FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bowling, CB Batten, A O'Hare, AM AF Bowling, C. Barrett Batten, Adam O'Hare, Ann M. TI Distribution of Survival Times in a Real-World Cohort of Older Adults with Chronic Kidney Disease: The Median May Not Be the Message SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID STAGE RENAL-DISEASE; DECISION-MAKING C1 [Bowling, C. Barrett] Atlanta Vet Affairs Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Decatur, GA 30033 USA. [Bowling, C. Barrett] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Batten, Adam; O'Hare, Ann M.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Hlth Serv Res & Dev Ctr Innovat, Seattle, WA USA. [O'Hare, Ann M.] Univ Washington, Dept Med, Seattle, WA USA. RP Bowling, CB (reprint author), Atlanta Vet Affairs Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Decatur, GA 30033 USA. FU Beeson Career Development Award from the National Institute on Aging; National Institute on Aging [R03AG042336-01]; T. Franklin Williams Scholarship Award - Atlantic Philanthropies, Inc.; John A. Hartford Foundation; Association of Specialty Professors; American Society of Nephrology; American Geriatrics Society; Department of Veterans Affairs [1IK2CX000856-01A1] FX Original data extraction for this project was supported by a Beeson Career Development Award to Dr. O'Hare from the National Institute on Aging. Additional support was provided through the National Institute on Aging (R03AG042336-01), the T. Franklin Williams Scholarship Award (funding provided by Atlantic Philanthropies, Inc., the John A. Hartford Foundation, the Association of Specialty Professors, the American Society of Nephrology, and the American Geriatrics Society), and the Department of Veterans Affairs (1IK2CX000856-01A1). 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 U.S. government. NR 7 TC 1 Z9 1 U1 1 U2 1 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 MAY PY 2015 VL 63 IS 5 BP 1033 EP 1035 DI 10.1111/jgs.13425 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CI4NH UT WOS:000354726400029 PM 25989569 ER PT J AU Ettinger, DS Wood, DE Akerley, W Bazhenova, LA Borghaei, H Camidge, DR Cheney, RT Chirieac, LR D'Amico, TA Demmy, TL Dilling, TJ Dobelbower, MC Govindan, R Grannis, FW Horn, L Jahan, TM Komaki, R Krug, LM Lackner, RP Lanuti, M Lilenbaum, R Lin, J Loo, BW Martins, R Otterson, GA Patel, JD Pisters, KM Reckamp, K Riely, GJ Rohren, E Schild, SE Shapiro, TA Swanson, SJ Tauer, K Yang, SC Gregory, K Hughes, M AF Ettinger, David S. Wood, Douglas E. Akerley, Wallace Bazhenova, Lyudmila A. Borghaei, Hossein Camidge, David Ross Cheney, Richard T. Chirieac, Lucian R. D'Amico, Thomas A. Demmy, Todd L. Dilling, Thomas J. Dobelbower, M. Chris Govindan, Ramaswamy Grannis, Frederic W., Jr. Horn, Leora Jahan, Thierry M. Komaki, Ritsuko Krug, Lee M. Lackner, Rudy P. Lanuti, Michael Lilenbaum, Rogerio Lin, Jules Loo, Billy W., Jr. Martins, Renato Otterson, Gregory A. Patel, Jyoti D. Pisters, Katherine M. Reckamp, Karen Riely, Gregory J. Rohren, Eric Schild, Steven E. Shapiro, Theresa A. Swanson, Scott J. Tauer, Kurt Yang, Stephen C. Gregory, Kristina Hughes, Miranda TI Non-Small Cell Lung Cancer, Version 6.2015 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITORS; ESMO CONSENSUS CONFERENCE; ALK GENE REARRANGEMENT; ACQUIRED-RESISTANCE; EGFR MUTATION; CLINICOPATHOLOGICAL CHARACTERISTICS; MOLECULAR-PATHOLOGY; PERSONALIZED CANCER; TUMOR SPECIMENS AB These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy is very effective in patients with advanced NSCLC who have specific genetic alterations. Therefore, it is important to test tumor tissue from patients with advanced NSCLC to determine whether they have genetic alterations that make them candidates for specific targeted therapies. These NCCN Guidelines Insights describe the different testing methods currently available for determining whether patients have genetic alterations in the 2 most commonly actionable genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements and sensitizing epidermal growth factor receptor (EGFR) mutations. C1 [Ettinger, David S.; Shapiro, Theresa A.; Yang, Stephen C.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA. [Wood, Douglas E.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Bazhenova, Lyudmila A.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Camidge, David Ross] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Cheney, Richard T.; Demmy, Todd L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Chirieac, Lucian R.; Swanson, Scott J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [D'Amico, Thomas A.] Duke Canc Inst, Durham, NC 27705 USA. [Dilling, Thomas J.] Moffit Canc Ctr, Tampa, FL 33612 USA. [Dobelbower, M. Chris] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Govindan, Ramaswamy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO 63110 USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Grannis, Frederic W., Jr.; Reckamp, Karen] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Jahan, Thierry M.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Komaki, Ritsuko; Pisters, Katherine M.; Rohren, Eric] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Krug, Lee M.; Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lackner, Rudy P.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Lanuti, Michael] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Lilenbaum, Rogerio] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Lin, Jules] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Loo, Billy W., Jr.] Stanford Canc Inst, Palo Alto, CA USA. [Martins, Renato] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Otterson, Gregory A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Otterson, Gregory A.] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Patel, Jyoti D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Schild, Steven E.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Tauer, Kurt] Univ Tennessee, St Jude Childrens Hosp, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Gregory, Kristina] Natl Comprehens Canc Network, Ft Washington, PA USA. RP Ettinger, DS (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA. RI Mendez, Pedro /J-8955-2016; OI Mendez, Pedro /0000-0001-6713-7907; Reckamp, Karen/0000-0002-9213-0325 FU Eisai; Bristol-Myers Squibb; Genentech BioOncology; Merck; Novartis Oncology; Novocure; Boehringer Ingelheim Pharmaceuticals, Inc. FX Supported by an educational grant from Eisai; a contribution from Exelixis Inc.; educational grants from Bristol-Myers Squibb, Genentech BioOncology, Merck, Novartis Oncology, Novocure; and by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. NR 80 TC 83 Z9 89 U1 6 U2 15 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2015 VL 13 IS 5 BP 515 EP 524 PG 10 WC Oncology SC Oncology GA CH8JY UT WOS:000354283800004 PM 25964637 ER PT J AU Hoppe, RT Advani, RH Ai, WYZ Ambinder, RF Aoun, P Bello, CM Benitez, CM Bierman, PJ Blum, KA Chen, R Dabaja, B Forero, A Gordon, LI Hernandez-Ilizaliturri, FJ Hochberg, EP Huang, JY Johnston, PB Khan, N Maloney, DG Mauch, PM Metzger, M Moore, JO Morgan, D Moskowitz, CH Mulroney, C Poppe, M Rabinovitch, R Seropian, S Tsien, C Winter, JN Yahalom, J Burns, JL Sundar, H AF Hoppe, Richard T. Advani, Ranjana H. Ai, Weiyun Z. Ambinder, Richard F. Aoun, Patricia Bello, Celeste M. Benitez, Cecil M. Bierman, Philip J. Blum, Kristie A. Chen, Robert Dabaja, Bouthaina Forero, Andres Gordon, Leo I. Hernandez-Ilizaliturri, Francisco J. Hochberg, Ephraim P. Huang, Jiayi Johnston, Patrick B. Khan, Nadia Maloney, David G. Mauch, Peter M. Metzger, Monika Moore, Joseph O. Morgan, David Moskowitz, Craig H. Mulroney, Carolyn Poppe, Matthew Rabinovitch, Rachel Seropian, Stuart Tsien, Christina Winter, Jane N. Yahalom, Joachim Burns, Jennifer L. Sundar, Hema TI Hodgkin Lymphoma, Version 2.2015 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; INVOLVED-FIELD RADIOTHERAPY; STEM-CELL TRANSPLANTATION; FINE-NEEDLE-ASPIRATION; HIGH-DOSE CHEMOTHERAPY; INTENSITY-MODULATED RADIOTHERAPY; BONE-MARROW-TRANSPLANTATION; COOPERATIVE-ONCOLOGY-GROUP; LONG-TERM SURVIVORS; INTERIM FDG-PET AB Hodgkin lymphoma (HL) is an uncommon malignancy involving lymph nodes and the lymphatic system. Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma are the 2 main types of HL. CHL accounts for most HL diagnosed in the Western countries. Chemotherapy or combined modality therapy, followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale), is the standard initial treatment for patients with newly diagnosed CHL. Brentuximab vedotin, a CD30-directed antibody-drug conjugate, has produced encouraging results in the treatment of relapsed or refractory disease. The potential long-term effects of treatment remain an important consideration, and long-term follow-up is essential after completion of treatment. C1 [Hoppe, Richard T.; Advani, Ranjana H.; Benitez, Cecil M.] Stanford Canc Inst, Palo Alto, CA 94304 USA. [Ai, Weiyun Z.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Ambinder, Richard F.] Sidney Kimmel Comprehens Canc Ctr John Hopkins, Baltimore, MD USA. [Aoun, Patricia; Chen, Robert] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Bello, Celeste M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Bierman, Philip J.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Blum, Kristie A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Blum, Kristie A.] Solove Res Inst, Columbus, OH USA. [Dabaja, Bouthaina] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Forero, Andres] Univ Alabama, Ctr Comprehens Canc, Tuscaloosa, AL 35487 USA. [Gordon, Leo I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Hernandez-Ilizaliturri, Francisco J.] Roswell Pk Canc Inst, Buffalo, NY USA. [Hochberg, Ephraim P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Huang, Jiayi] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Huang, Jiayi] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Johnston, Patrick B.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Khan, Nadia] Fox Chase Canc Ctr, St Louis, MO USA. [Maloney, David G.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Mauch, Peter M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Metzger, Monika] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Moore, Joseph O.] Duke Canc Inst, Durham, NC USA. [Morgan, David] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Moskowitz, Craig H.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Mulroney, Carolyn] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA USA. [Poppe, Matthew] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Rabinovitch, Rachel] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Seropian, Stuart] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Tsien, Christina] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Winter, Jane N.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY USA. RP Hoppe, RT (reprint author), Stanford Canc Inst, Palo Alto, CA 94304 USA. RI Huang, Jiaxing/B-7521-2009 FU NCI NIH HHS [P30 CA006973]; NIGMS NIH HHS [T32 GM007790] NR 124 TC 9 Z9 9 U1 2 U2 8 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2015 VL 13 IS 5 BP 554 EP 586 PG 33 WC Oncology SC Oncology GA CH8JY UT WOS:000354283800008 PM 25964641 ER PT J AU Ghasemi-Rad, M England, JS Brinegar, KN Ferrone, CR Oklu, R AF Ghasemi-Rad, Mohammad England, Jonathan S. Brinegar, Katelyn N. Ferrone, Cristina R. Oklu, Rahmi TI Endovascular Diagnosis of Radiographically and Intraoperatively Occult Insulinoma SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter ID LOCALIZATION C1 [Ghasemi-Rad, Mohammad; Brinegar, Katelyn N.; Oklu, Rahmi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Intervent Radiol, Boston, MA 02114 USA. [England, Jonathan S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ferrone, Cristina R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Ghasemi-Rad, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Intervent Radiol, 55 Fruit St,290 GRB, Boston, MA 02114 USA. NR 4 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAY PY 2015 VL 26 IS 5 BP 760 EP 762 DI 10.1016/j.jvir.2014.12.614 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA CI1KV UT WOS:000354504000022 PM 25921459 ER PT J AU Unkelbach, J Papp, D AF Unkelbach, Jan Papp, David TI The emergence of nonuniform spatiotemporal fractionation schemes within the standard BED model SO MEDICAL PHYSICS LA English DT Article DE intensity-modulated proton therapy (IMPT); nonuniform fractionation; biologically equivalent dose (BED) ID LINEAR-QUADRATIC MODEL; RADIATION-THERAPY; DOSE DISTRIBUTION; OPTIMIZATION AB Purpose: Nonuniform spatiotemporal radiotherapy fractionation schemes, i.e., delivering distinct dose distributions in different fractions can potentially improve the therapeutic ratio. This is possible if the dose distributions are designed such that similar doses are delivered to normal tissues (exploit the fractionation effect) while hypofractionating subregions of the tumor. In this paper, the authors develop methodology for treatment planning with nonuniform fractions and demonstrate this concept in the context of intensity-modulated proton therapy (IMPT). Methods: Treatment planning is performed by simultaneously optimizing (possibly distinct) IMPT dose distributions for multiple fractions. This is achieved using objective and constraint functions evaluated for the cumulative biologically equivalent dose (BED) delivered at the end of treatment. BED based treatment planning formulations lead to nonconvex optimization problems, such that local gradient based algorithms require adequate starting positions to find good local optima. To that end, the authors develop a combinatorial algorithm to initialize the pencil beam intensities. Results: The concept of nonuniform spatiotemporal fractionation schemes is demonstrated for a spinal metastasis patient treated in two fractions using stereotactic body radiation therapy. The patient is treated with posterior oblique beams with the kidneys being located in the entrance region of the beam. It is shown that a nonuniform fractionation scheme that hypofractionates the central part of the tumor allows for a skin and kidney BED reduction of approximately 10%-20%. Conclusions: Nonuniform spatiotemporal fractionation schemes represent a novel approach to exploit fractionation effects that deserves further exploration for selected disease sites. (C) 2015 American Association of Physicists in Medicine. C1 [Unkelbach, Jan; Papp, David] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Unkelbach, Jan; Papp, David] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Unkelbach, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM junkelbach@mgh.harvard.edu NR 17 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2015 VL 42 IS 5 BP 2234 EP 2241 DI 10.1118/1.4916684 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI5ER UT WOS:000354776800014 PM 25979017 ER PT J AU Grassberger, C Dowdell, S Sharp, G Paganetti, H AF Grassberger, Clemens Dowdell, Stephen Sharp, Greg Paganetti, Harald TI Motion mitigation for lung cancer patients treated with active scanning proton therapy SO MEDICAL PHYSICS LA English DT Article DE lung cancer; motion mitigation; active scanning proton therapy; interplay effect ID PARTICLE THERAPY; RESPIRATORY MOTION; MONTE-CARLO; INTERPLAY; BEAM; QUANTIFICATION; PARAMETERS; RADIATION; DELIVERY; TARGETS AB Purpose: Motion interplay can affect the tumor dose in scanned proton beam therapy. This study assesses the ability of rescanning and gating to mitigate interplay effects during lung treatments. Methods: The treatments of five lung cancer patients [48 Gy(RBE)/4fx] with varying tumor size (21.1-82.3 cm(3)) and motion amplitude (2.9-30.6 mm) were simulated employing 4D Monte Carlo. The authors investigated two spot sizes (sigma similar to 12 and similar to 3 mm), three rescanning techniques (layered, volumetric, breath-sampled volumetric) and respiratory gating with a 30% duty cycle. Results: For 4/5 patients, layered rescanning 6/2 times (for the small/large spot size) maintains equivalent uniform dose within the target >98% for a single fraction. Breath sampling the timing of rescanning is similar to 2 times more effective than the same number of continuous rescans. Volumetric rescanning is sensitive to synchronization effects, which was observed in 3/5 patients, though not for layered rescanning. For the large spot size, rescanning compared favorably with gating in terms of time requirements, i.e., 2x-rescanning is on average a factor similar to 2.6 faster than gating for this scenario. For the small spot size however, 6x-rescanning takes on average 65% longer compared to gating. Rescanning has no effect on normal lung V-20 and mean lung dose (MLD), though it reduces the maximum lung dose by on average 6.9 +/- 2.4/16.7 +/- 12.2 Gy(RBE) for the large and small spot sizes, respectively. Gating leads to a similar reduction in maximum dose and additionally reduces V-20 and MLD. Breath-sampled rescanning is most successful in reducing the maximum dose to the normal lung. Conclusions: Both rescanning (2-6 times, depending on the beam size) as well as gating was able to mitigate interplay effects in the target for 4/5 patients studied. Layered rescanning is superior to volumetric rescanning, as the latter suffers from synchronization effects in 3/5 patients studied. Gating minimizes the irradiated volume of normal lung more efficiently, while breath-sampled rescanning is superior in reducing maximum doses to organs at risk. (C) 2015 American Association of Physicists in Medicine. C1 [Grassberger, Clemens; Dowdell, Stephen; Sharp, Greg; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Grassberger, Clemens; Dowdell, Stephen; Sharp, Greg; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Grassberger, Clemens] Paul Scherrer Inst, CH-5232 Villigen, Switzerland. RP Grassberger, C (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM Grassberger.Clemens@mgh.harvard.edu FU National Cancer Institute [R01CA111590] FX The authors would like to acknowledge Dr. Anthony Lomax for improving this paper through lively discussion, Dr. Brian Healy for his insights into statistics, Dr. Ben Clasie for sharing his knowledge about active scanning proton delivery systems, Dr. Henning Willers for fruitful discussions concerning clinical relevance, and Dr. Jon Jackson and Partners Research Computing for maintenance of the computing cluster. This work was supported by the National Cancer Institute under R01CA111590. The authors report no conflicts of interest in conducting the research. NR 23 TC 10 Z9 10 U1 1 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2015 VL 42 IS 5 BP 2462 EP 2469 DI 10.1118/1.4916662 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI5ER UT WOS:000354776800036 PM 25979039 ER PT J AU Yin, Z Yao, YY Montillo, A Wu, MY Edic, PM Kalra, M De Man, B AF Yin, Zhye Yao, Yangyang Montillo, Albert Wu, Mingye Edic, Peter M. Kalra, Mannudeep De Man, Bruno TI Acquisition, preprocessing, and reconstruction of ultralow dose volumetric CT scout for organ-based CT scan planning SO MEDICAL PHYSICS LA English DT Article DE 3D volumetric scout; ultralow dose; organ segmentation and localization; scan planning ID TUBE CURRENT MODULATION; REDUCTION; SEGMENTATION; SIMULATION; PHANTOM; MODELS; NOISE AB Purpose: Traditionally, 2D radiographic preparatory scan images (scout scans) are used to plan diagnostic CT scans. However, a 3D CT volume with a full 3D organ segmentation map could provide superior information for customized scan planning and other purposes. A practical challenge is to design the volumetric scout acquisition and processing steps to provide good image quality (at least good enough to enable 3D organ segmentation) while delivering a radiation dose similar to that of the conventional 2D scout. Methods: The authors explored various acquisition methods, scan parameters, postprocessing methods, and reconstruction methods through simulation and cadaver data studies to achieve an ultralow dose 3D scout while simultaneously reducing the noise and maintaining the edge strength around the target organ. Results: In a simulation study, the 3D scout with the proposed acquisition, preprocessing, and reconstruction strategy provided a similar level of organ segmentation capability as a traditional 240 mAs diagnostic scan, based on noise and normalized edge strength metrics. At the same time, the proposed approach delivers only 1.25% of the dose of a traditional scan. In a cadaver study, the authors' pictorial-structures based organ localization algorithm successfully located the major abdominal-thoracic organs from the ultralow dose 3D scout obtained with the proposed strategy. Conclusions: The authors demonstrated that images with a similar degree of segmentation capability (interpretability) as conventional dose CT scans can be achieved with an ultralow dose 3D scout acquisition and suitable postprocessing. Furthermore, the authors applied these techniques to real cadaver CT scans with a CTDI dose level of less than 0.1 mGy and successfully generated a 3D organ localization map. (C) 2015 American Association of Physicists in Medicine. C1 [Yin, Zhye; De Man, Bruno] GE Global Res, Image Reconstruct Lab, Niskayuna, NY 12309 USA. [Yao, Yangyang; Wu, Mingye] GE Global Res, Xray & CT Lab, Shanghai 201203, Peoples R China. [Montillo, Albert] GE Global Res, Biomed Image Proc Lab, Niskayuna, NY 12309 USA. [Edic, Peter M.] GE Global Res, Xray & Funct Imaging, CT, Niskayuna, NY 12309 USA. [Kalra, Mannudeep] Massachusetts Gen Hosp, Thorac & Cardiac Imaging, Boston, MA 02114 USA. RP Yin, Z (reprint author), GE Global Res, Image Reconstruct Lab, Niskayuna, NY 12309 USA. EM yin@ge.com NR 27 TC 2 Z9 2 U1 1 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2015 VL 42 IS 5 BP 2730 EP 2739 DI 10.1118/1.4921065 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI5ER UT WOS:000354776800067 PM 25979071 ER PT J AU De Man, B Wu, MY FitzGerald, P Kalra, M Yin, Z AF De Man, Bruno Wu, Mingye FitzGerald, Paul Kalra, Mannudeep Yin, Zhye TI Dose reconstruction for real-time patient-specific dose estimation in CT SO MEDICAL PHYSICS LA English DT Article DE computed tomography; radiation dose estimation ID MONTE-CARLO-CALCULATION; COMPUTED-TOMOGRAPHY; TUBE CURRENT; SUPERPOSITION/CONVOLUTION; MODULATION; RADIATION; NOISE AB Purpose: Many recent computed tomography (CT) dose reduction approaches belong to one of three categories: statistical reconstruction algorithms, efficient x-ray detectors, and optimized CT acquisition schemes with precise control over the x-ray distribution. The latter category could greatly benefit from fast and accurate methods for dose estimation, which would enable real-time patient-specific protocol optimization. Methods: The authors present a new method for volumetrically reconstructing absorbed dose on a per-voxel basis, directly from the actual CT images. The authors' specific implementation combines a distance-driven pencil-beam approach to model the first-order x-ray interactions with a set of Gaussian convolution kernels to model the higher-order x-ray interactions. The authors performed a number of 3D simulation experiments comparing the proposed method to a Monte Carlo based ground truth. Results: The authors' results indicate that the proposed approach offers a good trade-off between accuracy and computational efficiency. The images show a good qualitative correspondence to Monte Carlo estimates. Preliminary quantitative results show errors below 10%, except in bone regions, where the authors see a bigger model mismatch. The computational complexity is similar to that of a low-resolution filtered-backprojection algorithm. Conclusions: The authors present a method for analytic dose reconstruction in CT, similar to the techniques used in radiation therapy planning with megavoltage energies. Future work will include refinements of the proposed method to improve the accuracy as well as a more extensive validation study. The proposed method is not intended to replace methods that track individual x-ray photons, but the authors expect that it may prove useful in applications where real-time patient-specific dose estimation is required. (C) 2015 American Association of Physicists in Medicine. C1 [De Man, Bruno; Yin, Zhye] GE Global Res, Image Reconstruct Lab, Niskayuna, NY 12309 USA. [Wu, Mingye] GE Global Res, Xray & CT Lab, Shanghai 201203, Peoples R China. [FitzGerald, Paul] GE Global Res, Radiat Syst Lab, Niskayuna, NY 12309 USA. [Kalra, Mannudeep] Massachusetts Gen Hosp, Div Thorac, Boston, MA 02114 USA. [Kalra, Mannudeep] Massachusetts Gen Hosp, Div Cardiac Imaging, Boston, MA 02114 USA. RP De Man, B (reprint author), GE Global Res, Image Reconstruct Lab, Niskayuna, NY 12309 USA. EM deman@ge.com NR 22 TC 2 Z9 2 U1 1 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2015 VL 42 IS 5 BP 2740 EP 2751 DI 10.1118/1.4921066 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI5ER UT WOS:000354776800068 PM 25979072 ER PT J AU Pahwa, R Tanner, CM Hauser, RA Sethi, K Isaacson, S Truong, D Struck, L Ruby, AE McClure, NL Went, GT Stempien, MJ AF Pahwa, Rajesh Tanner, Caroline M. Hauser, Robert A. Sethi, Kapil Isaacson, Stuart Truong, Daniel Struck, Lynn Ruby, April E. McClure, Natalie L. Went, Gregory T. Stempien, Mary Jean TI Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study) SO MOVEMENT DISORDERS LA English DT Article DE clinical trial; randomized controlled trial; Parkinson's disease; levodopa-induced dyskinesia; amantadine ID MOTOR FLUCTUATIONS; SCALE; PSYCHOSIS AB ADS-5102 is a long-acting, extended-release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS-5102 in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. This was a randomized, double-blind, placebo-controlled, parallel-group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS-5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks. The primary efficacy analysis compared change from baseline to week 8 in Unified Dyskinesia Rating Scale (UDysRS) total score for 340 mg ADS-5102 versus placebo. Secondary outcome measures included change in UDysRS for 260 mg, 420 mg, Fatigue Severity Scale (FSS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), patient diary, Clinician's Global Impression of Change, and Parkinson's Disease Questionnaire (PDQ-39). ADS-5102 340 mg significantly reduced dyskinesia versus placebo (27% reduction in UDysRS, P=0.005). In addition, ADS-5102 significantly increased ON time without troublesome dyskinesia, as assessed by PD patient diaries, at 260 mg (P=0.004), 340 mg (P=0.008) and 420 mg (P=0.018). Adverse events (AEs) were reported for 82%, 80%, 95%, and 90% of patients in the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. Constipation, hallucinations, dizziness, and dry mouth were the most frequent AEs. Study withdrawal rates were 9%, 15%, 14%, and 40% for the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. All study withdrawals in the active treatment groups were attributable to AEs. ADS-5102 was generally well tolerated and resulted in significant and dose-dependent improvements in dyskinesia in PD patients. (c) 2015 Adamas Pharmaceuticals, Inc. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. C1 [Pahwa, Rajesh] Univ Kansas, Med Ctr, Kansas City, KS 66160 USA. [Tanner, Caroline M.] Parkinsons Inst, Sunnyvale, CA USA. [Tanner, Caroline M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Tanner, Caroline M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hauser, Robert A.] Univ S Florida, Tampa, FL USA. [Sethi, Kapil] Georgia Regents Univ, Augusta, GA USA. [Isaacson, Stuart] Parkinsons Dis & Movement Disorders Ctr, Boca Raton, FL USA. [Truong, Daniel] Parkinsons & Movement Disorder Inst, Fountain Valley, CA USA. [Struck, Lynn] Iowa Hlth Phys, Des Moines, IA USA. [Ruby, April E.; McClure, Natalie L.; Went, Gregory T.; Stempien, Mary Jean] Adamas Pharmaceut Inc, Emeryville, CA USA. RP Pahwa, R (reprint author), Univ Kansas, Med Ctr, Dept Neurol, 3599 Rainbow Blvd,Mailstop 2012, Kansas City, KS 66160 USA. EM rpahwa@kumc.edu FU Adamas Pharmaceuticals, Inc. FX This study was supported by Adamas Pharmaceuticals, Inc. NR 18 TC 18 Z9 19 U1 1 U2 8 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 MAY PY 2015 VL 30 IS 6 BP 788 EP 795 DI 10.1002/mds.26159 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CI4OT UT WOS:000354731500009 PM 25650051 ER PT J AU Swanson, CR Li, K Unger, TL Gallagher, MD Van Deerlin, VM Agarwal, P Leverenz, J Roberts, J Samii, A Gross, RG Hurtig, H Rick, J Weintraub, D Trojanowski, JQ Zabetian, C Chen-Plotkin, AS AF Swanson, Christine R. Li, Katherine Unger, Travis L. Gallagher, Michael D. Van Deerlin, Vivianna M. Agarwal, Pinky Leverenz, James Roberts, John Samii, Ali Gross, Rachel Goldmann Hurtig, Howard Rick, Jacqueline Weintraub, Daniel Trojanowski, John Q. Zabetian, Cyrus Chen-Plotkin, Alice S. TI Lower plasma apolipoprotein A1 levels are found in Parkinson's disease and associate with apolipoprotein A1 genotype SO MOVEMENT DISORDERS LA English DT Article DE Apolipoprotein A1; Parkinson's disease; biomarker; genotype; ApoA1 ID CEREBRAL AMYLOID ANGIOPATHY; PROMOTER REGION; I GENE; CEREBROSPINAL-FLUID; HDL-CHOLESTEROL; ALPHA-SYNUCLEIN; LIPID LEVELS; POLYMORPHISM; BIOMARKERS; POPULATION AB The discovery of novel plasma-based biomarkers could lead to new approaches in the treatment of Parkinson's disease (PD). Here, we explore the role of plasma apolipoprotein A1 (ApoA1) as a risk marker for PD and evaluate the influence of APOA1 promoter variation on plasma ApoA1 levels. Plasma ApoA1 and the single-nucleotide polymorphism, rs670, were assayed in a discovery cohort (cohort 1) of 301 PD patients, 80 normal controls (NCs), and 165 subjects with other neurodegenerative diseases, as well as a cohort (cohort 2) of 158 PD patients from a second clinical site. Additionally, rs670 was genotyped in a third cohort of 1,494 PD and 925 NC subjects from both clinical sites. Compared to both normal and disease controls, PD patients have lower plasma ApoA1 (P<0.001 for both comparisons). Moreover, in PD patients, plasma ApoA1 levels are correlated with genotype at the APOA1 promoter polymorphism, rs670. Specifically, lower plasma ApoA1 levels were found in rs670 major allele (G) homozygotes in both cohort 1 (P=0.009) and in a replication cohort (cohort 2; n=158 PD patients; P=0.024). Finally, evaluating rs670 genotype frequencies in 1,930 PD cases versus 997 NCs, the rs670 GG genotype shows a trend toward association (odds ratio: 1.1; P=0.10) with PD. Our results are compatible with a model whereby circulating ApoA1 levels may be useful in risk-stratifying subjects for the development of PD, with higher ApoA1 levels suggesting relative protection. Future studies evaluating modulation of ApoA1 as a novel therapeutic strategy in PD are warranted. (c) 2014 International Parkinson and Movement Disorder Society C1 [Swanson, Christine R.; Li, Katherine; Unger, Travis L.; Gallagher, Michael D.; Gross, Rachel Goldmann; Hurtig, Howard; Rick, Jacqueline; Chen-Plotkin, Alice S.] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gallagher, Michael D.] Univ Penn, Cellular & Mol Biol Grad Grp, Perelman Sch Med, Philadelphia, PA 19104 USA. [Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Agarwal, Pinky] Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Washington, DC USA. [Leverenz, James] Cleveland Clin, Ruvo Ctr Brain Hlth, Cleveland, OH 44106 USA. [Roberts, John] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Samii, Ali; Zabetian, Cyrus] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Samii, Ali; Zabetian, Cyrus] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Chen-Plotkin, AS (reprint author), Univ Penn, Dept Neurol, Perelman Sch Med, 3 West Gates,3400 Spruce St, Philadelphia, PA 19104 USA. EM chenplot@mail.med.upenn.edu RI Gallagher, Michael/G-7113-2015; OI Gallagher, Michael/0000-0002-2109-1293; Zabetian, Cyrus/0000-0002-7739-4306 FU National Institute of Neurological Disorders and Stroke [P50 NS053488, P50NS062684]; National Institutes of Health (NIH) [UO1 NS082134, R01 NS065070]; Burroughs Wellcome Fund Career Award for Medical Scientists; Doris Duke Clinician Scientist Development Award; Benaroya Fund; Department of Veterans Affairs [1101BX000531] FX The clinical data in this project were collected though the support of the University of Pennsylvania and University of Washington Morris K. Udall Parkinson's Disease Research Center of Excellence grants from the National Institute of Neurological Disorders and Stroke (P50 NS053488 and P50NS062684). A.S.C.-P. is supported by the National Institutes of Health (NIH; UO1 NS082134), the Burroughs Wellcome Fund Career Award for Medical Scientists, a Doris Duke Clinician Scientist Development Award, and the Benaroya Fund. C.Z. is supported by the NIH (R01 NS065070) and the Department of Veterans Affairs (Merit Award 1101BX000531). NR 43 TC 5 Z9 6 U1 0 U2 2 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 MAY PY 2015 VL 30 IS 6 BP 805 EP 812 DI 10.1002/mds.26022 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CI4OT UT WOS:000354731500011 PM 25227208 ER PT J AU Riley, LE Ecker, JL AF Riley, Laura E. Ecker, Jeffrey L. TI Anticipating the Next Arrival Ebola in the Pregnant Woman SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 [Riley, Laura E.; Ecker, Jeffrey L.] Massachusetts Gen Hosp, Dept Obstet & Maternal Fetal Med, Boston, MA 02114 USA. RP Riley, LE (reprint author), Massachusetts Gen Hosp, Dept Obstet & Maternal Fetal Med, Boston, MA 02114 USA. EM lriley@partners.org; jecker@partners.org NR 6 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2015 VL 125 IS 5 BP 1033 EP 1034 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CI7SP UT WOS:000354965200001 PM 25932828 ER PT J AU Memon, HU Blomquist, JL Dietz, HP Pierce, CB Weinstein, MM Handa, VL AF Memon, Hafsa U. Blomquist, Joan L. Dietz, Hans P. Pierce, Christopher B. Weinstein, Milena M. Handa, Victoria L. TI Comparison of Levator Ani Muscle Avulsion Injury After Forceps-Assisted and Vacuum-Assisted Vaginal Childbirth SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PELVIC FLOOR DISORDERS; ORGAN PROLAPSE; TRAUMA; WOMEN; ULTRASOUND; URETHRA; HIATUS; BIRTH AB OBJECTIVE: Using three-dimensional transperineal ultrasonography, we compared the prevalence of levator ani muscle injury after forceps with vacuum-assisted vaginal delivery. METHODS: This was a retrospective cohort study. Women who experienced at least one forceps delivery (across all deliveries) were compared with women who had at least one vacuum birth. On average, participants were 10 years from the index delivery. Three-dimensional transperineal ultrasound volumes were captured as cine loops at rest with Valsalva and with pelvic floor muscle contraction. The primary outcome was levator ani muscle avulsion. Secondary outcomes included hiatal diameter and area. Prevalence of pelvic floor disorders was also compared between the two delivery groups. RESULTS: Among 45 participants in the forceps group and 28 participants in the vacuum group, there were no differences between groups in maternal age at first delivery, parity, body mass index, birth weight, episiotomy, or duration of second stage. History of anal sphincter laceration was more common in the forceps group. The prevalence of levator ani muscle avulsion was significantly higher after forceps compared with vacuum delivery (22/45 [49%] compared with 5/28 [18%], P=.012, prevalence ratio 2.74, 95% confidence interval [CI] 1.17-6.40, odds ratio 4.40 [95% CI 1.42-13.62]). Controlling for delivery type, levator ani muscle avulsion was associated with symptoms of prolapse (P=.036), although objective evidence of prolapse was not significantly different between groups (P=.20). CONCLUSION: Ten years after delivery, the prevalence of levator avulsion is almost tripled after forceps compared with vacuum-assisted vaginal delivery. C1 Johns Hopkins Univ, Dept Gynecol & Obstet, Dept Gynecol, Greater Baltimore Med Ctr, Baltimore, MD 21224 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Sydney Med Sch Nepean, Dept Obstet Gynecol & Neonatol, Kingswood, NSW, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Memon, HU (reprint author), Johns Hopkins Univ, Dept Gynecol & Obstet, 4940 Eastern Ave,301 Bldg, Baltimore, MD 21224 USA. EM hafsa.memon@gmail.com FU American College of Obstetricians and Gynecologists/Kenneth Gottesfeld-Charles Hohler Memorial Foundation; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD056275] FX Supported by an American College of Obstetricians and Gynecologists/Kenneth Gottesfeld-Charles Hohler Memorial Foundation grant and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD056275). NR 20 TC 6 Z9 7 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2015 VL 125 IS 5 BP 1080 EP 1087 DI 10.1097/AOG.0000000000000825 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CI7SP UT WOS:000354965200010 PM 25932835 ER PT J AU Kennedy, DJ Levin, J Rosenquist, R Singh, V Smith, C Stojanovic, MP Vorobeychik, Y AF Kennedy, David J. Levin, Joshua Rosenquist, Richard Singh, Virtaj Smith, Clark Stojanovic, Milan P. Vorobeychik, Yakov TI Epidural Steroid Injections are Safe and Effective: Multisociety Letter in Support of the Safety and Effectiveness of Epidural Steroid Injections SO PAIN MEDICINE LA English DT Article DE Epidural; Steroid; Injection; Safety; Effectiveness ID LUMBAR RADICULAR PAIN; PERIRADICULAR CORTICOSTEROID INJECTIONS; LOW-BACK-PAIN; DOUBLE-BLIND; NERVE-ROOT; TRANSFORAMINAL INJECTION; DISC HERNIATION; NONPARTICULATE CORTICOSTEROIDS; CONTROLLED-TRIAL; PUBLISHED DATA AB Background: In April 2014, the Food and Drug Administration (FDA) issued a Drug Safety Communication requesting that corticosteroid labeling include warnings that injection of corticosteroids into the epidural space of the spine may result in rare but serious adverse events, including loss of vision, stroke, paralysis, and death. Results: The International Spine Intervention Society spearheaded a collaboration of more than a dozen other medical societies in submitting the letter below to the FDA on November 7, 2014. We are publishing the letter to ensure that the readership of Pain Medicine is aware of the multisociety support for the safety and effectiveness of these procedures. A special note of thanks to all of the societies who signed on in support of the message. C1 [Kennedy, David J.] Stanford Univ, Dept Orthopaed, Redwood City, CA 94063 USA. [Levin, Joshua] Stanford Univ, Dept Orthopaed & Neurosurg, Palo Alto, CA 94304 USA. [Rosenquist, Richard] Cleveland Clin, Dept Pain Management, Cleveland, OH 44106 USA. [Singh, Virtaj] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Smith, Clark] Columbia Univ, Dept Rehabil & Regenerat Med, New York, NY USA. [Stojanovic, Milan P.] VA Boston Healthcare Syst, Dept Anesthesiol, Crit Care & Pain Med Serv, Boston, MA USA. [Vorobeychik, Yakov] Penn State Hershey Med Ctr, Dept Anesthesiol & Neurol, Hershey, PA USA. RP Kennedy, DJ (reprint author), Stanford Univ, Dept Orthopaed, 450 Broadway St,Pavil C,MC 6342, Redwood City, CA 94063 USA. EM djkenned@stanford.edu NR 41 TC 2 Z9 2 U1 1 U2 2 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 MAY PY 2015 VL 16 IS 5 BP 833 EP 838 DI 10.1111/pme.12667 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CI4SC UT WOS:000354742300001 PM 25586082 ER PT J AU Dobscha, SK Morasco, BJ Kovas, AE Peters, DM Hart, K McFarland, BH AF Dobscha, Steven K. Morasco, Benjamin J. Kovas, Anne E. Peters, Dawn M. Hart, Kyle McFarland, Bentson H. TI Short-Term Variability in Outpatient Pain Intensity Scores in a National Sample of Older Veterans with Chronic Pain SO PAIN MEDICINE LA English DT Article DE Chronic Pain; Veterans; Numeric Rating Scale; Aged ID CHRONIC NONCANCER PAIN; PRESCRIPTION OPIOID USE; NUMERIC RATING-SCALE; HEALTH-CARE-SYSTEM; PERSISTENT PAIN; RACIAL-DIFFERENCES; MENTAL-HEALTH; BACK-PAIN; DEPRESSION; PATTERNS AB ObjectiveThe Department of Veterans Affairs (VA) uses the 11-point pain numeric rating scale (NRS) to gather pain intensity information from veterans at outpatient appointments. Yet, little is known about how NRS scores may vary over time within individuals; NRS variability may have important ramifications for treatment planning. Our main objective was to describe variability in NRS scores within a 1-month timeframe, as obtained during routine outpatient care in older patients with chronic pain treated in VA hospitals. A secondary objective was to explore for patient characteristics associated with within-month NRS score variability. DesignRetrospective cohort study. SubjectsNational sample of veterans 65 years or older seen in VA in 2010 who had multiple elevated NRS scores indicating chronic pain. MethodsVA datasets were used to identify the sample and demographic and clinical variables including NRS scores. For the main analysis, we identified subjects with two or more NRS scores obtained in each of two or more months in a 12-month period; we examined ranges in NRS scores across the first two qualifying months. ResultsAmong 4,336 individuals in the main analysis cohort, the mean and median of the average NRS score range across the 2 months were 2.7 and 2.5, respectively. In multivariable models, main significant predictors of within-month NRS score variability were baseline pain intensity, overall medical comorbidity, and being divorced/separated. ConclusionsThe majority of patients in the sample had clinically meaningful variation in pain scores within a given month. This finding highlights the need for clinicians and their patients to consider multiple NRS scores when making chronic pain treatment decisions. C1 [Dobscha, Steven K.; Morasco, Benjamin J.; Kovas, Anne E.; Hart, Kyle] Portland VA Med Ctr, Ctr Improve Vet Involvement Care, Portland, OR 97207 USA. [Dobscha, Steven K.; Morasco, Benjamin J.; McFarland, Bentson H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Peters, Dawn M.; McFarland, Bentson H.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, POB 1034 R&D 66, Portland, OR 97207 USA. EM steven.dobscha@va.gov FU National Institutes of Health, National Institute on Aging [R03-AG042756]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [CIN 13-404] FX This material is based upon work supported by the National Institutes of Health, National Institute on Aging, R03-AG042756 (PI: Dobscha) and the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, CIN 13-404 (PI: Dobscha). Dr. Dobscha is the Director of 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, National Institutes of Health, or United States government. NR 52 TC 5 Z9 5 U1 0 U2 2 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 MAY PY 2015 VL 16 IS 5 BP 855 EP 865 DI 10.1111/pme.12643 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CI4SC UT WOS:000354742300004 PM 25545398 ER PT J AU Weiner, DK AF Weiner, Debra K. TI Introduction to Special Series: Deconstructing Chronic Low Back Pain in the Older Adult: Shifting the Paradigm from the Spine to the Person SO PAIN MEDICINE LA English DT Editorial Material DE Back Pain; Chronic Low Back Pain; Chronic Pain; Elderly; Geriatric; Homeostenosis; Low Back Pain; Lumbar; Magnetic Resonance Imaging; Older Adults; Pain Management; Treatment Outcome ID HEALTH-CARE; MANAGEMENT; PREVALENCE; PROGRAMS; US C1 [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Weiner, Debra K.] Univ Pittsburgh, Div Geriatr Med, 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.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. RP Weiner, DK (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. EM debra.weiner@va.gov NR 19 TC 9 Z9 9 U1 2 U2 4 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 MAY PY 2015 VL 16 IS 5 BP 881 EP 885 DI 10.1111/pme.12759 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CI4SC UT WOS:000354742300008 PM 25846799 ER PT J AU Weiner, DK Fang, MK Gentili, A Kochersberger, G Marcum, ZA Rossi, MI Semla, TP Shega, J AF Weiner, Debra K. Fang, Meika Gentili, Angela Kochersberger, Gary Marcum, Zachary A. Rossi, Michelle I. Semla, Todd P. Shega, Joseph TI Deconstructing Chronic Low Back Pain in the Older AdultStep by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part I: Hip Osteoarthritis SO PAIN MEDICINE LA English DT Review DE Aged; Assessment; Hip Osteoarthritis; Chronic Pain; Elderly; Low Back Pain; Primary Care; Chronic Low Back Pain ID RANDOMIZED CLINICAL-TRIAL; SPINE SYNDROME; KNEE OSTEOARTHRITIS; EXERCISE THERAPY; SELF-MANAGEMENT; MANUAL THERAPY; PREVALENCE; ARTHRITIS; OUTCOMES; CRITERIA AB ObjectiveTo present the first in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of twelve important contributors to pain and disability in older adults with CLBP. This article focuses on hip osteoarthritis (OA). MethodsThe evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a five-member content expert panel and a nine-member primary care panel were involved in the iterative development of these materials. The algorithm was developed keeping in mind medications and other resources available within Veterans Health Administration (VHA) facilities. As panelists were not exclusive to the VHA, the materials can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributor's clinical practice. ResultsWe present an algorithm and supportive materials to help guide the care of older adults with hip OA, an important contributor to CLBP. The case illustrates an example of complex hip-spine syndrome, in which hip OA was an important contributor to disability in an older adult with CLBP. ConclusionsHip OA is common and should be evaluated routinely in the older adult with CLBP so that appropriately targeted treatment can be designed. C1 [Weiner, Debra K.; Rossi, Michelle I.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Weiner, Debra K.; Marcum, Zachary A.; Rossi, Michelle I.] Univ Pittsburgh, Dept Med, Div Geriatr 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.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. [Fang, Meika] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fang, Meika] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gentili, Angela] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. [Gentili, Angela] Hunter Holmes McGuire VA Med Ctr, Richmond, VA USA. [Kochersberger, Gary] Univ Rochester, Div Geriatr, Rochester, NY USA. [Kochersberger, Gary] VA Med Ctr, Canandaigua, NY USA. [Semla, Todd P.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Semla, Todd P.] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Shega, Joseph] VITAS Hlth Care, Miami, FL USA. RP Weiner, DK (reprint author), VA Pittsburgh Healthcare Syst, Univ Drive,Bldg 30,00GR, Pittsburgh, PA 15240 USA. EM debra.weiner@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service FX This material is based on work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service. The contents of this report do not represent the views of the Department of Veterans Affairs or the US government. The author thanks Dave Newman, Dr. Rollin Gallagher, and Dr. Eric Rodriguez for their thoughtful review of the manuscript. NR 48 TC 5 Z9 5 U1 3 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 MAY PY 2015 VL 16 IS 5 BP 886 EP 897 DI 10.1111/pme.12757 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CI4SC UT WOS:000354742300009 PM 25846648 ER PT J AU Zhang, Y Ahmed, S Vo, T St Hilaire, K Houghton, M Cohen, AS Mao, JR Chen, L AF Zhang, Yi Ahmed, Shihab Trang Vo St Hilaire, Kristin Houghton, Mary Cohen, Abigail S. Mao, Jianren Chen, Lucy TI Increased Pain Sensitivity in Chronic Pain Subjects on Opioid Therapy: A Cross-Sectional Study Using Quantitative Sensory Testing SO PAIN MEDICINE LA English DT Article DE Opioids; Hyperalgesia; Chronic Pain ID INDUCED ABNORMAL PAIN; LOW-BACK-PAIN; INDUCED HYPERALGESIA; HEAT PAIN; PERCEPTION; TOLERANCE; RATS; ASSOCIATIONS; METHADONE AB ObjectiveThe aim of this study was to compare the sensitivity to experimental pain of chronic pain patients on opioid therapy vs chronic pain patients on non-opioid therapy and healthy subjects by quantitative sensory testing (QST). SettingThere is a growing body of evidence demonstrating that chronic use of opioid drugs may alter pain sensitivity. Identifying the characteristic changes in thermal pain sensitivity in chronic opioid users will be helpful in diagnosing pain sensitivity alterations associated with chronic opioid use. MethodsUtilizing an office-based QST technique, we examined thermal pain threshold, tolerance, and temporal summation in 172 chronic pain subjects receiving opioid therapy, 121 chronic pain subjects receiving non-opioid therapy, and 129 healthy subjects. ResultsIn chronic pain subjects receiving opioid therapy, there were detectable differences in QST characteristics compared with both chronic pain subjects receiving non-opioid therapy and healthy subjects. Specifically, in chronic pain subjects receiving opioid therapy, 1) sensitivity to heat pain was increased; threshold to heat pain was significantly lower; 2) tolerance to supra-threshold heat pain was significantly decreased; and 3) temporal pain summation was exacerbated, as compared with chronic pain subjects receiving non-opioid therapy. In a subgroup of chronic pain subjects receiving opioid therapy with increased heat pain sensitivity, their average opioid medication dosage was significantly higher than those who had an above-average heat pain threshold. Moreover, a subset of chronic pain subjects on opioid therapy exhibited a significant decrease in diffuse noxious inhibitory control (DNIC) compared with chronic pain subjects on non-opioid therapy. ConclusionThese findings suggest that a subset of QST parameters can reflect opioid-associated thermal pain sensitivity alteration, including decreased heat pain threshold, decreased cold and heat pain tolerance, diminished DNIC, and/or exacerbated temporal summation. C1 [Zhang, Yi; Ahmed, Shihab; Trang Vo; St Hilaire, Kristin; Houghton, Mary; Cohen, Abigail S.; Mao, Jianren; Chen, Lucy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,Ctr Translat, Boston, MA USA. RP Chen, L (reprint author), Massachusetts Gen Hosp, Ctr Ambulatory Care, Ctr Pain Med, 15 Parkman St, Boston, MA 02114 USA. EM llchen@partners.org FU NIH [DA036564, DA022576] FX This work was supported by NIH R01 grants DA036564 and DA022576. NR 32 TC 4 Z9 4 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD MAY PY 2015 VL 16 IS 5 BP 911 EP 922 DI 10.1111/pme.12606 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CI4SC UT WOS:000354742300012 PM 25376890 ER PT J AU Cornejo-Olivas, MR Torres, L Mata, IF Mazzetti, P Rivas, D Cosentino, C Inca-Martinez, M Cuba, JM Zabetian, CP Leverenz, JB AF Cornejo-Olivas, Mario R. Torres, Luis Mata, Ignacio F. Mazzetti, Pilar Rivas, Diana Cosentino, Carlos Inca-Martinez, Miguel Cuba, Juan M. Zabetian, Cyrus P. Leverenz, James B. TI A Peruvian family with a novel PARK2 mutation: Clinical and pathological characteristics SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Familial parkinsonism; Parkin; Mutations; Pathology ID RECESSIVE JUVENILE PARKINSONISM; EARLY-ONSET PARKINSONISM; LEWY BODIES; DISEASE; GENE; IDENTIFICATION; DELETION; PATIENT AB Background: Mutations in PARK2 result in autosomal recessive young onset Parkinson's disease (YOPD). Although there have been a number of reports on the clinical characteristics of PARK2-related PD, there is limited information available on the associated neuropathologic changes. Design: We describe the clinical and pathological characteristics of a Peruvian family with YOPD. The proband and one unaffected sibling were screened for PARK2 dosage and point mutations. One affected sibling had detailed neuropathologic examination. Setting: Instituto Nacional de Ciencias Neurologicas (INCN) in Lima, Peru. Results: The proband and two of her four siblings developed YOPD and both parents were unaffected. The clinical course has been characterized by akinetic-rigid parkinsonism predominantly affecting the lower limbs and dyskinesias. Analysis of PARK2 showed that the proband is compound heterozygous for a novel acceptor splice site mutation in intron 5 (IVS5-1G>A) and an exon 7 deletion. Neuropathologic assessment of an affected sibling revealed severe neuronal loss in the substantia nigra (SN) and loss of tyrosine hydroxylase immunopositive fibers in the striatum. No Lewy body pathology was observed using standard histology or immunohistochemistry for alpha-synuclein. Conclusions: Consistent with most neuropathologic reports of patients with PARK2 mutations, we did not observe Lewy body inclusions, despite marked SN degeneration and severe dopaminergic denervation of the striatum. These data describe a novel splice site mutation and further extend the clinicopathological characterization of PARK2-associated PD. