Comprehens Canc, New Haven, CT USA. [Gross, Cary P.] Yale Univ, Sch Med, New Haven, CT USA. [Feng, Tao; Ramani, Rupal; Katheria, Vani; Zavala, Laura; Hurria, Arti] City Hope Natl Med Ctr, Ctr Comprehens Canc, Duarte, CA 91001 USA. [Tew, William P.; Lichtman, Stuart M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mohile, Supriya G.] Univ Rochester, Rochester, NY USA. [Owusu, Cynthia] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Klepin, Heidi D.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Gajra, Ajeet] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Gajra, Ajeet] Syracuse Vet Affairs Med Ctr, Syracuse, NY USA. RP Hurria, A (reprint author), City Hope Natl Med Ctr, Canc & Aging Res Program, 1500 E Duarte Rd, Duarte, CA 91001 USA. EM ahurria@coh.org FU Paul Beeson Career Development Award in Aging Research [K23 AG026749-01, 1 K08 AG24842]; American Society of Clinical Oncology; Association of Specialty Professors; Junior Development Award in Geriatric Oncology; National Institute on Aging Geriatric Research Training Grant [T32 AG19134]; John A. Hartford Center of Excellence in Geriatrics FX This research was supported by Paul Beeson Career Development Award in Aging Research K23 AG026749-01, (PI: Dr. Hurria) and American Society of Clinical Oncology, Association of Specialty Professors, Junior Development Award in Geriatric Oncology (PI: Dr. Hurria). Dr. Maggiore's efforts are supported by National Institute on Aging Geriatric Research Training Grant T32 AG19134 under the guidance of Drs. Gross, Hurria, and Thomas Gill. Dr. Dale's efforts are supported by the John A. Hartford Center of Excellence in Geriatrics. Dr. Gross's efforts are supported by Paul Beeson Career Development Award in Aging Research 1 K08 AG24842. NR 38 TC 17 Z9 17 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2014 VL 62 IS 8 BP 1505 EP 1512 DI 10.1111/jgs.12942 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AN3JE UT WOS:000340482800011 PM 25041361 ER PT J AU Gillespie, SM Brandt, LE Chang, A Chao, SH Corcoran, AM Miller, R Harper, GM Levine, SA Medina-Walpole, A AF Gillespie, Suzanne M. Brandt, Lynsey E. Chang, Anna Chao, Serena H. Corcoran, Amy M. Miller, Rachel Harper, G. Michael Levine, Sharon A. Medina-Walpole, Annette TI Staying in the Game: The 10-Step Approach to Sustaining Geriatrics Education in Hospitalists and Subspecialty Providers SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE geriatrics education; Donald W. Reynolds Foundation; hospitalist and subspecialist education ID FACULTY-DEVELOPMENT PROGRAM; MEDICAL-STUDENTS; CURRICULUM; PATIENT; CARE AB Geriatrics as a field has been fortunate to have the support of several philanthropic organizations to advance geriatrics education and training in the past two decades. Awardees of such grants were presented with unparalleled opportunities to develop new and innovative educational initiatives affecting learners at multiple levels and in multiple disciplines and specialties. The lessons learned from the Donald W. Reynolds Foundation initiatives about effect and sustainability are invaluable to the ongoing strategic development of geriatrics nationally. This article highlights successful educational initiatives developed at four institutions with past and current Donald W. Reynolds Foundation funding. Following an ice hockey playbook, this article identifies 10 strategies and initiatives to "stay in the geriatrics game" by training hospitalists and subspecialty providers. The authors' collective experience suggests that geriatrics educational initiatives can not only influence provider education, but also improve the care of older adults in multiple settings. C1 [Gillespie, Suzanne M.; Medina-Walpole, Annette] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Brandt, Lynsey E.; Corcoran, Amy M.; Miller, Rachel] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chang, Anna; Harper, G. Michael] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Chang, Anna; Harper, G. Michael] San Francisco VA Med Ctr, San Francisco, CA USA. [Chao, Serena H.; Levine, Sharon A.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Medina-Walpole, A (reprint author), Monroe Community Hosp, 435 East Henrietta Rd, Rochester, NY 14620 USA. EM annette_medinawalpole@urmc.rochester.edu FU Donald W. Reynold's Foundation FX Sponsor's Role: The educational initiatives described in this manuscript were developed through financial support from the Donald W. Reynold's Foundation. NR 20 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2014 VL 62 IS 8 BP 1575 EP 1582 DI 10.1111/jgs.12934 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AN3JE UT WOS:000340482800021 PM 25040491 ER PT J AU Kannan, TR Krishnan, M Ramasamy, K Becker, A Pakhomova, ON Hart, PJ Baseman, JB AF Kannan, Thirumalai R. Krishnan, Manickam Ramasamy, Kumaraguruparan Becker, Argentina Pakhomova, Olga N. Hart, P. John Baseman, Joel B. TI Functional mapping of community-acquired respiratory distress syndrome (CARDS) toxin of Mycoplasma pneumoniae defines regions with ADP-ribosyltransferase, vacuolating and receptor-binding activities SO MOLECULAR MICROBIOLOGY LA English DT Article ID TOXIGENIC ESCHERICHIA-COLI; PROTEIN HOMOLOGY DETECTION; SITE-DIRECTED MUTAGENESIS; HEAT-LABILE ENTEROTOXIN; CHOLERA-TOXIN; PERTUSSIS TOXIN; HELICOBACTER-PYLORI; RIBOSYLATING TOXINS; ASTHMA; INFECTIONS AB Community-acquired respiratory distress syndrome (CARDS) toxin from Mycoplasma pneumoniae is a 591-amino-acid virulence factor with ADP-ribosyltransferase (ADPRT) and vacuolating activities. It is expressed at low levels during in vitro growth and at high levels during colonization of the lung. Exposure of experimental animals to purified recombinant CARDS toxin alone is sufficient to recapitulate the cytopathology and inflammatory responses associated with M. pneumoniae infection in humans and animals. Here, by molecular modelling, serial truncations and site-directed mutagenesis, we show that the N-terminal region is essential for ADP-ribosylating activity. Also, by systematic truncation and limited proteolysis experiments we identified a portion of the C-terminal region that mediates toxin binding to mammalian cell surfaces and subsequent internalization. In addition, the C-terminal region alone induces vacuolization in a manner similar to full-length toxin. Together, these data suggest that CARDS toxin has a unique architecture with functionally separable N-terminal and C-terminal domains. C1 [Kannan, Thirumalai R.; Krishnan, Manickam; Ramasamy, Kumaraguruparan; Baseman, Joel B.] Univ Texas Hlth Sci Ctr San Antonio, Ctr Airway Inflammat Res, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Becker, Argentina; Pakhomova, Olga N.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Kannan, TR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Ctr Airway Inflammat Res, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. EM kannan@uthscsa.edu; baseman@uthscsa.edu FU National Institute of Allergy and Infectious Diseases [U19AI070412]; Kleberg Foundation; Robert A. Welch Foundation [AQ-1399]; National Center for Research Resources at the National Institute of Health [RR-15301]; US Department of Energy, Office of Basic Energy Sciences [W-31-109-ENG-38]; Cancer Therapy & Research Center (CTRC) Cancer Center Support Grant [NCI P30CA054174]; UTHSCSA Executive Research Committee FX We thank Tiffany McDonald Marsh, Pramod Gowda, Brandon Guin and Dr Sowmya Balasubramanian for their technical assistance. We would like to thank Rose Garza for assembling the manuscript. This work was supported by Award Number U19AI070412 from the National Institute of Allergy and Infectious Diseases, The Kleberg Foundation, and the Robert A. Welch Foundation Grant AQ-1399 (PJH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. This work is partially the result of research conducted at the Northeastern Collaborative Access Team (NE-CAT) beam lines of the Advanced Photon Source, supported by award RR-15301 from the National Center for Research Resources at the National Institute of Health. Use of the Advanced Photon Source is supported by the US Department of Energy, Office of Basic Energy Sciences, under contract No. W-31-109-ENG-38. This work was also supported in part by the Cancer Therapy & Research Center (CTRC) Cancer Center Support Grant, NCI P30CA054174 and support for the X-ray Crystallography Core Laboratory by the UTHSCSA Executive Research Committee is gratefully acknowledged. NR 52 TC 8 Z9 9 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 2014 VL 93 IS 3 BP 568 EP 581 DI 10.1111/mmi.12680 PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA AN1VF UT WOS:000340371200014 PM 24948331 ER PT J AU Chong, EW Guymer, RH Klein, R Klein, BE Cotch, MF Wang, JJ Shlipak, MG Wong, TY AF Chong, Elaine W. Guymer, Robyn H. Klein, Ronald Klein, Barbara E. Cotch, Mary Frances Wang, Jie Jin Shlipak, Michael G. Wong, Tien Y. TI Is Renal Function Associated with Early Age-Related Macular Degeneration? SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE age-related macular degeneration; kidney; renal function ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; COMPLEMENT-FACTOR-H; BLUE-MOUNTAINS-EYE; GLOMERULONEPHRITIS TYPE-II; SERUM CYSTATIN-C; BEAVER DAM EYE; FUNDUS CHANGES; RISK; PREVALENCE AB Purpose. Age-related macular degeneration (AMD) and chronic kidney disease both involve immune dysregulation and may share underlying pathophysiologic changes to systemic homeostasis. Hence, we aim to evaluate associations between impaired kidney function and early AMD, in a search for urinary biomarkers for AMD. Methods. A population-based, cross-sectional analysis of persons aged 45 to 84 years was conducted with renal function measured using serum creatinine and cystatin C levels and the estimated glomerular filtration rate (eGFR) calculated. Age-related macular degeneration status was ascertained from retinal photographs. Results. Of 5874 participants, 221 had early AMD. High serum cystatin C and low eGFR (<= 60 ml/min/1.73 m(2)) were not associated with early AMD in our multivariate analyses. Among normotensive persons, however, highest versus other deciles of cystatin C were associated with an increased prevalence of early AMD (odds ratio, 1.80; 95% confidence interval, 1.00 to 3.23). Conclusions. Results could not confirm an association between kidney function and early AMD. The borderline association between cystatin C and early AMD in normotensive persons require further verification. C1 [Chong, Elaine W.; Guymer, Robyn H.; Wang, Jie Jin; Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, East Melbourne, Vic 3002, Australia. [Klein, Ronald; Klein, Barbara E.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. [Wang, Jie Jin] Univ Sydney, Ctr Vis Res, Sydney, NSW 2006, Australia. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117595, Singapore. RP Chong, EW (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, East Melbourne, Vic 3002, Australia. EM elainechongwt@alumni.unimelb.edu.au RI Wang, Jie Jin/P-1499-2014 OI Wang, Jie Jin/0000-0001-9491-4898; Cotch, Mary Frances/0000-0002-2046-4350 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165, N01-HC-95169] FX This study was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute. NR 40 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 EI 1538-9235 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD AUG PY 2014 VL 91 IS 8 BP 860 EP 864 PG 5 WC Ophthalmology SC Ophthalmology GA AN4KL UT WOS:000340556500008 PM 24879085 ER PT J AU Coltrera, MD AF Coltrera, Marc D. TI Clinician-Performed Thyroid Ultrasound SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Ultrasound; Office-based; Thyroid cancer; Training; Validation; Competency ID FINE-NEEDLE-ASPIRATION; PREDICTIVE-VALUE; 3 SETS; NODULES; CARCINOMA; PAPILLARY; SONOGRAPHY; MANAGEMENT; BIOPSY; GUIDELINES AB This article is intended to demystify the process for those with a potential interest in acquiring ultrasound skills. It is not intended to be a comprehensive review of head and neck ultrasound but, rather, is focused on the bare minimum requirements and considerations involved in clinician-performed ultrasound. The article covers the initial diagnosis and the unparalleled usefulness of ultrasound for surgical planning just before incision. Further readings are listed at the end of the article to direct the reader to some excellent texts to help build confidence and experience. C1 [Coltrera, Marc D.] Univ Washington, Dept OTO HNS, Seattle, WA 98195 USA. [Coltrera, Marc D.] VA Puget Sound, OTO HNS Div, Seattle, WA 98108 USA. RP Coltrera, MD (reprint author), Univ Washington, Dept OTO HNS, 1959 Northeast Pacific,Box 356515, Seattle, WA 98195 USA. EM Coltrera@u.washington.edu NR 37 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 EI 1557-8259 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD AUG PY 2014 VL 47 IS 4 BP 491 EP + DI 10.1016/j.otc.2014.04.001 PG 18 WC Otorhinolaryngology SC Otorhinolaryngology GA AN2UH UT WOS:000340440800005 PM 25041953 ER PT J AU Banks, CA Schlosser, RJ Wang, EW Casey, SE Mulligan, RM Mulligan, JK AF Banks, Caroline A. Schlosser, Rodney J. Wang, Eric W. Casey, Sarah E. Mulligan, Ryan M. Mulligan, Jennifer K. TI Macrophage Infiltrate Is Elevated in CRSwNP Sinonasal Tissue Regardless of Atopic Status SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE macrophage; chronic rhinosinusitis; nasal polyps; atopy ID RELATIVE CORTICOSTEROID INSENSITIVITY; CHRONIC RHINOSINUSITIS; DENDRITIC CELLS; NASAL POLYPS; ALLERGIC RHINITIS; ALTERNATIVE ACTIVATION; ALVEOLAR MACROPHAGES; CHRONIC SINUSITIS; SEVERE ASTHMA; DISEASE AB Objective. Macrophages are major producers of inflammatory cytokines; however, their role in chronic rhinosinusitis (CRS) has not been clearly defined. The aim of this study was to quantify macrophages in sinus tissue of patients with various subtypes of CRS and determine the impact of atopic status on macrophage infiltrate. Study Design. Prospective immunohistochemical study of human sinonasal tissue. Setting. Academic medical center. Subjects and Methods. Human sinonasal tissue was taken from patients with CRS with nasal polyposis (CRSwNP, n = 8), CRS without nasal polyposis (CRSsNP, n = 8), and controls (n = 8) undergoing surgery for CSF leak repair or endoscopic excision of non-secreting pituitary tumor. Samples were immunohistochemically stained for macrophage/monocyte markers Mac387 and CD68. Results. CRSwNP patients had significantly increased numbers of Mac387 and CD68 cells compared to control patients (P < .05) or CRSsNP patients (P < .01). CRSsNP had significantly increased number of cells staining for CD68 compared to controls (P < .05). The increased presence of macrophages measured by either marker in CRSwNP was independent of atopic status. Conclusion. Macrophages are increased in CSRwNP patients regardless of atopic status and may contribute to the immunopathology of CRS. C1 [Banks, Caroline A.; Schlosser, Rodney J.; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Dept Surg, Charleston, SC USA. [Wang, Eric W.] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA. [Casey, Sarah E.; Mulligan, Ryan M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Banks, CA (reprint author), Med Univ S Carolina, Dept Otolaryngol, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM Caroline_Banks@MEEI.HARVARD.EDU OI Wang, Eric/0000-0002-1180-5854 NR 39 TC 3 Z9 3 U1 1 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD AUG PY 2014 VL 151 IS 2 BP 215 EP 220 DI 10.1177/0194599814528672 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AN2YZ UT WOS:000340453300005 PM 24705220 ER PT J AU Davis, KS Byrd, JK Mehta, V Chiosea, SI Kim, S Ferris, RL Johnson, JT Duvvuri, U AF Davis, Kara S. Byrd, J. Kenneth Mehta, Vikas Chiosea, Simon I. Kim, Seungwon Ferris, Robert L. Johnson, Jonas T. Duvvuri, Umamaheswar TI Occult Primary Head and Neck Squamous Cell Carcinoma: Utility of Discovering Primary Lesions SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE unknown primary tumor; oropharyngeal; HPV; cervical metastases; squamous cell carcinoma; unknown primary; human papilloma virus; base of tongue; tonsil; oropharyngeal cancer ID HUMAN-PAPILLOMAVIRUS; UNKNOWN PRIMARY; OROPHARYNGEAL CANCER; POSITIVE HEAD; MANAGEMENT; SURVIVAL; HPV; DIAGNOSIS; STRATEGY; TUMORS AB Objective. Cancer of an unknown primary (CUP) squamous cell carcinoma metastatic to cervical lymph nodes is a challenging problem for the treating physician. Our aim is to determine if identification of the primary tumor is associated with improved oncologic outcomes and/or tumor characteristics including human papilloma virus (HPV) status. Study Design. Retrospective, matched-pairs analysis contrasting 2 cohorts based upon discovery of primary lesion. Setting. Tertiary teaching hospital. Subjects and Methods. Records of 136 patients initially diagnosed as carcinoma of unknown primary were retrospectively reviewed (1980-2010) and divided into 2 cohorts based on discovery of the primary lesion. Primary outcome measures were overall survival and time to recurrence according to Kaplan-Meier analysis. A nested subset of 22 patients in which the primary was discovered were matched to 22 patients remaining undiscovered according to nodal stage and age. Results. Discovered lesions were more likely to exhibit HPV positivity (P < .001). Matched-pairs analyses demonstrated that discovery of the primary was associated with better overall survival (HR = 0.125; 95% confidence interval [CI], 0.019-0.822; P = .030). Discovery of the primary was associated with improved cause-specific survival (HR = 0.142; 95% CI, 0.021-0.93; P = .0418) and disease-free survival (HR = 0.25; 95% CI, 0.069-0.91; P = .03). Conclusion. HPV positivity is associated with discovery of the primary tumor. Discovery of the primary lesion is associated with improved overall survival, cause-specific survival, and disease-free survival in patients initially presenting as CUP in matched-pair and cohort comparison analyses. C1 [Davis, Kara S.; Byrd, J. Kenneth; Kim, Seungwon; Ferris, Robert L.; Johnson, Jonas T.; Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Dept Otolaryngol Head & Neck Surg, Pittsburgh, PA 15213 USA. [Mehta, Vikas] Louisiana State Univ, Hlth Sci Ctr Shreveport, Dept Otolaryngol Head & Neck Surg, Shreveport, LA 71105 USA. [Chiosea, Simon I.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Davis, KS (reprint author), Univ Pittsburgh, Med Ctr, Dept Otolaryngol Head & Neck Surg, 200 Lothrop St Suite 500, Pittsburgh, PA 15213 USA. EM davisks@upmc.edu FU NIH [UL1 RR024153, UL1TR000005]; Department of Veterans Affairs, BLS RD; PNC Foundation FX NIH grants (UL1 RR024153 and UL1TR000005) funded statistical analysis. This was supported in part by funds from the Department of Veterans Affairs, BLS R&D and the PNC Foundation (U.D.). NR 20 TC 13 Z9 13 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD AUG PY 2014 VL 151 IS 2 BP 272 EP 278 DI 10.1177/0194599814533494 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AN2YZ UT WOS:000340453300014 PM 24812081 ER PT J AU Maglione, MA Das, L Raaen, L Smith, A Chari, R Newberry, S Shanman, R Perry, T Goetz, MB Gidengil, C AF Maglione, Margaret A. Das, Lopamudra Raaen, Laura Smith, Alexandria Chari, Ramya Newberry, Sydne Shanman, Roberta Perry, Tanja Goetz, Matthew Bidwell Gidengil, Courtney TI Safety of Vaccines Used for Routine Immunization of US Children: A Systematic Review SO PEDIATRICS LA English DT Review DE evidence-based medicine; vaccine/immunization; infectious disease ID HUMAN ROTAVIRUS VACCINE; INACTIVATED INFLUENZA VACCINE; MUMPS-RUBELLA VACCINATION; CONJUGATE VACCINE; DOUBLE-BLIND; DATALINK PROJECT; HEALTHY INFANTS; UNITED-STATES; THROMBOCYTOPENIC PURPURA; POSTMARKETING EVALUATION AB BACKGROUND: Concerns about vaccine safety have led some parents to decline recommended vaccination of their children, leading to the resurgence of diseases. Reassurance of vaccine safety remains critical for population health. This study systematically reviewed the literature on the safety of routine vaccines recommended for children in the United States. METHODS: Data sources included PubMed, Advisory Committee on Immunization Practices statements, package inserts, existing reviews, manufacturer information packets, and the 2011 Institute of Medicine consensus report on vaccine safety. We augmented the Institute of Medicine report with more recent studies and increased the scope to include more vaccines. Only studies that used active surveillance and had a control mechanism were included. Formulations not used in the United States were excluded. Adverse events and patient and vaccine characteristics were abstracted. Adverse event collection and reporting was evaluated by using the McHarm scale. We were unable to pool results. Strength of evidence was rated as high, moderate, low, or insufficient. RESULTS: Of 20 478 titles identified, 67 were included. Strength of evidence was high for measles/mumps/rubella (MMR) vaccine and febrile seizures; the varicella vaccine was associated with complications in immunodeficient individuals. There is strong evidence that MMR vaccine is not associated with autism. There is moderate evidence that rotavirus vaccines are associated with intussusception. Limitations of the study include that the majority of studies did not investigate or identify risk factors for AEs; and the severity of AEs was inconsistently reported. CONCLUSIONS: We found evidence that some vaccines are associated with serious AEs; however, these events are extremely rare and must be weighed against the protective benefits that vaccines provide. C1 [Maglione, Margaret A.; Das, Lopamudra; Raaen, Laura; Smith, Alexandria; Chari, Ramya; Newberry, Sydne; Shanman, Roberta; Perry, Tanja; Gidengil, Courtney] RAND Corp, Santa Monica, CA 90407 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gidengil, Courtney] Boston Childrens Hosp, Boston, MA USA. RP Maglione, MA (reprint author), RAND Corp, 1776 Main St Mailstop 4W, Santa Monica, CA 90407 USA. EM maglione@rand.org OI Goetz, Matthew/0000-0003-4542-992X FU Agency for Healthcare Research and Quality [HHSA290200710062I]; US Department of Health and Human Services FX Supported under Contract No. HHSA290200710062I from the Agency for Healthcare Research and Quality, US Department of Health and Human Services. NR 97 TC 35 Z9 38 U1 12 U2 229 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD AUG PY 2014 VL 134 IS 2 BP 325 EP 337 DI 10.1542/peds.2014-1079 PG 13 WC Pediatrics SC Pediatrics GA AN0HS UT WOS:000340266000059 PM 25086160 ER PT J AU Xu, S Shetterly, S Raebel, MA Ho, PM Tsai, TT Magid, D AF Xu, Stanley Shetterly, Susan Raebel, Marsha A. Ho, P. Michael Tsai, Thomas T. Magid, David TI Estimating the effects of time-varying exposures in observational studies using Cox models with stabilized weights adjustment SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE drug-eluting stent; clopidogrel; time-varying exposure; Cox model; stabilized weights; pharmacoepidemiology ID MARGINAL STRUCTURAL MODELS; PROPENSITY SCORE; COVARIANCE ANALYSIS; COUNTING-PROCESSES; REGRESSION-MODEL; SURVIVAL-DATA; CLOPIDOGREL; THERAPY; STENT; IMPLANTATION AB Purpose Assessing the safety and effectiveness of medical products with observational electronic medical record data is challenging when the treatment is time-varying. The objective of this paper is to develop a Cox model stratified by event times with stabilized weights (SWs) adjustment to examine the effect of time-varying treatment in observational studies. Methods Time-varying SWs are calculated at unique event times and are used in a Cox model stratified by event times to estimate the effect of time-varying treatment. We applied this method in examining the effect of an antiplatelet agent, clopidogrel, on events, including bleeding, myocardial infarction, and death after a drug-eluting stent was implanted in coronary artery. Clopidogrel use may change over time on the basis of patients' behavior (e. g., non-adherence) and physicians' recommendations (e. g., end of duration of therapy). We also compared the results with those from a Cox model for counting processes adjusting for all covariates used in creating SWs. Results We demonstrate that the (i) results from the stratified Cox model without SWs adjustment and the Cox model for counting processes without covariate adjustment are identical in analyzing the clopidogrel data; and (ii) the effects of clopidogrel on bleeding, myocardial infarction, and death are larger in the stratified Cox model with SWs adjustment compared with those from the Cox model for counting processes with covariate adjustment. Conclusions The Cox model stratified by event times with time-varying SWs adjustment is useful in estimating the effect of time-varying treatments in observational studies while balancing for known confounders. Copyright (C) 2014 John Wiley & Sons, Ltd. C1 [Xu, Stanley; Shetterly, Susan; Raebel, Marsha A.; Ho, P. Michael; Tsai, Thomas T.; Magid, David] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80237 USA. [Xu, Stanley; Raebel, Marsha A.; Ho, P. Michael; Tsai, Thomas T.; Magid, David] Univ Colorado, Denver, CO 80202 USA. [Ho, P. Michael; Tsai, Thomas T.] Denver VA Med Ctr, Denver, CO USA. RP Xu, S (reprint author), Kaiser Permanente Colorado, Inst Hlth Res, POB 378066, Denver, CO 80237 USA. EM stan.xu@kp.org FU Strategic Initiatives Funds of Kaiser Permanente Colorado; Agency for Healthcare Research and Quality, US Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness 16 (DEcIDE) program [290-05-0033]; National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) Colorado Clinical and Translational Sciences Institute [UL1 TR001082] FX This project was supported by the Strategic Initiatives Funds of Kaiser Permanente Colorado and funded under Contract No. 290-05-0033 from the Agency for Healthcare Research and Quality, US Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness 16 (DEcIDE) program. Xu was also supported by National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) Colorado Clinical and Translational Sciences Institute Grant Number UL1 TR001082. Contents are the authors' sole responsibility and do not necessarily represent official NIH views. NR 36 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2014 VL 23 IS 8 BP 812 EP 818 DI 10.1002/pds.3601 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AN1PG UT WOS:000340355200005 PM 24596337 ER PT J AU Van Hyfte, GJ Kozak, LE Lepore, M AF Van Hyfte, Gregory J. Kozak, Leila E. Lepore, Michael TI A Survey of the Use of Complementary and Alternative Medicine in Illinois Hospice and Palliative Care Organizations SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE complementary and alternative medicine; integrative palliative care; complementary therapies; hospice care; hospice administration; end-of-life care; family caregivers; service delivery ID THERAPY; CANCER AB This research assesses complementary and alternative medicine (CAM) use and administration for patients and family caregivers in Illinois hospice and palliative care organizations. An online survey was administered to a sample of 108 contacts of Illinois organizations listed in the National Hospice and Palliative Care Organization website, and 90.3% of the responding organizations offered some type of CAM. The top 5 most frequently offered CAM modalities to patients were pet therapy (64.5%), music therapy (61.3%), massage therapy (54.8%), art therapy (29.0%), and energy therapies (25.8%); these were the same top 5 offered to families but with different frequencies. Findings regarding utilization, administration, financing, and spiritual/ cultural competency are discussed with policy recommendations for data collection, administrative improvements, and integration of CAM providers into service delivery. C1 [Van Hyfte, Gregory J.] Dept Hlth Educ, Chicago, IL 60622 USA. [Kozak, Leila E.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Kozak, Leila E.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Lepore, Michael] Planetree, Dept Qual Res & Evaluat, Derby, CT USA. [Lepore, Michael] Brown Univ, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. RP Van Hyfte, GJ (reprint author), Dept Hlth Educ, 2611W Chicago Ave, Chicago, IL 60622 USA. EM gregory@uchicago.edu FU Arthur Quern Fellowship at the University of Chicago; Graduate Program in Health Administration; Policy in the School of Social Service Administration; VA Puget Sound Health Care System, Seattle, Washington through Health Services Research and Development Service as part of Dr Kozak's fellowship [TPP 61-61-023] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Arthur Quern Fellowship at the University of Chicago, Graduate Program in Health Administration and Policy in the School of Social Service Administration. Dr Kozak's work was supported in part by resources from the VA Puget Sound Health Care System, Seattle, Washington through Health Services Research and Development Service as part of Dr Kozak's fellowship, grant # TPP 61-61-023. NR 19 TC 0 Z9 0 U1 2 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD AUG PY 2014 VL 31 IS 5 BP 553 EP 561 DI 10.1177/1049909113500378 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AM8BV UT WOS:000340095200013 PM 23943631 ER PT J AU Borson, S Chodosh, J AF Borson, Soo Chodosh, Joshua TI Developing Dementia-Capable Health Care Systems: A 12-Step Program SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Dementia; Alzheimer disease; Primary care; Comprehensive management; Care coordination; Partnership; Quality measurement; Annual wellness visit ID AMERICAN GERIATRICS SOCIETY; RANDOMIZED CONTROLLED-TRIAL; PATIENT-CENTERED CARE; SERVICES-TASK-FORCE; OLDER-ADULTS; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; MANAGEMENT INTERVENTION; MEDICAL HOME; DIABETES-MELLITUS AB Improving the quality, comprehensiveness, and coordination of health care for people with dementia is a primary goal of the National Alzheimer's Plan. In this article, the key principles of high-quality dementia care for nonspecialist clinicians and health care leaders are synthesized, a framework for operationalizing its components is presented, and simple steps for developing dementia-capable health care systems are offered. C1 [Borson, Soo] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Borson, Soo] Univ Washington, Sch Nursing, Dept Psychosocial & Community Hlth, Seattle, WA 98195 USA. [Chodosh, Joshua] Univ Calif Los Angeles, David Geffen Sch Med, V CAMP, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Borson, S (reprint author), 2375 South Toledo Ave, Palm Springs, CA 92264 USA. EM soob@uw.edu OI Chodosh, Joshua/0000-0001-7784-4306 NR 92 TC 4 Z9 4 U1 6 U2 23 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2014 VL 30 IS 3 BP 395 EP + DI 10.1016/j.cger.2014.05.001 PG 27 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AM7UH UT WOS:000340073700002 PM 25037288 ER PT J AU Wang, LY Borisovskaya, A Maxwell, AL Pascualy, M AF Wang, Lucy Y. Borisovskaya, Anna Maxwell, Andrea L. Pascualy, Marcella TI Common Psychiatric Problems in Cognitively Impaired Older Patients Causes and Management SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Dementia; Behavioral and psychological symptoms; Agitation; Depression; Psychosis; Anxiety ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED-TRIAL; NURSING-HOME RESIDENTS; SEVERE ALZHEIMERS-DISEASE; PSYCHOLOGICAL SYMPTOMS; DOUBLE-BLIND; NEUROPSYCHIATRIC SYMPTOMS; BEHAVIORAL SYMPTOMS; ATYPICAL ANTIPSYCHOTICS; GENERALIZED ANXIETY AB Although dementias are defined by their cognitive and functional deficits, psychiatric problems are common, contribute to patient distress and burden, and precipitate institutionalization. Successful treatment involves understanding that physiologic, psychological, and environmental factors can contribute to the development of these symptoms. By carefully assessing each of these factors, clinicians can individualize treatment and flexibly use nonpharmacologic and pharmacologic approaches tailored to patients and the context of care. Although there exist limitations to many treatment options, clinicians can still adapt current knowledge to develop a multifaceted treatment approach that improves the quality of life for patients and their caregivers. C1 [Wang, Lucy Y.; Borisovskaya, Anna; Maxwell, Andrea L.; Pascualy, Marcella] VA Puget Sound Healthcare Syst, Mental Hlth Serv, Seattle, WA 98108 USA. [Wang, Lucy Y.; Borisovskaya, Anna; Maxwell, Andrea L.; Pascualy, Marcella] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. RP Wang, LY (reprint author), VA Puget Sound Healthcare Syst, Mental Hlth Serv, 1660 South Columbian Way,S-116, Seattle, WA 98108 USA. EM lucy.wang@va.gov FU VA Clinical Science Research and Development (CSR&D) Career Development Award Program [3125]; VA Puget Sound Health Care System, Seattle, Washington FX This work is supported by resources from the VA Puget Sound Health Care System, Seattle, Washington. Dr. Wang is supported by the VA Clinical Science Research and Development (CSR&D) Career Development Award Program (Project ID: 3125). NR 105 TC 3 Z9 3 U1 2 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2014 VL 30 IS 3 BP 443 EP + DI 10.1016/j.cger.2014.04.002 PG 26 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AM7UH UT WOS:000340073700004 PM 25037290 ER PT J AU Merel, S DeMers, S Vig, E AF Merel, Susan DeMers, Shaune Vig, Elizabeth TI Palliative Care in Advanced Dementia SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Dementia; Palliative care; End-of-life care; Cognitive impairment; Skilled nursing facilities; Advance directives ID NURSING-HOME RESIDENTS; OF-LIFE CARE; PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; SURROGATE DECISION-MAKERS; PLACEBO-CONTROLLED TRIAL; FEEDING-TUBE INSERTION; NEUROPSYCHIATRIC SYMPTOMS; ALZHEIMER-DISEASE; HOSPICE CARE; MEDICATION USE AB Because neurodegenerative dementias are progressive and ultimately fatal, a palliative approach focusing on comfort, quality of life, and family support can have benefits for patients, families, and the health system. Elements of a palliative approach include discussion of prognosis and goals of care, completion of advance directives, and a thoughtful approach to common complications of advanced dementia. Physicians caring for patients with dementia should formulate a plan for end-of-life care in partnership with patients, families, and caregivers, and be prepared to manage common symptoms at the end of life in dementia, including pain and delirium. C1 [Merel, Susan] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. [DeMers, Shaune] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Vig, Elizabeth] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Vig, Elizabeth] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Merel, S (reprint author), Univ Washington, Dept Med, Div Gen Internal Med, 1959 NE Pacific St,Box 356429, Seattle, WA 98195 USA. EM smerel@uw.edu NR 114 TC 2 Z9 2 U1 9 U2 34 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2014 VL 30 IS 3 BP 469 EP + DI 10.1016/j.cger.2014.04.004 PG 25 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AM7UH UT WOS:000340073700005 PM 25037291 ER PT J AU Inampudi, C Parvataneni, S Morgan, CJ Deedwania, P Fonarow, GC Prabhu, SD Butler, J Zile, MR Aronow, WS Sanders, PW Allman, RM Ahmed, A AF Inampudi, Chakradhari Parvataneni, Sridivya Morgan, Charity J. Deedwania, Prakash Fonarow, Gregg C. Prabhu, Sumanth D. Butler, Javed Zile, Michael R. Aronow, Wilbert S. Sanders, Paul W. Allman, Richard M. Ahmed, Ali TI Lack of Association Between Spironolactone Use and 30-Day All-Cause Readmission In Hospitalized Medicare Beneficiaries With Systolic Heart Failure Eligible for Spironolactone Therapy SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the Heart-Failure-Society-of-America (HFSA) CY SEP 14-17, 2014 CL Las Vegas, NV SP Heart Failure Soc Amer C1 [Inampudi, Chakradhari] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Parvataneni, Sridivya; Morgan, Charity J.; Prabhu, Sumanth D.; Sanders, Paul W.; Ahmed, Ali] Univ Alabama Birmingham, Birmingham, AL USA. [Deedwania, Prakash] Univ Calif San Francisco, Fresno, CA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Prabhu, Sumanth D.; Ahmed, Ali] Birmingham VA Med Ctr, Birmingham, AL USA. [Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Aronow, Wilbert S.] Westchester Cty Med Ctr, Valhalla, NY 10595 USA. [Allman, Richard M.] Dept Vet Affairs Geriatr & Extended Care Serv, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2014 VL 20 IS 8 SU S MA 141 BP S58 EP S58 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AM9PS UT WOS:000340214100140 ER PT J AU Zamani, P Rawat, D Kumar, PS Geraci, S Bhuva, R Konda, P Doulias, PT Ischiropoulos, H Chirinos, JA AF Zamani, Payman Rawat, Deepa Kumar, Prithvi Shiva Geraci, Sam Bhuva, Rushik Konda, Prasad Doulias, Paschalis-Thomas Ischiropoulos, Harry Chirinos, Julio A. TI Inorganic Nitrate Supplementation Improves Exercise Capacity in Subjects with HF with Preserved EF - A Pilot Study SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the Heart-Failure-Society-of-America (HFSA) CY SEP 14-17, 2014 CL Las Vegas, NV SP Heart Failure Soc Amer C1 [Zamani, Payman; Kumar, Prithvi Shiva; Konda, Prasad; Chirinos, Julio A.