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Cornejo-Olivas, Mario R.] Northern Pacific Global Hlth Res Fellows Training, Bethesda, MD USA. [Cornejo-Olivas, Mario R.; Mazzetti, Pilar; Inca-Martinez, Miguel] Neurogenet Res Ctr, Inst Nacl Ciencias Neurol, Lima, Peru. [Torres, Luis; Cosentino, Carlos; Cuba, Juan M.] Inst Natl Ciencias Neurol, Movement Disorders Unit, Lima, Peru. [Rivas, Diana] Inst Natl Ciencias Neurol, Dept Neuropathol, Lima, Peru. [Mata, Ignacio F.; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Mata, Ignacio F.; Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Leverenz, James B.] Cleveland Clin, Neurol Inst, Lou Ruvo Ctr Brain Hlth, Cleveland, OH 44106 USA. RP Leverenz, JB (reprint author), 9500 Euclid Ave U10, Cleveland, OH 44195 USA. EM leverej@ccf.org OI Zabetian, Cyrus/0000-0002-7739-4306; Cornejo-Olivas, Mario /0000-0001-6313-5680 FU Department of Veterans Affairs; National Institutes of Health [R01 NS065070, P50 NS062684, P50 NS040256]; Parkinson's Disease Foundation; Jane and Lee Seidman Fund; NIH [R24 TW007988]; Northern Pacific Global Health Research Fellows Training Consortium [R25 TW009345] FX This work was supported by the Department of Veterans Affairs, National Institutes of Health (R01 NS065070, P50 NS062684, P50 NS040256), the Parkinson's Disease Foundation, and the Jane and Lee Seidman Fund. Dr Cornejo-Olivas is the recipient of an NIH Fogarty International Clinical Research Fellowship at Vanderbilt University (R24 TW007988) and Northern Pacific Global Health Research Fellows Training Consortium (R25 TW009345). NR 30 TC 2 Z9 3 U1 0 U2 3 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 MAY PY 2015 VL 21 IS 5 BP 444 EP 448 DI 10.1016/j.parkreldis.2015.01.005 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA CI8PL UT WOS:000355034100004 PM 25817512 ER PT J AU Katz, M Won, SJ Park, Y Orr, A Jones, DP Swanson, RA Glass, GA AF Katz, Maya Won, Seok Joon Park, Youngja Orr, Adrienne Jones, Dean P. Swanson, Raymond A. Glass, Graham A. TI Cerebrospinal fluid concentrations of N-acetylcysteine after oral administration in Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Glutathione; Cysteine; Neuroprotection; Therapeutics; Parkinson's disease ID ACETYL-CYSTEINE; GLUTATHIONE; MOUSE; MICE AB Introduction: Depletion of neuronal glutathione may contribute to the pathogenesis of Parkinson's disease (PD). N-acetylcysteine (NAC) can restore neuronal glutathione levels, but it has not been established whether NAC can cross the blood brain barrier in humans. Methods: Twelve patients with PD were given oral NAC twice daily for 2 days. Three doses were compared: 7 mg/kg, 35 mg/kg, and 70 mg/kg. NAC, cysteine, and glutathione were measured in the cerebrospinal fluid (CSF) at baseline and 90 min after the last dose. Cognitive and motor functions were assessed pre- and post-NAC administration using the Montreal Cognitive Assessment (MoCA) and the Unified Parkinson's Disease Rating Scale part III motor subscore (UPDRS-III). Results: Oral NAC produced a dose-dependent increase in CSF NAC concentrations (p < 0.001), with the highest dose producing a CSF concentration of 9.26 +/- 1.62 mu M. There were no significant adverse events. NAC had no acute effect on motor or cognitive function. Conclusion: Orally administered NAC produces biologically relevant CSF NAC concentrations at doses that are well tolerated. The findings support the feasibility of NAC as a potential disease-modifying therapy for PD. Published by Elsevier Ltd. C1 [Katz, Maya; Won, Seok Joon; Orr, Adrienne; Swanson, Raymond A.; Glass, Graham A.] San Francisco VA Med Ctr, Neurol Serv, San Francisco, CA 94121 USA. [Katz, Maya; Won, Seok Joon; Orr, Adrienne; Swanson, Raymond A.; Glass, Graham A.] Univ Calif San Francisco, San Francisco Med Ctr, Dept Neurol, San Francisco, CA 94143 USA. [Park, Youngja; Jones, Dean P.] Emory Univ, Dept Med, Div Pulm Allergy & Crit Care Med, Atlanta, GA 30322 USA. RP Katz, M (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Neurol Serv, 4150 Clement St,1B-31 127P, San Francisco, CA 94121 USA. EM maya.katz@ucsfmedctr.org FU San Luis Obispo County Community Foundation; Singing Field Foundation; Department of Veterans Affairs FX We would like to acknowledge the hard work of, Elaine Lanier NP and Mary McCormack, who made this study possible. This study was supported by the San Luis Obispo County Community Foundation, the Singing Field Foundation, and the Department of Veterans Affairs. NR 23 TC 6 Z9 6 U1 2 U2 5 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 MAY PY 2015 VL 21 IS 5 BP 500 EP 503 DI 10.1016/j.parkreldis.2015.02.020 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA CI8PL UT WOS:000355034100014 PM 25765302 ER PT J AU Ferrer, RA Green, PA Barrett, LF AF Ferrer, Rebecca A. Green, Paige A. Barrett, Lisa Feldman TI Affective Science Perspectives on Cancer Control: Strategically Crafting a Mutually Beneficial Research Agenda SO PERSPECTIVES ON PSYCHOLOGICAL SCIENCE LA English DT Article DE affective science; cancer control; emotion ID SERVICES TASK-FORCE; QUALITY-OF-LIFE; BREAST-CANCER; RECOMMENDATION STATEMENT; EMOTION REGULATION; RISK PERCEPTIONS; BASIC EMOTIONS; PSYCHOLOGICAL CONSTRUCTION; PSYCHOSOCIAL INTERVENTION; FUNCTIONAL ARCHITECTURE AB Cancer control research involves the conduct of basic and applied behavioral and social sciences to reduce cancer incidence, morbidity, and mortality and improve quality of life. Given the importance of behavior in cancer control, fundamental research is necessary to identify psychological mechanisms underlying cancer risk, prevention, and management behaviors. Cancer prevention, diagnosis, and treatment are often emotionally laden. As such, affective science research to elucidate questions related to the basic phenomenological nature of emotion, stress, and mood is necessary to understand how cancer control can be hindered or facilitated by emotional experiences. To date, the intersection of basic affective science research and cancer control remains largely unexplored. The goal of this article is to outline key questions in the cancer control research domain that provide an ecologically valid context for new affective science discoveries. We also provide examples of ways in which basic affective discoveries could inform future cancer prevention and control research. These examples are not meant to be exhaustive or prescriptive but instead are offered to generate creative thought about the promise of a cancer research context for answering basic affective science questions. Together, these examples provide a compelling argument for fostering collaborations between affective and cancer control scientists. C1 [Ferrer, Rebecca A.; Green, Paige A.] NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. RP Ferrer, RA (reprint author), NCI, Basic Biobehav & Psychol Sci Branch, 9609 Med Ctr Dr,3E114, Rockville, MD 20850 USA. EM ferrerra@mail.nih.gov OI Green, Paige/0000-0001-7886-8924 FU Intramural NIH HHS [Z99 CA999999] NR 193 TC 0 Z9 0 U1 2 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1745-6916 EI 1745-6924 J9 PERSPECT PSYCHOL SCI JI Perspect. Psychol. Sci. PD MAY PY 2015 VL 10 IS 3 BP 328 EP 345 DI 10.1177/1745691615576755 PG 18 WC Psychology, Multidisciplinary SC Psychology GA CI5DY UT WOS:000354774400004 PM 25987511 ER PT J AU Ruchi, R Genovese, G Lee, J Charoonratana, VT Bernhardy, AJ Alper, SL Kopp, JB Thadhani, R Friedman, DJ Pollak, MR AF Ruchi, Rupam Genovese, Giulio Lee, Jessica Charoonratana, Victoria T. Bernhardy, Andrea J. Alper, Seth L. Kopp, Jeffrey B. Thadhani, Ravi Friedman, David J. Pollak, Martin R. TI Copy Number Variation at the APOL1 Locus SO PLOS ONE LA English DT Article ID APOLIPOPROTEIN-L GENE; SEGMENTAL DUPLICATIONS; HUMAN GENOME; KIDNEY-DISEASE; EVOLUTION; VARIANTS; AFRICAN; REARRANGEMENTS; ARCHITECTURE; INITIATION AB Two coding variants in the APOL1 gene (G1 and G2) explain most of the high rate of kidney disease in African Americans. APOL1-associated kidney disease risk inheritance follows an autosomal recessive pattern: The relative risk of kidney disease associated with inheritance of two high-risk variants is 7-30 fold, depending on the specific kidney phenotype. We wished to determine if the variability in phenotype might in part reflect structural differences in APOL1 gene. We analyzed sequence coverage from 1000 Genomes Project Phase 3 samples as well as exome sequencing data from African American kidney disease cases for copy number variation. 8 samples sequenced in the 1000 Genomes Project showed increased coverage over a similar to 100kb region that includes APOL2, APOL1 and part of MYH9, suggesting the presence of APOL1 copy number greater than 2. We reasoned that such duplications should be enriched in apparent G1 heterozygotes with kidney disease. Using a PCR-based assay, we observed the presence of this duplication in additional samples from apparent G0G1 or G0G2 individuals. The frequency of this APOL1 duplication was compared among cases (n = 123) and controls (n = 255) with apparent G0G1 heterozygosity. The presence of APOL1 duplication was observed in 4.06% of cases and 0.78% controls, preliminary evidence that this APOL1 duplication may alter susceptibility to kidney disease (p = 0.03). Taqman-based copy number assays confirmed the presence of 3 APOL1 copies in individuals positive for this specific duplication by PCR assay, but also identified a small number of individuals with additional APOL1 copies of presumably different structure. These observations motivate further studies to better assess the contribution of APOL1 copy number on kidney disease risk and on APOL1 function. Investigators and clinicians genotyping APOL1 should also consider whether the particular genotyping platform used is subject to technical errors when more than two copies of APOL1 are present. C1 [Ruchi, Rupam; Lee, Jessica; Charoonratana, Victoria T.; Bernhardy, Andrea J.; Alper, Seth L.; Friedman, David J.; Pollak, Martin R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Ruchi, Rupam] Univ Florida, Dept Med, Div Nephrol, Gainesville, FL USA. [Ruchi, Rupam; Alper, Seth L.; Friedman, David J.; Pollak, Martin R.] Harvard Univ, Sch Med, Boston, MA USA. [Genovese, Giulio; Alper, Seth L.] Broad Inst Harvard & MIT, Stanley Ctr, Cambridge, MA USA. [Genovese, Giulio; Pollak, Martin R.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Kopp, Jeffrey B.] NIH, Kidney Dis Branch, Bethesda, MD 20892 USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. [Friedman, David J.] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02215 USA. RP Pollak, MR (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. EM mpollak@bidmc.harvard.edu FU NIH [MD007092]; NephCure Foundation FX The work was supported by NIH MD007092 and NephCure Foundation. NR 26 TC 4 Z9 4 U1 0 U2 2 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 MAY 1 PY 2015 VL 10 IS 5 AR e0125410 DI 10.1371/journal.pone.0125410 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH2XA UT WOS:000353887100108 PM 25933006 ER PT J AU Seok, J Davis, RW Xiao, WZ AF Seok, Junhee Davis, Ronald W. Xiao, Wenzhong TI A Hybrid Approach of Gene Sets and Single Genes for the Prediction of Survival Risks with Gene Expression Data SO PLOS ONE LA English DT Article ID BREAST-CANCER; MOLECULAR CLASSIFICATION; MULTIPLE-MYELOMA; LYMPHOMA; MICROARRAYS; SIGNATURES; PROGNOSIS; DISCOVERY; NETWORKS; DISEASE AB Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn't been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge. C1 [Seok, Junhee] Korea Univ, Sch Elect Engn, Seoul 136713, South Korea. [Davis, Ronald W.; Xiao, Wenzhong] Stanford Genome Technol Ctr, Palo Alto, CA USA. [Xiao, Wenzhong] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Xiao, Wenzhong] Shriners Hosp Children, Boston, MA USA. RP Seok, J (reprint author), Korea Univ, Sch Elect Engn, Seoul 136713, South Korea. EM jseok14@korea.ac.kr; wenzhong.xiao@mgh.harvard.edu FU National Research Foundation of Korea (NRF) - Korea government [NRF-2014R1A1A2A16050527]; Korea University; National Institutes of Health [PO1-HG00205, U54-GM62119, R01-GM101401]; Shriners Research Grant [85500-BOS] FX This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2014R1A1A2A16050527) and Korea University grant, as well as grants from the National Institutes of Health (PO1-HG00205, U54-GM62119, R01-GM101401) and Shriners Research Grant (85500-BOS). NR 35 TC 0 Z9 0 U1 1 U2 11 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 MAY 1 PY 2015 VL 10 IS 5 AR e0122103 DI 10.1371/journal.pone.0122103 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH2XA UT WOS:000353887100006 PM 25933378 ER PT J AU Sulzgruber, P Koller, L Reiberger, T El-Hamid, F Forster, S Rothgerber, DJ Goliasch, G Wojta, J Niessner, A AF Sulzgruber, Patrick Koller, Lorenz Reiberger, Thomas El-Hamid, Feras Forster, Stefan Rothgerber, David-Jonas Goliasch, Georg Wojta, Johann Niessner, Alexander TI Butyrylcholinesterase Predicts Cardiac Mortality in Young Patients with Acute Coronary Syndrome SO PLOS ONE LA English DT Article ID MYOCARDIAL-INFARCTION; ARTERY-DISEASE; RISK-FACTORS; COLLABORATION; GUIDELINES; SURVIVAL AB Background The incidence of acute coronary syndrome (ACS) in young people (<= 65 years) is continuously rising. While prognostic factors in ACS are well-investigated less attention has been paid to their age-dependent prognostic value and their particular relevance in younger patients. The aim of our study was to assess the age-dependent prognostic impact of butyrylcholinesterase (BChE). Methods Retrospective cohort study including 624 patients with ACS. Patients were stratified by age into equal groups (n = 208) corresponding to "young patients" (45-64 years), "middle-aged patients" (65-84 years) and "old patients" (85-100 years). Cox regression hazard analysis was used to assess the influence of BChE on survival. Results After a mean follow-up time of 4.0 (interquartile range [IQR] 2.0-6.4) years, 154 patients (24.7%) died due to a cardiac cause. In the overall cohort, BChE was indirectly associated with cardiac mortality-free survival (adjusted hazard ratio (HR): 0.70 (95% confidence interval [CI] 0.53-0.93, p = 0.01). The primary-analysis of BChE by age strata showed the strongest effect in the age group 45-64 years with an adjusted HR per 1-SD of 0.28 (95% CI 0.12-0.64, p = 0.003), a weaker association with mortality in middle aged (65-84 years: adjusted HR per 1-SD 0.66 [95% CI: 0.41-1.06], p = 0.087), and no association in older patients (85-100 years: adjusted HR per 1-SD 0.89 [95% CI: 0.58-1.38], p = 0.613). Conclusion BChE is a strong predictor for cardiac mortality specifically in younger patients with ACS aged between 45 and 64 years. No significant association of BChE with cardiac-mortality was detected in other age classes. C1 [Sulzgruber, Patrick; Koller, Lorenz; El-Hamid, Feras; Forster, Stefan; Rothgerber, David-Jonas; Goliasch, Georg; Wojta, Johann; Niessner, Alexander] Med Univ Vienna, Dept Internal Med 2, Div Cardiol, Vienna, Austria. [Reiberger, Thomas] Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Vienna, Austria. [Reiberger, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Reiberger, Thomas] Harvard Univ, Sch Med, Boston, MA USA. RP Niessner, A (reprint author), Med Univ Vienna, Dept Internal Med 2, Div Cardiol, Vienna, Austria. EM alexander.niessner@meduniwien.ac.at FU Verein zur Forderung der Forschung - ATVB (Vienna, Austria) FX The authors received funding from Verein zur Forderung der Forschung - ATVB (Vienna, Austria) to support this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 17 TC 2 Z9 2 U1 0 U2 2 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 MAY 1 PY 2015 VL 10 IS 5 AR e0123948 DI 10.1371/journal.pone.0123948 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH2XA UT WOS:000353887100026 PM 25933219 ER PT J AU Talbot, LS Rao, MN Cohen, BE Richards, A Inslicht, SS O'Donovan, A Maguen, S Metzler, TJ Neylan, TC AF Talbot, Lisa S. Rao, Madhu N. Cohen, Beth E. Richards, Anne Inslicht, Sabra S. O'Donovan, Aoife Maguen, Shira Metzler, Thomas J. Neylan, Thomas C. TI Metabolic Risk Factors and Posttraumatic Stress Disorder: The Role of Sleep in Young, Healthy Adults SO PSYCHOSOMATIC MEDICINE LA English DT Article DE posttraumatic stress disorder; cholesterol; triglycerides; lipoproteins; visceral adiposity; sleep duration ID SERUM-LIPID CONCENTRATIONS; ADMINISTERED PTSD SCALE; VIETNAM VETERANS; VISCERAL OBESITY; POLICE OFFICERS; INSOMNIA; SYMPTOMS; ASSOCIATION; DURATION; METAANALYSIS AB Objective: Posttraumatic stress disorder (PTSD) is associated with indicators of poor physical health and sleep disturbance. This study investigated the relationship between PTSD and metabolic risk factors and examined the role of sleep duration in medically healthy and medication-free adults. Methods: Participants with PTSD (n = 44, mean age = 30.6 years) and control participants free of lifetime psychiatric history (n = 50, mean age = 30.3 years) recorded sleep using sleep diary for 10 nights and actigraphy for 7 nights. We assessed metabolic risk factors including fasting triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol, as well as abdominal fat using dual-energy x-ray absorptiometry. Results: PTSD was associated with shorter sleep duration (based on self-report, not actigraphy) and higher metabolic risks (controlling for body fat percentage), including increased triglycerides (p = .03), total cholesterol (p < .001), LDL cholesterol (p = .006), very low density lipoprotein cholesterol (p = .002), and cholesterol/high-density lipoprotein ratio (p = .024). In addition, sleep duration was associated with metabolic risks in PTSD (significant correlations ranged from r = -0.20 to r = -0.40) but did not fully account for the association between PTSD and metabolic measures. Conclusions: Metabolic risk factors are associated with PTSD even in early adulthood, which highlights the need for early intervention. Future longitudinal research should assess whether sleep disturbance in PTSD is a mechanism that contributes to heightened metabolic risk to elucidate the pathway from PTSD to higher rates of medical disorders such as obesity, diabetes, and heart disease. C1 [Talbot, Lisa S.; Rao, Madhu N.; Cohen, Beth E.; Richards, Anne; Inslicht, Sabra S.; O'Donovan, Aoife; Maguen, Shira; Metzler, Thomas J.; Neylan, Thomas C.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Rao, Madhu N.; Cohen, Beth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Talbot, Lisa S.; Richards, Anne; Inslicht, Sabra S.; O'Donovan, Aoife; Maguen, Shira; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Talbot, LS (reprint author), San Francisco VA Med Ctr, 116-H,4150 Clement St, San Francisco, CA 94121 USA. EM lisa.talbot@gmail.com FU National Institute for Mental Health [5R01MH073978-04, 5R34MH077667-03]; Mental Illness Research and Education Clinical Center of the US Veterans Health Administration; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 RR024131]; Department of Defense; Department of Veterans Affairs FX This research was supported by grants from the National Institute for Mental Health (TCN: 5R01MH073978-04, 5R34MH077667-03) and the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration. This project was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant No. UL1 RR024131. Dr. Cohen reported that her spouse is employed by Gilead Sciences, Inc. Dr. Neylan reported receiving study medication from Actelion for a study funded by the Department of Defense and receiving study medication from GlaxoSmithKline for a study funded by the Department of Veterans Affairs. For the remaining authors, no conflicts of interest were declared. NR 53 TC 5 Z9 5 U1 5 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAY PY 2015 VL 77 IS 4 BP 383 EP 391 DI 10.1097/PSY.0000000000000176 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA CI2CR UT WOS:000354553000004 PM 25886830 ER PT J AU Radtke, AJ Tse, SW Zavala, F AF Radtke, Andrea J. Tse, Sze-Wah Zavala, Fidel TI From the draining lymph node to the liver: the induction and effector mechanisms of malaria-specific CD8(+) T cells SO SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE Plasmodium; CD8(+) T cell responses; Dendritic cells (DCs); T cell memory; In vivo imaging; Vaccines ID CD8-ALPHA(+) DENDRITIC CELLS; ANTIGEN-PRESENTING CELLS; IN-VIVO; PLASMODIUM-BERGHEI; SKIN-RESIDENT; CIRCUMSPOROZOITE PROTEIN; LANGERHANS CELLS; GAMMA-INTERFERON; IMMUNITY; INFECTION AB Parasitic protozoa cause considerable disease in humans and, due to their intracellular life cycle, induce robust CD8(+) T cell responses. A greater understanding of the factors that promote and maintain CD8(+) T cell-mediated immunity against these pathogens is likely needed for the development of effective vaccines. Immunization with radiation-attenuated sporozoites, the infectious stage of the malaria parasite transmitted by mosquitoes, is an excellent model to study these questions as CD8(+) T cells specific for a single epitope can completely eliminate parasite infection in the liver. Furthermore, live, radiation-attenuated parasites represent the "gold standard" for malaria vaccination. Here, we will highlight recent studies aimed at understanding the factors required for the induction, recruitment, and maintenance of effector and memory CD8(+) T cells against malaria liver stages. C1 [Radtke, Andrea J.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Tse, Sze-Wah] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. [Zavala, Fidel] Johns Hopkins Bloomberg Sch Publ Hlth, Johns Hopkins Malaria Res Inst, Baltimore, MD 21205 USA. [Zavala, Fidel] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. RP Zavala, F (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Johns Hopkins Malaria Res Inst, Baltimore, MD 21205 USA. EM fzavala@jhsph.edu FU NIAID, NIH; NIH [AI44375] FX This work was supported in part by the Intramural Research Program, NIAID, NIH; AJR was supported by the Intramural Research Program of NIAID, NIH. FZ is supported by NIH grant AI44375. NR 85 TC 4 Z9 4 U1 2 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2297 EI 1863-2300 J9 SEMIN IMMUNOPATHOL JI Semin. Immunopathol. PD MAY PY 2015 VL 37 IS 3 BP 211 EP 220 DI 10.1007/s00281-015-0479-3 PG 10 WC Immunology; Pathology SC Immunology; Pathology GA CI5NU UT WOS:000354804700002 PM 25917387 ER PT J AU Chartier, M Blais, RK Steinberg, T Catella, S Dehon, E Ross, D Zeiss, RA AF Chartier, Maggie Blais, Rebecca K. Steinberg, Tara Catella, Stephanie Dehon, Erin Ross, David Zeiss, Robert A. TI A Psychology Postdoctoral Fellowship Program in Integrated HIV and Hepatitis C Clinical Care: Rationale, Progress, and Future Directions SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE postdoctoral fellowship; training; HIV; hepatitis C; integrated care ID SUBSTANCE USE DISORDERS; OF-VETERANS-AFFAIRS; VIRUS-INFECTION; PSYCHIATRIC-DISORDERS; DISEASE PROGRESSION; ANTIVIRAL TREATMENT; MENTAL-ILLNESS; STIGMA; PREVALENCE; THERAPY AB Individuals with HIV/AIDS and hepatitis C virus (HCV) often present with complex mental health (MH) and substance use disorder (SUD) treatment needs. Evidence shows that providing MH and SUD services in integrated care settings results in improved medical treatment outcomes and disease management for these populations. Given the importance of addressing the MH and SUD needs of veterans seeking care at Veterans Health Administration (VHA) facilities for HIV and HCV, the Office of Public Health is collaborating with VHA's Office of Academic Affiliations to support a clinical psychology postdoctoral training program with this emphasis. Through a discussion of fellowship competencies, structure, and implementation, this article highlights the unique contribution that a psychology postdoctoral training program with a focus on these populations provides. C1 [Chartier, Maggie; Ross, David] Off Publ Hlth, Clin Publ Hlth, Washington, DC USA. [Blais, Rebecca K.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Steinberg, Tara] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Catella, Stephanie] San Francisco VA Med Ctr, San Francisco, CA USA. [Dehon, Erin] GV Sonny Montgomery VA Med Ctr, Jackson, MS USA. [Zeiss, Robert A.] VA Cent Off, Off Acad Affiliat, Hlth Educ, Washington, DC USA. RP Chartier, M (reprint author), San Francisco VA Med Ctr 116B, 4150 Clement St, San Francisco, CA 94121 USA. EM maggie.chartier@va.gov FU VHA Office of Public Health; Office of Academic Affiliations FX THIS FELLOWSHIP WAS FUNDED by the VHA Office of Public Health in collaboration with the Office of Academic Affiliations. NR 46 TC 0 Z9 0 U1 1 U2 4 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 EI 1931-3926 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD MAY PY 2015 VL 9 IS 2 BP 77 EP 84 DI 10.1037/tep0000038 PG 8 WC Psychology, Educational SC Psychology GA CI2VZ UT WOS:000354607000001 ER PT J AU Reinherz, EL Wang, JH AF Reinherz, Ellis L. Wang, Jia-huai TI Codification of bidentate pMHC interaction with TCR and its co-receptor SO TRENDS IN IMMUNOLOGY LA English DT Review DE TER; antigen recognition; co-receptor; mechanobiology ID T-CELL-RECEPTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I INTERACTION; MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; LYMPHOCYTES-T; STRUCTURAL BASIS; PEPTIDE-MHC; HUMAN CD4; DEVELOPMENTAL DILEMMA AB A 1983 Immunology Today rostrum hypothesized that each T cell has two recognition units: a T cell receptor (TCR) complex, which binds antigen associated with a polymorphic region of a MHC molecule (pMHC), and a CD4 or CD8 molecule that binds to a conserved region of that same MHC gene product (class II or I, respectively). Structural biology has since precisely revealed those bidentate pMHC interactions. TCR alpha beta ligates the membrane-distal antigen-binding MHC platform, whereas CD8 clamps a membrane-proximal MHCI alpha 3 domain loop and CD4 docks to a hydrophobic crevice between MHCII alpha 2 and beta 2 domains. Here, we review how MHC class-restricted binding impacts signaling and lineage commitment, discussing TCR force-driven conformational transitions that may optimally expose the co-receptor docking site on MHC. C1 [Reinherz, Ellis L.; Wang, Jia-huai] Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. [Reinherz, Ellis L.; Wang, Jia-huai] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU NIAID NIH HHS [R37 AI019807, U01 AI090043, R56 AI019807, R01 AI019807] NR 67 TC 3 Z9 3 U1 4 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 EI 1471-4981 J9 TRENDS IMMUNOL JI Trends Immunol. PD MAY PY 2015 VL 36 IS 5 BP 300 EP 306 DI 10.1016/j.it.2015.03.004 PG 7 WC Immunology SC Immunology GA CI8TY UT WOS:000355045800007 PM 25818864 ER PT J AU Ginat, DT de Venecia, RK Curtin, HD AF Ginat, Daniel Thomas de Venecia, Ronald K. Curtin, Hugh D. TI Stapediovestibular dislocation depicted on temporal bone computed tomography with 3D rendering SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID CT AB Stapediovestibular dislocation is an unusual form of ossicular trauma. In this article, a case of medial stapediovestibular dislocation and pneumolabyrinth due to penetrating injury with a stick diagnosed on temporal bone CT is described. In particular, 3D CT renderings can aid in the evaluation of the displaced ossicles. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ginat, Daniel Thomas] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [de Venecia, Ronald K.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Curtin, Hugh D.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Ginat, DT (reprint author), Univ Chicago, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM ginatd01@gmail.com NR 8 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 EI 1532-818X J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD MAY-JUN PY 2015 VL 36 IS 3 BP 435 EP 436 DI 10.1016/j.amjoto.2014.08.019 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA CI2QU UT WOS:000354592900024 PM 25577029 ER PT J AU Karimkhani, C Boyers, LN Naghavi, M Coffeng, LE Lott, JP Wulf, S Hay, R Williams, HC Weinstock, MA Norton, SA Armstrong, AW Dunnick, CA Norris, DA Dellavalle, RP AF Karimkhani, C. Boyers, L. N. Naghavi, M. Coffeng, L. E. Lott, J. P. Wulf, S. Hay, R. Williams, H. C. Weinstock, M. A. Norton, S. A. Armstrong, A. W. Dunnick, C. A. Norris, D. A. Dellavalle, R. P. TI The global burden of disease associated with alopecia areata SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter ID HIDRADENITIS SUPPURATIVA; PREVALENCE; PSORIASIS; SEVERITY; ACNE C1 [Karimkhani, C.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Boyers, L. N.] Georgetown Univ, Sch Med, Washington, DC USA. [Naghavi, M.; Coffeng, L. E.; Wulf, S.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Lott, J. P.] Yale Univ, Sch Med, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT USA. [Lott, J. P.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Hay, R.] Kings Coll Hosp NHS Trust, Dept Dermatol, London, England. [Williams, H. C.] Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham NG7 2RD, England. [Weinstock, M. A.] VA Med Ctr Providence, Dermatoepidemiol Unit, Providence, RI USA. [Weinstock, M. A.] Rhode Isl Hosp, Dept Dermatol, Providence, RI USA. [Weinstock, M. A.] Brown Univ, Dept Dermatol, Providence, RI 02912 USA. [Weinstock, M. A.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Norton, S. A.] Childrens Natl Med Ctr, Div Dermatol, Washington, DC 20010 USA. [Armstrong, A. W.; Dunnick, C. A.; Norris, D. A.; Dellavalle, R. P.] Univ Colorado, Sch Publ Hlth, Dept Dermatol, Aurora, CO 80045 USA. [Dellavalle, R. P.] Univ Colorado, Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Armstrong, A. W.; Dunnick, C. A.; Norris, D. A.; Dellavalle, R. P.] Eastern Colorado Hlth Care Syst, US Dept Vet Affairs, Dermatol Serv, Denver, CO USA. RP Dellavalle, RP (reprint author), Univ Colorado, Sch Publ Hlth, Dept Dermatol, Anschutz Med Campus, Aurora, CO 80045 USA. EM robert.dellavalle@ucdenver.edu NR 10 TC 1 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAY PY 2015 VL 172 IS 5 BP 1424 EP 1426 DI 10.1111/bjd.13559 PG 3 WC Dermatology SC Dermatology GA CH9XU UT WOS:000354390800097 PM 25422028 ER PT J AU Cohen, JM Nambudiri, VE Kulke, MH Todd, DJ Murphy, GF Leboeuf, NR AF Cohen, J. M. Nambudiri, V. E. Kulke, M. H. Todd, D. J. Murphy, G. F. Leboeuf, N. R. TI Cutaneous paraneoplastic granulomatous eruptions secondary to metastatic carcinoid tumour SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter ID HIDROTIC ECTODERMAL DYSPLASIA; PACHYONYCHIA-CONGENITA; MISSENSE MUTATION; CLOUSTON-SYNDROME C1 [Cohen, J. M.; Nambudiri, V. E.; Leboeuf, N. R.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Todd, D. J.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Murphy, G. F.] Brigham & Womens Hosp, Dept Pathol, Div Dermatopathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Program Neuroendocrine & Carcinoid Tumors, Boston, MA 02115 USA. [Leboeuf, N. R.] Dana Farber Brigham & Womens Canc Ctr, Dept Dermatol, Ctr Cutaneous Oncol, Boston, MA 02115 USA. RP Leboeuf, NR (reprint author), Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA. EM nleboeuf@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAY PY 2015 VL 172 IS 5 BP 1451 EP 1454 DI 10.1111/bjd.13516 PG 4 WC Dermatology SC Dermatology GA CH9XU UT WOS:000354390800108 PM 25388104 ER PT J AU Sprich, SE Burbridge, J Lerner, JA Safren, SA AF Sprich, Susan E. Burbridge, Jennifer Lerner, Jonathan A. Safren, Steven A. TI Cognitive-Behavioral Therapy for ADHD in Adolescents: Clinical Considerations and a Case Series SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE cognitive-behavioral therapy; CBT; ADHD; adolescents ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; MEDICATION-TREATED ADULTS; III-R DIAGNOSES; PSYCHOSOCIAL TREATMENTS; RESEARCH CRITERIA; CHILDREN; PREVALENCE; STUDENTS; COMORBIDITY AB Although ADHD in adolescents is an impairing and prevalent condition, with community prevalence estimates between 2% and 6%, psychosocial treatments for adolescents compared to younger children are relatively understudied. Our group has successfully developed an evidence base for cognitive-behavioral therapy (CBT) for ADHD in medication-treated adults with ADHD with clinically significant symptoms. In the current paper, we describe an adaptation of this treatment to adolescents, and provide case reports on 3 adolescents who participated in an open pilot trial. The results suggest that the treatment approach was well tolerated by the adolescents and that they experienced clinical benefit. This early report of the approach in adolescents is promising and requires further efficacy testing. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Sprich, SE (reprint author), One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ssprich@partners.org FU NIMH NIH HHS [R01 MH069812, R34 MH083063] NR 49 TC 1 Z9 1 U1 6 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 EI 1878-187X J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD MAY PY 2015 VL 22 IS 2 BP 116 EP 126 PG 11 WC Psychology, Clinical SC Psychology GA CI1LN UT WOS:000354505800002 PM 27616874 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI Neurological Complications Associated with Epidural Steroid Injections SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Epidural steroid injections; Cervical transforaminal epidural injections; Interlaminar epidural injections; Caudal epidural injections; Neurological complications; Intraarterial injection of steroids ID 2-YEAR FOLLOW-UP; LOW-BACK-PAIN; ACTIVE-CONTROL TRIAL; RANDOMIZED CONTROLLED-TRIAL; CERVICAL RADICULAR PAIN; CENTRAL SPINAL STENOSIS; LUMBAR DISC HERNIATION; DOUBLE-BLIND TRIAL; TRANSFORAMINAL INJECTION; INTRATHECAL METHYLPREDNISOLONE AB Multiple case reports of neurological complications resulting from intraarterial injection of corticosteroids have led the Food and Drug Administration (FDA) to issue a warning, requiring label changes, warning of serious neurological events, some resulting in death. The FDA has identified 131 cases of neurological adverse events, including 41 cases of arachnoiditis. A review of the literature reveals an overwhelming proportion of the complications are related to transforaminal epidural injections, of which cervical transforaminal epidural injections constituted the majority of neurological complications. Utilization data of epidural injections in the Medicare population revealed that cervical transforaminal epidural injections constitute only 2.4 % of total epidural injections and <5 % of all transforaminal epidural injections. Multiple theories have been proposed as the cause of neurological injury including particulate steroid, arterial intimal flaps, arterial dissection, dislodgement of plaque causing embolism, arterial muscle spasm, and embolism of a fresh thrombus following disruption of the intima. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com; HIrsch@snisonline.org NR 98 TC 7 Z9 7 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1531-3433 EI 1534-3081 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD MAY PY 2015 VL 19 IS 5 AR 10 DI 10.1007/s11916-015-0482-3 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA CI0XF UT WOS:000354462200002 ER PT J AU del Carmen, MG Rice, LW Schmeler, KM AF del Carmen, Marcela G. Rice, Laurel W. Schmeler, Kathleen M. TI Global health perspective on gynecologic oncology SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Global; Health; Low-middle income countries ID MIDDLE-INCOME COUNTRIES; LONG-TERM SURVIVAL; CERVICAL-CANCER; RESECTION; COLOMBIA; AMERICA; PROGRAM; BURDEN; WORLD; CARE AB Objective. To describe challenges faced by low-middle income countries (LMICs) across the cancer spectrum, with specific focus on gynecologic cancers. Methods. MEDLINE was searched for research articles published in English between January 1, 2000 and February 1, 2015 which reported on global health efforts in LMICs. Results. An estimated 80% of global cancer burden and only 5% of global cancer spending affect LMICs. The overwhelming majority of cervical cancer cases and related deaths occur in LMICs. The charge to close this cancer divide is at the center of global health efforts. Conclusions. Prevention is central to global health efforts to close the cancer divide. The gynecologic oncology community is well positioned to lead efforts in global health by partnering with institutions, professional societies and advocacy groups. (C) 2015 Elsevier Inc. All rights reserved. C1 [del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. [Rice, Laurel W.] Univ Wisconsin, Hosp & Clin, Dept Obstet & Gynecol, Madison, WI 53792 USA. [Schmeler, Kathleen M.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 49 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2015 VL 137 IS 2 BP 329 EP 334 DI 10.1016/j.ygyno.2015.03.009 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CI1KW UT WOS:000354504100022 PM 25782635 ER PT J AU Schwartz, RS Olds, J AF Schwartz, Richard S. Olds, Jacqueline TI The Psychiatry of Light SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE chronotherapy; circadian rhythm; mood disorders; phototherapy; seasonal affective disorder ID SEASONAL AFFECTIVE-DISORDER; MAJOR DEPRESSIVE DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; RESISTANT BIPOLAR DEPRESSION; BRIGHT-LIGHT; SLEEP-DEPRIVATION; THERAPY; EXPOSURE; DIM; TRIAL AB Bright light therapy and the broader realm of chronotherapy remain underappreciated and underutilized, despite their empirical support. Efficacy extends beyond seasonal affective disorder and includes nonseasonal depression and sleep disorders, with emerging evidence for a role in treating attention-deficit/hyperactivity disorder, delirium, and dementia. A practical overview is offered, including key aspects of underlying biology, indications for treatment, parameters of treatment, adverse effects, and transformation of our relationship to light and darkness in contemporary life. C1 [Schwartz, Richard S.] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Schwartz, Richard S.] McLean Hosp, Belmont, MA 02178 USA. [Olds, Jacqueline] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Schwartz, RS (reprint author), 30 Hillside Ave, Cambridge, MA 02140 USA. EM richard_schwartz@hms.harvard.edu NR 66 TC 3 Z9 3 U1 3 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2015 VL 23 IS 3 BP 188 EP 194 DI 10.1097/HRP.0000000000000078 PG 7 WC Psychiatry SC Psychiatry GA CI2LC UT WOS:000354578100003 PM 25839643 ER PT J AU Choice, T Rubin, D Danforth, N Gorrindo, T AF Choice, Tanishia Rubin, David Danforth, Nicole Gorrindo, Tristan TI Building Bridges in a Fractured Family: Developing New Conversations Around Technology and Sexual Orientation SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE attachment; conflict resolution; divorce; family therapy; gay adolescent; Internet; parent-child conflict; sexual identity; video games ID GAY; YOUTH; RISK C1 [Choice, Tanishia; Rubin, David; Gorrindo, Tristan] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Choice, Tanishia; Rubin, David; Gorrindo, Tristan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Danforth, Nicole] Newton Wellesley Hosp, Dept Psychiat, Newton, MA USA. RP Choice, T (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 6A, Boston, MA 02114 USA. EM tchoice@partners.org NR 15 TC 0 Z9 0 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2015 VL 23 IS 3 BP 201 EP 211 DI 10.1097/HRP.0000000000000091 PG 11 WC Psychiatry SC Psychiatry GA CI2LC UT WOS:000354578100005 PM 25943314 ER PT J AU Malone, JC Dayton, CJ AF Malone, Johanna C. Dayton, Carolyn Joy TI WHAT IS THE CONTAINER/CONTAINED WHEN THERE ARE GHOSTS IN THE NURSERY?: JOINING BION AND FRAIBERG IN DYADIC INTERVENTIONS WITH MOTHER AND INFANT SO INFANT MENTAL HEALTH JOURNAL LA English DT Article ID PRENATAL MATERNAL REPRESENTATIONS; ATTACHMENT RESEARCH; DOMESTIC VIOLENCE; ORGANIZATION; STRATEGIES; DIALOGUE; MIND AB Ghosts in the nursery. Visitors from the unremembered past. Fraiberg, Adelson, and Shapiro's (1975) words convey the relational intruders that they perceived while working with mothers and infants. A mother's unresolved past is a driving force within the treatment of mother-infant dyads. Working with these families, the therapist strives to process and metabolize the distress of the dyad while enabling the mother to contain the infant more fully. This article proposes that Fraiberg etal.'s metaphor may be newly elaborated utilizing Bion's (1962) original theoretical conceptualization of the container and contained. He posited that an infant projects distressing affective states upon the mother, who contains the experience, transforms the feelings, and then enables the infant to reintroject a more tolerable experience. This lays the foundation for the relational experience of being known by another and facilitates the infant's development of self-knowledge and emotional regulation. We utilize Fraiberg etal.'s original case material to identify ways in which ghosts in the nursery disrupt the processes of the container and contained. Bion's ideas may help enrich our understanding of how the therapeutic relationship enables cycles of containment, transitioning the material ghosts from being contained by the infant to being contained by the therapist, and to ultimately being transformed so that the mother can reattribute them to the past. C1 [Malone, Johanna C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Malone, Johanna C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dayton, Carolyn Joy] Wayne State Univ, Detroit, MI 48202 USA. RP Malone, JC (reprint author), One Arnold Circle 7, Cambridge, MA 02139 USA. EM johanna.malone@gmail.com FU American Psychological Association Division 39 Early Career Award at the spring meeting in Chicago FX An earlier version of this article was the recipient of the American Psychological Association Division 39 Early Career Award at the spring meeting in Chicago, 2010. We thank Marilyn Charles and Malcolm Slavin for their comments and suggestions. We have no conflicts of interest to report. NR 54 TC 0 Z9 0 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0163-9641 EI 1097-0355 J9 INFANT MENT HEALTH J JI Infant Ment. Health J. PD MAY-JUN PY 2015 VL 36 IS 3 BP 262 EP 274 DI 10.1002/imhj.21509 PG 13 WC Psychology, Developmental SC Psychology GA CI1FI UT WOS:000354487800003 PM 25931380 ER PT J AU Zantek, ND Hsu, P Meijer, P Smock, KJ Plumhoff, EA Refaai, MA Van Cott, EM AF Zantek, N. D. Hsu, P. Meijer, P. Smock, K. J. Plumhoff, E. A. Refaai, M. A. Van Cott, E. M. TI Quality of factor XI activity testing in North American Specialized Coagulation Laboratories SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Article; Proceedings Paper CT 28th International Symposium on Technological Innovation in Laboratory Hematology CY 2015 CL Chicago, IL DE Factor XI; proficiency testing; quality; North American Specialized Laboratory Association; intrinsic pathway ID BLOOD-COAGULATION; ASSOCIATION EXPERIENCE; ASSAY PERFORMANCE; REDUCED INCIDENCE; DEFICIENCY; ACTIVATION; THROMBIN; FIBRINOLYSIS AB IntroductionThe performance of factor XI activity (FXI) by laboratories in the North American Specialized Coagulation Laboratory Association proficiency testing program was analyzed. MethodsOver 10years (2003-2013), 80 samples were distributed; 33-55 laboratories participated per exercise providing 3833 total responses. Analysis was performed on numeric results and qualitative classification of results. ResultsThe sample FXI levels ranged from 3.8 to 154.0 IU/dL. The overall interlaboratory average coefficient of variation (CV%) was 17.5%; the CV was higher for a sample with low (3.8 IU/dL) FXI. Results were correctly classified as abnormal (100%) for a sample with 3.8 IU/dL FXI and normal/borderline normal (97.7%) for 45 samples with 80 to<140 IU/dL FXI. The classification was heterogeneous for samples with FXI of 50 to<80 IU/dL. Six specimens were repeat-tested from 2007 to 2013. The mean FXI was not significantly different in laboratories using the same method on both exercises, suggesting good intralaboratory precision over time. Univariate analysis of data from 2011 to 2012 did not find a consistent significant difference among the activators, analyzers, calibrators, and FXI-deficient plasmas. ConclusionLaboratories generally performed well in assessment of FXI based on interlaboratory precision when FXI >30 IU/dL and on classification of samples with very low or normal FXI. C1 [Zantek, N. D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Hsu, P.] Hofstra North Shore Long Isl Jewish Sch Med, Dept Pathol Lab Med, Lake Success, NY USA. [Meijer, P.] ECAT Fdn, Voorschoten, Netherlands. [Smock, K. J.] Univ Utah, Dept Pathol, ARUP Labs, Salt Lake City, UT USA. [Plumhoff, E. A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Refaai, M. A.] Univ Rochester, Sch Med & Dent, Dept Pathol & Lab Med, Rochester, NY USA. [Van Cott, E. M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Coagulat Lab, GRJ235,55 Fruit St, Boston, MA 02114 USA. EM evancott@partners.org FU Sekisui Diagnostics, Inc. FX NDZ has received research funding from Sekisui Diagnostics, Inc. The other authors have no relevant disclosures. NR 24 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-5521 EI 1751-553X J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD MAY PY 2015 VL 37 SU 1 SI SI BP 99 EP 107 DI 10.1111/ijlh.12359 PG 9 WC Hematology SC Hematology GA CI2FO UT WOS:000354561000016 PM 25976967 ER PT J AU Zietman, AL AF Zietman, Anthony L. TI Fifty Years From Paris: The Remarkable Story of the Lymphomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 [Zietman, Anthony L.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Zietman, AL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 302,100 Blossom St, Boston, MA 02114 USA. EM azietman@partners.org NR 8 TC 0 Z9 0 U1 0 U2 1 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 MAY 1 PY 2015 VL 92 IS 1 SI SI BP 1 EP 2 DI 10.1016/j.ijrobp.2015.03.009 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CH4FH UT WOS:000353988200001 PM 25863746 ER PT J AU Alkhairy, OK Rezaei, N Graham, RR Abolhassani, H Borte, S Hultenby, K Wu, CL Aghamohammadi, A Williams, DA Behrens, TW Hammarstrom, L Pan-Hammarstrom, Q AF Alkhairy, Omar K. Rezaei, Nima Graham, Robert R. Abolhassani, Hassan Borte, Stephan Hultenby, Kjell Wu, Chenglin Aghamohammadi, Asghar Williams, David A. Behrens, Timothy W. Hammarstrom, Lennart Pan-Hammarstrom, Qiang TI RAC2 loss-of-function mutation in 2 siblings with characteristics of common variable immunodeficiency SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID RHO GTPASE; T-CELLS; EXPRESSION; DISORDERS C1 [Alkhairy, Omar K.; Abolhassani, Hassan; Borte, Stephan; Wu, Chenglin; Hammarstrom, Lennart; Pan-Hammarstrom, Qiang] Karolinska Inst, Div Clin Immunol & Transfus Med, Stockholm, Sweden. [Alkhairy, Omar K.; Abolhassani, Hassan; Borte, Stephan; Wu, Chenglin; Hammarstrom, Lennart; Pan-Hammarstrom, Qiang] Karolinska Inst, Clin Res Ctr, Dept Lab Med, Stockholm, Sweden. [Alkhairy, Omar K.; Abolhassani, Hassan; Borte, Stephan; Wu, Chenglin; Hammarstrom, Lennart; Pan-Hammarstrom, Qiang] Karolinska Univ Hosp Huddinge, Stockholm, Sweden. [Alkhairy, Omar K.] King Abdul Aziz Med City, Dept Pathol & Lab Med, Riyadh, Saudi Arabia. [Rezaei, Nima; Abolhassani, Hassan; Aghamohammadi, Asghar] Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Childrens Med Ctr, Pediat Ctr Excellence, Tehran, Iran. [Rezaei, Nima] Univ Tehran Med Sci, Dept Immunol, Sch Med, Tehran, Iran. [Rezaei, Nima] Univ Tehran Med Sci, Mol Immunol Res Ctr, Tehran, Iran. [Graham, Robert R.; Behrens, Timothy W.] Genentech Inc, Immunol Biomarkers Grp, San Francisco, CA 94080 USA. [Borte, Stephan] Univ Leipzig, Translat Ctr Regenerat Med TRM, D-04109 Leipzig, Germany. [Williams, David A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. [Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Alkhairy, OK (reprint author), Karolinska Inst, Div Clin Immunol & Transfus Med, Stockholm, Sweden. EM Qiang.Pan-Hammarstrom@ki.se RI Rezaei, Nima/B-4245-2008; OI Rezaei, Nima/0000-0002-3836-1827; Abolhassani, Hassan/0000-0002-4838-0407 FU European Research Council [242551]; NIDDK NIH HHS [5R01DK062757-12, R01 DK062757] NR 18 TC 10 Z9 10 U1 0 U2 4 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 MAY PY 2015 VL 135 IS 5 BP 1380 EP + DI 10.1016/j.jaci.2014.10.039 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA CH4DA UT WOS:000353980700034 PM 25512081 ER PT J AU Akoum, N Wilber, D Hindricks, G Jais, P Cates, J Marchlinski, F Kholmovski, E Burgon, N Hu, N Mont, L Deneke, T Duytschaever, M Neumann, T Mansour, M Mahnkopf, C Hutchinson, M Herweg, B Daoud, E Wissner, E Brachmann, J Marrouche, NF AF Akoum, Nazem Wilber, David Hindricks, Gerhard Jais, Pierre Cates, Josh Marchlinski, Francis Kholmovski, Eugene Burgon, Nathan Hu, Nan Mont, Lluis Deneke, Thomas Duytschaever, Mattias Neumann, Thomas Mansour, Moussa Mahnkopf, Christian Hutchinson, Mathew Herweg, Bengt Daoud, Emile Wissner, Erik Brachmann, Johannes Marrouche, Nassir F. TI MRI Assessment of Ablation-Induced Scarring in Atrial Fibrillation: Analysis from the DECAAF Study SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; cardiac MRI; catheter ablation; pulmonary vein isolation; atrial scar ID PULMONARY VEIN ISOLATION; DELAYED-ENHANCEMENT MRI; CATHETER ABLATION; FOLLOW-UP; CONTRACTILE; LESIONS; INJURY AB MRI Assessment of Ablation-Induced Scarring in Atrial Fibrillation BackgroundThere is limited knowledge on the extent and location of scarring that results from catheter ablation and its role in suppressing atrial fibrillation (AF). We examined the effect of atrial fibrosis and ablation-induced scarring on catheter ablation outcomes in AF. MethodsWe conducted a prospective multicenter study that enrolled 329 AF patients presenting for catheter ablation. Delayed enhancement magnetic resonance imaging (DE-MRI) of the left atrium was obtained preablation. Scarring was evaluated in 177 patients with a DE-MRI scan obtained 90 days postablation. We evaluated residual fibrosis, defined as preablation atrial fibrosis not covered by ablation scar. The primary outcome was freedom from recurrent atrial arrhythmia. ResultsIn the analysis cohort of 177 patients, preablation fibrosis was 18.7 8.7% of the atrial wall. Ablation aimed at pulmonary vein (PV) isolation was performed in 163 patients (92.1%). Ablation-induced scar averaged 10.6 +/- 4.4% of the atrial wall. Scarring completely encircled all 4 PVs only in 12 patients (7.3%). Residual fibrosis was calculated at 15.8 +/- 8.0%. At 325 days follow-up, 35% of patients experienced recurrent arrhythmia. Multivariable Cox proportional hazards models demonstrated that baseline atrial fibrosis (HR and 95% CIs) (1.09 [1.06-1.12], P < 0.001) and residual fibrosis (1.09 [1.05-1.13], P < 0.001) were associated with atrial arrhythmia recurrence, while PV encirclement and overall scar were not. ConclusionsCatheter ablation of AF targeting PVs rarely achieves permanent encircling scar in the intended areas. Overall atrial fibrosis present at baseline and residual fibrosis uncovered by ablation scar are associated with recurrent arrhythmia. C1 [Akoum, Nazem] Univ Washington, Atrial Fibrillat Program, Seattle, WA 98195 USA. [Cates, Josh; Kholmovski, Eugene; Burgon, Nathan; Hu, Nan; Marrouche, Nassir F.] Univ Utah, Sch Med, Comprehens Arrhythmia & Res Management CARMA, Salt Lake City, UT 84132 USA. [Wilber, David] Loyola Univ, Med Ctr, Chicago, IL USA. [Hindricks, Gerhard] Univ Leipzig, D-04109 Leipzig, Germany. [Jais, Pierre; Hutchinson, Mathew] Ctr Hosp Univ Bordeaux, Bordeaux, France. [Marchlinski, Francis] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Mont, Lluis] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi Sunyer IDIBAPS, Barcelona, Spain. [Deneke, Thomas] Ruhr Univ Bochum, BG Kliniken Bergmannsheil, Bochum, Germany. [Duytschaever, Mattias] Univ Hosp Ghent, Ghent, Belgium. [Neumann, Thomas] Kerckhoff Heart Ctr, Bad Nauheim, Germany. [Mansour, Moussa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mahnkopf, Christian; Brachmann, Johannes] Klinikum Coburg, Med Klin 2, Coburg, Germany. [Herweg, Bengt] USF Morsani Coll Med, Tampa, FL USA. [Daoud, Emile] Ohio State Univ, Columbus, OH 43210 USA. [Wissner, Erik] Asklepios Klin St Georg, Hamburg, Germany. RP Marrouche, NF (reprint author), Univ Utah, Div Cardiovasc Med, 50 North Med Dr, Salt Lake City, UT 84132 USA. EM nassir.marrouche@hsc.utah.edu FU Medtronic FX D. Wilber reports a contractual relationship between Merisight and Loyola Medical Center for processing of scans. E. Kholmovski reports patent ownership for MRI techniques for imaging of the left atrium. L. Mont reports research grants to his institution from Biosense Webster, Boston Scientific, and Medtronic, for whom he serves as consultant/advisory board member. B. Herweg reports compensation for participation on a speaker's bureau from St. Jude Medical, for whom he serves as consultant/advisory board member; Medtronic supplied Fellowship support. N. Marrouche reports ownership shares in Marrek, LLC. Other authors: No disclosures. NR 22 TC 11 Z9 12 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAY PY 2015 VL 26 IS 5 BP 473 EP 480 DI 10.1111/jce.12650 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH9YR UT WOS:000354393100001 PM 25727106 ER PT J AU Calvi, AR Gliesing, J Eapen, B AF Calvi, Ashley R. Gliesing, Julie Eapen, Blessen TI Syndrome of the Trephined: Improvement in Neurolinguistic Deficits and Global Aphasia After Cranioplasty SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Meeting Abstract C1 [Calvi, Ashley R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Rehabil Med, San Antonio, TX 78229 USA. [Gliesing, Julie; Eapen, Blessen] South Texas Vet Hlth Care Syst, Audie L Murphy VA Med Ctr, Polytrauma Rehabil Ctr, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD MAY-JUN PY 2015 VL 30 IS 3 MA 0119 BP E111 EP E111 PG 1 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CH8PJ UT WOS:000354298100117 ER PT J AU Jaramillo, C Swan, A Eapen, B Pugh, MJ AF Jaramillo, Carlos Swan, Alicia Eapen, Blessen Pugh, Mary Jo TI Vestibular Dysfunction and Traumatic Brain Injury in Veterans of the Wars in Iraq and Afghanistan SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Meeting Abstract C1 [Jaramillo, Carlos; Swan, Alicia; Eapen, Blessen; Pugh, Mary Jo] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD MAY-JUN PY 2015 VL 30 IS 3 MA 0116 BP E109 EP E110 PG 2 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CH8PJ UT WOS:000354298100114 ER PT J AU Swan, A Jaramillo, C Eapen, B Pugh, MJ AF Swan, Alicia Jaramillo, Carlos Eapen, Blessen Pugh, Mary Jo TI Tinnitus: Prevalence and Co-morbidities in a Cohort of Iraq and Afghanistan Veterans SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Meeting Abstract C1 [Swan, Alicia; Jaramillo, Carlos; Eapen, Blessen; Pugh, Mary Jo] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD MAY-JUN PY 2015 VL 30 IS 3 MA 0113 BP E109 EP E109 PG 1 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CH8PJ UT WOS:000354298100112 ER PT J AU Yehuda, R Lehrner, A Rosenbaum, TY AF Yehuda, Rachel Lehrner, Amy Rosenbaum, Talli Y. TI PTSD and Sexual Dysfunction in Men and Women SO JOURNAL OF SEXUAL MEDICINE LA English DT Review DE Sexual Dysfunction; Posttraumatic Stress Disorder; Neurobiology; Neuroendocrinology ID POSTTRAUMATIC-STRESS-DISORDER; COMBAT VETERANS; CONDITIONED FEAR; TRAUMATIC EVENT; EX-PRISONERS; WAR VETERANS; RESPONSES; AROUSAL; PREDICTORS; SYMPTOMS AB IntroductionDifficulties in sexual desire and function often occur in persons with posttraumatic stress disorder (PTSD), but many questions remain regarding the mechanisms underlying the occurrence of sexual problems in PTSD. AimThe aim of this review was to present a model of sexual dysfunction in PTSD underpinned by an inability to regulate and redirect the physiological arousal needed for healthy sexual function away from aversive hyperarousal and intrusive memories. MethodA literature review pertaining to PTSD and sexual function was conducted. Evidence for the comorbidity of sexual dysfunction and PTSD is presented, and biological and psychological mechanisms that may underlie this co-occurrence are proposed. Main Outcome MeasuresThis manuscript presents evidence of sexual dysfunction in conjunction with PTSD, and of the neurobiology and neuroendocrinology of PTSD and sexual function. ResultsSexual dysfunction following trauma exposure may be mediated by PTSD-related biological, cognitive, and affective processes. ConclusionsThe treatment of PTSD must include attention to sexual dysfunction and vice versa. Yehuda R, Lehrner A, and Rosenbaum TY. PTSD and sexual dysfunction in men and women. J Sex Med 2015;12:1107-1119. C1 [Yehuda, Rachel; Lehrner, Amy] James J Peters Vet Affairs Med Ctr, Mental Hlth Care Ctr, Bronx, NY 10468 USA. [Yehuda, Rachel; Lehrner, Amy] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Rosenbaum, Talli Y.] Inner Stabil Ltd, Dept Sex Therapy, Bet Shemesh, Israel. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, Mental Hlth Primary Care Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@va.gov NR 75 TC 3 Z9 3 U1 5 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD MAY PY 2015 VL 12 IS 5 BP 1107 EP 1119 DI 10.1111/jsm.12856 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA CI1UW UT WOS:000354531400003 PM 25847589 ER PT J AU Morris, BJ Krieger, JN AF Morris, Brian J. Krieger, John N. TI The Literature Supports Policies Promoting Neonatal Male Circumcision in North America SO JOURNAL OF SEXUAL MEDICINE LA English DT Letter C1 [Morris, Brian J.] Univ Sydney, Sch Med Sci, Sydney, NSW 2006, Australia. [Krieger, John N.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Urol, Seattle, WA USA. RP Morris, BJ (reprint author), Univ Sydney, Sch Med Sci, Sydney, NSW 2006, Australia. NR 5 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD MAY PY 2015 VL 12 IS 5 BP 1305 EP 1305 DI 10.1111/jsm.12855 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CI1UW UT WOS:000354531400029 PM 25757531 ER PT J AU Paul, AB Oklu, R Saini, S Prabhakar, AM AF Paul, Aaron B. Oklu, Rahmi Saini, Sanjay Prabhakar, Anand M. TI How Much Is That Head CT? Price Transparency and Variability in Radiology SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Price transparency; medical imaging; noncontrast head CT ID HEALTH-CARE AB Purpose: To extend the investigation of price transparency and variability to medical imaging. Methods: Eighteen upper-tier academic hospitals identified by U.S. News & World Report and 14 of the 100 largest private radiology practices in the country identified by the Radiology Business Journal were contacted by telephone between December 2013 and February 2014 to determine the cash price for a noncontrast head CT. The price for a noncontrast head CT was chosen to assess price transparency in medical imaging because it represents a standard imaging examination with minimal differences in quality. Results: Fourteen upper-tier academic hospitals (78%) and 11 private practices (79%) were able to provide prices for a noncontrast head CT. There was no significant difference between the proportions of upper-tier academic hospitals and private practices that were able to provide prices for a noncontrast head CT (P = .96). The average total price for the upper-tier academic hospitals was $1,390.12 +/- $686.13, with the price ranging from $391.62 to $2,015. The average total price for the private practices was $681.60 +/- $563.58, with the total price ranging from $211 to $2,200. Conclusions: Prices for a noncontrast head CT study were readily available from the vast majority of upper-tier academic hospitals and private practices, although there was tremendous variation in the price estimates both within and between the upper-tier academic hospitals and private practices. Routine medical imaging thus appears to be more price transparent compared with other health care services. Copyright (C) 2015 American College of Radiology C1 [Paul, Aaron B.; Saini, Sanjay] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Intervent Radiol, Boston, MA 02114 USA. [Prabhakar, Anand M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Cardiovasc Imaging, Boston, MA 02114 USA. RP Prabhakar, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,FND-216, Boston, MA 02114 USA. EM aprabhakar@mgh.harvard.edu NR 12 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2015 VL 12 IS 5 BP 453 EP 457 DI 10.1016/j.jacr.2014.12.016 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI0IS UT WOS:000354420900007 PM 25841864 ER PT J AU Arasu, VA Abujudeh, HH Biddinger, PD Noble, VE Halpern, EF Thrall, JH Novelline, RA AF Arasu, Vignesh A. Abujudeh, Hani H. Biddinger, Paul D. Noble, Vicki E. Halpern, Elkan F. Thrall, James H. Novelline, Robert A. TI Diagnostic Emergency Imaging Utilization at an Academic Trauma Center From 1996 to 2012 SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Emergency department; radiology; diagnostic imaging; economics; utilization ID COMPUTED-TOMOGRAPHY; MEDICAL-CENTER; CT; DEPARTMENTS; RADIOLOGY; VISITS; TRENDS; INJURY; MANAGEMENT; COSTS AB Purpose: The aim of this study was to retrospectively review the growth rate in emergency radiology volume at an urban academic trauma center from 1996 to 2012. Methods: The authors reviewed aggregated billing data, for which the requirement for institutional review board approval was waived, from 1,458,230 diagnostic radiologic examinations ordered for emergency department (ED) visits from 1996 to 2012. The growth rate was calculated as the average annual percentage change in imaging examinations per ED visits. The growth rates between 1996 to 2003 and 2004 to 2012 were statistically compared using a t test. Results: ED patient visits showed continual growth at an average of 3% per year. Total imaging per ED visit grew from 1996 to 2003 at 4 +/- 4% per year but significantly decreased from 2004 to 2012 at 2 3% per year (P = .01). By modality, statistically significant decreased growth was observed in CT and MRI from 2004 to 2012. Ultrasound and x-ray showed unchanged growth from 1996 through 2012. ED physician ultrasound data available for 2002 to 2011 also showed increased growth. Conclusions: When adjusting ED imaging volume by ED visits, significantly decreased growth of overall ED imaging, specifically CT and MRI, was observed during the past 9 years. This may be due to slowing of new imaging indications, improved awareness of practice guidelines, and increased use of ultrasound. Although the national health care discussion focuses on continual imaging growth, these results demonstrate that long-term stability in ED imaging utilization is achievable. Copyright (C) 2015 American College of Radiolog C1 [Arasu, Vignesh A.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94115 USA. [Abujudeh, Hani H.; Halpern, Elkan F.; Thrall, James H.; Novelline, Robert A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Biddinger, Paul D.; Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Arasu, VA (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 1600 Divisadero St,Room C250,Box 1667, San Francisco, CA 94115 USA. EM vignesh.ansu@ucsf.edu FU National Institutes of Health (Bethesda, Maryland) [TL1 RR024129] FX This research was supported by grant TL1 RR024129 from the National Institutes of Health (Bethesda, Maryland). The views expressed are those of the study authors alone and not an official position of the affiliated institutions or funding source. NR 31 TC 9 Z9 9 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2015 VL 12 IS 5 BP 467 EP 474 DI 10.1016/j.jacr.2014.11.018 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI0IS UT WOS:000354420900010 PM 25622765 ER PT J AU Patel, TY Glover, M AF Patel, Tirath Y. Glover, McKinley TI The Time Is Now: Revisiting the Case for the 3-Year Radiology Residency SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID SUBSPECIALIZATION-THE ACR; MODEL; GENERALISM C1 [Patel, Tirath Y.] Univ Toledo, Med Ctr, Dept Radiol, Toledo, OH 43614 USA. [Glover, McKinley] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patel, TY (reprint author), Univ Toledo, Med Ctr, Dept Radiol, 3000 Arlington Ave, Toledo, OH 43614 USA. EM tirath.patel@utoledo.edu NR 24 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2015 VL 12 IS 5 BP 481 EP 483 DI 10.1016/j.jacr.2015.01.009 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI0IS UT WOS:000354420900012 PM 25840806 ER PT J AU Maximin, S Moshiri, M Bhargava, P AF Maximin, Suresh Moshiri, Mariam Bhargava, Puneet TI Understanding the Cost of Conflict and an Approach to Conflict-Management Design SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Maximin, Suresh; Moshiri, Mariam; Bhargava, Puneet] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98108 USA. [Maximin, Suresh; Bhargava, Puneet] Vet Affairs Puget Sound Hlth Care Syst, Diagnost Imaging Serv, Seattle Div, Seattle, WA 98108 USA. RP Bhargava, P (reprint author), Univ Washington, Sch Med, Dept Radiol, S-1 14 Radiol,1660 S Columbian Way, Seattle, WA 98108 USA. EM bhargp@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 13 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2015 VL 12 IS 5 BP 507 EP 509 DI 10.1016/j.jacr.2014.07.006 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI0IS UT WOS:000354420900018 PM 25156203 ER PT J AU Glover, M Choy, G Boland, GW Saini, S Prabhakar, AM AF Glover, McKinley Choy, Garry Boland, Giles W. Saini, Sanjay Prabhakar, Anand M. TI Radiology and Social Media: Are Private Practice Radiology Groups More Social Than Academic Radiology Departments? SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Social media; patient engagement academic radiology; private practice radiology ID HEALTH-CARE; RATING SITES; FACEBOOK; TWITTER; CRISIS AB Purpose: This study assesses the prevalence of use of the most commonly used social media sites among private radiology groups (PRGs) and academic radiology departments (ARDs). Methods: The 50 largest PRGs and the 50 ARDs with the highest level of funding from the National Institutes of Health were assessed for presence of a radiology-specific social media account on Facebook, Twitter, Instagram, Pinterest, YouTube, and Linkedln. Measures of organizational activity and end-user activity were collected, including the number of posts and followers, as appropriate; between-group comparisons were performed. Results: PRGs adopted Facebook 12 months earlier (P = .02) and Twitter 18 months earlier (P = .02) than did ARDs. A total of 76% of PRGs maintained >= 1 account on the social media sites included in the study, compared with 28% of ARDs (P < .0001). The prevalence of having an account on the social media sites for PRGs was: Facebook, 66%; Linkedln, 56%; Twitter, 42%; YouTube, 20%; Pinterest, 4%; and Instagram, 2%. The prevalence of radiology-specific social media accounts for ARDs was: Facebook, 18%; LinkedIn, 0%; Twitter, 24%; YouTube, 6%; Pinterest, 0%; and Instagram, 0%. There was no significant difference between ARDs and PRGs in measures of end-user or organizational activity on Facebook or Twitter. Conclusions: Use of social media in health care is emerging as mainstream, with PRGs being early adopters of Facebook and Twitter in comparison with ARDs. Competitive environments and institutional policies may be strong factors that influence how social media is used by radiologists at the group and department levels. C1 [Glover, McKinley; Choy, Garry; Boland, Giles W.; Saini, Sanjay; Prabhakar, Anand M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Glover, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 216, Boston, MA 02114 USA. EM mckinley.glover@mgh.harvard.edu NR 37 TC 10 Z9 10 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2015 VL 12 IS 5 BP 513 EP 518 DI 10.1016/j.jacr.2014.11.005 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI0IS UT WOS:000354420900022 PM 25707884 ER PT J AU Morey, JM Haney, NM Schoppe, K Hawkins, CM AF Morey, Jose M. Haney, Nora M. Schoppe, Kurt Hawkins, C. Matthew TI Adding Value as Young Radiologists: Challenges and Opportunities, Part 1 SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID ACCOUNTABLE CARE ORGANIZATIONS; HEALTH-CARE; STRATEGIES; IMPACT; COMMUNICATION; REFORM C1 [Morey, Jose M.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Morey, Jose M.] US Dept Vet Affairs, Hampton, VA USA. [Haney, Nora M.] Tulane Univ, Sch Med, New Orleans, LA 70130 USA. [Schoppe, Kurt] Radiol Associates North Texas, Arlington, TX USA. [Hawkins, C. Matthew] Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Haney, NM (reprint author), Tulane Univ, Sch Med, 929 Washington Ave, New Orleans, LA 70130 USA. EM nhaney@tulane.edu NR 37 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2015 VL 12 IS 5 BP 533 EP 536 DI 10.1016/j.jacr.2015.02.003 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CI0IS UT WOS:000354420900027 PM 25940366 ER PT J AU Baldini, EH Richards, WG Gill, RR Goodman, BM Winfrey, OK Eisen, HM Mak, RH Chen, AB Kozono, DE Bueno, R Sugarbaker, DJ AF Baldini, Elizabeth H. Richards, William G. Gill, Ritu R. Goodman, Brian M. Winfrey, Olivia K. Eisen, Hannah M. Mak, Raymond H. Chen, Aileen B. Kozono, David E. Bueno, Raphael Sugarbaker, David J. TI Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MODULATED RADIATION-THERAPY; MACROSCOPIC COMPLETE RESECTION; DOSE HEMITHORACIC RADIATION; PHASE-II TRIAL; EXTRAPLEURAL PNEUMONECTOMY; TRIMODALITY THERAPY; INDUCTION CHEMOTHERAPY; HYPERTHERMIC CISPLATIN; SURGICAL-TREATMENT; CLINICAL-OUTCOMES AB Objective: We have previously described patterns of failure after extrapleural pneumonectomy and multimodality therapy for malignant pleural mesothelioma and sought to update our results with a larger cohort of recent patients. Methods: A total of 169 patients underwent extrapleural pneumonectomy without preoperative chemotherapy between 2001 and 2010. Data for treatment, recurrence, and survival were determined from medical records. A thoracic radiologist reviewed postoperative computed tomography or positron emission tomography computed tomography scans to determine sites of recurrence. Time to recurrence was estimated by the Kaplan-Meier method. Rates were compared using the Fisher exact test. Results: The median age of patients was 62 years. Histology on final pathology was epithelial for 104 patients (62%) and nonepithelial for 65 patients (38%). A total of 132 patients (78%) received heated intraoperative chemotherapy; 77 patients (45%) received adjuvant chemotherapy, and 71 patients (42%) received adjuvant radiation therapy. Most chemotherapy regimens included platinum or pemetrexed. Median radiation therapy dose was 54 Gy. Among 158 evaluable patients, a recurrence developed in 118 (75%). Median follow-up was 83 months, median time to recurrence was 13.1 months, and median survival was 15 months. Sites of first recurrence were in the ipsilateral hemithorax or mediastinum for 54% of patients, in the abdomen for 39% of patients, in the contralateral hemithorax for 28% of patients, and in other distant sites for 5% of patients. Some patients had simultaneous recurrences in multiple sites. Conclusions: The most common site of recurrence after extrapleural pneumonectomy and planned multimodality therapy remains the ipsilateral hemithorax (including mediastinum), and true distant failure (other than the abdomen or contralateral hemithorax) remains unusual. The distribution of recurrences is strikingly similar to our prior report. C1 [Baldini, Elizabeth H.; Mak, Raymond H.; Chen, Aileen B.; Kozono, David E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Richards, William G.; Eisen, Hannah M.; Bueno, Raphael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thorac Surg, Boston, MA 02115 USA. [Gill, Ritu R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Goodman, Brian M.] Geisinger Hlth Syst, Div Thorac Surg, Wilkes Barre, PA USA. [Winfrey, Olivia K.] Univ Kentucky, Coll Med, Lexington, KY USA. [Sugarbaker, David J.] Debakey Inst, Div Thorac Surg, Houston, TX USA. RP Baldini, EH (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, L2,75 Francis St, Boston, MA 02115 USA. EM ebaldini@partners.org FU Genzyme/Sanofi; Boehringer-Ingelheim, Inc; Myriad Genetics, Inc; Novartis Inst. Biomedical Research; Verastem, Inc Study 1; Verastem, Inc Study 2; Castle Biosciences; Meso Study; Esoph Study Genentech Inc; Siemens Medical Solutions, Inc; Exosome Diagnostics, Inc FX David E. Kozono reports consulting fees from Genzyme/Sanofi. Raymond H. Mak reports consulting fees for Boehringer-Ingelheim, Inc and equity ownership in Celgene. Raphael Bueno reports consulting fees for Myriad Genetics, Inc, Novartis Inst. Biomedical Research, Verastem, Inc Study 1, Verastem, Inc Study 2, Castle Biosciences, Meso Study, Castle Biosciences, Esoph Study Genentech Inc, Siemens Medical Solutions, Inc and Exosome Diagnostics, Inc. All other authors have nothing to disclose with regard to commercial support. NR 36 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2015 VL 149 IS 5 BP 1374 EP 1381 DI 10.1016/j.jtcvs.2014.10.128 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CI2HP UT WOS:000354567100036 PM 25772281 ER PT J AU Weinstein, S Mabray, MC Aslam, R Hope, T Yee, J Owens, C AF Weinstein, Stefanie Mabray, Marc C. Aslam, Riz Hope, Tom Yee, Judy Owens, Christopher TI Intraoperative Sonography During Carotid Endarterectomy Normal Appearance and Spectrum of Complications SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE carotid; endarterectomy; intraoperative; thromboembolic; vascular; vascular ultrasound ID DUPLEX ULTRASONOGRAPHY; BLOOD-FLOW; ULTRASOUND; STENOSIS; ANGIOGRAPHY; OUTCOMES; DEFECTS; DOPPLER; IMPACT; FATE AB Carotid endarterectomy is a commonly performed procedure for prevention of stroke related to carotid stenosis. Intraoperative sonography is used to identify potentially correctable technical defects during carotid endarterectomy. The main risk of endarterectomy is perioperative stroke, and great effort has been put into trying to reduce this risk through various surgical techniques and evaluation of the surgical bed. Postoperative carotid thrombosis, or thombo-embolization from the arterectomy site, remains a common cause of perioperative stroke and is often related to technical defects in the arterial reconstruction procedure. Re-exploration and repair of any imperfections have the potential to improve outcomes. Intraoperative imaging can identify potentially occult lesions, provide the option for correction, and thus reduce chance of stroke. Familiarity with the spectrum of intraoperative sonographic findings helps correctly identify residual intimal dissection flaps, plaque, thrombi, and stenosis, which may require immediate surgical revision. Our objective is to illustrate the spectrum of intraoperative findings and their importance. C1 [Weinstein, Stefanie; Mabray, Marc C.; Aslam, Riz; Hope, Tom; Yee, Judy; Owens, Christopher] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Weinstein, S (reprint author), San Francisco VA Med Ctr, Serv Radiol, 4150 Clement St, San Francisco, CA 94121 USA. EM stefanie.weinstein@ucsf.edu NR 33 TC 0 Z9 0 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAY PY 2015 VL 34 IS 5 BP 885 EP 894 DI 10.7863/ultra.34.5.885 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA CH4ON UT WOS:000354012900019 PM 25911722 ER PT J AU Yildiz, HM Carlson, TL Goldstein, AM Carrier, RL AF Yildiz, Hasan M. Carlson, Taylor L. Goldstein, Allan M. Carrier, Rebecca L. TI Mucus Barriers to Microparticles and Microbes are Altered in Hirschsprung's Disease SO MACROMOLECULAR BIOSCIENCE LA English DT Article DE Hirschsprung's disease; intestine; microbe transport; mucus; nanoparticle diffusion AB Mucus forms a protective hydrogel layer over the intestinal epithelium, presenting a selective and robust barrier to the uptake of particulates and microbe invasion. Disease can alter mucus production and composition, thus potentially modifying mucosal barrier properties. Hirschsprung's disease (HD) is a developmental abnormality of the nervous system often complicated by intestinal infection. An investigation of colonic mucus barrier properties in an HD animal model, endothelin receptor B mutant mice, revealed significantly reduced microsphere (passive) and microbe (active) transport rates (7-fold and 3.6-fold, respectively, in proximal colonic mucus) relative to wild-type. Transport differences were evident in both the ganglionic and aganglionic colon segments, in agreement with the risk of HD-associated enterocolitis after surgery to remove aganglionic colon segments. The development of therapies aimed at altering colonic mucus barrier properties could be explored towards preventing the onset of enterocolitis in HD. C1 [Yildiz, Hasan M.; Carlson, Taylor L.; Carrier, Rebecca L.] Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. [Goldstein, Allan M.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. RP Carrier, RL (reprint author), Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. EM rebecca@coe.neu.edu FU National Institutes of Health [R21EB015750] FX We thank Sarah Alyce Miller for her valuable contributions to tissue extractions. The authors also thank Professor Slava Epstein, Paul Miller, and David Stancyk for culturing and providing GFP expressing E. coli ASV bacteria. We gratefully acknowledge financial support from National Institutes of Health Grant R21EB015750. NR 33 TC 2 Z9 2 U1 2 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1616-5187 EI 1616-5195 J9 MACROMOL BIOSCI JI Macromol. Biosci. PD MAY PY 2015 VL 15 IS 5 BP 712 EP 718 DI 10.1002/mabi.201400473 PG 7 WC Biochemistry & Molecular Biology; Materials Science, Biomaterials; Polymer Science SC Biochemistry & Molecular Biology; Materials Science; Polymer Science GA CI0AB UT WOS:000354396800012 PM 25644515 ER PT J AU Bennett, JL de Seze, J Lana-Peixoto, M Palace, J Waldman, A Schippling, S Tenembaum, S Banwell, B Greenberg, B Levy, M Fujihara, K Chan, KH Kim, HJ Asgari, N Sato, DK Saiz, A Wuerfel, J Zimmermann, H Green, A Villoslada, P Paul, F Iorio, R Paul, F Wuerfel, J Cabre, P Marignier, R de Seze, J Tenembaum, S Villoslada, P Levy, M Chitnis, T Klawiter, EC Wingerchuk, D Weinshenker, B Kim, HJ Pandit, L Leite, MI Palace, J Simon, J Apiwattanakul, M Kleiter, I Broadley, S Prayoonwiwat, N Han, M Hellwig, K Banwell, B van Herle, K John, G Hooper, DC Fujihara, K Nakashima, I Sato, D Bichuetti, D Yeaman, MR Waubant, E Zamvil, S Bennett, J Smith, T Lana-Peixoto, M Stuve, O Greenberg, B Aktas, O Wuerfel, J Asgari, N Jacob, A O'Connor, K Saiz, A AF Bennett, J. L. de Seze, J. Lana-Peixoto, M. Palace, J. Waldman, A. Schippling, S. Tenembaum, S. Banwell, B. Greenberg, B. Levy, M. Fujihara, K. Chan, K. H. Kim, H. J. Asgari, N. Sato, D. K. Saiz, A. Wuerfel, J. Zimmermann, H. Green, A. Villoslada, P. Paul, F. Iorio, Raffaele Paul, Friedemann Wuerfel, Jens Cabre, Philippe Marignier, Romain de Seze, Jerome Tenembaum, Silvia Villoslada, Pablo Levy, Michael Chitnis, Tanuja Klawiter, Eric C. Wingerchuk, Dean Weinshenker, Brian Kim, Ho Jin Pandit, Lekha Leite, Maria Isabel Palace, Jacqueline Simon, Jack Apiwattanakul, Metha Kleiter, Ingo Broadley, Simon Prayoonwiwat, Naraporn Han, May Hellwig, Kerstin Banwell, Brenda van Herle, Katja John, Gareth Hooper, D. Craig Fujihara, Kazuo Nakashima, Ichiro Sato, Douglas Bichuetti, Denis Yeaman, Michael R. Waubant, Emmanuelle Zamvil, Scott Bennett, Jeffrey Smith, Terry Lana-Peixoto, Marco Stuve, Olaf Greenberg, Benjamin Aktas, Orhan Wuerfel, Jens Asgari, Nasrin Jacob, Anu O'Connor, Kevin Saiz, Albert CA GJCF-ICC BR TI Neuromyelitis optica and multiple sclerosis: Seeing differences through optical coherence tomography SO MULTIPLE SCLEROSIS JOURNAL LA English DT Review DE Neuromyelitis optica; optical coherence tomography; multiple sclerosis; optic neuritis; retinal nerve fiber layer; ganglion cell layer ID NERVE-FIBER LAYER; MICROCYSTIC MACULAR EDEMA; INTERFERON-BETA TREATMENT; INNER NUCLEAR LAYER; SPECTRUM DISORDERS; GANGLION-CELL; RETINAL ABNORMALITIES; AQUAPORIN 4; NEURITIS; THICKNESS AB Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel aquaporin-4 present in up to 80% of NMO patients enables distinction from MS. Optic neuritis may occur in either condition resulting in neuro-anatomical retinal changes. Optical coherence tomography (OCT) has become a useful tool for analyzing retinal damage both in MS and NMO. Numerous studies showed that optic neuritis in NMO typically results in more severe retinal nerve fiber layer (RNFL) and ganglion cell layer thinning and more frequent development of microcystic macular edema than in MS. Furthermore, while patients' RNFL thinning also occurs in the absence of optic neuritis in MS, subclinical damage seems to be rare in NMO. Thus, OCT might be useful in differentiating NMO from MS and serve as an outcome parameter in clinical studies. C1 [Bennett, J. L.] Univ Colorado, Dept Neurol, Denver, CO 80202 USA. [Bennett, J. L.] Univ Colorado, Dept Ophthalmol, Denver, CO 80202 USA. [de Seze, J.] Univ Hosp Strasbourg, Neurol Serv, Strasbourg, France. [Lana-Peixoto, M.] Univ Fed Minas Gerais, Sch Med, CIEM MS Res Ctr, Belo Horizonte, MG, Brazil. [Palace, J.] Natl Hlth Serv Trust, Oxford Univ Hosp, Dept Neurol, Oxford, England. [Waldman, A.; Banwell, B.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Div Neurol, Philadelphia, PA 19104 USA. [Schippling, S.] Univ Zurich Hosp, Dept Neurol, Neuroimmunol & Multiple Sclerosis Res Sect, Zurich, Switzerland. [Tenembaum, S.] Natl Pediat Hosp Dr Juan P Garrahan, Dept Neurol, Buenos Aires, DF, Argentina. [Greenberg, B.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Greenberg, B.] Univ Texas SW Med Ctr Dallas, Dept Neurotherapeut, Dallas, TX 75390 USA. [Levy, M.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Fujihara, K.] Tohoku Univ, Grad Sch Med, Dept Multiple Sclerosis Therapeut, Sendai, Miyagi 980, Japan. [Chan, K. H.] Univ Hong Kong, LKS Fac Med, Univ Dept Med, Hong Kong, Hong Kong, Peoples R China. [Kim, H. J.] Natl Canc Ctr, Res Inst & Hosp, Goyang, South Korea. [Asgari, N.] Univ Southern Denmark, Inst Mol Med, Odense, Denmark. [Asgari, N.] Vejle Hosp, Dept Neurol, Odense, Denmark. [Sato, D. K.] Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 980, Japan. [Saiz, A.] Hosp Clin Barcelona, Serv Neurol, Ctr Neuroimmunol, Barcelona, Spain. [Saiz, A.] Inst Biomed Res August Pi Sunyer, Barcelona, Spain. [Wuerfel, J.; Zimmermann, H.; Paul, F.] Charite Univ Med Berlin, NeuroCure Clin Res Ctr, Berlin, Germany. [Wuerfel, J.] Univ Med Gottingen, Inst Intervent & Diagnost Neuroradiol, Gottingen, Germany. [Green, A.] UCSF Dept Neurol, Multiple Sclerosis Ctr, San Francisco, CA USA. [Green, A.] UCSF Dept Ophthalmol, Neuroophthalmol Serv, San Francisco, CA USA. [Paul, F.] Charite, NeuroCure Clin Res, D-13353 Berlin, Germany. [Paul, F.] Charite, Dept Neurol, D-13353 Berlin, Germany. [Paul, F.] Charite, Expt & Clin Res Ctr, D-13353 Berlin, Germany. [Paul, F.] Max Delbruck Ctr Mol Med, Berlin, Germany. [Iorio, Raffaele] Catholic Univ, Rome, Italy. [Paul, Friedemann; Wuerfel, Jens] Charite, Berlin, Germany. [Cabre, Philippe] CHU Ft France, Martinique, France. [Marignier, Romain] CHU Lyon, Lyon, France. [de Seze, Jerome] CHU Strasbourg, Strasbourg, France. [Tenembaum, Silvia] Dr Juan P Garrahan Natl Pediat Hosp, Buenos Aires, DF, Argentina. [Villoslada, Pablo; Saiz, Albert] IDIBAPS, Barcelona, Spain. [Levy, Michael] Johns Hopkins Univ, Baltimore, MD USA. [Chitnis, Tanuja; Klawiter, Eric C.] Massachusetts Gen Hosp, Boston, MA USA. [Wingerchuk, Dean; Weinshenker, Brian] Mayo Clin, Scottsdale, AZ USA. [Kim, Ho Jin] Res Inst & Hosp Natl Canc Ctr, Goyang, South Korea. [Pandit, Lekha] Nitte Univ, Mangalore, India. [Leite, Maria Isabel; Palace, Jacqueline] Oxford Univ Hosp, Natl Hlth Serv Trust, Oxford, England. [Simon, Jack] Portland VA Med Ctr, VA Med Ctr, Portland, OR USA. [Simon, Jack] Oregon Hlth & Sci Univ, Portland, OR USA. [Apiwattanakul, Metha] Prasat Neurol Inst, Bangkok, Thailand. [Kleiter, Ingo] Ruhr Univ Bochum, Bochum, Germany. [Broadley, Simon] Griffith Univ, Sch Med, Nathan, Qld 4111, Australia. [Prayoonwiwat, Naraporn] Mahidol Univ, Siriraj Hosp, Bangkok, Thailand. [Han, May] Stanford Univ, Sch Med, Palo Alto, CA USA. [Hellwig, Kerstin] St Josef Hosp, Bochum, Germany. [Banwell, Brenda] Childrens Hosp Philadelphia, Philadelphia, PA USA. [van Herle, Katja] Guthy Jackson Charitable Fdn, San Diego, CA USA. [John, Gareth] Mt Sinai Hosp, New York, NY USA. [Hooper, D. Craig] Thomas Jefferson Univ, Philadelphia, PA USA. [Fujihara, Kazuo; Nakashima, Ichiro; Sato, Douglas] Tohoku Univ, Sendai, Miyagi, Japan. [Bichuetti, Denis] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Yeaman, Michael R.] Univ Calif Los Angeles, Los Angeles, CA USA. [Waubant, Emmanuelle; Zamvil, Scott] Univ Calif San Francisco, San Francisco, CA USA. [Bennett, Jeffrey] Univ Colorado, Denver, CO USA. [Smith, Terry] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Lana-Peixoto, Marco] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [Stuve, Olaf; Greenberg, Benjamin] Univ Texas Southwestern, Dallas, TX USA. [Aktas, Orhan] Univ Dusseldorf, Dusseldorf, Germany. [Wuerfel, Jens] Univ Gottingen, Gottingen, Germany. [Asgari, Nasrin] Univ Southern Denmark, Odense, Denmark. [Jacob, Anu] Walton Ctr, Liverpool, Merseyside, England. [O'Connor, Kevin] Yale Univ, Sch Med, Dept Neurol, New Haven, CT USA. RP Paul, F (reprint author), Charite Univ Med Berlin, NeuroCure Clin Res Ctr, Berlin, Germany. EM friedemann.paul@charite.de RI Sato, Douglas/F-2508-2013; De Seze, Jerome/M-8316-2016 OI Sato, Douglas/0000-0002-7695-6020; De Seze, Jerome/0000-0002-7197-7578 FU NEI NIH HHS [R01 EY022936]; NINDS NIH HHS [K08 NS078555, K23 NS069806] NR 80 TC 33 Z9 33 U1 1 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD MAY PY 2015 VL 21 IS 6 BP 678 EP 688 DI 10.1177/1352458514567216 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH8AR UT WOS:000354258600002 PM 25662342 ER PT J AU Gartner, J Banwell, B Ghezzi, A Karlsson, G Chen, Y Merschhemke, M Putzki, N Chitnis, T AF Gaertner, J. Banwell, B. Ghezzi, A. Karlsson, G. Chen, Y. Merschhemke, M. Putzki, N. Chitnis, T. TI Oral Fingolimod Versus Interferon-beta 1a in Paediatric Multiple Sclerosis: Design of A Double-blind Trial SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract C1 [Gaertner, J.] Univ Med Gottingen, Gottingen, Germany. [Banwell, B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Ghezzi, A.] Osped Gallarate, Gallarate, Italy. [Karlsson, G.; Merschhemke, M.; Putzki, N.] Novartis Pharma AG, Basel, Switzerland. [Chen, Y.] Novartis Pharmaceut, E Hanover, NJ USA. [Chitnis, T.] Massachusetts Gen Hosp, Partners Paediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD MAY PY 2015 VL 21 IS 6 MA P-26 BP 819 EP 819 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH8AR UT WOS:000354258600082 ER PT J AU Chitnis, T Karlsson, G Haring, DA Ghezzi, A Pohl, D Gartner, J Putzki, N AF Chitnis, T. Karlsson, G. Haering, D. A. Ghezzi, A. Pohl, D. Gaertner, J. Putzki, N. TI Effect of Age on Efficacy of Fingolimod Treatment: Young Adult Patients with Multiple Sclerosis Demonstrate Higher Relative Reduction of Relapse Rates SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract C1 [Chitnis, T.] Massachusetts Gen Hosp, Partners Paediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. [Karlsson, G.; Haering, D. A.; Putzki, N.] Novartis Pharma AG, Basel, Switzerland. [Ghezzi, A.] Ctr Studi Sclerosi Multipla, Gallarate, Italy. [Pohl, D.] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. [Gaertner, J.] Univ Med Gottingen, Gottingen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD MAY PY 2015 VL 21 IS 6 MA P-27 BP 820 EP 820 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH8AR UT WOS:000354258600083 ER PT J AU Farid, H Karmon, AE Styer, AK AF Farid, Huma Karmon, Anatte Emma Styer, Aaron Kyle TI Inpatient Management of Tubo-Ovarian Abscesses What Is the Threshold of Parenteral Antibiotic Treatment Failure? SO OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 61st Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists - Women's Health Care Physicians CY MAY 07, 2013 CL New Orleans, LA SP Amer Coll Obstetricians & Gynecologists C1 [Farid, Huma] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2015 VL 125 SU 1 MA 45 BP 23S EP 23S PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CH6EI UT WOS:000354128700073 ER PT J AU Mehta, P Carter, T Vinoya, C Kangovi, S Srinivas, SK AF Mehta, Pooja Carter, Tamala Vinoya, Cjloe Kangovi, Shreya Srinivas, Sindhu Kikkeri TI Understanding High Utilization of Emergency Obstetric Care in Pregnant Women of Low Socioeconomic Status SO OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 61st Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists - Women's Health Care Physicians CY MAY 07, 2013 CL New Orleans, LA SP Amer Coll Obstetricians & Gynecologists C1 [Mehta, Pooja] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2015 VL 125 SU 1 MA 170 BP 58S EP 58S PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CH6EI UT WOS:000354128700191 ER PT J AU Karmon, AE Cardozo, ER Petrozza, JC AF Karmon, Anatte Emma Cardozo, Eden Rebecca Petrozza, John Christopher TI Clomid Compared With Follicle-Stimulating Hormone Treatment Similar Follicle Number Means Different Success Rates SO OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 61st Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists - Women's Health Care Physicians CY MAY 07, 2013 CL New Orleans, LA SP Amer Coll Obstetricians & Gynecologists C1 [Karmon, Anatte Emma] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2015 VL 125 SU 1 MA 178 BP 60S EP 60S PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CH6EI UT WOS:000354128700199 ER PT J AU Kamihara, J Nyborn, JA Olcese, ME Nickerson, T Mack, JW AF Kamihara, Junne Nyborn, Justin A. Olcese, Maura E. Nickerson, Taylor Mack, Jennifer W. TI Parental Hope for Children With Advanced Cancer SO PEDIATRICS LA English DT Article ID QUALITATIVE CONTENT-ANALYSIS; PROGNOSIS; CARE; DISCLOSURE; COMMUNICATION; COLLUSION; TRUTH AB BACKGROUND: Previous work suggests that parents of children with cancer can remain hopeful despite receiving prognostic information, but we know little about what hope means to such parents, or the extent to which parents can feel hopeful even while facing the child's impending death. METHODS: We audiotaped conversations between clinicians and parents of 32 children with relapsed or refractory cancer, and then interviewed parents about their hopes and expectations for their child. RESULTS: Parent statements about prognosis in interviews mirrored those made by clinicians during discussions about the child's diagnosis with refractory or relapsed cancer. Clinicians used language referring to hope during these conversations but did not ask parents directly about their hopes. Parents expressed a range of hopes for their children, from hopes related to cure or treatment response, to quality of life, normalcy, and love and relationships for the child. For most parents, expectations about prognosis were not aligned with their hopes for the child; for example, many parents hoped for a cure and also reported that they did not believe cure was possible. Many parents were able to acknowledge this incongruence. CONCLUSIONS: Parents accurately conveyed the reality of their child's serious condition in the setting of advanced cancer, and yet maintained hope. Hopes were not limited to hope for cure/treatment response. Clinicians should be encouraged to engage in direct conversations about hope with parents as a means to elicit realistic hopes that can help to focus the most meaningful plans for the child and family. C1 [Kamihara, Junne; Nyborn, Justin A.; Nickerson, Taylor; Mack, Jennifer W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Kamihara, Junne; Nyborn, Justin A.; Nickerson, Taylor; Mack, Jennifer W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Olcese, Maura E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Nickerson, Taylor] Florida Atlantic Univ, Charles E Schmidt Coll Med, Boca Raton, FL 33431 USA. RP Kamihara, J (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_mack@dfci.harvard.edu FU National Palliative Care Research Center; Hyundai Hope on Wheels Grant FX Supported by the National Palliative Care Research Center, and by a Hyundai Hope on Wheels Grant. NR 25 TC 6 Z9 6 U1 1 U2 7 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 MAY PY 2015 VL 135 IS 5 BP 868 EP 874 DI 10.1542/peds.2014-2855 PG 7 WC Pediatrics SC Pediatrics GA CH0QX UT WOS:000353728400049 PM 25847801 ER PT J AU Antommaria, AHM Collura, CA Antiel, RM Lantos, JD AF Antommaria, Armand H. Matheny Collura, Christopher A. Antiel, Ryan M. Lantos, John D. TI Two Infants, Same Prognosis, Different Parental Preferences SO PEDIATRICS LA English DT Article ID MEDICAL-TREATMENT; TRACHEOSTOMY; CHILDREN; EXPERIENCE; CARE; EXEMPTIONS; HEALTH; LIFE AB A central principle of justice is that similar cases should be decided in similar ways. In pediatrics, however, there are cases in which 2 infants have similar diagnoses and prognoses, but their parents request different treatments. In this Ethics Rounds, we present such a situation that occurred in a single NICU. Three physician-ethicists analyze the issues. C1 [Antommaria, Armand H. Matheny] Cincinnati Childrens Hosp, Med Ctr, Eth Ctr, Cincinnati, OH USA. [Antommaria, Armand H. Matheny] Cincinnati Childrens Hosp, Med Ctr, Div Hosp Med, Cincinnati, OH USA. [Collura, Christopher A.] Mayo Clin, Dept Pediat & Adolescent, Rochester, MN USA. [Antiel, Ryan M.] Mayo Clin, Dept Surg, Rochester, MN USA. [Collura, Christopher A.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Palliat Care, Boston, MA 02115 USA. [Collura, Christopher A.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Collura, Christopher A.] Univ Minnesota, Ctr Bioeth, Minneapolis, MN USA. [Lantos, John D.] Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA. [Lantos, John D.] Childrens Mercy Hosp, Ctr Bioeth, Kansas City, MO 64108 USA. RP Lantos, JD (reprint author), Childrens Mercy Hosp Bioeth Ctr, 2401 Gillham Rd, Kansas City, MO 64108 USA. EM jlantos@cmh.edu NR 22 TC 0 Z9 1 U1 0 U2 1 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 MAY PY 2015 VL 135 IS 5 BP 918 EP 923 DI 10.1542/peds.2013-4044 PG 6 WC Pediatrics SC Pediatrics GA CH0QX UT WOS:000353728400055 PM 25847802 ER PT J AU van Essen, TH Len, DLR Williams, KA Jager, MJ AF van Essen, T. H. Len, D. L. Roe Williams, K. A. Jager, M. J. TI Matching for Human Leukocyte Antigens (HLA) in corneal transplantation - To do or not to do SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Article DE Cornea; Transplantation; Human Leukocyte Antigen; Survival; Matching ID MINOR HISTOCOMPATIBILITY ANTIGENS; ENDOTHELIAL GROWTH-FACTOR; DEEP ANTERIOR LAMELLAR; NORMAL-RISK KERATOPLASTY; TERM GRAFT-SURVIVAL; MESENCHYMAL STEM-CELLS; NECROSIS-FACTOR-ALPHA; CADAVER RENAL-TRANSPLANTATION; OCULAR INFLAMMATORY DISEASE; LEBERS CONGENITAL AMAUROSIS AB As many patients with severe corneal disease are not even considered as candidates for a human graft due to their high risk of rejection, it is essential to find ways to reduce the chance of rejection. One of the options is proper matching of the cornea donor and recipient for the Human Leukocyte Antigens (HLA), a subject of much debate. Currently, patients receiving their first corneal allograft are hardly ever matched for HLA and even patients undergoing a regraft usually do not receive an HLA-matched graft. While anterior and posterior lamellar grafts are not immune to rejection, they are usually performed in low risk, non-vascularized cases. These are the cases in which the immune privilege due to the avascular status and active immune inhibition is still intact. Once broken due to infection, sensitization or trauma rejection will occur. There is enough data to show that when proper DNA-based typing techniques are being used, even low risk perforating corneal transplantations benefit from matching for HLA Class I, and high risk cases from HLA Class I and probably Class II matching. Combining HLA class I and class II matching, or using the HLAMatchmaker could further improve the effect of HLA matching. However, new techniques could be applied to reduce the chance of rejection. Options are the local or systemic use of biologics, or gene therapy, aiming at preventing or suppressing immune responses. The goal of all these approaches should be to prevent a first rejection, as secondary grafts are usually at higher risk of complications including rejections than first grafts. (C) 2015 Elsevier Ltd. All rights reserved. C1 [van Essen, T. H.; Jager, M. J.] Leiden Univ, Med Ctr, Dept Ophthalmol, NL-2300 RC Leiden, Netherlands. [Len, D. L. Roe] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2300 RC Leiden, Netherlands. [Williams, K. A.] Flinders Univ S Australia, Dept Ophthalmol, Adelaide, SA 5001, Australia. [Jager, M. J.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Jager, M. J.] Harvard Univ, Sch Med, Boston, MA USA. [Jager, M. J.] Peking Univ, Hlth Sci Ctr, Ctr Eye, Beijing 100871, Peoples R China. RP van Essen, TH (reprint author), Leiden Univ, Med Ctr, Dept Ophthalmol, J3-S,POB 9600, NL-2300 RC Leiden, Netherlands. EM T.H.van_Essen@lumc.nl; M.J.Jager@lumc.nl NR 268 TC 3 Z9 3 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD MAY PY 2015 VL 46 BP 84 EP 110 DI 10.1016/j.preteyeres.2015.01.001 PG 27 WC Ophthalmology SC Ophthalmology GA CI2PZ UT WOS:000354590800004 PM 25601193 ER PT J AU Kontos, N Querques, J Freudenreich, O AF Kontos, Nicholas Querques, John Freudenreich, Oliver TI Capable of More: Some Underemphasized Aspects of Capacity Assessment SO PSYCHOSOMATICS LA English DT Article ID DECISION-MAKING CAPACITY; MACARTHUR TREATMENT COMPETENCE; MILD COGNITIVE IMPAIRMENT; DEEP-BRAIN-STIMULATION; INFORMED-CONSENT; MEDICAL DECISIONS; AUTONOMY; SCHIZOPHRENIA; CONSULTATION; DISEASE AB Background: The 4-abilities model of decision-making capacity is vulnerable to constricted application and teaching. Objective: The authors attempt to assert the fundamentally clinical nature of capacity evaluations, while acknowledging that the concept of decisionmaking capacity must be legally grounded. Methods: Relevant aspects of clinical care are examined and emphasized as they apply to the evaluation of capacity for medical decision making. Results: Accessing patients' maximal abilities, attending to noncognitive aspects of choice, and identifing diagnostic explanations for patients' difficulties are important components of these assessments. Discussion: The evaluation of medical decisionmaking capacity is not a purely forensic task; it is enhanced by an approach that bridges the clinical-forensic divide. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kontos, N (reprint author), Massachusetts Gen Hosp, 55 Fruit St Warren 605, Boston, MA 02114 USA. EM nkontos@partners.org NR 96 TC 3 Z9 3 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2015 VL 56 IS 3 BP 217 EP 226 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CI0DJ UT WOS:000354405900001 PM 25648077 ER PT J AU Zalpuri, I Byatt, N Gramann, SB Dresner, N Brendel, R AF Zalpuri, Isheeta Byatt, Nancy Gramann, Stacey B. Dresner, Nehama Brendel, Rebecca TI Decisional Capacity in Pregnancy: A Complex Case of Pregnancy Termination SO PSYCHOSOMATICS LA English DT Article ID PSYCHIATRIC-DISORDERS; SCHIZOPHRENIA; WOMEN; CONSENT C1 [Zalpuri, Isheeta; Byatt, Nancy] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01605 USA. [Byatt, Nancy] Univ Massachusetts, Sch Med, Dept Obstet Gynecol, Worcester, MA 01605 USA. [Gramann, Stacey B.] Portland VA Med Ctr, Portland, OR USA. [Dresner, Nehama] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Dresner, Nehama] Wellsprings Hlth Assoc, Chicago, IL USA. [Brendel, Rebecca] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Brendel, Rebecca] Massachusetts Gen Hosp, Ctr Law Brain & Behav, Boston, MA 02114 USA. RP Zalpuri, I (reprint author), 401 Quarry Rd, Palo Alto, CA 94304 USA. EM zalpuri.isheeta@gmail.com FU National Center fir Research Resources, USA; National Center for Advancing Translational Sciences, National Institutes of Health, USA [KL2TR000160] FX Drs, Zalpuri, Gramann, Dresner, and Brendel report no proprietary or commercial interest in any product mentioned or concept discussed in this article. Dr. Byatt received funding support for this work from the National Center fir Research Resources, USA and the National Center for Advancing Translational Sciences, National Institutes of Health, USA through Grant number KL2TR000160. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 12 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2015 VL 56 IS 3 BP 292 EP 297 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CI0DJ UT WOS:000354405900009 PM 25591494 ER PT J AU Shah, KS Marston, NA Mueller, C Neath, SX Christenson, RH McCord, J Nowak, RM Vilke, GM Daniels, LB Hollander, JE Apple, FS Cannon, CM Nagurney, J Schreiber, D deFilippi, C Hogan, CJ Diercks, DB Limkakeng, A Anand, IS Wu, AHB Clopton, P Jaffe, AS Peacock, WF Maisel, AS AF Shah, Kevin S. Marston, Nicholas A. Mueller, Christian Neath, Sean-Xavier Christenson, Robert H. McCord, James Nowak, Richard M. Vilke, Gary M. Daniels, Lori B. Hollander, Judd E. Apple, Fred S. Cannon, Chad M. Nagurney, John Schreiber, Donald deFilippi, Christopher Hogan, Christopher J. Diercks, Deborah B. Limkakeng, Alexander Anand, Inder S. Wu, Alan H. B. Clopton, Paul Jaffe, Allan S. Peacock, W. Frank Maisel, Alan S. TI Midregional Proadrenomedullin Predicts Mortality and Major Adverse Cardiac Events in Patients Presenting With Chest Pain: Results From the CHOPIN Trial SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID REGIONAL PRO-ADRENOMEDULLIN; ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; ACUTE HEART-FAILURE; RISK STRATIFICATION; EMERGENCY-DEPARTMENT; TROPONIN-T; PEPTIDE; DISEASE; SCORE AB ObjectivesChest pain is a common complaint to emergency departments (EDs) and clinical risk factors are used to predict which patients are at risk for worse outcomes and mortality. The goal was to assess the novel biomarker midregional proadrenomedullin (MR-proADM) in prediction of mortality and major adverse cardiac events (MACE). MethodsThis was a subanalysis of the CHOPIN study, a 16-center prospective trial that enrolled 2,071 patients presenting with chest pain within 6hours of onset. The primary endpoint was 6-month all-cause mortality and the secondary endpoint was 30-day and 6-month MACE: ED visits or hospitalization for acute myocardial infarction, unstable angina, reinfarction, revascularization, and heart failure. ResultsMR-proADM performed similarly to troponin (cTnI; c-statistic=0.845 and 0.794, respectively) for mortality prediction in all subjects and had similar results in those with noncardiac diagnoses. MR-proADM concentrations were stratified by decile, and the cohort in the top decile had a 9.8% 6-month mortality risk versus 0.9% risk for those in the bottom nine deciles (p<0.0001). MR-proADM, history of coronary artery disease (CAD), and hypertension were predictors of short-term MACE, while history of CAD, hypertension, cTnI, and MR-proADM were predictors of long-term MACE. ConclusionsIn patients with chest pain, MR-proADM predicts mortality and MACE in all-comers with chest pain and has similar prediction in those with a noncardiac diagnosis. This exploratory analysis is primarily hypotheses-generating and future prospective studies to identify its utility in risk stratification should be considered. (C) 2015 by the Society for Academic Emergency Medicine C1 [Neath, Sean-Xavier; Vilke, Gary M.] Univ Calif San Diego, Dept Emergency Med, San Diego, CA 92103 USA. [Daniels, Lori B.; Maisel, Alan S.] Univ Calif San Diego, Dept Cardiol, San Diego, CA 92103 USA. [Shah, Kevin S.; Marston, Nicholas A.] Univ Calif San Diego, Dept Internal Med, San Diego, CA 92103 USA. [Mueller, Christian] Univ Basel Hosp, Dept Cardiol, CH-4031 Basel, Switzerland. [McCord, James; Nowak, Richard M.] Henry Ford Hlth Syst, Dept Emergency Med, Detroit, MI USA. [Hollander, Judd E.] Thomas Jefferson Univ, Dept Emergency Med, Philadelphia, PA 19107 USA. [Apple, Fred S.] Hennepin Cty Med Ctr, Dept Pathol, Minneapolis, MN 55415 USA. [Apple, Fred S.] Univ Minnesota, Minneapolis, MN USA. [Cannon, Chad M.] Univ Kansas Hosp, Dept Emergency Med, Kansas City, KS USA. [Nagurney, John] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Schreiber, Donald] Stanford Univ, Sch Med, Dept Emergency Med, Palo Alto, CA 94304 USA. [Christenson, Robert H.; deFilippi, Christopher] Univ Maryland, Dept Cardiol, Baltimore, MD 21201 USA. [Hogan, Christopher J.] Virginia Commonwealth Univ, Dept Surg, Richmond, VA USA. [Diercks, Deborah B.] Univ Calif Davis, Med Ctr, Dept Emergency Med, Sacramento, CA 95817 USA. [Limkakeng, Alexander] Duke Univ, Med Ctr, Dept Emergency Med, Durham, NC USA. [Anand, Inder S.] Vet Adm Hosp, Dept Cardiol, Minneapolis, MN USA. [Wu, Alan H. B.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Maisel, Alan S.] Vet Affairs Med Ctr, Dept Cardiol, San Diego, CA 92161 USA. [Clopton, Paul] Vet Affairs Med Ctr, Dept Res, San Diego, CA 92161 USA. [Jaffe, Allan S.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. RP Shah, KS (reprint author), Univ Calif San Diego, Dept Internal Med, San Diego, CA 92103 USA. EM kevinshah@ucsd.edu OI Hollander, Judd/0000-0002-1318-2785 FU ThermoFisher Scientific FX The CHOPIN trial was sponsored by Brahms, now known as ThermoFisher Scientific; Clinical Trial Registration: http://clinicaltrials.gov/show/NCT00952744. Unique identifier: NCT00952744. NR 46 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2015 VL 22 IS 5 SI SI BP 554 EP 563 DI 10.1111/acem.12649 PG 10 WC Emergency Medicine SC Emergency Medicine GA CH6ZR UT WOS:000354185800006 PM 25908114 ER PT J AU Mills, AM Raja, AS Marin, JR AF Mills, Angela M. Raja, Ali S. Marin, Jennifer R. TI Optimizing Diagnostic Imaging in the Emergency Department SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID COMPUTED-TOMOGRAPHY USE; SUSPECTED PULMONARY-EMBOLISM; CLINICAL-PRACTICE GUIDELINES; CUMULATIVE RADIATION-EXPOSURE; PHYSICIAN RISK TOLERANCE; PEDIATRIC HEAD TRAUMA; DECISION-SUPPORT; ABDOMINAL-PAIN; UNITED-STATES; ORDER ENTRY AB While emergency diagnostic imaging use has increased significantly, there is a lack of evidence for corresponding improvements in patient outcomes. Optimizing emergency department (ED) diagnostic imaging has the potential to improve the quality, safety, and outcomes of ED patients, but to date, there have not been any coordinated efforts to further our evidence-based knowledge in this area. The objective of this article is to discuss six aspects of diagnostic imaging to provide background information on the underlying framework for the 2015 Academic Emergency Medicine consensus conference, Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization. The consensus conference aims to generate a high priority research agenda for emergency diagnostic imaging that will inform the design of future investigations. The six components herein will serve as the group topics for the conference: 1) patient-centered outcomes research; 2) clinical decision rules; 3) training, education, and competency; 4) knowledge translation and barriers to image optimization; 5) use of administrative data; and 6) comparative effectiveness research: alternatives to traditional CT use. (C) 2015 by the Society for Academic Emergency Medicine C1 [Mills, Angela M.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Raja, Ali S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Raja, Ali S.] Brigham & Womens Hosp, Ctr Evidence Based Imaging, Boston, MA 02115 USA. [Raja, Ali S.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Marin, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. [Marin, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Emergency Med, Pittsburgh, PA USA. RP Mills, AM (reprint author), Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. EM millsa@uphs.upenn.edu FU AHRQ; 3rd Rock Ultrasound, LLC FX Dr. Marin is supported by an R13 pertaining to diagnostic imaging from the AHRQ, and Dr. Marin teaches for and receives compensation from 3rd Rock Ultrasound, LLC. NR 80 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2015 VL 22 IS 5 SI SI BP 625 EP 631 DI 10.1111/acem.12640 PG 7 WC Emergency Medicine SC Emergency Medicine GA CH6ZR UT WOS:000354185800016 PM 25731864 ER PT J AU Weinstein, DF AF Weinstein, Debra F. TI Feedback in Clinical Education: Untying the Gordian Knot SO ACADEMIC MEDICINE LA English DT Editorial Material AB Feedback is essential to clinical education, especially in the era of competencies, milestones, and entrustable professional activities. It is, however, an area where medical educators often fall short. Although educational leaders and faculty supervisors provide feedback in a variety of clinical settings, surveys show important gaps in medical student and resident satisfaction with the feedback received, suggesting lost opportunities to identify performance problems as well as to help each learner reach his or her greatest potential. In this issue of Academic Medicine, Telio and colleagues extend the empirically validated concept of a "therapeutic alliance" to propose the "educational alliance" as a framework for enhancing feedback in medical education. They highlight the importance of source credibility, which depends on the teacher-learner relationship and alignment of values, the teacher's understanding of the learner's role and goals, the teacher's direct observation of the learner, and the learner's perception of the teacher's good intentions. The author of this Commentary suggests that the educational alliance framework should prompt medical educators to reconsider feedback and explore opportunities for optimizing it. Most medical schools and graduate medical education programs are not designed in a way that supports the education alliance model, but the Commentary author offers suggestions for cultivating educational alliances, including rethinking supervisor selection criteria. Such interventions should be combined with ongoing faculty development and efforts to improve coaching and mentoring for students, residents, and fellows. Untying the Gordian knot of effective feedback will require innovative approaches, exchange of successful strategies, and continued research. C1 [Weinstein, Debra F.] Partners HealthCare Syst, Grad Med Educ, Boston, MA USA. [Weinstein, Debra F.] Massachusetts Gen Hosp, Dept Med, Med, Boston, MA 02114 USA. [Weinstein, Debra F.] Harvard Univ, Sch Med, Boston, MA USA. RP Weinstein, DF (reprint author), Massachusetts Gen Hosp, Bultinch 230,55 Fruit St, Boston, MA 02114 USA. EM dweinstein@partners.org NR 5 TC 4 Z9 4 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD MAY PY 2015 VL 90 IS 5 BP 559 EP 561 DI 10.1097/ACM.0000000000000559 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CH2UH UT WOS:000353879700011 PM 25406602 ER PT J AU Taylor, JJ Williams, NR George, MS AF Taylor, Joseph J. Williams, Nolan R. George, Mark S. TI Beyond Neural Cubism: Promoting a Multidimensional View of Brain Disorders by Enhancing the Integration of Neurology and Psychiatry in Education SO ACADEMIC MEDICINE LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; OBSESSIVE-COMPULSIVE DISORDER; GRAY-MATTER DENSITY; CONTROLLED-TRIAL; STROKE PATIENTS; DOUBLE-BLIND; NEUROPSYCHIATRY; DEPRESSION; LAMOTRIGINE; 21ST-CENTURY AB Cubism was an influential early-20th-century art movement characterized by angular, disjointed imagery. The two-dimensional appearance of Cubist figures and objects is created through juxtaposition of angles. The authors posit that the constrained perspectives found in Cubism may also be found in the clinical classification of brain disorders. Neurological disorders are often separated from psychiatric disorders as if they stemmed from different organ systems. Maintaining two isolated clinical disciplines fractionalizes the brain in the same way that Pablo Picasso fractionalized figures and objects in his Cubist art. This Neural Cubism perpetuates a clinical divide that does not reflect the scope and depth of neuroscience. All brain disorders are complex and multidimensional, with aberrant circuitry and resultant psychopharmacology manifesting as altered behavior, affect, mood, or cognition. Trainees should receive a multidimensional education based on modern neuroscience, not a partial education based on clinical precedent. The authors briefly outline the rationale for increasing the integration of neurology and psychiatry and discuss a nested model with which clinical neuroscientists (neurologists and psychiatrists) can approach and treat brain disorders. C1 [Taylor, Joseph J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Williams, Nolan R.