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Rawat, Deepa; Kumar, Prithvi Shiva; Geraci, Sam; Bhuva, Rushik; Chirinos, Julio A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Doulias, Paschalis-Thomas; Ischiropoulos, Harry] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA. NR 0 TC 2 Z9 2 U1 1 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2014 VL 20 IS 8 SU S MA 009 BP S4 EP S4 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AM9PS UT WOS:000340214100010 ER PT J AU Fung, SJ Chase, MH AF Fung, Simon J. Chase, Michael H. TI Control of hypoglossal motoneurones during naturally occurring sleep and wakefulness in the intact, unanaesthetized cat: a field potential study SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE atonia; excitability; genioglossus; obstructive sleep apnea; rapid eye movement sleep; sleep-disordered breathing ID REM-SLEEP; GENIOGLOSSUS MUSCLE; MOTO-NEURONS; WAKE STATES; NUCLEUS; MICRODIALYSIS; EXCITABILITY; INHIBITION; ATONIA; APNEA AB The present electrophysiological study was designed to determine the discharge threshold of hypoglossal motoneurones during naturally occurring states of sleep and wakefulness in the intact, unanaesthetized cat. The antidromic field potential, which reflects the net level of membrane excitability of motoneurones and therefore their discharge threshold, was recorded in the hypoglossal nucleus following stimulation of the hypoglossal nerve. The amplitude of the antidromic field potential was larger during wakefulness and non-rapid eye movement (NREM) sleep compared with REM sleep. There was no significant difference in the amplitude of the field potential when wakefulness was compared with NREM sleep (P = 0.103, df = 3, t = 2.324). However, there was a 46% reduction in amplitude during REM sleep compared with NREM sleep (P < 0.001, df = 10, t = 6.421) or wakefulness (P < 0.01, df = 4, t = -4.598). These findings indicate that whereas the excitability of motoneurones that comprise the hypoglossal motor pool is relatively constant during wakefulness and NREM sleep, their excitability is significantly reduced during REM sleep. This state-dependent pattern of control of hypoglossal motoneurones during REM sleep is similar to that reported for motoneurones in other motor nuclei at all levels of the neuraxis. The decrease in the evoked response of hypoglossal motoneurones, which reflects a significant increase in the discharge threshold of individual motoneurones, results in atonia of the lingual and related muscles during REM sleep. C1 [Fung, Simon J.; Chase, Michael H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fung, Simon J.; Chase, Michael H.] WebSci Int, Los Angeles, CA 90024 USA. [Chase, Michael H.] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. RP Fung, SJ (reprint author), WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90024 USA. EM sfung@websciences.org FU [1\01BX00819]; [TGS-109219]; [1R01HL116845] FX We are grateful to Francisco Morales, Jack Yamuy, MingChu Xi and Pablo Torterolo for their collaborative support in successfully developing the intact, unanaesthetized cat preparation employed in the present study. We are also indebted to Peter Soja and Ron Harper for their advice with respect to the fabrication of the cuff electrode for the hypoglossal nerve implant. We also thank Ida Shakhverdyan, Pandi Perumal, Naira Manukian, Andrui Nazarian and Reza Khorsan for their excellent technical assistance. This work was supported by grants 1 vertical bar 01BX00819, TGS-109219 and 1R01HL116845. NR 40 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD AUG PY 2014 VL 23 IS 4 BP 469 EP 474 DI 10.1111/jsr.12137 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN0EL UT WOS:000340256000014 PM 24605864 ER PT J AU Wong, ES Hebert, PL Maciejewski, ML Perkins, M Bryson, CL Au, DH Liu, CF AF Wong, Edwin S. Hebert, Paul L. Maciejewski, Matthew L. Perkins, Mark Bryson, Chris L. Au, David H. Liu, Chuan-Fen TI Does Favorable Selection Among Medicare Advantage Enrollees Affect Measurement of Hospital Readmission Rates? SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE Veterans; Medicare; readmission; risk adjustment; selection bias ID AFFAIRS HEALTH-CARE; SAMPLE SELECTION; HEART-FAILURE; VETERANS-AFFAIRS; ENROLLMENT; HMOS; PROGRAM; PLANS; BIAS; DISENROLLMENT AB Literature indicates favorable selection among Medicare Advantage (MA) enrollees compared with fee-for-service (FFS) enrollees. This study examined whether favorable selection into MA affected readmission rates among Medicare-eligible veterans following hospitalization for congestive heart failure in the Veterans Affairs Health System (VA). We measured total (VA + Medicare FFS) 30-day all-cause readmission rates across hospitals and all of VA. We used Heckman's correction to adjust readmission rates to be representative of all Medicare-eligible veterans, not just FFS-enrolled veterans. The adjusted all-cause readmission rate among FFS veterans was 27.1% (95% confidence interval [CI] = 26.5% to 27.7%), while the adjusted readmission rate among Medicare-eligible veterans was 25.3% (95% CI = 23.6% to 27.1%) after correcting for favorable selection. Readmission rate estimates among FFS veterans generalize to all Medicare-eligible veterans only after accounting for favorable selection into MA. Estimation of quality metrics should carefully consider sample selection to produce valid policy inferences. C1 [Wong, Edwin S.; Hebert, Paul L.; Perkins, Mark; Bryson, Chris L.; Au, David H.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Wong, Edwin S.; Hebert, Paul L.; Bryson, Chris L.; Au, David H.; Liu, Chuan-Fen] Univ Washington, Seattle, WA 98195 USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Durham, NC USA. RP Wong, ES (reprint author), Ctr Innovat Vet Ctr & Value Driven Care, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM edwin.wong@va.gov FU Health Services Research and Development (HSR&D) Service, Office of Research and Development, Department of Veterans Affairs [IIR 09-354]; VA HSR&D Career Development Award [CDA 13-024] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Health Services Research and Development (HSR&D) Service, Office of Research and Development, Department of Veterans Affairs, IIR 09-354. Dr. Wong is supported by a VA HSR&D Career Development Award (CDA 13-024). Dr. Maciejewski is a VA Research Career Scientist (RCS 10-391). NR 30 TC 1 Z9 1 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 EI 1552-6801 J9 MED CARE RES REV JI Med. Care Res. Rev. PD AUG PY 2014 VL 71 IS 4 BP 367 EP 383 DI 10.1177/1077558714533823 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AM8IA UT WOS:000340115600004 PM 24811933 ER PT J AU Egede, LE Gebregziabher, M Zhao, YM Dismuke, CE Walker, RJ Hunt, KJ Axon, RN AF Egede, Leonard E. Gebregziabher, Mulugeta Zhao, Yumin Dismuke, Clara E. Walker, Rebekah J. Hunt, Kelly J. Axon, R. Neal TI Impact of Mental Health Visits on Healthcare Cost in Patients with Diabetes and Comorbid Mental Health Disorders SO PLOS ONE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED-TRIAL; PSYCHOLOGICAL DISTRESS; MEDICAL-CARE; VETERANS; INDIVIDUALS; DEPRESSION; OUTCOMES; TELEPSYCHIATRY; MANAGEMENT AB Purpose: To assess the impact of mental health visits (MHV) on the cost of care for Veterans with diabetes and comorbid mental health conditions. Methods: A national cohort of 120,852 Veterans with diabetes and at least one mental health diagnosis (i.e., substance abuse, depression or psychoses) in 2002 was followed through 2006. Outcomes were pharmacy, inpatient and outpatient costs in 2012 dollars. Results: Least-square covariate adjusted estimates from the joint model of total VA costs of the number of MHV using December 31, 2012 value dollars indicate that relative to those with fewer MHV, those with 3+ MHV had the lowest mean inpatient cost ($21,406), but the highest mean outpatient and pharmacy cost ($9,727 and $2,015, respectively). If all Veterans who received zero MHV actually received 3+ MHV, we estimate through simulated scenarios that between $32,272,329 and $181,460,247 in inpatient costs would be saved. However, these savings would be offset by additional expenditures of between $1,166,017,547 and $1,166,224,787 in outpatient costs and between $151,604,683 and $161,439,632 in pharmacy costs. Conclusions: Among Veterans with diabetes and comorbid mental disorders having three or more mental health visits is associated with marginally decreased inpatient cost, but these potential savings seem to be offset by increased outpatient and pharmacy costs. C1 [Gebregziabher, Mulugeta; Zhao, Yumin; Dismuke, Clara E.; Walker, Rebekah J.; Hunt, Kelly J.; Axon, R. Neal] Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equity & Rural Outreach Innovat Ctr, Charleston, SC USA. [Egede, Leonard E.; Zhao, Yumin; Dismuke, Clara E.; Walker, Rebekah J.; Axon, R. Neal] Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta; Hunt, Kelly J.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU VHA Health Services Research and Development (HSRD) program [IIR-06-219] FX This study was supported by grant #IIR-06-219 funded by the VHA Health Services Research and Development (HSR&D) program. The funding agency did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 26 TC 3 Z9 3 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 1 PY 2014 VL 9 IS 8 AR e103804 DI 10.1371/journal.pone.0103804 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AM4JL UT WOS:000339819800081 PM 25083903 ER PT J AU Ikeda, AJ Grabowski, AM Lindsley, A Sadeghi-Demneh, E Reisinger, KD AF Ikeda, Andrea J. Grabowski, Alena M. Lindsley, Alida Sadeghi-Demneh, Ebrahim Reisinger, Kim D. TI A scoping literature review of the provision of orthoses and prostheses in resource-limited environments 2000-2010. Part one: Considerations for success SO PROSTHETICS AND ORTHOTICS INTERNATIONAL LA English DT Review DE Orthotics; prosthetics; developing countries; developing world; low-income countries ID TRANS-TIBIAL AMPUTEES; CIR CASTING SYSTEM; PONSETI METHOD; DEVELOPING-WORLD; TRANSTIBIAL PROSTHESES; CLUBFOOT DEFORMITY; SOCKETS; FOOT; LIMB; STRENGTH AB Study Design: Literature Review Background: We estimate that over 29 million people worldwide in resource-limited environments (RLEs) are in need of orthotic and prosthetic (O&P) devices and services. Objectives: Our goal was to ascertain the current state of O&P provision in RLEs and identify factors that may lead to more successful O&P provision. Methods: We conducted a comprehensive scoping literature review of all information related to O&P provision in RLEs published from 2000 to 2010. We targeted Vietnam, Cambodia, Tanzania, Malawi, Colombia, and the Navajo Nation, but also included information about developing countries in general. We searched academic databases and grey literature. We extracted information from each article in the areas of design, manufacturing, distribution, service provision, and technology transfer. Results: We identified commonly reported considerations and strategies for O&P provision from 431 articles. Analysis of expert consensus documents revealed recurring themes for improving O&P provision. We found that some suggestions from the consensus documents are being followed, but many are overlooked or have not yet been implemented. Conclusions: Areas for improvement include conducting field testing during the design process, providing services to rural environments, offering follow-up services, considering government collaboration, and encouraging an active role of the orthosis/prosthesis user. Outcomes and research studies will be further discussed in Part Two. C1 [Ikeda, Andrea J.; Lindsley, Alida; Reisinger, Kim D.] San Francisco State Univ, Whirlwind Wheelchair Int, San Francisco, CA 94132 USA. [Grabowski, Alena M.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. [Sadeghi-Demneh, Ebrahim] Isfahan Univ Med Sci, Orthot & Prosthet Dept, Musculoskeletal Res Ctr, Esfahan, Iran. US Dept Vet Affairs, Eastern Colorado Healthcare Syst, Denver, CO USA. RP Ikeda, AJ (reprint author), San Francisco State Univ, Whirlwind Wheelchair Int, 1600 Holloway Ave,SCI 251, San Francisco, CA 94132 USA. EM andrea@whirlwindwheelchair.org RI Sadeghi-Demenh, Ebrahim/E-8110-2012 OI Sadeghi-Demenh, Ebrahim/0000-0003-0590-8512; GRABOWSKI, ALENA/0000-0002-4432-618X FU U.S. Department of Education, National Institute on Disability and Rehabilitation Research [H133A090020] FX This work was supported by the U.S. Department of Education, National Institute on Disability and Rehabilitation Research [grant number H133A090020]. NR 137 TC 0 Z9 0 U1 2 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0309-3646 EI 1746-1553 J9 PROSTHET ORTHOT INT JI Prosthet. Orthot. Int. PD AUG PY 2014 VL 38 IS 4 BP 269 EP 286 DI 10.1177/0309364613500690 PG 18 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA AM8WM UT WOS:000340159500001 PM 24026045 ER PT J AU Kaatz, A Gutierrez, B Carnes, M AF Kaatz, Anna Gutierrez, Belinda Carnes, Molly TI Threats to objectivity in peer review: the case of gender SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Editorial Material ID SHIFTING STANDARDS; PUBLICATION; STEREOTYPES; BIAS C1 [Kaatz, Anna; Gutierrez, Belinda; Carnes, Molly] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Gutierrez, Belinda; Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Carnes, Molly] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Med, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Psychiat, Madison, WI 53715 USA. RP Carnes, M (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. EM mlcarnes@wisc.edu FU NIGMS NIH HHS [R01 GM111002] NR 17 TC 11 Z9 11 U1 1 U2 15 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD AUG PY 2014 VL 35 IS 8 BP 371 EP 373 DI 10.1016/j.tips.2014.06.005 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AN1KQ UT WOS:000340341600002 PM 25086743 ER PT J AU Smucny, J Wylie, KP Tregellas, JR AF Smucny, Jason Wylie, Korey P. Tregellas, Jason R. TI Functional magnetic resonance imaging of intrinsic brain networks for translational drug discovery SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review DE biomarker; connectivity; graph theory; neuroimaging; resting state; schizophrenia ID RESTING-STATE NETWORKS; DEFAULT-MODE NETWORK; BOLD HEMODYNAMIC-RESPONSES; SMALL-WORLD NETWORKS; SCHIZOPHRENIA; CONNECTIVITY; FMRI; ARCHITECTURE; MODULATION; SYSTEMS AB Developing translational biomarkers is a priority for psychiatry research. Task-independent functional brain imaging is a relatively novel technique that allows examination of the brain's intrinsic networks, defined as functionally and (often) structurally connected populations of neurons whose properties reflect fundamental neurobiological organizational principles of the central nervous system. The ability to study the activity and organization of these networks has opened a promising new avenue for translational investigation, because they can be analogously examined across species and disease states. Interestingly, imaging studies have revealed shared spatial and functional characteristics of the intrinsic network architecture of the brain across species, including mice, rats, non-human primates, and humans. Using schizophrenia as an example, we show how intrinsic networks may show similar abnormalities in human diseases and animal models of these diseases, supporting their use as biomarkers in drug development. C1 [Smucny, Jason; Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. [Smucny, Jason; Wylie, Korey P.; Tregellas, Jason R.] Univ Colorado, Dept Psychiat, Aurora, CO USA. [Smucny, Jason; Tregellas, Jason R.] Univ Colorado, Neurosci Program, Aurora, CO USA. RP Tregellas, JR (reprint author), Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. EM Jason.tregellas@ucdenver.edu RI Tregellas, Jason/J-3637-2015 OI Smucny, Jason/0000-0001-5656-7987 FU NIMH NIH HHS [F31 MH102879] NR 64 TC 23 Z9 23 U1 1 U2 15 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD AUG PY 2014 VL 35 IS 8 BP 397 EP 403 DI 10.1016/j.tips.2014.05.001 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AN1KQ UT WOS:000340341600005 PM 24906509 ER PT J AU Yehuda, R Daskalakis, NP Lehrner, A Desarnaud, F Bader, HN Makotkine, I Flory, JD Bierer, LM Meaney, MJ AF Yehuda, Rachel Daskalakis, Nikolaos P. Lehrner, Amy Desarnaud, Frank Bader, Heather N. Makotkine, Iouri Flory, Janine D. Bierer, Linda M. Meaney, Michael J. TI Influences of Maternal and Paternal PTSD on Epigenetic Regulation of the Glucocorticoid Receptor Gene in Holocaust Survivor Offspring SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PARENTAL PTSD; CHILDHOOD; METHYLATION; DEPRESSION; TRAUMA; MALTREATMENT; VALIDATION; RESPONSES; EXPOSURE AB Objective: Differential effects of maternal and paternal posttraumatic stress disorder (PTSD) have been observed in adult offspring of Holocaust survivors in both glucocorticoid receptor sensitivity and vulnerability to psychiatric disorder. The authors examined the relative influences of maternal and paternal PTSD on DNA methylation of the exon 1(F) promoter of the glucocorticoid receptor (GR-1(F)) gene (NR3C1) in peripheral blood mononuclear cells and its relationship to glucocorticoid receptor sensitivity in Holocaust offspring. Method: Adult offspring with at least one Holocaust survivor parent (N=80) and demographically similar participants without parental Holocaust exposure or parental PTSD (N=15) completed clinical interviews, self-report measures, and biological procedures. Blood samples were collected for analysis of GR-1(F) promoter methylation and of cortisol levels in response to low-dose dexamethasone, and two-way analysis of covariance was performed using maternal and paternal PTSD as main effects. Hierarchical clustering analysis was used to permit visualization of maternal compared with paternal PTSD effects on clinical variables and GR-1(F). promoter methylation. Results: A significant interaction demonstrated that in the absence of maternal PTSD, offspring with paternal PTSD showed higher GR-1(F) promoter methylation, whereas offspring with both maternal and paternal PTSD showed lower methylation. Lower GR-1(F) promoter methylation was significantly associated with greater post-dexamethasone cortisol suppression. The clustering analysis revealed that maternal and paternal PTSD effects were differentially associated with clinical indicators and GR-1(F) promoter methylation. Conclusions: This is the first study to demonstrate alterations of GR-1(F) promoter methylation in relation to parental PTSD and neuroendocrine outcomes. The moderation of paternal PTSD effects by maternal PTSD suggests different mechanisms for the intergenerational transmission of trauma-related vulnerabilities. C1 [Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. McGill Univ, Douglas Mental Hlth Univ Inst, Ludmer Ctr Neuroinformat & Mental Hlth, Montreal, PQ, Canada. Agcy Sci Technol & Res, Singapore Inst Clin Sci, Singapore, Singapore. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. EM rachel.yehuda@va.gov RI Daskalakis, Nikolaos/B-7930-2014 OI Daskalakis, Nikolaos/0000-0003-1660-9112 FU NIMH [1RC1MH088101-01]; National Center for Advancing Translational Sciences (NCATS), a component of NIH [UL1TR000067] FX Supported by a grant from NIMH (1RC1MH088101-01) and by grant UL1TR000067 from the National Center for Advancing Translational Sciences (NCATS), a component of NIH. NIMH, NIH, and NCATS had no role in the study design, in the collection, analysis, and interpretation of the data, in writing the study, or in the decision to submit the study for publication. NR 40 TC 74 Z9 76 U1 11 U2 65 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2014 VL 171 IS 8 BP 872 EP 880 DI 10.1176/appi.ajp.2014.13121571 PG 9 WC Psychiatry SC Psychiatry GA AM6QE UT WOS:000339988900013 PM 24832930 ER PT J AU Elvington, M Blichmann, P Qiao, F Scheiber, M Wadsworth, C Luzinov, I Lucero, J Vertegel, A Tomlinson, S AF Elvington, M. Blichmann, P. Qiao, F. Scheiber, M. Wadsworth, C. Luzinov, I. Lucero, J. Vertegel, A. Tomlinson, S. TI A novel protocol allowing oral delivery of a protein complement inhibitor that subsequently targets to inflamed colon mucosa and ameliorates murine colitis SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE colitis; complement; mouse model; oral delivery ID INFLAMMATORY-BOWEL-DISEASE; SODIUM-INDUCED COLITIS; DECAY-ACCELERATING FACTOR; DEXTRAN ESTER PRODRUGS; ULCERATIVE-COLITIS; CROHNS-DISEASE; GI TRACT; ACTIVATION; EXPRESSION; EPITHELIUM AB While there is evidence of a pathogenic role for complement in inflammatory bowel disease, there is also evidence for a protective role that relates to host defence and protection from endotoxaemia. There is thus concern regarding the use of systemic complement inhibition as a therapeutic strategy. Local delivery of a complement inhibitor to the colon by oral administration would ameliorate such concerns, but while formulations exist for oral delivery of low molecular weight drugs to the colon, they have not been used successfully for oral delivery of proteins. We describe a novel pellet formulation consisting of cross-linked dextran coated with an acrylic co-polymer that protects the complement inhibitor CR2-Crry from destruction in the gastrointestinal tract. CR2-Crry containing pellets administered by gavage, were characterized using a therapeutic protocol in a mouse model of dextran sulphate sodium (DSS)-induced colitis. Oral treatment of established colitis over a 5-day period significantly reduced mucosal inflammation and injury, with similar therapeutic benefit whether or not the proton pump inhibitor, omeprazole, was co-administered. Reduction in injury was associated with the targeting of CR2-Crry to the mucosal surface and reduced local complement activation. Treatment had no effect on systemic complement activity. This novel method for oral delivery of a targeted protein complement inhibitor will reduce systemic effects, thereby decreasing the risk of opportunistic infection, as well as lowering the required dose and treatment cost and improving patient compliance. Furthermore, the novel delivery system described here may provide similar benefits for administration of other protein-based drugs, such as anti-tumour necrosis factor-a antibodies. C1 [Elvington, M.; Qiao, F.; Scheiber, M.; Wadsworth, C.; Tomlinson, S.] Med Univ S Carolina, Dept Microbiol & Immunol, Darby Childrens Res Inst, Charleston, SC 29425 USA. [Tomlinson, S.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Blichmann, P.; Lucero, J.; Vertegel, A.] Clemson Univ, Dept Bioengn, Clemson, SC USA. [Luzinov, I.] Clemson Univ, Dept Mat Sci & Engn, Clemson, SC USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU Crohn's and Colitis Foundation of America FX This work was supported by the Crohn's and Colitis Foundation of America. NR 30 TC 2 Z9 2 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD AUG PY 2014 VL 177 IS 2 BP 500 EP 508 DI 10.1111/cei.12350 PG 9 WC Immunology SC Immunology GA AL9SI UT WOS:000339480700014 PM 24730624 ER PT J AU Deyo, RA Dworkin, SF Amtmann, D Andersson, G Borenstein, D Carragee, E Carrino, J Chou, R Cook, K DeLitto, A Goertz, C Khalsa, P Loeser, J Mackey, S Panagis, J Rainville, J Tosteson, T Turk, D Von Korff, M Weiner, DK AF Deyo, Richard A. Dworkin, Samuel F. Amtmann, Dagmar Andersson, Gunnar Borenstein, David Carragee, Eugene Carrino, John Chou, Roger Cook, Karon DeLitto, Anthony Goertz, Christine Khalsa, Partap Loeser, John Mackey, Sean Panagis, James Rainville, James Tosteson, Tor Turk, Dennis Von Korff, Michael Weiner, Debra K. TI Focus Article Report of the NIH Task Force on Research Standards for Chronic Low Back Pain SO CLINICAL JOURNAL OF PAIN LA English DT Article DE low back pain; chronic low back pain; research standards; minimum dataset; NIH Task Force ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM PROMIS; FUNCTION ITEM BANK; QUALITY-OF-LIFE; PRIMARY-CARE; PROGNOSTIC APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES AB Background: Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Methods: The NIH Pain Consortium therefore charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. Results: The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimum dataset to describe research participants (drawing heavily on the PROMIS methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. Conclusions: The RTF believes these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect that the RTF recommendations will become a dynamic document and undergo continual improvement. C1 [Deyo, Richard A.; Chou, Roger] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Dworkin, Samuel F.; Amtmann, Dagmar; Loeser, John; Turk, Dennis] Univ Washington, Seattle, WA 98195 USA. [Andersson, Gunnar] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Borenstein, David] George Washington Univ, Washington, DC USA. [Carragee, Eugene; Mackey, Sean] Stanford Univ, Stanford, CA 94305 USA. [Carrino, John] Johns Hopkins Univ, Baltimore, MD USA. [Cook, Karon] Northwestern Univ, Evanston, IL USA. [DeLitto, Anthony; Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [DeLitto, Anthony; Weiner, Debra K.] Univ Pittsburgh, Pittsburgh, PA USA. [Goertz, Christine] Palmer Coll Chiropract, Davenport, IA USA. [Khalsa, Partap] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Panagis, James] NIAMSD, Bethesda, MD 20892 USA. [Rainville, James] New England Baptist Hosp, Roxbury Crossing, MA USA. [Tosteson, Tor] Dartmouth Coll, Hanover, NH USA. [Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code FM, Portland, OR 97239 USA. EM deyor@ohsu.edu FU National Center for Complementary and Alternative Medicine; National Institute for Arthritis, Musculoskeletal, and Skin Diseases FX This study was supported by the National Center for Complementary and Alternative Medicine and the National Institute for Arthritis, Musculoskeletal, and Skin Diseases. The authors declare no conflict of interest. NR 124 TC 4 Z9 5 U1 9 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0749-8047 EI 1536-5409 J9 CLIN J PAIN JI Clin. J. Pain PD AUG PY 2014 VL 30 IS 8 BP 701 EP 712 PG 12 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA AM2DI UT WOS:000339658900008 PM 24988192 ER PT J AU Cameron, MH Bethoux, F Davis, N Frederick, M AF Cameron, Michelle H. Bethoux, Francois Davis, Nina Frederick, Meredith TI Botulinum Toxin for Symptomatic Therapy in Multiple Sclerosis SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Multiple sclerosis; Spasticity; Botulinum toxin; Tremor; Incontinence ID NEUROGENIC DETRUSOR OVERACTIVITY; URINARY-INCONTINENCE; CONTROLLED-TRIAL; DOUBLE-BLIND; A TOXIN; SPASTICITY; INJECTIONS; TREMOR; ONABOTULINUMTOXINA; NEUROTOXIN AB Botulinumtoxin (BT) is a neurotoxin that paralyzes muscles by inhibiting release of acetylcholine from presynaptic vesicles at the neuromuscular junction. In people with multiple sclerosis (MS), clinical experience and research studies show that local injection of minute quantities of BT can temporarily control skeletal muscle spasticity, bladder detrusor hyperreflexia, and tremor. Specifically, BT injections have been shown to reduce muscle tone and improve passive function, and possibly improve active function, in patients with spasticity. Injection of BT into the bladder wall is a uniquely effective, safe, and durable treatment in patients with neurogenic detrusor hyperreflexia due to MS who have insufficient response or who do not tolerate oral antimuscarinic medications. This procedure has markedly reduced the need for indwelling catheters and bladder surgery. In addition, a recent study suggests BT may be effective for select patients with MS-associated upper extremity tremor. Appropriate use of BT can improve quality of life for many patients with MS. C1 [Cameron, Michelle H.; Frederick, Meredith] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Cameron, Michelle H.; Davis, Nina; Frederick, Meredith] Portland VA Med Ctr, Portland, OR USA. [Bethoux, Francois] Cleveland Clin, Mellen Ctr MS Treatment & Res, Cleveland, OH 44195 USA. [Davis, Nina] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR 97201 USA. RP Cameron, MH (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,L226, Portland, OR 97201 USA. EM cameromi@ohsu.edu; bethouf@ccf.org; davisni@ohsu.edu; frederim@ohsu.edu FU Concert Pharmaceuticals; Merz Pharma; Medtronic; GW Pharma; Allergan for development of educational presentations; Astellas Pharmaceuticals for development of educational presentations FX Francois Bethoux has received consultancy fees from Concert Pharmaceuticals, Merz Pharma, Medtronic, and GW Pharma, along with grants from Merz Pharma and Medtronic. He has also received payments from Allergan for development of educational presentations.; Nina Davis has received payments from Astellas Pharmaceuticals for development of educational presentations. NR 33 TC 4 Z9 4 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 EI 1534-6293 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD AUG PY 2014 VL 14 IS 8 AR 463 DI 10.1007/s11910-014-0463-7 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AM3EB UT WOS:000339734100011 PM 24952479 ER PT J AU Cristancho, MA Thase, ME AF Cristancho, Mario A. Thase, Michael E. TI Drug safety evaluation of olanzapine/fluoxetine combination SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE bipolar depression; olanzapine-fluoxetine combination; safety and tolerability; treatment-resistant depression ID TREATMENT-RESISTANT DEPRESSION; BIPOLAR-I DEPRESSION; DOUBLE-BLIND; RANDOMIZED-TRIALS; BINDING PROFILE; OPEN-LABEL; FLUOXETINE; OLANZAPINE; DISORDER; MONOTHERAPY AB Introduction: Bipolar disorder and treatment-resistant depression (TRD) are common and recurrent conditions associated with significant disability, morbidity and mortality. Despite the clear need for effective treatments, only a few medications have been approved in the US for these indications. The combined formulation of olanzapine-fluoxetine (OFC) has been available for a decade now, thus a review on its safety profile and comparative efficacy is timely and can help clinicians to determine the benefit/risk profile of OFC within the context of other treatment alternatives. Areas covered: This paper summarizes the rationale and evidence supporting the use of OFC for both bipolar I depressive episodes and TRD with a focus on safety and tolerability. Product labels and the search engine PubMed was used to obtain relevant information on this subject. Expert opinion: Although further comparative studies are needed, the literature confirms that the OFC is an effective treatment for bipolar I depressive episodes, as well as major depressive episodes that have not responded to several adequate courses of antidepressant therapy. Its use as a first-line treatment for bipolar I depressive episodes and at a higher rung of algorithms for patients with TRD is limited by its propensity to cause weight gain and associated metabolic symptoms. C1 [Cristancho, Mario A.; Thase, Michael E.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. RP Thase, ME (reprint author), Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu FU Agency for Healthcare Research and Quality; Eli Lilly and Co.; Forest Pharmaceuticals; National Institute of Mental Health; Otsuka Pharmaceuticals FX M Thase has participated as an advisor/consultant for Alkermes, AstraZeneca, Bristol-Myerb Squibb, Eli Lilly & Co, Forest Laboratories (Incl PGx), Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, Janssen Pharmaceuticals, MedAvante, Inc., Merck and Co., Inc. (Incl Schering Plough and Organon), Neuronetics, Inc., Ortho-McNeil Pharmaceuticals (Incl Johnson & Johnson), Otsuka, Pfizer (Ind Wyeth Ayerst Pharmaceuticals, Roche, Shire US, Inc., Sunovion Pharmaceuticals, Inc., Takeda and Transcept Pharmaceuticals. He has received grant support from the Agency for Healthcare Research and Quality, Eli Lilly and Co., Forest Pharmaceuticals, the National Institute of Mental Health and Otsuka Pharmaceuticals. He has received honoraria for talks from AstraZeneca, Bristol-Myers Squibb Co., Eli Lilly & Co., Merck and Co., Inc., and Pfizer (Incl Wyeth Ayerst Pharmaceuticals). He has equity holdings in MedAvante, Inc. and has received royalties from the American Psychiatric Foundation, Guilford Publications, Herald House and W.W. Norton & Co., Inc. His spouse is employed by Peloton Advantage (formerly Advogent and Embryon) which does business with Pfizer/Wyeth. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 39 TC 2 Z9 2 U1 2 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 EI 1744-764X J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD AUG PY 2014 VL 13 IS 8 BP 1133 EP 1141 DI 10.1517/14740338.2014.933804 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AM4YM UT WOS:000339862100012 PM 24972823 ER PT J AU Ithapu, V Singh, V Lindner, C Austin, BP Hinrichs, C Carlsson, CM Bendlin, BB Johnson, SC AF Ithapu, Vamsi Singh, Vikas Lindner, Christopher Austin, Benjamin P. Hinrichs, Chris Carlsson, Cynthia M. Bendlin, Barbara B. Johnson, Sterling C. TI Extracting and Summarizing White Matter Hyperintensities Using Supervised Segmentation Methods in Alzheimer's Disease Risk and Aging Studies SO HUMAN BRAIN MAPPING LA English DT Article DE white matter hyperintensities; support vector machines; random forests; segmentation ID MILD COGNITIVE IMPAIRMENT; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; LESION SEGMENTATION; NATIONAL INSTITUTE; IMAGE SEGMENTATION; MR-IMAGES; DEMENTIA; VOLUME; RECOMMENDATIONS AB Precise detection and quantification of white matter hyperintensities (WMH) observed in T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Images (MRI) is of substantial interest in aging, and age-related neurological disorders such as Alzheimer's disease (AD). This is mainly because WMH may reflect co-morbid neural injury or cerebral vascular disease burden. WMH in the older population may be small, diffuse, and irregular in shape, and sufficiently heterogeneous within and across subjects. Here, we pose hyperintensity detection as a supervised inference problem and adapt two learning models, specifically, Support Vector Machines and Random Forests, for this task. Using texture features engineered by texton filter banks, we provide a suite of effective segmentation methods for this problem. Through extensive evaluations on healthy middle-aged and older adults who vary in AD risk, we show that our methods are reliable and robust in segmenting hyperintense regions. A measure of hyperintensity accumulation, referred to as normalized effective WMH volume, is shown to be associated with dementia in older adults and parental family history in cognitively normal subjects. We provide an open source library for hyperintensity detection and accumulation (interfaced with existing neuroimaging tools), that can be adapted for segmentation problems in other neuroimaging studies. (c) 2014 Wiley Periodicals, Inc. C1 [Ithapu, Vamsi; Singh, Vikas; Lindner, Christopher] Univ Wisconsin, Dept Comp Sci, Madison, WI 53706 USA. [Ithapu, Vamsi; Singh, Vikas; Austin, Benjamin P.; Carlsson, Cynthia M.; Bendlin, Barbara B.; Johnson, Sterling C.] Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Singh, Vikas] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Austin, Benjamin P.; Carlsson, Cynthia M.; Bendlin, Barbara B.; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Madison, WI USA. [Hinrichs, Chris] Univ Wisconsin, Dept Elect & Comp Engn, Madison, WI 53706 USA. [Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Ithapu, V (reprint author), 5765 Med Sci Ctr, 1300 Univ Ave, Madison, WI 53706 USA. EM ithapu@wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU NIH [R01 AG040396, R01 G021155]; NSF [RI 1116584]; Wisconsin Partnership Fund, University of Wisconsin ADRC [P50 AG033514]; University of Wisconsin ICTR [1UL1RR025011]; Veterans Administration Merit Review Grant [I01CX000165]; CIBM [2T15LM007359] FX Contract grant sponsor: NIH; Contract grant numbers: R01 AG040396 and R01 G021155); Contract grant sponsor: NSF; Contract grant number: RI 1116584; Contract grant sponsor: Wisconsin Partnership Fund, University of Wisconsin ADRC; Contract grant number: P50 AG033514; Contract grant sponsor: University of Wisconsin ICTR; Contract grant number: 1UL1RR025011; Contract grant sponsor: Veterans Administration Merit Review Grant; Contract grant number: I01CX000165; Contract grant sponsor: CIBM postdoctoral fellowship via grant NLM; Contract grant number: 2T15LM007359 (to C. H.). NR 49 TC 14 Z9 14 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD AUG PY 2014 VL 35 IS 8 BP 4219 EP 4235 DI 10.1002/hbm.22472 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AL8YV UT WOS:000339426700049 PM 24510744 ER PT J AU Cao, H Yu, F Zhao, Y Zhang, XX Tai, J Lee, J Darehzereshki, A Bersohn, M Lien, CL Chi, NC Tai, YC Hsiai, TK AF Cao, Hung Yu, Fei Zhao, Yu Zhang, Xiaoxiao Tai, Joyce Lee, Juhyun Darehzereshki, Ali Bersohn, Malcolm Lien, Ching-Ling Chi, Neil C. Tai, Yu-Chong Hsiai, Tzung K. TI Wearable multi-channel microelectrode membranes for elucidating electrophysiological phenotypes of injured myocardium SO INTEGRATIVE BIOLOGY LA English DT Article ID HEART REGENERATION; ZEBRAFISH HEART; APOPTOSIS AB Understanding the regenerative capacity of small vertebrate models has provided new insights into the plasticity of injured myocardium. Here, we demonstrate the application of flexible microelectrode arrays (MEAs) in elucidating electrophysiological phenotypes of zebrafish and neonatal mouse models of heart regeneration. The 4-electrode MEA membranes were designed to detect electrical signals in the aquatic environment. They were micro-fabricated to adhere to the non-planar body surface of zebrafish and neonatal mice. The acquired signals were processed to display an electrocardiogram (ECG) with high signal-to-noise-ratios, and were validated via the use of conventional micro-needle electrodes. The 4-channel MEA provided signal stability and spatial resolution, revealing the site-specific electrical injury currents such as ST-depression in response to ventricular cryo-injury. Thus, our polymer-based and wearable MEA membranes provided electrophysiological insights into long-term conduction phenotypes for small vertebral models of heart injury and regeneration with a translational implication for monitoring cardiac patients. C1 [Cao, Hung; Yu, Fei; Lee, Juhyun; Hsiai, Tzung K.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Cao, Hung; Lee, Juhyun; Bersohn, Malcolm; Hsiai, Tzung K.] Univ Calif Los Angeles, Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90073 USA. [Zhao, Yu; Zhang, Xiaoxiao; Tai, Yu-Chong] CALTECH, Dept Elect Engn, Pasadena, CA 91125 USA. [Tai, Joyce] Tufts Univ, Medford, MA 02155 USA. [Darehzereshki, Ali; Lien, Ching-Ling] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Chi, Neil C.] Univ Calif San Diego, Sch Med, Dept Med, Div Cardiol, La Jolla, CA 92093 USA. [Cao, Hung; Lee, Juhyun; Bersohn, Malcolm; Hsiai, Tzung K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Hsiai, TK (reprint author), Univ Calif Los Angeles, Henry Samueli Sch Engn & Appl Sci, David Geffen Sch Med, Dept Med Cardiol Bioengn & Physiol, Los Angeles, CA 90073 USA. EM THsiai@mednet.ucla.edu FU National Institutes of Health [HL-068689, HL-083015, HD069305-01, 1R01HL111437-01, R01HL096121-03] FX These studies were supported by National Institutes of Health HL-068689 (T.K.H), HL-083015 (T.K.H.), HD069305-01 (N.C.C., T.K.H.), 1R01HL111437-01 (T.K.H., N.C.C.), and R01HL096121-03 (C.L.L) NR 21 TC 5 Z9 5 U1 1 U2 21 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 EI 1757-9708 J9 INTEGR BIOL-UK JI Integr. Biol. PD AUG PY 2014 VL 6 IS 8 BP 789 EP 795 DI 10.1039/c4ib00052h PG 7 WC Cell Biology SC Cell Biology GA AM5WA UT WOS:000339930500006 PM 24945366 ER PT J AU Ullrich, PM Lavela, SL Evans, CT Miskevics, S Weaver, FM Goldstein, B AF Ullrich, Philip M. Lavela, Sherri L. Evans, Charlesnika T. Miskevics, Scott Weaver, Frances M. Goldstein, Barry TI Associations between perceptions of evidence and adoption of H1N1 influenza infection prevention strategies among healthcare workers providing care to persons with spinal cord injury SO JOURNAL OF ADVANCED NURSING LA English DT Article DE adherence; evidence; guideline implementation; influenza prevention; promoting action on research implementation in health services; nursing ID PARIHS FRAMEWORK; IMPLEMENTATION STRATEGIES; ORGANIZATIONAL READINESS; GUIDELINE DISSEMINATION; UNIVERSAL PRECAUTIONS; DECISION-MAKING; INFORMATION; VACCINATION; ATTITUDES; SERVICES AB Aim. To examine associations between perceptions of evidence (research evidence, clinical expertise, patient preferences) and outcomes of a nationwide programme to implement H1N1 influenza prevention guidelines. Background. Healthcare workers do not consistently adhere to recommended infection control practices and this may be associated with their perceptions of evidence sources. Design. Cross-sectional mailed survey. Method. A survey of healthcare workers was administered in August 2010 after implementation of H1N1 prevention guidelines. Outcomes of interest were ratings of adherence to H1N1 prevention guidelines. Findings. Respondents with complete data (N = 283) were included in analyses. Facility-level adherence to guidelines was associated with opinions of clinical experts. Healthcare workers who rated clinical expertise as aligning with recommendations also rated their facilities as being more adherent to guidelines. Perceptions of research evidence and patient preferences were not associated with facility adherence. Personal adherence was not associated with perceptions of evidence, except among those healthcare workers who rated both clinical experts and patients as unsupportive of guidelines; these practitioners were less likely to adhere to recommended personal hygiene practices. Conclusion. Efforts to implement guidelines might be most effective when capitalizing on the influence of clinical experts. To better explain variability in guideline adherence, inclusion of a broader array of variables is recommended for future studies. C1 [Ullrich, Philip M.] Spinal Cord Injury Qual Enhancement Res Initiat S, Seattle, WA 98108 USA. [Ullrich, Philip M.; Goldstein, Barry] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Lavela, Sherri L.; Evans, Charlesnika T.; Miskevics, Scott; Weaver, Frances M.] SCI QUERI, Hines, IL USA. [Lavela, Sherri L.; Evans, Charlesnika T.; Miskevics, Scott; Weaver, Frances M.] VA Hosp, Edward Hines Jr Dept Vet Affairs, Ctr Innovat Complex Chron Healthcare, Hines, IL USA. [Goldstein, Barry] SCI QUERI, Seattle, WA USA. RP Ullrich, PM (reprint author), Spinal Cord Injury Qual Enhancement Res Initiat S, Seattle, WA 98108 USA. EM philip.ullrich@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, Spinal Cord Injury Quality Enhancement Initiative (SCI QUERI) [RRP 10-046] FX This research was supported by a grant from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, Spinal Cord Injury Quality Enhancement Initiative (SCI QUERI, RRP 10-046). This paper presents the views of the authors; it does not necessarily represent the views or policies of the Department of Veterans Affairs or the Health Services Research and Development Service. NR 28 TC 0 Z9 0 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-2402 EI 1365-2648 J9 J ADV NURS JI J. Adv. Nurs. PD AUG PY 2014 VL 70 IS 8 BP 1793 EP 1800 DI 10.1111/jan.12336 PG 8 WC Nursing SC Nursing GA AL9VW UT WOS:000339492500011 PM 24341504 ER PT J AU Ather, S Iqbal, F Gulotta, J Aljaroudi, W Heo, J Iskandrian, AE Hage, FG AF Ather, Sameer Iqbal, Fahad Gulotta, John Aljaroudi, Wael Heo, Jaekyeong Iskandrian, Ami E. Hage, Fadi G. TI Comparison of three commercially available softwares for measuring left ventricular perfusion and function by gated SPECT myocardial perfusion imaging SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Myocardial perfusion imaging; single-photon emission-computed tomography; left ventricular ejection fraction; perfusion defect size ID EMISSION COMPUTED-TOMOGRAPHY; CORONARY-ARTERY-DISEASE; EJECTION FRACTION; NUCLEAR CARDIOLOGY; AUTOMATIC QUANTIFICATION; PACKAGES; DEFECTS; VALIDATION; 4D-MSPECT; ACCURACY AB The three softwares, Quantitative Perfusion SPECT (QPS), Emory Cardiac Toolbox, and 4 Dimension-Myocardial SPECT (4DM) are widely used with myocardial perfusion imaging (MPI) to determine perfusion defect size (PDS) and left ventricular (LV) function. There are limited data on the degree of agreement between these methods in quantifying the LV perfusion pattern and function. In 120 consecutive patients who had abnormal regadenoson SPECT MPI with a visually derived summed stress score a parts per thousand yen4, the correlation between the softwares for measurements of PDS, reversible, and fixed defects was poor to fair (Spearman's rho = 0.18-0.72). Overall, estimation of defect size was smaller by QPS and larger by 4DM. There was discordance among the softwares in 62% of the cases in defining PDS as small/moderate/large. The correlation between the softwares was better for measuring LVEF, volumes and mass (rho = 0.84-0.97), and discrepant results for defining normal/mild-moderate/severe LV systolic dysfunction were prevalent in 28% of the patients. There are significant differences between the softwares in measuring PDS as well as LV function, and more importantly in defining small, moderate, or large ischemic burden. These results suggest the necessity of using the same software when assessing interval changes by serial imaging. C1 [Ather, Sameer; Heo, Jaekyeong; Iskandrian, Ami E.; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Iqbal, Fahad] Univ Minnesota, Med Ctr, Div Cardiovasc Dis, Minneapolis, MN 55455 USA. [Gulotta, John] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Aljaroudi, Wael] Amer Univ Beirut, Beirut, Lebanon. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI ather, sameer/0000-0002-5579-0658; Hage, Fadi/0000-0002-1397-4942 FU Astellas Pharma USA FX Dr Iskandrian is a scientific advisor for Rapidscan, Pharma and has received research grants from Astellas Pharma USA. Dr Hage is a scientific advisor for Astellas Pharma USA and has received investigator-initiated grant support from Astellas Pharma USA. The other authors report no financial disclosures. NR 32 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD AUG PY 2014 VL 21 IS 4 BP 673 EP 681 DI 10.1007/s12350-014-9885-5 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AM6EU UT WOS:000339956900002 PM 24715622 ER PT J AU Aggarwal, H AlJaroudi, WA Mehta, S Mannon, R Heo, J Iskandrian, AE Hage, FG AF Aggarwal, Himanshu AlJaroudi, Wael A. Mehta, Shikha Mannon, Roslyn Heo, Jaekyeong Iskandrian, Ami E. Hage, Fadi G. TI The prognostic value of left ventricular mechanical dyssynchrony using gated myocardial perfusion imaging in patients with end-stage renal disease SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE LV dyssynchrony; Phase analysis; End-stage renal disease; Myocardial perfusion imaging; Left ventricular ejection fraction ID EMISSION COMPUTED-TOMOGRAPHY; PHASE-ANALYSIS; SURVIVAL; THERAPY; SPECT AB Prior studies show that left ventricular mechanical dyssynchrony (LVD), measured by gated SPECT myocardial perfusion imaging (MPI), identifies patients with end-stage renal disease (ESRD) at higher risk for all-cause mortality but these were in small number of patients. We sought to assess the interaction between LVD and LV perfusion pattern in risk-stratification of a large sample size of patients with ESRD. From the renal transplantation database maintained at the University of Alabama at Birmingham, we identified consecutive patients with ESRD who had gated SPECT MPI between 2003 and 2007. MPIs were reprocessed to derive LV ejection fraction (EF), perfusion defect size, and LVD [phase bandwidth (BW) and phase standard deviation (SD)]. The primary end-point was all-cause mortality, which was prospectively collected and verified against the social security death index database. There were 828 patients aged 52.6 +/- A 0.36 years (45% were women and 60% had diabetes mellitus). The LVEF was 54.8 +/- A 0.4% and the perfusion pattern was abnormal in 334 patients (41%). During a follow-up period of 61 +/- A 0.9 months, 230 patients (28%) received renal transplants and 290 patients (35%) died. The phase BW (73.1 +/- A 2.6A degrees vs 66.3 +/- A 1.8A degrees, P = .02) and SD (25.2 +/- A 0.8A degrees vs 23.4 +/- A 0.5A degrees, P = .06) were greater in patients who died than those who survived indicating greater dyssynchrony. Patients with phase BW > 56A degrees or SD a parts per thousand yen21A degrees (median values) had worse 5-year survival (64% vs 72%, and 66% vs 71%, log-rank P = .005 and P = .07, respectively). After adjusting for demographics, co-morbidities, LVEF, and perfusion pattern, phase BW was associated with worse outcome (hazard ratio 1.289 95% CI 1.010-1.644, P = .04). LVD by phase analysis of gated SPECT MPI provides prognostic value in ESRD beyond myocardial perfusion and EF. C1 [Aggarwal, Himanshu; Heo, Jaekyeong; Iskandrian, Ami E.; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [AlJaroudi, Wael A.] Amer Univ Beirut, Div Cardiovasc Dis, Med Ctr, Beirut, Lebanon. [Mehta, Shikha; Mannon, Roslyn] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 FU Astellas Pharma USA FX Dr Iskandrian is a scientific advisor for Rapidscan, Pharma and has received research grants from the Astellas Pharma USA. Dr Hage has received research grants from the Astellas Pharma USA. Dr Hage is a scientific advisor for Astellas Pharma USA. The other authors report no financial disclosures. NR 23 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD AUG PY 2014 VL 21 IS 4 BP 739 EP 746 DI 10.1007/s12350-014-9886-4 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AM6EU UT WOS:000339956900011 PM 24858622 ER PT J AU Okon, L Werth, VP AF Okon, Lauren Werth, Victoria P. TI Challenges in measuring outcomes: Size assessment of an individual cutaneous lesion SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material ID SURFACE-AREA; ULCERS C1 [Okon, Lauren; Werth, Victoria P.] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Werth, VP (reprint author), Perelman Ctr Adv Med, Dept Dermatol, Ste 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [K24-AR 02207] NR 11 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2014 VL 71 IS 2 BP 402 EP 404 DI 10.1016/j.jaad.2014.04.032 PG 3 WC Dermatology SC Dermatology GA AM6TJ UT WOS:000339997700049 PM 25037795 ER PT J AU Kottyan, LC Davis, BP Sherrill, JD Liu, K Rochman, M Kaufman, K Weirauch, MT Vaughn, S Lazaro, S Rupert, AM Kohram, M Stucke, EM Kemme, KA Magnusen, A He, H Dexheimer, P Chehade, M Wood, RA Pesek, RD Vickery, BP Fleischer, DM Lindbad, R Sampson, HA Mukkada, VA Putnam, PE Abonia, JP Martin, LJ Harley, JB Rothenberg, ME AF Kottyan, Leah C. Davis, Benjamin P. Sherrill, Joseph D. Liu, Kan Rochman, Mark Kaufman, Kenneth Weirauch, Matthew T. Vaughn, Samuel Lazaro, Sara Rupert, Andrew M. Kohram, Mojtaba Stucke, Emily M. Kemme, Katherine A. Magnusen, Albert He, Hua Dexheimer, Phillip Chehade, Mirna Wood, Robert A. Pesek, Robbie D. Vickery, Brian P. Fleischer, David M. Lindbad, Robert Sampson, Hugh A. Mukkada, Vincent A. Putnam, Phil E. Abonia, J. Pablo Martin, Lisa J. Harley, John B. Rothenberg, Marc E. TI Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease SO NATURE GENETICS LA English DT Article ID INTERLEUKIN-4 RECEPTOR-ALPHA; REGULATORY T-CELLS; SUSCEPTIBILITY LOCI; ATOPIC-DERMATITIS; GENE-EXPRESSION; CHROMOSOME 11Q13.5; EPITHELIAL-CELLS; DIETARY THERAPY; METAANALYSIS; VARIANTS AB Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in EoE cases of European ancestry and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replicating association of the 5q22 locus (meta-analysis P = 1.9 x 10(-16)), we identified an association at 2p23 spanning CAPN14 (P = 2.5 x 10(-10)). CAPN14 was specifically expressed in the esophagus, was dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to interleukin (IL)-13, and was located in an epigenetic hotspot modified by IL-13. Genes neighboring the top 208 EoE-associated sequence variants were enriched for esophageal expression, and multiple loci for allergic sensitization were associated with EoE susceptibility (4.8 x 10(-2) < P < 5.1 x 10(-11)). We propose a model to explain the tissue-specific nature of EoE that involves the interplay of allergic sensitization with an EoE-specific, IL-13-inducible esophageal response involving CAPN14. C1 [Kottyan, Leah C.; Kaufman, Kenneth; Weirauch, Matthew T.; Vaughn, Samuel; Lazaro, Sara; Magnusen, Albert; Harley, John B.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Ctr Autoimmune Genom & Etiol,Div Rheumatol, Cincinnati, OH USA. [Kottyan, Leah C.; Kaufman, Kenneth; Lazaro, Sara; Magnusen, Albert; Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Kottyan, Leah C.; Davis, Benjamin P.; Sherrill, Joseph D.; Liu, Kan; Rochman, Mark; Stucke, Emily M.; Kemme, Katherine A.; Abonia, J. Pablo; Rothenberg, Marc E.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH 45220 USA. [Weirauch, Matthew T.; Kohram, Mojtaba; Dexheimer, Phillip] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH USA. [He, Hua; Martin, Lisa J.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Human Genet, Cincinnati, OH USA. [Chehade, Mirna; Sampson, Hugh A.] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Pesek, Robbie D.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72205 USA. [Vickery, Brian P.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. [Fleischer, David M.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. [Lindbad, Robert] EMMES Corp, Rockville, MD USA. [Mukkada, Vincent A.; Putnam, Phil E.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Gastroenterol Hepatol & Nutr, Cincinnati, OH USA. RP Rothenberg, ME (reprint author), Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH 45220 USA. EM rothenberg@cchmc.org RI ; Martin, Lisa/E-2425-2016 OI Abonia, Juan/0000-0003-3788-6485; Martin, Lisa/0000-0001-8702-9946; Kottyan, Leah/0000-0003-3979-2220 FU US NIH, National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Heart, Lung, and Blood Institute (NHLBI); National Human Genome Research Institute (NHGRI) [U19 AI066738, U01 HG006828, U01 HG006828-S1, U01 HG006828-S2, U01 AI066560, R37 AI024717, P01 AI083194, T32 HL7752-19, K23 AI099083, P01 AR049084]; US NIH from NIAID and NIDDK [U19 AI066738]; National Center for Research Resources (NCRR), a component of the US NIH [UL1 TR001082, UL1 TR-000067, UL1 TR-000039, UL1 TR-000083, UL1 TR-000424]; US Department of Veteran Affairs [IMMA 9]; US Department of Defense [PR094002]; Cincinnati Children's Research Foundation and its Cincinnati Genomic Control Cohort; Campaign Urging Research for Eosinophilic Diseases (CURED); Buckeye Foundation; Food Allergy Research Education (FARE) Foundation; Foundation of the American College of Allergy, Asthma and Immunology FX Funding for this project was provided by the US NIH, National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Heart, Lung, and Blood Institute (NHLBI) and National Human Genome Research Institute (NHGRI) (U19 AI066738, U01 HG006828, U01 HG006828-S1, U01 HG006828-S2, U01 AI066560, R37 AI024717, P01 AI083194, T32 HL7752-19, K23 AI099083 and P01 AR049084). The CoFAR arm of the study was supported by US NIH grant U19 AI066738 from NIAID and NIDDK. The project was also supported by several grants from the National Center for Research Resources (NCRR), a component of the US NIH: UL1 TR001082 (National Jewish), UL1 TR-000067 (Mount Sinai), UL1 TR-000039 (Arkansas), UL1 TR-000083 (University of North Carolina) and UL1 TR-000424 (Johns Hopkins). Support was also received from the US Department of Veteran Affairs (IMMA 9) and the US Department of Defense (PR094002). This research was supported in part by the Cincinnati Children's Research Foundation and its Cincinnati Genomic Control Cohort. Other support was derived from the Campaign Urging Research for Eosinophilic Diseases (CURED), the Buckeye Foundation, the Food Allergy Research Education (FARE) Foundation and the Foundation of the American College of Allergy, Asthma and Immunology. NR 53 TC 54 Z9 54 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD AUG PY 2014 VL 46 IS 8 BP 895 EP 900 DI 10.1038/ng.3033 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AM2TT UT WOS:000339704400021 PM 25017104 ER PT J AU Hepner, KA Paddock, SM Watkins, KE Solomon, J Blonigen, DM Pincus, HA AF Hepner, Kimberly A. Paddock, Susan M. Watkins, Katherine E. Solomon, Jacob Blonigen, Daniel M. Pincus, Harold Alan TI Veterans' Perceptions of Behavioral Health Care in the Veterans Health Administration: A National Survey SO PSYCHIATRIC SERVICES LA English DT Article ID PATIENT-CENTERED CARE; POSTTRAUMATIC-STRESS-DISORDER; INPATIENT CARE; MENTAL-HEALTH; UNITED-STATES; SATISFACTION; OUTCOMES; QUALITY; PERFORMANCE; IMPROVEMENT AB Objective: This study provided national estimates of perceptions of behavioral health care services among patients of the Veterans Health Administration (YHA) with a diagnosis of bipolar I disorder, major depression, posttraumatic stress disorder, schizophrenia, or substance use disorder. Methods: A stratified random sample of 6,190 patients completed telephone interviews from November 2008 through August 2009. Patients (N=5,185) who reported receiving VHA behavioral health care in the prior 12 months were asked about their need for housing and employment services, timeliness and recovery orientation of their care, satisfaction with care, and perceived improvement. Results: Half of patients reported always receiving routine appointments as soon as requested, and 42% were highly satisfied with their YHA mental health care. Approximately 74% of patients reported being helped by the treatment they received, yet only 32% reported that their symptoms had improved. After controlling for covariates, the analyses showed that patients with a substance use disorder reported lower satisfaction with care and perceived their treatment to be less helpful compared with patients without a substance use disorder. Conclusions: Although matched sample comparison data were not available, the results showed that overall patient perceptions of VHA mental health care were favorable, but there was significant room for improvement across all areas of assessment. A majority reported being helped by treatment, but few reported symptom improvement. Variations in perceptions among patients with different disorders suggest the potential importance of psychiatric diagnosis, particularly substance use disorder, in assessing patient perceptions of care. C1 [Hepner, Kimberly A.; Paddock, Susan M.; Watkins, Katherine E.; Solomon, Jacob; Pincus, Harold Alan] RAND Corp, Santa Monica, CA 90401 USA. [Pincus, Harold Alan] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Pincus, Harold Alan] New York Presbyterian Hosp, New York, NY USA. [Blonigen, Daniel M.] US Dept Vet Affairs, Ctr Hlth Care Evaluat, Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Hepner, KA (reprint author), RAND Corp, Santa Monica, CA 90401 USA. EM hepner@rand.org FU U.S. Department of Veterans Affairs (VA) [GS 10 F-0261K, 101-G67214/101-G67215]; Veterans Health Administration Mental Health Services; VA Substance Use Disorder Quality Enhancement Research Initiative [SUDQ-LIP 1206]; VA Office of Research and Development (Clinical Sciences Research and Development); Robert Wood Johnson Foundation; John A. Hartford Foundation; Heinz Endowments; Atlantic Philanthropies; UPMC Health Plan (Community Care Behavioral Health); Highmark Foundation; Staunton Farm Foundation; FISA Foundation; Eden Hall Foundation; SCAN Foundation; Graham Boeckh Foundation; Johnson and Johnson; Lifespan Health System; Alberta Innovates Health Solutions FX This project was funded by the U.S. Department of Veterans Affairs (VA) (contract number GS 10 F-0261K, 101-G67214/101-G67215; program evaluation of Veterans Health Administration Mental Health Services; and the VA Substance Use Disorder Quality Enhancement Research Initiative-SUDQ-LIP 1206). Dr. Blonigen was supported by a Career Development Award-2 from the VA Office of Research and Development (Clinical Sciences Research and Development). The authors thank Q. Burkhart, M.S., of the RAND Corporation for conducting study analyses. The opinions expressed here are the authors' and do not necessarily represent the views of the VA or any other entity of the U.S. government.; Dr. Pincus has received research funding from the Robert Wood Johnson Foundation, the John A. Hartford Foundation, the Heinz Endowments, the Atlantic Philanthropies, the UPMC Health Plan (Community Care Behavioral Health), the Highmark Foundation, the Staunton Farm Foundation, the FISA Foundation, the Eden Hall Foundation, the SCAN Foundation, and the Graham Boeckh Foundation; has served as a consultant or as a member of the advisory board for Value Options, Altarum Institute, and Manila Consulting; and has been paid for presentations by Johnson and Johnson, the Lifespan Health System, and Alberta Innovates Health Solutions. The other authors report no competing interests. NR 40 TC 5 Z9 5 U1 1 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD AUG PY 2014 VL 65 IS 8 BP 988 EP 996 DI 10.1176/appi.ps.201200385 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA AM3TU UT WOS:000339776500006 PM 24733444 ER PT J AU Shaikh, H Morales, D Laghi, F AF Shaikh, Hameeda Morales, Daniel Laghi, Franco TI Weaning from Mechanical Ventilation SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE mechanical ventilation; weaning; monitoring; diagnostic tests; screening; extubation ID INTENSIVE-CARE-UNIT; RANDOMIZED CONTROLLED-TRIAL; CRITICALLY-ILL PATIENTS; PRESSURE SUPPORT VENTILATION; CUFF-LEAK TEST; OBSTRUCTIVE PULMONARY-DISEASE; SPONTANEOUS BREATHING TRIAL; POSITIVE AIRWAY PRESSURE; POSTEXTUBATION STRIDOR; NATRIURETIC PEPTIDE AB For many critically ill patients admitted to an intensive care unit, the insertion of an endotracheal tube and the initiation of mechanical ventilation (MV) can be lifesaving procedures. Subsequent patient care often requires intensivists to manage the complex interaction of multiple failing organ systems. The shift in the intensivists' focus toward the discontinuation of MV can thus occur late in the course of critical illness. The dangers of MV, however, make it imperative to wean patients at the earliest possible time. Premature weaning trials, however, trigger significant respiratory distress, which can cause setbacks in the patient's clinical course. Premature extubation is also risky. To reduce delayed weaning and premature extubation, a three-step diagnostic strategy is suggested: measurement of weaning predictors, a trial of unassisted breathing (T-tube trial), and a trial of extubation. Since each step constitutes a diagnostic test, clinicians must not only command a thorough understanding of each test but must also be aware of the principles of clinical decision making when interpreting the information generated by each step. Many difficult aspects of pulmonary pathophysiology encroach on weaning management. Accordingly, weaning commands sophisticated, individualized care. Few other responsibilities of an intensivist require a more analytical effort and carry more promise for improving patient outcome than the application of physiologic principles in the weaning of patients. C1 [Shaikh, Hameeda; Laghi, Franco] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Morales, Daniel; Laghi, Franco] Loyola Univ, Div Pulm & Crit Care, Maywood, IL 60153 USA. RP Laghi, F (reprint author), Loyola Univ Chicago, Div Pulm & Crit Care Med, Dept Med, Stritch Sch Med,Edward Hines Jr VA Hosp, 111N,5th Ave & Roosevelt Rd, Hines, IL 60141 USA. EM flaghi@lumc.edu FU Veterans Administration Research Service FX This study was supported by grants from the Veterans Administration Research Service. NR 135 TC 0 Z9 0 U1 0 U2 14 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 EI 1098-9048 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD AUG PY 2014 VL 35 IS 4 BP 451 EP 468 DI 10.1055/s-0034-1381953 PG 18 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AM4YW UT WOS:000339863100006 PM 25141162 ER PT J AU Kranzler, HR AF Kranzler, Henry R. TI Commentary on Garbutt et al. (2014): Can we predict who benefits from naltrexone in the treatment of alcohol dependence? SO ADDICTION LA English DT Editorial Material DE Clinical predictors; critical review; family history of alcoholism; moderators; naltrexone; pharmacogenetics ID PROJECT MATCH C1 [Kranzler, Henry R.] Univ Penn, Perelman Sch Med, Ctr Studies Addict, Dept Psychiat, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. RP Kranzler, HR (reprint author), Univ Penn, Perelman Sch Med, Ctr Studies Addict, Dept Psychiat, Philadelphia, PA 19104 USA. EM kranzler@mail.med.upenn.edu FU NIAAA NIH HHS [K24 AA013736, R01 AA021164] NR 9 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD AUG PY 2014 VL 109 IS 8 BP 1285 EP 1286 DI 10.1111/add.12618 PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AL9QV UT WOS:000339476700014 PM 25041200 ER PT J AU Wong, ES Bryson, CL Hebert, PL Liu, CF AF Wong, Edwin S. Bryson, Chris L. Hebert, Paul L. Liu, Chuan-Fen TI Estimating the Impact of Oral Diabetes Medication Adherence on Medical Costs in VA SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE medication adherence; diabetes; medical costs; instrumental variables; Department of Veterans Affairs ID HEALTH-CARE COST; ISSUES; HOSPITALIZATION; IDENTIFICATION; NONADHERENCE; ENDOGENEITY; MORTALITY; VETERANS; MODELS; RISK AB Background: Despite evidence demonstrating clinical benefits of oral hypoglycemic agents (OHAs), adherence to OHAs is generally poor. The economic benefit of OHA adherence among patients in the Veterans Affairs Health System (VA) is unknown. Objective: This study assessed the impact of OHA adherence on medical costs and hospitalization probability in a VA population. Methods: This retrospective cohort study included 26 051 VA patients with diabetes who completed the 2006 Survey of Health Care Experiences of Patients. We calculated total costs in fiscal year (FY) 2007 from the VA perspective as the sum of costs for all inpatient and outpatient services provided by VA. We measured adherence using the medication possession ratio (MPR), which reflected the proportion of days covered in FY2007. Patients were classified as adherent if MPR >= 80%. Analyses using instrumental variables (IVs) addressed potential biases from unobserved confounding. Results: On average, adherent patients incurred lower total medical costs ($4051 vs $5133, P < 0.001) and were less likely to be hospitalized (4.6% vs 7.2%, P < 0.001) compared with nonadherent patients. After covariate adjustment, adherence was associated with a $170 reduction in total costs (P < 0.011) and a 1.5 percentage point decrease (P < 0.001) in hospitalization probability. IV estimates indicated that the impacts of OHA adherence were larger in magnitude. Conclusion: On average, OHA adherence was associated with lower medical costs of at least $170 per patient over a I-year period. Results from this study are important for informing policy decisions to broadly disseminate programs to promote diabetes medication adherence, particularly in a VA setting. C1 [Wong, Edwin S.; Bryson, Chris L.; Hebert, Paul L.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Wong, Edwin S.; Bryson, Chris L.; Hebert, Paul L.; Liu, Chuan-Fen] Univ Washington, Seattle, WA 98195 USA. RP Wong, ES (reprint author), Ctr Innovat Vet Ctr & Value Driven Care, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM edwin.wong@va.gov FU Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs [IIR 07-068]; VA Health Services Research and Development Career Development Award [CDA 13-024] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: All authors are employed by the Department of Veterans Affairs. This research was supported by the Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs (IIR 07-068). Dr Wong is supported by VA Health Services Research and Development Career Development Award (CDA 13-024). The views expressed are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs and the University of Washington. NR 30 TC 7 Z9 7 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD AUG PY 2014 VL 48 IS 8 BP 978 EP 985 DI 10.1177/1060028014536981 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AL9LE UT WOS:000339461800004 PM 24847159 ER PT J AU Adams, TG Badour, CL Cisler, JM Feldner, MT AF Adams, Thomas G., Jr. Badour, Christal L. Cisler, Joshua M. Feldner, Matthew T. TI Contamination Aversion and Posttraumatic Stress Symptom Severity Following Sexual Trauma SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Contamination; Sexual assault; Aversion; PTSD; OCD ID OBSESSIVE-COMPULSIVE DISORDER; ADMINISTERED PTSD SCALE; MENTAL CONTAMINATION; LATENT STRUCTURE; DISGUST; MEDIATION; PRODUCT; ASSAULT; MODELS; FEAR AB Contamination concerns have been linked to increased posttraumatic stress symptoms. The present study offered a preliminary test of the roles of domain-specific contamination aversions in posttraumatic stress. Fifty women with a history of sexual or physical assault were recruited from the community and assessed for posttraumatic stress symptom severity and individual differences in mental contamination, direct contamination aversion [aversion to normative contaminants (e.g., garbage)], indirect contamination aversion [aversion to perceived contaminants (e.g., handrails)], and symptoms of contamination-based obsessive-compulsive disorder. We observed large and significant relations between posttraumatic stress symptoms and all forms of contamination fears and aversions among participants reporting sexual trauma, but minimal and non-significant relations among victims of physical assault. Exploratory tests revealed that the effects of basic contamination aversions on posttraumatic stress symptom severity were largely mediated by mental contamination. The present study suggests that contamination fears and aversions (i.e., normal or perceived) are highly related to posttraumatic stress symptoms among sexual trauma victims and highlights the importance of assessing and targeting feelings and evaluations related to contamination when treating posttraumatic stress symptoms among sexual trauma victims. C1 [Adams, Thomas G., Jr.; Badour, Christal L.; Feldner, Matthew T.] Univ Arkansas, Fayetteville, AR 72701 USA. [Adams, Thomas G., Jr.; Badour, Christal L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Adams, Thomas G., Jr.; Badour, Christal L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Cisler, Joshua M.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Feldner, Matthew T.] Laureate Inst Brain Res, Tulsa, OK USA. RP Adams, TG (reprint author), Univ Arkansas, 212 Mem Hall, Fayetteville, AR 72701 USA. EM tomadams@uark.edu; mfelde@uark.edu NR 43 TC 0 Z9 0 U1 2 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 EI 1573-2819 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD AUG PY 2014 VL 38 IS 4 BP 449 EP 457 DI 10.1007/s10608-014-9609-9 PG 9 WC Psychology, Clinical SC Psychology GA AL8IO UT WOS:000339382000009 ER PT J AU Halpern, NA Shaz, D AF Halpern, Neil A. Shaz, David TI Return on Investment: Just Knowing the Price Is Not Enough! SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE critical care; healthcare informatics; return on investment ID INTENSIVE-CARE-UNIT; TECHNOLOGY; SAFETY; SYSTEM; COST C1 [Halpern, Neil A.; Shaz, David] Mem Sloan Kettering Canc Ctr, Dept Anesthesiol & Crit Care, New York, NY 10021 USA. [Shaz, David] James J Peters VA Med Ctr, Dept Med, Bronx, NY USA. RP Halpern, NA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Anesthesiol & Crit Care, 1275 York Ave, New York, NY 10021 USA. NR 18 TC 0 Z9 0 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD AUG PY 2014 VL 42 IS 8 BP 1952 EP 1953 DI 10.1097/CCM.0000000000000422 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AL7QV UT WOS:000339330700055 PM 25029139 ER PT J AU Ho, EY Cozen, ML Shen, H Lerrigo, R Trimble, E Ryan, JC Corvera, CU Monto, A AF Ho, Edith Y. Cozen, Myrna L. Shen, Hui Lerrigo, Robert Trimble, Erica Ryan, James C. Corvera, Carlos U. Monto, Alexander CA HOVAS Grp Hepatocellular Carcinoma TI Expanded use of aggressive therapies improves survival in early and intermediate hepatocellular carcinoma SO HPB LA English DT Article ID HEPATITIS-C INFECTION; UNITED-STATES; LIVER-TRANSPLANTATION; RADIOFREQUENCY ABLATION; RESECTION; VETERANS; CHEMOEMBOLIZATION; MULTICENTER; POPULATION; RECURRENCE AB Background: Despite the increasing annual incidence of hepatocellular carcinoma (HCC) in the USA, now estimated at 2.7 cases per 100 000 population, only a small proportion of patients receive treatment and 5-year survival rates range from 9% to 17%. Objectives: The present study examines the effects of multimodal treatment on survival in a mixed-stage HCC cohort, focusing on the impact of radical therapy in patients with Barcelona Clinic Liver Cancer (BCLC) stage B disease. Methods: A retrospective review of the medical records of 254 patients considered for HCC treatment between 2003 and 2011 at a large tertiary referral centre was conducted. Results: A total of 195 (76.8%) patients were treated with a median of two liver-directed interventions. Median survival time was 16 months. In proportional hazards analysis, radiofrequency ablation (RFA) and resection were associated with significantly improved 1- and 5-year survival among patients with BCLC stage 0-A disease. In patients with BCLC stage B disease, RFA conferred a survival benefit at 1 year and resection was associated with significantly improved survival at 5 years. Conclusions: As one of few studies to track the complete course of sequential HCC therapies, the findings of the present study suggest that HCC patients with intermediate-stage (BCLC stage B) disease may benefit from aggressive interventions not currently included in societal guidelines. C1 [Ho, Edith Y.; Monto, Alexander] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA USA. [Cozen, Myrna L.; Shen, Hui; Lerrigo, Robert; Ryan, James C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Corvera, Carlos U.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Cozen, Myrna L.; Shen, Hui; Trimble, Erica; Ryan, James C.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Corvera, Carlos U.] San Francisco VA Med Ctr, Dept Surg, San Francisco, CA USA. [Monto, Alexander] San Francisco VA Med Ctr, Dept Med, Div Gastroenterol, San Francisco, CA USA. RP Monto, A (reprint author), San Francisco VA Med Ctr, Gastroenterol Sect 111 B, 4150 Clement St, San Francisco, CA 94121 USA. EM alexander.monto@va.gov FU Veterans Affairs Merit Award Program [1I01-CX000295-01A1]; Veterans Affairs Hepatitis C Resource Center FX Veterans Affairs Merit Award Program (1I01-CX000295-01A1) and Veterans Affairs Hepatitis C Resource Center. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 38 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1365-182X EI 1477-2574 J9 HPB JI HPB PD AUG PY 2014 VL 16 IS 8 BP 758 EP 767 DI 10.1111/hpb.12214 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AM2FQ UT WOS:000339665600010 PM 24467780 ER PT J AU Jin, J Zhang, X Lu, Z Li, Y Lopes-Virella, MF Yu, H Haycraft, CJ Li, Q Kirkwood, KL Huang, Y AF Jin, J. Zhang, X. Lu, Z. Li, Y. Lopes-Virella, M. F. Yu, H. Haycraft, C. J. Li, Q. Kirkwood, K. L. Huang, Y. TI Simvastatin inhibits lipopolysaccharide-induced osteoclastogenesis and reduces alveolar bone loss in experimental periodontal disease SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE alveolar bone; inflammation; lipopolysaccharide; periodontal disease; simvastatin ID NF-KAPPA-B; CARDIOVASCULAR-DISEASE; OVARIECTOMIZED RATS; MONONUCLEAR-CELLS; STATIN THERAPY; IN-VIVO; EXPRESSION; SUPPRESSES; ACTIVATION; MECHANISMS AB Background and Objective: Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and have anti-inflammatory effects independent of cholesterol lowering. Recent clinical studies have indicated that statin intake has a beneficial effect on periodontal disease. However, the underlying mechanisms have not been well understood. In the current study, we employed a rat model with lipopolysaccharide (LPS)-induced periodontal disease and determined the effect of simvastatin, a commonly prescribed statin, on osteoclastogenesis, gingival inflammation and alveolar bone loss. Material and Methods: Sprague-Dawley rats were injected with Aggregatibacter actinomycetemcomitans LPS in periodontal tissue three times per week for 8 wk and part of the rats with LPS injection were also given simvastatin via gavage. After the treatments, the rat maxillae were scanned by microcomputed tomography and the images were analyzed to determine alveolar bone loss. To explore the underlying mechanisms, the effect of simvastatin on osteoclastogenesis and gingival expression of proinflammatory cytokines were also determined by tartrate-resistant acid phosphatase staining and real-time polymerase chain reaction assays, respectively. Results: Results showed that LPS treatment markedly increased bone loss, but administration of simvastatin significantly alleviated the bone loss. Results also showed that LPS treatment stimulated osteoclastogenesis and the expression of inflammatory cytokines, but simvastatin significantly modulates the stimulatory effect of LPS on osteoclastogenesis and cytokine expression. Conclusion: This study demonstrated that simvastatin treatment inhibits LPS-induced osteoclastogenesis and gingival inflammation and reduces alveolar bone loss, indicating that the intake of simvastatin may hinder the progression of periodontal disease. C1 [Jin, J.; Zhang, X.; Lu, Z.; Li, Y.; Lopes-Virella, M. F.; Huang, Y.] Med Univ S Carolina, Coll Med, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Lopes-Virella, M. F.; Huang, Y.