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [George, Mark S.] Med Univ S Carolina, Charleston, SC 29403 USA. [George, Mark S.] Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29403 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Taylor, JJ (reprint author), Brain Stimulat Lab, Inst Psychiat, 67 President St,Room 504 North, Charleston, SC 29414 USA. EM taylorjj@musc.edu OI Williams, Nolan/0000-0003-4368-3203 FU National Institute on Drug Abuse [F30 DA033748]; National Institute of Mental Health [R25 DA020537] FX Mr. Taylor is funded by the National Institute on Drug Abuse (F30 DA033748), and Dr. Williams is funded by the National Institute of Mental Health (R25 DA020537). NR 58 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD MAY PY 2015 VL 90 IS 5 BP 581 EP 586 DI 10.1097/ACM.0000000000000530 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CH2UH UT WOS:000353879700016 PM 25340364 ER PT J AU Bowen, JL Hirsh, D Aagaard, E Kaminetzky, CP Smith, M Hardman, J Chheda, SG AF Bowen, Judith L. Hirsh, David Aagaard, Eva Kaminetzky, Catherine P. Smith, Marie Hardman, Joseph Chheda, Shobhina G. TI Advancing Educational Continuity in Primary Care Residencies: An Opportunity for Patient-Centered Medical Homes SO ACADEMIC MEDICINE LA English DT Article ID CAMBRIDGE INTEGRATED CLERKSHIP; ENTRUSTABLE PROFESSIONAL ACTIVITIES; INTERNAL-MEDICINE; INTERPERSONAL CONTINUITY; CLINICAL EDUCATION; PERSONAL PHYSICIAN; TASK-FORCE; OUTCOMES; REDESIGN; PROGRAM AB Continuity of care is a core value of patients and primary care physicians, yet in graduate medical education (GME), creating effective clinical teaching environments that emphasize continuity poses challenges. In this Perspective, the authors review three dimensions of continuity for patient care-informational, longitudinal, and interpersonal-and propose analogous dimensions describing continuity for learning that address both residents learning from patient care and supervisors and interprofessional team members supporting residents' competency development. The authors review primary care GME reform efforts through the lens of continuity, including the growing body of evidence that highlights the importance of longitudinal continuity between learners and supervisors for making competency judgments. The authors consider the challenges that primary care residency programs face in the wake of practice transformation to patient-centered medical home models and make recommendations to maximize the opportunity that these practice models provide. First, educators, researchers, and policy makers must be more precise with terms describing various dimensions of continuity. Second, research should prioritize developing assessments that enable the study of the impact of interpersonal continuity on clinical outcomes for patients and learning outcomes for residents. Third, residency programs should establish program structures that provide informational and longitudinal continuity to enable the development of interpersonal continuity for care and learning. Fourth, these educational models and continuity assessments should extend to the level of the interprofessional team. Fifth, policy leaders should develop a meaningful recognition process that rewards academic practices for training the primary care workforce. C1 [Bowen, Judith L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bowen, Judith L.] Vet Hlth Adm, Off Acad Affiliat, Washington, DC USA. [Hirsh, David] Harvard Univ, Sch Med, Med, Boston, MA USA. [Hirsh, David] Cambridge Hlth Alliance, Dept Med, Cambridge, MA USA. [Aagaard, Eva] Univ Colorado, Med, Dept Med, Div Gen Internal Med, Aurora, CO USA. [Kaminetzky, Catherine P.] VA Puget Sound Hlth Care Syst, Staff Educ, Seattle, WA USA. [Kaminetzky, Catherine P.] Univ Washington, Sch Med, Seattle, WA USA. [Smith, Marie] Univ Connecticut, Community Pharm Practice, Storrs, CT USA. [Smith, Marie] Univ Connecticut, Practice & Publ Policy Partnerships, Storrs, CT USA. [Hardman, Joseph] Oregon Hlth & Sci Univ, Internal Med Resident Practice, Portland, OR 97201 USA. [Chheda, Shobhina G.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Gen Internal Med,Med Pediat, Madison, WI USA. RP Chheda, SG (reprint author), 750 Highland Ave,42870 HSLC, Madison, WI 53705 USA. EM sgc@medicine.wisc.edu FU Josiah Macy Jr. Foundation; United Health Foundation FX The authors wish to thank the Josiah Macy Jr. Foundation for financial support of the 2011 Society of General Internal Medicine Education Summit where the formative work for this paper took place. They also thank the United Health Foundation for financial support and the American College of Physicians, Primary Care Progress, and the Veterans Health Administration Office of Academic Affiliations for in-kind support of the Education Summit. Leaders from the American Board of Internal Medicine, American College of Physicians, Association of Program Directors in Internal Medicine, Association of Subspecialty Professors, Clerkship Directors in Internal Medicine, and the Society of General Internal Medicine served as advisors in designing the Education Summit. Although the majority of summit participants were university-, Veterans Affairs-, and community-based physician educators in internal medicine and family medicine, participants from nursing and pharmacy provided crucial contributions. NR 71 TC 1 Z9 1 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD MAY PY 2015 VL 90 IS 5 BP 587 EP 593 DI 10.1097/ACM.0000000000000589 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CH2UH UT WOS:000353879700017 PM 25470307 ER PT J AU Stein, D Chen, C Ackerly, DC AF Stein, Daniel Chen, Christopher Ackerly, D. Clay TI Disruptive Innovation in Academic Medical Centers: Balancing Accountable and Academic Care SO ACADEMIC MEDICINE LA English DT Article ID HEALTH CENTERS; MISSION; COSTS AB Numerous academic medicine leaders have argued that academic referral centers must prepare for the growing importance of accountability-driven payment models by adopting population health initiatives. Although this shift has merit, execution of this strategy will prove significantly more problematic than most observers have appreciated. The authors describe how successful implementation of an accountable care health strategy within a referral academic medical center (AMC) requires navigating a critical tension: The academic referral business model, driven by tertiary-level care, is fundamentally in conflict with population health. Referral AMCs that create successful value-driven population health systems within their organizations will in effect disrupt their own existing tertiary care businesses. The theory of disruptive innovation suggests that balancing the push and pull of academic and accountable care within a single organization is achievable. However, it will require significant shifts in resource allocation and changes in management structure to enable AMCs to make the inherent difficult choices and trade-offs that will ensue. On the basis of the theories of disruptive innovation, the authors present recommendations for how academic health systems can successfully navigate these issues as they transition toward accountability-driven care. C1 [Stein, Daniel] Walmart, Med & Clin Serv, Bentonville, AR USA. [Chen, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ackerly, D. Clay] Harvard Univ, Sch Med, Populat Hlth & Continuing Care Partners Healthcar, Boston, MA USA. RP Stein, D (reprint author), 702 SW 8th St, Bentonville, AR 72716 USA. EM Daniel.Stein@wal-mart.com NR 19 TC 4 Z9 4 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD MAY PY 2015 VL 90 IS 5 BP 594 EP 598 DI 10.1097/ACM.0000000000000606 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CH2UH UT WOS:000353879700018 PM 25517702 ER PT J AU Sabeti, H Kahn, MJ Sachs, BP AF Sabeti, Heerad Kahn, Marc J. Sachs, Benjamin P. TI The "For-Benefit" Academic Medical Center: A Solution for Survival SO ACADEMIC MEDICINE LA English DT Article ID HOSPITALS AB Academic medical centers (AMCs) are the backbone of the U.S. health care system. They provide a disproportionate share of charity care and serve as a training ground for future physicians. Yet, AMCs face profound economic challenges, from changes in funding to changes in the health care market. To survive, many AMCs will need to form integrated health systems, a process expected to cost tens, if not hundreds, of millions of dollars. Nearly all AMCs are structured as not-for-profit entities, which places restrictions on their ability to forge partnerships, pursue joint ventures, and access private capital, often essential elements for forming such integrated systems. An alternative model known as the "for-benefit" corporation can allow AMCs to retain their important social mission and the other advantages of their not-for-profit status while allowing them flexibility and access to both investment and philanthropic capital. To pursue the for-benefit pathway, AMCs have two options-either they could work within the constraints of existing laws to restructure themselves as for-benefit entities, or they could create, under federal law, a new for-benefit AMC model, allowing for the orderly conversion of not-for-profit AMCs. Essential components of a for-benefit AMC include a social purpose, access to multiple forms of capital, the use of earnings to support its purpose, transparency, aligned compensation, and tax exemptions. Restructuring an AMC as a for-benefit entity enables it to both advance shareholder value and further the public good. C1 [Sabeti, Heerad] Fourth Sector Networks, Raleigh, NC USA. [Kahn, Marc J.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Sachs, Benjamin P.] Harvard Univ, Sch Med, Boston, MA USA. [Sachs, Benjamin P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sachs, BP (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. EM bsachs@mgh.harvard.org NR 17 TC 0 Z9 0 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD MAY PY 2015 VL 90 IS 5 BP 599 EP 602 DI 10.1097/ACM.0000000000000583 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CH2UH UT WOS:000353879700019 PM 25426740 ER PT J AU Mansh, M White, W Gee-Tong, L Lunn, MR Obedin-Maliver, J Stewart, L Goldsmith, E Brenman, S Tran, E Wells, M Fetterman, D Garcia, G AF Mansh, Matthew White, William Gee-Tong, Lea Lunn, Mitchell R. Obedin-Maliver, Juno Stewart, Leslie Goldsmith, Elizabeth Brenman, Stephanie Tran, Eric Wells, Maggie Fetterman, David Garcia, Gabriel TI Sexual and Gender Minority Identity Disclosure During Undergraduate Medical Education: "In the Closet" in Medical School SO ACADEMIC MEDICINE LA English DT Article ID STUDENT MISTREATMENT; UNITED-STATES; GAY MEN; POPULATIONS; ORIENTATION; HEALTH; TIME AB Purpose To assess identity disclosure among sexual and gender minority (SGM) students pursuing undergraduate medical training in the United States and Canada. Method From 2009 to 2010, a survey was made available to all medical students enrolled in the 176 MD-and DO-granting medical schools in the United States and Canada. Respondents were asked about their sexual and gender identity, whether they were "out" (i.e., had publicly disclosed their identity), and, if they were not, their reasons for concealing their identity. The authors used a mixed-methods approach and analyzed quantitative and qualitative survey data. Results Of 5,812 completed responses (of 101,473 eligible respondents; response rate 5.7%), 920 (15.8%) students from 152 (of 176; 86.4%) institutions identified as SGMs. Of the 912 sexual minorities, 269 (29.5%) concealed their sexual identity in medical school. Factors associated with sexual identity concealment included sexual minority identity other than lesbian or gay, male gender, East Asian race, and medical school enrollment in the South or Central regions of North America. The most common reasons for concealing one's sexual identity were "nobody's business" (165/269; 61.3%), fear of discrimination in medical school (117/269; 43.5%), and social or cultural norms (110/269; 40.9%). Of the 35 gender minorities, 21 (60.0%) concealed their gender identity, citing fear of discrimination in medical school (9/21; 42.9%) and lack of support (9/21; 42.9%). Conclusions SGM students continue to conceal their identity during undergraduate medical training. Medical institutions should adopt targeted policies and programs to better support these individuals. C1 [Mansh, Matthew; White, William; Gee-Tong, Lea; Lunn, Mitchell R.; Obedin-Maliver, Juno; Stewart, Leslie; Goldsmith, Elizabeth; Brenman, Stephanie; Tran, Eric; Wells, Maggie; Fetterman, David; Garcia, Gabriel] Stanford Univ, Sch Med, Lesbian Gay Bisexual & Transgender Med Educ Res G, Stanford, CA 94305 USA. [Mansh, Matthew; White, William; Wells, Maggie] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Lunn, Mitchell R.] Univ Calif San Francisco, Sch Med, Dept Med, Div Nephrol, San Francisco, CA USA. [Obedin-Maliver, Juno] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Obedin-Maliver, Juno] Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Stewart, Leslie] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Goldsmith, Elizabeth] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Goldsmith, Elizabeth] Univ Minnesota, Sch Med, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Brenman, Stephanie] Univ Calif Los Angeles, Sch Med, Dept Emergency Med, Los Angeles, CA USA. [Tran, Eric] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Fetterman, David] Arkansas Evaluat Ctr, Pine Bluff, AR USA. [Fetterman, David] Charleston Univ, Sch Business & Leadership, Charleston, WV USA. [Fetterman, David] Univ Arkansas, Dept Educ, Pine Bluff, AR USA. [Fetterman, David] San Jose State Univ, Dept Anthropol, San Jose, CA 95192 USA. [Fetterman, David] Fetterman & Associates, San Jose, CA USA. [Garcia, Gabriel] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. RP Mansh, M (reprint author), Stanford Univ, Sch Med, 291 Campus Dr, Stanford, CA 94305 USA. EM mmansh@stanford.edu FU Stanford University School of Medicine; Office of the Dean, Stanford University School of Medicine; Office of Diversity and Leadership, Stanford University School of Medicine; Haas Center for Public Service at Stanford University; Stanford University Lesbian, Gay, Bisexual, and Transgender (LGBT) Community Resources Center; Stanford University School of Medicine Medical Scholars Fellowship Program FX This work was supported by Stanford University School of Medicine; Office of the Dean, Stanford University School of Medicine; Office of Diversity and Leadership, Stanford University School of Medicine; Haas Center for Public Service at Stanford University; and the Stanford University Lesbian, Gay, Bisexual, and Transgender (LGBT) Community Resources Center. W. White, J. Obedin-Maliver, and S. Brenman report receipt of support from the Stanford University School of Medicine Medical Scholars Fellowship Program. NR 36 TC 9 Z9 9 U1 5 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD MAY PY 2015 VL 90 IS 5 BP 634 EP 644 DI 10.1097/ACM.0000000000000657 PG 11 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CH2UH UT WOS:000353879700027 PM 25692563 ER PT J AU DesRoches, CM Buerhaus, P Dittus, RS Donelan, K AF DesRoches, Catherine M. Buerhaus, Peter Dittus, Robert S. Donelan, Karen TI Primary Care Workforce Shortages and Career Recommendations From Practicing Clinicians SO ACADEMIC MEDICINE LA English DT Article ID INTERNAL-MEDICINE RESIDENTS; OF-PRACTICE REGULATIONS; MANAGED HEALTH CENTERS; NURSE-PRACTITIONERS; REGISTERED NURSES; PHYSICIAN ASSISTANTS; JOB-SATISFACTION; WORK-ENVIRONMENT; NATIONAL SURVEYS; RNS AB Purpose The success of efforts to bolster the primary care workforce rests in part on how these clinicians view their professions and their willingness to recommend their careers to others. The authors sought to examine career and job satisfaction, perceptions of workforce shortages, and willingness to make career recommendations among primary care physicians (PCPs) and primary care nurse practitioners (PCNPs). Method In 2012, the authors mailed a national survey concerning the issues above to 1,914 randomly chosen clinicians found on national databases: 957 PCPs and 957 PCNPs. Results A total of 972 eligible clinicians (505 PCPs, 467 PCNPs) returned the survey. Using standard opinion research procedures, the authors estimated there were approximately 1,589 eligible clinicians in their sample (response rate, 61.2%). PCNPs and PCPs were more likely to recommend a career as a PCNP than as a PCP, despite the perception among all clinicians of a serious shortage of PCPs nationally and in their own communities. This finding held among PCNPs who reported low workplace autonomy and among PCPs reporting that they were satisfied with their own careers. Conclusions Efforts to solve the primary care workforce shortage that ignore the significant dissatisfaction of PCPs with their own careers are unlikely to be successful. Simply adding training slots and increasing reimbursement rates will do little to solve the problem if PCPs continue to view their own careers as ones they cannot recommend to others. C1 [DesRoches, Catherine M.] Math Policy Res, Cambridge, MA 02139 USA. [Buerhaus, Peter] Vanderbilt Univ, Ctr Interdisciplinary Hlth Workforce Studies, Nashville, TN 37235 USA. [Dittus, Robert S.] Vanderbilt Univ, Publ Hlth & Hlth care, Nashville, TN 37235 USA. [Dittus, Robert S.] VA Tennessee Valley Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Donelan, Karen] Massachusetts Gen Hosp, Dept Med, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP DesRoches, CM (reprint author), Math Policy Res, 955 Massachusetts Ave,Suite 900, Cambridge, MA 02139 USA. EM cdesroches@mathematica-mpr.com FU Robert Wood Johnson Foundation; Gordon and Betty Moore Foundation; Johnson & Johnson Campaign for Nursing's Future FX This work was supported by grants from the Robert Wood Johnson Foundation, the Gordon and Betty Moore Foundation, and Johnson & Johnson Campaign for Nursing's Future. NR 47 TC 2 Z9 2 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD MAY PY 2015 VL 90 IS 5 BP 671 EP 677 DI 10.1097/ACM.0000000000000591 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CH2UH UT WOS:000353879700031 PM 25539519 ER PT J AU Mugo, PM Sanders, EJ Mutua, G van der Elst, E Anzala, O Barin, B Bangsberg, DR Priddy, FH Haberer, JE AF Mugo, Peter Mwangi Sanders, Eduard J. Mutua, Gaudensia van der Elst, Elisabeth Anzala, Omu Barin, Burc Bangsberg, David R. Priddy, Frances H. Haberer, Jessica E. TI Understanding Adherence to Daily and Intermittent Regimens of Oral HIV Pre-exposure Prophylaxis Among Men Who Have Sex with Men in Kenya SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Pre-exposure prophylaxis; Intermittent PrEP adherence; Men who have sex with men ID ANTIRETROVIRAL PROPHYLAXIS; TRANSGENDER WOMEN; PREVENTION; TRANSMISSION; INFECTION; TENOFOVIR; AFRICA; TRIALS AB A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:1:2:1), and followed for 4 months. By electronic monitoring, median adherence for daily dosing was 80 %. Median adherence for intermittent dosing was 71 % per a "relaxed" definition (accounting for off-prescription dosing) and 40 % per a "strict" definition (limited to the prescription). Factors associated with lower adherence included travel, transactional sex, and longer follow-up; higher adherence was associated with daily dosing and an income. The definition of intermittent dosing strongly affects interpretation of adherence. These findings suggest interventions should address challenges of mobility, sex work, and long-term PrEP. C1 [Mugo, Peter Mwangi; Sanders, Eduard J.; van der Elst, Elisabeth] Kenya Govt Med Res Ctr, Ctr Geog Med Coast, Kilifi, Kenya. [Sanders, Eduard J.] Univ Oxford, Nuffield Dept Clin Med, Headington, England. [Mutua, Gaudensia; Anzala, Omu] Univ Nairobi, Inst Clin Res, Kenya AIDS Vaccine Initiat, Nairobi, Kenya. [Barin, Burc] EMMES Corp, Rockville, MD USA. [Bangsberg, David R.; Haberer, Jessica E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bangsberg, David R.; Haberer, Jessica E.] Harvard Univ, Sch Med, Boston, MA USA. [Priddy, Frances H.] Int AIDS Vaccine Initiat, New York, NY USA. RP Mugo, PM (reprint author), Kenya Govt Med Res Ctr, Ctr Geog Med Coast, Kilifi, Kenya. EM pmugo@kemri-wellcome.org FU Bill & Melinda Gates Foundation; Ministry of Foreign Affairs of Denmark; Irish Aid; Ministry of Finance of Japan; Ministry of Foreign Affairs of the Netherlands; Norwegian Agency for Development Cooperation (NORAD); United Kingdom Department for International Development (DFID); United States Agency for International Development (USAID) FX We would like to acknowledge the contributions of the study volunteers to this research. We would like to thank the research center staff in Kilifi and Nairobi. IAVI's work is made possible by generous support from many donors including: the Bill & Melinda Gates Foundation; the Ministry of Foreign Affairs of Denmark; Irish Aid; the Ministry of Finance of Japan; the Ministry of Foreign Affairs of the Netherlands; the Norwegian Agency for Development Cooperation (NORAD); the United Kingdom Department for International Development (DFID), and the United States Agency for International Development (USAID). The full list of IAVI donors is available at www.iavi.org. This paper was published with permission from the Director of KEMRI. NR 32 TC 3 Z9 4 U1 2 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD MAY PY 2015 VL 19 IS 5 BP 794 EP 801 DI 10.1007/s10461-014-0958-x PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CH2WU UT WOS:000353886500006 PM 25432877 ER PT J AU Ware, NC Pisarski, EE Haberer, JE Wyatt, MA Tumwesigye, E Baeten, JM Celum, CL Bangsberg, DR AF Ware, Norma C. Pisarski, Emily E. Haberer, Jessica E. Wyatt, Monique A. Tumwesigye, Elioda Baeten, Jared M. Celum, Connie L. Bangsberg, David R. TI Lay Social Resources for Support of Adherence to Antiretroviral Prophylaxis for HIV Prevention Among Serodiscordant Couples in sub-Saharan Africa: A Qualitative Study SO AIDS AND BEHAVIOR LA English DT Article DE HIV Prevention; PrEP; Adherence; Serodiscordant Couples; Sub-Saharan Africa; HIV Health Care Delivery in Africa ID PREEXPOSURE PROPHYLAXIS; DISCORDANT COUPLES; TRANSPORT COSTS; RURAL UGANDA; THERAPY; TRANSMISSION; INFECTION; PROGRAM; TRIALS; WOMEN AB Effectiveness of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention will require high adherence. Using qualitative data, this paper identifies potential lay social resources for support of PrEP adherence by HIV serodiscordant couples in Uganda, laying the groundwork for incorporation of these resources into adherence support initiatives as part of implementation. The qualitative analysis characterizes support for PrEP adherence provided by HIV-infected spouses, children, extended family members, and the larger community. Results suggest social resources for support of PrEP adherence in Africa are plentiful outside formal health care settings and health systems and that couples will readily use them. The same shortage of health professionals that impeded scale-up of antiretroviral treatment for HIV/AIDS in Africa promises to challenge delivery of PrEP. Building on the treatment scale-up experience, implementers can address this challenge by examining the value of lay social resources for adherence support in developing strategies for delivery of PrEP. C1 [Ware, Norma C.; Pisarski, Emily E.; Wyatt, Monique A.; Bangsberg, David R.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02163 USA. [Ware, Norma C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Haberer, Jessica E.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Haberer, Jessica E.; Bangsberg, David R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Tumwesigye, Elioda] Kabwohe Clin Res Ctr, Kabwohe, Uganda. [Baeten, Jared M.; Celum, Connie L.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Baeten, Jared M.; Celum, Connie L.] Univ Washington, Dept Med, Seattle, WA USA. [Baeten, Jared M.; Celum, Connie L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Dept Med, Mbarara, Uganda. RP Ware, NC (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, 641 Huntington Ave, Boston, MA 02163 USA. EM norma_ware@hms.harvard.edu FU Bill and Melinda Gates Foundation [OPP52516] FX The authors gratefully acknowledge the contributions of Jacqueline Karuhanga and Deo Agaba, who conducted the qualitative interviews. Alex Kintu provided supervision and support in Uganda for the qualitative data collection process. Katherine K. Thomas provided data on rates of adherence for qualitative participants and responded to requests for information as part of the revision process. Lara Kidoguchi helped in identifying study participants. Melanie Tam provided support for the revision process. Financial support was provided by a grant from the Bill and Melinda Gates Foundation to David R. Bangsberg [OPP52516]. Sincere thanks to all who gave of their time to participate in the qualitative interviews. NR 73 TC 3 Z9 3 U1 1 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD MAY PY 2015 VL 19 IS 5 BP 811 EP 820 DI 10.1007/s10461-014-0899-4 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CH2WU UT WOS:000353886500008 PM 25267114 ER PT J AU Murooka, TT Sharaf, RR Mempel, TR AF Murooka, Thomas T. Sharaf, Radwa R. Mempel, Thorsten R. TI Large Syncytia in Lymph Nodes Induced by CCR5-Tropic HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material ID LYMPHOCYTES C1 [Murooka, Thomas T.] Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada. [Murooka, Thomas T.] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. [Sharaf, Radwa R.; Mempel, Thorsten R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA USA. RP Murooka, TT (reprint author), Univ Manitoba, Apotex Ctr, Room 433,750 McDermot Ave, Winnipeg, MB R3E 0T5, Canada. EM thomas.murooka@umanitoba.ca FU NIAID NIH HHS [R01 AI097052]; NIDA NIH HHS [R01 DA036298] NR 4 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 2015 VL 31 IS 5 BP 471 EP 472 DI 10.1089/aid.2014.0378 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA CH0FN UT WOS:000353695000001 PM 25835064 ER PT J AU Pitcher, A Emberson, J Lacro, RV Sleeper, LA Stylianou, M Mahony, L Pearson, GD Groenink, M Mulder, BJ Zwinderman, AH De Backer, J De Paepe, AM Arbustini, E Erdem, G Jin, XY Flather, MD Mullen, MJ Child, AH Forteza, A Evangelista, A Chiu, HH Wu, MH Sandor, G Bhatt, AB Creager, MA Devereux, RB Loeys, B Forfar, JC Neubauer, S Watkins, H Boileau, C Jondeau, G Dietz, HC Baigent, C AF Pitcher, Alex Emberson, Jonathan Lacro, Ronald V. Sleeper, Lynn A. Stylianou, Mario Mahony, Lynn Pearson, Gail D. Groenink, Maarten Mulder, Barbara J. Zwinderman, Aeilko H. De Backer, Julie De Paepe, Anne M. Arbustini, Eloisa Erdem, Guliz Jin, Xu Yu Flather, Marcus D. Mullen, Michael J. Child, Anne H. Forteza, Alberto Evangelista, Arturo Chiu, Hsin-Hui Wu, Mei-Hwan Sandor, George Bhatt, Ami B. Creager, Mark A. Devereux, Richard B. Loeys, Bart Forfar, J. Colin Neubauer, Stefan Watkins, Hugh Boileau, Catherine Jondeau, Guillaume Dietz, Harry C. Baigent, Colin TI Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration SO AMERICAN HEART JOURNAL LA English DT Article ID AORTIC-ROOT DILATION; CLINICAL-TRIAL; YOUNG-ADULTS; BETA-BLOCKER; LOSARTAN; ATENOLOL; THERAPY; PROGRESSION; ANEURYSM; CHILDREN AB Rationale A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of beta-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial. Design A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus beta-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will bemade available online (http:// www.ctsu.ox.ac.uk/research/meta-trials). C1 [Pitcher, Alex] Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford OX3 9DU, England. [Emberson, Jonathan; Baigent, Colin] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 9DU, England. [Emberson, Jonathan; Baigent, Colin] Univ Oxford, Epidemiol Studies Unit, Oxford OX3 9DU, England. [Lacro, Ronald V.; Pearson, Gail D.] Childrens Hosp Boston, Boston, MA USA. [Lacro, Ronald V.; Pearson, Gail D.; Creager, Mark A.] Harvard Univ, Sch Med, Boston, MA USA. [Sleeper, Lynn A.] New England Res Inst, Watertown, MA 02172 USA. [Stylianou, Mario] NHLBI, NIH, Bethesda, MD 20892 USA. [Mahony, Lynn] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Groenink, Maarten; Mulder, Barbara J.; Zwinderman, Aeilko H.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [De Backer, Julie; De Paepe, Anne M.] Univ Hosp Ghent, Ctr Med Genet, Ghent, Belgium. [De Backer, Julie] Univ Hosp Ghent, Dept Cardiol, Ghent, Belgium. [Arbustini, Eloisa] IRCCS Fdn, San Matteo Hosp, Ctr Inherited Cardiovasc Dis, Pavia, Italy. [Erdem, Guliz] Royal Brompton & Harefield NHS Trust, Clin Trials & Evaluat Unit, London, England. [Jin, Xu Yu; Forfar, J. Colin] John Radcliffe Hosp, Oxford OX3 9DU, England. [Flather, Marcus D.] Univ E Anglia, UCL Inst Cardiovasc Sci, Norwich NR4 7TJ, Norfolk, England. [Mullen, Michael J.; Child, Anne H.] Univ London, St Georges Hosp, Dept Cardiac & Vasc Sci, London, England. [Forteza, Alberto] Hosp Univ 12 de Octubre, Madrid, Spain. [Evangelista, Arturo] Hosp Valle De Hebron, Dept Cardiol, Marfan Sydrome Unit, Barcelona, Spain. [Chiu, Hsin-Hui] Taipei Med Univ Hosp, Dept Pediat, Taipei, Taiwan. [Chiu, Hsin-Hui] Taipei Med Univ Hosp, Adult Congenital Heart Ctr, Taipei, Taiwan. [Wu, Mei-Hwan] Natl Taiwan Univ Hosp, Dept Pediat, Taipei 10016, Taiwan. [Wu, Mei-Hwan] Natl Taiwan Univ Hosp, Adult Congenital Heart Ctr, Taipei, Taiwan. [Sandor, George] British Columbia Childrens Hosp, Childrens Heart Ctr, Vancouver, BC, Canada. [Bhatt, Ami B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Creager, Mark A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Devereux, Richard B.] Weill Cornell Med Coll, New York, NY USA. [Devereux, Richard B.] New York Presbyterian Hosp, New York, NY USA. [Loeys, Bart] Univ Antwerp, Fac Med & Hlth Sci, Ctr Med Genet, B-2020 Antwerp, Belgium. [Loeys, Bart] Univ Antwerp Hosp, Antwerp, Belgium. [Neubauer, Stefan] Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford Ctr Clin Magnet Resonance Res, Oxford OX3 9DU, England. [Watkins, Hugh] Univ Oxford, Radcliffe Dept Med, Oxford OX3 9DU, England. [Boileau, Catherine] Hop Xavier Bichat Claude Bernard, Dept Genet, Inserm LVTS U1148, Paris, France. [Jondeau, Guillaume] Hop Bichat Claude Bernard, AP HP, Ctr Natl Reference Syndrome Marfan & Apparentes, Serv Cardiol,INSERM LVTS U1148, F-75877 Paris, France. [Dietz, Harry C.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Dietz, Harry C.] Howard Hughes Med Inst, Baltimore, MD USA. RP Pitcher, A (reprint author), Univ Oxford, John Radcliffe Hosp, Radcliffe Dept Med, Div Cardiovasc Med, Oxford OX3 9DU, England. EM alex.pitcher@cardiov.ox.ac.uk FU Arthritis Research UK; British Heart Foundation [FS/08/077/26366, RE/13/1/30181]; Medical Research Council [, MC_U137686849]; Wellcome Trust NR 33 TC 12 Z9 13 U1 2 U2 10 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 MAY PY 2015 VL 169 IS 5 BP 605 EP 612 DI 10.1016/j.ahj.2015.01.011 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH6US UT WOS:000354172400006 PM 25965707 ER PT J AU O'Donoghue, ML Glaser, R Aylward, PE Cavender, MA Crisp, A Fox, KAA Laws, I Lopez-Sendon, JL Steg, PG Theroux, P Sabatine, MS Morrow, DA AF O'Donoghue, Michelle L. Glaser, Ruchira Aylward, Philip E. Cavender, Matthew A. Crisp, Adam Fox, Keith A. A. Laws, Ian Lopez-Sendon, Jose L. Steg, P. Gabriel Theroux, Pierre Sabatine, Marc S. Morrow, David A. TI Rationale and design of the LosmApimod To Inhibit p38 MAP kinase as a TherapeUtic target and moDify outcomes after an acute coronary syndromE trial SO AMERICAN HEART JOURNAL LA English DT Article ID ACTIVATED PROTEIN-KINASE; HEART-FAILURE; INTERLEUKIN-6 RECEPTOR; MYOCARDIAL-INFARCTION; RHEUMATOID-ARTHRITIS; IN-VIVO; DISEASE; INFLAMMATION; ATHEROSCLEROSIS; PREVENTION AB Background p38 mitogen-activated protein kinase (MAPK) mediates cytokine production and amplification of the inflammatory cascade. Through inhibition of p38 MAPK, losmapimod appears to attenuate the inflammatory response in the vascular wall and thus may help stabilize plaques. Study design The LATITUDE-TIMI 60 trial is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study planned to be conducted in a 3-stage design. Overall, the trial is designed to include 25,500 patients hospitalized with non-ST-elevation or ST-elevation myocardial infarction (MI) randomized to oral losmapimod (7.5 mg twice daily) versus matching placebo. Part A consists of a leading cohort (n = 3,500) that will provide an initial assessment of safety and exploratory efficacy before progressing to part B. Part B (n = similar to 22,000) of the study is event driven and will provide the primary assessment of efficacy. An independent safety review will be conducted after 3,500 patients in part B1 to determine whether a more focused schedule of clinic visits and laboratory assessments can be implemented (part B2). All patients are to be treated with study drug until week 12 and followed up until week 24. The primary end point is the composite of cardiovascular death, MI, or severe recurrent ischemia requiring urgent coronary revascularization. The key secondary end point is the composite of cardiovascular death or MI. The trial is designed to provide = 90% power for the primary end point. Conclusions The LATITUDE-TIMI60 trial will determine the efficacy and safety of short-term p38MAPK inhibition with losmapimod in acute MI. The trial design adopts a stepwise approach to decision making and collection of data. C1 [O'Donoghue, Michelle L.; Cavender, Matthew A.; Sabatine, Marc S.; Morrow, David A.] Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. [Glaser, Ruchira; Crisp, Adam; Laws, Ian] GlaxoSmithKline, King Of Prussia, PA USA. [Aylward, Philip E.] Flinders Univ S Australia, Med Ctr, South Australian Hlth & Med Res Inst, Adelaide, SA 5001, Australia. [Fox, Keith A. A.] Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland. [Lopez-Sendon, Jose L.] Univ Hosp La Paz, Cardiovasc Div, Madrid, Spain. [Steg, P. Gabriel] Univ Paris Diderot, Sorbonne Paris Cite, DHU FIRE, FACT, Paris, France. [Steg, P. Gabriel] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, NHLI, London, England. [Theroux, Pierre] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Theroux, Pierre] Univ Montreal, Montreal, PQ H1T 1C8, Canada. RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. NR 24 TC 10 Z9 11 U1 0 U2 4 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 MAY PY 2015 VL 169 IS 5 BP 622 EP U60 DI 10.1016/j.ahj.2015.02.012 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH6US UT WOS:000354172400008 PM 25965709 ER PT J AU Bentley-Lewis, R Aguilar, D Riddle, MC Claggett, B Diaz, R Dickstein, K Gerstein, HC Johnston, P Kober, LV Lawson, F Lewis, EF Maggioni, AP McMurray, JJV Ping, L Probstfield, JL Solomon, SD Tardif, JC Wu, Y Pfeffer, MA AF Bentley-Lewis, Rhonda Aguilar, David Riddle, Matthew C. Claggett, Brian Diaz, Rafael Dickstein, Kenneth Gerstein, Hertzel C. Johnston, Peter Kober, Lars V. Lawson, Francesca Lewis, Eldrin F. Maggioni, Aldo P. McMurray, John J. V. Ping, Lin Probstfield, Jeffrey L. Solomon, Scott D. Tardif, Jean-Claude Wu, Yujun Pfeffer, Marc A. CA ELIXA Investigators TI Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo SO AMERICAN HEART JOURNAL LA English DT Article ID TYPE-2 DIABETES-MELLITUS; ELEVATION MYOCARDIAL-INFARCTION; RECEPTOR AGONIST LIXISENATIDE; RANDOMIZED CLINICAL-TRIALS; ONCE-DAILY LIXISENATIDE; REPERFUSION INJURY; EXENATIDE TWICE; GLUCOSE CONTROL; HEART-FAILURE; DOUBLE-BLIND AB Background Cardiovascular (CV) disease is the leading cause of morbidity andmortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. Methods ELIXA (www.clinicaltrials.govno.NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. Results Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean +/- SD age was 60.3 +/- 9.7 years, body mass index was 30.2 +/- 5.7 kg/m(2), and duration of T2DM was 9.3 +/- 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. Conclusion ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk. C1 [Bentley-Lewis, Rhonda] Massachusetts Gen Hosp, Diabet Unit, Dept Med, Boston, MA 02114 USA. [Aguilar, David] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Riddle, Matthew C.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Claggett, Brian; Lewis, Eldrin F.; Solomon, Scott D.; Pfeffer, Marc A.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Boston, MA 02115 USA. [Diaz, Rafael] Estudios Cardiol Latinoamer, Rosario, Santa Fe, Argentina. [Dickstein, Kenneth] Univ Bergen, Stavanger Univ Hosp, Stavanger, Norway. [Gerstein, Hertzel C.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Gerstein, Hertzel C.] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada. [Gerstein, Hertzel C.] Hamilton Hlth Sci, Hamilton, ON, Canada. [Johnston, Peter; Lawson, Francesca; Ping, Lin; Wu, Yujun] Sanofi Aventis, Bridgewater, NJ USA. [Kober, Lars V.] Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Ctr Heart, Copenhagen, Denmark. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [McMurray, John J. V.] Univ Glasgow, British Heart Fdn Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Probstfield, Jeffrey L.] Univ Washington, Med Ctr, Dept Med Cardiol, Seattle, WA 98195 USA. [Tardif, Jean-Claude] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. RP Bentley-Lewis, R (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM rbentleylewis@partners.org RI Delgado, Elias/B-2634-2013; Rafalskiy, Vladimir/G-3172-2013; Zadionchenko, Vladimir/A-7445-2016; Del Prato, Stefano/K-3405-2016; Ponikowski, Piotr/O-6454-2015; Saravanan, Ponnusamy/M-6142-2016; scarpa, aldo/K-6832-2016; OI Delgado, Elias/0000-0001-6114-9712; Rafalskiy, Vladimir/0000-0002-2503-9580; Zadionchenko, Vladimir/0000-0003-2377-5266; Del Prato, Stefano/0000-0002-5388-0270; Ponikowski, Piotr/0000-0002-3391-7064; Saravanan, Ponnusamy/0000-0002-9566-2626; scarpa, aldo/0000-0003-1678-739X; Podoleanu, Cristian/0000-0001-9987-2519; Giordano, Carla/0000-0003-1731-9395; Ntsekhe, Mpiko/0000-0002-0851-7675; Jendle, Johan/0000-0003-1025-1682; Barbarash, Olga/0000-0002-4642-3610; Papademetriou, Vasilios/0000-0002-2882-2757; Maggioni, Aldo Pietro/0000-0003-2764-6779; mcmurray, john/0000-0002-6317-3975; Castro, Maria Graciela/0000-0003-2237-2756 NR 53 TC 22 Z9 24 U1 1 U2 12 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 MAY PY 2015 VL 169 IS 5 BP 631 EP U75 DI 10.1016/j.ahj.2015.02.002 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH6US UT WOS:000354172400009 PM 25965710 ER PT J AU Sharma, AK Vegh, E Orencole, M Miller, A Blendea, D Moore, S Lewis, GD Singh, JP Parks, KA Heist, EK AF Sharma, Ajay K. Vegh, Eszter Orencole, Mary Miller, Alexandra Blendea, Dan Moore, Stephanie Lewis, Gregory D. Singh, Jagmeet P. Parks, Kimberly A. Heist, E. Kevin TI Association of Hypothyroidism With Adverse Events in Patients With Heart Failure Receiving Cardiac Resynchronization Therapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SUBCLINICAL THYROID-DYSFUNCTION; CARDIOVASCULAR HEALTH; HORMONE METABOLISM; GENE-EXPRESSION; RISK; DISEASE; SYSTEM; T-3 AB Hypothyroidism is associated with an adverse prognosis in cardiac patients in general and in particular in patients with heart failure (HF). The aim of this study was to evaluate the impact of hypothyroidism on patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the, impact of level of control of hypothyroidism on risk of adverse events after CRT implantation was also evaluated. We included consecutive patients in whom a CRT device was implanted from April 2004 to April 2010 at our institution with sufficient follow-up data available for analysis; 511 patients were included (age 68.5 +/- 12.4 years, women 20.4%); 84 patients with a clinical history of hypothyroidism, on treatment with thyroid hormone repletion or serum thyroid-stimulating hormone level >= 5.00 mu U/ml, were included in the hypothyroid group. The patients were followed for up to 3 years after implant for a composite end point of hospitalization for HF, left ventricular assist device placement, or heart transplant and cardiac death; 215 composite end point events were noted in this period. In a multivariate model, hypothyroidism (hazard ratio [HR] 1.46, 95% confidence interval, [CI] 1.027 to 2.085, p = 0.035), female gender (HR 0.64, 95% CI 0.428 to 0.963, p = 0.032), and creatinine (BR 1.26, 95% CI 1.145 to 1.382, p <0.001) were significantly associated with occurrence of the composite end point; 53.6% of patients with hypothyroidism at baseline developed the composite end point compared with 39.8% of those with euthyroidism (p = 0.02). In conclusion, hypothyroidism is associated with a worse prognosis after CRT implantation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Sharma, Ajay K.; Vegh, Eszter; Orencole, Mary; Miller, Alexandra; Blendea, Dan; Moore, Stephanie; Lewis, Gregory D.; Singh, Jagmeet P.; Parks, Kimberly A.; Heist, E. Kevin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Heart Ctr, Boston, MA 02115 USA. RP Heist, EK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Heart Ctr, Boston, MA 02115 USA. EM kheist@partners.org NR 29 TC 0 Z9 0 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2015 VL 115 IS 9 BP 1249 EP 1253 DI 10.1016/j.amjcard.2015.01.559 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH3JK UT WOS:000353926800013 PM 25743211 ER PT J AU Tamers, SL Thompson, B Cheadle, AD Zheng, YY Bishop, SK Beresford, SAA AF Tamers, Sara L. Thompson, Beti Cheadle, Allen D. Zheng, Yingye Bishop, Sonia K. Beresford, Shirley A. A. TI Promoting Changes in Obesogenic Behaviors: Does Coworker Social Support Play a Role? SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Nutritional Status; Physical Activity; Body Mass Index; Social Support; Worksite Prevention Research ID RANDOMIZED CONTROLLED-TRIAL; IMPROVE WARFARIN ADHERENCE; FINANCIAL INCENTIVES; SMOKING-CESSATION; UNITED-STATES; WEIGHT-LOSS; LEVEL DATA; HEALTH; ECONOMICS; ADULTS AB Purpose. To examine the association between worksite social support and changes in diet, physical activity, and body mass index (BMI). Design. Cohort analysis of an underlying randomized, controlled weight gain prevention worksite trial: Promoting Activity and Changes in Eating. Setting. The trial occurred in the greater Seattle area. Subjects. Baseline and follow-up data were obtained on a nested cohort of employees (n = 958-1078) from 33 small- to medium-sized worksites. Measures. Worksite social support, diet, physical activity, and BMI measures were assessed using a self-reported questionnaire. Analysis. To adjust for multilevel data and multiple time points, we used generalized estimating equations and logistic mixed models. Results. Higher baseline worksite social support was associated with greater changes in fruit and vegetable intake (p = .001; summary food-frequency questions). Conclusion. This study does not support a conclusive relationship between worksite social support and health behavior change. C1 [Tamers, Sara L.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Tamers, Sara L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tamers, Sara L.; Thompson, Beti; Cheadle, Allen D.; Zheng, Yingye; Beresford, Shirley A. A.] Univ Washington, Seattle, WA 98195 USA. [Tamers, Sara L.; Thompson, Beti; Zheng, Yingye; Bishop, Sonia K.; Beresford, Shirley A. A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Tamers, SL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave, Boston, MA 02115 USA. EM stamers@post.harvard.edu FU NCI NIH HHS [R25 CA057713, R25 CA092408]; NHLBI NIH HHS [R01 HL079491] NR 40 TC 0 Z9 0 U1 1 U2 6 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 EI 2168-6602 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD MAY-JUN PY 2015 VL 29 IS 5 BP 311 EP 323 DI 10.4278/ajhp.130709-ARB-352 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH5JO UT WOS:000354072100007 PM 24670072 ER PT J AU Rao, SR Reisman, JI Kressin, NR Berlowitz, DR Ash, AS Ozonoff, A Miller, DR Hylek, EM Zhao, SB Rose, AJ AF Rao, Sowmya R. Reisman, Joel I. Kressin, Nancy R. Berlowitz, Dan R. Ash, Arlene S. Ozonoff, Al Miller, Donald R. Hylek, Elaine M. Zhao, Shibei Rose, Adam J. TI Explaining Racial Disparities in Anticoagulation Control: Results From a Study of Patients at the Veterans Administration SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE racial and ethnic disparities; anticoagulants; quality of health care; warfarin ID QUALITY-OF-CARE; IMPROVE ANTICOAGULATION; ATRIAL-FIBRILLATION; ORAL ANTICOAGULANT; GEOCODING PROJECT; HEALTH; AFFAIRS; RANGE; WARFARIN; THERAPY AB Higher rates of stroke, major hemorrhage, and death among black patients receiving warfarin, compared with white patients, is likely related to poorer anticoagulation control. The research team investigated patient-level and site-level factors that might account for this group difference. A summary measure of anticoagulation control (percent time in therapeutic range [TTR]), patient characteristics, and site-level process of care measures were obtained for 9572 black and 88 481 white patients at the Veterans Health Administration. The research team studied disparity in TTR adjusting for patient and site characteristics. Mean unadjusted TTR for black patients was 6.5% lower than for white patients (P < .001). After accounting for the younger age of blacks, greater degrees of medication use, hospitalization, poverty, living in the South, and 11 other patient characteristics, only 2.0% of this racial disparity persisted. Process of care measures had minimal additional effect. These findings may inform efforts to reduce this racial disparity in achieving good anticoagulation control. C1 [Rao, Sowmya R.; Reisman, Joel I.; Berlowitz, Dan R.; Ash, Arlene S.; Ozonoff, Al; Miller, Donald R.; Zhao, Shibei; Rose, Adam J.] Bedford VA Med Ctr, Bedford, MA USA. [Rao, Sowmya R.; Ash, Arlene S.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Kressin, Nancy R.; Berlowitz, Dan R.; Hylek, Elaine M.; Rose, Adam J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Berlowitz, Dan R.; Miller, Donald R.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Ozonoff, Al] Boston Childrens Hosp, Boston, MA USA. RP Rao, SR (reprint author), Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, 368 Plantation St, Worcester, MA 01605 USA. EM sowmya.rao@umassmed.edu FU Veterans Affairs Health Services Research and Development Service [IIR-10-374, RCS-02-066-1]; National Institutes of Health [R01NS070307] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was supported by a grant from the Veterans Affairs Health Services Research and Development Service (IIR-10-374). Dr Kressin is supported by a Senior Research Career Scientist award from the Veterans Affairs Health Services Research and Development Service (RCS-02-066-1). Dr Hylek is supported by National Institutes of Health grant R01NS070307. NR 39 TC 1 Z9 1 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAY-JUN PY 2015 VL 30 IS 3 BP 214 EP 222 DI 10.1177/1062860614526282 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CH4GH UT WOS:000353991400002 PM 24642366 ER PT J AU Butwick, AJ Carvalho, B Blumenfeld, YJ El-Sayed, YY Nelson, LM Bateman, BT AF Butwick, Alexander J. Carvalho, Brendan Blumenfeld, Yair J. El-Sayed, Yasser Y. Nelson, Lorene M. Bateman, Brian T. TI Second-line uterotonics and the risk of hemorrhage-related morbidity SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology CY MAY 05-09, 2014 CL Toronto, CANADA SP Soc Obstet Anesthesia & Perinatol DE cesarean delivery; hemorrhage; morbidity; uterine atony ID POSTPARTUM HEMORRHAGE; UNITED-STATES; MATERNAL MORBIDITY; OXYTOCIN RECEPTORS; CESAREAN-DELIVERY; LABOR; HOSPITALIZATIONS; MYOMETRIUM; MANAGEMENT; INCREASE AB OBJECTIVE: Uterine atony is a leading cause of postpartum hemorrhage. Although most cases of postpartum hemorrhage respond to first-line therapy with uterine massage and oxytocin administration, second-line uterotonics including methylergonovine and carboprost are integral for the management of refractory uterine atony. Despite their ubiquitous use, it is uncertain whether the risk of hemorrhage-related morbidity differs in women exposed to methylergonovine or carboprost at cesarean delivery. STUDY DESIGN: We performed a secondary analysis using the Maternal-Fetal Medicine Units Network Cesarean Registry. We identified women who underwent cesarean delivery and received either methylergonovine or carboprost for refractory uterine atony. The primary outcome was hemorrhage-related morbidity defined as intraoperative or postoperative red blood cell transfusion or the need for additional surgical interventions including uterine artery ligation, hypogastric artery ligation, or peripartum hysterectomy for atony. We compared the risk of hemorrhage-related morbidity in those exposed to methylergonovine vs carboprost. Propensity-score matching was used to account for potential confounders. RESULTS: The study cohort comprised 1335 women; 870 (65.2%) women received methylergonovine and 465 (34.8%) women received carboprost. After accounting for potential confounders, the risk of hemorrhage-related morbidity was higher in the carboprost group than the methylergonovine group (relative risk, 1.7; 95% confidence interval, 1.2-2.6). CONCLUSION: In this propensity score-matched analysis, methylergonovine was associated with reduced risk of hemorrhage-related morbidity during cesarean delivery compared to carboprost. Based on these results, methylergonovine may be a more effective second-line uterotonic. C1 [Butwick, Alexander J.; Carvalho, Brendan] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. [Blumenfeld, Yair J.; El-Sayed, Yasser Y.] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Stanford, CA 94305 USA. [Nelson, Lorene M.] Stanford Univ, Sch Med, Dept Hlth Res Policy, Stanford, CA 94305 USA. [Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Massachusetts Gen Hosp, Div Pharmacoepidemiol & Pharmacoecon,Dept Med,Dep, Boston, MA 02115 USA. RP Butwick, AJ (reprint author), Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. EM ajbut@stanford.edu OI Butwick, Alexander/0000-0002-2048-0879 FU NICHD NIH HHS [1K23HD070972, K08 HD075831, K08HD075831, K23 HD070972] NR 33 TC 4 Z9 4 U1 0 U2 1 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 MAY PY 2015 VL 212 IS 5 AR 642.e1 DI 10.1016/j.ajog.2015.01.008 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CG8XH UT WOS:000353598500025 PM 25582104 ER PT J AU Mitchell, CM Haick, A Nkwopara, E Garcia, R Rendi, M Agnew, K Fredricks, DN Eschenbach, D AF Mitchell, Caroline M. Haick, Anoria Nkwopara, Evangelyn Garcia, Rochelle Rendi, Mara Agnew, Kathy Fredricks, David N. Eschenbach, David TI Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE endometritis; endometrium; intrauterine bacteria; reproductive tract microbiota; sterile; upper genital tract infection; uterine cavity ID CERVICAL-MUCUS PLUG; IN-VITRO FERTILIZATION; HYSTERECTOMY SPECIMENS; ANTIMICROBIAL FACTORS; PRETERM DELIVERY; UTERINE CAVITY; VAGINOSIS; PREGNANCY; UTERUS; ENDOMETRITIS AB OBJECTIVE: The objective of the study was to evaluate the upper genital tract (UGT) presence of vaginal bacterial species using sensitive molecular methods capable of detecting fastidious bacterial vaginosis (BV)-associated bacteria. STUDY DESIGN: Vaginal swabs were collected prior to hysterectomy. The excised uterus was sterilely opened and swabs collected from the endometrium and upper endocervix. DNA was tested in 11 quantitative polymerase chain reaction (PCR) assays for 12 bacterial species: Lactobacillus iners, L crispatus, L jensenii, Gardnerella vaginalis, Atopobium vaginae, Megasphaera spp, Prevotella spp, Leptotrichia/Sneathia, BVAB1, BVAB2, BVAB3, and a broad-range16S ribosomal ribonucleic acid gene assay. Endometrial fluid was tested with Luminex and an enzyme-linked immunosorbent assay for cytokines and defensins and tissue for gene expression of defensins and cathelicidin. RESULTS: We enrolled 58 women: mean aged 43 +/- 7 years, mostly white (n = 46; 79%) and BV negative (n = 43; 74%). By species-specific quantitative PCR, 55 (95%) had UGT colonization with at least 1 species (n = 52) or were positive by 16S PCR (n = 3). The most common species were L iners (45% UGT, 61% vagina), Prevotella spp (33% UGT, 76% vagina) and L crispatus (33% UGT, 56% vagina). Median quantities of bacteria in the UGT were lower than vaginal levels by 2-4 log(10) ribosomal ribonucleic acid gene copies per swab. There were no differences in the endometrial inflammatory markers between women with no bacteria, Lactobacillus only, or any BV-associated species in the UGT. CONCLUSION: Our data suggest that the endometrial cavity is not sterile in most women undergoing hysterectomy and that the presence of low levels of bacteria in the uterus is not associated with significant inflammation. C1 [Mitchell, Caroline M.; Haick, Anoria; Nkwopara, Evangelyn; Agnew, Kathy; Eschenbach, David] Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Garcia, Rochelle; Rendi, Mara] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Fredricks, David N.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. RP Mitchell, CM (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. EM caroline.mitchell@mgh.harvard.edu FU National Institute of Allergy and Infectious Diseases [1K08AI087969-01]; University of Washington Royalty Research Fund FX This work was supported by grants from the National Institute of Allergy and Infectious Diseases (1K08AI087969-01) and the University of Washington Royalty Research Fund (both to C.M.). NR 40 TC 7 Z9 8 U1 2 U2 9 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 MAY PY 2015 VL 212 IS 5 AR 611.e1 DI 10.1016/j.ajog.2014.11.043 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CG8XH UT WOS:000353598500015 PM 25524398 ER PT J AU Page, JM Pilliod, RA Snowden, JM Caughey, AB AF Page, Jessica M. Pilliod, Rachel A. Snowden, Jonathan M. Caughey, Aaron B. TI The risk of stillbirth and infant death by each additional week of expectant management in twin pregnancies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med DE expectant management; infant death; stillbirth; twin pregnancy ID GESTATIONAL-AGE; LATE-PRETERM; TERM PREGNANCY; MONOCHORIONIC TWINS; UNITED-STATES; FETAL-DEATH; DELIVERY; MORBIDITY; MORTALITY; COMPLICATIONS AB OBJECTIVE: The objective of the study was to compare the fetal/infant mortality risk associated with each additional week of expectant management with the mortality risk of immediate delivery in women with twin gestations. STUDY DESIGN: A retrospective cohort study was performed utilizing 2006-2008 National linked birth certificate and death certificate data. The incidence of stillbirth and infant death were determined for each week of pregnancy from 32 0/7 weeks' through 40 6/7 weeks' gestation. Pregnancies complicated by fetal anomalies were excluded. These measures were combined to estimate the theoretic risk of remaining pregnant an additional week by adding the risk of stillbirth during the extra week of pregnancy with the risk of infant death encountered with delivery during the following week. This composite fetal/infant mortality risk was compared with the risk of infant death associated with delivery at the corresponding gestational age. RESULTS: The risk of stillbirth increased with increasing gestational age, for example, between 37 and 38 weeks' gestation (12.5 per 10,000 vs 22.5 per 10,000; P < .05). As expected, the risk of infant death following delivery gradually decreased as pregnancies approached term gestation. Week-by-week differences were statistically significant (P < .05) between 32 and 36 weeks with decreasing risk of infant death at advancing gestational ages. The composite risk of stillbirth and infant death associated with an additional week of pregnancy had a significant increase from 37 to 38 weeks' gestation (43.9 per 10,000 vs 59.2 per 10,000; P < .05). At 37 weeks' gestation, the relative risk of mortality was statistically significantly lower with immediate delivery as compared with expectant management (relative risk, 0.87; 95% confidence interval, 0.77-0.99). CONCLUSION: Our results suggest that fetal/infant death risk is minimized at 37 weeks' gestation; however, individual maternal and fetal characteristics must also be taken into account when determining the optimal timing of delivery for twin pregnancies. C1 [Page, Jessica M.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. [Pilliod, Rachel A.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Pilliod, Rachel A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Snowden, Jonathan M.; Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. RP Page, JM (reprint author), Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. EM jessica.page@hsc.utah.edu OI Page, Jessica/0000-0002-2570-4333 FU NICHD NIH HHS [K99 HD079658-01] NR 34 TC 3 Z9 3 U1 0 U2 4 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 MAY PY 2015 VL 212 IS 5 AR 630.e1 DI 10.1016/j.ajog.2015.03.033 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CG8XH UT WOS:000353598500021 PM 25797235 ER PT J AU Rauh-Hain, JA Foley, OW Winograd, D Andrade, C Clark, RM Vargas, RJ Hinchcliff, EM Esselen, KM Horowitz, NS del Carmen, MG AF Rauh-Hain, Jose Alejandro Foley, Olivia Wysong Winograd, Dina Andrade, Carolina Clark, Rachel Marie Vargas, Roberto Javier Hinchcliff, Emily Moss Esselen, Katherine McKinley Horowitz, Neil Stuart del Carmen, Marcela Guadalupe TI Clinical characteristics and outcomes of patients with stage I epithelial ovarian cancer compared with fallopian tube cancer SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the New-England-Association-of-Gynecologic-Oncologists CY JUN 12-15, 2014 CL Newport, RI SP New England Assoc Gyncol Oncologists DE BRCA; breast cancer; fallopian tube cancer; ovarian cancer ID GYNECOLOGIC-ONCOLOGY-GROUP; CARCINOMA; ADENOCARCINOMA; TRIAL AB OBJECTIVE: The purpose of this study was to compare clinical characteristics and survival between patients with stage I epithelial ovarian cancer and fallopian tube cancer. STUDY DESIGN: We identified women with stage I epithelial ovarian cancer and fallopian tube cancer who underwent treatment from 2000-2010. Correlation between categoric variables was assessed with chi(2) test. The Kaplan-Meier survival analysis was used to generate overall survival data. Factors predictive of outcome were compared with the use of the log-rank test and Cox proportional hazards model. RESULTS: The study group consisted of 385 women with epithelial ovarian cancer and 43 women with fallopian tube cancer. Patients with fallopian tube cancer had a higher rate of stage IA disease (65% vs 48%; P = .02) and grade 3 tumors (60.4% vs 30.9%; P < .001). Patients with fallopian tube cancer had a significantly higher rate of breast cancer (25.6% vs 5.7%; P < .001) and BRCA 1 mutations (45.8% vs 9.1%; P < .001). There was no difference in the rates of platinum-based and paclitaxel chemotherapy between the groups. Women with fallopian tube cancer were more likely to have received >= 6 cycles of chemotherapy (58.1% vs 44.1%; P = .02). The 5-year disease-free survival rates were 100% in women with fallopian tube cancer and 93% in patients with epithelial ovarian cancer (P = .04). The 5-year overall survival rates were 100% and 95% for fallopian tube cancer and epithelial ovarian cancer, respectively (P = .7). CONCLUSION: We found a higher rate of stage IA, grade 3, and serous carcinoma in fallopian tube cancer. Women with fallopian tube cancer had a higher rate of breast cancer. There was no difference in overall survival between the groups. C1 [Rauh-Hain, Jose Alejandro; Foley, Olivia Wysong; Winograd, Dina; Andrade, Carolina; Clark, Rachel Marie; Vargas, Roberto Javier; Hinchcliff, Emily Moss; del Carmen, Marcela Guadalupe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gynecol Oncol,Vincent Dept Obstet & Gynecol, Boston, MA 02138 USA. [Vargas, Roberto Javier; Hinchcliff, Emily Moss; Esselen, Katherine McKinley; Horowitz, Neil Stuart] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA 02115 USA. RP del Carmen, MG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gynecol Oncol,Vincent Dept Obstet & Gynecol, Boston, MA 02138 USA. EM mdelcarmen@partners.org NR 21 TC 0 Z9 1 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 MAY PY 2015 VL 212 IS 5 AR 600.e1 DI 10.1016/j.ajog.2014.12.013 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CG8XH UT WOS:000353598500011 PM 25514761 ER PT J AU Wang, W Young, BA Fulop, T de Boer, IH Boulware, LE Katz, R Correa, A Griswold, ME AF Wang, Wei Young, Bessie A. Fueloep, Tibor de Boer, Ian H. Boulware, L. Ebony Katz, Ronit Correa, Adolfo Griswold, Michael E. TI Effects of Serum Creatinine Calibration on Estimated Renal Function in African Americans: The Jackson Heart Study SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Calibration; Chronic kidney disease; CKD-EPI equation; Deming regression; Serum creatinine ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; CKD-EPI EQUATION; CYSTATIN C; RISK; GFR AB Background: The calibration to isotope dilution mass spectrometry-traceable creatinine is essential for valid use of the new Chronic Kidney Disease Epidemiology Collaboration equation to estimate the glomerular filtration rate. Methods: For 5,210 participants in the Jackson Heart Study (JHS), serum creatinine was measured with a multipoint enzymatic spectrophotometric assay at the baseline visit (2000-2004) and remeasured using the Roche enzymatic method, traceable to isotope dilution mass spectrometry in a subset of 206 subjects. The 200 eligible samples (6 were excluded, 1 for failure of the remeasurement and 5 for outliers) were divided into 3 disjoint sets-training, validation and test-to select a calibration model, estimate true errors and assess performance of the final calibration equation. The calibration equation was applied to serum creatinine measurements of 5,210 participants to estimate glomerular filtration rate and the prevalence of chronic kidney disease (CKD). Results: The selected Deming regression model provided a slope of 0.968 (95% confidence interval [CI], 0.904-1.053) and intercept of 20.0248 (95% CI, -0.0862 to 0.0366) with R-2 value of 0.9527. Calibrated serum creatinine showed high agreement with actual measurements when applying to the unused test set (concordance correlation coefficient 0.934, 95% CI, 0.894-0.960). The baseline prevalence of CKD in the JHS (2000-2004) was 6.30% using calibrated values compared with 8.29% using noncalibrated serum creatinine with the Chronic Kidney Disease Epidemiology Collaboration equation (P<0.001). Conclusions: A Deming regression model was chosen to optimally calibrate baseline serum creatinine measurements in the JHS, and the calibrated values provide a lower CKD prevalence estimate. C1 [Wang, Wei; Griswold, Michael E.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA. [Young, Bessie A.; de Boer, Ian H.; Katz, Ronit] Vet Affairs Puget Sound Hlth Care Syst, Ctr Innovat & Hosp & Specialty Care, Seattle, WA USA. [Young, Bessie A.; de Boer, Ian H.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Young, Bessie A.; de Boer, Ian H.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Fueloep, Tibor; Correa, Adolfo] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Boulware, L. Ebony] Duke Univ, Dept Med, Durham, NC USA. RP Wang, W (reprint author), Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, 2500 North State St, Jackson, MS 39216 USA. EM wwang@umc.edu FU National Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities; National Institute of Diabetes, Digestive, and Kidney Disease [1R01DK102134-01]; Veterans Affairs Puget Sound Health Care System; Abbvie FX The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. Additional support was provided by Dr. Young's National Institute of Diabetes, Digestive, and Kidney Disease grant 1R01DK102134-01. B.A.Y. is also supported in part by funding from the Veterans Affairs Puget Sound Health Care System. I.H.d.B. received research funding from Abbvie. NR 20 TC 4 Z9 4 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAY PY 2015 VL 349 IS 5 BP 379 EP 384 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CH2IE UT WOS:000353848100001 PM 25806862 ER PT J AU Carpenter, R Estrada, CA Medrano, M Smith, A Massie, FS AF Carpenter, Riley Estrada, Carlos A. Medrano, Martha Smith, Ann Massie, F. Stanford, Jr. TI A Web-Based Cultural Competency Training for Medical Students: A Randomized Trial SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Cultural competence; Medical education; Educational intervention ID ACHIEVABLE BENCHMARKS; HEALTH; EDUCATION; CURRICULUM; KNOWLEDGE; TOOL AB The objectives of this research were to compare a Web-based curriculum with a traditional lecture format on medical students' cultural competency attitudes using a standardized instrument and to examine the internal consistency of the standardized instrument. Methods: In 2010, we randomized all 180 1st-year medical students into a Web-based (intervention group) or a lecture-based (control group) cultural competency training. The main outcome was the overall score on the Health Belief Attitudes Survey (1 5 lowest, 6 5 highest). We examined internal consistency with factor analysis. Results: No differences were observed in the overall median scores between the intervention (median 5.2; 25th percentile [Q1] 4.9, 75th percentile [Q3] 5.5) and the control groups (median 5.3, Q1 4.9, Q3 5.6) (P = 0.77). The internal consistency of the 2 main subcomponents was good (Cronbach's alpha = 0.83) to acceptable (Cronbach's alpha = 0.69). Conclusions: A Web-based and a lecture-based cultural competency training strategies were associated with equally high positive attitudes among 1st-year medical students. These findings warrant further evaluation of Web-based cultural competency educational interventions. C1 [Carpenter, Riley] Univ Alabama Birmingham, Sch Med, Birmingham, AL 35294 USA. [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Vet Affairs Qual Scholars Program, Birmingham, AL USA. [Estrada, Carlos A.; Massie, F. Stanford, Jr.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Medrano, Martha] Univ Texas Hlth Sci Ctr San Antonio, Continuing Med Educ & Family Practice & Psychiat, San Antonio, TX 78229 USA. [Medrano, Martha] Med Hispan Ctr Excellence, San Antonio, TX USA. [Smith, Ann] Univ Alabama Birmingham, UAB Minor Hlth & Hlth Dispar Res Ctr, Div Prevent Med, Birmingham, AL 35294 USA. RP Estrada, CA (reprint author), Univ Alabama Birmingham, 720 Fac Off Tower,510 20th St South, Birmingham, AL 35294 USA. EM cestrada@uab.edu FU National Heart, Lung, and Blood Institute [K07 HL081373-01]; Department of Veterans Affairs Office of Academic Affiliations (OAA) FX Supported by the National Heart, Lung, and Blood Institute (K07 HL081373-01 to C.A.E.).; The Department of Veterans Affairs Quality Scholars Fellowship (VAQS) is funded by the Department of Veterans Affairs Office of Academic Affiliations (OAA). The opinions expressed in this article are those of the authors alone and do not reflect the views of the Department of Veterans Affairs. NR 21 TC 2 Z9 2 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAY PY 2015 VL 349 IS 5 BP 442 EP 446 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CH2IE UT WOS:000353848100011 PM 25325193 ER PT J AU Sundararajan, R Mwanga-Amumpaire, J Adrama, H Tumuhairwe, J Mbabazi, S Mworozi, K Carroll, R Bangsberg, D Boum, Y Ware, NC AF Sundararajan, Radhika Mwanga-Amumpaire, Juliet Adrama, Harriet Tumuhairwe, Jackline Mbabazi, Sheilla Mworozi, Kenneth Carroll, Ryan Bangsberg, David Boum, Yap, II Ware, Norma C. TI Sociocultural and Structural Factors Contributing to Delays in Treatment for Children with Severe Malaria: A Qualitative Study in Southwestern Uganda SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID HEALTH-SEEKING BEHAVIOR; PREVENTION; MANAGEMENT; TANZANIA; AFRICA; CARE; TRANSMISSION; MORBIDITY; HIV/AIDS; MEDICINE AB Malaria is a leading cause of pediatric mortality, and Uganda has among the highest incidences in the world. Increased morbidity and mortality are associated with delays to care. This qualitative study sought to characterize barriers to prompt allopathic care for children hospitalized with severe malaria in the endemic region of southwestern Uganda. Minimally structured, qualitative interviews were conducted with guardians of children admitted to a regional hospital with severe malaria. Using an inductive and content analytic approach, transcripts were analyzed to identify and define categories that explain delayed care. These categories represented two broad themes: sociocultural and structural factors. Sociocultural factors were 1) interviewee's distinctions of "traditional" versus "hospital" illnesses, which were mutually exclusive and 2) generational conflict, where deference to one's elders, who recommended traditional medicine, was expected. Structural factors were 1) inadequate distribution of health-care resources, 2) impoverishment limiting escalation of care, and 3) financial impact of illness on household economies. These factors perpetuate a cycle of illness, debt, and poverty consistent with a model of structural violence. Our findings inform a number of potential interventions that could alleviate the burden of this preventable, but often fatal, illness. Such interventions could be beneficial in similarly endemic, low-resource settings. C1 [Sundararajan, Radhika] Univ Calif San Diego, Dept Emergency Med, San Diego, CA 92103 USA. Univ Calif San Diego, Div Global Publ Hlth, San Diego, CA 92103 USA. Epictr Res Base, Mbarara, Uganda. Mbarara Univ Sci & Technol, Mbarara, Uganda. [Bangsberg, David] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Ware, Norma C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Mwanga-Amumpaire, Juliet; Adrama, Harriet; Tumuhairwe, Jackline; Mbabazi, Sheilla; Mworozi, Kenneth; Boum, Yap, II] Uganda Res Base, Epictr, Mbarara, Uganda. [Carroll, Ryan] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Sundararajan, R (reprint author), Univ Calif San Diego, Dept Emergency Med, 200 West Arbor Dr,MC 8676, San Diego, CA 92103 USA. EM rsundararajan@ucsd.edu; juliet.mwanga@epicentre.msf.org; harriet.adrama@gmail.com; tumuhairwejackline@gmail.com; sheilla.mbabazi@gmail.com; mworozikenneth@gmail.com; rcarroll4@partners.org; dbangsberg@partners.org; yap.boum@epicentre.msf.org; norma_ware@hms.harvard.edu FU Harvard-affiliated Emergency Medicine Residency Povinelli Research Award; Brigham and Women's Hospital Biomedical Research Institute/Center for Faculty Development FX Funding for this project was provided by the Harvard-affiliated Emergency Medicine Residency Povinelli Research Award, as well as the Brigham and Women's Hospital Biomedical Research Institute/Center for Faculty Development. NR 36 TC 0 Z9 0 U1 2 U2 8 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2015 VL 92 IS 5 BP 933 EP 940 DI 10.4269/ajtmh.14-0784 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CH5KQ UT WOS:000354074900011 PM 25802438 ER PT J AU Bateman, BT Brenner, GJ AF Bateman, Brian T. Brenner, Gary J. TI An Important Step Forward in the Safe Use of Epidural Steroid Injections SO ANESTHESIOLOGY LA English DT Editorial Material ID PAIN C1 [Bateman, Brian T.; Brenner, Gary J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02138 USA. [Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP Bateman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02138 USA. EM bbateman@partners.org FU NICHD NIH HHS [K08 HD075831, K08HD075831] NR 8 TC 1 Z9 1 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2015 VL 122 IS 5 BP 964 EP 966 DI 10.1097/ALN.0000000000000615 PG 3 WC Anesthesiology SC Anesthesiology GA CH5PT UT WOS:000354088500003 PM 25668413 ER PT J AU Rathmell, JP Benzon, HT Dreyfuss, P Huntoon, M Wallace, M Baker, R Riew, KD Rosenquist, RW Aprill, C Rost, NS Buvanendran, A Kreiner, DS Bogduk, N Fourney, DR Fraifeld, E Horn, S Stone, J Vorenkamp, K Lawler, G Summers, J Kloth, D O'Brien, D Tutton, S AF Rathmell, James P. Benzon, Honorio T. Dreyfuss, Paul Huntoon, Marc Wallace, Mark Baker, Ray Riew, K. Daniel Rosenquist, Richard W. Aprill, Charles Rost, Natalia S. Buvanendran, Asokumar Kreiner, D. Scott Bogduk, Nikolai Fourney, Daryl R. Fraifeld, Eduardo Horn, Scott Stone, Jeffrey Vorenkamp, Kevin Lawler, Gregory Summers, Jeffrey Kloth, David O'Brien, David, Jr. Tutton, Sean TI Safeguards to Prevent Neurologic Complications after Epidural Steroid Injections Consensus Opinions from a Multidisciplinary Working Group and National Organizations SO ANESTHESIOLOGY LA English DT Article ID CERVICAL TRANSFORAMINAL INJECTION; OF-THE-LITERATURE; DIGITAL-SUBTRACTION-ANGIOGRAPHY; LUMBAR RADICULAR PAIN; SPINAL-CORD-INJURY; NERVE ROOT BLOCK; INTRAVASCULAR INJECTION; VERTEBRAL ARTERY; PARAPLEGIA; INFARCTION AB Background: Epidural corticosteroid injections are a common treatment for radicular pain caused by intervertebral disc herniations, spinal stenosis, and other disorders. Although rare, catastrophic neurologic injuries, including stroke and spinal cord injury, have occurred with these injections. Methods: A collaboration was undertaken between the U.S. Food and Drug Administration Safe Use Initiative, an expert multi-disciplinary working group, and 13 specialty stakeholder societies. The goal of this collaboration was to review the existing evidence regarding neurologic complications associated with epidural corticosteroid injections and produce consensus procedural clinical considerations aimed at enhancing the safety of these injections. U.S. Food and Drug Administration Safe Use Initiative representatives helped convene and facilitate meetings without actively participating in the deliberations or decision-making process. Results: Seventeen clinical considerations aimed at improving safety were produced by the stakeholder societies. Specific clinical considerations for performing transforaminal and interlaminar injections, including the use of nonparticulate steroid, anatomic considerations, and use of radiographic guidance are given along with the existing scientific evidence for each clinical consideration. Conclusion: Adherence to specific recommended practices when performing epidural corticosteroid injections should lead to a reduction in the incidence of neurologic injuries. C1 [Rathmell, James P.; Rost, Natalia S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rathmell, James P.; Rost, Natalia S.] Harvard Univ, Sch Med, Boston, MA 02116 USA. [Benzon, Honorio T.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Dreyfuss, Paul; Baker, Ray] EvergreenHealth, Kirkland, WA USA. [Huntoon, Marc] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Wallace, Mark] Univ Calif San Diego, San Diego, CA 92103 USA. [Riew, K. Daniel] Washington Univ, Sch Med, St Louis, MO USA. [Rosenquist, Richard W.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Aprill, Charles] Intervent Spine Specialists, Kenner, LA USA. [Buvanendran, Asokumar] Rush Med Coll, Chicago, IL 60612 USA. [Kreiner, D. Scott] Ahwatukee Sports & Spine, Phoenix, AZ USA. [Bogduk, Nikolai] Univ Newcastle, Newcastle, NSW 2300, Australia. [Fourney, Daryl R.] Univ Saskatchewan, Saskatoon, SK, Canada. [Fraifeld, Eduardo] Southside Pain Solut, Danville, VA USA. [Horn, Scott] APM Spine & Sports Phys, Virginia Beach, VA USA. [Stone, Jeffrey] Mayo Clin Florida, Jacksonville, FL USA. [Vorenkamp, Kevin] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Lawler, Gregory] Neuroimaging & Intervent Spine Serv LLC, Ridgefield, CT USA. [Summers, Jeffrey] NewSouth NeuroSpine, Flowood, MS USA. [Kloth, David] Danbury Hosp, Danbury, CT USA. [O'Brien, David, Jr.] Univ N Carolina, Sch Med, Winston Salem, NC USA. [Tutton, Sean] Med Coll Wisconsin, Froedtert Hosp, Milwaukee, WI 53226 USA. RP Rathmell, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Gray Bigelow 444, Boston, MA 02116 USA. EM rathmell.james@mgh.harvard.edu FU AOSpine; Cerapedics; Medtronic; Orthopaedic Research and Education Foundation; Spinal Dynamics FX Dr. Riew is receiving grants and/or research support from AOSpine, Cerapedics, Medtronic, Orthopaedic Research and Education Foundation, and Spinal Dynamics and receives honoraria from New England Spine Society Group and North American Spine Society. NR 67 TC 44 Z9 46 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2015 VL 122 IS 5 BP 974 EP 984 DI 10.1097/ALN.0000000000000614 PG 11 WC Anesthesiology SC Anesthesiology GA CH5PT UT WOS:000354088500007 PM 25668411 ER PT J AU Kashiwagi, A Hosokawa, S Maeyama, Y Ueki, R Kaneki, M Martyn, JAJ Yasuhara, S AF Kashiwagi, Aki Hosokawa, Sachiko Maeyama, Yoshihiro Ueki, Ryusuke Kaneki, Masao Martyn, J. A. Jeevendra Yasuhara, Shingo TI Anesthesia with Disuse Leads to Autophagy Up-regulation in the Skeletal Muscle SO ANESTHESIOLOGY LA English DT Article ID DUCHENNES MUSCULAR-DYSTROPHY; MICE; MITOCHONDRIA; RHABDOMYOLYSIS; PROLIFERATION; ANTIOXIDANT; MECHANISMS; INHIBITOR; MITOPHAGY; PATHWAYS AB Background: It has been known that skeletal muscles show atrophic changes after prolonged sedation or general anesthesia. Whether these effects are due to anesthesia itself or disuse during anesthesia has not been fully clarified. Autophagy dysregulation has been implicated in muscle-wasting conditions. This study tested the hypothesis that the magnitude of skeletal muscle autophagy is affected by both anesthesia and immobility. Methods: The extent of autophagy was analyzed chronologically during general anesthesia. In vivo microscopy was performed using green fluorescent protein-tagged LC3 for the detection of autophagy using sternomastoid muscles of live mice during pentobarbital anesthesia (n = 6 and 7). Western blotting and histological analyses were also conducted on tibialis anterior muscles (n = 3 to 5). To distinguish the effect of anesthesia from that due to disuse, autophagy was compared between animals anesthetized with pentobarbital and those immobilized by short-term denervation without continuation of anesthesia. Conversely, tibialis anterior and sternomastoid muscles were electrically stimulated during anesthesia. Results: Western blots and microscopy showed time-dependent autophagy up-regulation during pentobarbital anesthesia, peaking at 3 h (728.6 +/- 93.5% of basal level, mean +/- SE). Disuse by denervation without sustaining anesthesia did not lead to equivalent autophagy, suggesting that anesthesia is essential to cause autophagy. In contrast, contractile stimulation of the tibialis anterior and sternomastoid muscles significantly reduced the autophagy up-regulation during anesthesia (85% at 300 min). Ketamine, ketamine plus xylazine, isoflurane, and propofol also up-regulated autophagy. Conclusions: Short-term disuse without anesthesia does not lead to autophagy, but anesthesia with disuse leads to marked up-regulation of autophagy. C1 [Kashiwagi, Aki; Hosokawa, Sachiko; Ueki, Ryusuke; Kaneki, Masao; Martyn, J. A. Jeevendra; Yasuhara, Shingo] Shriners Hosp Children, Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Kashiwagi, Aki; Hosokawa, Sachiko; Ueki, Ryusuke; Kaneki, Masao; Martyn, J. A. Jeevendra; Yasuhara, Shingo] Harvard Univ, Sch Med, Boston, MA USA. [Maeyama, Yoshihiro] Hyogo Coll Med, Dept Surg, Kobe, Hyogo, Japan. RP Yasuhara, S (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM shingoyasuhara136@gmail.com FU Shriners Hospital (Tampa, Florida); Massachusetts General Hospital, Department of Anesthesia, Critical Care and Pain Medicine Department Fund (Boston, Massachusetts); National Institutes of Health (Bethesda, Maryland) [P-50 GM2500] FX Supported by a research grant funded by Shriners Hospital (Tampa, Florida; to Dr. Yasuhara), by Massachusetts General Hospital, Department of Anesthesia, Critical Care and Pain Medicine Department Fund (Boston, Massachusetts; to Dr. Yasuhara), and partly by National Institutes of Health P-50 GM2500: Project-I (Bethesda, Maryland; to Dr. Martyn). NR 39 TC 4 Z9 4 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2015 VL 122 IS 5 BP 1075 EP 1083 DI 10.1097/ALN.0000000000000561 PG 9 WC Anesthesiology SC Anesthesiology GA CH5PT UT WOS:000354088500016 PM 25501690 ER PT J AU Steadman, RH Burden, AR Huang, YM Gaba, DM Cooper, JB AF Steadman, Randolph H. Burden, Amanda R. Huang, Yue Ming Gaba, David M. Cooper, Jeffrey B. TI Practice Improvements Based on Participation in Simulation for the Maintenance of Certification in Anesthesiology Program SO ANESTHESIOLOGY LA English DT Article ID CONTINUING MEDICAL-EDUCATION; RANDOMIZED CONTROLLED-TRIAL; CLOSED CLAIMS PROJECT; HEALTH-CARE; UNITED-STATES; COMMITMENT; PHYSICIANS; QUALITY; PERSPECTIVE; PERFORMANCE AB Background: This study describes anesthesiologists' practice improvements undertaken during the first 3 yr of simulation activities for the Maintenance of Certification in Anesthesiology Program. Methods: A stratified sampling of 3 yr (2010-2012) of participants' practice improvement plans was coded, categorized, and analyzed. Results: Using the sampling scheme, 634 of 1,275 participants in Maintenance of Certification in Anesthesiology Program simulation courses were evaluated from the following practice settings: 41% (262) academic, 54% (339) community, and 5% (33) military/other. A total of 1,982 plans were analyzed for completion, target audience, and topic. On follow-up, 79% (1,558) were fully completed, 16% (310) were partially completed, and 6% (114) were not completed within the 90-day reporting period. Plans targeted the reporting individual (89% of plans) and others (78% of plans): anesthesia providers (50%), non-anesthesia physicians (16%), and non-anesthesia non-physician providers (26%). From the plans, 2,453 improvements were categorized as work environment or systems changes (33% of improvements), teamwork skills (30%), personal knowledge (29%), handoff (4%), procedural skills (3%), or patient communication (1%). The median word count was 63 (interquartile range, 30 to 126) for each participant's combined plans and 147 (interquartile range, 52 to 257) for improvement follow-up reports. Conclusions: After making a commitment to change, 94% of anesthesiologists participating in a Maintenance of Certification in Anesthesiology Program simulation course successfully implemented some or all of their planned practice improvements. This compares favorably to rates in other studies. Simulation experiences stimulate active learning and motivate personal and collaborative practice improvement changes. Further evaluation will assess the impact of the improvements and further refine the program. C1 [Steadman, Randolph H.; Huang, Yue Ming] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Los Angeles, CA 90095 USA. [Steadman, Randolph H.; Huang, Yue Ming] UCLA Simulat Ctr, Los Angeles, CA USA. [Burden, Amanda R.] Rowan Univ, Cooper Univ Hosp, Cooper Med Sch, Dept Anesthesiol,Simulat Ctr, Camden, NJ USA. [Gaba, David M.] Stanford Univ, Sch Med, Ctr Immers & Simulat Based Learning, Palo Alto, CA 94304 USA. [Gaba, David M.] Vet Affairs Palo Alto Hlth Care Syst, Anesthesiol & Perioperat Care Serv, Palo Alto, CA USA. [Cooper, Jeffrey B.] Ctr Med Simulat, Boston, MA USA. [Cooper, Jeffrey B.] Harvard Univ, Sch Med, Boston, MA USA. [Cooper, Jeffrey B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Steadman, RH (reprint author), Univ Calif Los Angeles, UCLA Simulat Ctr, David Geffen Sch Med, Dept Anesthesiol, 700 Westwood Plaza,Suite A222 LRC, Los Angeles, CA 90095 USA. EM rsteadman@mednet.ucla.edu FU Department of Anesthesiology, David Geffen School of Medicine at the University of California, Los Angeles (UCLA); UCLA Simulation Center, Los Angeles, California; Department of Anesthesiology, Cooper Medical School of Rowan University, Camden, New Jersey; Center for Medical Simulation, Boston, Massachusetts; Harvard Medical School and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts; Stanford University School of Medicine, Palo Alto, California FX This study was supported by the authors' institutions: Department of Anesthesiology, David Geffen School of Medicine at the University of California, Los Angeles (UCLA); UCLA Simulation Center, Los Angeles, California; Department of Anesthesiology, Cooper Medical School of Rowan University, Camden, New Jersey; Center for Medical Simulation, Boston, Massachusetts; Harvard Medical School and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, and the Stanford University School of Medicine, Palo Alto, California. NR 42 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2015 VL 122 IS 5 BP 1154 EP 1169 DI 10.1097/ALN.0000000000000613 PG 16 WC Anesthesiology SC Anesthesiology GA CH5PT UT WOS:000354088500025 PM 25985025 ER PT J AU Bellera, CA Penel, N Ouali, M Bonvalot, S Casali, PG Nielsen, OS Delannes, M Litiere, S Bonnetain, F Dabakuyo, TS Benjamin, RS Blay, JY Bui, BN Collin, F Delaney, TF Duffaud, F Filleron, T Fiore, M Gelderblom, H George, S Grimer, R Grosclaude, P Gronchi, A Haas, R Hohenberger, P Issels, R Italiano, A Jooste, V Krarup-Hansen, A Le Pechoux, C Mussi, C Oberlin, O Patel, S Piperno-Neumann, S Raut, C Ray-Coquard, I Rutkowski, P Schuetze, S Sleijfer, S Stoeckle, E Van Glabbeke, M Woll, P Gourgou-Bourgade, S Mathoulin-Pelissier, S AF Bellera, C. A. Penel, N. Ouali, M. Bonvalot, S. Casali, P. G. Nielsen, O. S. Delannes, M. Litiere, S. Bonnetain, F. Dabakuyo, T. S. Benjamin, R. S. Blay, J. -Y. Bui, B. N. Collin, F. Delaney, T. F. Duffaud, F. Filleron, T. Fiore, M. Gelderblom, H. George, S. Grimer, R. Grosclaude, P. Gronchi, A. Haas, R. Hohenberger, P. Issels, R. Italiano, A. Jooste, V. Krarup-Hansen, A. Le Pechoux, C. Mussi, C. Oberlin, O. Patel, S. Piperno-Neumann, S. Raut, C. Ray-Coquard, I. Rutkowski, P. Schuetze, S. Sleijfer, S. Stoeckle, E. Van Glabbeke, M. Woll, P. Gourgou-Bourgade, S. Mathoulin-Pelissier, S. TI Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) SO ANNALS OF ONCOLOGY LA English DT Review DE guidelines; randomized controlled trial; time-to-event end point; efficacy measure; sarcoma; gastrointestinal stromal tumors ID HIGH-DOSE METHOTREXATE; SOFT-TISSUE SARCOMA; CLINICAL-TRIALS; RESPONSE CRITERIA; MURAMYL TRIPEPTIDE; PEDIATRIC-ONCOLOGY; RANDOMIZED-TRIALS; PLUS DOXORUBICIN; EWINGS-SARCOMA; BREAST-CANCER AB Background: The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or timeto-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). Methods: We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. Results: Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. Conclusion: Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities. C1 [Bellera, C. A.; Mathoulin-Pelissier, S.] Ctr Comprehens Canc, Inst Bergonie, Clin & Epidemiol Res Unit, Bordeaux, France. [Bellera, C. A.; Mathoulin-Pelissier, S.] INSERM CIC 14 01 Clin Epidemiol, Clin Epidemiol Unit, F-33000 Bordeaux, France. [Penel, N.] Ctr Comprehens Canc, Ctr Oscar Lambret, Dept Med Oncol, Lille, France. [Ouali, M.; Litiere, S.; Van Glabbeke, M.] European Org Res Treatment Canc, Dept Biostat, Brussels, Belgium. [Ouali, M.; Filleron, T.] Ctr Comprehens Canc, Inst Claudius Regaud, Biostat Unit, Toulouse, France. [Bonvalot, S.] Ctr Comprehens Canc, Inst Gustave Roussy, Dept Surg, Villejuif, France. [Casali, P. G.] Fdn IRCCS Ist Nazl Tumori, Med Oncol, Milan, Italy. [Nielsen, O. S.] Aarhus Univ, Fac Hlth Sci, Aarhus, Denmark. [Delannes, M.] Ctr Comprehens Canc, Inst Claudius Regaud, Dept Radiotherapy, Toulouse, France. [Bonnetain, F.] CHU Besancon, Methodol & Qual Life Unit Oncol EA3181, F-25030 Besancon, France. [Dabakuyo, T. S.] Ctr Comprehens Canc, Ctr Georges Francois Leclerc, Biostat & Qual Life Unit EA4184, Dijon, France. [Benjamin, R. S.; Patel, S.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA. [Benjamin, R. S.; Patel, S.] Univ Texas MD Anderson Canc Ctr, Sarcoma Ctr, Houston, TX 77030 USA. [Blay, J. -Y.; Ray-Coquard, I.] Ctr Comprehens Canc, Ctr Leon Berard, Dept Med Oncol, Lyon, France. [Blay, J. -Y.] Univ Lyon 1, F-69365 Lyon, France. [Blay, J. -Y.] Hop Edouard Herriot, Med Oncol Unit, Lyon, France. [Bui, B. N.; Italiano, A.] Ctr Comprehens Canc, Inst Bergonie, Dept Med Oncol, Bordeaux, France. [Collin, F.] Ctr Comprehens Canc, Ctr Georges Francois Leclerc, Dept Biol & Pathol, Dijon, France. [Delaney, T. F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Delaney, T. F.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Duffaud, F.] La Timone Hosp Univ, Dept Med Oncol, Marseille, France. [Fiore, M.] Fdn IRCCS Ist Nazl Tumori, Dept Surg, Milan, Italy. [Fiore, M.; Gronchi, A.] Fdn IRCCS Ist Nazl Tumori, Dept Surg, Sarcoma Unit, Sarcoma Serv, Milan, Italy. [Gelderblom, H.] Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. [George, S.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol,Med Sch, Boston, MA 02115 USA. [Grimer, R.] Royal Orthopaed Hosp NHS Trust, Birmingham, W Midlands, England. [Grosclaude, P.] Ctr Comprehens Canc, Inst Claudius Regaud, Canc Registry Tarn, Toulouse, France. [Haas, R.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Radiat Oncol, Amsterdam, Netherlands. [Hohenberger, P.] Univ Mannheim, Med Ctr, Div Surg Oncol & Thorac Surg, D-68131 Mannheim, Germany. [Issels, R.] Univ Munich, Sarcoma Ctr, Munich, Germany. [Issels, R.] Univ Munich, Klinikum Grosshadern Med Ctr, Dept Internal Med, Munich, Germany. [Jooste, V.] Univ Burgundy, INSERM, U866, Burgundy Digest Canc Registry, Dijon, France. [Krarup-Hansen, A.] Univ Copenhagen, Herlev Hosp, Dept Oncol, DK-2730 Herlev, Denmark. [Le Pechoux, C.] Ctr Comprehens Canc, Inst Gustave Roussy, Dept Radiotherapy, Villejuif, France. [Mussi, C.] Humanitas Clin & Res Ctr, Dept Surg, Milan, Italy. [Oberlin, O.] Ctr Comprehens Canc, Inst Gustave Roussy, Dept Surg, Villejuif, France. [Oberlin, O.] Ctr Comprehens Canc, Inst Gustave Roussy, Dept Pediat & Adolescent Oncol, Villejuif, France. [Piperno-Neumann, S.] Ctr Comprehens Canc, Inst Curie, Dept Med Oncol, Paris, France. [Raut, C.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg,Med Sch, Boston, MA 02115 USA. [Rutkowski, P.] Maria Sklodowska Curie Mem Canc Ctr, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland. [Rutkowski, P.] Inst Oncol, Warsaw, Poland. [Schuetze, S.] Univ Michigan, Dept Med Oncol, Ann Arbor, MI 48109 USA. [Sleijfer, S.] Erasmus Univ, Med Ctr, Daniel den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. [Stoeckle, E.] Ctr Comprehens Canc, Inst Bergonie, Dept Surg Oncol, Bordeaux, France. [Woll, P.] Weston Pk Hosp, Sheffield Canc Res Ctr, Dept Oncol, Sheffield, S Yorkshire, England. [Gourgou-Bourgade, S.] Ctr Comprehens Canc, Montpellier Canc Inst, Montpellier, France. RP Bellera, CA (reprint author), INSERM CIC 14 01 Clin Epidemiol, Ctr Comprehens Canc, Clin & Epidemiol Res Unit, Inst Bergonie, 229 Cours Argonne, F-33000 Bordeaux, France. EM c.bellera@bordeaux.unicancer.fr RI filleron, thomas/C-3554-2014; Blay, Jean-Yves/N-3966-2016; Fiore, Marco/M-6587-2016 OI filleron, thomas/0000-0003-0724-0659; Blay, Jean-Yves/0000-0001-7190-120X; Fiore, Marco/0000-0001-8220-424X FU French National League Against Cancer (Ligue Nationale Contre le Cancer; national grant for Clinical Research); French National Cancer Institute (Institut National du Cancer) FX This work was supported by grants from the French National League Against Cancer (Ligue Nationale Contre le Cancer; 2009 national grant for Clinical Research) and the French National Cancer Institute (Institut National du Cancer; financial support for organizing the in-person meeting held in Chicago). NR 29 TC 9 Z9 9 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2015 VL 26 IS 5 BP 865 EP 872 DI 10.1093/annonc/mdu360 PG 8 WC Oncology SC Oncology GA CH2BS UT WOS:000353830000006 PM 25070543 ER PT J AU Blumenschein, GR Smit, EF Planchard, D Kim, DW Cadranel, J De Pas, T Dunphy, F Udud, K Ahn, MJ Hanna, NH Kim, JH Mazieres, J Kim, SW Baas, P Rappold, E Redhu, S Puski, A Wu, FS Janne, PA AF Blumenschein, G. R., Jr. Smit, E. F. Planchard, D. Kim, D. -W. Cadranel, J. De Pas, T. Dunphy, F. Udud, K. Ahn, M. -J. Hanna, N. H. Kim, J. -H. Mazieres, J. Kim, S. -W. Baas, P. Rappold, E. Redhu, S. Puski, A. Wu, F. S. Jaenne, P. A. TI A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC) SO ANNALS OF ONCOLOGY LA English DT Article DE trametinib; MEK inhibitor; docetaxel; NSCLC; KRAS; progression-free survival ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITORS; MEK INHIBITION; MUTATIONS; SURVIVAL; EFFICACY; ADENOCARCINOMAS; ONCOGENE; BEHAVIOR; CRITERIA AB Background: KRAS mutations are detected in 25% of non-small-cell lung cancer (NSCLC) and no targeted therapies are approved for this subset population. Trametinib, a selective allosteric inhibitor of MEK1/MEK2, demonstrated preclinical and clinical activity in KRAS-mutant NSCLC. We report a phase II trial comparing trametinib with docetaxel in patients with advanced KRAS-mutant NSCLC. Patients and methods: Eligible patients with histologically confirmed KRAS-mutant NSCLC previously treated with one prior platinum-based chemotherapy were randomly assigned in a ratio of 2:1 to trametinib (2 mg orally once daily) or docetaxel (75 mg/m(2) i.v. every 3 weeks). Crossover to the other arm after disease progression was allowed. Primary end point was progression-free survival (PFS). The study was prematurely terminated after the interim analysis of 92 PFS events, which showed the comparison of trametinib versus docetaxel for PFS crossed the futility boundary. Results: One hundred and twenty-nine patients with KRAS-mutant NSCLC were randomized; of which, 86 patients received trametinib and 43 received docetaxel. Median PFS was 12 weeks in the trametinib arm and 11 weeks in the docetaxel arm (hazard ratio [HR] 1.14; 95% CI 0.75-1.75; P = 0.5197). Median overall survival, while the data are immature, was 8 months in the trametinib arm and was not reached in the docetaxel arm (HR 0.97; 95% CI 0.52-1.83; P = 0.934). There were 10 (12%) partial responses (PRs) in the trametinib arm and 5 (12%) PRs in the docetaxel arm (P = 1.0000). The most frequent adverse events (AEs) in >= 20% of trametinib patients were rash, diarrhea, nausea, vomiting, and fatigue. The most frequent grade 3 treatment-related AEs in the trametinib arm were hypertension, rash, diarrhea, and asthenia. Conclusion: Trametinib showed similar PFS and a response rate as docetaxel in patients with previously treated KRAS-mutant-positive NSCLC. C1 [Blumenschein, G. R., Jr.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77230 USA. [Smit, E. F.] Vrije Univ Amsterdam, VU Med Ctr, Dept Pulm Dis, Amsterdam, Netherlands. [Planchard, D.] Gustave Roussy, Med Oncol Dept, Villejuif, France. [Kim, D. -W.] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Cadranel, J.] Hop Tenon, AP HP, Dept Resp Med, F-75970 Paris, France. [De Pas, T.] European Inst Oncol, Milan, Italy. [Dunphy, F.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Udud, K.] Koranyi Natl Inst TB & Pulmonol, Budapest, Hungary. [Ahn, M. -J.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med,Div Hematol Oncol, Seoul, South Korea. [Hanna, N. H.] IU Melvin & Bren Simon Canc Ctr, Indianapolis, IN USA. [Kim, J. -H.] Yonsei Univ, Coll Med, Div Med Oncol, Yonsei Canc Ctr, Seoul, South Korea. [Mazieres, J.] CHU Toulouse, Hop Larrey, Toulouse, France. [Kim, S. -W.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Baas, P.] Netherlands Canc Inst, Amsterdam, Netherlands. [Rappold, E.; Redhu, S.; Wu, F. S.] GlaxoSmithKline, Collegeville, PA USA. [Puski, A.] GlaxoSmithKline Kft, Budapest, Hungary. [Jaenne, P. A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Lowe Ctr Thorac Oncol, Boston, MA USA. RP Blumenschein, GR (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77230 USA. EM gblumens@mdanderson.org OI MAZIERES, JULIEN/0000-0002-5921-7613 FU GlaxoSmithKline [NCT01362296] FX This study was funded, initiated, administrated, and sponsored by GlaxoSmithKline (NCT01362296), which also provided data analysis services. NR 28 TC 27 Z9 27 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2015 VL 26 IS 5 BP 894 EP 901 DI 10.1093/annonc/mdv072 PG 9 WC Oncology SC Oncology GA CH2BS UT WOS:000353830000010 PM 25722381 ER PT J AU Fuchs, CS Azevedo, S Okusaka, T Van Laethem, JL Lipton, LR Riess, H Szczylik, C Moore, MJ Peeters, M Bodoky, G Ikeda, M Melichar, B Nemecek, R Ohkawa, S Swieboda-Sadlej, A Tjulandin, SA Cutsem, E Loberg, R Haddad, V Gansert, JL Bach, BA Carrato, A AF Fuchs, C. S. Azevedo, S. Okusaka, T. Van Laethem, J. -L. Lipton, L. R. Riess, H. Szczylik, C. Moore, M. J. Peeters, M. Bodoky, G. Ikeda, M. Melichar, B. Nemecek, R. Ohkawa, S. Swieboda-Sadlej, A. Tjulandin, S. A. Van Cutsem, E. Loberg, R. Haddad, V. Gansert, J. L. Bach, B. A. Carrato, A. TI A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial SO ANNALS OF ONCOLOGY LA English DT Article DE ganitumab; gemcitabine; pancreatic cancer; IGF-1 receptor; biomarker ID DUCTAL ADENOCARCINOMA; MONOCLONAL-ANTIBODY; SOLID TUMORS; AMG 479; CANCER; GROWTH; SURVIVAL; CONATUMUMAB; BEVACIZUMAB; BIOMARKERS AB Background: This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment of metastatic pancreatic cancer. Patients and methods: Patients with previously untreated metastatic pancreatic adenocarcinoma were randomly assigned 2 : 2 : 1 to receive intravenous gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) plus placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (days 1 and 15 of each cycle). The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), safety, and efficacy by levels of circulating biomarkers. Results: Overall, 322 patients were randomly assigned to placebo, 318 to ganitumab 12 mg/kg, and 160 to ganitumab 20 mg/kg. The study was stopped based on results from a preplanned futility analysis; the final results are reported. Median OS was 7.2 months [95% confidence interval (CI), 6.3-8.2] in the placebo arm, 7.0 months (95% CI, 6.2-8.5) in the ganitumab 12-mg/kg arm [hazard ratio (HR), 1.00; 95% CI, 0.82-1.21; P = 0.494], and 7.1 months (95% CI, 6.4-8.5) in the ganitumab 20-mg/kg arm (HR, 0.97; 95% CI, 0.76-1.23; P = 0.397). Median PFS was 3.7, 3.6 (HR, 1.00; 95% CI, 0.84-1.20; P = 0.520), and 3.7 months (HR, 0.97; 95% CI, 0.77-1.22; P = 0.403), respectively. No unexpected toxicity was observed with ganitumab plus gemcitabine. The circulating biomarkers assessed [insulin-like growth factor-1 (IGF-1), IGF-binding protein-2, and -3] were not associated with a treatment effect on OS or PFS by ganitumab. Conclusion: Ganitumab combined with gemcitabine had manageable toxicity but did not improve OS, compared with gemcitabine alone in unselected patients with metastatic pancreatic cancer. C1 [Fuchs, C. S.] Dana Farber Canc Inst, Dept Med Oncol Solid Tumor Oncol, Boston, MA 02215 USA. [Azevedo, S.] Hosp Clin Porto Alegre, Oncol Serv, Porto Alegre, RS, Brazil. [Okusaka, T.] Natl Canc Ctr, Dept Hepatobiliary & Pancreat Oncol, Tokyo, Japan. [Van Laethem, J. -L.] Erasme Univ Hosp, Dept Gastroenterol, B-1070 Brussels, Belgium. [Lipton, L. R.] Royal Melbourne Hosp, Med Oncol, Parkville, Vic 3050, Australia. [Riess, H.] Charite, Dept Hematol Oncol & Tumor Immunol, D-13353 Berlin, Germany. [Szczylik, C.] Mil Inst Hlth Serv, Dept Oncol, Warsaw, Poland. [Moore, M. J.] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Peeters, M.] Univ Antwerp Hosp, Dept Oncol, Edegum, Belgium. [Bodoky, G.] St Laszlo Hosp, Dept Oncol, Budapest, Hungary. [Ikeda, M.] Natl Canc Ctr Hosp East, Dept Hepatobiliary & Pancreat Oncol, Kashiwa, Chiba, Japan. [Melichar, B.] Palacky Univ, Sch Med, Dept Oncol, CR-77147 Olomouc, Czech Republic. [Melichar, B.] Teaching Hosp, Olomouc, Czech Republic. [Nemecek, R.] Masaryk Univ, Sch Med, Dept Oncol, Brno, Czech Republic. [Nemecek, R.] Masaryk Mem Canc Inst, Brno, Czech Republic. [Ohkawa, S.] Kanagawa Canc Ctr, Dept Gastroenterol, Yokohama, Kanagawa 2410815, Japan. [Swieboda-Sadlej, A.] Med Univ Warsaw, Dept Haematol Oncol & Internal Med, Warsaw, Poland. [Tjulandin, S. A.] Russian Canc Res Ctr, Dept Clin Pharmacol & Chemotherapy, Moscow, Russia. [Van Cutsem, E.] Univ Hosp Gasthuisberg Leuven, Digest Oncol, Leuven, Belgium. [Van Cutsem, E.] Katholieke Univ Leuven, Leuven, Belgium. [Loberg, R.] Amgen Inc, Med Sci, Thousand Oaks, CA 91320 USA. [Haddad, V.] Amgen Ltd, Global Biostat Sci, Cambridge, England. [Gansert, J. L.] Global Dev, Thousand Oaks, CA USA. [Bach, B. A.] Amgen Inc, Dev Oncol Therapeut, Thousand Oaks, CA 91320 USA. [Carrato, A.] Univ Hosp Ramon y Cajal, Dept Med Oncol, Madrid, Spain. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, Dept Med Oncol Solid Tumor Oncol, Mailstop Dana 1220,450 Brookline Ave, Boston, MA 02215 USA. EM charles_fuchs@dfci.harvard.edu RI Peeters, Marc/C-5525-2013 OI Peeters, Marc/0000-0003-4969-2303 FU Amgen Inc.; Takeda Global Research & Development Center, Inc. FX This study was supported by Amgen Inc. in collaboration with Takeda Global Research & Development Center, Inc. There were no grants or applicable grant numbers for this study. NR 28 TC 26 Z9 28 U1 3 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2015 VL 26 IS 5 BP 921 EP 927 DI 10.1093/annonc/mdv027 PG 7 WC Oncology SC Oncology GA CH2BS UT WOS:000353830000014 PM 25609246 ER PT J AU Martin-Harris, B McFarland, D Hill, EG Strange, CB Focht, KL Wan, Z Blair, J McGrattan, K AF Martin-Harris, Bonnie McFarland, David Hill, Elizabeth G. Strange, Charlton B. Focht, Kendrea L. Wan, Zhuang Blair, Julie McGrattan, Katlyn TI Respiratory-Swallow Training in Patients With Head and Neck Cancer SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Deglutition disorders; Feedback, sensory; Head and neck neoplasms; Rehabilitation; Respiratory aspiration ID SWALLOW/RESPIRATORY PHASE-RELATIONSHIPS; OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; OROPHARYNGEAL CANCER; DYSPHAGIC PATIENTS; NORMAL ADULTS; BOLUS VOLUME; PHARYNGEAL PHASES; APNEA DURATION; ORAL-CANCER AB Objective: To test a novel intervention to train swallowing to occur in the midexpiratory to low expiratory phase of quiet breathing to improve swallowing safety and efficiency. Design: Safety and efficacy nonrandomized controlled trial with 1-month follow-up. Setting: Ambulatory clinics. Participants: Patients (N=30) with head and neck cancer (HNC) and chronic dysphagia completed the intervention. Fifteen of these patients participated in a 1-month follow-up visit. Interventions: Training protocol based on hierarchy of motor skill acquisition to encourage autonomous and optimal respiratory-swallowing coordination. Visual feedback of respiratory phase and volume for swallowing initiation was provided by nasal airflow and rib cage/abdomen signals. Main Outcome Measures: Respiratory-swallow phase pattern, Modified Barium Swallow Impairment Profile (MBSIrnP) scores, Penetration-Aspiration Scale (PAS) scores, and MD Anderson Dysphagia Inventory scores. Results: Using visual feedback, patients were trained to initiate swallows during the midexpiratory phase of quiet breathing and continue to expire after swallowing. This optimal phase patterning increased significantly after treatment (P<.0001). Changes in respiratory-swallowing coordination were associated with improvements in 3 MBSIrnP component scores: laryngeal vestibular closure (P=.0004), tongue base retraction (P<.0001), and pharyngeal residue (P=.01). Significant improvements were also seen in PAS scores (P<.0001). Relative to pretreatment values, patients participating in 1-month follow-up had increased optimal phase patterning (P<.0001), improved laryngeal vestibular closure (P=.01), tongue base retraction (P=.003), and pharyngeal residue (P=.006) MBSImP scores and improved PAS scores (P<.0001). Conclusions: Improvements in respiratory-swallowing coordination can be trained using a systematic protocol and respiratory phase-lung volume-related biofeedback in patients with HNC and chronic dysphagia, with favorable effects on airway protection and bolus clearance. (C) 2015 by the American Congress of Rehabilitation Medicine C1 [Martin-Harris, Bonnie; Focht, Kendrea L.; McGrattan, Katlyn] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Coll Med, Charleston, SC 29425 USA. [Martin-Harris, Bonnie; Focht, Kendrea L.; Blair, Julie; McGrattan, Katlyn] Med Univ S Carolina, Evelyn Trammell Inst Voice & Swallowing, Charleston, SC 29425 USA. [Martin-Harris, Bonnie; Focht, Kendrea L.; Blair, Julie] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [McFarland, David] Univ Montreal, Fac Med, Montreal, PQ H3C 3J7, Canada. [McFarland, David] McGill Univ, Fac Med, Montreal, PQ, Canada. [Hill, Elizabeth G.; Wan, Zhuang] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Strange, Charlton B.] Med Univ S Carolina, Coll Med, Div Pulm & Crit Med, Charleston, SC 29425 USA. RP Martin-Harris, B (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM harrisbm@musc.edu FU Department of Veterans Affairs [C7135R]; National Institutes of Health [R21DC010480] FX Supported by the Department of Veterans Affairs (grant no. C7135R); and the National Institutes of Health (grant no. R21DC010480). NR 74 TC 6 Z9 6 U1 2 U2 15 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 MAY PY 2015 VL 96 IS 5 BP 885 EP 893 DI 10.1016/j.apmr.2014.11.022 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CH6JL UT WOS:000354142800016 PM 25498307 ER PT J AU Hughes, AJ Beier, M Hartoonian, N Turner, AP Amtmann, D Ehde, DM AF Hughes, Abbey J. Beier, Meghan Hartoonian, Narineh Turner, Aaron P. Amtmann, Dagmar Ehde, Dawn M. TI Self-Efficacy as a Longitudinal Predictor of Perceived Cognitive Impairment in Individuals With Multiple Sclerosis SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Cognition; Executive function; Longitudinal studies; Multiple sclerosis; Rehabilitation; Self efficacy; Self report ID QUALITY-OF-LIFE; DISABILITY STATUS SCALE; TRAUMATIC BRAIN-INJURY; PHYSICAL-ACTIVITY; HEALTH-STATUS; DEPRESSION; ADJUSTMENT; MANAGEMENT; DISORDERS; ADHERENCE AB Objectives: To determine whether self-efficacy longitudinally predicts 2 types of perceived cognitive impairment (PCI) in multiple sclerosis (MS): general cognitive functioning and executive functioning; and secondarily to assess whether self-efficacy mediates the relationships between depression, fatigue, and PCI. Design: Longitudinal analysis of self-report survey data collected over 3 years. Hierarchical regression analyses examined the relationship between self-efficacy and PCI, adjusting for depression and fatigue. Additional analyses tested self-efficacy as a mediator between depression, fatigue, and PCI. Setting: Community. Participants: Community-dwelling individuals with MS (N=233; age range, 22-83y) were recruited from a larger longitudinal survey study of individuals with MS (N=562). Interventions: Not applicable. Main Outcome Measures: Primary outcome measures were the Applied Cognition General Concerns and the Applied Cognition Executive Function domains of the Quality of Life in Neurological Disorders (NeuroQoL) measures. Results: Self-efficacy was significantly correlated with PCI at baseline (r=.40.53) and 3 years later (r=.36.44). In multivariate regression analyses, self-efficacy was a significant longitudinal predictor of PCI, both for general cognitive functioning (13=20, P<.01) and executive functioning (13=.16, P<.05). Self-efficacy partially mediated the relationships between depression, fatigue, and PCI. Conclusions: Self-efficacy may influence how individuals with MS perceive their cognitive functioning over time. Interventions that target self-efficacy, particularly early in the disease course, may lead to improvements in PCI, as well as improvements in fatigue and depression. (C) 2015 by the American Congress of Rehabilitation Medicine C1 [Hughes, Abbey J.; Beier, Meghan; Turner, Aaron P.; Amtmann, Dagmar; Ehde, Dawn M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98104 USA. [Hughes, Abbey J.; Hartoonian, Narineh; Turner, Aaron P.] Vet Affairs Puget Sound Hlth Care Syst, Multiple Sclerosis Ctr Excellence West, Seattle, WA USA. RP Hughes, AJ (reprint author), Univ Washington, Dept Rehabil Med, 325 Ninth Ave,Box 359612, Seattle, WA 98104 USA. EM ajhughes@uw.edu RI Hughes, Abbey/K-8861-2015 OI Hughes, Abbey/0000-0002-7612-6887 FU Department of Education, National Institute on Disability and Rehabilitation Research [H133B031129, H133B080025]; National Institutes of Health (NIH) through the NIH Roadmap for Medical Research [5U01AR052171-03]; National Multiple Sclerosis Society [MB 0026] FX Supported by the Department of Education, National Institute on Disability and Rehabilitation Research (grant nos. H133B031129, H133B080025); the National Institutes of Health (NIH) through the NIH Roadmap for Medical Research (grant no. 5U01AR052171-03); and the National Multiple Sclerosis Society (grant no. MB 0026). The contents of this article do not necessarily represent the policy of the Department of Education and should not assume endorsement by the Federal Government. NR 51 TC 3 Z9 3 U1 2 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 MAY PY 2015 VL 96 IS 5 BP 913 EP 919 DI 10.1016/j.apmr.2015.01.008 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CH6JL UT WOS:000354142800019 PM 25597915 ER PT J AU Lord, SP Sheng, E Imel, ZE Baer, J Atkins, DC AF Lord, Sarah Peregrine Sheng, Elisa Imel, Zac E. Baer, John Atkins, David C. TI More Than Reflections: Empathy in Motivational Interviewing Includes Language Style Synchrony Between Therapist and Client SO BEHAVIOR THERAPY LA English DT Article DE empathy; motivational interviewing; synchrony; linguistic inquiry word count; motivational interviewing treatment integrity ID SOCIAL-INTERACTION; PSYCHOTHERAPY; METAANALYSIS; COUNSELORS; BEHAVIORS AB Empathy is a basic psychological process that involves the development of synchrony in dyads. It is also a foundational ingredient in specific, evidence-based behavioral treatments like motivational interviewing (MI). Ratings of therapist empathy typically rely on a gestalt, "felt sense" of therapist understanding and the presence of specific verbal behaviors like reflective listening. These ratings do not provide a direct test of psychological processes like behavioral synchrony that are theorized to be an important component of empathy in psychotherapy. To explore a new objective indicator of empathy, we hypothesized that synchrony in language style (i.e., matching how statements are phrased) between client and therapists would predict gestalt ratings of empathy over and above the contribution of reflections. We analyzed 122 MI transcripts with high and low empathy ratings based on the Motivational Interviewing Treatment Integrity global rating scale. Linguistic inquiry and word count was used to estimate language style synchrony (LSS) of adjacent client and therapist talk turns. High-empathy sessions showed greater LSS across 11 language style categories compared with low-empathy sessions (p<.01), and overall, average LSS was notably higher in high-empathy versus low-empathy sessions (d = 0.62). Regression analyses showed that LSS was predictive of empathy ratings over and above reflection counts; a 1 SD increase in LSS is associated with a 2.4 times increase in the odds of a high-empathy rating, controlling for therapist reflections (odds ratio = 2.4; 95% CI: 1.36; 4.24, p<.01). These findings suggest empathy ratings are related to synchrony in language style, over and above synchrony of content as measured by therapist reflections. Novel indicators of therapist empathy may have implications for the study of MI process as well as the training of therapists. C1 [Lord, Sarah Peregrine; Sheng, Elisa; Baer, John; Atkins, David C.] Univ Washington, Seattle, WA 98195 USA. [Imel, Zac E.] Univ Utah, Salt Lake City, UT 84112 USA. [Baer, John] VA Puget Sound Healthcare Syst, Seattle Div, Seattle, WA USA. RP Lord, SP (reprint author), Univ Washington, Ctr Study Hlth & Risk Behav, Dept Psychiat & Behav Sci, 1100 Northeast 45th St,Suite 300,Box 354944, Seattle, WA 98195 USA. EM grinlord@uw.edu OI Atkins, David/0000-0002-5781-9880 FU University of Utah; National Institute of Drug Abuse (NIDA) of the National Institutes of Health [R34/DA034860]; National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01/AA018673]; NIDA [R01/DA016360] FX Funding for the preparation of this manuscript was provided by a University of Utah Seed Grant and was also supported by the National Institute of Drug Abuse (NIDA) of the National Institutes of Health under award number R34/DA034860 and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) under award number R01/AA018673. The original trial was supported by a grant from NIDA (R01/DA016360). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 47 TC 4 Z9 4 U1 6 U2 15 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD MAY PY 2015 VL 46 IS 3 BP 296 EP 303 PG 8 WC Psychology, Clinical SC Psychology GA CH6LP UT WOS:000354148400002 PM 25892166 ER PT J AU Wang, TY McElroy, A Halaney, D Vela, D Fung, E Hossain, S Phipps, J Wang, BQ Yin, BW Feldman, MD Milner, TE AF Wang, Tianyi McElroy, Austin Halaney, David Vela, Deborah Fung, Edmund Hossain, Shafat Phipps, Jennifer Wang, Bingqing Yin, Biwei Feldman, Marc D. Milner, Thomas E. TI Dual-modality fiber-based OCT-TPL imaging system for simultaneous microstructural and molecular analysis of atherosclerotic plaques SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; COMBINED 2-PHOTON MICROSCOPY; CORONARY-ARTERY-DISEASE; IN-VIVO; FLUORESCENCE MICROSCOPY; MULTIPHOTON MICROSCOPY; GOLD NANORODS; INFLAMMATION; MACROPHAGES; CATHETER AB New optical imaging techniques that provide contrast to study both the anatomy and composition of atherosclerotic plaques can be utilized to better understand the formation, progression and clinical complications of human coronary artery disease. We present a dual-modality fiber-based optical imaging system for simultaneous microstructural and molecular analysis of atherosclerotic plaques that combines optical coherence tomography (OCT) and two-photon luminescence (TPL) imaging. Experimental results from ex vivo human coronary arteries show that OCT and TPL optical contrast in recorded OCT-TPL images is complimentary and in agreement with histological analysis. Molecular composition (e. g., lipid and oxidized-LDL) detected by TPL imaging can be overlaid onto plaque microstructure depicted by OCT, providing new opportunities for atherosclerotic plaque identification and characterization. (C) 2015 Optical Society of America C1 [Wang, Tianyi; McElroy, Austin; Fung, Edmund; Hossain, Shafat; Wang, Bingqing; Yin, Biwei; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Halaney, David; Phipps, Jennifer; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Div Cardiol, San Antonio, TX 78229 USA. [Halaney, David; Feldman, Marc D.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Vela, Deborah] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX 77030 USA. RP Wang, TY (reprint author), Univ Texas Austin, Dept Biomed Engn, 1 Univ Stn C0800, Austin, TX 78712 USA. EM Tianyi.Wang@utexas.edu OI Halaney, David/0000-0003-4437-0516 FU ASLMS Research Grant; Veterans Health Administration Merit Grant [I01 BX000397]; American Heart Association [13POST17080074]; Clayton Foundation for Biomedical Research; University of Texas at Austin FX The authors would like to acknowledge the technical support from Chris Hoy, PhD and Jingjing Sun, ME. This work is supported by ASLMS Research Grant to Wang, Veterans Health Administration Merit Grant (I01 BX000397) to Feldman, American Heart Association Grant (13POST17080074) to Phipps, Research Grant from Clayton Foundation for Biomedical Research to Milner and Feldman, and Biomedical Engineering Advancement Fund from the University of Texas at Austin to Milner. NR 63 TC 3 Z9 3 U1 1 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD MAY 1 PY 2015 VL 6 IS 5 BP 1665 EP 1678 DI 10.1364/BOE.6.001665 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CH3JN UT WOS:000353927100009 PM 26137371 ER PT J AU Tamari, R Mughal, TI Rondelli, D Hasserjian, R Gupta, V Odenike, O Fauble, V Finazzi, G Pane, F Mascarenhas, J Prchal, J Giralt, S Hoffman, R AF Tamari, R. Mughal, T. I. Rondelli, D. Hasserjian, R. Gupta, V. Odenike, O. Fauble, V. Finazzi, G. Pane, F. Mascarenhas, J. Prchal, J. Giralt, S. Hoffman, R. TI Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era? SO BONE MARROW TRANSPLANTATION LA English DT Review ID STEM-CELL TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; BONE-MARROW FIBROSIS; PROGNOSTIC SCORING SYSTEM; NEGATIVE MYELOPROLIFERATIVE NEOPLASMS; CHRONIC IDIOPATHIC MYELOFIBROSIS; INTERNATIONAL WORKING GROUP; CANCER-TESTIS ANTIGEN; VERSUS-HOST-DISEASE; ESSENTIAL THROMBOCYTHEMIA AB At present, allo-SCT is the only curative treatment for patients with myelofibrosis (MF). Unfortunately, a significant proportion of candidate patients are considered transplant ineligible due to their poor general condition and advanced age at the time of diagnosis. The approval of the first JAK inhibitor, ruxolitinib, for patients with advanced MF in 2011 has had a qualified impact on the treatment algorithm. The drug affords substantial improvement in MF-associated symptoms and splenomegaly but no major effect on the natural history. There has, therefore, been considerable support for assessing the drug's candidacy in the peritransplant period. The drug's precise impact on clinical outcome following allo-SCT is currently not known; nor are the drug's long-term efficacy and safety known. Considering the rarity of MF and the small proportion of patients who undergo allo-SCT, well designed collaborative efforts are required. In order to address some of the principal challenges, an expert panel of laboratory and clinical experts in this field was established, and an independent workshop held during the 54th American Society of Hematology Annual Meeting in New Orleans, USA on 6 December 2013, and the European Hematology Association's Annual Meeting in Milan, Italy on 13 June 2014. This document summarizes the results of these efforts. C1 [Tamari, R.; Giralt, S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mughal, T. I.] Tufts Med Ctr, Div Hematol & Oncol, Boston, MA 02111 USA. [Rondelli, D.] Univ Illinois, Chicago, IL USA. [Hasserjian, R.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gupta, V.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Odenike, O.] Univ Chicago, Chicago, IL 60637 USA. [Fauble, V.] Mayo Clin, Ctr Canc, Scottsdale, AZ USA. [Finazzi, G.] Papa Giovani XXIII Hosp & Res Ctr, Bergamo, Italy. [Pane, F.] Univ Naples Federico II, Naples, Italy. [Mascarenhas, J.; Hoffman, R.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Prchal, J.] Huntsman Canc Ctr, Salt Lake City, UT USA. RP Mughal, TI (reprint author), Tufts Med Ctr, Div Hematol & Oncol, Boston, MA 02111 USA. EM tmughal911@hotmail.com FU Novartis; Incyte; Eisai Pharmaceuticals; TopoTarget Pharmaceuticals FX VG was a member of the Scientific Advisory Board at Novartis and Incyte, and received research support from Novartis and Incyte. RHa was a member of the Scientific Advisory Board at Incyte. JM received research support from Novartis and Incyte. TIM was a consultant at Novartis and Incyte. OO was a member of the Scientific Advisory Board at Sanofi-Aventis, Incyte, Spectrum Pharmaceuticals, Sunesis Pharmaceuticals and Algeta Pharmaceuticals, and received research support from Eisai Pharmaceuticals and TopoTarget Pharmaceuticals. All other authors declare no conflict of interest. NR 109 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2015 VL 50 IS 5 BP 628 EP 636 DI 10.1038/bmt.2014.323 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CH4ZI UT WOS:000354042900003 PM 25665047 ER PT J AU Wu, WL Adams, CE Stevens, KE Chow, KH Freedman, R Patterson, PH AF Wu, Wei-Li Adams, Catherine E. Stevens, Karen E. Chow, Ke-Huan Freedman, Robert Patterson, Paul H. TI The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Maternal immune activation (MIA); Maternal infection; Poly(I:C); Nicotinic acetylcholine receptor alpha 7 subunit (alpha 7AChR, CHRNA7, Chrna7); Choline supplementation; Interleukin-6 (IL-6); Schizophrenia; Autism ID FETAL-BRAIN-DEVELOPMENT; CHOLINE SUPPLEMENTATION; GENE-EXPRESSION; ADULT PSYCHOPATHOLOGY; C57BL/6 SUBSTRAINS; SENSORY INHIBITION; ANIMAL-MODELS; MOUSE; SCHIZOPHRENIA; AUTISM AB Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.3 is CHRNA7, which encodes the nicotinic acetylcholine receptor alpha 7 subunit (alpha 7nAChR) associated with schizophrenia in clinical studies,and rodent models. This study investigates the role of alpha 7nAChR in maternal immune activation (MIA) mice model, a murine model of environmental risk factor for autism and schizophrenia. We provided choline, a selective alpha 7nAChR agonist among its several developmental roles, in the diet of C57BL/6N wild-type dams throughout the gestation and lactation period and induced MIA at mid-gestation. The adult offspring behavior and gene expression profile in the maternal-placental-fetal axis at mid-gestation were investigated. We found that choline supplementation prevented several MIA-induced behavioral abnormalities in the wild-type offspring. Pro-inflammatory cytokine interleukin-6 (Il6) and Chrna7 gene expression in the wild-type fetal brain were elevated by poly(I:C) injection and were suppressed by gestational choline supplementation. We further investigated the gene expression level of Il6 in Chrna7 mutant mice. We found that the basal level of Il6 was higher in Chrna7 mutant fetal brain, which suggests that alpha 7nAChR may serve an anti-inflammatory role in the fetal brain during development. Lastly, we induced MIA in Chrna7(+/-) offspring. The Chrna7(+/-) offspring were more vulnerable to MIA, with increased behavioral abnormalities. Our study shows that alpha 7nAChR modulates inflammatory response affecting the fetal brain and demonstrates its effects on offspring behavior development after MIA. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wu, Wei-Li; Chow, Ke-Huan; Patterson, Paul H.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA. [Adams, Catherine E.] Denver VA Med Ctr, Denver, CO 80220 USA. [Adams, Catherine E.; Stevens, Karen E.; Freedman, Robert] Univ Colorado, Dept Psychiat, Aurora, CO 80045 USA. RP Wu, WL (reprint author), MC 156-29,1200 E Calif Blvd, Pasadena, CA 91125 USA. EM wlwu@caltech.edu OI Wu, Wei-Li/0000-0003-2610-1881 FU NIH Conte Center Award, United States [NIH 5P50MH086383-04]; Autism Speaks, United States [7670]; National Science Council, Taiwan [NSC 101-2917-I-564-039] FX We acknowledge Laura Rodriguez for administrative assistance; Jan Ko, Elaine Y. Hsiao and Natalia Malkova for technical assistance; Lorena C. Sandoval, Kwan F. Lee and Jaime Rodriguez for caring for the animals. This work was supported by NIH Conte Center Award, United States (to P.H.P.; NIH 5P50MH086383-04), Autism Speaks, United States (to P.H.P; #7670), and postdoctoral fellowship from National Science Council, Taiwan (to W.-L.W.; NSC 101-2917-I-564-039). NR 63 TC 11 Z9 11 U1 5 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 EI 1090-2139 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD MAY PY 2015 VL 46 BP 192 EP 202 DI 10.1016/j.bbi.2015.02.005 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CH0ZO UT WOS:000353751100023 PM 25683697 ER PT J AU Baumuller, E Schaller, SJ Lama, YC Frick, CG Bauhofer, T Eikermann, M Fink, H Blobner, M AF Baumueller, E. Schaller, S. J. Lama, Y. Chiquito Frick, C. G. Bauhofer, T. Eikermann, M. Fink, H. Blobner, M. TI Postoperative impairment of motor function at train-of-four ratio >= 0.9 cannot be improved by sugammadex (1 mg kg(-1)) SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE neuromuscular blocking agent; postoperative residual paralysis; quantitative neuromuscular monitoring; sugammadex ID RESIDUAL NEUROMUSCULAR BLOCKADE; NEGATIVE PHARYNGEAL PRESSURE; GENIOGLOSSUS MUSCLE-ACTIVITY; PARTIALLY PARALYZED HUMANS; ADDUCTOR POLLICIS MUSCLES; RELAXANT BINDING-AGENT; QUANTITATIVE ASSESSMENT; ANTIDEPOLARIZING BLOCK; AIRWAY COLLAPSIBILITY; GRIP STRENGTH AB Background. A train-of-four ratio (TOFR) >= 0.9 measured by quantitative neuromuscular monitoring is accepted as an indication of sufficient neuromuscular recovery for extubation, even though many postsynaptic acetylcholine receptors may still be inhibited. We investigated whether antagonism with sugammadex after spontaneous recovery to TOFR >= 0.9 further improves muscle function or subjective well-being. Methods. Following recovery to TOFR >= 0.9 and emergence from anaesthesia, 300 patients randomly received either sugammadex 1.0 mg kg(-1) or placebo. Fine motor function (Purdue Pegboard Test) and maximal voluntary grip strength were measured before and after surgery (before and after test drug administration). At discharge from the postanaesthesia care unit, well-being was assessed with numerical analogue scales and the Quality-of-Recovery Score 40 (QoR-40). Results. Patients' fine motor function [6 (SD 4) vs 15 (3) pegs (30 s)(-1), P<0.05] and maximal voluntary grip strength (284 (126) vs 386 (125) N, P<0.05) were significantly lower after anaesthesia compared with the pre-anaesthesia baseline. After sugammadex or placebo, motor function was significantly improved in both groups but did not reach the preoperative level. There was no difference between groups at any time. Global well-being was unaffected (QoR-40: placebo, 174 vs 185; sugammadex, 175 vs 186, P>0.05). Conclusions. Antagonizing rocuronium at TOF >= 0.9 with sugammadex 1.0 mg kg(-1) did not improve patients' motor function or well-being when compared with placebo. Our data support the view that TOFR >= 0.9 measured by electromyography signifies sufficient recovery of neuromuscular function. C1 [Baumueller, E.; Schaller, S. J.; Lama, Y. Chiquito; Frick, C. G.; Bauhofer, T.; Fink, H.; Blobner, M.] Tech Univ Munich, Klinikum Rechts Isar, Klin Anaesthesiol, D-81675 Munich, Germany. [Eikermann, M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Eikermann, M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Baumuller, E (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Klin Anaesthesiol, Ismaninger Str 22, D-81675 Munich, Germany. EM eva.baumueller@lrz.tu-muenchen.de OI Schaller, Stefan/0000-0002-6683-9584 FU Klinik fur Anaesthesiologie, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger, Munchen, Germany FX Klinik fur Anaesthesiologie, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Stage 22, 81675 MUnchen, Germany. NR 44 TC 3 Z9 3 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 EI 1471-6771 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD MAY PY 2015 VL 114 IS 5 BP 785 EP 793 DI 10.1093/bja/aeu453 PG 9 WC Anesthesiology SC Anesthesiology GA CH6NO UT WOS:000354153500011 PM 25586724 ER PT J AU Gulur, P Tsui, B Pathak, R Koury, KM Lee, H AF Gulur, P. Tsui, B. Pathak, R. Koury, K. M. Lee, H. TI Retrospective analysis of the incidence of epidural haematoma in patients with epidural catheters and abnormal coagulation parameters SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE anticoagulant; epidural analgesia; international normalized ratio; partial thromboplastin time; spinal epidural haematoma ID NEURAXIAL ANESTHESIA; REGIONAL-ANESTHESIA; INVASIVE PROCEDURES; ANTICOAGULATION; COMPLICATIONS; RISK AB Background. Epidural haematoma is a rare but potentially catastrophic complication associated with epidural catheterization. The times of insertion and removal of epidural catheters are high-risk periods for epidural haematoma formation, especially with abnormal coagulation parameters. There is a lack of data on the incidence of epidural haematoma in patients with abnormal coagulation parameters. Methods. A retrospective analysis was undertaken from 2002 to 2009 on patients with an epidural catheter. Queries were performed on the coagulation parameters for the dates of placement and removal of the catheters and on all documented epidural haennatoma cases. Results. During the study period, 11 600 epidural catheters were placed. In the setting of abnormal coagulation parameters, 278 (2.4%) epidural catheters were placed and 351 (3%) were removed. Two epidural haematomas occurred; both patients had epidural catheters and spinal drains placed for vascular procedures with abnormal coagulation parameters after operatation. The haematomas occurred after removal of the catheters. Based on our study, the incidence of epidural haematoma in patients with abnormal coagulation parameters is 1 in 315 patients, with the lower limit of the 95% confidence interval at 87 and the upper limit at 2597. Conclusions. The risk of epidural haematoma is clearly elevated with abnormal coagulation parameters. Our data suggest that as the incidence of epidural haematoma with neuraxial access in patients with abnormal coagulation is not 100%, individual risk-benefit evaluations are warranted. C1 [Gulur, P.; Tsui, B.; Pathak, R.; Koury, K. M.; Lee, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gulur, P (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 330, Boston, MA 02114 USA. EM pgulur@yahoo.com NR 13 TC 7 Z9 7 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 EI 1471-6771 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD MAY PY 2015 VL 114 IS 5 BP 808 EP 811 DI 10.1093/bja/aeu461 PG 4 WC Anesthesiology SC Anesthesiology GA CH6NO UT WOS:000354153500014 PM 25614136 ER PT J AU Swords, RT Erba, HP DeAngelo, DJ Bixby, DL Altman, JK Maris, M Hua, ZW Blakemore, SJ Faessel, H Sedarati, F Dezube, BJ Giles, FJ Medeiros, BC AF Swords, Ronan T. Erba, Harry P. DeAngelo, Daniel J. Bixby, Dale L. Altman, Jessica K. Maris, Michael Hua, Zhaowei Blakemore, Stephen J. Faessel, Helene Sedarati, Farhad Dezube, Bruce J. Giles, Francis J. Medeiros, Bruno C. TI Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE MLN4924; acute myeloid leukaemia; NEDD8; NEDD8-activating enzyme; pevonedistat ID NEDD8 CONJUGATION PATHWAY; MANTLE CELL LYMPHOMA; PROTEIN-DEGRADATION; MULTIPLE-MYELOMA; CUL1 EXPRESSION; KAPPA-B; BORTEZOMIB; CANCER; UBIQUITIN; TRIAL AB This trial was conducted to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the first in class NEDD8-activating enzyme (NAE) inhibitor, pevonedistat, and to investigate pevonedistat pharmacokinetics and pharmacodynamics in patients with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Pevonedistat was administered via a 60-min intravenous infusion on days 1, 3 and 5 (schedule A, n=27), or days 1, 4, 8 and 11 (schedule B, n=26) every 21-days. Dose escalation proceeded using a standard 3+3' design. Responses were assessed according to published guidelines. The MTD for schedules A and B were 59 and 83mg/m(2), respectively. On schedule A, hepatotoxicity was dose limiting. Multi-organ failure (MOF) was dose limiting on schedule B. The overall complete (CR) and partial (PR) response rate in patients treated at or below the MTD was 17% (4/23, 2 CRs, 2 PRs) for schedule A and 10% (2/19, 2 PRs) for schedule B. Pevonedistat plasma concentrations peaked after infusion followed by elimination in a biphasic pattern. Pharmacodynamic studies of biological correlates of NAE inhibition demonstrated target-specific activity of pevonedistat. In conclusion, administration of the first-in-class agent, pevonedistat, was feasible in patients with MDS and AML and modest clinical activity was observed. C1 [Swords, Ronan T.] Sylvester Comprehens Canc Ctr, Leukemia Program, Miami, FL USA. [Erba, Harry P.; Bixby, Dale L.] Univ Michigan, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Altman, Jessica K.; Giles, Francis J.] Northwestern Univ, Northwestern Med Dev Therapeut Inst, Chicago, IL 60611 USA. [Maris, Michael] Colorado Blood Canc Inst, Denver, CO USA. [Hua, Zhaowei; Blakemore, Stephen J.; Faessel, Helene; Sedarati, Farhad; Dezube, Bruce J.] Takeda Pharmaceut Int Co, Cambridge, MA USA. [Medeiros, Bruno C.] Stanford Univ, Sch Med, Div Hematol, Stanford, CA 94305 USA. RP Swords, RT (reprint author), Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Leukemia Program, 1475 NW 12th Ave, Miami, FL 33136 USA. EM rswords@med.miami.edu NR 50 TC 37 Z9 37 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2015 VL 169 IS 4 BP 534 EP 543 DI 10.1111/bjh.13323 PG 10 WC Hematology SC Hematology GA CH3WN UT WOS:000353961600007 PM 25733005 ER PT J AU Demark-Wahnefried, W Rogers, LQ Alfano, CM Thomson, CA Courneya, KS Meyerhardt, JA Stout, NL Kvale, E Ganzer, H Ligibel, JA AF Demark-Wahnefried, Wendy Rogers, Laura Q. Alfano, Catherine M. Thomson, Cynthia A. Courneya, Kerry S. Meyerhardt, Jeffrey A. Stout, Nicole L. Kvale, Elizabeth Ganzer, Heidi Ligibel, Jennifer A. TI Practical clinical interventions for diet, physical activity, and weight control in cancer survivors SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review DE diet; physical activity; exercise; weight control; cancer survivors; neoplasms; exercise; oncology; primary care ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; RESEARCH FUND/AMERICAN INSTITUTE; POSTMENOPAUSAL BREAST-CANCER; PATIENTS RECEIVING CHEMOTHERAPY; BODY-MASS INDEX; HOME-BASED DIET; PROSTATE-CANCER; EXERCISE INTERVENTION; BEHAVIOR-CHANGE AB The importance of expanding cancer treatment to include the promotion of overall long-term health is emphasized in the Institute of Medicine report on delivering quality oncology care. Weight management, physical activity, and a healthy diet are key components of tertiary prevention but may be areas in which the oncologist and/or the oncology care team may be less familiar. This article reviews current diet and physical activity guidelines, the evidence supporting those recommendations, and provides an overview of practical interventions that have resulted in favorable improvements in lifestyle behavior change in cancer survivors. It also describes current lifestyle practices among cancer survivors and the role of the oncologist in helping cancer patients and survivors embark upon changes in lifestyle behaviors, and it calls for the development of partnerships between oncology providers, primary care providers, and experts in nutrition, exercise science, and behavior change to help positively orient cancer patients toward longer and healthier lives. CA Cancer J Clin 2015;65: 167-189. (c) 2015 American Cancer Society. C1 [Demark-Wahnefried, Wendy; Rogers, Laura Q.] Univ Alabama Birmingham, Dept Nutr Sci, Nutr Sci, Birmingham, AL 35294 USA. [Alfano, Catherine M.] Natl Canc Inst, Behav Res Program, Bethesda, MD USA. [Thomson, Cynthia A.] Univ Arizona, Dept Hlth Promot Sci, Hlth Promot Sci, Tucson, AZ USA. [Courneya, Kerry S.] Univ Alberta, Fac Phys Educ & Recreat, Edmonton, AB, Canada. [Meyerhardt, Jeffrey A.; Ligibel, Jennifer A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stout, Nicole L.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. [Kvale, Elizabeth] Univ Alabama Birmingham, Dept Med, Med, Birmingham, AL 35294 USA. [Ganzer, Heidi] MN Oncol, St Paul, MN USA. RP Demark-Wahnefried, W (reprint author), Wallace Tumor Inst, 1824 Sixth Ave,Room 310-D, Birmingham, AL 35295 USA. EM demark@uab.edu FU American Cancer Society [121093-CCCDA-11-191-01-CCCDA]; [CRP-14-111-01-CPPB] FX Dr. Demark-Wahnefried was supported by grant CRP-14-111-01-CPPB, and Dr. Kvale was supported by grant 121093-CCCDA-11-191-01-CCCDA from the American Cancer Society. NR 178 TC 19 Z9 19 U1 8 U2 39 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 EI 1542-4863 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAY-JUN PY 2015 VL 65 IS 3 BP 167 EP 189 DI 10.3322/caac.21265 PG 23 WC Oncology SC Oncology GA CH8GM UT WOS:000354274400003 PM 25683894 ER PT J AU Berger, AM Mitchell, SA Jacobsen, PB Pirl, WF AF Berger, Ann M. Mitchell, Sandra A. Jacobsen, Paul B. Pirl, William F. TI Screening, evaluation, and management of cancer-related fatigue: Ready for implementation to practice? SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review DE cancer-related fatigue; evidence-based interventions; multidisciplinary management; patient-reported outcomes; screening ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; L-CARNITINE SUPPLEMENTATION; COGNITIVE-BEHAVIOR THERAPY; STAGE BREAST-CANCER; PATIENTS RECEIVING CHEMOTHERAPY; III CLINICAL-TRIAL; METASTATIC COLORECTAL-CANCER; PATIENT-REPORTED OUTCOMES; STEM-CELL TRANSPLANTATION AB Evidence regarding cancer-related fatigue (fatigue) has accumulated sufficiently such that recommendations for screening, evaluation, and/or management have been released recently by 4 leading cancer organizations. These evidence-based fatigue recommendations are available for clinicians, and some have patient versions; but barriers at the patient, clinician, and system levels hinder dissemination and implementation into practice. The underlying biologic mechanisms for this debilitating symptom have not been elucidated completely, hindering the development of mechanistically driven interventions. However, significant progress has been made toward methods for screening and comprehensively evaluating fatigue and other common symptoms using reliable and valid self-report measures. Limited data exist to support the use of any pharmacologic agent; however, several nonpharmacologic interventions have been shown to be effective in reducing fatigue in adults. Never before have evidence-based recommendations for fatigue management been disseminated by 4 premier cancer organizations (the National Comprehensive Cancer, the Oncology Nursing Society, the Canadian Partnership Against Cancer/Canadian Association of Psychosocial Oncology, and the American Society of Clinical Oncology). Clinicians may ask: Are we ready for implementation into practice? The reply: A variety of approaches to screening, evaluation, and management are ready for implementation. To reduce fatigue severity and distress and its impact on functioning, intensified collaborations and close partnerships between clinicians and researchers are needed, with an emphasis on system-wide efforts to disseminate and implement these evidence-based recommendations. CA Cancer J Clin 2015;65: 190-211. (c) 2015 American Cancer Society. C1 [Berger, Ann M.] Univ Nebraska Med Ctr, Coll Nursing, Fred & Pamela Buffett Canc Ctr, Omaha, NE 68198 USA. [Mitchell, Sandra A.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Jacobsen, Paul B.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Tampa, FL 33612 USA. [Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA. [Pirl, William F.] Harvard Univ, Sch Med, Boston, MA USA. RP Berger, AM (reprint author), Univ Nebraska Med Ctr, 985330 Nebraska Med Ctr, Omaha, NE 68198 USA. EM aberger@unmc.edu NR 315 TC 21 Z9 21 U1 7 U2 41 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 EI 1542-4863 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAY-JUN PY 2015 VL 65 IS 3 BP 190 EP 211 DI 10.3322/caac.21268 PG 22 WC Oncology SC Oncology GA CH8GM UT WOS:000354274400004 PM 25760293 ER PT J AU Nayar, R Wilbur, DC AF Nayar, Ritu Wilbur, David C. TI The Pap test and Bethesda 2014 SO CANCER CYTOPATHOLOGY LA English DT Article ID OF-AMERICAN-PATHOLOGISTS; TERMINOLOGY STANDARDIZATION PROJECT; CANCER SCREENING-TESTS; ASCUS-LSIL TRIAGE; CONSENSUS GUIDELINES; INTEROBSERVER REPRODUCIBILITY; CERVICAL PATHOLOGY; CYTOLOGY; MANAGEMENT; SOCIETY AB The history of The Bethesda System for reporting cervical cytology goes back almost 3 decades. This terminology and the process that created it have had a profound impact on the practice of cervical cytology for laboratorians and clinicians alike. Herein, we summarize the process and rationale by which updates were made to the terminology in 2014 and outline the contents of the new, third edition of the Bethesda atlas and corresponding website. C1 [Nayar, Ritu] Northwestern Univ, Feinberg Sch Med, Northwestern Med, Dept Pathol, Chicago, IL 60611 USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wilbur, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Nayar, R (reprint author), Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. EM r-nayar@northwestern.edu NR 22 TC 5 Z9 5 U1 5 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD MAY PY 2015 VL 123 IS 5 BP 271 EP 281 DI 10.1002/cncy.21521 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA CI1CF UT WOS:000354477500003 PM 25931431 ER PT J AU Tanoue, S Chang, LY Li, YH Kaplan, DE AF Tanoue, Shiroh Chang, Li-Yuan Li, Yonghai Kaplan, David E. TI Monocyte-derived dendritic cells from cirrhotic patients retain similar capacity for maturation/activation and antigen presentation as those from healthy subjects SO CELLULAR IMMUNOLOGY LA English DT Article DE Dendritic cell; Cirrhosis; Hepatitis C; Monocyte; M1 macrophage; M2 macrophage; Human; Glypican-3 ID HEPATITIS-C VIRUS; HEPATOCELLULAR-CARCINOMA PATIENTS; CONSTITUTIVELY ACTIVE TLR4; CELLULAR IMMUNE-RESPONSES; MESSENGER-RNA; IN-VITRO; ALLOSTIMULATORY CAPACITY; ADOPTIVE IMMUNOTHERAPY; PERIPHERAL-BLOOD; PHASE-I/II AB Few studies have investigated the impact of liver cirrhosis on dendritic cell function. The purpose of this study was to compare the activation and antigen-presentation capacity of monocyte-derived dendritic cells (MoDC) from cirrhotic patients (CIR) relative to healthy donors (HD). MoDC from CIR and HD were matured, phenotyped, irradiated and pulsed with 15mer peptides for two hepatocellular carcinoma-related antigens, alphafetoprotein and glypican-3, then co-cultured with autologous T-cells. Expanded T-cells were evaluated by interferon-gamma ELISPOT and intracellular staining. 15 CIR and 7 HD were studied. While CD14+ monocytes from CIR displayed enhanced M2 polarization, under MoDC-polarizing conditions, we identified no significant difference between HD and CIR in maturation-induced upregulation of co-stimulation markers. Furthermore, no significant differences were observed between CIR and HD in subsequent expansion of tumor antigen-specific IFN gamma+ T-cells. Conclusion: MoDCs isolated from cirrhotic individuals retain similar capacity for in vitro activation, maturation and antigen-presentation as those from healthy donors. Published by Elsevier Inc. C1 Philadelphia VA Med Ctr, Med & Res Serv, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. RP Kaplan, DE (reprint author), Philadelphia VA Med Ctr, Res Bldg 21,A402A,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM dakaplan@mail.med.upenn.edu FU NIH [R01 CA166111]; Pennsylvania Commonwealth Universal Research Endowment FX This work was supported by the NIH R01 CA166111 (DEK) and the Pennsylvania Commonwealth Universal Research Endowment. The content of this article does not reflect the views of the VA or of the US Government. NR 52 TC 1 Z9 3 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 EI 1090-2163 J9 CELL IMMUNOL JI Cell. Immunol. PD MAY PY 2015 VL 295 IS 1 BP 36 EP 45 DI 10.1016/j.cellimm.2015.02.008 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA CH5KN UT WOS:000354074600004 PM 25734547 ER PT J AU Pozdnyakova, O Hasserjian, RP Verstovsek, S Orazi, A AF Pozdnyakova, Olga Hasserjian, Robert P. Verstovsek, Srdan Orazi, Attilio TI Impact of Bone Marrow Pathology on the Clinical Management of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Review DE Bone marrow fibrosis; Essential thrombocythemia; Polycythemia vera; Primary myelofibrosis; Ruxolitinib ID INTERNATIONAL WORKING GROUP; EARLY PRIMARY MYELOFIBROSIS; WORLD-HEALTH-ORGANIZATION; RECOMBINANT INTERFERON-ALPHA; PROGNOSTIC SCORING SYSTEM; STEM-CELL TRANSPLANTATION; MASKED POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; DISEASE TRANSFORMATION; RETICULIN FIBROSIS AB Philadelphia chromosome-negative myeloproliferative neoplasms include primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocythemia (ET). Although these 3 entities share many pathogenic characteristics, such as dysregulated Janus kinase (JAK)/signal transducer and activator of transcription signaling, they differ substantially regarding prognosis, progression to myelofibrosis (MF), risk of leukemic transformation, and specific medical needs. Accurate diagnosis and classification of myeloproliferative neoplasms are prerequisites for appropriate risk-based therapy and should be based on an integrated approach following the World Health Organization guidelines that, in addition to clinical, molecular, and cytogenetic evaluation, includes the examination of bone marrow morphology. Reticulin fibrosis at presentation in ET and PV is associated with increased risk of myelofibrotic transformation, and higher fibrosis grade in patients with MF is associated with worse prognosis. Additional assessment of collagen deposition and osteosclerosis may further increase diagnostic and prognostic precision. Moreover, the evaluation of bone marrow pathology has become very important in the new era of disease-modifying agents. In randomized controlled phase 3 studies, the JAK1/JAK2 inhibitor ruxolitinib provided rapid and lasting improvement in MF-related splenomegaly and symptom burden as well as a survival advantage compared with placebo or best available therapy. Follow-up for up to 5 years of patients who participated in a phase 1/2 study of ruxolitinib, revealed stabilization or reversal of bone marrow fibrosis in a proportion of patients with MF. Combinations of JAK inhibitors with other therapies, including agents with antifibrotic and/or anti-inflammatory properties, may possibly decrease bone marrow fibrosis further and favorably influence clinical outcomes. (C) 2015 The Authors. Published by Elsevier Inc. All rights reserved. C1 [Pozdnyakova, Olga] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Verstovsek, Srdan] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Orazi, Attilio] Cornell Univ, Weill Med Coll, New York, NY 10065 USA. RP Orazi, A (reprint author), Cornell Univ, Weill Med Coll, Room ST-707,525 E 68th St, New York, NY 10065 USA. EM ato9002@med.cornell.edu FU Incyte Corporation FX Medical writing assistance was provided by Roland Tacke, PhD, of Evidence Scientific Solutions and was funded by Incyte Corporation. NR 83 TC 5 Z9 5 U1 0 U2 9 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 EI 2152-2669 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD MAY PY 2015 VL 15 IS 5 BP 253 EP 261 DI 10.1016/j.clml.2014.11.002 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA CH6OM UT WOS:000354155900002 PM 25515354 ER PT J AU Djulbegovic, B van den Ende, J Hamm, RM Mayrhofer, T Hozo, I Pauker, SG AF Djulbegovic, Benjamin van den Ende, Jef Hamm, Robert M. Mayrhofer, Thomas Hozo, Iztok Pauker, Stephen G. CA Int Threshold Working Grp ITWG TI When is rational to order a diagnostic test, or prescribe treatment: the threshold model as an explanation of practice variation SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Review DE Clinical cognition; decision making; diagbnostic threshold; practice variation; rationality; treatment threshold ID DECISION CURVE ANALYSIS; NEGATIVE PULMONARY TUBERCULOSIS; ACCEPTABLE REGRET APPROACH; HEALTH-CARE; REGIONAL-VARIATIONS; PREDICTION MODELS; BACKGROUND RISK; PROSPECT-THEORY; PHYSICIANS; PREFERENCES AB BackgroundThe threshold model represents an important advance in the field of medical decision-making. It is a linchpin between evidence (which exists on the continuum of credibility) and decision-making (which is a categorical exercise - we decide to act or not act). The threshold concept is closely related to the question of rational decision-making. When should the physician act, that is order a diagnostic test, or prescribe treatment? The threshold model embodies the decision theoretic rationality that says the most rational decision is to prescribe treatment when the expected treatment benefit outweighs its expected harms. However, the well-documented large variation in the way physicians order diagnostic tests or decide to administer treatments is consistent with a notion that physicians' individual action thresholds vary. MethodsWe present a narrative review summarizing the existing literature on physicians' use of a threshold strategy for decision-making. ResultsWe found that the observed variation in decision action thresholds is partially due to the way people integrate benefits and harms. That is, explanation of variation in clinical practice can be reduced to a consideration of thresholds. Limited evidence suggests that non-expected utility threshold (non-EUT) models, such as regret-based and dual-processing models, may explain current medical practice better. However, inclusion of costs and recognition of risk attitudes towards uncertain treatment effects and comorbidities may improve the explanatory and predictive value of the EUT-based threshold models. ConclusionsThe decision when to act is closely related to the question of rational choice. We conclude that the medical community has not yet fully defined criteria for rational clinical decision-making. The traditional notion of rationality rooted in EUT may need to be supplemented by reflective rationality, which strives to integrate all aspects of medical practice - medical, humanistic and socio-economic - within a coherent reasoning system. C1 [Djulbegovic, Benjamin] Univ S Florida, Dept Internal Med, USF Program Comparat Res Effectiveness, Div Evidence Based Med,Morsani Coll Med, Tampa, FL 33612 USA. [Djulbegovic, Benjamin] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [van den Ende, Jef] Inst Trop Med, B-2000 Antwerp, Belgium. [Hamm, Robert M.] Univ Oklahoma, Hlth Sci Ctr, Dept Family & Prevent Med, Oklahoma City, OK USA. [Mayrhofer, Thomas] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Mayrhofer, Thomas] Harvard Univ, Sch Med, Boston, MA USA. [Hozo, Iztok] Indiana Univ Northwest, Dept Math, Gary, IN USA. [Pauker, Stephen G.] Tufts Med Ctr, Div Clin Decis Making, Dept Med, Boston, MA 02111 USA. RP Djulbegovic, B (reprint author), Tufts Med Ctr, Med & Psychiat, Div Clin Decis Making, Box 302,800 Washington St, Boston, MA 02111 USA. EM bdjulbeg@health.usf.edu; spauker@tuftsmedicalcenter.org RI Djulbegovic, Benjamin/I-3661-2012; Hozo, Iztok/R-3498-2016 OI Djulbegovic, Benjamin/0000-0003-0671-1447; Hozo, Iztok/0000-0003-2349-5707 FU DoD [W81 XWH 09-2-0175] FX Supported in part by DoD grant (#W81 XWH 09-2-0175 (Djulbegovic). NR 82 TC 6 Z9 6 U1 4 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 EI 1365-2362 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD MAY PY 2015 VL 45 IS 5 BP 485 EP 493 DI 10.1111/eci.12421 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CH3XU UT WOS:000353965300006 PM 25675907 ER PT J AU Kwon, JY Guss, D Lin, DE Abousayed, M Jeng, C Kang, S Ellington, JK AF Kwon, John Y. Guss, Daniel Lin, Darius E. Abousayed, Mostafa Jeng, Clifford Kang, Steve Ellington, J. Kent TI Effect of Delay to Definitive Surgical Fixation on Wound Complications in the Treatment of Closed, Intra-articular Calcaneus Fractures SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE calcaneus; fracture; wound complication; time to fixation; delay; risk factors; operative approach ID PRIMARY SUBTALAR ARTHRODESIS; HEALING RISK-FACTORS; INTERNAL-FIXATION; OPEN REDUCTION; OPERATIVE TREATMENT; NONOPERATIVE TREATMENT; RETROSPECTIVE ANALYSIS; MANAGEMENT; INFECTION; PROTOCOL AB Background: There are conflicting data regarding the benefits of delaying operative fixation of calcaneus fractures to decrease wound complication rates. The purpose of this study was to examine the effect of delaying fixation on wound complication rates as well as to identify other risk factors. Methods: A retrospective review at 4 institutions, including 24 surgeons, identified 405 closed, operatively treated, intra-articular calcaneus fractures. We compared fractures with and without wound complications with regards to patient demographics, medical risk factors, fracture severity, time to fixation, operative approach, primary subtalar arthrodesis, and surgeon experience. Results: Wound complications were observed in 21% (87/405) of fractures, of which 33% (29/87) required operative intervention. Male sex (P = .032), smoking (P = .028), and the extensile lateral approach (P < .001) were associated with higher complication rates. Fractures treated with an extensile lateral approach had an overall wound complication rate of 32.1%, while those treated with a sinus tarsi or percutaneous approach had an overall wound complication rate of 8.3% (odds ratio [OR], 5.3; 95% confidence interval [CI], 2.9-9.5; P < .001). Among patients treated with an extensile lateral approach, delayed operative fixation did not decrease wound complication rates despite comparable fracture severity across time points. In contrast, among fractures treated with less invasive approaches, delayed fixation beyond 2 weeks resulted in a significantly increased wound complication rate of 15.2% as compared to a wound complication rate of only 2.1% among fractures treated within a week of injury (OR, 3.2; 95% CI, 1.3-9.5; P = .01). This was observed despite similar fracture severity across time points. Primary subtalar arthrodesis did not impact complication rates. A higher wound complication rate among senior surgeons was likely secondary to their predilection for the extensile lateral approach. Conclusion: Delaying definitive fixation of closed, intra-articular calcaneus fractures did not decrease wound complication rates when using the extensile lateral approach, and we found an increased wound complication rate when using less invasive approaches. C1 [Kwon, John Y.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Guss, Daniel; Lin, Darius E.; Abousayed, Mostafa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jeng, Clifford] Mercy Med Ctr, Baltimore, MD USA. [Kang, Steve] Univ So Calif, Los Angeles, CA USA. [Ellington, J. Kent] OrthoCarolina, Charlotte, NC USA. RP Guss, D (reprint author), Massachusetts Gen Hosp, 32 Fruit St,YAW 3-3300, Boston, MA 02114 USA. EM dguss@partners.org FU Arthrex; Synthes FX The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: John Y. Kwon, MD, reports royalty compensation from Trimed Inc and royalty and consulting compensation from Paragon 28, outside the submitted work. Clifford Jeng, MD, is a consultant for OrthoHelix/Tornier and receives fellowship financial support from Arthrex and Synthes, outside the submitted work. NR 42 TC 6 Z9 7 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD MAY PY 2015 VL 36 IS 5 BP 508 EP 517 DI 10.1177/1071100714565178 PG 10 WC Orthopedics SC Orthopedics GA CH4BD UT WOS:000353975000005 PM 25589541 ER PT J AU Koukos, G Polytarchou, C Kaplan, JL Oikonomopoulos, A Ziring, D Hommes, DW Wahed, R Kokkotou, E Pothoulakis, C Winter, HS Iliopoulos, D AF Koukos, Georgios Polytarchou, Christos Kaplan, Jess L. Oikonomopoulos, Angelos Ziring, David Hommes, Daniel W. Wahed, Renaisa Kokkotou, Efi Pothoulakis, Charalabos Winter, Harland S. Iliopoulos, Dimitrios TI A MicroRNA Signature in Pediatric Ulcerative Colitis: Deregulation of the miR-4284/CXCL5 Pathway in the Intestinal Epithelium SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE noncoding RNA; colonic epithelial cells; inflammatory bowel disease ID INFLAMMATORY-BOWEL-DISEASE; CHEMOKINE ENA-78; EXPRESSION; COLON; THERAPY; TARGETS; MICE AB Background:Twenty to 25% of the patients with inflammatory bowel disease (IBD) present the disease before the age of 18 to 20, with worse extent and severity, compared with adult-onset IBD. We sought to identify the differential expression of microRNAs in pediatric ulcerative colitis (UC) and their association with different clinical phenotypes.Methods:MicroRNA expression analysis was performed in colonic tissues derived from pediatric patients with UC and controls without IBD. MiR-4284 levels were verified by real-time quantitative polymerase chain reaction in 2 additional cohorts of pediatric patients with UC. Bioinformatics analysis was performed to predict the targets of miR-4284. In vitro experiments using luciferase reporter assays and real-time polymerase chain reaction evaluated the direct effect of miR-4284 on CXCL5 mRNA. In vivo experiments were performed in 2 mouse models of experimental colitis.Results:A 24-microRNA signature was identified in colonic tissues derived from pediatric patients with UC. The most downregulated microRNA in the tissue of pediatric patients UC, relative to non-IBD controls, was miR-4284. In situ hybridization revealed that miR-4284 is present in colonic epithelial cells, and its levels correlate with the disease activity. Furthermore, we found that miR-4284 regulates CXCL5 mRNA expression through binding to its 3UTR. CXCL5 had increased mRNA levels in colonic tissue from pediatric patients with UC and correlated with disease activity. Furthermore, we found an inverse correlation between miR-4284 and CXCL5 levels in the colonic pediatric UC tissues and in 2 mouse models of experimental colitis.Conclusions:Our data reveal a novel microRNA pediatric UC signature and provide evidence that miR-4284 directly regulates CXCL5 and correlates with the disease activity. C1 [Koukos, Georgios; Polytarchou, Christos; Iliopoulos, Dimitrios] Univ Calif Los Angeles, Ctr Syst Biomed, Div Digest Dis, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kaplan, Jess L.; Winter, Harland S.] MassGen Hosp Children, Pediat IBD Ctr, Boston, MA USA. [Oikonomopoulos, Angelos; Ziring, David; Hommes, Daniel W.; Pothoulakis, Charalabos] Univ Calif Los Angeles, Ctr Inflammatory Bowel Dis, Div Digest Dis, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Wahed, Renaisa; Kokkotou, Efi] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. RP Iliopoulos, D (reprint author), Univ Calif Los Angeles, Ctr Syst Biomed, Div Digest Dis, David Geffen Sch Med, 650 Charles E Young Dr,CHS 44-133, Los Angeles, CA 90095 USA. EM diliopoulos@mednet.ucla.edu FU NIH [DK60729, DK080058]; Pediatric IBD Foundation; B. Hasso Family Foundation FX Supported in part by NIH grants DK60729 (C.P. and D.I.) and DK080058 (E.K.).; The biorepository was supported in part by funding from the Pediatric IBD Foundation (H.S.W.), Martin Schlaff (H.S.W.), and the B. Hasso Family Foundation (H.S.W.). The authors have no conflicts of interest to disclose. NR 32 TC 9 Z9 9 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2015 VL 21 IS 5 BP 996 EP 1005 DI 10.1097/MIB.0000000000000339 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CH5FU UT WOS:000354061500006 PM 25738378 ER PT J AU Moran, CJ Klein, C Muise, AM Snapper, SB AF Moran, Christopher J. Klein, Christoph Muise, Aleixo M. Snapper, Scott B. TI Very Early-onset Inflammatory Bowel Disease: Gaining Insight Through Focused Discovery SO INFLAMMATORY BOWEL DISEASES LA English DT Review DE Crohn's disease; ulcerative colitis; inflammatory bowel disease; genetics; very early onset IBD; immunodeficiency; pediatric; genome-wide association studies; whole exome sequencing ID GENOME-WIDE ASSOCIATION; CHRONIC GRANULOMATOUS-DISEASE; WISKOTT-ALDRICH-SYNDROME; LINKED LYMPHOPROLIFERATIVE SYNDROME; ULCERATIVE-COLITIS SUSCEPTIBILITY; CROHNS-DISEASE; PATHWAY ANALYSIS; SYNDROME PROTEIN; NATURAL-HISTORY; RISK LOCI AB The pathogenesis of pediatric inflammatory bowel disease (IBD) is only partially understood. Strong evidence implicates a strong genetic component including high monozygotic twin concordance and familial disease phenotype concordance rates. Genome-wide association studies have identified associations between >160 genetic loci and the risk for developing IBD. The roles of implicated genes are largely immune-mediated, although other functions include cellular migration, oxidative stress, and carbohydrate metabolism. Additionally, growing literature describes monogenic causes of IBD that frequently present as infantile or very early-onset IBD. The interplay between IBD risk single nucleotide polymorphisms and rare genetic variants has yet to be determined. Studying patients with very early-onset IBD may elicit genetic factors that could be applied to broader populations of IBD. This review describes what is known about the genetic causes of very early-onset IBD and genetic strategies that may unravel more of the genetic causes of IBD. C1 [Moran, Christopher J.] MassGen Hosp Children, Div Pediat Gastroenterol Hepatol & Nutr, Dept Pediat, Boston, MA 02114 USA. [Moran, Christopher J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Klein, Christoph] Univ Munich, Dr von Hauner Childrens Hosp, Munich, Germany. [Muise, Aleixo M.] Univ Toronto, Hosp Sick Children, Div Gastroenterol Hepatol & Nutr, Dept Paediat, Toronto, ON M5G 1X8, Canada. [Muise, Aleixo M.] Hosp Sick Children, Res Inst, SickKids Inflammatory Bowel Dis Ctr & Cell Biol P, Toronto, ON M5G 1X8, Canada. [Snapper, Scott B.] Childrens Hosp Boston, Div Pediat Gastroenterol Hepatol & Nutr, Dept Med, Boston, MA USA. [Snapper, Scott B.] Brigham & Womens Hosp, Div Gastroenterol & Hepatol, Boston, MA 02115 USA. [Snapper, Scott B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Moran, CJ (reprint author), MassGen Hosp Children, Div Pediat Gastroenterol Hepatol & Nutr, Boston, MA 02114 USA. EM cjmoran@mgh.harvard.edu FU NIH [HL59561, DK034854, AI50950]; Helmsley Charitable Trust; Wolpow Family Chair in IBD Treatment and Research FX S. B. Snapper is supported by NIH Grants HL59561, DK034854, and AI50950, the Helmsley Charitable Trust, and the Wolpow Family Chair in IBD Treatment and Research. NR 156 TC 4 Z9 4 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2015 VL 21 IS 5 BP 1166 EP 1175 DI 10.1097/MIB.0000000000000329 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CH5FU UT WOS:000354061500025 PM 25895007 ER PT J AU Maesta, I Horowitz, NS Goldstein, DP Bernstein, MR Ramirez, LAC Moulder, J Berkowitz, RS AF Maesta, Izildinha Horowitz, Neil S. Goldstein, Donald P. Bernstein, Marilyn R. Ramirez, Luz Angela C. Moulder, Janelle Berkowitz, Ross S. TI Response to Chemotherapy in Overweight/Obese Patients With Low-Risk Gestational Trophoblastic Neoplasia SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Low-risk gestational trophoblastic neoplasia; Overweight; obesity; Chemotherapy; Outcomes ID BODY-MASS INDEX; EPITHELIAL OVARIAN-CANCER; FOLINIC ACID; PRIMARY THERAPY; OBESITY; METHOTREXATE; DISEASE; MANAGEMENT; METAANALYSIS; CLASSIFICATION AB Objective Despite rising global obesity rates, the impact of obesity on gestational trophoblastic neoplasia (GTN) remains uninvestigated. This study aimed at investigating whether overweight/obesity relates to response to chemotherapy in low-risk GTN patients. Methods This nonconcurrent cohort study included 300 patients with International Federation of Gynecology and Obstetrics-defined postmolar low-risk GTN treated with a single-agent chemotherapymethotrexate or actinomycin-D (actD)between 1973 and 2012 at the New England Trophoblastic Disease Center. Chemotherapy dosing was based on actual body weight regardless of obesity status, except for 5-day courses or pulse regimens of actD. Patients were classified as overweight/obese (body mass index [BMI] 25 kg/m(2)) or non-overweight/obese (BMI <25 kg/m(2)). Information on patient characteristics and response to chemotherapy (need for second-line chemotherapy, reason for changing to an alternative chemotherapy, number of cycles, need for combination chemotherapy, and time to human chorionic gonadotropin remission) was obtained. Results Of 300 low-risk GTN patients, 81 (27%) were overweight/obese. Overweight/obese patients were older than the non-overweight/obese patients (median age: 30 vs 28 years, P = 0.004). First-line therapy using actD was more frequent in overweight/obese patients (6.2% vs 1.4%, P = 0.036). Resistance and toxicity were similar between groups. No significant difference in the number of chemotherapy cycles needed for remission or time required to achieve remission was found between groups. Conclusions No association between overweight/obesity and low-risk GTN outcomes was found. Current chemotherapy dosing using BMI seems to be appropriate for overweight/obese patients with low-risk GTN. C1 [Maesta, Izildinha; Ramirez, Luz Angela C.] UNESP Sao Paulo State Univ, Dept Gynecol & Obstet, BR-18618970 Sao Paulo, Brazil. [Maesta, Izildinha] UNESP Sao Paulo State Univ, Botucatu Med Sch, Trophoblast Dis Ctr, BR-18618970 Sao Paulo, Brazil. [Horowitz, Neil S.; Goldstein, Donald P.; Bernstein, Marilyn R.; Moulder, Janelle; Berkowitz, Ross S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Horowitz, Neil S.; Goldstein, Donald P.; Bernstein, Marilyn R.; Berkowitz, Ross S.] Donald P Goldstein MD Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. [Horowitz, Neil S.; Goldstein, Donald P.; Bernstein, Marilyn R.; Berkowitz, Ross S.] Dana Farber Canc Inst, Harvard Canc Ctr, Boston, MA 02115 USA. [Horowitz, Neil S.; Goldstein, Donald P.; Bernstein, Marilyn R.; Moulder, Janelle; Berkowitz, Ross S.] Harvard Univ, Sch Med, Boston, MA USA. [Ramirez, Luz Angela C.] Caldas Univ, Clin Dept, Manizales, Caldas, Colombia. [Moulder, Janelle] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Maesta, I (reprint author), UNESP Sao Paulo State Univ, Botucatu Med Sch, Dept Gynecol & Obstet, Av Prof Montenegro S-N, BR-18618970 