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Yu, H.; Haycraft, C. J.; Li, Q.; Kirkwood, K. L.] Med Univ S Carolina, Coll Dent Med, Dept Craniofacial Biol, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Ralph H Johnson Vet Aairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU National Institutes of Health [DE016353]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; National Institute of General Medicine [P30 GM103331] FX This work was supported by National Institutes of Health grant DE016353 and the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs (to Y.H.). This project used facilities, resources and/or technical assistance of the Laboratory of the Center for Oral Health Research (L-COHR) that is supported by the National Institute of General Medicine grant P30 GM103331. NR 39 TC 6 Z9 8 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3484 EI 1600-0765 J9 J PERIODONTAL RES JI J. Periodont. Res. PD AUG PY 2014 VL 49 IS 4 BP 518 EP 526 DI 10.1111/jre.12132 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AM0AB UT WOS:000339503800012 PM 24117880 ER PT J AU Norton, S Matthews, FE Barnes, DE Yaffe, K Brayne, C AF Norton, Sam Matthews, Fiona E. Barnes, Deborah E. Yaffe, Kristine Brayne, Carol TI Potential for primary prevention of Alzheimer's disease: an analysis of population-based data SO LANCET NEUROLOGY LA English DT Article ID PUBLIC-HEALTH IMPACT; RISK-FACTOR; COGNITIVE FUNCTION; UNITED-STATES; DEMENTIA; PREVALENCE; METAANALYSIS; PROJECTIONS; DEPRESSION AB Background Recent estimates suggesting that over half of Alzheimer's disease burden worldwide might be attributed to potentially modifiable risk factors do not take into account risk-factor non-independence. We aimed to provide specific estimates of preventive potential by accounting for the association between risk factors. Methods Using relative risks from existing meta-analyses, we estimated the population-attributable risk (PAR) of Alzheimer's disease worldwide and in the USA, Europe, and the UK for seven potentially modifiable risk factors that have consistent evidence of an association with the disease (diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking, and low educational attainment). The combined PAR associated with the risk factors was calculated using data from the Health Survey for England 2006 to estimate and adjust for the association between risk factors. The potential of risk factor reduction was assessed by examining the combined effect of relative reductions of 10% and 20% per decade for each of the seven risk factors on projections for Alzheimer's disease cases to 2050. Findings Worldwide, the highest estimated PAR was for low educational attainment (19.1%, 95% CI 12.3-25.6). The highest estimated PAR was for physical inactivity in the USA (21.0%, 95% CI 5.8-36.6), Europe (20.3%, 5.6-35.6), and the UK (21.8%, 6.1-37.7). Assuming independence, the combined worldwide PAR for the seven risk factors was 49.4% (95% CI 25.7-68.4), which equates to 16.8 million attributable cases (95% CI 8.7-23.2 million) of 33.9 million cases. However, after adjustment for the association between the risk factors, the estimate reduced to 28.2% (95% CI 14.2-41.5), which equates to 9.6 million attributable cases (95% CI 4.8-14.1 million) of 33.9 million cases. Combined PAR estimates were about 30% for the USA, Europe, and the UK. Assuming a causal relation and intervention at the correct age for prevention, relative reductions of 10% per decade in the prevalence of each of the seven risk factors could reduce the prevalence of Alzheimer's disease in 2050 by 8.3% worldwide. Interpretation After accounting for non-independence between risk factors, around a third of Alzheimer's diseases cases worldwide might be attributable to potentially modifiable risk factors. Alzheimer's disease incidence might be reduced through improved access to education and use of effective methods targeted at reducing the prevalence of vascular risk factors (eg, physical inactivity, smoking, midlife hypertension, midlife obesity, and diabetes) and depression. C1 [Norton, Sam] Kings Coll London, Inst Psychiat, Dept Psychol, London, England. [Matthews, Fiona E.] Inst Publ Hlth, Med Res Council Biostat, Cambridge, England. [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Barnes, Deborah E.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Brayne, Carol] Univ Cambridge, Inst Publ Hlth, Cambridge CB2 0SR, England. RP Brayne, C (reprint author), Univ Cambridge, Inst Publ Hlth, Cambridge CB2 0SR, England. EM carol.brayne@medschl.cam.ac.uk RI Norton, Sam/A-1898-2009 OI Norton, Sam/0000-0003-1714-9963; Matthews, Fiona/0000-0002-1728-2388 FU National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough FX National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough. NR 32 TC 250 Z9 256 U1 21 U2 128 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD AUG PY 2014 VL 13 IS 8 BP 788 EP 794 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AL9JB UT WOS:000339456300013 PM 25030513 ER PT J AU Tse, JR Long, JL AF Tse, Justin R. Long, Jennifer L. TI Microstructure Characterization of a Decellularized Vocal Fold Scaffold for Laryngeal Tissue Engineering SO LARYNGOSCOPE LA English DT Article DE Vocal folds; Young's modulus; scaffolds; tissue engineering; decellularized ID BOVINE ACELLULAR SCAFFOLD; EXTRACELLULAR-MATRIX; CANINE MODEL; STEM-CELLS; RECONSTRUCTION; COLLAGEN; ELASTIN; SCAR AB Objectives/Hypothesis: One potential treatment for vocal fold injury or neoplasia is to replace the entire vocal fold with a tissue-engineered scaffold. This scaffold should ideally have similar mechanical properties and extracellular matrix composition as the native vocal fold. As one approach toward this goal, we decellularized human vocal folds and characterized their mechanical properties and extracellular matrix microstructure. Study Design: Basic science investigation. Methods: Human vocal folds were dissected from the laryngeal framework and treated with sodium dodecyl sulfate (SDS) to remove all cells. Mechanical properties were measured by indentation before and after SDS treatment. The extracellular matrix components of collagen, laminin, elastin, and hyaluronic acid were also characterized before and after decellularization using histology and immunofluorescence. Results: After 4 days of SDS treatment, we obtained a scaffold that retained the original geometry of the vocal fold but was devoid of cells. The elastic modulus of the vocal folds did not change significantly before and after decellularization. Upon qualitative inspection, the decellularized vocal folds retained the original collagen, elastin, and laminin content and orientation but lost the original hyaluronic acid. Conclusions: Vocal folds can be decellularized using SDS without adversely affecting its mechanical stiffness and fibrous extracellular matrix. This preliminary study demonstrates the potential of a decellularized scaffold to serve as a tissue-engineered construct for vocal fold replacement. C1 [Long, Jennifer L.] Univ Calif Los Angeles, Dept Head & Neck Surg, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Long, Jennifer L.] VA Greater Los Angeles Med Ctr, Los Angeles, CA USA. RP Long, JL (reprint author), Univ Calif Los Angeles, Dept Head & Neck Surg, CHS Room 62-132,650 Charles Young Dr, Los Angeles, CA 90095 USA. EM jlong@mednet.ucla.edu OI Long, Jennifer/0000-0002-4185-2328 FU National Institute of Child Health and Human Development FX The authors thank Drs. Melody Xuan, Zhaoyan Zhang, and Ivan Lopez for their technical support. The laminin B2 monoclonal antibody developed by J. R. Sanes was obtained from the Developmental Studies Hybridoma Bank, developed under the auspices of the National Institute of Child Health and Human Development and maintained by the University of Iowa, Department of Biology, Iowa City, Iowa. NR 28 TC 7 Z9 7 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 2014 VL 124 IS 8 BP E326 EP E331 DI 10.1002/lary.24605 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AL9ST UT WOS:000339482100005 PM 24448829 ER PT J AU Kertesz, SG Pollio, DE Jones, RN Steward, J Stringfellow, EJ Gordon, AJ Johnson, NK Kim, TA Daigle, SG Austin, EL Young, AS Chrystal, JG Davis, LL Roth, DL Holt, CL AF Kertesz, Stefan G. Pollio, David E. Jones, Richard N. Steward, Jocelyn Stringfellow, Erin J. Gordon, Adam J. Johnson, Nancy K. Kim, Theresa A. Daigle, Shanette G. Austin, Erika L. Young, Alexander S. Chrystal, Joya G. Davis, Lori L. Roth, David L. Holt, Cheryl L. TI Development of the Primary Care Quality-Homeless (PCQ-H) Instrument A Practical Survey of Homeless Patients' Experiences in Primary Care SO MEDICAL CARE LA English DT Article DE patient satisfaction; item response theory; patient-centered care; survey methodology; patient-centered outcomes research; homeless persons; homeless health care ID HEALTH-CARE; PSYCHOMETRIC PROPERTIES; CONSUMER ASSESSMENT; COMPARING HOMELESS; MEDICAL-CARE; ADULTS; VETERANS; SERVICES; PERCEPTIONS; PERFORMANCE AB Background: Homeless patients face unique challenges in obtaining primary care responsive to their needs and context. Patient experience questionnaires could permit assessment of patient-centered medical homes for this population, but standard instruments may not reflect homeless patients' priorities and concerns. Objectives: This report describes (a) the content and psychometric properties of a new primary care questionnaire for homeless patients; and (b) the methods utilized in its development. Methods: Starting with quality-related constructs from the Institute of Medicine, we identified relevant themes by interviewing homeless patients and experts in their care. A multidisciplinary team drafted a preliminary set of 78 items. This was administered to homeless-experienced clients (n = 563) across 3 VA facilities and 1 non-VA Health Care for the Homeless Program. Using Item Response Theory, we examined Test Information Function (TIF) curves to eliminate less informative items and devise plausibly distinct subscales. Results: The resulting 33-item instrument (Primary Care Quality-Homeless) has 4 subscales: Patient-Clinician Relationship (15 items), Cooperation among Clinicians (3 items), Access/Coordination (11 items), and Homeless-specific Needs (4 items). Evidence for divergent and convergent validity is provided. TIF graphs showed adequate informational value to permit inferences about groups for 3 subscales (Relationship, Cooperation, and Access/Coordination). The 3-item Cooperation subscale had lower informational value (TIF < 5) but had good internal consistency (alpha = 0.75) and patients frequently reported problems in this aspect of care. Conclusions: Systematic application of qualitative and quantitative methods supported the development of a brief patient-reported questionnaire focused on the primary care of homeless patients and offers guidance for future population-specific instrument development. C1 [Kertesz, Stefan G.] Univ Alabama Birmingham, Sch Med, Birmingham VA Med Ctr, Birmingham, AL USA. [Pollio, David E.] Univ Alabama Birmingham, Dept Social Work, Birmingham, AL USA. [Jones, Richard N.] Brown Univ, Alpert Sch Med, Providence, RI 02912 USA. [Steward, Jocelyn] Univ Alabama Birmingham, Sch Hlth Related Profess, Birmingham, AL USA. [Stringfellow, Erin J.] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Ctr Hlth Equ Res & Promot, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Johnson, Nancy K.; Austin, Erika L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Kim, Theresa A.] Boston Univ, Sch Med, Boston Hlth Care Homeless Program, Boston, MA 02118 USA. [Daigle, Shanette G.] Univ Alabama Birmingham, Dept Vet Affairs, Birmingham Atlanta Geriatr Res Educ & Clin Ctr GR, Birmingham, AL USA. [Young, Alexander S.; Chrystal, Joya G.] Univ Calif Los Angeles, VA Desert Pacific Mental Illness Res Educ & Clin, Los Angeles, CA USA. [Young, Alexander S.; Chrystal, Joya G.] Univ Calif Los Angeles, Dept Psychiat, Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Davis, Lori L.] Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA. [Roth, David L.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. [Holt, Cheryl L.] Univ Maryland, Sch Publ Hlth, College Pk, MD 20742 USA. RP Kertesz, SG (reprint author), Div Prevent Med, MT 608,1720 2nd Ave S, Birmingham, AL 35294 USA. EM skertesz@uabmc.edu RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X; Kertesz, Stefan/0000-0001-6101-8421 FU VA Health Services Research and Development FX The authors are obligated both to acknowledge their funding (VA Health Services Research and Development) and a VA disclaimer to indicate that the views are their own and not those of the Federal Government. NR 63 TC 3 Z9 3 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD AUG PY 2014 VL 52 IS 8 BP 734 EP 742 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AL7RQ UT WOS:000339332900011 PM 25023918 ER PT J AU Gulati, T Ramanathan, DS Wong, CC Ganguly, K AF Gulati, Tanuj Ramanathan, Dhakshin S. Wong, Chelsea C. Ganguly, Karunesh TI Reactivation of emergent task-related ensembles during slow-wave sleep after neuroprosthetic learning SO NATURE NEUROSCIENCE LA English DT Article ID MOTOR MEMORY CONSOLIDATION; BRAIN-COMPUTER INTERFACE; SUBSEQUENT SLEEP; CELL ASSEMBLIES; NEURONS; CORTEX; RAT; ARM; TETRAPLEGIA; PLASTICITY AB Brain-machine interfaces can allow neural control over assistive devices. They also provide an important platform for studying neural plasticity. Recent studies have suggested that optimal engagement of learning is essential for robust neuroprosthetic control. However, little is known about the neural processes that may consolidate a neuroprosthetic skill. On the basis of the growing body of evidence linking slow-wave activity (SWA) during sleep to consolidation, we examined whether there is 'offline' processing after neuroprosthetic learning. Using a rodent model, we found that, after successful learning, task-related units specifically experienced increased locking and coherency to SWA during sleep. Moreover, spike-spike coherence among these units was substantially enhanced. These changes were not present with poor skill acquisition or after control awake periods, demonstrating the specificity of our observations to learning. Notably, the time spent in SWA predicted the performance gains. Thus, SWA appears to be involved in offline processing after neuroprosthetic learning. C1 [Gulati, Tanuj; Ramanathan, Dhakshin S.; Wong, Chelsea C.; Ganguly, Karunesh] San Francisco VA Med Ctr, Neurol & Rehabil Dept, San Francisco, CA 94121 USA. [Gulati, Tanuj; Wong, Chelsea C.; Ganguly, Karunesh] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Ramanathan, Dhakshin S.] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA. [Ramanathan, Dhakshin S.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Ganguly, K (reprint author), San Francisco VA Med Ctr, Neurol & Rehabil Dept, San Francisco, CA 94121 USA. EM karunesh.ganguly@ucsf.edu FU Department of Veterans Affairs [B6674]; Burroughs Wellcome Fund [1009855]; American Heart/Stroke Association [0875016N]; VA Psychiatric Research Advanced Fellowship FX This work was supported by the Department of Veterans Affairs (B6674 to KG.), the Burroughs Wellcome Fund (1009855 to K.G.), the American Heart/Stroke Association (0875016N to K.G.) and a VA Psychiatric Research Advanced Fellowship (to D.S.R.). NR 45 TC 18 Z9 18 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD AUG PY 2014 VL 17 IS 8 BP 1107 EP 1113 DI 10.1038/nn.3759 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AM1XA UT WOS:000339641400017 PM 24997761 ER PT J AU Merkow, RP Bilimoria, KY Tomlinson, JS Paruch, JL Fleming, JB Talamonti, MS Ko, CY Bentrem, DJ AF Merkow, Ryan P. Bilimoria, Karl Y. Tomlinson, James S. Paruch, Jennifer L. Fleming, Jason B. Talamonti, Mark S. Ko, Clifford Y. Bentrem, David J. TI Postoperative Complications Reduce Adjuvant Chemotherapy Use in Resectable Pancreatic Cancer SO ANNALS OF SURGERY LA English DT Article DE ACS NSQIP; adjuvant therapy; complications; NCDB; pancreatic cancer; surgery ID RANDOMIZED CONTROLLED-TRIAL; PHASE-III TRIAL; PERIAMPULLARY REGION; CURATIVE RESECTION; COOPERATIVE GROUP; SURGICAL QUALITY; PATIENT SAFETY; UNITED-STATES; RISK; SURGERY AB Objective: To assess the impact of postoperative complications on the receipt of adjuvant chemotherapy. Background: Randomized trials have demonstrated that adjuvant chemotherapy is associated with improved long-term survival. However, pancreatic surgery is associated with significant morbidity and the degree to which complications limit subsequent treatment options is unknown. Methods: Patients from the American College of Surgeons National Surgical Quality Improvement Program and the National Cancer Data Base who underwent pancreatic resection for cancer were linked (2006-2009). The associations between complications and adjuvant chemotherapy use or treatment delay (>= 70 days from surgery) were assessed using multivariable regression methods. Results: From 149 hospitals, 2047 patients underwent resection for stage I-III pancreatic adenocarcinoma of which 23.2% had at least 1 serious complication. Overall adjuvant chemotherapy receipt was 57.7%: 61.8% among patients not experiencing any complication and 43.6% among those who had a serious complication. Serious complications increased the likelihood of not receiving adjuvant therapy over twofold [odds ratio (OR) = 2.20, 95% confidence interval (CI): 1.73-2.80]. Specific complications associated with adjuvant chemotherapy omission were reintubation (OR = 7.79, 95% CI: 3.59-16.87), prolonged ventilation (OR = 5.92, 95% CI: 3.23-10.86), pneumonia (OR = 2.83, 95% CI: 1.63-4.90), sepsis/shock (OR = 2.76, 95% CI: 2.02-3.76), organ space/deep surgical site infection (OR = 2.19, 95% CI: 1.53-3.13), venous thromboembolism (OR = 1.92, 95% CI: 1.08-3.43), and urinary tract infection (OR = 1.61, 95% CI: 1.02-2.54). Serious complications also doubled the likelihood of delaying adjuvant treatment administration (OR = 2.08, 95% CI: 1.42-3.05). Sensitivity analysis in a younger, healthier patient cohort demonstrated similar associations. Conclusions: Postoperative complications are common following pancreatic surgery and are associated with adjuvant chemotherapy omission and treatment delays. C1 [Merkow, Ryan P.; Bilimoria, Karl Y.; Paruch, Jennifer L.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Merkow, Ryan P.; Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Feinberg Sch Med, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Merkow, Ryan P.; Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Dept Surg, Northwestern Inst Comparat Effectiveness Res NICE, Feinberg Sch Med, Chicago, IL 60611 USA. [Merkow, Ryan P.; Paruch, Jennifer L.; Talamonti, Mark S.] Univ Chicago, Pritzker Sch Med, Dept Surg, Chicago, IL 60637 USA. [Tomlinson, James S.; Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Tomlinson, James S.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fleming, Jason B.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Talamonti, Mark S.] Northshore Univ Hlth Syst, Dept Surg, Evanston, IL USA. [Bentrem, David J.] Jesse Brown Vet Affairs Med Ctr, Dept Surg, Chicago, IL USA. RP Merkow, RP (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM RMerkow@facs.org FU American Cancer Society [280521]; Genetech FX The authors have no conflicts of interest to disclose. This study was supported by a grant from the American Cancer Society (No. 280521) to R. P. M. and K.Y.B. J.L.P. is supported by a grant from Genetech. NR 30 TC 24 Z9 24 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD AUG PY 2014 VL 260 IS 2 BP 372 EP 377 DI 10.1097/SLA.0000000000000378 PG 6 WC Surgery SC Surgery GA AL5KW UT WOS:000339173500033 PM 24374509 ER PT J AU Pensinger, DA Aliota, MT Schaenzer, AJ Boldon, KM Ansari, IU Vincent, WJB Knight, B Reniere, ML Striker, R Sauer, JD AF Pensinger, Daniel A. Aliota, Matthew T. Schaenzer, Adam J. Boldon, Kyle M. Ansari, Israr-ul H. Vincent, William J. B. Knight, Benjamin Reniere, Michelle L. Striker, Rob Sauer, John-Demian TI Selective Pharmacologic Inhibition of a PASTA Kinase Increases Listeria monocytogenes Susceptibility to beta-Lactam Antibiotics SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SERINE/THREONINE PROTEIN-KINASE; STAPHYLOCOCCUS-AUREUS; SER/THR KINASE; ANTIMICROBIAL SUSCEPTIBILITY; MYCOBACTERIUM-TUBERCULOSIS; ENTEROCOCCUS-FAECALIS; MEDICAL-CENTERS; PKNB; RESISTANCE; BACTERIA AB While beta-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of the penicillin binding protein and serine/threonine kinase-associated protein (PASTA) kinase in methicillin-resistant Staphylococcus aureus (MRSA) has been shown to restore beta-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase in Listeria monocytogenes by the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase of L. monocytogenes ( PrkA). Importantly, staurosporine did not inhibit a L. monocytogenes kinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization of L. monocytogenes to beta-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of beta-lactam antibiotics. C1 [Pensinger, Daniel A.; Aliota, Matthew T.; Schaenzer, Adam J.; Boldon, Kyle M.; Vincent, William J. B.; Knight, Benjamin; Striker, Rob; Sauer, John-Demian] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. [Aliota, Matthew T.; Schaenzer, Adam J.; Boldon, Kyle M.; Ansari, Israr-ul H.; Striker, Rob] Univ Wisconsin, Dept Med, Madison, WI USA. [Striker, Rob] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Reniere, Michelle L.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Sauer, JD (reprint author), Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. EM sauer3@wisc.edu FU Hartwell Foundation; NIH [U54 AI57153] FX This work was supported by an individual biomedical research award from The Hartwell Foundation to R. S. and by an NIH grant (U54 AI57153) to J.-D.S. NR 42 TC 7 Z9 8 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2014 VL 58 IS 8 BP 4486 EP 4494 DI 10.1128/AAC.02396-14 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AL6RA UT WOS:000339259200029 PM 24867981 ER PT J AU Egelund, EF Weiner, M Singh, RP Prihoda, TJ Gelfond, JAL Derendorf, H Mac Kenzie, WR Peloquin, CA AF Egelund, Eric F. Weiner, Marc Singh, Rajendra P. Prihoda, Thomas J. Gelfond, Jonathon A. L. Derendorf, Hartmut Mac Kenzie, William R. Peloquin, Charles A. TI Protein Binding of Rifapentine and Its 25-Desacetyl Metabolite in Patients with Pulmonary Tuberculosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SERUM-ALBUMIN; MYCOBACTERIUM-TUBERCULOSIS; RIFAMPICIN; PLASMA; HIV AB Rifapentine is highly protein bound in blood, but the free, unbound drug is the microbiologically active fraction. In this exploratory study, we characterized the free plasma fraction of rifapentine in 41 patients with tuberculosis. We found a lower total rifapentine concentration but significantly higher free rifapentine levels in African patients of black race compared to non-Africans. These data support larger pharmacokinetic/pharmacodynamic studies to confirm these findings and assess free rifapentine in relation to microbiological and clinical outcomes. C1 [Egelund, Eric F.; Derendorf, Hartmut; Peloquin, Charles A.] Univ Florida, Coll Pharm, Gainesville, FL USA. [Weiner, Marc] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Weiner, Marc] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Singh, Rajendra P.] GlaxoSmithKline, Clin Pharmacol Modeling & Simulat, King Of Prussia, PA USA. [Prihoda, Thomas J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Gelfond, Jonathon A. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol, San Antonio, TX 78229 USA. [Gelfond, Jonathon A. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biostat, San Antonio, TX 78229 USA. [Mac Kenzie, William R.] Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. RP Weiner, M (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM weiner@uthscsa.edu FU Centers for Disease Control and Prevention through the Tuberculosis Trials Consortium; Veterans Affairs Administration FX This work was supported by the Centers for Disease Control and Prevention through the Tuberculosis Trials Consortium and the Veterans Affairs Administration. NR 16 TC 5 Z9 5 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2014 VL 58 IS 8 BP 4904 EP 4910 DI 10.1128/AAC.01730-13 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AL6RA UT WOS:000339259200078 PM 24841270 ER PT J AU Bentov, I Damodarasamy, M Plymate, S Reed, MJ AF Bentov, Itay Damodarasamy, Mamatha Plymate, Stephen Reed, May J. TI Decreased proliferative capacity of aged dermal fibroblasts in a three dimensional matrix is associated with reduced IGF1R expression and activation SO BIOGERONTOLOGY LA English DT Article DE Dermal fibroblasts; IGF1R; IGF-1; 3D matrix; Proliferation; Erk phosphorylation ID GROWTH-FACTOR-I; LIFE-SPAN; FACTOR RECEPTOR; HUMAN-CELLS; SKIN; INSULIN; GENE; SENESCENCE; ADHESIONS; MIGRATION AB Skin aging results in increased susceptibility to injury and impaired wound healing. Proliferation of fibroblasts is reduced in aged dermis, which contributes to delays in wound closure. Age-associated differences are regulated, in part, by local or systemic factors such as the IGF-1/IGF1R system. The aim of this study was to determine if expression and activation of IGF1R in aged human dermal fibroblasts, when compared to young fibroblasts, is associated with altered proliferative capacity in a 3D collagen matrix that better simulates the dermal extracellular matrix in vivo. The proliferation of young and aged human dermal fibroblasts in 3D collagen and its association with baseline levels of IGF1R expression were measured. The effect of stimulation and inhibition of Erk phosphorylation on the proliferative capacity of fibroblasts in a 3D collagen matrix was defined. Our results show that proliferation and Erk phosphorylation is reduced in aged dermal fibroblasts relative to young fibroblasts. Activation of Erk phosphorylation in aged fibroblasts is associated with a significant increase in fibroblast proliferation in 3D collagen. C1 [Bentov, Itay] Univ Washington, Dept Anesthesiol & Pain Med, Harborview Med Ctr, Seattle, WA 98104 USA. [Damodarasamy, Mamatha; Plymate, Stephen; Reed, May J.] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98104 USA. [Plymate, Stephen] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Bentov, I (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, Harborview Med Ctr, Box 359724,325 Ninth Ave, Seattle, WA 98104 USA. EM itayb@uw.edu FU ITHS; Department of Anesthesiology & Pain Medicine pilot grant; [R03 AG042353]; [R21 AG33391] FX This work was supported by R03 AG042353 (I. B.), ITHS and Department of Anesthesiology & Pain Medicine pilot grant (I. B.), and R21 AG33391 (M.J.R.). We would like to thank Dr. Kathryn Houmiel for her technical assistance. NR 38 TC 5 Z9 5 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-5729 EI 1573-6768 J9 BIOGERONTOLOGY JI Biogerontology PD AUG PY 2014 VL 15 IS 4 BP 329 EP 337 DI 10.1007/s10522-014-9501-8 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AL7UW UT WOS:000339342500002 PM 24770843 ER PT J AU Bates, BS Rodriguez, AL Felts, AS Morrison, RD Venable, DF Blobaum, AL Byers, FW Lawson, KP Daniels, JS Niswender, CM Jones, CK Conn, PJ Lindsley, CW Emmitte, KA AF Bates, Brittney S. Rodriguez, Alice L. Felts, Andrew S. Morrison, Ryan D. Venable, Daryl F. Blobaum, Anna L. Byers, Frank W. Lawson, Kera P. Daniels, J. Scott Niswender, Colleen M. Jones, Carrie K. Conn, P. Jeffrey Lindsley, Craig W. Emmitte, Kyle A. TI Discovery of VU0431316: A negative allosteric modulator of mGlu(5) with activity in a mouse model of anxiety SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Glutamate; CNS; mGlu(5); Allosteric modulator; Anxiety ID MGLUR5 ANTAGONIST MPEP; METABOTROPIC GLUTAMATE-RECEPTOR-5 ANTAGONIST; ESOPHAGEAL SPHINCTER RELAXATIONS; CUE-INDUCED REINSTATEMENT; RECEPTOR ANTAGONIST; GLUTAMATE RECEPTORS; GASTROESOPHAGEAL-REFLUX; NUCLEUS-ACCUMBENS; SQUIRREL-MONKEYS; SEEKING BEHAVIOR AB Development of SAR in an aryl ether series of mGlu(5) NAMs leading to the identification of pyrazine analog VU0431316 is described in this Letter. VU0431316 is a potent and selective non-competitive antagonist of mGlu(5) that binds at a known allosteric binding site. VU0431316 demonstrates an attractive DMPK profile, including moderate clearance and good bioavailability in rats. Intraperitoneal (IP) dosing of V1J0431316 in a mouse marble burying model of anxiety, an assay known to be sensitive to mGlu(5) antagonists and other anxiolytics, produced dose proportional effects. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Bates, Brittney S.; Rodriguez, Alice L.; Felts, Andrew S.; Morrison, Ryan D.; Venable, Daryl F.; Blobaum, Anna L.; Byers, Frank W.; Lawson, Kera P.; Daniels, J. Scott; Niswender, Colleen M.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. [Bates, Brittney S.; Rodriguez, Alice L.; Felts, Andrew S.; Morrison, Ryan D.; Venable, Daryl F.; Blobaum, Anna L.; Byers, Frank W.; Lawson, Kera P.; Daniels, J. Scott; Niswender, Colleen M.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Lindsley, Craig W.; Emmitte, Kyle A.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [Jones, Carrie K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. RP Emmitte, KA (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. EM kyle.a.emmitte@vanderbilt.edu FU NIDA [R01 DA023947]; Seaside Therapeutics [VUMC33842] FX We thank NIDA (R01 DA023947) and Seaside Therapeutics (VUMC33842) for their support of our programs in the development of non-competitive antagonist of mGlu5. We also thank Tammy S. Santomango for technical contributions with the protein binding assays. NR 70 TC 2 Z9 2 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 1 PY 2014 VL 24 IS 15 BP 3307 EP 3314 DI 10.1016/j.bmcl.2014.06.003 PG 8 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA AL6FT UT WOS:000339228700017 PM 24969015 ER PT J AU Yazdany, J Trupin, L Schmajuk, G Katz, PP Yelin, EH AF Yazdany, Jinoos Trupin, Laura Schmajuk, Gabriela Katz, Patricia P. Yelin, Edward H. TI Quality of care in systemic lupus erythematosus: the association between process and outcome measures in the Lupus Outcomes Study SO BMJ QUALITY & SAFETY LA English DT Article ID LARGE OBSERVATIONAL COHORT; ACTIVITY QUESTIONNAIRE; HEALTH PLANS; OSTEOPOROSIS; DISPARITIES; INDICATORS; VALIDATION; DISEASE AB Objectives Although process measures to assess quality of care in systemic lupus erythematosus (SLE) are available, their relationship to long-term outcomes has not been studied. Using a prospective, longitudinal cohort study, we examined the associations between high-quality care and two important SLE outcomes, disease activity and damage. Methods Data were derived from the University of California, San Francisco Lupus Outcomes Study. Participants were followed from 2009 through 2013, responding to yearly surveys. Primary outcomes in this study were clinically meaningful increases in disease activity and damage, assessed by the Systemic Lupus Activity Questionnaire (SLAQ) and the Brief Index of Lupus Damage (BILD), respectively. Using multivariable regression, we examined the relationship between high performance on 13 validated quality measures (receipt of >= 85% of quality measures), and disease outcomes, adjusting for disease status, sociodemographic characteristics, healthcare services and follow-up time. Results The 737 participants were eligible for a mean of five quality measures (SD 2, range 2-12). There were 155 and 162 participants who had clinically meaningful increases in SLAQ and BILD, respectively. In our models, we found no statistically significant relationship between performance on quality measures and changes in SLAQ. However, receiving higher-quality SLE care was significantly protective against increased disease damage (adjusted OR 0.4, 95% CI 0.4 to 0.7), even after adjusting for covariates. Discussion In this community-based cohort, we illustrate for the first time a strong link between processes of care, defined by SLE quality measures, and the subsequent accumulation of disease damage, an important outcome. C1 [Yazdany, Jinoos; Trupin, Laura; Katz, Patricia P.; Yelin, Edward H.] Univ Calif San Francisco, Div Rheumatol, Dept Med, San Francisco, CA 94143 USA. [Schmajuk, Gabriela] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Katz, Patricia P.; Yelin, Edward H.] Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Yazdany, J (reprint author), Univ Calif San Francisco, Div Rheumatol, Box 0920, San Francisco, CA 94143 USA. EM jinoos.yazdany@ucsf.edu FU National Institute of Arthritis and Musculoskeletal and Skin diseases [K23 AR060259, P60 AR053308, 2R01 AR056476] FX Research reported in this manuscript was supported by the National Institute of Arthritis and Musculoskeletal and Skin diseases under award numbers K23 AR060259, P60 AR053308 and 2R01 AR056476. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 24 TC 8 Z9 8 U1 0 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD AUG PY 2014 VL 23 IS 8 BP 659 EP 666 DI 10.1136/bmjqs-2013-002494 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AL5MC UT WOS:000339176900008 PM 24614054 ER PT J AU Connizzo, BK Yannascoli, SM Tucker, JJ Caro, AC Riggin, CN Mauck, RL Soslowsky, LJ Steinberg, DR Bernstein, J AF Connizzo, Brianne K. Yannascoli, Sarah M. Tucker, Jennica J. Caro, Adam C. Riggin, Corinne N. Mauck, Robert L. Soslowsky, Louis J. Steinberg, David R. Bernstein, Joseph TI The Detrimental Effects of Systemic Ibuprofen Delivery on Tendon Healing Are Time-Dependent SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ROTATOR CUFF TEARS; COMPOSITIONAL PROPERTIES; MECHANICAL-PROPERTIES; INSERTION SITE; ANIMAL-MODEL; RAT MODEL; FRACTURE; REPAIR; INHIBITION AB Current clinical treatment after tendon repairs often includes prescribing NSAIDs to limit pain and inflammation. The negative influence of NSAIDs on bone repair is well documented, but their effects on tendon healing are less clear. While NSAIDs may be detrimental to early tendon healing, some evidence suggests that they may improve healing if administered later in the repair process. We asked whether the biomechanical and histologic effects of systemic ibuprofen administration on tendon healing are influenced by either immediate or delayed drug administration. After bilateral supraspinatus detachment and repair surgeries, rats were divided into groups and given ibuprofen orally for either Days 0 to 7 (early) or Days 8 to 14 (delayed) after surgery; a control group did not receive ibuprofen. Healing was evaluated at 1, 2, and 4 weeks postsurgery through biomechanical testing and histologic assessment. Biomechanical evaluation resulted in decreased stiffness and modulus at 4 weeks postsurgery for early ibuprofen delivery (mean +/- SD [95% CI]: 10.8 +/- 6.4 N/mm [6.7-14.8] and 8.9 +/- 5.9 MPa [5.4-12.3]) when compared to control repair (20.4 +/- 8.6 N/mm [16.3-24.5] and 15.7 +/- 7.5 MPa [12.3-19.2]) (p = 0.003 and 0.013); however, there were no differences between the delayed ibuprofen group (18.1 +/- 7.4 N/mm [14.2-22.1] and 11.5 +/- 5.6 MPa [8.2-14.9]) and the control group. Histology confirmed mechanical results with reduced fiber reorganization over time in the early ibuprofen group. Early administration of ibuprofen in the postoperative period was detrimental to tendon healing, while delayed administration did not affect tendon healing. Historically, clinicians have often prescribed ibuprofen after tendon repair, but this study suggests that the timing of ibuprofen administration is critical to adequate tendon healing. This research necessitates future clinical studies investigating the use of ibuprofen for pain control after rotator cuff repair and other tendon injuries. C1 [Connizzo, Brianne K.; Yannascoli, Sarah M.; Tucker, Jennica J.; Caro, Adam C.; Riggin, Corinne N.; Mauck, Robert L.; Soslowsky, Louis J.] Univ Penn, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. [Steinberg, David R.; Bernstein, Joseph] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Soslowsky, LJ (reprint author), Univ Penn, McKay Orthopaed Res Lab, 424 Stemmler Hall,34th & Hamilton Walk, Philadelphia, PA 19104 USA. EM soslowsk@mail.med.upenn.edu FU Penn Center for Musculoskeletal Disorders (Philadelphia, PA, USA) (NIH Grant) [P30 AR050950]; NIH (Bethesda, MD, USA) (NIH Training Grant) [T32 AR007132]; Orthopaedic Research and Education Foundation (Rosemont, IL, USA) (OREF Resident Clinician Scientist Training Grant) [12-027] FX The institution of one or more of the authors (BKC, SMY, JJT, ACC, CNR, RLM, LJS) has received, during the study period, funding from the Penn Center for Musculoskeletal Disorders (Philadelphia, PA, USA) (NIH Grant P30 AR050950) and the NIH (Bethesda, MD, USA) (NIH Training Grant T32 AR007132). One of the authors certifies that she (SMY), or a member of her immediate family, has received or may receive, during the study period, funding from the Orthopaedic Research and Education Foundation (Rosemont, IL, USA) (OREF Resident Clinician Scientist Training Grant 12-027). Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. NR 34 TC 17 Z9 17 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD AUG PY 2014 VL 472 IS 8 BP 2433 EP 2439 DI 10.1007/s11999-013-3258-2 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AL3AK UT WOS:000338997100021 PM 23982408 ER PT J AU Glasgow, SC Heafner, TA Watson, JDB Aden, JK Perry, WB AF Glasgow, Sean C. Heafner, Thomas A. Watson, J. Devin B. Aden, James K. Perry, W. Brian TI Initial Management and Outcome of Modern Battlefield Anal Trauma SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Anorectal surgery; Ostomy; Outcomes research; Colorectal surgery; General surgery; Trauma ID OPERATION IRAQI FREEDOM; RECTAL INJURIES; SURGICAL-MANAGEMENT; ENDURING FREEDOM; SPHINCTER REPAIR; COMBAT WOUNDS; COLOSTOMY; EPIDEMIOLOGY; COLON AB BACKGROUND: Despite the potential for morbidity and permanent lifestyle alteration, few reports exist examining traumatic injury to the anal canal, particularly among modern-day combatants. OBJECTIVE: The aim of this study was to document the incidence, initial surgical management, and long-term outcomes of wartime anal trauma. DESIGN: This study is a retrospective review. DATA SOURCES: Data were compiled from multiple electronic medical record systems, including the Department of Defense Trauma Registry, the Patient Administration Systems and Biostatistics Activity, and the Armed Forces Health Longitudinal Tracking Application. SETTINGS: Combatants were treated at military treatment facilities with surgical capability during the wars in Iraq and Afghanistan, 2003 through early 2011. PATIENTS: All US and coalition combatants sustaining trauma to the anal canal or sphincter musculature were included. MAIN OUTCOME MEASURES: The quantification of incidence, the evaluation of initial treatment approach, and the determination of clinical and surgical factors correlating with restoration or preservation of GI tract continuity were the primary outcomes measured. RESULTS: Anal trauma occurred in 46 combatants, predominantly from blast injury (76.1%). Most (36, 78.2%) underwent fecal diversion. Concurrent severe systemic or intra-abdominal injuries correlated with colostomy creation. Acute anoplasty was attempted in 11 patients (23.7%) but did not influence eventual colostomy reversal. Among 33 US personnel, the permanent colostomy rate was 30.3%. Concurrent injury to the abdomen strongly predicted long-term colostomy (p = 0.009), along with hypogastric arterial ligation (p = 0.05) and pelvic fracture (p = 0.06). LIMITATIONS: This study was limited by the potential underdiagnosis of anal injury and the restricted follow-up of non-US personnel. CONCLUSIONS: Other injuries besides anal trauma typically have guided the decision for fecal diversion, and acute anal repair has rarely been indicated. The majority of patients with anal trauma regained normal GI continuity, although certain pelvic injuries increased the likelihood of permanent colostomy. C1 [Glasgow, Sean C.] St Louis Univ, Dept Surg, St Louis, MO 63110 USA. [Glasgow, Sean C.] US Air Force, Ctr Sustainment Trauma & Readiness Skills, St Louis, MO USA. [Heafner, Thomas A.; Watson, J. Devin B.] San Antonio Mil Med Ctr, Dept Surg, Ft Sam Houston, TX USA. [Aden, James K.] US Army, Inst Surg Res, Ft Sam Houston, TX 78234 USA. [Perry, W. Brian] Audie L Murphy Vet Hosp, San Antonio, TX USA. RP Glasgow, SC (reprint author), St Louis Univ, Dept Surg, 3635 Vista & Grand Blvd,3 FDT, St Louis, MO 63110 USA. EM glasgowsc@slu.edu FU Defense Health Program [6.7 FY12] FX Research was funded in part by Defense Health Program 6.7 FY12 grant, "Quality of Life and Obstacles to Care in Injured Personnel with Ostomies," principle investigator Major Sean C. Glasgow. NR 32 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 EI 1530-0358 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD AUG PY 2014 VL 57 IS 8 BP 1012 EP 1018 DI 10.1097/DCR.0000000000000141 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AL6KO UT WOS:000339241500015 PM 25003297 ER PT J AU Wechsler, RT Leroy, R Van Cott, A Hammer, AE Vuong, A Huffman, R VanLandingham, K Messenheinner, JA AF Wechsler, Robert T. Leroy, Robert Van Cott, Anne Hammer, Anne E. Vuong, Alain Huffman, Russell VanLandingham, Kevan Messenheinner, John A. TI Lamotrigine extended-release as adjunctive therapy with optional conversion to monotherapy in older adults with epilepsy SO EPILEPSY RESEARCH LA English DT Article DE Lamottigine; Extended-release; Epilepsy; Elderly; Monotherapy ID NEWLY-DIAGNOSED EPILEPSY; TONIC-CLONIC SEIZURES; NEW-ONSET EPILEPSY; IMMEDIATE-RELEASE; ELDERLY-PATIENTS; CLINICAL-TRIAL; DOUBLE-BLIND; CARBAMAZEPINE; SAFETY; MULTICENTER AB Purpose: To determine the tolerability and efficacy of lamotrigine extended-release (LTG XR) as adjunctive therapy with optional conversion to monotherapy in patients ages >= 65 years with epilepsy. Methods: This open-label study included the standard LTG XR dose escalation, an 8-week Adjunctive Maintenance Phase (AMP), a 13-week Adjunctive Optimization Phase or Conversion and Monotherapy Phase, and a Taper/Follow-Up Phase. At the end of the AMP, patients on a single concomitant antiepileptic drug (AED) were converted to LTG XR monotherapy over 5 weeks and then remained in the Monotherapy Maintenance Phase for 8 weeks. All other patients remained in the study on concomitant AEDs for an additional 13 weeks in the Adjunctive Optimization Phase. Key findings: The number of patients who took >= 1 dose of study medication was 121. Of the 92 patients completing the AMP, 68 patients (74%) were deemed by their treating physician to be eligible to proceed with monotherapy; the remaining 24 patients (26%) continued in the Adjunctive Optimization Phase. The types of adverse events reported with LTG XR were similar to those in studies of LTG XR in younger adult patients with epilepsy and studies of LTG immediate-release (IR) across age groups with epilepsy. No serious rashes were reported. For subjects who were not seizure free at baseline (n=55), the median baseline seizure frequency was 0.5 seizures per week. During the entire treatment period, the median percent change from baseline was 90% (p < 0.0001). Fifty-two (52) patients (76%) of the 68 who entered the monotherapy phase successfully converted to monotherapy. Significance: In this small open label study, LTG-XR was safe and effective when added to the AED regimen of older patients with epilepsy. Many patients were able to be converted to LTG-XR monotherapy. (C) 2014 Elsevier B.V. All rights reserved. C1 [Wechsler, Robert T.] Idaho Comprehens Epilepsy Ctr, Boise, ID USA. [Leroy, Robert] Texas Epilepsy Grp, Dallas, TX USA. [Van Cott, Anne] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Van Cott, Anne] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hammer, Anne E.; Vuong, Alain; Huffman, Russell; VanLandingham, Kevan; Messenheinner, John A.] GlaxoSmithKline, Brentford, England. RP Wechsler, RT (reprint author), Consultants Epilepsy & Neurol PLLC, Idaho Comprehens Epilepsy Ctr, 1499 West Hays St, Boise, ID 83702 USA. EM rtw@idahoepilepsy.com FU GlaxoSmithKline FX Jane Saiers, PhD (The WriteMedicine Inc.) assisted with development of initial drafts of the manuscript in collaboration with all co-authors. Dr. Saiers' work was funded by GlaxoSmithKline. NR 41 TC 2 Z9 2 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD AUG PY 2014 VL 108 IS 6 BP 1128 EP 1136 DI 10.1016/j.eplepsyres.2014.04.009 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AL4XS UT WOS:000339138700015 PM 24888248 ER PT J AU Sprenger, CCT Plymate, SR AF Sprenger, Cynthia C. T. Plymate, Stephen R. TI The Link Between Androgen Receptor Splice Variants and Castration-Resistant Prostate Cancer SO HORMONES & CANCER LA English DT Review ID INCREASED SURVIVAL; AR-45 VARIANT; CELL-LINES; GROWTH; GENE; DOMAIN; MODEL; TRANSCRIPTION; ENZALUTAMIDE; ABIRATERONE AB Resistance to the latest advanced prostate cancer therapies, including abiraterone and enzalutamide, is associated with increased expression of constitutively active androgen receptor splice variants (AR-Vs). The exact mechanism by which these therapies result in AR-Vs is unknown, but may include genomic rearrangement of the androgen receptor gene as well as alternative splicing of the AR pre-messenger RNA (mRNA). An additional complication that hinders further development of effective AR strategies is that the mechanisms by which the directed therapies are bypassed may vary. Finally, the question must be addressed as to whether the androgen receptor remains to be the driver of most castration resistant disease or whether truly AR-independent tumors arise after successful androgen ablation therapy. In this review, we will examine androgen receptor splice variants as an alternative mechanism by which prostate cancer becomes resistant to androgen receptor-directed therapy. C1 [Sprenger, Cynthia C. T.; Plymate, Stephen R.] Univ Washington, Dept Med, Seattle, WA 98104 USA. [Plymate, Stephen R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Sprenger, Cynthia C. T.] Univ Washington, Seattle, WA 98104 USA. RP Sprenger, CCT (reprint author), Univ Washington, Harborview Res & Training Bldg,325 9th Ave,Box 35, Seattle, WA 98104 USA. EM cts2501@u.washington.edu FU NCI NIH HHS [P01 CA085859, P01 CA163227, P50 CA097186] NR 60 TC 24 Z9 25 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-8497 EI 1868-8500 J9 HORM CANCER-US JI Horm. Cancer PD AUG PY 2014 VL 5 IS 4 BP 207 EP 217 DI 10.1007/s12672-014-0177-y PG 11 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA AL7QW UT WOS:000339330800002 PM 24798453 ER PT J AU Ibrahim, MK Barnes, JL Osorio, EY Anstead, GM Jimenez, F Osterholzer, JJ Travi, BL Ahuja, SS White, AC Melby, PC AF Ibrahim, Marwa K. Barnes, Jeffrey L. Osorio, E. Yaneth Anstead, Gregory M. Jimenez, Fabio Osterholzer, John J. Travi, Bruno L. Ahuja, Seema S. White, A. Clinton, Jr. Melby, Peter C. TI Deficiency of Lymph Node-Resident Dendritic Cells (DCs) and Dysregulation of DC Chemoattractants in a Malnourished Mouse Model of Leishmania donovani Infection SO INFECTION AND IMMUNITY LA English DT Article ID INNATE IMMUNE-RESPONSE; VISCERAL LEISHMANIASIS; BONE-MARROW; IN-VIVO; CONDUIT SYSTEM; RISK-FACTOR; MALNUTRITION; MONOCYTES; MIGRATION; RECRUITMENT AB Malnutrition is thought to contribute to more than one-third of all childhood deaths via increased susceptibility to infection. Malnutrition is a significant risk factor for the development of visceral leishmaniasis, which results from skin inoculation of the intracellular protozoan Leishmania donovani. We previously established a murine model of childhood malnutrition and found that malnutrition decreased the lymph node barrier function and increased the early dissemination of L. donovani. In the present study, we found reduced numbers of resident dendritic cells (conventional and monocyte derived) but not migratory dermal dendritic cells in the skin-draining lymph nodes of L. donovani-infected malnourished mice. Expression of chemokines and their receptors involved in trafficking of dendritic cells and their progenitors to the lymph nodes was dysregulated. C-C chemokine receptor type 2 (CCR2) and its ligands (CCL2 and CCL7) were reduced in the lymph nodes of infected malnourished mice, as were CCR2-bearing monocytes/macrophages and monocyte-derived dendritic cells. However, CCR7 and its ligands (CCL19 and CCL21) were increased in the lymph node and CCR7 was increased in lymph node macrophages and dendritic cells. CCR2-deficient mice recapitulated the profound reduction in the number of resident (but not migratory dermal) dendritic cells in the lymph node but showed no alteration in the expression of CCL19 and CCL21. Collectively, these results suggest that the malnutrition-related reduction in the lymph node barrier to dissemination of L. donovani is related to insufficient numbers of lymph node-resident but not migratory dermal dendritic cells. This is likely driven by the altered activity of the CCR2 and CCR7 chemoattractant pathways. C1 [Ibrahim, Marwa K.; Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Ibrahim, Marwa K.; Barnes, Jeffrey L.; Anstead, Gregory M.; Jimenez, Fabio; Ahuja, Seema S.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Ibrahim, Marwa K.] Natl Res Ctr, Genet Engn Div, Dept Microbial Biotechnol, Giza, Egypt. [Barnes, Jeffrey L.; Anstead, Gregory M.; Jimenez, Fabio; Ahuja, Seema S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Osterholzer, John J.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Osterholzer, John J.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Osorio, E. Yaneth; Travi, Bruno L.; White, A. Clinton, Jr.; Melby, Peter C.] Univ Texas, Med Branch, Dept Internal Med, Galveston, TX USA. [Osorio, E. Yaneth; Travi, Bruno L.; White, A. Clinton, Jr.; Melby, Peter C.] Univ Texas, Med Branch, Ctr Trop Dis, Galveston, TX USA. [Travi, Bruno L.; Melby, Peter C.] Univ Texas, Med Branch Galveston, Dept Microbiol & Immunol, Galveston, TX USA. [Melby, Peter C.] Univ Texas, Med Branch Galveston, Dept Pathol, Galveston, TX USA. RP Melby, PC (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. EM pcmelby@utmb.edu OI White, A Clinton/0000-0002-9668-4632; Ibrahim, Marwa/0000-0002-2603-8280 FU U.S. Department of Veterans Affairs; Department of Internal Medicine at the University of Texas Medical Branch FX This work was supported by funding from the U.S. Department of Veterans Affairs and the Department of Internal Medicine at the University of Texas Medical Branch (to P.C.M.). NR 68 TC 3 Z9 3 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2014 VL 82 IS 8 BP 3098 EP 3112 DI 10.1128/IAI.01778-14 PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL5GK UT WOS:000339161400002 PM 24818662 ER PT J AU Pfeiffer, CD Beldavs, ZG AF Pfeiffer, Christopher D. Beldavs, Zintars G. TI Much to Do about Carbapenem-Resistant Enterobacteriaceae: Why Supplementing Surveillance May Be the Key to Stopping Spread SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID KLEBSIELLA-PNEUMONIAE; INTERVENTION; HOSPITALS; REGION C1 [Pfeiffer, Christopher D.] Portland VA Med Ctr, Dept Hosp & Specialty Med, Portland, OR 97239 USA. [Pfeiffer, Christopher D.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Beldavs, Zintars G.] Oregon Hlth Author, Publ Hlth Div, Portland, OR USA. RP Pfeiffer, CD (reprint author), Portland VA Med Ctr, POB 1034 P3-ID, Portland, OR 97239 USA. EM pfeiffec@ohsu.edu NR 18 TC 2 Z9 2 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD AUG PY 2014 VL 35 IS 8 BP 984 EP 986 DI 10.1086/677158 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AL3RQ UT WOS:000339046900007 PM 25026613 ER PT J AU Singh, A Bartsch, SM Muder, RR Lee, BY AF Singh, Ashima Bartsch, Sarah M. Muder, Robert R. Lee, Bruce Y. TI An Economic Model: Value of Antimicrobial-Coated Sutures to Society, Hospitals, and Third-Party Payers in Preventing Abdominal Surgical Site Infections SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; STERNAL WOUND INFECTIONS; POLYGLACTIN 910 VICRYL; COLORECTAL SURGERY; TOPICAL ANTIBIOTICS; ACQUIRED INFECTION; COST-EFFECTIVENESS; TRICLOSAN; CLOSURE; RISK AB BACKGROUND. While the persistence of high surgical site infection (SSI) rates has prompted the advent of more expensive sutures that are coated with antimicrobial agents to prevent SSIs, the economic value of such sutures has yet to be determined. METHODS. Using Tree Age Pro, we developed a decision analytic model to determine the cost-effectiveness of using antimicrobial sutures in abdominal incisions from the hospital, third-party payer, and societal perspectives. Sensitivity analyses systematically varied the risk of developing an SSI (range, 5%-20%), the cost of tridosan-coated sutures (range, $5-$25/inch), and triclosan-coated suture efficacy in preventing infection (range, 5%-50%) to highlight the range of costs associated with using such sutures. RESULTS. Triclosan-coated sutures saved $4,109-$13,975 (hospital perspective), $4,133-$14,297 (third-party payer perspective), and $40,127-$53,244 (societal perspective) per SSI prevented, when a surgery had a 15% SSI risk, depending on their efficacy. If the SSI risk was no more than 5% and the efficacy in preventing SSIs was no more than 10%, tridosan-coated sutures resulted in extra expenditure for hospitals and third-party payers (resulting in extra costs of $1,626 and $1,071 per SSI prevented for hospitals and third-party payers, respectively; SSI risk, 5%; efficacy, 10%). CONCLUSIONS. Our results suggest that switching to triclosan-coated sutures from the uncoated sutures can both prevent SSIs and save substantial costs for hospitals, third-party payers, and society, as long as efficacy in preventing SSIs is at least 10% and SSI risk is at least 10%. C1 [Singh, Ashima] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Bartsch, Sarah M.; Lee, Bruce Y.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Muder, Robert R.] Univ Pittsburgh, Div Infect Dis, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Lee, BY (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 855 North Wolfe St,Suite 600, Baltimore, MD 21205 USA. EM bruceleemdmba@gmail.com FU National Institute of General Medical Sciences; Pennsylvania Department of Health FX This study was supported by the National Institute of General Medical Sciences Models of Infectious Disease Agent Study and the Pennsylvania Department of Health. The funders had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 60 TC 10 Z9 10 U1 3 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD AUG PY 2014 VL 35 IS 8 BP 1013 EP 1020 DI 10.1086/677163 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AL3RQ UT WOS:000339046900012 PM 25026618 ER PT J AU Garrett, SM Whitaker, RM Beeson, CC Schnellmann, RG AF Garrett, Sara M. Whitaker, Ryan M. Beeson, Craig C. Schnellmann, Rick G. TI Agonism of the 5-Hydroxytryptamine 1F Receptor Promotes Mitochondrial Biogenesis and Recovery from Acute Kidney Injury SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; PGC-1-ALPHA MESSENGER-RNA; PROXIMAL TUBULE CELLS; INDUCED LIVER-INJURY; 5-HT1F RECEPTOR; SKELETAL-MUSCLE; MIGRAINE TREATMENT; ENDOTHELIAL-CELLS; ACTIVATION; DYSFUNCTION AB Many acute and chronic conditions, such as acute kidney injury, chronic kidney disease, heart failure, and liver disease, involve mitochondrial dysfunction. Although we have provided evidence that drug-induced stimulation of mitochondrial biogenesis (MB) accelerates mitochondrial and cellular repair, leading to recovery of organ function, only a limited number of chemicals have been identified that induce MB. The goal of this study was to assess the role of the 5-hydroxytryptamine 1F (5-HT1F) receptor in MB. Immunoblot and quantitative polymerase chain reaction analyses revealed 5-HT1F receptor expression in renal proximal tubule cells (RPTC). A MB screening assay demonstrated that two selective 5-HT1F receptor agonists, LY334370 (4-fluoro-N-[3-(1-methyl- 4-piperidinyl)-1H-indol-5-yl] benzamide) and LY344864 (N-[(3R)-3-(dimethylamino)-2,3,4,9-tetrahydro-1H-carbazol-6-yl]- 4-fluorobenzamide; 1-100 nM) increased carbonylcyanide-p-trifluoromethoxyphenylhydrazone-uncoupled oxygen consumption in RPTC, and validation studies confirmed both agonists increased mitochondrial proteins [e.g., ATP synthase beta, cytochrome c oxidase 1 (Cox1), and NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 (NDUFB8)] in vitro. Small interfering RNA knockdown of the 5-HT1F receptor blocked agonist-induced MB. Furthermore, LY344864 increased peroxisome proliferator-activated receptor coactivator 1-alpha, Cox1, and NDUFB8 transcript levels and mitochondrial DNA (mtDNA) copy number in murine renal cortex, heart, and liver. Finally, LY344864 accelerated recovery of renal function, as indicated by decreased blood urea nitrogen and kidney injury molecule 1 and increased mtDNA copy number following ischemia/reperfusion-induced acute kidney injury (AKI). In summary, these studies reveal that the 5-HT1F receptor is linked to MB, 5-HT1F receptor agonism promotes MB in vitro and in vivo, and 5-HT1F receptor agonism promotes recovery from AKI injury. Induction of MB through 5-HT1F receptor agonism represents a new target and approach to treat mitochondrial organ dysfunction. C1 [Garrett, Sara M.; Whitaker, Ryan M.; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health National Institute of General Medical Sciences [R01-GM084147]; National Institutes of Health National Center for Research Resources [UL1RR029882]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [1BX000851]; South Carolina Clinical and Translational Research Institute; Medical University of South Carolina; National Institutes of Health Ruth L. Kirschstein National Research Service Award [5T32-DK083262-03]; National Institutes of Health [C06-RR015455] FX This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grant R01-GM084147]; the National Institutes of Health National Center for Research Resources [Grant UL1RR029882]; the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [1BX000851]; the South Carolina Clinical and Translational Research Institute, with an academic home at the Medical University of South Carolina; and the National Institutes of Health Ruth L. Kirschstein National Research Service Award [Grant 5T32-DK083262-03]. Animal facilities were funded by the National Institutes of Health National Center for Research Resources [Grant C06-RR015455]. NR 51 TC 7 Z9 7 U1 1 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 2014 VL 350 IS 2 BP 257 EP 264 DI 10.1124/jpet.114.214700 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AL6VJ UT WOS:000339270800008 PM 24849926 ER PT J AU Lin, XC Kraut, JA Wu, DM AF Lin, Xinchun Kraut, Jeffrey A. Wu, Dongmei TI Coadministration of a Na+-H+ exchange inhibitor and sodium bicarbonate for the treatment of asphyxia-induced cardiac arrest in piglets SO PEDIATRIC RESEARCH LA English DT Article ID LACTIC-ACIDOSIS; BLOOD-FLOW; REPERFUSION INJURY; RESUSCITATION; DYSFUNCTION; ACTIVATION; SABIPORIDE; ISCHEMIA; SM-20220; THERAPY AB BACKGROUND: The present study tested the hypothesis that addition of an inhibitor of Na+/H+ exchanger (NHE1) to sodium bicarbonate might improve the response to base therapy from prolonged asphyxial cardiac arrest in piglets. METHODS: Asphyxial cardiac arrest was induced by endotracheal tube clamping. Animals were randomly assigned to four study groups: (i) vehicle control, (ii) administration of sabiporide (NHE1 inhibitor), (iii) administration of sodium bicarbonate, and (iv) administration of sabiporide and sodium bicarbonate. RESULTS: Administration of sodium bicarbonate alone did not affect survival, hemodynamic measures, and regional blood flow to critical tissues such as brain, heart, kidney, liver, and spleen. In contrast, sabiporide given alone or combined with sodium bicarbonate improved these. Furthermore, treatment with sabiporide reduced accumulation of neutrophils, reduced cytokine production in the lung, and reduced plasma levels of cardiac troponin-I, alanine aminotransferase, aspartate aminotransferase, and urea. In addition, the combined use of sabiporide and sodium bicarbonate had more profound reduction in interleukin (IL)-6 and IL-10, compared to sabiporide alone. CONCLUSION: These results suggest that addition of sabiporide to the administration of sodium bicarbonate might improve hemodynamic response and dampen the inflammatory cascade noted with cardiac arrest, and therefore being an attractive option in the treatment of cardiac arrest. C1 [Lin, Xinchun; Wu, Dongmei] Mt Sinai Med Ctr, Dept Res, Miami Beach, FL 33140 USA. [Kraut, Jeffrey A.] Vet Adm Greater Los Angeles Healthcare Syst, Med & Res Serv, Los Angeles, CA USA. [Kraut, Jeffrey A.] Vet Adm Greater Los Angeles Healthcare Syst, Div Nephrol, Los Angeles, CA USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Wu, Dongmei] Chonbuk Natl Univ, Dept Biotechnol Informat Sci & Nanotechnol BIN Fu, Jeonju, South Korea. RP Wu, DM (reprint author), Mt Sinai Med Ctr, Dept Res, Miami Beach, FL 33140 USA. EM dongmeiwu@bellsouth.net RI Wu, Dongmei/I-3213-2016 FU US Army Medical Research and Material Command [W81XWH-06-1-0719]; Basic Science Research Program of the National Research Foundation of Korea [NRF-2012007331] FX This work was supported in part by a US Army Medical Research and Material Command grant W81XWH-06-1-0719 (D.W.) and by the Basic Science Research Program of the National Research Foundation of Korea (NRF-2012007331). NR 40 TC 2 Z9 2 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD AUG PY 2014 VL 76 IS 2 BP 118 EP 126 DI 10.1038/pr.2014.65 PG 9 WC Pediatrics SC Pediatrics GA AL6GO UT WOS:000339230800001 PM 24796369 ER PT J AU Robinson, ES Okawa, J Feng, R Payne, AS Werth, V AF Robinson, E. S. Okawa, J. Feng, R. Payne, A. S. Werth, V. TI The incidence of herpes zoster in patients with cutaneous lupus erythematosus, dermatomyositis, and pemphigus vulgaris is increased compared to the average US population SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Robinson, E. S.; Okawa, J.; Werth, V.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Robinson, E. S.; Okawa, J.; Payne, A. S.; Werth, V.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Feng, R.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2014 VL 134 IS 8 MA LB827 BP S6 EP S6 PG 1 WC Dermatology SC Dermatology GA AL4SW UT WOS:000339126100073 ER PT J AU Xu, J Jiang, Y Wang, J Shi, X Liu, Q Liu, Z Li, Y Scott, MJ Xiao, G Li, S Fan, L Billiar, TR Wilson, MA Fan, J AF Xu, J. Jiang, Y. Wang, J. Shi, X. Liu, Q. Liu, Z. Li, Y. Scott, M. J. Xiao, G. Li, S. Fan, L. Billiar, T. R. Wilson, M. A. Fan, J. TI Macrophage endocytosis of high-mobility group box 1 triggers pyroptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Article ID GLYCATION END-PRODUCTS; CELL-DEATH; INFLAMMASOME ACTIVATION; NLRP3 INFLAMMASOME; NALP3 INFLAMMASOME; NEURITE OUTGROWTH; ENDOTHELIAL-CELLS; LATE MEDIATOR; RECEPTOR; HMGB1 AB Macrophages can be activated and regulated by high-mobility group box 1 (HMGB1), a highly conserved nuclear protein. Inflammatory functions of HMGB1 are mediated by binding to cell surface receptors, including the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, TLR4, and TLR9. Pyroptosis is a caspase-1-dependent programmed cell death, which features rapid plasma membrane rupture, DNA fragmentation, and release of proinflammatory intracellular contents. Pyroptosis can be triggered by various stimuli, however, the mechanism underlying pyroptosis remains unclear. In this study, we identify a novel pathway of HMGB1-induced macrophage pyroptosis. We demonstrate that HMGB1, acting through RAGE and dynamin-dependent signaling, initiates HMGB1endocytosis, which in turn induces cell pyroptosis. The endocytosis of HMGB1 triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. We further confirm that HMGB1-induced macrophage pyroptosis also occurs in vivo during endotoxemia, suggesting a pathophysiological significance for this form of pyroptosis in the development of inflammation. These findings shed light on the regulatory role of ligand-receptor internalization in directing cell fate, which may have an important role in the progress of inflammation following infection and injury. C1 [Xu, J.; Wang, J.; Shi, X.; Liu, Z.; Li, Y.; Scott, M. J.; Billiar, T. R.; Wilson, M. A.; Fan, J.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Xu, J.; Jiang, Y.; Wang, J.; Liu, Z.] Southern Med Univ, Dept Pathophysiol, Guangzhou 510515, Guangdong, Peoples R China. [Shi, X.] Xi An Jiao Tong Univ, Coll Med, Dept Pharmacol, Xian 710049, Peoples R China. [Liu, Q.] Univ Pittsburgh, Sch Med, Thomas E Starzl Transplantat Inst, Dept Surg, Pittsburgh, PA USA. [Liu, Q.] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiovasc Surg, Harbin, Peoples R China. [Xiao, G.] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. [Li, S.] Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Dept Pharmaceut Sci, Pittsburgh, PA USA. [Fan, L.] Univ Pittsburgh, Sch Arts & Sci, Pittsburgh, PA USA. [Billiar, T. R.; Fan, J.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Wilson, M. A.; Fan, J.] Vet Affairs Pittsburgh Healthcare Syst, Res & Dev, Pittsburgh, PA USA. RP Jiang, Y (reprint author), Southern Med Univ, Dept Pathophysiol, Guangzhou 510515, Guangdong, Peoples R China. EM jiang48231@163.com; jif7@pitt.edu FU National Institutes of Health [R01-HL-079669, P50-GM-53789]; VA Merit Award; National Key Basic Research Program (China) [2010CB529704]; PCSIRT [IRT0731]; National Natural Science Foundation of China [30670828] FX This work was supported by the National Institutes of Health Grant R01-HL-079669 (JF and MAW), National Institutes of Health Center Grant P50-GM-53789 (TRB and JF), a VA Merit Award (JF), National Key Basic Research Program 2010CB529704 (YJ, China), PCSIRT IRT0731 (YJ), and National Natural Science Foundation of China 30670828 (YJ). NR 37 TC 24 Z9 26 U1 4 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD AUG PY 2014 VL 21 IS 8 BP 1229 EP 1239 DI 10.1038/cdd.2014.40 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AK8UQ UT WOS:000338704500005 PM 24769733 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Ubiquitous occurrence of birth-cohort patterns in inflammatory bowel disease SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE birth-cohort pattern; Crohn's disease; death rates; ethnicity; time trends; ulcerative colitis ID ULCERATIVE-COLITIS; CROHNS-DISEASE; TIME TRENDS; PREVALENCE; MORTALITY AB Background and aims The aim of the present study was to demonstrate the ubiquitous occurrence of the birth-cohort phenomenon of inflammatory bowel disease among US whites and nonwhites, as well as males and females. Methods Mortality from Crohn's disease and ulcerative colitis in the USA between 1950 and 2010 were analyzed to discern underlying birth-cohort patterns affecting both their time trends. Age-standardized cohort mortality ratio was used as a summary statistic to represent the overall mortality associated with consecutive birth-cohorts. Results The cohort-age contours of Crohn's disease aligned to form one hyperbola with an initial rise between 1865 and 1935 and a subsequent decline. This pattern was confirmed by the time trends of the corresponding standardized cohort mortality ratio values. In ulcerative colitis, the individual cohort-age contours also aligned into one hyperbola that appeared shifted towards earlier generations by about 30 years when compared with Crohn's disease. Similar trends were observed in men and women or whites and nonwhites analyzed separately. Conclusion The birth-cohort patterns indicate that exposure to two separate risk factors must have occurred in both diseases during an early period of life. In the USA, these exposures have changed over historical times similarly in both sexes and different ethnic groups. Eur J Gastroenterol Hepatol 26: 888- 893 (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X EI 1473-5687 J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD AUG PY 2014 VL 26 IS 8 BP 888 EP 893 DI 10.1097/MEG.0000000000000118 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AK9BK UT WOS:000338722300009 PM 24987824 ER PT J AU Akber, A Portale, AA Johansen, KL AF Akber, Aalia Portale, Anthony A. Johansen, Kirsten L. TI Use of pedometers to increase physical activity among children and adolescents with chronic kidney disease SO PEDIATRIC NEPHROLOGY LA English DT Article DE Physical activity; Children; Adolescents; Health-related quality of life; Physical performance ID QUALITY-OF-LIFE; AMBULATORY PATIENTS; PEDIATRIC-PATIENTS; HEALTH; HEMODIALYSIS; TRANSPLANT; STEPS/DAY; DIALYSIS; EXERCISE; ADULTS AB Children and adolescents with chronic kidney disease (CKD) are inactive relative to their peers. Forty-four children and adolescents aged 7-20 years with CKD, end-stage renal disease (ESRD) on dialysis or a kidney transplant participated in a 12-week pedometer-based intervention to increase physical activity. Patients recorded daily step counts and reported them weekly. Pediatric Quality of Life Inventory (PedsQL) and 6-min walk (6 MW) were administered at baseline and after 12 weeks. Age was 15.1 +/- 3.4 years; 27 % had CKD, 16 % were receiving dialysis, and 57 % had received a kidney transplant. Mean daily step count did not change significantly (+48, 95 % CI -48 to +145 steps/day per week). Transplant recipients and patients with CKD increased their activity by 100 steps/day (95 % CI -14 to 208) and 73 steps/day (95 % CI -115 to 262) each week, respectively, and patients on dialysis decreased by 133 steps/day (95 % CI -325 to 58; p value for interaction 0.03) in multivariable analysis. Change in physical activity was associated with change in 6 MW distance (r = 0.74, p < 0.001) and change in physical functioning (r = 0.53, p = 0.001). Youths with CKD did not significantly increase their activity over 12 weeks of a pedometer-based intervention. However, changes in physical activity were associated with changes in physical functioning and performance. C1 [Akber, Aalia] Kaiser Oakland Med Ctr, Div Nephrol, Dept Pediat, Oakland, CA USA. [Portale, Anthony A.] Univ Calif San Francisco, Dept Pediat, Div Nephrol, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU Genzyme Corp; Abbott Laboratories FX Dr. Johansen serves on the National Nephrology Advisory Board of Amgen and as Deputy Editor for the Clinical Journal of the American Society of Nephrology. Dr. Portale receives research support from Genzyme Corp and Abbott Laboratories. NR 25 TC 2 Z9 2 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X EI 1432-198X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD AUG PY 2014 VL 29 IS 8 BP 1395 EP 1402 DI 10.1007/s00467-014-2787-6 PG 8 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA AK8TH UT WOS:000338700400014 PM 24648129 ER PT J AU Le, H Khankhanian, P Joshi, N Maa, J Crevensten, H AF Le, Hai Khankhanian, Pouya Joshi, Neha Maa, John Crevensten, Henry TI Patients Recovering From Abdominal Surgery Who Walked With Volunteers Had Improved Postoperative Recovery Profiles during Their Hospitalization SO WORLD JOURNAL OF SURGERY LA English DT Article ID COLORECTAL SURGERY; ENHANCED RECOVERY; CARE; PATHWAY; LENGTH; STAY AB Early walking as part of a perioperative care program benefits patients who have had surgery. However, the impact of early walking by itself on the mental and physical recovery of postoperative patients has not been examined. We established a program called walking to recovery (WTR) in which college volunteers provided walking assistance to patients recovering after abdominal surgery. Patients who participated in the program were compared with patients who did not. The postoperative recovery profile survey (PRP-17) was administered on day of discharge to 15 participants and 15 non-participants. Medical records were reviewed to obtain indication for surgery, type of surgery, length of hospital stay, and postoperative complications. At 1 month post-discharge, a short form (SF)-12v2 questionnaire was administered by telephone to assess postoperative quality of life as defined by mental and physical level of function and measured with the mental component score (MCS) and the physical component score (PCS). The average age of participants and non-participants was similar (48.9 +/- A 9.8 vs. 51.4 +/- A 8.7 years; p = 0.28). When the two groups were approximately matched by type and severity of surgery, participants had lower PRP-17 composite scores (9.9 vs. 12.5, p = 0.003) and higher indicator sums (9.8 vs. 8.4, p = 0.04) than non-participants, both of which indicate better postoperative recovery in participants. The mean immobilization score was significantly lower in participants (0.3 vs. 0.8, p = 0.04). Postoperative length of stay and MCS did not differ between the two groups, but in participants there was a trend for higher scores in the PCS. Walking with volunteers was associated with a better PRP during the hospitalization period but not at 1 month follow-up. The WTR program is a sustainable, cost-effective model program for other hospitals to emulate as part of the standard of care of postoperative patients. C1 [Le, Hai; Khankhanian, Pouya; Joshi, Neha] Univ Calif San Francisco, Sch Med, San Francisco, CA 94115 USA. [Maa, John] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Crevensten, Henry] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Crevensten, Henry] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Le, H (reprint author), Univ Calif San Francisco, Sch Med, San Francisco, CA 94115 USA. EM hai.le@ucsf.edu; hcrevensten@medicine.ucsf.edu NR 15 TC 2 Z9 2 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD AUG PY 2014 VL 38 IS 8 BP 1961 EP 1965 DI 10.1007/s00268-014-2491-5 PG 5 WC Surgery SC Surgery GA AK7WV UT WOS:000338639300015 PM 24615609 ER PT J AU Bensing, BA Seepersaud, R Yen, YT Sullam, PM AF Bensing, Barbara A. Seepersaud, Ravin Yen, Yihfen T. Sullam, Paul M. TI Selective transport by SecA2: An expanding family of customized motor proteins SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE Accessory Sec system; Glycoprotein transport; Bacterial glycoprotein; Asp1; Asp2; S-layer ID STREPTOCOCCUS-GORDONII DL1; ACID-BINDING ADHESIN; ALGA CYANIDIOSCHYZON-MEROLAE; SIGNAL-SEQUENCE RECOGNITION; SURFACE GLYCOPROTEINS GSPB; FIMBRIA-ASSOCIATED ADHESIN; RICH REPEAT GLYCOPROTEIN; STAPHYLOCOCCUS-AUREUS; TRANSLOCATION CHANNEL; LISTERIA-MONOCYTOGENES AB The SecA2 proteins are a special class of transport-associated ATPases that are related to the SecA component of the general Sec system, and are found in an increasingly large number of Gram-positive bacterial species. The SecA2 substrates are typically linked to the cell wall, but may be lipid-linked, peptidoglycan-linked, or non-covalently associated S-layer proteins. These substrates can have a significant impact on virulence of pathogenic organisms, but may also aid colonization by commensals. The SecA2 orthologues range from being highly similar to their SecA paralogues, to being distinctly different in apparent structure and function. Two broad classes of SecA2 are evident One transports multiple substrates, and may interact with the general Sec system, or with an as yet unidentified transmembrane channel. The second type transports a single substrate, and is a component of the accessory Sec system, which includes the SecY paralogue SecY2 along with the accessory Sec proteins Asp1-3. Recent studies indicate that the latter three proteins may have a unique role in coordinating post-translational modification of the substrate with transport by SecA2. Comparative functional and phylogenetic analyses suggest that each SecA2 may be uniquely adapted for a specific type of substrate. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. Published by Elsevier B.V. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Bensing, BA (reprint author), VA Med Ctr 111W2, Div Infect Dis, 4150 Clement St, San Francisco, CA 94121 USA. EM barbara.bensing@ucsf.edu FU Department of Veterans Affairs; VA Merit Review program; Northern California Institute for Research and Education; NIH [R01-AI41513]; American Heart Association (AHA), Western Affiliate FX This work was supported by the Department of Veterans Affairs and the VA Merit Review program; the Northern California Institute for Research and Education; grant R01-AI41513 from the NIH (P.M.S.); and a Fellowship Award from the American Heart Association (AHA), Western Affiliate (YY). NR 97 TC 13 Z9 13 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 EI 0006-3002 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD AUG PY 2014 VL 1843 IS 8 SI SI BP 1674 EP 1686 DI 10.1016/j.bbamcr.2013.10.019 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AK7GE UT WOS:000338595800025 PM 24184206 ER PT J AU Wang, JY Shi, YJ Zhang, LL Zhang, F Hu, XM Zhang, WT Leak, RK Gao, YQ Chen, L Chen, J AF Wang, Jiayin Shi, Yejie Zhang, Lili Zhang, Feng Hu, Xiaoming Zhang, Wenting Leak, Rehana K. Gao, Yanqin Chen, Ling Chen, Jun TI Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Angiogenesis; Angiopoietin 2; Astrocyte; Neuroprotection; Omega-3 polyunsaturated fatty acids; Stroke; VEGF ID ENDOTHELIAL GROWTH-FACTOR; BLOOD-BRAIN-BARRIER; DOCOSAHEXAENOIC ACID; ISCHEMIC-STROKE; VASCULAR-PERMEABILITY; CELL TRANSPLANTATION; SIGNALING PATHWAY; FISH-OIL; IN-VIVO; INJURY AB Stroke is a devastating neurological disorder and one of the leading causes of death and serious disability. After cerebral ischemia, revascularization in the ischemic boundary zone provides nutritive blood flow as well as various growth factors to promote the survival and activity of neurons and neural progenitor cells. Enhancement of angiogenesis and the resulting improvement of cerebral microcirculation are key restorative mechanisms and represent an important therapeutic strategy for ischemic stroke. In the present study, we tested the hypothesis that post-stroke angiogenesis would be enhanced by omega-3 polyunsaturated fatty acids (n - 3 PUFAs), a major component of dietary fish oil. To this end, we found that transgenic fat-1 mice that overproduce n - 3 PUFAs exhibited long-term behavioral and histological protection against transient focal cerebral ischemia (tECI). Importantly, fat-1 transgenic mice also exhibited robust improvements in revascularization and angiogenesis compared to wild type littermates, suggesting a potential role for n - 3 fatty acids in post-stroke cerebrovascular remodeling. Mechanistically, n - 3 PUFAs induced upregulation of angiopoietin 2 (Ang 2) in astrocytes after tFCI and stimulated extracellular Ang 2 release from cultured astrocytes after oxygen and glucose deprivation. Ang 2 facilitated endothelial proliferation and barrier formation in vitro by potentiating the effects of VEGF on phospholipase C gamma 1 and Src signaling. Consistent with these findings, blockade of Src activity in post-stroke fat-1 mice impaired n - 3 PUFA-induced angiogenesis and exacerbated long-term neurological outcomes. Taken together, our findings strongly suggest that n - 3 PUPA supplementation is a potential angiogenic treatment capable of augmenting brain repair and improving long-term functional recovery after cerebral ischemia. (C) 2014 Elsevier Inc All rights reserved. C1 [Wang, Jiayin; Shi, Yejie; Zhang, Lili; Zhang, Feng; Hu, Xiaoming; Zhang, Wenting; Leak, Rehana K.; Gao, Yanqin; Chen, Ling; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. [Wang, Jiayin; Zhang, Feng; Hu, Xiaoming; Chen, Jun] Capital Med Univ, Xuanwu Hosp, Cell Therapy Ctr, Beijing 100053, Peoples R China. [Chen, Ling] Chinese Peoples Liberat Army Gen Hosp, Dept Neurosurg, Beijing 100853, Peoples R China. [Chen, Ling] Chinese Peoples Liberat Army Gen Hosp, PLA Inst Neurosurg, Beijing 100853, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Grad Sch Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Shi, Yejie; Zhang, Lili; Zhang, Feng; Hu, Xiaoming; Leak, Rehana K.; Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. RP Chen, L (reprint author), Chinese Peoples Liberat Army Gen Hosp, Dept Neurosurg, 28 Fuxing Rd, Beijing 100853, Peoples R China. EM chlyz34@163.com; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417; Shi, Yejie/0000-0001-7502-9201 FU NIH [NS036736, NS045048, NS056118]; Research Career Scientist Award from Department of Veterans Affairs; VA RR D Merit Review; High Level Talent Fund of the Beijing Healthcare System [2011-3-093]; Program for New Century Excellent Talents in University [NCET-12-0612]; National Natural Science Foundation of China [81301066]; Beijing Nova Program [XX2013019] FX This project was supported by NIH grants NS036736, NS045048, and NS056118 (to J.C.), the Research Career Scientist Award from Department of Veterans Affairs and the VA RR & D Merit Review (to J.C.). L.C. was supported by the High Level Talent Fund of the Beijing Healthcare System (Grant No. 2011-3-093) and the Program for New Century Excellent Talents in University (Grant No. NCET-12-0612). J.W. was supported by the National Natural Science Foundation of China (Grant No. 81301066) and Beijing Nova Program (Grant No. XX2013019). The authors are indebted to Carol Culver for excellent editorial assistance and Pat Strickler for excellent administrative support. NR 56 TC 17 Z9 17 U1 1 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD AUG PY 2014 VL 68 BP 91 EP 103 DI 10.1016/j.nbd.2014.04.014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AJ8XV UT WOS:000337992300009 PM 24794156 ER PT J AU Back, SE Gros, DF McCauley, JL Flanagan, JC Cox, E Barth, KS Brady, KT AF Back, Sudie E. Gros, Daniel F. McCauley, Jenna L. Flanagan, Julianne C. Cox, Elizabeth Barth, Kelly S. Brady, Kathleen T. TI Laboratory-induced cue reactivity among individuals with prescription opioid dependence SO ADDICTIVE BEHAVIORS LA English DT Article DE Prescription opioids; Opiates; Prescription drugs; Drug cue reactivity; Drug cue paradigm ID DRUG-RELATED CUES; ADDICTION RESEARCH; HEROIN-ADDICTS; OPIATE ADDICTS; ALCOHOL; SMOKING; RELAPSE; ABUSE; METAANALYSIS; EXPOSURE AB Prescription opioid (PO) dependence is a critical health problem. Although examination of drug cue reactivity paradigms has advanced the understanding of risk factors for relapse for a variety of substances (e.g., cocaine, alcohol, nicotine), no PO specific drug cue paradigm has been developed. The current study addressed this gap in the literature and evaluated the ability of a newly developed PO drug cue paradigm to elicit subjective, physiological, and neuroendocrine changes among PO-dependent participants (n = 20) as compared to controls (n = 17). The drug cue paradigm included an induction script, viewing and handling paraphernalia (e.g., bottle of oxycontin pills, pill crusher) and watching a video depicting people using POs as well as places related to POs (e.g., pharmacies). Consistent with hypotheses, the PO group demonstrated significant pre- to post-cue increases on subjective ratings of craving, difficulty resisting POs, stress, and anger. The control group did not demonstrate significant changes on any of the subjective measures. Both the PO group and the control group evidenced significant pre- to post-cue increases in physiological responses (e.g., blood pressure, skin conductance), as expected given the arousing nature of the drug cue stimuli. The PO group, but not the control group, evidenced a significant pre- to post-cue increase in heart rate and salivary cortisol levels. The development and validation of a drug cue paradigm for POs may help inform future research and treatment development efforts for patients with PO dependence. Published by Elsevier Ltd. C1 [Back, Sudie E.; Gros, Daniel F.; McCauley, Jenna L.; Flanagan, Julianne C.; Barth, Kelly S.; Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, Charleston, SC 29425 USA. [Back, Sudie E.; Gros, Daniel F.; Brady, Kathleen T.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Cox, Elizabeth] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27514 USA. RP Back, SE (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, 67 President St,MSC861, Charleston, SC 29425 USA. EM backs@musc.edu FU National Institute on Drug Abuse [K23 DA021228, K12 DA031974, K12 HD055885]; National Institute of Health [5 UL1 RR029882] FX This work was supported in part by grants K23 DA021228 (Back), K12 DA031974 (Brady), and K12 HD055885 (Brady) from the National Institute on Drug Abuse, and National Institute of Health grant 5 UL1 RR029882 (Brady). NIDA and NIH had no further role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. NR 67 TC 3 Z9 3 U1 8 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD AUG PY 2014 VL 39 IS 8 BP 1217 EP 1223 DI 10.1016/j.addbeh.2014.04.007 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AI8YD UT WOS:000337212000002 PM 24813546 ER PT J AU Denneson, LM Corson, K Helmer, DA Bair, MJ Dobscha, SK AF Denneson, Lauren M. Corson, Kathryn Helmer, Drew A. Bair, Matthew J. Dobscha, Steven K. TI Mental health utilization of new-to-care Iraq and Afghanistan Veterans following suicidal ideation assessment SO PSYCHIATRY RESEARCH LA English DT Article DE Depression; Risk assessment; Suicide; Delivery of health care ID SERVICES TASK-FORCE; OEF/OIF VETERANS; ENDURING FREEDOM; DEPRESSION; RISK; PHQ-9; VA; THOUGHTS; VALIDITY; SCREENS AB We evaluated the impact of brief structured suicidal ideation (SI) assessments on mental health care among new-to-care Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) veterans. National datasets provided military, demographic, and clinical information. For all new-to-care OEF/OIF veterans administered depression screens (PHQ-2: Patient Health Questionnaire-2) and structured SI assessments in primary care or ambulatory mental health settings of three Veterans Affairs (VA) Medical Centers between April 2008 and September 2009 (N=465), generalized estimating equations were used to examine associations between SI and number of subsequent-year specialty mental health visits and antidepressant prescriptions. Approximately one-third of the veterans reported SI. In multivariate models, PTSD and anxiety diagnoses, severe depression symptoms, being married, and SI assessment by a mental health clinician were associated with more mental health visits in the subsequent year. Depression, PTSD, and anxiety diagnoses, and SI assessment by a mental health clinician were associated with receiving antidepressants. Presence of SI did not significantly affect subsequent year mental health utilization when adjusting for diagnostic and clinician variables, but inaugural visits involving mental health clinicians were consistently associated with subsequent mental health care. Published by Elsevier Ireland Ltd. C1 [Denneson, Lauren M.; Corson, Kathryn; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Improve Vet Involvement Care CIVIC, Portland, OR 97207 USA. [Denneson, Lauren M.; Corson, Kathryn; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Helmer, Drew A.] VA New Jersey Hlth Care Syst, War Related Illness & Injury Study Ctr, E Orange, NJ USA. [Helmer, Drew A.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med & Dent, Newark, NJ 07103 USA. [Bair, Matthew J.] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. RP Denneson, LM (reprint author), Portland VA Med Ctr, POB 1034 R&D66, Portland, OR 97207 USA. EM lauren.denneson@va.gov FU U.S. Department of Veterans Affairs, Veterans Health Administration; Health Services Research and Development Service Project [DHI-08-096]; Center to Improve Veteran Involvement in Care (CIVIC) at the Portland VA Medical Center; Department of Veterans Affairs or the United States government FX This material is based upon work supported by the U.S. Department of Veterans Affairs, Veterans Health Administration, and Health Services Research and Development Service Project DHI-08-096. Dr. Denneson is a core investigator in the Center to Improve Veteran Involvement in Care (CIVIC) at the Portland VA Medical Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 37 TC 2 Z9 2 U1 2 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL 30 PY 2014 VL 217 IS 3 BP 147 EP 153 DI 10.1016/j.psychres.2014.03.017 PG 7 WC Psychiatry SC Psychiatry GA AI5AS UT WOS:000336878400004 PM 24726814 ER PT J AU Gupta, A Wang, YF Spertus, JA Geda, M Lorenze, N Nkonde-Price, C D'Onofrio, G Lichtman, JH Krumholz, HM AF Gupta, Aakriti Wang, Yongfei Spertus, John A. Geda, Mary Lorenze, Nancy Nkonde-Price, Chileshe D'Onofrio, Gail Lichtman, Judith H. Krumholz, Harlan M. TI Trends in Acute Myocardial Infarction in Young Patients and Differences by Sex and Race, 2001 to 2010 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE acute myocardial infarction; hospitalization; sex differences; trends; young women ID CORONARY-HEART-DISEASE; UNITED-STATES; CARDIOVASCULAR-DISEASE; MORTALITY-RATES; RISK-FACTORS; PREVALENCE; WOMEN; HOSPITALIZATION AB BACKGROUND Various national campaigns launched in recent years have focused on young women with acute myocardial infarctions (AMIs). Contemporary longitudinal data about sex differences in clinical characteristics, hospitalization rates, length of stay (LOS), and mortality have not been examined. OBJECTIVES This study sought to determine sex differences in clinical characteristics, hospitalization rates, LOS, and in-hospital mortality by age group and race among young patients with AMIs using a large national dataset of U.S. hospital discharges. METHODS Using the National Inpatient Sample, clinical characteristics, AMI hospitalization rates, LOS, and in-hospital mortality were compared for patients with AMI across ages 30 to 54 years, dividing them into 5-year subgroups from 2001 to 2010, using survey data analysis techniques. RESULTS A total of 230,684 hospitalizations were identified with principal discharge diagnoses of AMI in 30- to 54-year-old patients from Nationwide Inpatient Sample data, representing an estimated 1,129,949 hospitalizations in the United States from 2001 to 2010. No statistically significant declines in AMI hospitalization rates were observed in the age groups <55 years or stratified by sex. Prevalence of comorbidities was higher in women and increased among both sexes through the study period. Women had longer LOS and higher in-hospital mortality than men across all age groups. However, observed in-hospital mortality declined significantly for women from 2001 to 2010 (from 3.3% to 2.3%, relative change 30.5%; p for trend < 0.0001) but not for men (from 2% to 1.8%, relative change 8.6%; p for trend = 0.60). CONCLUSIONS AMI hospitalization rates for young people have not declined over the past decade. Young women with AMIs have more comorbidity, longer LOS, and higher in-hospital mortality than young men, although their mortality rates are decreasing. (C) 2014 by the American College of Cardiology Foundation C1 [Gupta, Aakriti; Wang, Yongfei; Geda, Mary; Lorenze, Nancy; Lichtman, Judith H.; Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Gupta, Aakriti] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Wang, Yongfei; Nkonde-Price, Chileshe; Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. [Spertus, John A.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA. [Nkonde-Price, Chileshe] Philadelphia VA Med Ctr, VA Ctr Hlth Equity & Res Promot, Philadelphia, PA USA. [Nkonde-Price, Chileshe] Univ Penn, Dept Internal Med, Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA 19104 USA. [D'Onofrio, Gail] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT 06510 USA. [Lichtman, Judith H.] Yale Univ, Sch Med, Dept Chron Dis Epidemiol, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT 06510 USA. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Dept Internal Med, 1 Church St,Suite 200, New Haven, CT 06510 USA. EM harlan.krumholz@yale.edu OI D'Onofrio, Gail/0000-0002-3833-1871 FU Center for Cardiovascular Outcomes Research at Yale University [U01 HL105270-04]; Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients [R01 LH081153-06]; Genentech; National Heart, Lung, and Blood Institute; Eli Lilly and Company FX This work was supported by grant U01 HL105270-04 (Center for Cardiovascular Outcomes Research at Yale University) and grant R01 LH081153-06 (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), both from the National Heart, Lung, and Blood Institute. Dr. Spertus has received research grants from Genentech and Eli Lilly and Company. Dr. Krumholz has a research agreement to share data with Johnson & Johnson; and is chair of a scientific advisory board of UnitedHealthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 20 TC 60 Z9 62 U1 4 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 29 PY 2014 VL 64 IS 4 BP 337 EP 345 DI 10.1016/j.jacc.2014.04.054 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AM9ZN UT WOS:000340240700001 PM 25060366 ER PT J AU Merlin, LR Horak, HA Milligan, TA Kraakevik, JA Ali, II AF Merlin, Lisa R. Horak, Holli A. Milligan, Tracey A. Kraakevik, Jeff A. Ali, Imran I. TI A competency-based longitudinal core curriculum in medical neuroscience SO NEUROLOGY LA English DT Article ID NEUROLOGY CLERKSHIP; CLINICAL SKILLS; BASIC SCIENCES; EDUCATION; PERFORMANCE; SIMULATION; CARE AB Current medical educational theory encourages the development of competency-based curricula. The Accreditation Council for Graduate Medical Education's 6 core competencies for resident education (medical knowledge, patient care, professionalism, interpersonal and communication skills, practice-based learning, and systems-based practice) have been embraced by medical schools as the building blocks necessary for becoming a competent licensed physician. Many medical schools are therefore changing their educational approach to an integrated model in which students demonstrate incremental acquisition and mastery of all competencies as they progress through medical school. Challenges to medical schools include integration of preclinical and clinical studies as well as development of learning objectives and assessment measures for each competency. The Undergraduate Education Subcommittee (UES) of the American Academy of Neurology (AAN) assembled a group of neuroscience educators to outline a longitudinal competency-based curriculum in medical neuroscience encompassing both preclinical and clinical coursework. In development of this curriculum, the committee reviewed United States Medical Licensing Examination content outlines, Liaison Committee on Medical Education requirements, prior AAN-mandated core curricula for basic neuroscience and clinical neurology, and survey responses from educators in US medical schools. The newly recommended curriculum provides an outline of learning objectives for each of the 6 competencies, listing each learning objective in active terms. Documentation of experiences is emphasized, and assessment measures are suggested to demonstrate adequate achievement in each competency. These guidelines, widely vetted and approved by the UES membership, aspire to be both useful as a stand-alone curriculum and also provide a framework for neuroscience educators who wish to develop a more detailed focus in certain areas of study. C1 [Merlin, Lisa R.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Merlin, Lisa R.] Kings Cty Hosp, Brooklyn, NY USA. [Horak, Holli A.] Univ Arizona, Tucson, AZ USA. [Milligan, Tracey A.] Harvard Univ, Sch Med, Boston, MA USA. [Milligan, Tracey A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kraakevik, Jeff A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kraakevik, Jeff A.] Portland VA Med Ctr, Portland, OR USA. [Ali, Imran I.] Univ Toledo, Toledo, OH USA. RP Merlin, LR (reprint author), Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. EM lisa.merlin@downstate.edu NR 24 TC 3 Z9 4 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUL 29 PY 2014 VL 83 IS 5 BP 456 EP 462 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AN0DV UT WOS:000340253900017 PM 24975860 ER PT J AU Gold, MC McLaren, JE Reistetter, JA Smyk-Pearson, S Ladell, K Swarbrick, GM Yu, YYL Hansen, TH Lund, O Nielsen, M Gerritsen, B Kesmir, C Miles, JJ Lewinsohn, DA Price, DA Lewinsohn, DM AF Gold, Marielle C. McLaren, James E. Reistetter, Joseph A. Smyk-Pearson, Sue Ladell, Kristin Swarbrick, Gwendolyn M. Yu, Yik Y. L. Hansen, Ted H. Lund, Ole Nielsen, Morten Gerritsen, Bram Kesmir, Can Miles, John J. Lewinsohn, Deborah A. Price, David A. Lewinsohn, David M. TI MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID VITAMIN-B METABOLITES; BACTERIAL-INFECTION; ALPHA-CHAIN; RECOGNITION; MR1; EXPRESSION AB Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that detects microbial metabolites presented by the nonpolymorphic major histocompatibility complex (MHC)-like molecule MR1. The highly conserved nature of MR1 in conjunction with biased MAIT TCR. chain usage is widely thought to indicate limited ligand presentation and discrimination within a pattern-like recognition system. Here, we evaluated the TCR repertoire of MAIT cells responsive to three classes of microbes. Substantial diversity and heterogeneity were apparent across the functional MAIT cell repertoire as a whole, especially for TCR beta chain sequences. Moreover, different pathogen-specific responses were characterized by distinct TCR usage, both between and within individuals, suggesting that MAIT cell adaptation was a direct consequence of exposure to various exogenous MR1-restricted epitopes. In line with this interpretation, MAIT cell clones with distinct TCRs responded differentially to a riboflavin metabolite. These results suggest that MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, providing a basis for adaptive memory via recruitment of specific repertoires shaped by microbial exposure.\ C1 [Gold, Marielle C.; Reistetter, Joseph A.; Smyk-Pearson, Sue; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97239 USA. [Gold, Marielle C.; Lewinsohn, Deborah A.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Swarbrick, Gwendolyn M.; Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA. [Gold, Marielle C.; Lewinsohn, David M.] Portland VA Med Ctr, Portland, OR 97239 USA. [McLaren, James E.; Ladell, Kristin; Miles, John J.; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales. [Yu, Yik Y. L.; Hansen, Ted H.] Washington Univ, St Louis Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Lund, Ole; Nielsen, Morten] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Nielsen, Morten] Univ Nacl San Martin, Inst Invest Biotecnol, RA-1650 Buenos Aires, DF, Argentina. [Gerritsen, Bram; Kesmir, Can] Univ Utrecht, Theoret Biol & Bioinformat Grp, NL-3584 CH Utrecht, Netherlands. [Miles, John J.] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia. [Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Gold, MC (reprint author), Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97239 USA. EM goldm@ohsu.edu; lewinsod@ohsu.edu RI Lund, Ole/F-4437-2014; Price, David/C-7876-2013; Ladell, Kristin/C-8301-2013; Kesmir, Can/B-9410-2011; Lewinsohn, David/I-4936-2013 OI Lund, Ole/0000-0003-1108-0491; Price, David/0000-0001-9416-2737; Ladell, Kristin/0000-0002-9856-2938; Lewinsohn, David/0000-0001-9906-9494; Nielsen, Morten/0000-0001-7885-4311 FU Department of Veterans Affairs with resources and facility access provided by the Portland VA Medical Center; National Institutes of Health (NIH) via the Mucosal Immunology Studies Team (MIST) - National Institute of Allergy and Infectious Diseases (NIH grant) [U01 AI095776-01, AI046553]; Wellcome Trust (UK); Wellcome Trust Senior Investigator FX This work was supported by the Department of Veterans Affairs with resources and facility access provided by the Portland VA Medical Center, the National Institutes of Health (NIH) via the Mucosal Immunology Studies Team (MIST) U01 AI095776-01 funded by the National Institute of Allergy and Infectious Diseases (NIH grant AI046553), and the Wellcome Trust (UK). D.A. Price is a Wellcome Trust Senior Investigator. NR 29 TC 49 Z9 49 U1 4 U2 16 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD JUL 28 PY 2014 VL 211 IS 8 BP 1601 EP 1610 DI 10.1084/jem.20140507 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AQ4DV UT WOS:000342743500010 PM 25049333 ER PT J AU Mathes, DW Chang, J Hwang, B Graves, SS Storer, BE Butts-Miwongtum, T Sale, GE Storb, R AF Mathes, David W. Chang, Jeff Hwang, Billanna Graves, Scott S. Storer, Barry E. Butts-Miwongtum, Tiffany Sale, George E. Storb, Rainer TI Simultaneous Transplantation of Hematopoietic Stem Cells and a Vascularized Composite Allograft Leads to Tolerance SO TRANSPLANTATION LA English DT Article DE Dog; Nonmyeloablative conditioning regimen; Hematopoietic cell transplantation; Vascularized composite allograft; Skin allograft; FoxP3; Tolerance ID PRECLINICAL CANINE MODEL; LONG-TERM TOLERANCE; TISSUE-TRANSPLANTATION; RENAL-TRANSPLANTATION; HAND TRANSPLANTATION; KIDNEY ALLOGRAFTS; MINIATURE SWINE; BONE-MARROW; CHIMERISM; REJECTION AB Background. We have previously demonstrated that tolerance to a vascularized composite allograft (VCA) can be achieved after the establishment of mixed chimerism. We test the hypothesis that tolerance to a VCA in our dog leukocyte antigen-matched canine model is not dependent on the previous establishment of mixed chimerism and can be induced coincident with hematopoietic cell transplantation (HCT). Methods. Eight dog leukocyte antigen-matched, minor antigen mismatched dogs received 200 cGy of radiation and a VCA transplant. Four dogs received donor bone marrow at the time of VCA transplantation (group 1), whereas a second group of four dogs did not (group 2). All recipients received a limited course of postgrafting immunosuppression. All dogs that received HCT and VCA were given donor, third-party, and autologous skin grafts. Results. All group 1 recipients were tolerant to their VCA (962 weeks). Three of the four dogs in group 2 rejected their VCA transplants after the cessation of immunosuppression. Biopsies obtained from the muscle and skin of VCA from group 1 showed few infiltrating cells compared with extensive infiltrates in biopsies of VCA from group 2. Compared with autologous skin and muscle, elevated levels of CD3+ FoxP3+ T-regulatory cells were found in the skin and muscle obtained from the VCA of HCT recipients. All group 1 animals were tolerant to their donor skin graft and promptly rejected the third-party skin grafts. Conclusion. These data demonstrated that donor-specific tolerance to all components of the VCA can be established through simultaneous nonmyeloablative allogeneic HCT and VCA transplantation protocol. C1 [Mathes, David W.; Chang, Jeff; Hwang, Billanna; Graves, Scott S.; Storer, Barry E.; Butts-Miwongtum, Tiffany; Sale, George E.; Storb, Rainer] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Mathes, David W.; Chang, Jeff] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Mathes, David W.] VA Puget Sound Hlth Care Syst, Plast Surg Serv, Seattle, WA USA. [Graves, Scott S.; Storb, Rainer] Univ Washington, Dept Med, Seattle, WA USA. [Storer, Barry E.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Sale, George E.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Mathes, DW (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, POB 19024,D1-100 1100 Fairview Ave N, Seattle, WA 98109 USA. EM dwmathes@fhcrc.org FU National Institutes of Health, Bethesda, MD [P01CA078902, P30CA015704]; Plastic Surgery Foundation FX This study received research funding from the National Institutes of Health, Bethesda, MD, grants P01CA078902 and P30CA015704. In addition, D.W.M. received support from the National Endowment for Plastic Surgery Grant from the Plastic Surgery Foundation. This study was neither prepared nor funded in any part by a commercial organization, including educational grants. NR 29 TC 10 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUL 27 PY 2014 VL 98 IS 2 BP 131 EP 138 DI 10.1097/TP.0000000000000204 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AL6SB UT WOS:000339262000009 PM 24918616 ER PT J AU Karasawa, H Yakabi, S Wang, LX Tache, Y AF Karasawa, Hiroshi Yakabi, Seiichi Wang, Lixin Tache, Yvette TI Orexin-1 receptor mediates the increased food and water intake induced by intracerebroventricular injection of the stable somatostatin pan-agonist, ODT8-SST in rats SO NEUROSCIENCE LETTERS LA English DT Article DE Food intake; Orexin-A; ODT8-SST; SB-334867; Somatostatin 2 receptor; Water intake ID MELANIN-CONCENTRATING HORMONE; NEUROPEPTIDE-Y; HYPOTHALAMUS; DRINKING; STIMULATION; NEURONS; BEHAVIOR; BRAIN; HYPOCRETIN/OREXIN; LOCALIZATION AB Intracerebroventricular (icv) injection of the stable somatostatin pan-agonist, ODT8-SST induces a somatostatin 2 receptor (sst(2)) mediated robust feeding response that involves neuropeptide Y and opioid systems in rats. We investigated whether the orexigenic system driven by orexin also plays a role. Food and water intake after icv injection was measured concomitantly in non-fasted and non-water deprived rats during the light phase. In vehicle treated rats (100% DMSO, icv), ODT8-SST (1 mu g/rat, icv) significantly increased the 2-h food and water intake compared to icv vehicle plus saline (5.1 +/- 1.0 g vs. 1.2 +/- 0.4 g and 11.3 +/- 1.9 mL vs. 2.5 +/- 1.2 mL, respectively). The orexin-1 receptor antagonist, SB-334867 (16 mu g/rat, icv) completely inhibited the 2-h food and water intake induced by icv ODT8-SST. In contrast, the icv pretreatment with the selective somatostatin sst(2) antagonist, S-406-028, established to block the orexigenic effect of icv ODT8-SST, did not modify the increased food and water intake induced by icv orexin-A (10.7 mu g/rat). These data indicate that orexin-1 receptor signaling system is part of the brain neurocircuitry contributing to the orexigenic and dipsogenic responses induced by icv ODT8-SST and that orexin-A stimulates food intake independently from brain sst(2) activation. Published by Elsevier Ireland Ltd. C1 [Karasawa, Hiroshi; Yakabi, Seiichi; Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Ctr, Dept Med, Los Angeles, CA 90073 USA. [Karasawa, Hiroshi; Yakabi, Seiichi; Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, Ctr Neurobiol, Stress Digest Dis Div, Los Angeles, CA 90073 USA. [Karasawa, Hiroshi; Yakabi, Seiichi; Wang, Lixin; Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, CURE Digest Dis Ctr, Bldg 115,Rm 117B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU Veterans Administration Research Career Scientist Award; NIH [DK 33061]; [NIDDK-41303] FX The authors thank Mrs. Honghui Liang for excellent technical support. This work was supported by NIDDK-41303 (Animal core, YT, LW) and Veterans Administration Research Career Scientist Award (YT) and NIH DK 33061. We thank Dr. Jean Rivier (Clayton Foundation Laboratories for Biological Sciences, Salk Institutes, La Jolla, CA) for the generous supply of peptides. NR 43 TC 2 Z9 3 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 25 PY 2014 VL 576 BP 88 EP 92 DI 10.1016/j.neulet.2014.05.063 PG 5 WC Neurosciences SC Neurosciences & Neurology GA AN8KU UT WOS:000340853900017 PM 24915296 ER PT J AU Qin, WP Pan, JP Qin, YW Lee, DN Bauman, WA Cardozo, C AF Qin, Weiping Pan, Jiangping Qin, Yiwen Lee, David N. Bauman, William A. Cardozo, Christopher TI Identification of functional glucocorticoid response elements in the mouse FoxO1 promoter SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE FoxO1; Glucocorticoids; Glucocorticoid response element; Glucocorticoid receptor ID SKELETAL-MUSCLE ATROPHY; GENE-EXPRESSION; TRANSCRIPTION FACTORS; DENERVATION ATROPHY; UBIQUITIN LIGASES; RECEPTOR; INVOLVE; REDD1; MTOR AB Glucocorticoids stimulate muscle atrophy through a cascade of signals that includes activation of Fox transcription factors which then upregulate multiple genes to promote degradation of myofibrillar and other muscle proteins and inhibit protein synthesis. Our previous finding that glucocorticoids upregulate mRNA levels for FoxO1 in skeletal muscle led us to hypothesize that the FoxO1 gene contains one or more glucocorticoid response elements (GREs). Here we show that upregulation of FoxO1 expression by glucocorticoids requires the glucocorticoid receptor (GR) and binding of hormones to it. In cultured C2C12 myoblasts dexamethasone did not alter FoxO1 mRNA stability. Computational analysis predicted that the proximal promoter of the FoxO1 gene contained a cluster of eight GRE half sites and one highly conserved near-consensus SRE; the cluster is found between -800 and -2000 bp upstream of the first codon of the FoxO1 gene. A reporter gene constructed using the first 2 kb of the FoxO1 promoter was stimulated by dexamethasone. Removal of a 5' domain containing half of the GREs reduced reporter gene activity and removal of all GREs in this region ablated activation by dexamethasone. Restriction fragments of the cluster of 8 upstream GREs bound recombinant GR in gel shift assays. Collectively, the data demonstrate that the proximal promoter of the FoxO1 gene contains multiple functional GREs, indicating that upregulation of FoxO1 expression by glucocorticoids through GREs represents an additional mechanism by which the GR drives glucocorticoid-mediated muscle atrophy. These findings are also relevant to other physiological roles of FoxO1 such as regulation of hepatic metabolism. Published by Elsevier Inc. C1 [Qin, Weiping; Pan, Jiangping; Qin, Yiwen; Lee, David N.; Bauman, William A.; Cardozo, Christopher] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Qin, Weiping; Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, New York, NY USA. RP Qin, WP (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM weiping.qin@mssm.edu FU Department of Veterans Affairs Rehabilitation Research and Development Service [B9212C, B0687R, B1313R] FX Grant support: Department of Veterans Affairs Rehabilitation Research and Development Service B9212C, B0687R and B1313R. NR 22 TC 12 Z9 12 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 25 PY 2014 VL 450 IS 2 BP 979 EP 983 DI 10.1016/j.bbrc.2014.06.080 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AM4YD UT WOS:000339861200009 PM 24971545 ER PT J AU Friedberg, MW Schneider, EC Werner, RM AF Friedberg, Mark W. Schneider, Eric C. Werner, Rachel M. TI Evaluating a Multipayer Medical Home Intervention Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Friedberg, Mark W.; Schneider, Eric C.] RAND Corp, Boston, MA USA. [Werner, Rachel M.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Friedberg, MW (reprint author), 20 Pk Plaza,Ste 920, Boston, MA 02116 USA. EM mfriedbe@rand.org NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 23 PY 2014 VL 312 IS 4 BP 436 EP 436 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AL6QN UT WOS:000339257800034 PM 25038367 ER PT J AU Kaplan, DE Goldberg, DS AF Kaplan, David E. Goldberg, David S. TI Liver Transplants Among US Veterans Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Kaplan, David E.] Philadelphia VA Med Ctr, Gastroenterol Sect, Philadelphia, PA USA. [Goldberg, David S.] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. RP Goldberg, DS (reprint author), Univ Penn, Dept Med, Div Gastroenterol, 423 Guardian Dr, Philadelphia, PA 19104 USA. EM david.goldberg@uphs.upenn.edu OI Kaplan, David E./0000-0002-3839-336X FU Intramural VA [VA999999] NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 23 PY 2014 VL 312 IS 4 BP 437 EP 437 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AL6QN UT WOS:000339257800036 PM 25038369 ER PT J AU Barnes, DE Kaup, A Kirby, KA Byers, AL Diaz-Arrastia, R Yaffe, K AF Barnes, Deborah E. Kaup, Allison Kirby, Katharine A. Byers, Amy L. Diaz-Arrastia, Ramon Yaffe, Kristine TI Traumatic brain injury and risk of dementia in older veterans SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; HEAD-INJURY; COGNITIVE DECLINE; POPULATION; PLAYERS; DEATH; US AB Objectives: Traumatic brain injury (TBI) is common in military personnel, and there is growing concern about the long-term effects of TBI on the brain; however, few studies have examined the association between TBI and risk of dementia in veterans. Methods: We performed a retrospective cohort study of 188,764 US veterans aged 55 years or older who had at least one inpatient or outpatient visit during both the baseline (2000-2003) and follow-up (2003-2012) periods and did not have a dementia diagnosis at baseline. TBI and dementia diagnoses were determined using ICD-9 codes in electronic medical records. Fine-Gray proportional hazards models were used to determine whether TBI was associated with greater risk of incident dementia, accounting for the competing risk of death and adjusting for demographics, medical comorbidities, and psychiatric disorders. Results: Veterans were a mean age of 68 years at baseline. During the 9-year follow-up period, 16% of those with TBI developed dementia compared with 10% of those without TBI (adjusted hazard ratio, 1.57; 95% confidence interval: 1.35-1.83). There was evidence of an additive association between TBI and other conditions on risk of dementia. Conclusions: TBI in older veterans was associated with a 60% increase in the risk of developing dementia over 9 years after accounting for competing risks and potential confounders. Our results suggest that TBI in older veterans may predispose toward development of symptomatic dementia and raise concern about the potential long-term consequences of TBI in younger veterans and civilians. C1 [Barnes, Deborah E.; Kaup, Allison; Kirby, Katharine A.; Byers, Amy L.; Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Barnes, Deborah E.; Kaup, Allison; Kirby, Katharine A.; Byers, Amy L.; Yaffe, Kristine] San Francisco VA Med Ctr, Bethesda, MD USA. [Diaz-Arrastia, Ramon] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. [Diaz-Arrastia, Ramon] Ctr Neurosci & Regenerat Med, Bethesda, MD USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM Deborah.barnes@ucsf.edu FU Department of Defense/NCIRE [W81XWH-11-2-0189, 1610, 1614, W81XWH-12-1-0581]; NIH [K24 AG031155] FX Supported by the Department of Defense/NCIRE (Barnes: W81XWH-11-2-0189, project 1610; Byers: W81XWH-11-2-0189, project 1614; Yaffe: W81XWH-12-1-0581) and the NIH (Yaffe: K24 AG031155). The funders did not contribute to the design of the study, analysis or interpretation of data, or decision to publish. The views expressed do not necessarily reflect those of the funders. NR 39 TC 42 Z9 42 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUL 22 PY 2014 VL 83 IS 4 BP 312 EP 319 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AM9YH UT WOS:000340236500010 PM 24966406 ER PT J AU Kirschen, MP Tsou, A Nelson, SB Russell, JA Larriviere, D AF Kirschen, Matthew P. Tsou, Amy Nelson, Sarah Bird Russell, James A. Larriviere, Daniel CA Ethics Law Humanities Comm TI Legal and ethical implications in the evaluation and management of sports-related concussion SO NEUROLOGY LA English DT Article ID CHRONIC TRAUMATIC ENCEPHALOPATHY; HIGH-SCHOOL; PROFESSIONAL FOOTBALL; RECURRENT CONCUSSION; POSITION STATEMENT; BRAIN-INJURY; RUGBY UNION; PLAYERS; RISK; CARE AB Objective: To examine the ethical and legal issues physicians face when evaluating and managing athletes with sports-related concussions, and to offer guidance to physicians as they navigate these situations. Results: This position paper reviews and compares the components of sports-related concussion laws, including education, removal from play, and clearance for return to play. It highlights the challenges privacy laws present relevant to providing care to concussed athletes and suggests ways to help physicians overcome these obstacles. The report also explores the ethical considerations physicians should bear in mind as they evaluate and manage concussed athletes, addressing them through a framework that includes considerations of professionalism, informed decision-making, patient autonomy, beneficence, nonmaleficence, conflicts of interest, and distributive justice. Conclusions: Physicians caring for concussed athletes have an ethical obligation to ensure that their primary responsibility is to safeguard the current and future physical and mental health of their patients. Physicians have a duty to provide athletes and their parents with information about concussion risk factors, symptoms, and the risks for postconcussion neurologic impairments. Physicians should facilitate informed and shared decision-making among athletes, parents, and medical teams while protecting athletes from potential harm. Additionally, including concussion evaluation and management training in neurology residency programs, as well as developing a national concussion registry, will benefit patients by the development of policies and clinical guidelines that optimize prevention and treatment of concussive head injury. C1 [Kirschen, Matthew P.] Univ Penn, Perelman Sch Med, Dept Pediat, Div Neurol, Philadelphia, PA 19104 USA. [Kirschen, Matthew P.] Univ Penn, Perelman Sch Med, Dept Anesthesia & Crit Care Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Tsou, Amy] Emergency Care Res Inst, Plymouth, PA USA. [Tsou, Amy] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Nelson, Sarah Bird] Amer Acad Neurol, Minneapolis, MN USA. [Russell, James A.] Tufts Univ, Sch Med, Lahey Clin, Dept Neurol, Boston, MA 02111 USA. [Larriviere, Daniel] Ochsner Med Ctr, Ochner Neurosci Inst, New Orleans, LA USA. RP Kirschen, MP (reprint author), Univ Penn, Perelman Sch Med, Dept Pediat, Div Neurol, Philadelphia, PA 19104 USA. EM kirschenm@chop.edu NR 38 TC 8 Z9 8 U1 3 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUL 22 PY 2014 VL 83 IS 4 BP 352 EP 358 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AM9YH UT WOS:000340236500017 PM 25008394 ER PT J AU Chen, Y Chiang, HC Litchfield, P Pena, M Juang, C Riley, DJ AF Chen, Yumay Chiang, Huai-Chin Litchfield, Patricia Pena, Michelle Juang, Charity Riley, Daniel J. TI Expression of Nek1 during kidney development and cyst formation in multiple nephron segments in the Nek1-deficient kat2J mouse model of polycystic kidney disease SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE Kidney development; Primary cilium; Centromere ID DNA-DAMAGE RESPONSE; PLANAR CELL POLARITY; NIMA-RELATED KINASES; PROTEIN-KINASES; MURINE MODELS; ASPERGILLUS-NIDULANS; CHECKPOINT CONTROL; GENE-PRODUCT; PKD2; MUTATION AB Background: Neks, mammalian orthologs of the fungal protein kinase never-in-mitosis A, have been implicated in the pathogenesis of polycystic kidney disease. Among them, Nek1 is the primary protein inactivated in kat2J mouse models of PKD. Result: We report the expression pattern of Nek1 and characterize the renal cysts that develop in kat2J mice. Nek1 is detectable in all murine tissues but its expression in wild type and kat2J heterozygous kidneys decrease as the kidneys mature, especially in tubular epithelial cells. In the embryonic kidney, Nek1 expression is most prominent in cells that will become podocytes and proximal tubules. Kidney development in kat2J homozygous mice is aberrant early, before the appearance of gross cysts: developing cortical zones are thin, populated by immature glomeruli, and characterized by excessive apoptosis of several cell types. Cysts in kat2J homozygous mice form postnatally in Bowman's space as well as different tubular subtypes. Late in life, kat2J heterozygous mice form renal cysts and the cells lining these cysts lack staining for Nek1. The primary cilia of cells lining cysts in kat2J homozygous mice are morphologically diverse: in some cells they are unusually long and in others there are multiple cilia of varying lengths. Conclusion: Our studies indicate that Nek1 deficiency leads to disordered kidney maturation, and cysts throughout the nephron. C1 [Chen, Yumay; Juang, Charity] Univ Calif Irvine, Div Endocrinol, Dept Med, Irvine, CA 92697 USA. [Chiang, Huai-Chin; Litchfield, Patricia; Pena, Michelle; Riley, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, Dept Med, San Antonio, TX 78229 USA. [Riley, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Univ Transplant Ctr, San Antonio, TX 78229 USA. [Riley, Daniel J.] South Texas Vet Hlth Care Syst, Renal Res Div, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Chen, Y (reprint author), Univ Calif Irvine, Div Endocrinol, Dept Med, Gross Hall 1130,Mail Code 4086, Irvine, CA 92697 USA. EM yumayc@uci.edu; rileyd@uthscsa.edu FU PKD Foundation; American Society of Nephrology; National Kidney Foundation; NIH [RO1-DK067339, RO1-DK61626]; George M. O'Brien Kidney Research Center grant from the NIH [P50-DK061597] FX This work was initiated at University of Texas Health Science Center at San Antonio and completed at The University of California, Irvine. The work was supported by grants from the PKD Foundation, the American Society of Nephrology, the National Kidney Foundation, and the NIH (RO1-DK067339) to Y.C.; a George M. O'Brien Kidney Research Center grant from the NIH to Y.C. (P50-DK061597, Hanna E. Abboud, Program Director); and a grant from the NIH to D.J.R. (RO1-DK61626). We thank Rosaria Polci, and Sergio Garcia for assistance with early stages of the project and with technical matters; Dr. Phang-Lang Chen for critical reading the manuscript; and a Veterans Administration Renal Research Excellence Award Program to the South Texas Veterans Health Care System, Audie L. Murphy Division, for core facility support. NR 53 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 EI 1423-0127 J9 J BIOMED SCI JI J. Biomed. Sci. PD JUL 17 PY 2014 VL 21 AR 63 DI 10.1186/s12929-014-0063-5 PG 14 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AO1CJ UT WOS:000341049200001 PM 25030234 ER PT J AU Olfson, M Marcus, SC Bridge, JA AF Olfson, Mark Marcus, Steven C. Bridge, Jeffrey A. TI Addressing Suicide Risk in Emergency Department Patients Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID PREDICTORS C1 [Olfson, Mark] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Marcus, Steven C.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Bridge, Jeffrey A.] Nationwide Childrens Hosp, Res Inst, Ctr Innovat Pediat Practice, Columbus, OH USA. RP Olfson, M (reprint author), Columbia Univ Coll Phys & Surg, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@columbia.edu NR 6 TC 1 Z9 1 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 16 PY 2014 VL 312 IS 3 BP 298 EP 298 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AL2FC UT WOS:000338940300036 PM 25027154 ER PT J AU Harden, WD Prochazka, AV AF Harden, Wesley D. Prochazka, Allan V. TI Review: Preoperative behavioral interventions increase smoking cessation and reduce postoperative complications SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Harden, Wesley D.; Prochazka, Allan V.] Denver VA Med Ctr, Denver, CO 80220 USA. RP Harden, WD (reprint author), Denver VA Med Ctr, Denver, CO 80220 USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 15 PY 2014 VL 161 IS 2 AR JC2 DI 10.7326/0003-4819-161-2-201407150-02002 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AM3PJ UT WOS:000339764600001 PM 25023268 ER PT J AU Abdulhadi, MA Perno, JR Melhem, ER Nucifora, PGP AF Abdulhadi, Mike A. Perno, Joseph R. Melhem, Elias R. Nucifora, Paolo G. P. TI Characteristics of Spondylotic Myelopathy on 3D Driven-Equilibrium Fast Spin Echo and 2D Fast Spin Echo Magnetic Resonance Imaging: A Retrospective Cross-Sectional Study SO PLOS ONE LA English DT Article ID CERVICAL COMPRESSION MYELOPATHY; INCREASED SIGNAL INTENSITY; PREDICT PROGNOSIS; CORD; MRI; SURGERY; SEQUENCES; IMAGES; STENOSIS; RECOVERY AB In patients with spinal stenosis, magnetic resonance imaging of the cervical spine can be improved by using 3D driven-equilibrium fast spin echo sequences to provide a high-resolution assessment of osseous and ligamentous structures. However, it is not yet clear whether 3D driven-equilibrium fast spin echo sequences adequately evaluate the spinal cord itself. As a result, they are generally supplemented by additional 2D fast spin echo sequences, adding time to the examination and potential discomfort to the patient. Here we investigate the hypothesis that in patients with spinal stenosis and spondylotic myelopathy, 3D driven-equilibrium fast spin echo sequences can characterize cord lesions equally well as 2D fast spin echo sequences. We performed a retrospective analysis of 30 adult patients with spondylotic myelopathy who had been examined with both 3D driven-equilibrium fast spin echo sequences and 2D fast spin echo sequences at the same scanning session. The two sequences were inspected separately for each patient, and visible cord lesions were manually traced. We found no significant differences between 3D driven-equilibrium fast spin echo and 2D fast spin echo sequences in the mean number, mean area, or mean transverse dimensions of spondylotic cord lesions. Nevertheless, the mean contrast-to-noise ratio of cord lesions was decreased on 3D driven-equilibrium fast spin echo sequences compared to 2D fast spin echo sequences. These findings suggest that 3D driven-equilibrium fast spin echo sequences do not need supplemental 2D fast spin echo sequences for the diagnosis of spondylotic myelopathy, but they may be less well suited for quantitative signal measurements in the spinal cord. C1 [Abdulhadi, Mike A.] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA. [Perno, Joseph R.; Nucifora, Paolo G. P.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Melhem, Elias R.] Univ Maryland, Baltimore, MD 21201 USA. [Nucifora, Paolo G. P.] Univ Penn, Philadelphia, PA 19104 USA. RP Nucifora, PGP (reprint author), Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. EM paolo.nucifora@uphs.upenn.edu NR 40 TC 1 Z9 1 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 15 PY 2014 VL 9 IS 7 AR e100964 DI 10.1371/journal.pone.0100964 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AM6RN UT WOS:000339992400008 PM 25025170 ER PT J AU Kothari, A Morgan, M Haake, DA AF Kothari, Atul Morgan, Margie Haake, David A. TI Emerging Technologies for Rapid Identification of Bloodstream Pathogens SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE bloodstream infections; rapid diagnostics; molecular diagnostics; clinical microbiology; antimicrobial stewardship ID DESORPTION IONIZATION-TIME; IN-SITU HYBRIDIZATION; STAPHYLOCOCCUS-AUREUS BACTEREMIA; FLIGHT MASS-SPECTROMETRY; HUMAN SEPTIC SHOCK; METHICILLIN-RESISTANT; ANTIMICROBIAL THERAPY; CULTURE BOTTLES; CANDIDA-ALBICANS; CLINICAL IMPACT AB Technologies for rapid microbial identification are poised to revolutionize clinical microbiology and enable informed decision making for patients with life-threatening bloodstream infections. Species identification of microorganisms in positive blood cultures can be performed in minutes using commercial fluorescence in situ hybridization tests or mass spectroscopy. Microorganisms in positive blood cultures can also be identified within 1-2.5 hours using automated polymerase chain reaction-based systems that can also detect selected antibiotic resistance markers, such as methicillin resistance. When combined with antibiotic stewardship programs, these approaches improve clinical outcomes and reduce healthcare expenditures. Tests for direct detection in whole blood samples are highly desirable because of their potential to identify bloodstream pathogens without waiting 1-2 days for blood cultures to become positive. However, results for pathogen detection in whole blood do not overlap with those of conventional blood culture techniques and we are still learning how best to use these approaches. C1 [Kothari, Atul; Haake, David A.] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. [Morgan, Margie] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. RP Kothari, A (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, 111F,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dratulkothari@gmail.com FU NIAID NIH HHS [R21 AI109889] NR 46 TC 23 Z9 23 U1 2 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2014 VL 59 IS 2 BP 272 EP 278 DI 10.1093/cid/ciu292 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AM2FR UT WOS:000339665700021 PM 24771332 ER PT J AU Roman, BR Asch, DA AF Roman, Benjamin R. Asch, David A. TI Faded Promises: The Challenge of Deadopting Low-Value Care SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 Univ Penn, Robert Wood Johnson Fdn Clin Scholars Program, Ctr Hlth Equity Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Equity Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, Head & Neck Serv, New York, NY 10021 USA. RP Asch, DA (reprint author), Blockley Hall 1123,423 Guardian Dr, Philadelphia, PA 19104 USA. EM asch@wharton.upenn.edu NR 8 TC 19 Z9 19 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 15 PY 2014 VL 161 IS 2 BP 149 EP + DI 10.7326/M14-0212 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AM3PJ UT WOS:000339764600026 PM 24781317 ER PT J AU Gregory, CM Embry, A Perry, L Bowden, MG AF Gregory, Chris M. Embry, Aaron Perry, Lindsay Bowden, Mark G. TI Quantifying human movement across the continuum of care: From lab to clinic to community SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Walking; Biomechanics; Motion analysis; Rehabilitation ID GROUND REACTION FORCES; HEMIPARETIC WALKING; AMBULATORY ACTIVITY; RELIABILITY; SPEED; VALIDATION; SYSTEM AB The ability to precisely quantify human movement within the laboratory setting provides researchers with data that comprehensively describe movement dysfunction in clinical cohorts. Furthermore, these data can be effectively utilized to identify potential underlying mechanisms as targets for therapeutic intervention. Although the utility of these methodologies is evidenced by the number of laboratories incorporating these techniques to understand clinical pathologies, the direct translation to clinical practice remains elusive and there exists an information gap between researchers studying these populations and the clinicians developing treatment for the individuals. Method: Recent technological advancements allow researchers and their clinician counterparts to measure certain elements of human movement outside of the laboratory. Specifically, the use of portable accelerometers allows for calculation of acceleration of the center of mass (COMa) during walking. COMa can be then be used to infer information about force generation by the individual during walking. This information may then be used by researchers to integrate with laboratory based results as well as by clinicians to partner with clinical findings, thus guiding clinical decision making as well as treatment design. The extent to which these types of measurement devices can be used to generate specific data describing human movement away from the lab is in the early stages of investigation, however, the potential for their use is something that could help advance research and patient care in the future. Published by Elsevier B.V. C1 [Gregory, Chris M.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Embry, Aaron] Med Univ S Carolina, Div Phys Therapy, Charleston, SC 29425 USA. [Perry, Lindsay; Bowden, Mark G.] Ralph H Johnson VAMC, Res Serv, Charleston, SC USA. RP Gregory, CM (reprint author), Med Univ S Carolina, Coll Hlth Profess, Dept Hlth Sci & Res, 77 President St,MSC 700, Charleston, SC 29425 USA. EM gregoryc@musc.edu FU RRD VA [IK2 RX000787] NR 16 TC 3 Z9 3 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD JUL 15 PY 2014 VL 231 SI SI BP 18 EP 21 DI 10.1016/j.jneumeth.2014.04.029 PG 4 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AL5BN UT WOS:000339148600004 PM 24797226 ER PT J AU Ruel, N Markova, DZ Adams, SL Scanzello, C Cs-Szabo, G Gerard, D Shi, P Anderson, DG Zack, M An, HS Chen, D Zhang, YJ AF Ruel, Nancy Markova, Dessislava Z. Adams, Sherrill L. Scanzello, Carla Cs-Szabo, Gabriella Gerard, David Shi, Peng Anderson, D. Greg Zack, Marc An, Howard S. Chen, Di Zhang, Yejia TI Fibronectin Fragments and the Cleaving Enzyme ADAM-8 in the Degenerative Human Intervertebral Disc SO SPINE LA English DT Article DE intervertebral disc; fibronectin fragments; ADAM-8; human ID IN-VITRO; DOMAIN; CHONDROGENESIS; CARTILAGE; MATRIX; CELLS; VIVO AB Study Design. The presence of fibronectin fragments (FN-fs) and the cleaving enzyme, A disintegrin and metalloproteinase domain-containing protein (ADAM)-8 were examined in human intervertebral disc (IVD) tissue in vitro. Objective. To investigate the presence and pathophysiological concentration of FN-fs and their cleaving enzyme, ADAM-8, in the human IVD tissue. Summary of Background Data. The 29-kDa FN-f has been shown to result in extracellular matrix loss in rabbit IVDs. However, the concentration of this biologically active fragment in the degenerative human IVD tissue has previously not been determined. Furthermore, it is critical to identify the enzyme(s) responsible for FN cleavage in the IVD. Methods. Human degenerative IVD tissues were removed during spinal surgery. A normal seeming young adult and an infant human cadaveric sample were obtained as controls. Soluble proteins were extracted, and analyzed by Western blotting using antibodies specific for the human FN neoepitope VRAA 271. A purified 29-kDa FN-f was used to allow estimation of the concentration of FN-fs in the tissues. ADAM-8, a FN-cleaving enzyme, was analyzed by Western blotting and immunostaining. Results. All adult IVD tissues contain many FN-f species, but these species were absent from the infant disc tissue. Moderately degenerative discs contained the highest amount of FN-fs; the concentration was estimated to be in the nanomolar range per gram of tissue. ADAM-8, known to cleave FN resulting in the VRAA(271) neoepitope, was present in the human disc. ADAM-8 primarily localized in the pericellular matrix of the nucleus pulposus tissue, as determined by immunostaining. Conclusion. This is the first report that N-terminal FN-fs are consistently present in IVD tissues from adult subjects. The pathophysiological concentration of these fragments is estimated to be at nanomolar range per gram of IVD tissue. Furthermore, ADAM-8, known to cleave FN, is present at the pericellular matrix of disc cells. C1 [Ruel, Nancy; Shi, Peng; An, Howard S.; Zhang, Yejia] Rush Univ, Med Ctr, Dept Orthoped Surg, Chicago, IL 60612 USA. [Markova, Dessislava Z.; Anderson, D. Greg] Thomas Jefferson Univ, Dept Orthoped Surg, Philadelphia, PA 19107 USA. [Adams, Sherrill L.] Univ Penn, Sch Dent Med, Dept Biochem, Philadelphia, PA 19104 USA. [Scanzello, Carla] Univ Penn, Perelman Sch Med, Dept Med, Rheumatol Sect, Philadelphia, PA 19104 USA. [Scanzello, Carla] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Cs-Szabo, Gabriella; Gerard, David; Chen, Di] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. [Zhang, Yejia] Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Zhang, Yejia] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Zack, Marc] Dow Agrosci, Indianapolis, IN USA. RP Zhang, YJ (reprint author), Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM yejia.zhang@uphs.upenn.edu FU National Institute of Child Health and Human Development (NICHD) [1K08 HD049598-01] FX National Institute of Child Health and Human Development (NICHD, 1K08 HD049598-01) funds were received to support this work. NR 20 TC 4 Z9 5 U1 6 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD JUL 15 PY 2014 VL 39 IS 16 BP 1274 EP 1279 DI 10.1097/BRS.0000000000000397 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AL5IG UT WOS:000339166500011 PM 25010013 ER PT J AU Donnelly, J Wang, H Locke, J Mannon, R Baddley, J AF Donnelly, J. Wang, H. Locke, J. Mannon, R. Baddley, J. TI Healthcare Facility-Associated Clostridium difficile Infection in Solid Organ Transplant Recipients SO TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA SP Amer Soc Transplant Surg, Transplantat Soc, Amer Soc Transplantat C1 [Donnelly, J.; Wang, H.] Univ Alabama Birmingham, Dept Emergency Med, Birmingham, AL USA. [Locke, J.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Mannon, R.; Baddley, J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Baddley, J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. OI Donnelly, John/0000-0002-0646-9470 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 2014 VL 98 SU 1 MA D2397 BP 772 EP 772 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AL4LN UT WOS:000339104605074 ER PT J AU Myaskovsky, L Pleis, J Dew, M Switzer, G Shapiro, R AF Myaskovsky, L. Pleis, J. Dew, M. Switzer, G. Shapiro, R. TI Race, Experience of Discrimination, and Other Non-Medical Factors Predict Differences in Acceptance for Kidney Transplantation. SO TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA SP Amer Soc Transplant Surg, Transplantat Soc, Amer Soc Transplantat C1 [Myaskovsky, L.; Pleis, J.; Switzer, G.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Myaskovsky, L.; Pleis, J.; Dew, M.; Switzer, G.; Shapiro, R.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 2014 VL 98 SU 1 MA B1197 BP 827 EP 827 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AL4LN UT WOS:000339104605257 ER PT J AU Myaskovsky, L Pleis, J Ramkumar, M Langone, A Saha, S Thomas, C AF Myaskovsky, L. Pleis, J. Ramkumar, M. Langone, A. Saha, S. Thomas, C. TI Fewer Race Disparities in the National VA Kidney Transplant Program. SO TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA SP Amer Soc Transplant Surg, Transplantat Soc, Amer Soc Transplantat C1 [Myaskovsky, L.; Pleis, J.; Ramkumar, M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Myaskovsky, L.; Pleis, J.; Ramkumar, M.] Univ Pittsburgh, Pittsburgh, PA USA. [Langone, A.] VA Tennessee Valley Healthcare Syst, Nashville, TN USA. [Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Thomas, C.] Iowa City VA Healthcare Syst, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 2014 VL 98 SU 1 MA B1196 BP 827 EP 827 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AL4LN UT WOS:000339104605256 ER PT J AU Manickam, N Patel, M Griendling, KK Gorin, Y Barnes, JL AF Manickam, Nagaraj Patel, Mandakini Griendling, Kathy K. Gorin, Yves Barnes, Jeffrey L. TI RhoA/Rho kinase mediates TGF-beta(1)-induced kidney myofibroblast activation through Poldip2/Nox4-derived reactive oxygen species SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE fibrosis; NADPH oxidase; oxidative stress; GTPase; myofibroblast differentiation; Rho kinase; transforming growth factor-beta(1); polymerase (DNA-directed) delta-interacting protein 2 ID UNILATERAL URETERAL OBSTRUCTION; I COLLAGEN EXPRESSION; GROWTH-FACTOR-BETA; ANGIOTENSIN-II; TGF-BETA; RHO-KINASE; MESANGIAL CELLS; NADPH OXIDASES; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS AB The small G proteins Rac1 and RhoA regulate actin cytoskeleton, cell shape, adhesion, migration, and proliferation. Recent studies in our laboratory have shown that NADPH oxidase Nox4-derived ROS are involved in transforming growth factor (TGF)-beta(1)-induced rat kidney myofibroblast differentiation assessed by the acquisition of an alpha-smooth muscle actin (alpha-SMA) phenotype and expression of an alternatively spliced fibronectin variant (Fn-EIIIA). Rac1 and RhoA are essential in signaling by some Nox homologs, but their role as effectors of Nox4 in kidney myofibroblast differentiation is not known. In the present study, we explored a link among Rac1 and RhoA and Nox4-dependent ROS generation in TGF-beta(1)-induced kidney myofibroblast activation. TGF-beta(1) stimulated an increase in Nox4 protein expression, NADPH oxidase activity, and abundant alpha-SMA and Fn-EIIIA expression. RhoA but not Rac1 was involved in TGF-beta(1) induction of Nox4 signaling of kidney myofibroblast activation. TGF-beta(1) stimulated active RhoA-GTP and increased Rho kinase (ROCK). Inhibition of RhoA with small interfering RNA and ROCK using Y-27632 significantly reduced TGF-beta(1)-induced stimulation of Nox4 protein, NADPH oxidase activity, and alpha-SMA and Fn-EIIIA expression. Treatment with diphenyleneiodonium, an inhibitor of NADPH oxidase, did not decrease RhoA activation but inhibited TGF-beta(1)-induced alpha-SMA and Fn-EIIIA expression, indicating that RhoA is upstream of ROS generation. RhoA/ROCK also regulated polymerase (DNA-directed) delta-interacting protein 2 (Poldip2), a newly discovered Nox4 enhancer protein. Collectively, these data indicate that RhoA/ROCK is upstream of Poldip2-dependent Nox4 regulation and ROS production and induces redox signaling of kidney myofibroblast activation and may broader implications in the pathophysiology of renal fibrosis. C1 [Barnes, Jeffrey L.] South Texas Vet Hlth Care Syst, Audie Murphy Mem Vet Adm Hosp, Med Res Serv, San Antonio, TX USA. [Manickam, Nagaraj; Patel, Mandakini; Gorin, Yves; Barnes, Jeffrey L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Griendling, Kathy K.] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA. RP Barnes, JL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM barnesj@uthscsa.edu FU Veterans Administration Merit Review Program; National Institutes of Health (NIH) [RO1-DK-080106]; NIH George O'Brien Kidney Center and Morphology Core FX This work was supported by grants from the Veterans Administration Merit Review Program, National Institutes of Health (NIH) Grant RO1-DK-080106, and the NIH George O'Brien Kidney Center and Morphology Core. NR 67 TC 33 Z9 37 U1 0 U2 16 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL 15 PY 2014 VL 307 IS 2 BP F159 EP F171 DI 10.1152/ajprenal.00546.2013 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AL1XZ UT WOS:000338921000005 PM 24872317 ER PT J AU Tregellas, JR AF Tregellas, Jason R. TI Neuroimaging Biomarkers for Early Drug Development in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Review DE Biomarkers; default network; gamma; band; hippocampus; neuroimaging; schizophrenia ID DEFAULT MODE NETWORK; CEREBRAL-BLOOD-FLOW; FUNCTIONAL CONNECTIVITY; 1ST-EPISODE PSYCHOSIS; ACETYLCHOLINE-RECEPTOR; HIPPOCAMPAL-FORMATION; HEMODYNAMIC-RESPONSE; 1ST-DEGREE RELATIVES; GAMMA OSCILLATIONS; PREFRONTAL CORTEX AB Given the relative inability of currently available antipsychotic treatments to adequately provide sustained recovery and improve quality of life for patients with schizophrenia, new treatment strategies are urgently needed. One way to improve the therapeutic development process may be an increased use of biomarkers in early clinical trials. Reliable biomarkers that reflect aspects of disease pathophysiology can be used to determine if potential treatment strategies are engaging their desired biological targets. This review evaluates three potential neuroimaging biomarkers: hippocampal hyperactivity, gamma-band deficits, and default network abnormalities. These deficits have been widely replicated in the illness, correlate with measures of positive symptoms, are consistent with models of disease pathology, and have shown initial promise as biomarkers of biological response in early studies of potential treatment strategies. Two key features of these deficits, and a guiding rationale for the focus of this review, are that the deficits are not dependent upon patients' performance of specific cognitive tasks and they have analogues in animal models of schizophrenia, greatly increasing their appeal for use as biomarkers. Using neuroimaging biomarkers such as those proposed here to establish early in the therapeutic development process if treatment strategies are having their intended biological effect in humans may facilitate development of new treatments for schizophrenia. C1 [Tregellas, Jason R.] Univ Colorado, Sch Med, Denver Vet Affairs Med Ctr, Res Serv, Aurora, CO 80045 USA. [Tregellas, Jason R.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO 80045 USA. RP Tregellas, JR (reprint author), Univ Colorado, Sch Med, Dept Psychiat, 13001 East 17th Pl,MS F546, Aurora, CO 80045 USA. EM Jason.tregellas@ucdenver.edu RI Tregellas, Jason/J-3637-2015 FU Veterans Affairs Clinical Science Research and Development Service; National Institutes of Health [R01DK089095]; Brain and Behavior Research Foundation; Blowitz-Ridgeway Foundation FX Dr. Tregellas is supported by the Veterans Affairs Clinical Science Research and Development Service, National Institutes of Health Grant R01DK089095, the Brain and Behavior Research Foundation, and the Blowitz-Ridgeway Foundation. NR 117 TC 16 Z9 16 U1 7 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 15 PY 2014 VL 76 IS 2 BP 111 EP 119 DI 10.1016/j.biopsych.2013.08.025 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AK5FU UT WOS:000338450900006 PM 24094513 ER PT J AU Akl, TJ Wilson, MA Ericson, MN Farquhar, E Cote, GL AF Akl, Tony J. Wilson, Mark A. Ericson, M. Nance Farquhar, Ethan Cote, Gerard L. TI Wireless Monitoring of Liver Hemodynamics In Vivo SO PLOS ONE LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; IMPLANTABLE SENSOR; CEREBRAL OXIMETRY; ALLOGRAFT FAILURE; PULSE OXIMETRY; OXYGENATION; PERFUSION; TRANSPLANTATION; NIRS; SIGNALS AB Liver transplants have their highest technical failure rate in the first two weeks following surgery. Currently, there are limited devices for continuous, real-time monitoring of the graft. In this work, a three wavelengths system is presented that combines near-infrared spectroscopy and photoplethysmography with a processing method that can uniquely measure and separate the venous and arterial oxygen contributions. This strategy allows for the quantification of tissue oxygen consumption used to study hepatic metabolic activity and to relate it to tissue stress. The sensor is battery operated and communicates wirelessly with a data acquisition computer which provides the possibility of implantation provided sufficient miniaturization. In two in vivo porcine studies, the sensor tracked perfusion changes in hepatic tissue during vascular occlusions with a root mean square error (RMSE) of 0.135 mL/min/g of tissue. We show the possibility of using the pulsatile wave to measure the arterial oxygen saturation similar to pulse oximetry. The signal is also used to extract the venous oxygen saturation from the direct current (DC) levels. Arterial and venous oxygen saturation changes were measured with an RMSE of 2.19% and 1.39% respectively when no vascular occlusions were induced. This error increased to 2.82% and 3.83% when vascular occlusions were induced during hypoxia. These errors are similar to the resolution of a commercial oximetry catheter used as a reference. This work is the first realization of a wireless optical sensor for continuous monitoring of hepatic hemodynamics. C1 [Akl, Tony J.; Cote, Gerard L.] Texas A&M Univ, Dept Biomed Engn, College Stn, TX 77843 USA. [Wilson, Mark A.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Wilson, Mark A.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ericson, M. Nance; Farquhar, Ethan] Oak Ridge Natl Lab, Oak Ridge, TN USA. RP Akl, TJ (reprint author), Texas A&M Univ, Dept Biomed Engn, College Stn, TX 77843 USA. EM tja161@gmail.com RI Ericson, Milton/H-9880-2016 OI Ericson, Milton/0000-0002-6628-4865 FU National Institutes of Health (NIH) through a Bioengineering Research Partnership (BRP) grant [5R01-GM077150] FX This work was funded by the National Institutes of Health (NIH) through a Bioengineering Research Partnership (BRP) grant (#5R01-GM077150). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 3 Z9 3 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 14 PY 2014 VL 9 IS 7 AR e102396 DI 10.1371/journal.pone.0102396 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AM1PC UT WOS:000339618600076 PM 25019160 ER PT J AU Jim, B Mehta, S Qipo, A Kim, K Cohen, HW Moore, RM He, JC Sharma, S AF Jim, Belinda Mehta, Swati Qipo, Andi Kim, Kwanghee Cohen, Hillel W. Moore, Robert M. He, John C. Sharma, Shuchita TI A Comparison of Podocyturia, Albuminuria and Nephrinuria in Predicting the Development of Preeclampsia: A Prospective Study SO PLOS ONE LA English DT Article ID ANTIANGIOGENIC FACTORS; ANGIOGENIC FACTORS; URINARY-EXCRETION; PROTEINURIA; BIOMARKERS; PREGNANCY; HYPERTENSION; DISEASE; WOMEN AB Preeclampsia, a hypertensive multisystem disease that complicates 5-8% of all pregnancy, is a major cause for maternal and fetal mortality and morbidity. The disease is associated with increased spontaneous and evoked preterm birth and remote cardio-renal disorders in the mother and offspring. Thus the ability to predict the disease should lead to earlier care and decreased morbidity. This has led to fervent attempts to identify early predictive biomarkers and research endeavors that have expanded as we learn more regarding possible causes of the disease. As preeclampsia is associated with specific renal pathology including podocyte injury, early urinary podocyte (podocyturia), or the podocyte specific proteinuria nephrin in the urine (nephrinuria), as well as the more easily measured urinary albumin (albuminuria), have all been suggested as predictive markers. We performed a prospective study recruiting 91 pregnant women (78 of whom were high risk) and studied the predictive ability of these three urinary biomarkers. The subjects were recruited between 15-38 weeks of gestation. Fourteen patients, all in the high-risk obstetric group, developed preeclampsia. The levels of podocyturia, nephrinuria, and albuminuria were variably higher in the high-risk pregnant patients who developed preeclampsia. The sensitivities and specificities for podocyturia were 70% and 43%, for albuminuria were 36% and 96%, and for nephrinuria were 57% and 58%, respectively. Also, abnormal nephrinuria (69%) and podocyturia (38%) were detected in low risk women who had uncomplicated gestations; none of these women exhibited albuminuria. In our study, none of the three urinary markers achieved the minimum predictive values required for clinical testing. The lack of excessive albuminuria, however, may indicate a preeclampsia-free gestation. Given a discrepant literature, further studies with larger sample size should be considered. C1 [Jim, Belinda; Qipo, Andi] Albert Einstein Coll Med, Jacobi Med Ctr, Dept Nephrol Med, Bronx, NY 10467 USA. [Mehta, Swati; He, John C.] James J Peters VA Med Ctr, Dept Nephrol Med, Bronx, NY USA. [Kim, Kwanghee] Providence Alaska Med Ctr, Anchorage, AK USA. [Cohen, Hillel W.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Moore, Robert M.] Albert Einstein Coll Med, Dept Obstet & Gynecol, Jacobi Med Ctr, Bronx, NY 10467 USA. [He, John C.; Sharma, Shuchita] Mt Sinai Sch Med, Dept Nephrol Med, New York, NY USA. RP Jim, B (reprint author), Albert Einstein Coll Med, Jacobi Med Ctr, Dept Nephrol Med, Bronx, NY 10467 USA. EM belindajim286@gmail.com OI Cohen, Hillel/0000-0002-4524-0898 FU CTSA from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) [1 UL1 TR001073-01, 1 TL1 TR001072-01, 1 KL2 TR001071-01] FX This publication was supported in part by the CTSA Grant 1 UL1 TR001073-01, 1 TL1 TR001072-01, 1 KL2 TR001071-01 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 7 Z9 8 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 10 PY 2014 VL 9 IS 7 AR e101445 DI 10.1371/journal.pone.0101445 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AK9RG UT WOS:000338763800024 PM 25010746 ER PT J AU Perez, SM Carreno, FR Frazer, A Lodge, DJ AF Perez, Stephanie M. Carreno, Flavia R. Frazer, Alan Lodge, Daniel J. TI Vagal Nerve Stimulation Reverses Aberrant Dopamine System Function in the Methylazoxymethanol Acetate Rodent Model of Schizophrenia SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; hippocampus; schizophrenia; vagal nerve stimulation ID TREATMENT-RESISTANT DEPRESSION; RAT DORSAL HIPPOCAMPUS; PREFRONTAL CORTEX; ELECTROPHYSIOLOGICAL CHARACTERIZATION; ANTIPSYCHOTIC-DRUGS; EPILEPSY PATIENTS; GENE-EXPRESSION; BRAIN; NOREPINEPHRINE; DEFICITS AB Vagal nerve stimulation (VNS) is an alternative therapy for epilepsy and treatment refractory depression. Here we examine VNS as a potential therapy for the treatment of schizophrenia in the methylozoxymethanol acetate (MAM) rodent model of the disease. We have previously demonstrated that hyperactivity within ventral regions of the hippocampus (vHipp) drives the dopamine system dysregulation in this model. Moreover, by targeting the vHipp directly, we can reverse aberrant dopamine system function and associated behaviors in the MAM model. Although the central effects of VNS have not been completely delineated, positron emission topographic measurements of cerebral blood flow in humans have consistently reported that VNS stimulation induces bilateral decreases in hippocampal activity. Based on our previous observations, we performed in vivo extracellular electrophysiological recordings in MAM-and saline-treated rats to evaluate the effect of chronic (2 week) VNS treatment on the activity of putative vHipp pyramidal neurons, as well as downstream dopamine neuron activity in the ventral tegmental area. Here we demonstrate that chronic VNS was able to reverse both vHipp hyperactivity and aberrant mesolimbic dopamine neuron function in the MAM model of schizophrenia. Additionally, VNS reversed a behavioral correlate of the positive symptoms of schizophrenia. Because current therapies for schizophrenia are far from adequate, with a large number of patients discontinuing treatment due to low efficacy or intolerable side effects, it is important to explore alternative nonpharmacological treatments. These data provide the first preclinical evidence that VNS may be a possible alternative therapeutic approach for the treatment of schizophrenia. C1 [Perez, Stephanie M.; Carreno, Flavia R.; Frazer, Alan; Lodge, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Perez, Stephanie M.; Carreno, Flavia R.; Frazer, Alan; Lodge, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Ctr Biomed Neurosci, San Antonio, TX 78229 USA. [Frazer, Alan] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Lodge, DJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr,MC 7764, San Antonio, TX 78229 USA. EM LodgeD@uthscsa.edu RI Lodge, Daniel/K-4740-2014 OI Lodge, Daniel/0000-0002-6772-1748 FU NIH [R01 MH082933, R01 MH090067, F31 MH098564]; Cyberonics; Dey Pharmaceuticals FX This work was supported by NIH Grants R01 MH082933 (A.F.), R01 MH090067 (D.J.L.), and F31 MH098564 (S.M.P.).; S.M.P. and F.R.C. declare no competing financial interests. A.F. has served on advisory boards for Lundbeck, Takeda Pharmaceuticals International, and Eli Lilly; and as a consultant for Dey Pharmaceuticals. Previously, A.F. had received financial compensation as a consultant for Cyberonics and had also obtained grant support from them for a preclinical study. D.J.L. reports receiving consulting fees from Dey Pharmaceuticals. NR 51 TC 6 Z9 6 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 9 PY 2014 VL 34 IS 28 BP 9261 EP 9267 DI 10.1523/JNEUROSCI.0588-14.2014 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AL5EJ UT WOS:000339156000010 PM 25009259 ER PT J AU Karimkhani, C Boyers, LN Margolis, DJ Naghavi, M Hay, RJ Williams, HC Naldi, L Coffeng, LE Weinstock, MA Dunnick, CA Pederson, H Vos, T Murray, CJL Dellavalle, RP AF Karimkhani, Chante Boyers, Lindsay N. Margolis, David J. Naghavi, Mohsen Hay, Roderick J. Williams, Hywel C. Naldi, Luigi Coffeng, Luc E. Weinstock, Martin A. Dunnick, Cory A. Pederson, Hannah Vos, Theo Murray, Christopher J. L. Dellavalle, Robert P. TI Comparing Cutaneous Research Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases with 2010 Global Burden of Disease Results SO PLOS ONE LA English DT Article ID RESEARCH PRIORITIES; OF-HEALTH; LEPROSY; ASSOCIATION; PSORIASIS AB Importance: Disease burden data helps guide research prioritization. Objective: To determine the extent to which grants issued by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) reflect disease burden, measured by disability-adjusted life years (DALYs) from Global Burden of Disease (GBD) 2010 project. Design: Two investigators independently assessed 15 skin conditions studied by GBD 2010 in the NIAMS database for grants issued in 2013. The 15 skin diseases were matched to their respective DALYs from GBD 2010. Setting: The United States NIAMS database and GBD 2010 skin condition disability data. Main Outcome(s) and Measure(s): Relationship of NIAMS grant database topic funding with percent total GBD 2010 DALY and DALY rank for 15 skin conditions. Results: During fiscal year 2013, 1,443 NIAMS grants were issued at a total value of $424 million. Of these grants, 17.7% covered skin topics. Of the total skin disease funding, 82%(91 grants) were categorized as "general cutaneous research.'' Psoriasis, leprosy, and "other skin and subcutaneous diseases'' (ie; immunobullous disorders, vitiligo, and hidradenitis suppurativa) were over-represented when funding was compared with disability. Conversely, cellulitis, decubitus ulcer, urticaria, acne vulgaris, viral skin diseases, fungal skin diseases, scabies, and melanoma were under-represented. Conditions for which disability and funding appeared well-matched were dermatitis, squamous and basal cell carcinoma, pruritus, bacterial skin diseases, and alopecia areata. Conclusions and Relevance: Degree of representation in NIAMS is partly correlated with DALY metrics. Grant funding was well-matched with disability metrics for five of the 15 studied skin diseases, while two skin diseases were over-represented and seven were under-represented. Global burden estimates provide increasingly transparent and important information for investigating and prioritizing national research funding allocations. C1 [Karimkhani, Chante] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Boyers, Lindsay N.] Georgetown Univ, Sch Med, Washington, DC USA. [Margolis, David J.] Univ Penn, Dept Biostat & Epidemiol & Dermatol, Philadelphia, PA 19104 USA. [Naghavi, Mohsen; Coffeng, Luc E.; Vos, Theo; Murray, Christopher J. L.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Hay, Roderick J.] Kings Coll Hosp NHS Trust, Dept Dermatol, London, England. [Williams, Hywel C.] Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham NG7 2RD, England. [Naldi, Luigi] Azienda Osped Papa Giovanni XXIII, Dept Dermatol, Bergamo, Italy. [Weinstock, Martin A.] Vet Affairs Med Ctr, Dermatoepidemiol Unit, Providence, RI USA. [Weinstock, Martin A.] Rode Isl Hosp, Dept Dermatol, Providence, RI USA. [Weinstock, Martin A.] Brown Univ, Dept Dermatol, Providence, RI 02912 USA. [Weinstock, Martin A.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Dunnick, Cory A.; Dellavalle, Robert P.] Univ Colorado, Dept Dermatol, Aurora, CO 80045 USA. [Dunnick, Cory A.; Dellavalle, Robert P.] Eastern Colorado Hlth Care Syst, Dermatol Serv, US Dept Vet Affairs, Denver, CO USA. [Pederson, Hannah] Univ Colorado, Sch Med, Aurora, CO USA. [Dellavalle, Robert P.] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. RP Dellavalle, RP (reprint author), Univ Colorado, Dept Dermatol, Anschutz Med Campus, Aurora, CO 80045 USA. EM robert.dellavalle@ucdenver.edu RI Naldi, Luigi/K-6343-2016 OI Naldi, Luigi/0000-0002-3160-2835 FU Bill and Melinda Gates Foundation; US Department of Veterans Affairs FX This study was supported in part by the Bill and Melinda Gates Foundation (PI: Christoper Murray) and the US Department of Veterans Affairs (salary for Drs. Dellavalle, Dunnick, Weinstock). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 5 Z9 5 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 8 PY 2014 VL 9 IS 7 AR e102122 DI 10.1371/journal.pone.0102122 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AL6KZ UT WOS:000339242700112 PM 25003335 ER PT J AU Zeidel, ML Hoenig, MP Palevsky, PM AF Zeidel, Mark L. Hoenig, Melanie P. Palevsky, Paul M. TI A New CJASN Series: Renal Physiology for the Clinician SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material C1 [Zeidel, Mark L.; Hoenig, Melanie P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. RP Zeidel, ML (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. EM mzeidel@bidmc.harvard.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 2 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL 7 PY 2014 VL 9 IS 7 BP 1271 EP 1271 DI 10.2215/CJN.10191012 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AK7NP UT WOS:000338615300019 PM 25002526 ER PT J AU Rogal, SS Hu, A Bandi, R Shaikh, O AF Rogal, Shari S. Hu, Angela Bandi, Rupal Shaikh, Obaid TI Novel therapy for non-cirrhotic hyperammonemia due to a spontaneous splenorenal shunt SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Splenorenal shunt; Gastric bypass; Hyperammonemia; Encephalopathy ID ENCEPHALOPATHY AB Spontaneous splenorenal shunts in the absence of cirrhosis have rarely been reported as a cause hyperammonemia with encephalopathy. Several closure techniques of such lesions have been described. Here we report a case of a patient with no history of liver disease who developed significant confusion. After an extensive workup, he was found to have hyperammonemia and encephalopathy due to formation of a spontaneous splenorenal shunt. There was no evidence of cirrhosis on biopsy or imaging and no portal hypertension when directly measured. The shunt was 18 mm and too large for embolization so the segment of the splenic vein between the portal vein and the shunt was occluded using an Amplatzer plug. Thus, the superior mesenteric flow was directed entirely to the liver. After interventional radiology closure of the shunt using this technique there was complete resolution of symptoms. The case represents the first report of a successful closure of splenorenal shunt via percutaneous embolization of the splenic vein with an amplatzer plug using a common femoral vein approach. (C) 2014 Baishideng Publishing Group Inc. All rights reserved. C1 [Rogal, Shari S.] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Hu, Angela] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Bandi, Rupal] Vet Affairs Pittsburgh Healthcare Syst, Dept Radiol, Pittsburgh, PA 15240 USA. [Shaikh, Obaid] Vet Affairs Pittsburgh Healthcare Syst, Div Gastroenterol, Pittsburgh, PA 15240 USA. RP Rogal, SS (reprint author), Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, PUH, 200 Lothrop St,M Level,C Wing, Pittsburgh, PA 15213 USA. EM rogalss@upmc.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX Supported by Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development NR 6 TC 2 Z9 4 U1 0 U2 2 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JUL 7 PY 2014 VL 20 IS 25 BP 8288 EP 8291 DI 10.3748/wjg.v20.i25.8288 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AK6EM UT WOS:000338520900038 PM 25009405 ER PT J AU Sanchez, SH Sethi, SS Santos, SL Boockvar, K AF Sanchez, Sadie H. Sethi, Sanjum S. Santos, Susan L. Boockvar, Kenneth TI Implementing medication reconciliation from the planner's perspective: a qualitative study SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Medication reconciliation; Adverse drug event; Patient safety; Implementation; National patient safety goals AB Background: Medication reconciliation can reduce adverse events associated with prescribing errors at transitions between sites of care. Though a U.S. Joint Commission National Patient Safety Goal since 2006, at present organizations continue to have difficulty implementing it. The objective of this study was to examine medication reconciliation implementation from the perspective of individuals involved in the planning process in order to identify recurrent themes, including facilitators and barriers, that might inform other organizations' planning and implementation efforts. Methods: We performed semi-structured interviews with individuals who had a role in planning medication reconciliation implementation at a large urban academic medical center in the U.S. and its affiliated Veterans Affairs hospital. We queried respondents' perceptions of the implementation process and their experience with facilitators and barriers. Transcripts were coded and analyzed using a grounded theory approach. The themes that emerged were subsequently categorized using the Consolidated Framework for Implementation Research (CFIR). Results: There were 13 respondents, each with one or more organizational roles in quality improvement, information technology, medication safety, and education. Respondents described a resource-and time-intensivemedication reconciliation planning process. The planning teams' membership and functioning were recognized as important factors to a successful planning process. Implementation was facilitated by planners' understanding of the principles of performance improvement, in particular, fitting the new process into the workflow of multiple disciplines. Nevertheless, a need for significant professional role changes was recognized. Staff training was recognized to be an important part of roll-out, but training had several limitations. Planners monitored compliance to help sustain the process, but acknowledged that this did not ensure that medication reconciliation actually achieved its primary goal of reducing errors. Study findings fit multiple constructs in the CFIR model. Conclusions: Study findings suggest that to improve the likelihood of a successful implementation of medication reconciliation, planners should, among other considerations, involve a multidisciplinary planning team, recognize the significant professional role changes that may be needed, and consider devoting resources not just to compliance monitoring but also to monitoring of the process' impact on prescribing. C1 [Sanchez, Sadie H.; Boockvar, Kenneth] Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1057, New York, NY 10029 USA. [Sethi, Sanjum S.] Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. [Santos, Susan L.] VA New Jersey Hlth Care Syst, War Related Illness & Injury Study Ctr East Orang, E Orange, NJ 07018 USA. [Santos, Susan L.] Rutgers State Univ, Sch Publ Hlth Piscataway, Piscataway, NJ USA. [Boockvar, Kenneth] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Boockvar, Kenneth] Jewish Home Lifecare Res Inst Aging, New York, NY USA. RP Boockvar, K (reprint author), Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1057, New York, NY 10029 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU VA Health Services Research and Development [IAB-05-204, REA 08-260]; Greenwall Foundation FX The authors would like to acknowledge the contribution of Liz Rosen (Lehigh University) who helped enter and sort the coded files. This project was supported by VA Health Services Research and Development grants IAB-05-204 and REA 08-260. Dr. Boockvar was supported by the Greenwall Foundation. NR 23 TC 8 Z9 9 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD JUL 4 PY 2014 VL 14 AR 290 DI 10.1186/1472-6963-14-290 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA V42FM UT WOS:000209599700001 PM 24996538 ER PT J AU Wynn, JK Jahshan, C Green, MF AF Wynn, Jonathan K. Jahshan, Carol Green, Michael F. TI Multisensory integration in schizophrenia: a behavioural and eventrelated potential study SO COGNITIVE NEUROPSYCHIATRY LA English DT Article DE schizophrenia; multisensory integration; ERP; race model ID AUDIOVISUAL INTEGRATION; PROCESSING DEFICITS; RECOGNITION; INFORMATION; SPEECH; FACILITATION; PERSPECTIVE; STIMULI; BINDING; HUMANS AB IntroductionSuccessful processing of multisensory stimuli increases the likelihood of detection or identification of salient, biologically significant events faster and more efficiently than unisensory inputs. Schizophrenia (SZ) patients show deficits in unisensory processing, but it is unclear whether impairments are seen to multisensory stimuli, a process known as multisensory integration (MSI). We used behavioural and event-related potential (ERP) measures to examine MSI in SZ and healthy controls (HC).MethodsThirty-three SZ and 30 HC completed a target detection task with unisensory and multisensory stimuli. Reaction times (RT) were measured while their electroencephalogram (EEG) was recorded. Two auditory (N100 and P200) and visual (P100 and N160) ERPs were examined. MSI was analysed in terms of violations of RT to the race model and by comparing ERPs in the MSI condition to the sum of the unisensory ERPs.ResultsBoth groups showed faster RT in MSI compared to unisensory conditions. SZ had non-significantly fewer violations of the race model compared to HC. SZ had significantly smaller amplitudes to unisensory visual N160 and auditory P100 relative to HC; there were no significant group differences on any ERP measure of MSI.ConclusionsSZ showed relatively intact MSI with subtle (non-significant) differences at the neural and behavioural levels compared to HC. Our results suggest that neural processes associated with MSI are not an additional source of impairment in SZ. C1 [Wynn, Jonathan K.; Jahshan, Carol; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. RP Wynn, JK (reprint author), VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Wynn, Jonathan/H-3749-2014; Keil, Julian/I-3337-2016 OI Wynn, Jonathan/0000-0002-1763-8540; Keil, Julian/0000-0003-4195-7397 FU National Institute of Mental Health [MH043292, MH065707, MH091468] FX This work was supported by grants from the National Institute of Mental Health [grant number MH043292], [grant number MH065707] and [grant number MH091468]. NR 44 TC 2 Z9 2 U1 1 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1354-6805 EI 1464-0619 J9 COGN NEUROPSYCHIATRY JI Cogn. Neuropsychiatry PD JUL 4 PY 2014 VL 19 IS 4 BP 319 EP 336 DI 10.1080/13546805.2013.866892 PG 18 WC Psychiatry SC Psychiatry GA AE5VW UT WOS:000334058400003 PM 24397788 ER PT J AU Rinne, ST Feemster, LC Collins, BF Au, DH Perkins, M Bryson, CL O'Riordan, TG Liu, CF AF Rinne, Seppo T. Feemster, Laura C. Collins, Bridget F. Au, David H. Perkins, Mark Bryson, Christopher L. O'Riordan, Thomas G. Liu, Chuan-Fen TI Thiazolidinediones and the risk of asthma exacerbation among patients with diabetes: a cohort study SO ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY LA English DT Article DE Thiazolidinediones; Peroxisome proliferator-activated receptors; Glitazones; Asthma; Cohort study ID ACTIVATED-RECEPTOR-GAMMA; OBSTRUCTIVE PULMONARY-DISEASE; MURINE MODEL; PPAR-GAMMA; AIRWAY INFLAMMATION; ALLERGIC INFLAMMATION; AGONIST ROSIGLITAZONE; PIOGLITAZONE; SEVERITY; COSTS AB Background: Thiazolidinediones are oral diabetes medications that selectively activate peroxisome proliferator-activated receptor gamma and have potent anti-inflammatory properties. While a few studies have found improvements in pulmonary function with exposure to thiazolidinediones, there are no studies of their impact on asthma exacerbations. Our objective was to assess whether exposure to thiazolidinediones was associated with a decreased risk of asthma exacerbation. Methods: We performed a cohort study of diabetic Veterans who had a diagnosis of asthma and were taking oral diabetes medications during the period of 10/1/2005 - 9/30/2006. The risk of asthma exacerbations and oral steroid use during 10/1/2006 - 9/30/2007 was compared between patients who were prescribed thiazolidinediones and patients who were on alternative oral diabetes medications. Multivariable logistic regression and negative binomial regression analyses were used to characterize this risk. A sensitivity analysis was performed, restricting our evaluation to patients who were adherent to diabetes therapy. Results: We identified 2,178 patients who were on thiazolidinediones and 10,700 who were not. Exposure to thiazolidinediones was associated with significant reductions in the risk of asthma exacerbation (OR = 0.79, 95% CI, 0.62 - 0.99) and oral steroid prescription (OR = 0.73, 95% CI 0.63 - 0.84). Among patients who were adherent to diabetes medications, there were more substantial reductions in the risks for asthma exacerbation (OR = 0.64, 95% CI 0.47 - 0.85) and oral steroid prescription (OR = 0.68, 95% CI 0.57 - 0.81). Conclusions: Thiazolidinediones may provide a novel anti-inflammatory approach to asthma management by preventing exacerbations and decreasing the use of oral steroids. C1 [Rinne, Seppo T.; Feemster, Laura C.; Collins, Bridget F.; Au, David H.; Perkins, Mark; Bryson, Christopher L.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA 98104 USA. [Rinne, Seppo T.; Feemster, Laura C.; Collins, Bridget F.; Au, David H.] Univ Washington, Dept Pulm & Cri Care, Seattle, WA 98195 USA. [Bryson, Christopher L.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. [O'Riordan, Thomas G.] Gilead Sci Inc, Seattle, WA USA. [Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Rinne, ST (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, 1100 Olive Way Suite 1400, Seattle, WA 98104 USA. EM srinne@uw.edu FU VA HSRD [IIR 07-068-2]; Gilead Sciences Inc FX Research funding for this project was from a VA HSR&D grant (IIR 07-068-2) along with funding from Gilead Sciences Inc. Neither funding source had a role in the study design, analysis, or interpretation. NR 40 TC 3 Z9 3 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1710-1484 EI 1710-1492 J9 ALLERGY ASTHMA CL IM JI Allerg Asthma Clin. Immunol. PD JUL 3 PY 2014 VL 10 AR 34 DI 10.1186/1710-1492-10-34 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA AL3GY UT WOS:000339016100001 PM 25024717 ER PT J AU Honavar, J Bradley, E Bradley, K Oh, JY Vallejo, MO Kelley, EE Cantu-Medellin, N Doran, S Dell'italia, LJ Matalon, S Patel, RP AF Honavar, Jaideep Bradley, Eddie Bradley, Kelley Oh, Joo Yeun Vallejo, Matthew O. Kelley, Eric E. Cantu-Medellin, Nadiezhda Doran, Stephen Dell'italia, Louis J. Matalon, Sadis Patel, Rakesh P. TI Chlorine gas exposure disrupts nitric oxide homeostasis in the pulmonary vasculature SO TOXICOLOGY LA English DT Article DE Halogen; Lung; Inflammation ID INDUCED LUNG INJURY; EPITHELIAL NA+ CHANNELS; TRAIN DERAILMENT; MURINE MODEL; MICE; INHALATION; MECHANISMS; MITIGATION; HYPERREACTIVITY; SUPEROXIDE AB Exposure to chlorine (Cl-2) gas during industrial accidents or chemical warfare leads to significant airway and distal lung epithelial injury that continues post exposure. While lung epithelial injury is prevalent, relatively little is known about whether Cl-2 gas also promotes injury to the pulmonary vasculature. To determine this, rats were subjected to a sub-lethal Cl-2 gas exposure (400 ppm, 30 min) and then brought back to room air. Pulmonary arteries (PA) were isolated from rats at various times post-exposure and contractile (phenylephrine) and nitric oxide (NO)-dependent vasodilation (acetylcholine and mahmanonoate) responses measured ex vivo. PA contractility did not change, however significant inhibition of NO-dependent vasodilation was observed that was maximal at 24-48 h post exposure. Superoxide dismutase restored NO-dependent vasodilation suggesting a role for increased superoxide formation. This was supported by similar to 2-fold increase in superoxide formation (measured using 2-hydroethidine oxidation to 2-OH-E+) from PA isolated from Cl-2 exposed rats. We next measured PA pressures in anesthetized rats. Surprisingly, PA pressures were significantly (similar to 4 mmHg) lower in rats that had been exposed to Cl-2 gas 24 h earlier suggesting that deficit in NO-signaling observed in isolated PA experiments did not manifest as increased PA pressures in vivo. Administration of the iNOS selective inhibitor 1400W, restored PA pressures to normal in Cl-2 exposed, but not control rats suggesting that any deficit in NO-signaling due to increased superoxide formation in the PA, is offset by increased NO-formation from iNOS. These data indicate that disruption of endogenous NO-signaling mechanisms that maintain PA tone is an important aspect of post-Cl-2 gas exposure toxicity. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Honavar, Jaideep; Bradley, Kelley; Oh, Joo Yeun; Vallejo, Matthew O.; Patel, Rakesh P.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Bradley, Eddie; Dell'italia, Louis J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Doran, Stephen; Matalon, Sadis] Univ Alabama Birmingham, Dept Anesthesiol, Birmingham, AL 35294 USA. [Matalon, Sadis; Patel, Rakesh P.] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Matalon, Sadis; Patel, Rakesh P.] Univ Alabama Birmingham, Ctr Lung Injury & Repair, Birmingham, AL 35294 USA. [Kelley, Eric E.; Cantu-Medellin, Nadiezhda] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15260 USA. [Dell'italia, Louis J.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Patel, RP (reprint author), Univ Alabama Birmingham, Dept Pathol, 901 19th St South,BMR 2,Room 532, Birmingham, AL 35294 USA. EM rakeshp@uab.edu OI Patel, Rakesh/0000-0002-1526-4303 FU CounterACT Program; Office of the Director; National Institute of Environmental Health Sciences [1U01ES023759, 5U01ES015676]; National Institute of Health [T32 HL007457] FX This research was supported by the CounterACT Program, National Institutes of Health, Office of the Director, and the National Institute of Environmental Health Sciences, Grant Numbers 1U01ES023759 and 5U01ES015676 and a fellowship from the National Institute of Health to MOV (T32 HL007457). NR 35 TC 6 Z9 6 U1 0 U2 17 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 3 PY 2014 VL 321 BP 96 EP 102 DI 10.1016/j.tox.2014.04.005 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AJ7IO UT WOS:000337870600011 PM 24769334 ER PT J AU Koenig, CJ Wingard, LM Sabee, C Olsher, D Vandergriff, I AF Koenig, Christopher J. Wingard, Leah M. Sabee, Christina Olsher, David Vandergriff, Ilona TI Managing Patient-centered Communication across the Type 2 Diabetes Illness Trajectory: A Grounded Practical Theory of Interactional Sensitivity SO JOURNAL OF APPLIED COMMUNICATION RESEARCH LA English DT Article DE Treatment Decision-making; Type 2 Diabetes; Health Communication; Conversation Analysis; Physician-Patient Interaction; Patient-centered Communication; Grounded Practical Theory ID HEALTH-CARE; TREATMENT RECOMMENDATIONS; PARENT RESISTANCE; INSULIN THERAPY; ATTACHMENT; CONSULTATIONS; CONVERSATION; PATERNALISM; ADHERENCE; DELIVERY AB This article uses the theoretical and methodological framework of Grounded Practical Theory (GPT) to provide a lens for analyzing and interpreting discourse as a situated form of social action in routine Type 2 diabetes visits. Drawing on a total data-set of 400 audio-recorded routine visits, we randomly selected 55 visits for qualitative analysis. In this article, we use Conversation Analysis to document communication techniques, which we in turn use as evidence to ground our claims within the GPT framework. We use two single cases of interaction to analyze communication techniques physicians use when recommending a change from oral medication to insulin. We argue treatment intensification is a key moment in health communication to reflect about patient centeredness because physicians can find themselves in an interactional dilemma: while insulin may effectively help control unstable disease, an insulin recommendation may simultaneously counter patient values and treatment preferences. Our analysis suggests that physicians use what we call interactional sensitivity to balance medical need and patient preferences when making medical decisions by tailoring their communication according to the local situation and the patient's larger illness trajectory. We propose that interactional sensitivity is a type of communication work and a quality of patient-centered communication characterized by the theoretical relationship between tailoring communication to the contingencies of the local interaction and the global illness trajectory. Overall, this article contributes to health communication scholarship by proposing a normative model for reflecting on how physicians negotiate challenging interactions with patients during routine chronic illness visits. C1 [Koenig, Christopher J.] San Francisco Vet Adm Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Koenig, Christopher J.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA USA. [Wingard, Leah M.; Sabee, Christina] San Francisco State Univ, Dept Commun Studies, San Francisco, CA USA. [Olsher, David] San Francisco State Univ, Dept English, San Francisco, CA USA. [Vandergriff, Ilona] San Francisco State Univ, Dept Foreign Languages & Literatures, San Francisco, CA USA. RP Koenig, CJ (reprint author), San Francisco Vet Adm Med Ctr, Dept Med, 4150 Clement St,111-A1, San Francisco, CA 94121 USA. EM christopher.koenig@ucsf.edu OI Koenig, Christopher J./0000-0003-0884-4120 NR 62 TC 6 Z9 6 U1 0 U2 14 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0090-9882 EI 1479-5752 J9 J APPL COMMUN RES JI J. Appl. Commun. Res. PD JUL 3 PY 2014 VL 42 IS 3 SI SI BP 244 EP 267 DI 10.1080/00909882.2014.911943 PG 24 WC Communication SC Communication GA AH1MA UT WOS:000335883700002 ER PT J AU Meffert, SM Henn-Haase, C Metzler, TJ Qian, M Best, S Hirschfeld, A McCaslin, S Inslicht, S Neylan, TC Marmar, CR AF Meffert, Susan M. Henn-Haase, Clare Metzler, Thomas J. Qian, Meng Best, Suzanne Hirschfeld, Ayelet McCaslin, Shannon Inslicht, Sabra Neylan, Thomas C. Marmar, Charles R. TI Prospective Study of Police Officer Spouse/Partners: A New Pathway to Secondary Trauma and Relationship Violence? SO PLOS ONE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; EMERGENCY SERVICES PERSONNEL; MALE VIETNAM VETERANS; COMBAT VETERANS; WAR VETERANS; PSYCHOLOGICAL DISTRESS; PARTNERS PERCEPTIONS; MISSISSIPPI SCALE; MENTAL-HEALTH; PTSD AB Introduction: It has been reported that posttraumatic stress disorder (PTSD) is associated with secondary spouse/partner (S/P) emotional distress and relationship violence. Objective: To investigate the relationships between PTSD, S/P emotional distress and relationship violence among police recruits using a prospective design. Methods: Two hypotheses were tested in 71 S/Ps: (1) Police officer reports of greater PTSD symptoms after 12 months of police service will be associated with greater secondary trauma symptoms among S/Ps; (2) Greater secondary trauma symptoms among S/Ps at 12 months will be associated with S/P reports of greater relationship violence. Methods: 71 police recruits and their S/Ps were assessed at baseline and 12 months after the start of police officer duty. Using linear and logistic regression, we analyzed explanatory variables for 12 month S/P secondary traumatic stress symptoms and couple violence, including baseline S/P variables and couple violence, as well as exposure and PTSD reports from both S/P and officer. Results: S/P perception of officer PTSD symptoms predicted S/P secondary traumatic stress. OS/P secondary trauma was significantly associated with both total couple violence (.34, p = .004) and S/P to officer violence (.35, p = .003). Conclusions: Although results from this relatively small study of young police officers and their S/Ps must be confirmed by larger studies in general populations, findings suggest that S/P perception of PTSD symptoms may play a key role in the spread of traumatic stress symptoms across intimate partner relationships and intimate partner violence in the context of PTSD. C1 [Meffert, Susan M.; Inslicht, Sabra; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Metzler, Thomas J.; Hirschfeld, Ayelet; Inslicht, Sabra; Neylan, Thomas C.] San Francisco Vet Adm Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Henn-Haase, Clare; Qian, Meng; Marmar, Charles R.] NYU, Dept Psychiat, New York, NY 10016 USA. [Best, Suzanne] Lewis & Clark Coll, Grad Sch Educ & Counseling, Portland, OR 97219 USA. [McCaslin, Shannon] Natl Ctr PTSD, Disseminat & Training Div, Palo Alto, CA USA. RP Meffert, SM (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM susan.meffert@ucsf.edu OI meffert, susan/0000-0002-5882-7102 FU National Institute of Mental Health [R01 - MH056350-06] FX This research was supported by National Institute of Mental Health Grant (R01 - MH056350-06) to CRM. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of this manuscript. NR 44 TC 0 Z9 0 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 2 PY 2014 VL 9 IS 7 AR e100663 DI 10.1371/journal.pone.0100663 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO5BA UT WOS:000341354100036 PM 24987848 ER PT J AU Chang, ET Wells, KB Young, AS Stockdale, S Johnson, MD Fickel, JJ Jou, K Rubenstein, LV AF Chang, Evelyn T. Wells, Kenneth B. Young, Alexander S. Stockdale, Susan Johnson, Megan D. Fickel, Jacqueline J. Jou, Kevin Rubenstein, Lisa V. TI The Anatomy of Primary Care and Mental Health Clinician Communication: A Quality Improvement Case Study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care; mental health; communication; quality improvement; ambulatory care; primary care redesign ID OF-VETERANS-AFFAIRS; RESPECT-DEPRESSION TRIAL; COLLABORATIVE CARE; BEHAVIORAL HEALTH; OUTPATIENT CLINICS; INTEGRATED CARE; UNITED-STATES; MEDICAL HOME; DISORDERS; IMPLEMENTATION AB The high prevalence of comorbid physical and mental illnesses among veterans is well known. Therefore, ensuring effective communication between primary care (PC) and mental health (MH) clinicians in the Veterans Affairs (VA) health care system is essential. The VA's Patient Aligned Care Teams (PACT) initiative has further raised awareness of the need for communication between PC and MH. Improving such communication, however, has proven challenging. To qualitatively understand barriers to PC-MH communication in an academic community-based clinic by using continuous quality improvement (CQI) tools and then initiate a change strategy. An interdisciplinary quality improvement (QI) work group composed of 11 on-site PC and MH providers, administrators, and researchers identified communication barriers and facilitators using fishbone diagrams and process flow maps. The work group then verified and provided context for the diagram and flow maps through medical record review (32 patients who received both PC and MH care), interviews (6 stakeholders), and reports from four previously completed focus groups. Based on these findings and a previous systematic review of interventions to improve interspecialty communication, the team initiated plans for improvement. Key communication barriers included lack of effective standardized communication processes, practice style differences, and inadequate PC training in MH. Clinicians often accessed advice or formal consultation based on pre-existing across-discipline personal relationships. The work group identified collocated collaborative care, joint care planning, and joint case conferences as feasible, evidence-based interventions for improving communication. CQI tools enabled providers to systematically assess local communication barriers and facilitators and engaged stakeholders in developing possible solutions. A locally tailored CQI process focusing on communication helped initiate change strategies and ongoing improvement efforts. C1 [Chang, Evelyn T.; Rubenstein, Lisa V.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Chang, Evelyn T.; Young, Alexander S.; Stockdale, Susan; Johnson, Megan D.; Fickel, Jacqueline J.; Rubenstein, Lisa V.] VA Ctr Study Healthcare Innovat Implementat & Pol, North Hills, CA USA. [Wells, Kenneth B.; Rubenstein, Lisa V.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Wells, Kenneth B.; Young, Alexander S.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Johnson, Megan D.; Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. [Young, Alexander S.; Johnson, Megan D.; Jou, Kevin] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Chang, ET (reprint author), VA Greater Los Angeles Healthcare Syst, Dept GIM 111G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM evelyn.chang@va.gov FU VA Office of Patient Care Services; VA Office of Academic Affiliations, Health Services Research and Development through the Health Services Fellowship Training Program [TMP 65-020] FX This work was undertaken as part of the Veterans Administration's PACT Demonstration Laboratory initiative, supporting and evaluating VA's transition to a patient-centered medical home. Funding for the PACT Demonstration Laboratory initiative is provided by the VA Office of Patient Care Services.; Funding support provided by VA Office of Academic Affiliations, Health Services Research and Development through the Health Services Fellowship Training Program (TMP 65-020). NR 54 TC 1 Z9 1 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 598 EP 606 DI 10.1007/s11606-013-2731-7 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700009 ER PT J AU Rinker, JR Salter, AR Cutter, GR AF Rinker, John R., II Salter, Amber R. Cutter, Gary R. TI Improvement of multiple sclerosis-associated tremor as a treatment effect of natalizunnab SO MULTIPLE SCLEROSIS AND RELATED DISORDERS LA English DT Article DE Multiple sclerosis; Tremor; Neurologic symptoms; Natatizumab; Self-report; Questionnaires ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; CEREBELLAR TREMOR; ISONIAZID THERAPY; MULTICENTER; DISABILITY; PREVALENCE; SYMPTOMS; CANNABIS; EFFICACY AB Background: Tremor is among the most physically disabling symptoms associated with MS. The effect of MS disease modifying therapies (DMTs) on the severity of MS tremor is unclear. Objective: To compare the change over time in scores reflecting tremor severity between subjects treated with natalizumab and other disease modifying drugs. Methods: Questionnaires were sent to North American Research Committee on MS registrants reporting mild or greater tremor on semiannual updates. Respondents on natalizumab and other MS therapies completed a survey which included tremor-specific scales to indicate tremor severity both currently and when the current therapy was initiated. Differences between natalizumab and non-natalizumab groups were compared using ANOVA. Results: Surveys were returned by 567 registrants, including 202 taking natalizumab. Subjects on natalizumab were more likely to report tremor improvement (29.6%) than those never (15.2%) or previously (14.8%, p=0.0002) on natalizumab. Over a mean recall period of 6.2+4.6 years, the Tremor Related Activities of Daily Living score worsened by 1.8 points among natalizumab-treated subjects, 3.3 points among those previously on natalizumab, and 5.3 points among those who never took natalizumab (p=0.009). Conclusion: Respondents taking natalizumab were more likely to experience tremor improvement than those taking other MS disease modifying therapies. Published by Elsevier B.V. C1 [Rinker, John R., II] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Rinker, John R., II] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Salter, Amber R.; Cutter, Gary R.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.