Sao Paulo, Brazil. EM imaesta@fmb.unesp.br NR 40 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD MAY PY 2015 VL 25 IS 4 BP 734 EP 740 DI 10.1097/IGC.0000000000000398 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CH5VH UT WOS:000354103000030 PM 25675037 ER PT J AU Zhang, XL Shi, HJ Tang, HS Fang, ZY Wang, JP Cui, SZ AF Zhang, Xiangliang Shi, Huijuan Tang, Hongsheng Fang, Zhiyuan Wang, Jiping Cui, Shuzhong TI miR-218 inhibits the invasion and migration of colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE miR-218; PI3K/Akt/mTOR; invasion and migration; LoVo colon cancer cells ID COLORECTAL-CANCER; MATRIX METALLOPROTEINASES; PROSTATE-CANCER; CONCURRENT INHIBITION; EXPRESSION PROFILES; DOWN-REGULATION; IN-VITRO; CARCINOMA; APOPTOSIS; MICRORNA-218 AB Colon cancer is one of the most common and lethal malignancies worldwide. Despite major advances in the treatment of colon cancer, the prognosis remains very poor. Thus, novel and effective therapies for colon cancer are urgently needed. In the present study, the expression status of miR-218 and the role of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway were investigated in colon cancer samples. Firstly, we observed that miR-218 expression was significantly reduced, while PI3K/Akt/mTOR pathway activity was enhanced. The overexpression of miR-218 suppressed the proliferation, migration and invasion of LoVo colon cancer cells, whereas the inhibition of miR-218 promoted these processes. Furthermore, the PI3K/Akt/mTOR signaling pathway was identified as a direct target of miR-218. The upregulation of miR-218 inhibited the activation of the PI3K/Akt/mTOR signaling pathway, as well as the expression of matrix metalloproteinase (MMP)9. The downregulation of miR-218 activated the PI3K/Akt/mTOR signaling pathway and promoted MMP9 expression. Taken together, our results demonstrate that miR-218 suppresses the proliferation, migration and invasion of LoVo colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway and MMP9. Our data indicate that miR-218 is a potential target in the treatment of colon cancer. C1 [Zhang, Xiangliang; Tang, Hongsheng; Fang, Zhiyuan; Cui, Shuzhong] Guangzhou Med Univ, Affiliated Canc Hosp, Dept Abdominal Surg, Sect 2, Guangzhou 510095, Guangdong, Peoples R China. [Shi, Huijuan] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pathol, Guangzhou 510080, Guangdong, Peoples R China. [Wang, Jiping] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Wang, Jiping] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Wang, Jiping] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Cui, SZ (reprint author), Guangzhou Med Univ, Affiliated Canc Hosp, Dept Abdominal Surg, Sect 2, 78 Hengzhigang Rd, Guangzhou 510095, Guangdong, Peoples R China. EM 513340728@qq.com FU Guangdong Province Natural Science Fund [S2013010016662]; Health Bureau of Guangdong Province [A2014224, B2014196]; Science and Technology Planning Project of Guangdong Province [2013B021800284]; National Natural Science Foundation of China [81201932, 81372493] FX This study was supported by the Guangdong Province Natural Science Fund (no. S2013010016662), the Health Bureau of Guangdong Province (nos. A2014224 and B2014196), the Science and Technology Planning Project of Guangdong Province (no. 2013B021800284) and the National Natural Science Foundation of China (nos. 81201932 and 81372493). NR 51 TC 10 Z9 13 U1 0 U2 7 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PD MAY PY 2015 VL 35 IS 5 BP 1301 EP 1308 DI 10.3892/ijmm.2015.2126 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CH2IQ UT WOS:000353849300016 PM 25760926 ER PT J AU Xiang, J Wojtczak, HA Wachter, AM Lee, ML Burns, L Chen, D Stephen, J AF Xiang, Joyce Wojtczak, Henry Albert Wachter, Allan Mark Lee, Martin Laurence Burns, Lisa Chen, Diana Stephen, Joseph TI Understanding asthma medical nonadherence in an adult and pediatric population SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Letter ID MANAGEMENT; ADHERENCE C1 [Xiang, Joyce; Stephen, Joseph] VA Greater Los Angeles Med Ctr, Div Allergy Immunol, Los Angeles, CA 90073 USA. [Wojtczak, Henry Albert; Burns, Lisa; Chen, Diana] Naval Med Ctr San Diego, Dept Pediat, Div Pulm Med, San Diego, CA USA. [Wachter, Allan Mark] Fdn Asthma Res & Intervent, Phoenix, AZ USA. [Lee, Martin Laurence] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Stephen, Joseph] Phoenix VA Hlth Care Syst, Sect Allergy Immunol, Phoenix, AZ USA. RP Xiang, J (reprint author), VA Greater Los Angeles Med Ctr, 11301 Wilshire Blvd 111R, Los Angeles, CA 90073 USA. EM joycexianglee@gmail.com NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD MAY-JUN PY 2015 VL 3 IS 3 BP 436 EP 437 DI 10.1016/j.jaip.2014.11.022 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA CH7JS UT WOS:000354212900021 ER PT J AU Roux, BM Cheng, MH Brey, EM AF Roux, Brianna M. Cheng, Ming-Huei Brey, Eric M. TI Engineering clinically relevant volumes of vascularized bone SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE vascularization; bone tissue engineering; clinical applications ID MESENCHYMAL STEM-CELLS; ENDOTHELIAL GROWTH-FACTOR; MARROW STROMAL CELLS; BIOACTIVE GLASS SCAFFOLDS; PLATELET-RICH PLASMA; BIODEGRADABLE POLYMER SCAFFOLDS; TRICALCIUM PHOSPHATE SCAFFOLD; POROUS SPACE MAINTAINERS; SIZED CALVARIAL DEFECTS; IN-VIVO AB Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility. C1 [Roux, Brianna M.; Brey, Eric M.] IIT, Dept Biomed Engn, Chicago, IL 60616 USA. [Roux, Brianna M.; Brey, Eric M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. [Cheng, Ming-Huei] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Dept Plast & Reconstruct Surg, Taoyuan, Taiwan. [Cheng, Ming-Huei] Chang Gung Mem Hosp, Ctr Tissue Engn, Taoyuan, Taiwan. RP Brey, EM (reprint author), IIT, Dept Biomed Engn, 3255 South Dearborn St, Chicago, IL 60616 USA. EM brey@iit.edu FU Department of Veterans Affairs; Chang Gung Memorial Hospital [CMRPG3C1061]; National Institute of Health [R01AR061460]; National Science Foundation [CBET-1263994, IIS-1125412] FX The authors on this work are supported, in part, by funding from the Department of Veterans Affairs, Chang Gung Memorial Hospital (CMRPG3C1061), National Institute of Health (grant no: R01AR061460), and the National Science Foundation (CBET-1263994, IIS-1125412). NR 124 TC 11 Z9 11 U1 3 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1582-4934 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD MAY PY 2015 VL 19 IS 5 BP 903 EP 914 DI 10.1111/jcmm.12569 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CH4GE UT WOS:000353991100001 PM 25877690 ER PT J AU Baggish, AL AF Baggish, Aaron L. TI A decade of athlete ECG criteria: Where we've come and where we're going SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Review DE ECG criteria; Competitive athletes; Sudden death; Athlete screening; Preparticipaition screening ID ABNORMAL ELECTROCARDIOGRAPHIC FINDINGS; HYPERTROPHIC CARDIOMYOPATHY; EUROPEAN-SOCIETY; SEATTLE CRITERIA; CARDIOLOGY; DISEASE; DEATH; HEART AB Competitive athletes and highly active individuals commonly develop cardiovascular adaptations. Underlying features of exercise-induced cardiac remodeling often manifest as distinct patterns on the 12-lead electrocardiogram (ECG). Considerable effort has been directed toward defining the scope of ECG abnormalities in this population and numerous criteria have been proposed for the task of differentiating benign athletic ECG changes from patterns suggestive of underlying cardiovascular disease. This review will provide a historical overview of athlete ECG criteria development with a final emphasis on remaining areas of scientific and clinical uncertainty. (c) 2015 Elsevier Inc. All rights reserved. C1 [Baggish, Aaron L.] Cardiovasc Performance Program, Boston, MA USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, 55 Fruit St,Yawkey Suite 5B, Boston, MA 02114 USA. EM abaggish@partners.org NR 29 TC 2 Z9 2 U1 1 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD MAY-JUN PY 2015 VL 48 IS 3 BP 324 EP 328 DI 10.1016/j.jelectrocard.2015.02.002 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH9GD UT WOS:000354343100007 PM 25771161 ER PT J AU Kim, JH Baggish, AL AF Kim, Jonathan H. Baggish, Aaron L. TI Electrocardiographic right and left bundle branch block patterns in athletes: Prevalence, pathology, and clinical significance SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Review DE Bundle branch block; Athlete; ECG; Screening ID CARDIOVASCULAR-DISEASE; FOLLOW-UP; 12-LEAD ELECTROCARDIOGRAM; GENERAL-POPULATION; SEATTLE CRITERIA; YOUNG-PEOPLE; SUDDEN-DEATH; PARTICIPATION; ABNORMALITIES; HEART AB Differentiating benign electrocardiographic (ECG) patterns in athletes from those representative of underlying cardiac pathology is both clinically relevant and challenging. Complete right (RBBB) and left (LBBB) bundle branch block are relatively rare in asymptomatic athletic populations, and current expert consensus guidelines recommend further clinical investigation upon detection of either ECG pattern. However, present data suggest that typical RBBB is not associated with structural cardiac pathology and may alternatively represent an ECG marker of exercise-induced right ventricular remodeling. In accordance with current guidelines, the presence of asymptomatic LBBB in athletes is not associated with normal exercise physiology and more likely indicative of underlying cardiac pathology. While long-term outcomes for asymptomatic athletes with RBBB or LBBB remain unknown, current evidence regarding these ECG patterns should be considered to improve the specificity of future athlete-specific ECG interpretation guidelines. (c) 2015 Elsevier Inc. All rights reserved. C1 [Kim, Jonathan H.] Emory Clin Cardiovasc Res Inst, Atlanta, GA USA. [Baggish, Aaron L.] Cardiovasc Performance Program, Boston, MA USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, 55 Fruit St,Yawkey Suite 5B, Boston, MA 02114 USA. EM abaggish@partners.org NR 41 TC 3 Z9 3 U1 1 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD MAY-JUN PY 2015 VL 48 IS 3 BP 380 EP 384 DI 10.1016/j.jelectrocard.2015.03.015 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH9GD UT WOS:000354343100016 PM 25836379 ER PT J AU Slutzman, JE Curley, DP Macias-Konstantopoulos, W Brown, DFM AF Slutzman, Jonathan E. Curley, David P. Macias-Konstantopoulos, Wendy Brown, David F. M. TI ALTERED MENTAL STATUS AND TACHYCARDIA SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material C1 [Slutzman, Jonathan E.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Curley, David P.] Brown Univ, Alpert Med Sch, Dept Emergency Med, Providence, RI 02912 USA. [Macias-Konstantopoulos, Wendy; Brown, David F. M.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Macias-Konstantopoulos, Wendy; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders 110,55 Fruit St, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2015 VL 48 IS 5 BP 597 EP 602 PG 6 WC Emergency Medicine SC Emergency Medicine GA CH4VB UT WOS:000354030200015 PM 25656429 ER PT J AU Henderson, E AF Henderson, Elizabeth TI POTENTIALLY DANGEROUS PATIENTS: A REVIEW OF THE DUTY TO WARN SO JOURNAL OF EMERGENCY NURSING LA English DT Review ID TARASOFF; CONFIDENTIALITY; PERSPECTIVES; DISCLOSURE; VIOLENCE; PROTECT; TRIAGE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Henderson, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM EHENDERSON1@mgh.harvard.edu NR 40 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-1767 EI 1527-2966 J9 J EMERG NURS JI J. Emerg. Nurs. PD MAY PY 2015 VL 41 IS 3 BP 193 EP 200 DI 10.1016/j.jen.2014.08.012 PG 8 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA CH5EW UT WOS:000354059100011 PM 25441772 ER PT J AU Normandin, PA AF Normandin, Patricia A. TI PEDIATRIC EMERGENCY UPDATE: CYCLIC VOMITING SYNDROME SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material C1 [Normandin, Patricia A.] Tufts Med Ctr, Boston, MA USA. [Normandin, Patricia A.] Northeastern Univ, Boston, MA 02115 USA. [Normandin, Patricia A.] Brigham & Womens Hosp, Nursing Fac, Boston, MA 02115 USA. [Normandin, Patricia A.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Normandin, Patricia A.] Boston Childrens Hosp, Boston, MA USA. RP Normandin, PA (reprint author), 7 Bowl Rd, Chelmsford, MA 01824 USA. EM pnormandinrn@aol.com NR 3 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-1767 EI 1527-2966 J9 J EMERG NURS JI J. Emerg. Nurs. PD MAY PY 2015 VL 41 IS 3 BP 260 EP 262 DI 10.1016/j.jen.2015.03.003 PG 3 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA CH5EW UT WOS:000354059100025 PM 25814094 ER PT J AU Cronin, J Arnstein, P Flanagan, J AF Cronin, Julie Arnstein, Paul Flanagan, Jane TI Family Members' Perceptions of Most Helpful Interventions During End-of-Life Care SO JOURNAL OF HOSPICE & PALLIATIVE NURSING LA English DT Article DE end-of-life care; family members; perceived needs ID ONCOLOGY; QUALITY; NURSES; CANCER AB The aim of the study was to explore the following research question: What are the perceived needs of family members/friends while their loved one is receiving end-of-life care while in the hospital setting? This was a qualitative descriptive study using semistructured open-ended interview questions and content analysis. Seven family members or friends participated in this study. Four themes were identified. Results suggest that vigilance in the provision of nursing care for patients at the end of life provides family with a sense of being cared for and eases their feelings of uncertainty and anxiety. Support for family members and validation of difficult decision making is a vital component of communication, which is essential to increase family members' levels of comfort and trust in the health care team. C1 [Cronin, Julie; Arnstein, Paul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Flanagan, Jane] Massachusetts Gen Hosp, Yvonne L Munn Nursing Res Ctr, Boston, MA 02114 USA. RP Cronin, J (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM jcronin4@partners.org NR 18 TC 1 Z9 1 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1522-2179 EI 1539-0705 J9 J HOSP PALLIAT NURS JI J. Hosp. Palliat. Nurs. PD MAY-JUN PY 2015 VL 17 IS 3 BP 223 EP 228 DI 10.1097/NJH.0000000000000151 PG 6 WC Nursing SC Nursing GA CH3XM UT WOS:000353964300008 ER PT J AU Hong, K Low, G Weilburg, JB AF Hong, Kyungwan Low, Greg Weilburg, Jeffrey B. TI HEDIS Antidepressant Measures Biased by 2013 Revision SO JOURNAL OF MANAGED CARE PHARMACY LA English DT Letter C1 [Hong, Kyungwan] Univ Rhode Isl, Coll Pharm, Pharmacoepidemiol Pharmacoecon, Kingston, RI 02881 USA. [Low, Greg] Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Pharm Qual & Utilizat Program, Boston, MA 02114 USA. [Weilburg, Jeffrey B.] Massachusetts Gen Phys Org, Boston, MA USA. [Weilburg, Jeffrey B.] Massachusetts Gen Hosp, Clin Neuropsychiat, Boston, MA 02114 USA. [Weilburg, Jeffrey B.] Harvard Univ, Sch Med, Psychiat, Cambridge, MA 02138 USA. RP Hong, K (reprint author), Univ Rhode Isl, Coll Pharm, Pharmacoepidemiol Pharmacoecon, Kingston, RI 02881 USA. EM lgungwan_hong@my.uri.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU ACAD MANAGED CARE PHARMACY PI ALEXANDRIA PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA SN 1083-4087 J9 J MANAGE CARE PHARM JI J. Manag. Care Pharm. PD MAY PY 2015 VL 21 IS 5 BP 365 EP 366 PG 2 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA CH3MP UT WOS:000353935100001 PM 25942997 ER PT J AU Phelan, CH Schumacher, S Roiland, R Royer, H Roberts, T AF Phelan, Cynthia H. Schumacher, Sandra Roiland, Rachel Royer, Heather Roberts, Tonya TI Building Capacity for the Conduct of Nursing Research at a Veterans Administration Hospital SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID INFRASTRUCTURE; SUPPORT AB Evidence is the bedrock of nursing practice, and nursing research is the key source for this evidence. In this article, we draw distinctions between the use and the conduct of nursing research and provide a perspective for how the conduct of nursing research in a Veterans Administration hospital can build an organization's capacity for nursing research. C1 [Phelan, Cynthia H.; Schumacher, Sandra; Roiland, Rachel; Royer, Heather; Roberts, Tonya] William S Middleton Mem Vet Adm Med Ctr, GRECC Serv, Madison, WI 53705 USA. [Phelan, Cynthia H.; Schumacher, Sandra; Roiland, Rachel; Royer, Heather; Roberts, Tonya] Univ Wisconsin Madison, Sch Nursing, Madison, WI USA. RP Phelan, CH (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC Serv, 2500 Overlook Ter, Madison, WI 53705 USA. EM Cynthia.Phelan@va.gov FU US Department of Veterans Affairs, Clinical Sciences Research & Development Program [IK2 CX000535] FX This material is the result of work supported with resources and use of facilities at the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin. Dr Phelan's research is supported by Career Development Award IK2 CX000535 from the US Department of Veterans Affairs, Clinical Sciences Research & Development Program. The contents of this article do not represent the views of the Department of Veterans Affairs of the US Government. NR 23 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAY PY 2015 VL 45 IS 5 BP 270 EP 275 DI 10.1097/NNA.0000000000000197 PG 6 WC Nursing SC Nursing GA CH9AF UT WOS:000354327700008 PM 25906135 ER PT J AU Kirrane, EF Bowman, C Davis, JA Hoppin, JA Blair, A Chen, HL Patel, MM Sandler, DP Tanner, CM Vinikoor-Imler, L Ward, MH Luben, TJ Kamel, F AF Kirrane, Ellen F. Bowman, Christal Davis, J. Allen Hoppin, Jane A. Blair, Aaron Chen, Honglei Patel, Molini M. Sandler, Dale P. Tanner, Caroline M. Vinikoor-Imler, Lisa Ward, Mary H. Luben, Thomas J. Kamel, Freya TI Associations of Ozone and PM2.5 Concentrations With Parkinson's Disease Among Participants in the Agricultural Health Study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID FINE PARTICULATE MATTER; LONG-TERM EXPOSURE; AIR-POLLUTION; COGNITIVE FUNCTION; CARDIOVASCULAR MORTALITY; OXIDATIVE STRESS; OLDER-ADULTS; US ADULTS; BRAIN; COHORT AB Objective: This study describes associations of ozone and fine particulate matter with Parkinson's disease observed among farmers in North Carolina and Iowa. Methods: We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants' geocoded addresses. Results: We observed positive associations of Parkinson's disease with ozone (odds ratio = 1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95% CI: 0.93 to 1.93) in North Carolina but not in Iowa. Conclusions: The plausibility of an effect of ambient concentrations of these pollutants on Parkinson's disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed. C1 [Kirrane, Ellen F.; Bowman, Christal; Davis, J. Allen; Patel, Molini M.; Vinikoor-Imler, Lisa; Luben, Thomas J.] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Res Triangle Pk, NC 27709 USA. [Hoppin, Jane A.; Chen, Honglei; Sandler, Dale P.; Kamel, Freya] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Blair, Aaron; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD USA. [Tanner, Caroline M.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Tanner, Caroline M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Kirrane, EF (reprint author), US EPA, Natl Ctr Environm Assessment, Off Res & Dev, 109 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM kirrane.ellen@epa.gov OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018; Chen, Honglei/0000-0003-3446-7779 FU intramural research program of the National Institutes of Health; National Institute of Environmental Health Sciences [Z01-ES049030]; National Cancer Institute [Z01-CP010119] FX This work was supported in part by the intramural research program of the National Institutes of Health, the National Institute of Environmental Health Sciences (Z01-ES049030), and National Cancer Institute (Z01-CP010119). Data were obtained from Agricultural Health Study data release versions P1REL0906.00 (for phase 1), P2REL0907.00 (phase 2), and P3RREL0901 (phase 3). The views expressed in this article are those of the authors and do not necessarily represent the views or policies of the US Environmental Protection Agency. Dr Caroline Tanner has served as a consultant to Pfizer Pharmaceuticals, a manufacturer of treatments for Parkinson's disease. No other potential conflicts of interest were declared. NR 46 TC 5 Z9 5 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAY PY 2015 VL 57 IS 5 BP 509 EP 517 DI 10.1097/JOM.0000000000000451 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH7NY UT WOS:000354225000006 PM 25951420 ER PT J AU Petrik, ML Billera, M Kaplan, Y Matarazzo, B Wortzel, H AF Petrik, Megan L. Billera, Melodi Kaplan, Yuliya Matarazzo, Bridget Wortzel, Hal TI Balancing Patient Care and Confidentiality Considerations in Obtaining Collateral Information SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE ethics; confidentiality; autonomy; collateral information; multi-informant data AB Collateral information facilitates comprehensive mental health care and is consistent with recovery-oriented models of care. But providers are often faced with complex decisions about obtaining collateral information, particularly when patients do not consent to communication with third parties for information gathering. Such situations require a thoughtful balance of best clinical practices, legal and ethical responsibilities, and patient safety concerns. This column offers an overview of the clinical utility of collateral information as well as the ethical and legal regulations concerning confidentiality that guide the process of obtaining collateral information. The risk-benefit analysis process related to obtaining collateral information without patient permission is illustrated. Recommendations about clinical consultation and documentation that facilitate optimal and ethical patient care are offered. C1 [Petrik, Megan L.; Kaplan, Yuliya] Denver VA Med Ctr, Rocky Mt Mental Illness Res Educ & Clin Ctr MIREC, Denver, CO USA. [Petrik, Megan L.] Univ Colorado, Dept Psychiat, Aurora, CO USA. [Billera, Melodi] Rocky Mt MIRECC, Denver, CO USA. [Billera, Melodi] Univ Denver, Grad Sch Social Work, Denver, CO USA. [Matarazzo, Bridget] Rocky Mt MIRECC, Rocky Mt MIRECC Suicide Consultat Serv, Denver, CO USA. [Matarazzo, Bridget] Univ Colorado, Psychiat, Aurora, CO USA. [Wortzel, Hal] Univ Colorado, Neurocognit Dis, Aurora, CO USA. [Wortzel, Hal] Univ Colorado, Neuropsychiat, Aurora, CO USA. [Wortzel, Hal] Univ Colorado, Psychiat Neurol & Phys Med & Rehabil, Aurora, CO USA. [Wortzel, Hal] Univ Colorado, Forens Psychiat Fellowship, Aurora, CO USA. [Wortzel, Hal] Denver VA, Rocky Mt MIRECC, Neuropsychiat Serv, Denver, CO USA. RP Wortzel, H (reprint author), Univ Colorado Denver VA, 1055 Clermont St, Denver, CO 80217 USA. EM hal.wortzel@ucdenver.edu FU Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs FX Writing of this manuscript was supported by the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs. NR 15 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1527-4160 EI 1538-1145 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD MAY PY 2015 VL 21 IS 3 BP 220 EP 224 DI 10.1097/PRA.0000000000000072 PG 5 WC Psychiatry SC Psychiatry GA CH8PA UT WOS:000354297100007 PM 25955265 ER PT J AU Bi, RZ Dong, J Poh, CL Lee, K AF Bi, Renzhe Dong, Jing Poh, Chueh Loo Lee, Kijoon TI Optical methods for blood perfusion measurement-theoretical comparison among four different modalities SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID DIFFUSE CORRELATION SPECTROSCOPY; LASER-DOPPLER FLOWMETRY; DEEP-TISSUE FLOWMETRY; SPECKLE CONTRAST ANALYSIS; COHERENT BACKSCATTERING; MICROVASCULAR FUNCTION; FLOW MEASUREMENT; SCATTERING; MEDIA; TOMOGRAPHY AB Blood perfusion in human tissue can be measured in vivo by means of various optical methods, which seem to be very different from one another. The most prominent examples of them are laser Doppler flowmetry, laser speckle contrast imaging, diffuse correlation spectroscopy, and the most recently developed diffuse speckle contrast analysis. In this paper, we claim that these four seemingly different modalities are examining different aspects of the same entity-the temporal autocorrelation function of scattered photons. We will show how the observables in each modality can be theoretically derived from the temporal autocorrelation function, and will discuss the merits and drawbacks of each modality in its practical use. (C) 2015 Optical Society of America C1 [Bi, Renzhe; Dong, Jing; Poh, Chueh Loo] Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore 637457, Singapore. [Lee, Kijoon] Daegu Gyeongbuk Inst Sci & Technol, Sch Basic Sci, Daegu 711873, South Korea. [Dong, Jing] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dong, Jing] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee, K (reprint author), Daegu Gyeongbuk Inst Sci & Technol, Sch Basic Sci, Daegu 711873, South Korea. EM kjlee@dgist.ac.kr RI Poh, Chueh Loo/G-6211-2010 FU National Research Foundation [NRF2013NRF-POC001-026]; National Research Foundation, Singapore [NRF2013NRF-POC001-026] FX National Research Foundation (NRF2013NRF-POC001-026).; This work was made possible by generous support from the National Research Foundation, Singapore, Proof-of-Concept grant NRF2013NRF-POC001-026. Kijoon Lee would like to thank Gemma Instrument for providing inspirational ideas regarding the physiology of blood perfusion. NR 44 TC 5 Z9 6 U1 1 U2 9 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 EI 1520-8532 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD MAY PY 2015 VL 32 IS 5 BP 860 EP 866 DI 10.1364/JOSAA.32.000860 PG 7 WC Optics SC Optics GA CH3IT UT WOS:000353924900019 PM 26366910 ER PT J AU Maung, AA Johnson, DC Luckianow, GM Kaplan, LJ AF Maung, Adrian Anthony Johnson, Dirk C. Luckianow, Gina M. Kaplan, Lewis J. TI Ventilator gas delivery wave form substantially impacts plateau pressure and peak-to-plateau pressure gradient determination SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 73rd Annual Meeting of the American-Association-for-the-Surgery-of-Trauma / Clinical Congress of Acute Care Surgery CY SEP 09-13, 2014 CL Philadelphia, PA SP Amer Assoc Surg Trauma DE Mechanical ventilation; gas delivery wave forms; airway pressure; peak pressure; plateau pressure ID RESPIRATORY-DISTRESS-SYNDROME; CRITICAL-CARE MEDICINE; ACUTE LUNG INJURY; AIRWAY PRESSURE; RELEASE VENTILATION; VOLUME; TITRATION; STRAIN AB BACKGROUND: To determine whether plateau pressure (Pplat) measurement is lowered and peak airway pressure (Pawpeak)-to-Plat gradient is increased by measurement on a decelerating compared with square gas delivery wave form. METHODS: Prospective before and after study of mechanically ventilated injured and critically ill patients in an adult surgical intensive care unit. Pplat, Pawpeak, and Pawpeak-to-Pplat gradient were measured on decelerating and square gas delivery wave forms. RESULTS: Pplat and other routine ventilator parameters were measured in 82 (47 trauma, 35 emergency general surgery) consecutive convenience sampled adult intensive care unit patients on decelerating and then square gas delivery wave forms. Peak gas flow was fixed at 40 L/min; all other parameters (rate, tidal volume, positive end-expiratory pressure) were held constant. All patients were managed on assist control volume cycled ventilation using fentanyl and midazolam or propofol; no neuromuscular blockade was used. Patients with Pawpeak more than 35 cm H2O were excluded. Comparing decelerating with square gas delivery, mean Pawpeak was lower (25.1 perpendicular to 2.3 cm H2O vs. 33.1 perpendicular to 2.1 cm H2O; p < 0.0001) and mean Pplat was lower (21.3 perpendicular to 1.9 cm H2O vs. 24.8 + 2.5 cm H2O; p < 0.0001), resulting in a decreased Pawpeak-to-Pplat gradient (3.8 + 2.1 vs. 8.3 + 2.3; p < 0.0001). CONCLUSION: Changing from a decelerating to a square gas delivery wave form significantly increases Pplat and Pawpeak, thereby increasing the Pawpeak-to-Pplat gradient. This increase may prompt unwarranted therapy aimed at reducing the gradient to its normal value of 4 cm H2O pressure or less. Conversely, patients with a high Pawpeak on a square wave form may benefit from transitioning to a decelerating wave form before changing ventilation parameters. (J Trauma Acute Care Surg. 2015; 78: 976-979. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.) C1 [Maung, Adrian Anthony; Johnson, Dirk C.; Luckianow, Gina M.] Yale Univ, Sch Med, Dept Surg, Sect Trauma Surg Crit Care & Surg Emergencies, New Haven, CT 06510 USA. [Kaplan, Lewis J.] Univ Penn, Perelman Sch Med, Div Trauma Surg Crit Care & Emergency Surg, Philadelphia, PA 19104 USA. [Kaplan, Lewis J.] Philadelphia Vet Affairs Med Ctr, Dept Surg, Philadelphia, PA USA. RP Kaplan, LJ (reprint author), PVAMC Sect, Surg Crit Care, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Lewis.Kaplan@va.gov NR 21 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD MAY PY 2015 VL 78 IS 5 BP 976 EP 979 DI 10.1097/TA.0000000000000615 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CH3KR UT WOS:000353930100012 PM 25909418 ER PT J AU Carnes, M Vogelman, B AF Carnes, Molly Vogelman, Bennett TI Women's Health Fellowships: Examining the Potential Benefits and Harms of Accreditation SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material ID GENERAL-INTERNAL-MEDICINE; GENDER-DIFFERENCES; PHYSICIAN-RESEARCHERS; GERIATRIC-MEDICINE; NATIONAL-SURVEY; PROGRAMS; EDUCATION; GAP; SPECIALTIES; SEGREGATION AB This commentary responds to the assertions by Foreman et al. that credentialing of women's health (WH) fellows by the American Board of Medical Subspecialties and accreditation of current and future WH fellowships by the Accreditation Council for Graduate Medical Education would improve the health and healthcare of women by increasing the number of primary care providers competent to meet a growing clinical need. They speculate that such accreditation would raise the status of WH fellowships, increase the number of applicants, and result in more academic leaders in WH. They assert that curricular deficiencies in WH exist in physician training and that WH fellowships are the preferred means of training physicians to care for midlife women. We review the evidence to support or refute these claims and conclude that accrediting WH fellowships would not have the forecasted outcomes and would jeopardize the success of current WH fellowships. C1 [Carnes, Molly] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Carnes, Molly; Vogelman, Bennett] Univ Wisconsin, Dept Med, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Psychiat, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53715 USA. [Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Carnes, M (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, 700 Regent St,Suite 301, Madison, WI 53715 USA. EM mlcarnes@wisc.edu NR 53 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD MAY 1 PY 2015 VL 24 IS 5 BP 341 EP 348 DI 10.1089/jwh.2015.5289 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA CI0ZF UT WOS:000354468500004 PM 25919589 ER PT J AU Gorski, M Tin, A Garnaas, M McMahon, GM Chu, AY Tayo, BO Pattaro, C Teumer, A Chasman, DI Chalmers, J Hamet, P Tremblay, J Woodward, M Aspelund, T Eiriksdottir, G Gudnason, V Harris, TB Launer, LJ Smith, AV Mitchell, BD O'Connell, JR Shuldiner, AR Coresh, J Li, M Freudenberger, P Hofer, E Schmidt, H Schmidt, R Holliday, EG Mitchell, P Wang, JJ de Boer, IH Li, G Siscovick, DS Kutalik, Z Corre, T Vollenweider, P Waeber, G Gupta, J Kanetsky, PA Hwang, SJ Olden, M Yang, Q de Andrade, M Atkinson, EJ Kardia, SLR Turner, ST Stafford, JM Ding, JZ Liu, YM Barlassina, C Cusi, D Salvi, E Staessen, JA Ridker, PM Grallert, H Meisinger, C Muller-Nurasyid, M Kramer, BK Kramer, H Rosas, SE Nolte, IM Penninx, BW Snieder, H Del Greco, MF Franke, A Nothlings, U Lieb, W Bakker, SJL Gansevoort, RT van der Harst, P Dehghan, A Franco, OH Hofman, A Rivadeneira, F Sedaghat, S Uitterlinden, AG Coassin, S Haun, M Kollerits, B Kronenberg, F Paulweber, B Aumann, N Endlich, K Pietzner, M Volker, U Rettig, R Chouraki, V Helmer, C Lambert, JC Metzger, M Stengel, B Lehtimaki, T Lyytikainen, LP Raitakari, O Johnson, A Parsa, A Bochud, M Heid, IM Goessling, W Kottgen, A Kao, WHL Fox, CS Boger, CA AF Gorski, Mathias Tin, Adrienne Garnaas, Maija McMahon, Gearoid M. Chu, Audrey Y. Tayo, Bamidele O. Pattaro, Cristian Teumer, Alexander Chasman, Daniel I. Chalmers, John Hamet, Pavel Tremblay, Johanne Woodward, Marc Aspelund, Thor Eiriksdottir, Gudny Gudnason, Vilmundur Harris, Tamara B. Launer, Lenore J. Smith, Albert V. Mitchell, Braxton D. O'Connell, Jeffrey R. Shuldiner, Alan R. Coresh, Josef Li, Man Freudenberger, Paul Hofer, Edith Schmidt, Helena Schmidt, Reinhold Holliday, Elizabeth G. Mitchell, Paul Wang, Jie Jin de Boer, Ian H. Li, Guo Siscovick, David S. Kutalik, Zoltan Corre, Tanguy Vollenweider, Peter Waeber, Gerard Gupta, Jayanta Kanetsky, Peter A. Hwang, Shih-Jen Olden, Matthias Yang, Qiong de Andrade, Mariza Atkinson, Elizabeth J. Kardia, Sharon L. R. Turner, Stephen T. Stafford, Jeanette M. Ding, Jingzhong Liu, Yongmei Barlassina, Cristina Cusi, Daniele Salvi, Erika Staessen, Jan A. Ridker, Paul M. Grallert, Harald Meisinger, Christa Mueller-Nurasyid, Martina Kraemer, Bernhard K. Kramer, Holly Rosas, Sylvia E. Nolte, Ilja M. Penninx, Brenda W. Snieder, Harold Del Greco, M. Fabiola Franke, Andre Noethlings, Ute Lieb, Wolfgang Bakker, Stephan J. L. Gansevoort, Ron T. van der Harst, Pim Dehghan, Abbas Franco, Oscar H. Hofman, Albert Rivadeneira, Fernando Sedaghat, Sanaz Uitterlinden, Andre G. Coassin, Stefan Haun, Margot Kollerits, Barbara Kronenberg, Florian Paulweber, Bernhard Aumann, Nicole Endlich, Karlhans Pietzner, Mike Voelker, Uwe Rettig, Rainer Chouraki, Vincent Helmer, Catherine Lambert, Jean-Charles Metzger, Marie Stengel, Benedicte Lehtimaki, Terho Lyytikainen, Leo-Pekka Raitakari, Olli Johnson, Andrew Parsa, Afshin Bochud, Murielle Heid, Iris M. Goessling, Wolfram Kottgen, Anna Kao, W. H. Linda Fox, Caroline S. Boeger, Carsten A. TI Genome-wide association study of kidney function decline in individuals of European descent SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; genome-wide association study; kidney function decline; kidney development; population genetics; single nucleotide polymorphism; zebrafish ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; SYNDROME TYPE 1D; HYPERTENSIVE NEPHROSCLEROSIS; DIABETIC-NEPHROPATHY; DEAFNESS DFNB12; MORTALITY RISK; MOUSE MODEL; GENE; PROGRESSION AB Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline. C1 [Gorski, Mathias; Olden, Matthias; Heid, Iris M.] Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany. [Gorski, Mathias; Boeger, Carsten A.] Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany. [Tin, Adrienne; Coresh, Josef; Li, Man; Kottgen, Anna; Kao, W. H. Linda] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Garnaas, Maija] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. [McMahon, Gearoid M.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. [McMahon, Gearoid M.] Harvard Univ, Sch Med, Boston, MA USA. [McMahon, Gearoid M.; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Chu, Audrey Y.; Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Tayo, Bamidele O.; Kramer, Holly] Loyola Univ Chicago, Loyola Med Ctr, Dept Publ Hlth Serv, Maywood, IL USA. [Pattaro, Cristian; Del Greco, M. Fabiola] Univ Lubeck, European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Teumer, Alexander; Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany. [Chalmers, John; Woodward, Marc] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Hamet, Pavel] Univ Montreal, Ctr Hosp, Ctr Rech, Montreal, PQ, Canada. [Tremblay, Johanne] CHUM Res Center, Montreal, PQ, Canada. [Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Smith, Albert V.] Icelandic Heart Assoc, Res Inst, Kopavogur, Iceland. [Aspelund, Thor; Gudnason, Vilmundur; Smith, Albert V.] Univ Iceland, Reykjavik, Iceland. [Harris, Tamara B.; Launer, Lenore J.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shuldiner, Alan R.; Parsa, Afshin] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shuldiner, Alan R.; Parsa, Afshin] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. [Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA. [Coresh, Josef; Kao, W. H. Linda] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Freudenberger, Paul; Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [Hofer, Edith] Med Univ Graz, Inst Med Informat Stat & Documentat, Dept Neurol, Graz, Austria. [Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria. [Holliday, Elizabeth G.] Univ Newcastle, CReDITSS, HMRI, Ctr Clin Epidemiol & Biostat, Callaghan, NSW 2308, Australia. [Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Westmead Hosp, Westmead Millennium Inst, Ctr Vis Res, Sydney, NSW 2006, Australia. [de Boer, Ian H.] Univ Washington, Seattle, WA 98195 USA. [Li, Guo; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Siscovick, David S.] New York Acad Med, New York, NY USA. [Kutalik, Zoltan; Corre, Tanguy] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Kutalik, Zoltan] Swiss Inst Bioinformat, Dept Med Genet, Lausanne, Switzerland. [Vollenweider, Peter; Waeber, Gerard] Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland. [Gupta, Jayanta; Kanetsky, Peter A.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [de Andrade, Mariza; Atkinson, Elizabeth J.; Turner, Stephen T.] Mayo Clin, Rochester, MN USA. [Kardia, Sharon L. R.] Univ Michigan, Ann Arbor, MI 48109 USA. [Stafford, Jeanette M.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Barlassina, Cristina; Cusi, Daniele; Salvi, Erika] Univ Milan, Dept Hlth Sci, Milan, Italy. [Cusi, Daniele] San Paolo Hosp, Div Nephrol, Milan, Italy. [Staessen, Jan A.] Maastricht Univ, Dept Epidemiol, NL-6200 MD Maastricht, Netherlands. [Staessen, Jan A.] Univ Leuven, Dept Cardiovasc Sci, Div Hypertens & Cardiovasc Rehabil, Studies Coordinating Ctr, Leuven, Belgium. [Grallert, Harald; Meisinger, Christa] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany. [Grallert, Harald] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany. [Grallert, Harald] German Ctr Diabet Res, Neuherberg, Germany. [Mueller-Nurasyid, Martina] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany. [Mueller-Nurasyid, Martina; Heid, Iris M.] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Kraemer, Bernhard K.] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Med 5, Mannheim, Germany. [Rosas, Sylvia E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Rosas, Sylvia E.] Harvard Univ, Sch Med, Beth Israel Med Ctr, Boston, MA USA. [Nolte, Ilja M.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Nolte, Ilja M.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol FA40, Unit Genet Epidemiol & Bioinformat, NL-9713 AV Groningen, Netherlands. [Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Dept Psychiat, Amsterdam, Netherlands. [Penninx, Brenda W.] NESDA, EMGO Inst Vumc, Amsterdam, Netherlands. [Franke, Andre] Inst Clin Mol Biol, Kiel, Germany. [Noethlings, Ute] Univ Hosp Schleswig Holstein, Popgen Biobank, Kiel, Germany. [Noethlings, Ute] Univ Kiel, Inst Expt Med, Epidemiol Sect, Kiel, Germany. [Lieb, Wolfgang] Univ Kiel, Inst Epidemiol, Kiel, Germany. [Lieb, Wolfgang] Univ Kiel, Biobank Popgen, Kiel, Germany. [Bakker, Stephan J. L.; Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands. [van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Dehghan, Abbas; Hofman, Albert; Rivadeneira, Fernando; Sedaghat, Sanaz; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian] Med Univ Innsbruck, Div Genet Epidemiol, A-6020 Innsbruck, Austria. [Paulweber, Bernhard] Paracelsus Private Med Univ Salzburg, Dept Internal Med 1, Salzburg, Austria. [Aumann, Nicole] Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany. [Endlich, Karlhans] Univ Med Greifswald, Inst Anat & Cell Biol, Greifswald, Germany. [Pietzner, Mike] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany. [Chouraki, Vincent] Univ Lille Nord France, Inst Pasteur Lille, INSERM, U744,CHR&U Lille,Serv Epidemiol Reg,CHRU, Lille, France. [Helmer, Catherine] Univ Bordeaux 2, ISPED, INSERM, U897, F-33076 Bordeaux, France. [Lambert, Jean-Charles] Univ Lille Nord France, Inst Pasteur Lille, INSERM, U744, Lille, France. [Stengel, Benedicte] Univ Paris 11, INSERM, U1018, CESP Team 10, Villejuif, France. [Lehtimaki, Terho; Lyytikainen, Leo-Pekka] Fimlab Labs, Dept Clin Chem, Tampere, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Johnson, Andrew] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Framingham Heart Study, Framingham, MA USA. [Bochud, Murielle] Univ Lausanne Hosp, Inst Social & Prevent Med IUMSP, Epalinges, Switzerland. [Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Gastroenterol, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Goessling, Wolfram] Broad Inst MIT & Harvard, Cambridge, MA USA. [Kottgen, Anna] Freiburg Univ Clin, Div Renal, Freiburg, Germany. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. RP Boger, CA (reprint author), Univ Hosp Regensburg, Dept Nephrol, Franz Josef Strauss Allee 11, D-93042 Regensburg, Germany. EM carsten.boeger@klinik.uni-regensburg.de RI Lyytikainen, Leo-Pekka/C-8544-2016; Stengel, Benedicte/G-5730-2015; Cossette, Suzanne/I-8008-2016; Lambert, jean-charles/A-9553-2014; Smith, Albert/K-5150-2015; Bochud, Murielle/A-3981-2010; Johnson, Andrew/G-6520-2013; Franke, Andre/B-2151-2010; Lieb, Wolfgang/C-1990-2012; HELMER, Catherine/I-6581-2015; Bakker, Stephan/J-4023-2015; Staessen, Jan/A-1065-2011; Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; Woodward, Mark/D-8492-2015; Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; Rivadeneira, Fernando/O-5385-2015; Kronenberg, Florian/B-1736-2008; lambert, jean-charles/F-8787-2013; Colaus, PsyColaus/K-6607-2013; Grallert, Harald/B-3424-2013 OI Goessling, Wolfram/0000-0001-9972-1569; Meisinger, Christa/0000-0002-9026-6544; Salvi, Erika/0000-0002-2724-2291; Mitchell, Braxton/0000-0003-4920-4744; Dehghan, Abbas/0000-0001-6403-016X; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Lambert, jean-charles/0000-0003-0829-7817; Smith, Albert/0000-0003-1942-5845; Bochud, Murielle/0000-0002-5727-0218; Franke, Andre/0000-0003-1530-5811; McMahon, Gearoid/0000-0002-7723-2198; HELMER, Catherine/0000-0002-5169-7421; Bakker, Stephan/0000-0003-3356-6791; Staessen, Jan/0000-0002-3026-1637; Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433; Wang, Jie Jin/0000-0001-9491-4898; Rivadeneira, Fernando/0000-0001-9435-9441; Kronenberg, Florian/0000-0003-2229-1120; FU NIH [N01-AG-1-2100, R01 AG18728, R01 HL088119, U01 GM074518-04, U01 HL072515-06, U01 HL084756, K12RR023250, NIH P30 DK072488]; NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); University of Maryland General Clinical Research Center [M01 RR 16500]; Baltimore Veterans Administration Medical Center Geriatrics Research and Education Clinical Center; National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C]; component of the National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]; (Emmy Noether Programme) of the German Research Foundation [KO3598/2- 1]; Austrian Science Fond (FWF) [P20545-P05, P20545-P05 and P13180] FX AGES: This study has been funded by NIH contract N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. We are indebted to the participants for their willingness to participate in the study.; AMISH: The Amish studies are supported by grants and contracts from the NIH including R01 AG18728 (Amish Longevity Study), R01 HL088119 (Amish Calcification Study), U01 GM074518-04 (PAPI Study), U01 HL072515-06 (HAPI Study), U01 HL084756 and NIH K12RR023250 (University of Maryland MCRDP), NIH P30 DK072488 (Clinical Nutrition Research Unit), the University of Maryland General Clinical Research Center, grant M01 RR 16500, and the Baltimore Veterans Administration Medical Center Geriatrics Research and Education Clinical Center. We thank our Amish research volunteers for their long-standing partnership in research, and the research staff at the Amish Research Clinic for their hard work and dedication.; The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. We thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. AK was supported by the grant KO3598/2- 1 (Emmy Noether Programme) of the German Research Foundation.; ASPS: The research reported in this article was funded by the Austrian Science Fond (FWF) grant number P20545-P05 and P13180. The Medical University of Graz supports the databank of the ASPS. The authors thank the staff and the participants of the ASPS for their valuable contributions. We thank Birgit Reinhart for her long-term administrative commitment and Ing Johann Semmler for the technical assistance at creating the DNA bank. NR 53 TC 15 Z9 15 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2015 VL 87 IS 5 BP 1017 EP 1029 DI 10.1038/ki.2014.361 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA CH5HS UT WOS:000354066900019 PM 25493955 ER PT J AU Blay, JY Papai, Z Tolcher, AW Italiano, A Cupissol, D Lopez-Pousa, A Chawla, S Bompas, E Babovic, N Penel, N Isambert, N Staddon, AP Saada-Bouzid, E Santoro, A Franke, FA Cohen, P Le-Guennec, S Demetri, GD AF Blay, Jean-Yves Papai, Zsuzsanna Tolcher, Anthony W. Italiano, Antoine Cupissol, Didier Lopez-Pousa, Antonio Chawla, St P. Bompas, Emmanuelle Babovic, Nada Penel, Nicolas Isambert, Nicolas Staddon, Arthur P. Saada-Bouzid, Esma Santoro, Armando Franke, Fabio A. Cohen, Patrick Le-Guennec, Solenn Demetri, George D. TI Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID COMBRETASTATIN A4 PHOSPHATE; VASCULAR-DISRUPTING AGENTS; BLOOD-FLOW STASIS; TUMOR; BEVACIZUMAB; COMBINATION; DOXORUBICIN; SORAFENIB; ANGIOSARCOMA; MULTICENTER AB Background Ombrabulin (AVE8062) disrupts the vasculature of established tumours and has shown preclinical synergistic anti-tumour activity when combined with cisplatin. In this phase 3 trial, we aimed to assess the efficacy and safety of ombrabulin plus cisplatin compared with placebo plus cisplatin in patients with advanced soft-tissue sarcomas. Methods We did this multinational, randomised, double-blind, placebo-controlled phase 3 study at 44 centres in ten countries. Patients aged 18 years and older with metastatic soft-tissue sarcomas, an Eastern Cooperative Oncology Group performance status of 0-2, and who had previously received treatment with anthracycline and ifosfamide were randomly assigned (1:1) to intravenous infusion of ombrabulin 25 mg/m(2) plus cisplatin 75 mg/m(2) or intravenous infusion of placebo plus cisplatin 75 mg/m(2) every 3 weeks. Patients were allocated to treatment using a permuted blocks randomisation scheme (block size of four) via an interactive voice-response system, and stratified by histological subtype. Patients, medical staff, study investigators, and individuals who handled and analysed the data were masked to treatment assignment. Our primary endpoint was median progression-free survival in the intention-to-treat population. Safety analyses were done on all randomised patients who received at least one dose of study drug. This trial is now closed, and is registered with ClinicalTrials.gov, number NCT00699517. Findings Between June 13, 2008, and April 26, 2012, we randomly assigned 355 patients to ombrabulin plus cisplatin (n=176) or placebo plus cisplatin (n=179). Median duration of follow-up was 27.9 (IQR 20.9-33.2) in the placebo group and 30.5 months (20.7-37.6) in the ombrabulin group. Progression-free survival was slightly, but significantly, improved in the ombrabulin group compared with the placebo group (median 1.54 months [95% CI 1.45-2.69] vs 1.41 [1.38-1.58] months; hazard ratio 0.76 [95% CI 0.59-0.98]; p=0.0302). Grade 3 or 4 adverse events occurred more frequently in individuals in the ombrabulin group than in those in the placebo group and included neutropenia (34 [19%] in the ombrabulin group vs 14 [8%] in the placebo group) and thrombocytopenia (15 [8%] vs six [3%] for placebo). Adverse events leading to death occurred in 18 patients in the ombrabulin group and 10 patients in the placebo group. Interpretation The combination of ombrabulin and cisplatin significantly improved progression-free survival; however, it did not show a sufficient clinical benefit in patients with advanced soft-tissue sarcomas to support its use as a therapeutic option. Predictive biomarkers are needed for the rational clinical development of tumour vasculardisrupting drugs for soft-tissue sarcomas. C1 [Blay, Jean-Yves] Univ Lyon 1, European Org Res & Treatment Canc, French Sarcoma Grp, Ctr Leon Berard,Dept Med, F-69008 Lyon, France. [Papai, Zsuzsanna] State Med Ctr, Budapest, Hungary. [Tolcher, Anthony W.] South Texas Accelerated Res Therapeut, San Antonio, TX USA. [Italiano, Antoine] Inst Bergonie, Bordeaux, France. [Cupissol, Didier] Ctr Val Aurelle, Montpellier, France. [Lopez-Pousa, Antonio] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Lopez-Pousa, Antonio] Networking Res Ctr, Barcelona, Spain. [Chawla, St P.] St Johns Hosp, Santa Monica, CA USA. [Bompas, Emmanuelle] Ctr Rene Gauducheau, F-44035 Nantes, France. [Babovic, Nada] Inst Oncol & Radiol Serbia, Belgrade, Serbia. [Penel, Nicolas] Ctr Oscar Lambret, F-59020 Lille, France. [Isambert, Nicolas] Ctr Georges Francois Leclerc, Dijon, France. [Staddon, Arthur P.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Saada-Bouzid, Esma] Ctr Antoine Lacassagne, F-06054 Nice, France. [Santoro, Armando] Ist Clin Humanitas IRCCS, Humanitas Canc Ctr, Milan, Italy. [Franke, Fabio A.] Hosp Caridade Ijui, CACON, Ijui, Brazil. [Cohen, Patrick; Le-Guennec, Solenn] Sanofi, Vitry Sur Seine, France. [Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Demetri, George D.] Harvard Univ, Sch Med, Ludwig Ctr Harvard, Boston, MA USA. RP Blay, JY (reprint author), Univ Lyon 1, European Org Res & Treatment Canc, French Sarcoma Grp, Ctr Leon Berard,Dept Med, F-69008 Lyon, France. EM jean-yves.blay@lyon.unicancer.fr RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X FU EuroSARC (FP7) project [278742]; Sanofi FX We thank the patients, their families and caregivers, and the principal investigators and their study teams who participated in this study. Study concept developed in part within the Conticanet and EuroSARC (FP7-278742) projects. We also thank Anne-Francoise Peloux (clinical trial manager, Sanofi, Chilly-Mazarin, France). This trial was monitored by Andrea Lovaglio from inVentiv Health Clinica, Buenos Aires, Argentina (supplier of drug development services). Matthew Naylor (Articulate Science, London, UK) provided writing assistance, funded by Sanofi. NR 43 TC 14 Z9 15 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2015 VL 16 IS 5 BP 531 EP 540 DI 10.1016/S1470-2045(15)70102-6 PG 10 WC Oncology SC Oncology GA CH3DW UT WOS:000353908200047 PM 25864104 ER PT J AU Blay, JY Shen, L Kang, YK Rutkowski, P Qin, SK Nosov, D Wan, D Trent, J Srimuninnimit, V Papai, Z Le Cesne, A Novick, S Taningco, L Mo, S Green, S Reichardt, P Demetri, GD AF Blay, Jean-Yves Shen, Lin Kang, Yoon-Koo Rutkowski, Piotr Qin, Shukui Nosov, Dmitry Wan, Desen Trent, Jonathan Srimuninnimit, Vichien Papai, Zsuzsanna Le Cesne, Axel Novick, Steven Taningco, Lilia Mo, Shuyuan Green, Steven Reichardt, Peter Demetri, George D. TI Nilotinib versus imatinib as first-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumours (ENESTg1): a randomised phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID TYROSINE KINASE INHIBITORS; PROGRESSION-FREE SURVIVAL; DOSE IMATINIB; RESISTANT; MESYLATE; GIST; KIT; METAANALYSIS; SUNITINIB AB Background Nilotinib inhibits the tyrosine kinase activity of ABL1/BCR-ABL1 and KIT, platelet-derived growth factor receptors (PDGFRs), and the discoidin domain receptor. Gain-of-function mutations in KIT or PDGFR alpha are key drivers in most gastrointestinal stromal tumours (GISTs). This trial was designed to test the efficacy and safety of nilotinib versus imatinib as first-line therapy for patients with advanced GISTs. Methods In this randomised, open-label, multicentre, phase 3 trial (ENESTg1), participants from academic centres were aged 18 years or older and had previously untreated, histologically confirmed, metastatic or unresectable GISTs. Patients were stratified by previous adjuvant therapy and randomly assigned (1: 1) via a randomisation list to receive oral imatinib 400 mg once daily or oral nilotinib 400 mg twice daily. The primary endpoint was centrally reviewed progression-free survival. Efficacy endpoints were assessed by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00785785. Findings Because the futility boundary was crossed at a preplanned interim analysis, trial accrual terminated in April, 2011. Between March 16, 2009, and April 21, 2011, 647 patients were enrolled; of whom 324 were allocated nilotinib and 320 were allocated imatinib. At final analysis of the core study (data cutoff, October, 2012), 2-year progression-free survival was higher in the imatinib group (59.2% [95% CI 50.9-66.5]) than in the nilotinib group (51.6% [43.0-59.5]; hazard ratio 1.47 [95% CI 1.10-1.95]). In the imatinib group, the most common grade 3-4 adverse events were hypophosphataemia (19 [6%]), anaemia (17 [5%]), abdominal pain (13; 4%), and elevated lipase level (15; 5%), and in the nilotinib group were anaemia (18; 6%), elevated lipase level (15; 5%), elevated alanine aminotransferase concentration (12; 4%), and abdominal pain (11; 3%). The most common serious adverse event in both groups was abdominal pain (11 [4%] in the imatinib group, 14 [4%] in the nilotinib group). Interpretation Nilotinib cannot be recommended for broad use to treat first-line GIST. However, future studies might identify patient subsets for whom first-line nilotinib could be of clinical benefit. C1 [Blay, Jean-Yves] Univ Lyon 1, Ctr Leon Berard, F-69365 Lyon, France. [Shen, Lin] Peking Univ, Key Lab Carcinogenesis & Translat Res, Dept GastrointestinaI Oncol, Minist Educ,Canc Hosp & Inst, Beijing 100871, Peoples R China. [Kang, Yoon-Koo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Rutkowski, Piotr] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland. [Qin, Shukui] Nanjing Bayi Hosp, PLA Canc Ctr, Nanjing, Jiangsu, Peoples R China. [Nosov, Dmitry] Blokhin Canc Res Ctr, Dept Clin Pharmacol & Chemotherapy, Moscow, Russia. [Wan, Desen] Sun Yat Sen Univ, State Key Lab Southern China, Dept Colorectal Surg, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China. [Trent, Jonathan] Univ Miami, Sylvester Canc Ctr, Miami, FL USA. [Srimuninnimit, Vichien] Siriraj Hosp, Div Med Oncol, Bangkok, Thailand. [Papai, Zsuzsanna] Mil Hosp State Hlth Ctr, Dept Oncol, Budapest, Hungary. [Le Cesne, Axel] Inst Gustave Roussy, Dept Med, Villejuif, France. [Novick, Steven; Taningco, Lilia; Mo, Shuyuan] Novartis Pharmaceut, E Hanover, NJ USA. [Green, Steven] Novartis Pharma AG, Basel, Switzerland. [Reichardt, Peter] HELIOS Klinikum Berlin Buch, Dept Interdisciplinary Oncol, Berlin, Germany. [Demetri, George D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Demetri, George D.] Harvard Univ, Sch Med, Ludwig Ctr Harvard, Boston, MA USA. RP Blay, JY (reprint author), Ctr Leon Berard, Dept Med Oncol, F-69008 Lyon, France. EM jean-yves.blay@lyon.unicancer.fr RI Blay, Jean-Yves/N-3966-2016; OI Blay, Jean-Yves/0000-0001-7190-120X; Rutkowski, Piotr/0000-0002-8920-5429 FU Novartis Pharmaceuticals FX Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Justin Potuzak (Chameleon Communications, London, UK) and Pamela Tuttle (Articulate Science, Atlanta, GA, USA) for their medical editorial assistance with this report. NR 31 TC 17 Z9 19 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2015 VL 16 IS 5 BP 550 EP 560 DI 10.1016/S1470-2045(15)70105-1 PG 11 WC Oncology SC Oncology GA CH3DW UT WOS:000353908200049 PM 25882987 ER PT J AU Machiels, JPH Haddad, RI Fayette, J Licitra, LF Tahara, M Vermorken, JB Clement, PM Gauler, T Cupissol, D Grau, JJ Guigay, J Caponigro, F de Castro, G Viana, LD Keilholz, U del Campo, JM Cong, XYJL Ehrnrooth, E Cohen, EEW AF Machiels, Jean-Pascal H. Haddad, Robert I. Fayette, Jerome Licitra, Lisa F. Tahara, Makoto Vermorken, Jan B. Clement, Paul M. Gauler, Thomas Cupissol, Didier Jose Grau, Juan Guigay, Joel Caponigro, Francesco de Castro, Gilberto, Jr. Viana, Luciano de Souza Keilholz, Ulrich del Campo, Joseph M. Cong, Xiuyu Julie Ehrnrooth, Eva Cohen, Ezra E. W. CA LUX-H N 1 Investigators TI Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID ERBB FAMILY BLOCKER; CHEMOTHERAPY PLUS CETUXIMAB; HUMAN-PAPILLOMAVIRUS; RETROSPECTIVE ANALYSIS; CLINICAL-PRACTICE; SOLID TUMORS; EFFICACY; CANCER; P16(INK4A); BIOMARKER AB Background Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting. We aimed to assess the efficacy and safety of afatinib compared with methotrexate as second-line treatment in patients with recurrent or metastatic HNSCC progressing on or after platinum-based therapy. Methods In this open-label, phase 3, randomised controlled trial conducted in 101 centres in 19 countries, we enrolled patients aged 18 years or older with histologically or cytologically confirmed HNSCC that was recurrent, metastatic, or both who had progressed on or after first-line platinum-based therapy, were not amenable for salvage surgery or radiotherapy, and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Previous treatment with more than one systemic regimen in this setting was not allowed; previous treatment with EGFR-targeted antibody therapy (but not EGFR-targeted tyrosine-kinase inhibitors) was allowed. We randomly assigned eligible patients in a 2: 1 ratio to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2) per week), stratified by ECOG performance status and previous EGFR-targeted antibody therapy for recurrent or metastatic disease. Randomisation was done centrally with an interactive voice or web-based response system. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. The primary endpoint was progression-free survival as assessed by an independent, central imaging review committee. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01345682. Findings Between Jan 10, 2012, and Dec 12, 2013, we enrolled 483 patients and randomly assigned 322 to afatinib and 161 to methotrexate. After a median follow-up of 6.7 months (IQR 3.1-9.0), progression-free survival was longer in the afatinib group than in the methotrexate group (median 2.6 months [95% CI 2.0-2.7] for the afatinib group vs 1.7 months [1.5-2.4] for the methotrexate group; hazard ratio [HR] 0.80 [95% CI 0.65-0.98], p=0.030). The most frequent grade 3 or 4 drug-related adverse events were rash or acne (31 [10%] of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group), diarrhoea (30 [9%] vs three [2%]), stomatitis (20 [6%] vs 13 [8%]), fatigue (18 [6%] vs five [3%]), and neutropenia (1 [<1%] vs 11 [7%]); serious adverse events occurred in 44 (14%) of afatinib-treated patients and 18 (11%) of methotrexate-treated patients. Interpretation Afatinib was associated with significant improvements in progression-free survival and had a manageable safety profile. These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC. C1 [Machiels, Jean-Pascal H.] Clin Univ St Luc, Inst Roi Albert II, Med Oncol Serv, B-1200 Brussels, Belgium. [Machiels, Jean-Pascal H.] Catholic Univ Louvain, Inst Rech Clin & Expt, Pole MIRO, B-1200 Brussels, Belgium. [Haddad, Robert I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Haddad, Robert I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fayette, Jerome] Univ Lyon, Ctr Leon Berard, Lyon, France. [Fayette, Jerome] Univ Lyon, Hosp Civils Lyon, Lyon, France. [Licitra, Lisa F.] Ist Nazl Tumori, Fdn IRCCS, I-20133 Milan, Italy. [Tahara, Makoto] Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan. [Vermorken, Jan B.] Univ Antwerp Hosp, Edegem, Belgium. [Clement, Paul M.] Katholieke Univ Leuven, Dept Oncol, Leuven, Belgium. [Gauler, Thomas] Univ Hosp Essen, West German Canc Ctr, Essen, Germany. [Cupissol, Didier] Inst Canc Montpellier Val dAurelle, Montpellier, France. [Jose Grau, Juan] Univ Barcelona, Hosp Clin, E-08007 Barcelona, Spain. [Guigay, Joel] Gustave Roussy, Villejuif, France. [Guigay, Joel] Ctr Antoine Lacassagne, F-06054 Nice, France. [Caponigro, Francesco] IRCCS, Fdn G Pascale, Ist Nazl Tumori, Div Head & Neck Med Oncol, Naples, Italy. [de Castro, Gilberto, Jr.] Inst Canc Estado Sao Paulo, Sao Paulo, Brazil. [Viana, Luciano de Souza] Hosp Canc Barretos, Sao Paulo, Brazil. [Keilholz, Ulrich] Charite, Ctr Comprehens Canc, Berlin, Germany. [del Campo, Joseph M.] Hosp Univ Vall DHebron, Dept Med Oncol, Barcelona, Spain. [Cong, Xiuyu Julie] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Ehrnrooth, Eva] Danmark AS, Boehringer Ingelheim, Copenhagen, Denmark. [Cohen, Ezra E. W.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. RP Machiels, JPH (reprint author), Clin Univ St Luc, Inst Roi Albert II, Med Oncol Serv, B-1200 Brussels, Belgium. EM jean-pascal.machiels@uclouvain.be RI Guntinas-Lichius, Orlando/L-1871-2016; Madeddu, Clelia/C-2347-2014; Licitra, Lisa/C-6271-2017; Greil, Richard/C-7673-2017; Specenier, Pol/E-1679-2014 OI Guntinas-Lichius, Orlando/0000-0001-9671-0784; Licitra, Lisa/0000-0003-0623-4118; Greil, Richard/0000-0002-4462-3694; Specenier, Pol/0000-0002-2465-5197 FU Boehringer Ingelheim FX We thank the patients, their families, and all of the investigators who participated in this study. We would also like to thank Liz Svensson (Boehringer Ingelheim, Copenhagen, Denmark), for her contributions to the study. Medical writing assistance was provided by Katie McClendon (GeoMed, Macclesfield, UK [an Ashfield business, part of UDG Healthcare plc]) and was supported financially by Boehringer Ingelheim during the preparation of this report. NR 34 TC 67 Z9 67 U1 5 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2015 VL 16 IS 5 BP 583 EP 594 DI 10.1016/S1470-2045(15)70124-5 PG 12 WC Oncology SC Oncology GA CH3DW UT WOS:000353908200052 PM 25892145 ER PT J AU Wakeman, SE Rich, JD AF Wakeman, Sarah E. Rich, Josiah D. TI Substance use disorders and avoidable mortality after prison SO LANCET PSYCHIATRY LA English DT Editorial Material ID METHADONE; INMATES C1 [Wakeman, Sarah E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Subst Use Disorder Initiat, Boston, MA USA. [Rich, Josiah D.] Brown Univ, Miriam Hosp, Ctr Prisoner Hlth & Human Rights, Providence, RI 02906 USA. RP Rich, JD (reprint author), Brown Univ, Miriam Hosp, Ctr Prisoner Hlth & Human Rights, Providence, RI 02906 USA. EM JRich@Lifespan.org FU NIH [K24DA022112, P30AI42853] FX JDR was supported by NIH grants K24DA022112 and P30AI42853. JDR is a stockholder in Alkermes. SEW declares no competing interests. NR 14 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2215-0374 J9 LANCET PSYCHIAT JI Lancet Psychiatry PD MAY PY 2015 VL 2 IS 5 BP 369 EP 370 DI 10.1016/S2215-0366(15)00125-X PG 3 WC Psychiatry SC Psychiatry GA CH3DG UT WOS:000353906200008 PM 26069881 ER PT J AU Henderson, DC Vinvenzi, B Andrea, NV Ulloa, M Copeland, PM AF Henderson, David C. Vinvenzi, Brenda Andrea, Nicolas V. Ulloa, Melissa Copeland, Paul M. TI Pathophysiological mechanisms of increased cardiometabolic risk in people with schizophrenia and other severe mental illnesses SO LANCET PSYCHIATRY LA English DT Article ID INDUCED WEIGHT-GAIN; ATYPICAL ANTIPSYCHOTIC-DRUGS; INDUCED METABOLIC ALTERATIONS; CORONARY-HEART-DISEASE; GLUCOSE-TOLERANCE TEST; MINIMAL MODEL ANALYSIS; 5-HT2C RECEPTOR GENE; HEALTHY LIFE-STYLE; BODY-MASS INDEX; DIABETES-MELLITUS AB Patients with schizophrenia have increased mortality and morbidity compared with the general population. These patients have a 20-year shorter lifespan than peers without schizophrenia, mainly due to premature cardiovascular disease, suicide, and cancer. Patients with severe mental illness are at increased risk for cardiovascular disease related to increased incidence of diabetes, hypertension, smoking, poor diet, obesity, dyslipidaemia, metabolic syndrome, low physical activity, and side-effects of antipsychotic drugs. Some second-generation antipsychotics (eg, clozapine, olanzapine, quetiapine, and risperidone) are associated with an increased risk of weight gain and obesity, impaired glucose tolerance and new-onset diabetes, hyperlipidaemia, and cardiovascular disease. The mechanisms by which schizophrenia and patients with severe mental illness are susceptible to cardiometabolic disorders are complex and include lifestyle risks and direct and indirect effects of antipsychotic drugs. An understanding of these risks might lead to effective interventions for prevention and treatment of cardiometabolic disorders in schizophrenia and severe mental illness. C1 [Henderson, David C.] MGH Freedom Trail Clin, Boston, MA 02114 USA. [Henderson, David C.; Vinvenzi, Brenda; Andrea, Nicolas V.; Ulloa, Melissa] Massachusetts Gen Hosp, Dept Psychiat, Schizophrenia Clin & Res Program, Boston, MA 02114 USA. [Henderson, David C.] Harvard Univ, Sch Publ Hlth, Sch Med, Dept Psychiat & Epidemiol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Sch Med, Dept Med, Boston, MA USA. [Copeland, Paul M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Henderson, DC (reprint author), MGH Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@mgh.harvard.edu FU EVP (Forum Pharmaceuticals); Otsuka Pharmaceuticals; Reckitt Benckiser FX DCH has research grants from EVP (Forum Pharmaceuticals), Otsuka Pharmaceuticals, and Reckitt Benckiser, and has received honoraria for consulting from Otsuka, Alkermes, and Janssen. PMC has received honoraria for consulting from Sanofi. The other authors declare no competing interests. NR 135 TC 19 Z9 19 U1 6 U2 25 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2215-0374 J9 LANCET PSYCHIAT JI Lancet Psychiatry PD MAY PY 2015 VL 2 IS 5 BP 452 EP 464 PG 13 WC Psychiatry SC Psychiatry GA CH3DG UT WOS:000353906200033 PM 26360288 ER PT J AU Chwastiak, LA Freudenreich, O Tek, C McKibbin, C Han, J McCarron, R Wisse, B AF Chwastiak, Lydia A. Freudenreich, Oliver Tek, Cenk McKibbin, Christine Han, Jaesu McCarron, Robert Wisse, Brent TI Clinical management of comorbid diabetes and psychotic disorders SO LANCET PSYCHIATRY LA English DT Article ID SERIOUS MENTAL-ILLNESS; LIFE-STYLE INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; INDUCED WEIGHT-GAIN; SCHIZOPHRENIA SPECTRUM DISORDERS; CARDIOVASCULAR RISK-FACTORS; DOUBLE-BLIND; HEALTH-CARE; SMOKING-CESSATION; BARIATRIC SURGERY AB Individuals with psychotic disorders experience substantial health disparities with respect to diabetes, including increased risk of incident diabetes and of poor diabetes outcomes (eg, diabetes complications and mortality). Low-quality medical care for diabetes is a significant contributor to these poor health outcomes. A thoughtful approach to both diabetes pharmacotherapy and drug management for psychotic disorders is essential, irrespective of whether treatment is given by a psychiatrist, a primary care provider, or an endocrinologist. Exposure to drugs with high metabolic liability should be minimised, and both psychiatric providers and medical providers need to monitor patients to ensure that medical care for diabetes is adequate. Promising models of care management and team approaches to coordination and integration of care highlight the crucial need for communication and cooperation among medical and psychiatric providers to improve outcomes in these patients. Evidence-based programmes that promote weight loss or smoking cessation need to be more accessible for these patients, and should be available in all the settings where they access care. C1 [Chwastiak, Lydia A.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [Freudenreich, Oliver] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Tek, Cenk] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [McKibbin, Christine] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Han, Jaesu; McCarron, Robert] Univ Calif Davis, Dept Psychiat, Sacramento, CA 95817 USA. [Han, Jaesu; McCarron, Robert] Univ Calif Davis, Dept Family & Community Med, Sacramento, CA 95817 USA. [Wisse, Brent] Univ Washington, Sch Med, Dept Med, Div Endocrinol, Seattle, WA 98195 USA. RP Chwastiak, LA (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. EM lchwast@uw.edu FU Psychogenics and Forum; MGH Psychiatry Academy; Global Medical Education; BeaconHealth Strategies; UpToDate FX OF reports grants from Psychogenics and Forum, personal fees from MGH Psychiatry Academy, Global Medical Education, and BeaconHealth Strategies, non-financial support from Optimal Medicine, and personal fees and other from UpToDate, outside the submitted work. AB other authors declare no competing interests. NR 119 TC 5 Z9 5 U1 7 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2215-0374 J9 LANCET PSYCHIAT JI Lancet Psychiatry PD MAY PY 2015 VL 2 IS 5 BP 465 EP 476 PG 12 WC Psychiatry SC Psychiatry GA CH3DG UT WOS:000353906200034 PM 26360289 ER PT J AU Welling, DB AF Welling, D. Bradley TI Classics From The Laryngoscope SO LARYNGOSCOPE LA English DT Editorial Material C1 [Welling, D. Bradley] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Otol & Neurotol Div, Boston, MA 02114 USA. RP Welling, DB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM brad_welling@meei.harvard.edu NR 5 TC 0 Z9 0 U1 1 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 MAY PY 2015 VL 125 IS 5 BP 1031 EP 1032 DI 10.1002/lary.25289 PG 2 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CH4IJ UT WOS:000353996900008 PM 25917653 ER PT J AU Remenschneider, AK Scangas, G Meier, JC Gray, ST Holbrook, EH Gliklich, RE Metson, R AF Remenschneider, Aaron K. Scangas, George Meier, Josh C. Gray, Stacey T. Holbrook, Eric H. Gliklich, Richard E. Metson, Ralph TI EQ-5D-Derived Health Utility Values in Patients Undergoing Surgery for Chronic Rhinosinusitis SO LARYNGOSCOPE LA English DT Article DE Chronic rhinosinusitis; quality of life; EQ-5D; health utility; quality adjusted life years ID QUALITY-OF-LIFE; ENDOSCOPIC SINUS SURGERY; US ADULT-POPULATION; UNITED-STATES; EQ-5D; SCORES; OUTCOMES; EUROQOL; IMPACT; VALIDITY AB Objectives/HypothesisHealth utility value (HUV) is an index used to measure health-related quality of life for the valuation and comparison of treatments. The Euroqol 5-Dimension (EQ-5D) questionnaire is a widely used method for determining HUV, but it has not been applied for this purpose in patients with chronic rhinosinusitis (CRS) who undergo sinus surgery. Study DesignProspective cohort study. MethodsPatients with CRS, who were recruited from 11 different otolaryngologic practices, completed the EQ-5D questionnaire at baseline, as well as 3, 12, and 24 months after surgery. HUVs calculated from the results of this questionnaire were compared to those reported in the general U.S. population and to patients suffering from other chronic diseases. ResultsBaseline EQ-5D surveys were completed by 242 patients. Mean baseline HUV (standard deviation) was 0.81 (0.13). Female gender, revision surgery, and the use of intraoperative image guidance were associated was significantly lower baseline values. HUV rose at 3 months to 0.89 (0.12) and remained improved at 12 months 0.88 (0.10) and 24 months 0.89 (0.10) (P<0.001). Baseline HUV in CRS (0.81[0.13]) is lower than the general U.S. population (0.85 [0.18]) and appears appropriately positioned among other common chronic conditions including asthma (0.82-0.92), migraine (0.81-0.91), and seasonal allergies (0.94). ConclusionsSinus surgery provides improvement in HUV in patients with CRS. These values may be paired with costs of care to perform cost-utility analysis on this group of patients. Level of Evidence2c. Laryngoscope, 125:1056-1061, 2015 C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Remenschneider, AK (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Aaron_Remenschneider@meei.harvard.edu FU Board Committee on Quality at Massachusetts Eye and Ear Infirmary FX This work was supported by a funding grant from the Board Committee on Quality at Massachusetts Eye and Ear Infirmary. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 43 TC 13 Z9 13 U1 1 U2 2 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 MAY PY 2015 VL 125 IS 5 BP 1056 EP 1061 DI 10.1002/lary.25054 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CH4IJ UT WOS:000353996900013 PM 25431320 ER PT J AU Durand, ML Yarlagadda, BB Rich, DL Lin, DT Emerick, KS Rocco, JW Deschler, DG AF Durand, Marlene L. Yarlagadda, Bharat B. Rich, Debbie L. Lin, Derrick T. Emerick, Kevin S. Rocco, James W. Deschler, Daniel G. TI The Time Course and Microbiology of Surgical Site Infections After Head and Neck Free Flap Surgery SO LARYNGOSCOPE LA English DT Article DE Surgical site infection; free flap; reconstructive surgery; head and neck cancer; complications; microbiology ID RESISTANT STAPHYLOCOCCUS-AUREUS; CLEAN-CONTAMINATED HEAD; GRAM-NEGATIVE BACILLI; ANTIBIOTIC-PROPHYLAXIS; CANCER SURGERY; RISK-FACTORS; RECONSTRUCTIVE SURGERY; COMPLICATIONS; FLORA; BACTERIOLOGY AB Objectives/HypothesisDetermine the time of onset and microbiology of surgical site infections (SSIs) following head and neck free flap reconstructive surgeries. Study DesignRetrospective cohort study. MethodsAll 504 free flap surgical cases (484 patients) performed April 1, 2009 to September 30, 2013 were reviewed; SSIs occurring 30 days postoperatively were evaluated. Admission screening for methicillin-resistant Staphylococcus aureus (MRSA) colonization was performed on all patients. ResultsFlap-recipient site infections (flap SSIs) occurred in 67 cases (13.3%), one-third week 1 postoperatively, one-third week 2, one-third days 15 to 30; 45% occurred after hospital discharge. Wound cultures were polymicrobial, but 25% grew only normal oral flora, whereas 75% grew pathogens not part of normal oral flora, such as gram-negative bacilli (44% of cases), MRSA (20%), and methicillin-sensitive S aureus (MSSA) (16%). The frequency of these pathogens did not vary significantly by the time of SSI onset. In 67%, cultures included at least one pathogen resistant to the prophylactic antibiotic used. Clindamycin prophylaxis was a significant risk factor for flap SSI and for early partial or complete flap loss from infection. Donor SSIs occurred in 22 cases (4.4%), 95% >1 week postoperatively, and MRSA or MSSA were the primary pathogens in 89%. Of the 25 patients colonized with MRSA on admission, 40% developed a flap or donor SSI, a rate significantly higher than in non-colonized patients. ConclusionsGram-negative bacilli, MRSA, and MSSA were significant SSI pathogens, and late onset of infection was common. Better screening, decolonization, and prophylaxis may reduce SSI rates. Level of Evidence2b Laryngoscope, 125:1084-1089, 2015 C1 [Durand, Marlene L.] Massachusetts Eye & Ear Infirm, Infect Dis Serv, Boston, MA 02114 USA. [Yarlagadda, Bharat B.; Lin, Derrick T.; Emerick, Kevin S.; Rocco, James W.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Rich, Debbie L.] Massachusetts Eye & Ear Infirm, Dept Nursing, Boston, MA 02114 USA. [Durand, Marlene L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Durand, ML (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Cox 5,55 Fruit St, Boston, MA 02114 USA. EM mdurand@partners.org NR 40 TC 6 Z9 6 U1 0 U2 5 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 MAY PY 2015 VL 125 IS 5 BP 1084 EP 1089 DI 10.1002/lary.25038 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CH4IJ UT WOS:000353996900018 PM 25425457 ER PT J AU Kozin, ED Gulati, S Kaplan, AB Lehmann, AE Remenschneider, AK Landegger, LD Cohen, MS Lee, DJ AF Kozin, Elliott D. Gulati, Shawn Kaplan, Alyson B. Lehmann, Ashton E. Remenschneider, Aaron K. Landegger, Lukas D. Cohen, Michael S. Lee, Daniel J. TI Systematic Review of Outcomes Following Observational and Operative Endoscopic Middle Ear Surgery SO LARYNGOSCOPE LA English DT Review DE Endoscope; otology; middle ear surgery; tympanoplasty; cholesteatoma ID CHOLESTEATOMA SURGERY; ATTIC CHOLESTEATOMA; ACQUIRED CHOLESTEATOMA; MANAGEMENT; TYMPANOPLASTY; EXPERIENCE; CHILDREN AB ObjectivesMiddle ear surgery increasingly employs endoscopes as an adjunct to or replacement for the operative microscope. We provide a systematic review of endoscope applications in middle ear surgery with an emphasis on outcomes, including the need for conversion to microscope, audiometric findings, length of follow-up, as well as disease-specific outcomes. Data SourcesPubMed, Embase, and Cochrane CENTRAL database. MethodsA literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. Articles were categorized based on study design, indication, and use of an endoscope either as an adjunct to or as a replacement for a microscope. Qualitative and descriptive analyses of studies and outcomes data were performed. ResultsOne-hundred three articles met inclusion and exclusion criteria. Of the identified articles, 38 provided outcomes data. The majority of these studies were moderate quality, retrospective, case-series reports. The indications for use of the endoscope were broad, with the most common being resection of cholesteatoma. In cholesteatoma surgery, endoscope approaches routinely identified residual cholesteatoma in primary and second-look cases. Other outcomes, including robust audiometric data, operating room times, wound healing, and quality of life surveys were not well described. ConclusionsEndoscopes have consistently been used as an adjunct to the microscope to improve visualization of the tympanic cavity. Recent reports utilize the endoscope exclusively during surgical dissection; however, data comparing patient outcomes following the use of an endoscope to a microscope are lacking. Areas in need of additional research are highlighted. Level of EvidenceNA Laryngoscope, 125:1205-1214, 2015 C1 [Kozin, Elliott D.; Lehmann, Ashton E.; Remenschneider, Aaron K.; Cohen, Michael S.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kozin, Elliott D.; Gulati, Shawn; Kaplan, Alyson B.; Lehmann, Ashton E.; Remenschneider, Aaron K.; Landegger, Lukas D.; Cohen, Michael S.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu RI Kozin, Elliott/J-1225-2014; OI Kozin, Elliott/0000-0002-0305-0682; Landegger, Lukas D./0000-0002-9660-2625 FU NIDCD NIH HHS [T32 DC000020] NR 43 TC 21 Z9 21 U1 1 U2 5 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 MAY PY 2015 VL 125 IS 5 BP 1205 EP 1214 DI 10.1002/lary.25048 PG 10 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CH4IJ UT WOS:000353996900040 PM 25418475 ER PT J AU McGee, SF Kornblau, SM Qiu, Y Look, AT Zhang, N Yoo, SY Coombes, KR Kentsis, A AF McGee, S. F. Kornblau, S. M. Qiu, Y. Look, A. T. Zhang, N. Yoo, S-Y Coombes, K. R. Kentsis, A. TI Biological properties of ligand-dependent activation of the MET receptor kinase in acute myeloid leukemia SO LEUKEMIA LA English DT Letter ID TYROSINE KINASE; GROWTH; CELLS; EXPRESSION; SEQUENCE; KIT; AML C1 [McGee, S. F.] Mt Sinai St Lukes Roosevelt Hosp Ctr, Dept Med, New York, NY 10025 USA. [McGee, S. F.; Kentsis, A.] Sloan Kettering Inst, Mol Pharmacol & Chem Program, New York, NY USA. [Kornblau, S. M.; Qiu, Y.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Look, A. T.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Zhang, N.; Yoo, S-Y] Univ Texas MD Anderson Canc Ctr, Bioinformat & Computat Biol, Houston, TX 77030 USA. [Coombes, K. R.] Ohio State Univ, Coll Med, Dept Biomed Informat, Columbus, OH 43210 USA. [Kentsis, A.] Cornell Univ, Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Kentsis, A.] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA. RP McGee, SF (reprint author), Mt Sinai St Lukes Roosevelt Hosp Ctr, Dept Med, New York, NY 10025 USA. EM skornblau@mdanderson.org; kentsisresearchgroup@gmail.com OI Kentsis, Alex/0000-0002-8063-9191 FU NCI NIH HHS [K08 CA160660, K08CA160660, P30 CA008748, P30 CA016672] NR 20 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAY PY 2015 VL 29 IS 5 BP 1218 EP 1221 DI 10.1038/leu.2014.348 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA CH5JA UT WOS:000354070600027 PM 25541150 ER PT J AU Caverly, TJ Prochazka, AV Combs, BP Lucas, BP Mueller, SR Kutner, JS Binswanger, I Fagerlin, A McCormick, J Pfister, S Matlock, DD AF Caverly, Tanner J. Prochazka, Allan V. Combs, Brandon P. Lucas, Brian P. Mueller, Shane R. Kutner, Jean S. Binswanger, Ingrid Fagerlin, Angela McCormick, Jacqueline Pfister, Shirley Matlock, Daniel D. TI Doctors and Numbers: An Assessment of the Critical Risk Interpretation Test SO MEDICAL DECISION MAKING LA English DT Article DE medical decision making; risk perception; risk communication; numeracy ID MEDICAL DECISION-MAKING; NUMERACY SCALE; COMMUNICATION; COMPREHENSION; INFORMATION; STATISTICS; BENEFIT; SKILLS; CARE AB Background. Risk interpretation affects decision making. Yet, there is no valid assessment of how clinicians interpret the risk data that they commonly encounter. Objective. To establish the reliability and validity of a 20-item test of clinicians' risk interpretation. Methods. The Critical Risk Interpretation Test (CRIT) measures clinicians' abilities to 1) modify the interpretation based on meaningful differences in the outcome (e.g., disease specific v. all-cause mortality) and time period (e.g., lifetime v. 10-year mortality), 2) maintain a stable interpretation for different risk framings (e.g., relative v. absolute risk), and 3) correctly interpret how diagnostic testing modifies risk. There were 658 clinicians and medical trainees who participated: 116 nurse practitioners (NPs) at a national conference, 273 medical students at 1 institution, 148 residents in internal medicine at 2 institutions, and 121 internists at 1 institution. Participants completed a self-administered paper test during educational conferences. Seventeen evidence-based medicine experts took the test online and formally assessed content validity. Eighteen second-year medical students were recruited to take the test and a retest 3 weeks later to explore test-retest correlation. Results. Expert review supported test clarity and content validity. Factor analysis supported that the CRIT identifies at least 3 separable areas of clinician knowledge. Test-retest correlation was fair (intraclass correlation coefficient = 0.65; standard error = 0.15). Scores on our test correlated with other tests of related abilities. Mean test scores varied among groups, with differences in prior evidence-based medicine training and experience (93 for NPs, 101 for medical students, 101 for residents, 103 for academic internists, and 110 for physician experts; P < 0.001). Conclusions. Our results provide supporting evidence for the reliability and validity of the CRIT as an index of critical risk interpretation abilities, which is acceptable and feasible to administer in an educational setting. C1 [Caverly, Tanner J.; Fagerlin, Angela] Univ Michigan Med Sch, Ann Arbor Vet Affairs Hlth Syst, Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA. [Prochazka, Allan V.; Combs, Brandon P.; Mueller, Shane R.; Kutner, Jean S.; Binswanger, Ingrid; Matlock, Daniel D.] Univ Colorado Sch Med, Internal Med, Aurora, CO USA. [Prochazka, Allan V.; McCormick, Jacqueline; Pfister, Shirley] Denver Vet Affairs Med Ctr, Ambulatory Care, Denver, CO USA. [Lucas, Brian P.] John H Stroger Jr Hosp Cook Cty, Dept Med, Chicago, IL USA. RP Caverly, TJ (reprint author), Univ Michigan Sch Med, 2800 Plymouth Rd,Bldg 16,Room 326W, Ann Arbor, MI 48109 USA. EM tcaverly@med.umich.edu OI Binswanger, Ingrid/0000-0001-8862-8078 FU Society of General Internal Medicine [T32HP1006]; Society of General Internal Medicine FX Received 5 March 2014 from the Veterans Affairs Center for Clinical Management Research, Ann Arbor Veterans Affairs Health System, University of Michigan Medical School, Ann Arbor, MI (TJC, AF); Internal Medicine, University of Colorado School of Medicine, Aurora, CO (AVP, BPC, SRM, JSK, IB, DDM); Ambulatory Care, Denver Veterans Affairs Medical Center, Denver, CO (AVP, JM, SP); and Department of Medicine, John H. Stroger Jr. Hospital of Cook County, Chicago, IL (BPL). Dr. Caverly was supported by an institutional T32HP1006 grant and the 2012 Founder's Award from the Society of General Internal Medicine. Financial support for this study was provided entirely or in part by a grant (Founder's Award) from the Society of General Internal Medicine. The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. This research was previously presented in oral and abstract form at the 2013 annual meeting for the Society of General Internal Medicine, May 2013. There are no conflicts of interest. Revision accepted for publication 26 September 2014. NR 38 TC 1 Z9 1 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAY PY 2015 VL 35 IS 4 BP 512 EP 524 DI 10.1177/0272989X14558423 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CH6FJ UT WOS:000354131500011 PM 25378297 ER PT J AU Belchior, T Paschoal, VA Magdalon, J Chimin, P Farias, TM Chaves, AB Gorjao, R St-Pierre, P Miyamoto, S Kang, JX Deshaies, Y Marette, A Festuccia, W AF Belchior, Thiago Paschoal, Vivian A. Magdalon, Juliana Chimin, Patricia Farias, Talita M. Chaves-Filho, Adriano B. Gorjao, Renata St-Pierre, Philippe Miyamoto, Sayuri Kang, Jing X. Deshaies, Yves Marette, Andre Festuccia, William TI Omega-3 fatty acids protect from diet-induced obesity, glucose intolerance, and adipose tissue inflammation through PPAR gamma-dependent and PPAR gamma-independent actions SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE Adiposity; Glucose metabolism; Inflammation; Omega-3 polyunsaturated fatty acids; PPAR gamma antagonism ID POLYUNSATURATED FATTY-ACIDS; PROLIFERATOR-ACTIVATED RECEPTORS; INSULIN-RESISTANCE; LIPID MEDIATORS; EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID; OXIDATIVE STRESS; MICE; MACROPHAGES; MECHANISMS AB Scope: We tested herein the hypothesis that peroxisome proliferator activated receptor gamma (PPAR) is a major mediator of omega-3 (n-3) protective actions against high-fat diet (HFD) induced obesity, glucose intolerance, and adipose tissue inflammation. Methods and results: C57BL6 wild-type and fat-1 transgenic (fat-1) mice were fed a low-fat diet (LFD) or HFD, treated or not with PPAR gamma antagonist, and evaluated for energy balance, adiposity, glucose tolerance, and adipose tissue inflammation. Fat-1 mice were protected from obesity, fasting hyperglycemia, glucose intolerance, and adipose tissue inflammation. PPAR gamma inhibition completely abolished fat-1 protection against HFD-induced glucose intolerance, but not obesity or adipose tissue inflammation. To investigate the role of myeloid cell as mediator of n-3 beneficialmetabolic actions, mice with deletion (LyzM-PPAR gamma(KO)) or nondeletion (LyzM-PPAR gamma(WT)) of PPAR gamma in myeloid cells were fed either LFD or HFD (lard) or an HFD rich in n-3 (fish oil). Our findings indicate that myeloid cell associated PPAR gamma is not involved in the attenuation of HFD-induced glucose intolerance and adipose tissue inflammation induced by n-3. Conclusion: High endogenous n-3 fatty acid levels protect from HFD obesity, glucose intolerance, and adipose tissue inflammation. Among these, only protection against glucose intolerance is mediated by non-myeloid cell PPAR gamma. C1 [Belchior, Thiago; Paschoal, Vivian A.; Magdalon, Juliana; Chimin, Patricia; Farias, Talita M.; Festuccia, William] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo, Brazil. [Chaves-Filho, Adriano B.; Miyamoto, Sayuri] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05508000 Sao Paulo, Brazil. [Gorjao, Renata] Univ Cruzeiro Sul, Inst Phys Act & Sports, Sao Paulo, Brazil. [St-Pierre, Philippe; Deshaies, Yves; Marette, Andre] Univ Laval, Dept Med, Fac Med, Quebec Heart & Lung Inst Res Ctr, Quebec City, PQ G1K 7P4, Canada. [Kang, Jing X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Lipid Med & Technol, Boston, MA USA. RP Festuccia, W (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo, Brazil. EM william.festuccia@usp.br RI Belchior de Oliveira, Thiago/F-4281-2015; Chimin, Patricia/K-2434-2012; Magdalon, Juliana/G-8022-2015; CEPID, Redoxoma/J-2971-2015; Festuccia, William/C-7618-2012; Miyamoto, Sayuri/A-2144-2008 OI Belchior de Oliveira, Thiago/0000-0003-1985-8464; Festuccia, William/0000-0003-4769-0806; Miyamoto, Sayuri/0000-0002-5714-8984 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [09/15354-7, 10/52191-6, 11/14172-2]; Agence Universitaire de la Francophonie FX This work was supported by grants from the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP #09/15354-7 and 10/52191-6 to W.F.) and Agence Universitaire de la Francophonie (Y.D.). T.B. is the recipient of a Ph.D. studentship from FAPESP (#11/14172-2). We thank Roberto Mendonca for the invaluable technical assistance and Alex Yamashita for comments and revision. NR 47 TC 6 Z9 6 U1 5 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1613-4125 EI 1613-4133 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD MAY PY 2015 VL 59 IS 5 BP 957 EP 967 DI 10.1002/mnfr.201400914 PG 11 WC Food Science & Technology SC Food Science & Technology GA CH7TZ UT WOS:000354240800012 PM 25641959 ER PT J AU Bavamian, S Mellios, N Lalonde, J Fass, DM Wang, J Sheridan, SD Madison, JM Zhou, F Rueckert, EH Barker, D Perlis, RH Sur, M Haggarty, SJ AF Bavamian, S. Mellios, N. Lalonde, J. Fass, D. M. Wang, J. Sheridan, S. D. Madison, J. M. Zhou, Fen Rueckert, E. H. Barker, D. Perlis, R. H. Sur, M. Haggarty, S. J. TI Dysregulation of miR-34a links neuronal development to genetic risk factors for bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Article ID SCHIZOPHRENIA-RELATED MICRODELETION; GENOME-WIDE ASSOCIATION; PREFRONTAL CORTEX; EXPERIMENTAL VALIDATION; ANNOTATION DATABASE; MICRORNA BIOGENESIS; TARGET PREDICTION; MOUSE MODEL; EXPRESSION; BRAIN AB Bipolar disorder (BD) is a heritable neuropsychiatric disorder with largely unknown pathogenesis. Given their prominent role in brain function and disease, we hypothesized that microRNAs (miRNAs) might be of importance for BD. Here we show that levels of miR-34a, which is predicted to target multiple genes implicated as genetic risk factors for BD, are increased in postmortem cerebellar tissue from BD patients, as well as in BD patient-derived neuronal cultures generated by reprogramming of human fibroblasts into induced neurons or into induced pluripotent stem cells (iPSCs) subsequently differentiated into neurons. Of the predicted miR-34a targets, we validated the BD risk genes ankyrin-3 (ANK3) and voltage-dependent L-type calcium channel subunit beta-3 (CACNB3) as direct miR-34a targets. Using human iPSC-derived neuronal progenitor cells, we further show that enhancement of miR-34a expression impairs neuronal differentiation, expression of synaptic proteins and neuronal morphology, whereas reducing endogenous miR-34a expression enhances dendritic elaboration. Taken together, we propose that miR-34a serves as a critical link between multiple etiological factors for BD and its pathogenesis through the regulation of a molecular network essential for neuronal development and synaptogenesis. C1 [Bavamian, S.; Lalonde, J.; Fass, D. M.; Wang, J.; Sheridan, S. D.; Madison, J. M.; Zhou, Fen; Rueckert, E. H.; Perlis, R. H.; Haggarty, S. J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Chem Neurobiol Lab, Boston, MA 02114 USA. [Bavamian, S.; Lalonde, J.; Fass, D. M.; Wang, J.; Sheridan, S. D.; Madison, J. M.; Zhou, Fen; Rueckert, E. H.; Barker, D.; Perlis, R. H.; Haggarty, S. J.] Broad Inst & Harvard MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Mellios, N.; Sur, M.] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Lalonde, J.; Sheridan, S. D.; Haggarty, S. J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wang, J.; Sheridan, S. D.; Madison, J. M.; Zhou, Fen; Rueckert, E. H.; Perlis, R. H.; Haggarty, S. J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wang, J.; Sheridan, S. D.; Perlis, R. H.; Haggarty, S. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Expt Drugs & Diagnost, Boston, MA USA. RP Haggarty, SJ (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Chem Neurobiol Lab, 185 Cambridge St, Boston, MA 02114 USA. EM shaggarty@mgh.harvard.edu OI Lalonde, Jasmin/0000-0002-6797-1894; Haggarty, Stephen J./0000-0002-7872-168X FU Swiss National Science Foundation; Stanley Medical Research Institute; National Institute of Mental Health [R21MH093958, R33MH087896, R01MH091115, R01MH095088] FX We thank the Stanley Medical Research Institute (Dr Maree Webster) for providing RNA and tissue samples from their postmortem human brain collection, the Crabtree laboratory, especially Dr Alfred Sun, for contributing plasmids and help with the iN protocol and Dr Colm O'Dushlaine for his help with miR-34a target prediction. This work was supported through funding from the Swiss National Science Foundation, the Stanley Medical Research Institute and the National Institute of Mental Health (R21MH093958, R33MH087896, R01MH091115, R01MH095088). NR 75 TC 23 Z9 23 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 2015 VL 20 IS 5 BP 573 EP 584 DI 10.1038/mp.2014.176 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CH0JS UT WOS:000353706400007 PM 25623948 ER PT J AU Cornelis, MC Byrne, EM Esko, T Nalls, MA Ganna, A Paynter, N Monda, KL Amin, N Fischer, K Renstrom, F Ngwa, JS Huikari, V Cavadino, A Nolte, IM Teumer, A Yu, K Marques-Vidal, P Rawal, R Manichaikul, A Wojczynski, MK Vink, JM Zhao, JH Burlutsky, G Lahti, J Mikkila, V Lemaitre, RN Eriksson, J Musani, SK Tanaka, T Geller, F Luan, J Hui, J Magi, R Dimitriou, M Garcia, ME Ho, WK Wright, MJ Rose, LM Magnusson, PKE Pedersen, NL Couper, D Oostra, BA Hofman, A Ikram, MA Tiemeier, HW Uitterlinden, AG van Rooij, FJA Barroso, I Johansson, I Xue, L Kaakinen, M Milani, L Power, C Snieder, H Stolk, RP Baumeister, SE Biffar, R Gu, F Bastardot, F Kutalik, Z Jacobs, DR Forouhi, NG Mihailov, E Lind, L Lindgren, C Michaelsson, K Morris, A Jensen, M Khaw, KT Luben, RN Wang, JJ Mannisto, S Perala, MM Kahonen, M Lehtimaki, T Viikari, J Mozaffarian, D Mukamal, K Psaty, BM Doring, A Heath, AC Montgomery, GW Dahmen, N Carithers, T Tucker, KL Ferrucci, L Boyd, HA Melbye, M Treur, JL Mellstrom, D Hottenga, JJ Prokopenko, I Tonjes, A Deloukas, P Kanoni, S Lorentzon, M Houston, DK Liu, Y Danesh, J Rasheed, A Mason, MA Zonderman, AB Franke, L Kristal, BS Karjalainen, J Reed, DR Westra, HJ Evans, MK Saleheen, D Harris, TB Dedoussis, G Curhan, G Stumvoll, M Beilby, J Pasquale, LR Feenstra, B Bandinelli, S Ordovas, JM Chan, AT Peters, U Ohlsson, C Gieger, C Martin, NG Waldenberger, M Siscovick, DS Raitakari, O Eriksson, JG Mitchell, P Hunter, DJ Kraft, P Rimm, EB Boomsma, DI Borecki, IB Loos, RJF Wareham, NJ Vollenweider, P Caporaso, N Grabe, HJ Neuhouser, ML Wolffenbuttel, BHR Hu, FB Hypponen, E Jarvelin, MR Cupples, LA Franks, PW Ridker, PM van Duijn, CM Heiss, G Metspalu, A North, KE Ingelsson, E Nettleton, JA van Dam, RM Chasman, DI AF Cornelis, M. C. Byrne, E. M. Esko, T. Nalls, M. A. Ganna, A. Paynter, N. Monda, K. L. Amin, N. Fischer, K. Renstrom, F. Ngwa, J. S. Huikari, V. Cavadino, A. Nolte, I. M. Teumer, A. Yu, K. Marques-Vidal, P. Rawal, R. Manichaikul, A. Wojczynski, M. K. Vink, J. M. Zhao, J. H. Burlutsky, G. Lahti, J. Mikkila, V. Lemaitre, R. N. Eriksson, J. Musani, S. K. Tanaka, T. Geller, F. Luan, J. Hui, J. Maegi, R. Dimitriou, M. Garcia, M. E. Ho, W-K Wright, M. J. Rose, L. M. Magnusson, P. K. E. Pedersen, N. L. Couper, D. Oostra, B. A. Hofman, A. Ikram, M. A. Tiemeier, H. W. Uitterlinden, A. G. van Rooij, F. J. A. Barroso, I. Johansson, I. Xue, L. Kaakinen, M. Milani, L. Power, C. Snieder, H. Stolk, R. P. Baumeister, S. E. Biffar, R. Gu, F. Bastardot, F. Kutalik, Z. Jacobs, D. R., Jr. Forouhi, N. G. Mihailov, E. Lind, L. Lindgren, C. Michaelsson, K. Morris, A. Jensen, M. Khaw, K-T Luben, R. N. Wang, J. J. Mannisto, S. Perala, M-M Kahonen, M. Lehtimaki, T. Viikari, J. Mozaffarian, D. Mukamal, K. Psaty, B. M. Doering, A. Heath, A. C. Montgomery, G. W. Dahmen, N. Carithers, T. Tucker, K. L. Ferrucci, L. Boyd, H. A. Melbye, M. Treur, J. L. Mellstrom, D. Hottenga, J. J. Prokopenko, I. Toenjes, A. Deloukas, P. Kanoni, S. Lorentzon, M. Houston, D. K. Liu, Y. Danesh, J. Rasheed, A. Mason, M. A. Zonderman, A. B. Franke, L. Kristal, B. S. Karjalainen, J. Reed, D. R. Westra, H-J Evans, M. K. Saleheen, D. Harris, T. B. Dedoussis, G. Curhan, G. Stumvoll, M. Beilby, J. Pasquale, L. R. Feenstra, B. Bandinelli, S. Ordovas, J. M. Chan, A. T. Peters, U. Ohlsson, C. Gieger, C. Martin, N. G. Waldenberger, M. Siscovick, D. S. Raitakari, O. Eriksson, J. G. Mitchell, P. Hunter, D. J. Kraft, P. Rimm, E. B. Boomsma, D. I. Borecki, I. B. Loos, R. J. F. Wareham, N. J. Vollenweider, P. Caporaso, N. Grabe, H. J. Neuhouser, M. L. Wolffenbuttel, B. H. R. Hu, F. B. Hyppoenen, E. Jarvelin, M-R Cupples, L. A. Franks, P. W. Ridker, P. M. van Duijn, C. M. Heiss, G. Metspalu, A. North, K. E. Ingelsson, E. Nettleton, J. A. van Dam, R. M. Chasman, D. I. CA Coffee & Caffeine Genetics Consort Int Parkinson's Dis Genomics Conso North Amer Brain Expression Consor UK Brain Expression Consortium TI Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption SO MOLECULAR PSYCHIATRY LA English DT Article ID CAFFEINE; PROTEIN; VARIANTS; RECEPTOR; BRAIN; GLUCOKINASE; INVOLVEMENT; BINDING; BDNF AB Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in similar to 30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log(10)Bayes factor (BF) > 5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P < 5x10(-8)). 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RP Cornelis, MC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 401 Pk Dr, Boston, MA 02215 USA. EM mcorneli@hsph.harvard.edu; dchasman@research.bwh.harvard.edu RI Colaus, PsyColaus/K-6607-2013; Waldenberger, Melanie/B-5355-2014; Prokopenko, Inga/H-3241-2014; Wright, Margaret/A-4560-2016; Hypponen, Elina/B-2596-2014; Deloukas, Panos/B-2922-2013; Franke, Lude/P-7036-2016; Karjalainen, Juha/P-8624-2016; Magnusson, Patrik/C-4458-2017; OI Eriksson, Johan/0000-0002-2516-2060; Zonderman, Alan B/0000-0002-6523-4778; corvol, jean-christophe/0000-0001-7325-0199; Lahti, Jari/0000-0002-4310-5297; Ganna, Andrea/0000-0002-8147-240X; Tiemeier, Henning/0000-0002-4395-1397; Plagnol, Vincent/0000-0002-5597-9215; Ikram, Mohammad Arfan/0000-0003-0372-8585; Esko, Tonu/0000-0003-1982-6569; Gieger, Christian/0000-0001-6986-9554; van Dam, Rob/0000-0002-7354-8734; Mannisto, Satu/0000-0002-8668-3046; Mellstrom, Dan/0000-0003-2761-3723; Luben, Robert/0000-0002-5088-6343; Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; Forouhi, Nita/0000-0002-5041-248X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; HO, WEANG KEE/0000-0002-8269-7344; Magi, Reedik/0000-0002-2964-6011; Waldenberger, Melanie/0000-0003-0583-5093; Prokopenko, Inga/0000-0003-1624-7457; Wright, Margaret/0000-0001-7133-4970; Hypponen, Elina/0000-0003-3670-9399; Deloukas, Panos/0000-0001-9251-070X; Franke, Lude/0000-0002-5159-8802; Kaakinen, Marika/0000-0002-9228-0462 NR 43 TC 19 Z9 20 U1 6 U2 46 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 2015 VL 20 IS 5 BP 647 EP 656 DI 10.1038/mp.2014.107 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CH0JS UT WOS:000353706400016 ER PT J AU Corrigan-Curay, J O'Reilly, M Kohn, DB Cannon, PM Bao, G Bushman, FD Carroll, D Cathomen, T Joung, JK Roth, D Sadelain, M Scharenberg, AM von Kalle, C Zhang, F Jambou, R Rosenthal, E Hassani, M Singh, A Porteus, MH AF Corrigan-Curay, Jacqueline O'Reilly, Marina Kohn, Donald B. Cannon, Paula M. Bao, Gang Bushman, Frederic D. Carroll, Dana Cathomen, Toni Joung, J. Keith Roth, David Sadelain, Michel Scharenberg, Andrew M. von Kalle, Christof Zhang, Feng Jambou, Robert Rosenthal, Eugene Hassani, Morad Singh, Aparna Porteus, Matthew H. TI Genome Editing Technologies: Defining a Path to Clinic SO MOLECULAR THERAPY LA English DT News Item ID ZINC-FINGER NUCLEASES; ACUTE LYMPHOBLASTIC-LEUKEMIA; RAG-MEDIATED RECOMBINATION; MAMMALIAN-CELLS; GENE-THERAPY; IN-VITRO; T-CELLS; DNA; SPECIFICITY; CHALLENGES C1 [Corrigan-Curay, Jacqueline; O'Reilly, Marina; Jambou, Robert; Rosenthal, Eugene; Hassani, Morad; Singh, Aparna] NIH, Bethesda, MD 20892 USA. [Kohn, Donald B.] Univ Calif Los Angeles, Los Angeles, CA USA. [Cannon, Paula M.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Bao, Gang] Georgia Inst Technol, Atlanta, GA 30332 USA. [Bushman, Frederic D.; Roth, David] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Carroll, Dana] Univ Utah, Sch Med, Salt Lake City, UT USA. [Cathomen, Toni] Univ Med Ctr, Freiberg, Germany. [Joung, J. Keith] Massachusetts Gen Hosp, Charlestown, MA USA. [Joung, J. Keith] Harvard Univ, Sch Med, Boston, MA USA. [Sadelain, Michel] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Scharenberg, Andrew M.] Seattle Childrens Res Inst, Seattle, WA USA. [Scharenberg, Andrew M.] Univ Washington, Sch Med, Seattle, WA USA. [von Kalle, Christof] Natl Ctr Tumor Dis, Heidelberg, Germany. [von Kalle, Christof] German Canc Res Ctr, Heidelberg, Germany. [Zhang, Feng] MIT, Cambridge, MA 02139 USA. [Zhang, Feng] Harvard Univ, Cambridge, MA 02138 USA. [Porteus, Matthew H.] Stanford Univ, Stanford, CA 94305 USA. RP Corrigan-Curay, J (reprint author), NIH, Off Sci Policy, 6705 Rockledge Dr, Bethesda, MD 20892 USA. EM corrigaja@nhlbi.nih.gov OI Cathomen, Toni/0000-0002-7757-4630 NR 43 TC 25 Z9 25 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 IS 5 BP 796 EP 806 DI 10.1038/mt.2015.54 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CH3LW UT WOS:000353933200002 PM 25943494 ER PT J AU Gong, Y Mu, D Prabhakar, S Moser, A Musolino, P Ren, J Breakefield, XO Maguire, CA Eichler, FS AF Gong, Yi Mu, Dakai Prabhakar, Shilpa Moser, Ann Musolino, Patricia Ren, JiaQian Breakefield, Xandra O. Maguire, Casey A. Eichler, Florian S. TI Adenoassociated Virus Serotype 9-Mediated Gene Therapy for X-Linked Adrenoleukodystrophy SO MOLECULAR THERAPY LA English DT Article ID CHAIN FATTY-ACIDS; CENTRAL-NERVOUS-SYSTEM; PHASE-I TRIAL; NONHUMAN-PRIMATES; SPINAL-CORD; PARKINSONS-DISEASE; MASS-SPECTROMETRY; AAV9 DELIVERY; OPEN-LABEL; VECTOR AB X-linked adrenoleukodystrophy (X-ALD) is a devastating neurological disorder caused by mutations in the ABCD1 gene that encodes a peroxisomal ATP-binding cassette transporter (ABCD1) responsible for transport of CoA-activated very long-chain fatty acids (VLCFA) into the peroxisome for degradation. We used recombinant adenoassociated virus serotype 9 (rAAV9) vector for delivery of the human ABCD1 gene (ABCD1) to mouse central nervous system (CNS). In vitro, efficient delivery of ABCD1 gene was achieved in primary mixed brain glial cells from Abcd1(-/-) mice as well as X-ALD patient fibroblasts. Importantly, human ABCD1 localized to the peroxisome, and AAV-ABCD1 transduction showed a dose-dependent effect in reducing VLCFA. In vivo, AAV9-ABCD1 was delivered to Abcd1(-/-) mouse CNS by either stereotactic intracerebroventricular (ICV) or intravenous (IV) injections. Astrocytes, microglia and neurons were the major target cell types following ICV injection, while IV injection also delivered to microvascular endothelial cells and oligodendrocytes. IV injection also yielded high transduction of the adrenal gland. Importantly, IV injection of AAV9-ABCD1 reduced VLCFA in mouse brain and spinal cord. We conclude that AAV9-mediated ABCD1 gene transfer is able to reach target cells in the nervous system and adrenal gland as well as reduce VLCFA in culture and a mouse model of X-ALD. C1 [Gong, Yi; Mu, Dakai; Prabhakar, Shilpa; Musolino, Patricia; Ren, JiaQian; Breakefield, Xandra O.; Maguire, Casey A.; Eichler, Florian S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Moser, Ann] Hugo W Moser Res Inst, Peroxisome Dis Lab, Baltimore, MD USA. RP Eichler, FS (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,ACC 708, Boston, MA 02114 USA. EM feichler@partners.org FU Leblang Charitable Foundation; NIH [R21 NINDS, R01 NINDS]; NIH/NINDS [R21 NS081374-01]; American Brain Tumor Association Discovery Grant; NINDS [P30N5045776]; University of Pennsylvania Orphan Disease Center FX We thank the Leblang Charitable Foundation and NIH (R21 NINDS, R01 NINDS) for their support. CM was supported by an NIH/NINDS R21 NS081374-01 and an American Brain Tumor Association Discovery Grant. We would like to acknowledge the Neuroscience Center Nucleic Acid Quantitation Core and Image Analysis Core (supported by NINDS P30N5045776). Lastly, this work was supported in part by a research grant from the University of Pennsylvania Orphan Disease Center. We also thank Chuying Xia, Sandra Jimenez and Ankush Chandra for their assistance during mice dissection and protein verification. NR 44 TC 9 Z9 9 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 IS 5 BP 824 EP 834 DI 10.1038/mt.2015.6 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CH3LW UT WOS:000353933200006 PM 25592337 ER PT J AU Etchegaray, JP Chavez, L Huang, Y Ross, KN Choi, J Martinez-Pastor, B Walsh, RM Sommer, CA Lienhard, M Gladden, A Kugel, S Silberman, DM Ramaswamy, S Mostoslavsky, G Hochedlinger, K Goren, A Rao, A Mostoslavsky, R AF Etchegaray, Jean-Pierre Chavez, Lukas Huang, Yun Ross, Kenneth N. Choi, Jiho Martinez-Pastor, Barbara Walsh, Ryan M. Sommer, Cesar A. Lienhard, Matthias Gladden, Adrianne Kugel, Sita Silberman, Dafne M. Ramaswamy, Sridhar Mostoslavsky, Gustavo Hochedlinger, Konrad Goren, Alon Rao, Anjana Mostoslavsky, Raul TI The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine SO NATURE CELL BIOLOGY LA English DT Article ID GENOMIC INSTABILITY; MAMMALIAN DNA; SELF-RENEWAL; 5-METHYLCYTOSINE; METHYLATION; CONVERSION; REVEALS; 5-CARBOXYLCYTOSINE; DIFFERENTIATION; SPECIFICATION AB How embryonic stem cells (ESCs) commit to specific cell lineages and yield all cell types of a fully formed organism remains a major question. ESC differentiation is accompanied by large-scale histone and DNA modifications, but the relations between these epigenetic categories are not understood. Here we demonstrate the interplay between the histone deacetylase sirtuin 6 (SIRT6) and the ten-eleven translocation enzymes (TETs). SIRT6 targets acetylated histone H3 at Lys 9 and 56 (H3K9ac and H3K56ac), while TETs convert 5-methylcytosine into 5-hydroxymethylcytosine (5hmC). ESCs derived from Sirt6 knockout (S6KO) mice are skewed towards neuroectoderm development. This phenotype involves derepression of OCT4, SOX2 and NANOG, which causes an upregulation of TET-dependent production of 5hmC. Genome-wide analysis revealed neural genes marked with 5hmC in S6KO ESCs, thereby implicating TET enzymes in the neuroectoderm-skewed differentiation phenotype. We demonstrate that SIRT6 functions as a chromatin regulator safeguarding the balance between pluripotency and differentiation through Tet-mediated production of 5hmC. C1 [Etchegaray, Jean-Pierre; Ross, Kenneth N.; Choi, Jiho; Martinez-Pastor, Barbara; Walsh, Ryan M.; Kugel, Sita; Ramaswamy, Sridhar; Hochedlinger, Konrad; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Etchegaray, Jean-Pierre; Ross, Kenneth N.; Choi, Jiho; Martinez-Pastor, Barbara; Walsh, Ryan M.; Kugel, Sita; Ramaswamy, Sridhar; Hochedlinger, Konrad; Mostoslavsky, Raul] Harvard Univ, Sch Med, MGH Ctr Regenerat Med, Boston, MA 02114 USA. [Chavez, Lukas; Huang, Yun; Lienhard, Matthias; Rao, Anjana] UCSD Moores Canc Ctr, UCSD Dept Pharmacol, La Jolla Inst Allergy & Immunol, Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA. [Sommer, Cesar A.; Mostoslavsky, Gustavo] Boston Univ, Sch Med, Boston Med Ctr, CReM, Boston, MA 02118 USA. [Gladden, Adrianne; Goren, Alon] Broad Inst Harvard & MIT, BTL, Cambridge, MA 02142 USA. [Silberman, Dafne M.] UBA, CONICET, CEFyBO, Dept Human Biochem,Med Sch, RA-1121 Buenos Aires, DF, Argentina. [Hochedlinger, Konrad] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Etchegaray, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. EM etchegaray.jean-pierre@mgh.harvard.edu; agoren@broadinstitute.org; rmostoslavsky@mgh.harvard.edu OI Huang, Yun/0000-0001-5950-9168; Chavez, Lukas/0000-0002-8718-8848 FU NIH [GM 093072-01, DK088190-01A1, 5R01HD058013-05, HD065812, CA151535]; Alexander von Humboldt Foundation; Leukemia and Lymphoma Society; Broad Institute SPARC (Scientific Projects to Accelerate Research and Collaboration) program; Evans Center FX This work was supported in part by NIH grants GM 093072-01, DK088190-01A1 (R.M.), 5R01HD058013-05 (to K.H.) and HD065812, CA151535 (to A.R.). R.M. is the Kristine and Bob Higgins MGH Research Scholar, the Warshaw Institute Fellow, and a Howard Goodman Awardee. L.C. was the recipient of a Feodor Lynen Research Fellowship from the Alexander von Humboldt Foundation. Y.H. was supported by a postdoctoral fellowship from the Leukemia and Lymphoma Society. C.A.S. is the recipient of the Evans Center Fellow Award A. Gladden and A. Goren were the recipient of the Broad Institute SPARC (Scientific Projects to Accelerate Research and Collaboration) program. We thank O. Bar-Nur and S.Cheloufi for advice on there programming of neural progenitor cells, and E. Kelliher for setting up the automation of the ChIP-Seq experiments. NR 56 TC 25 Z9 26 U1 1 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY PY 2015 VL 17 IS 5 BP 545 EP U50 DI 10.1038/ncb3147 PG 33 WC Cell Biology SC Cell Biology GA CH1HG UT WOS:000353771500004 PM 25915124 ER PT J AU Liao, J Karnik, R Gu, HC Ziller, MJ Clement, K Tsankov, AM Akopian, V Gifford, CA Donaghey, J Galonska, C Pop, R Reyon, D Tsai, SQ Mallard, W Joung, JK Rinn, JL Gnirke, A Meissner, A AF Liao, Jing Karnik, Rahul Gu, Hongcang Ziller, Michael J. Clement, Kendell Tsankov, Alexander M. Akopian, Veronika Gifford, Casey A. Donaghey, Julie Galonska, Christina Pop, Ramona Reyon, Deepak Tsai, Shengdar Q. Mallard, William Joung, J. Keith Rinn, John L. Gnirke, Andreas Meissner, Alexander TI Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells SO NATURE GENETICS LA English DT Article ID HUMAN CANCER-CELLS; DE-NOVO METHYLATION; DNA METHYLATION; HUMAN GENOME; MAMMALIAN DEVELOPMENT; REGULATORY REGIONS; EPIGENETIC MEMORY; CPG METHYLATION; SOMATIC TISSUE; SELF-RENEWAL AB DNA methylation is a key epigenetic modification involved in regulating gene expression and maintaining genomic integrity. Here we inactivated all three catalytically active DNA methyltransferases (DNMTs) in human embryonic stem cells (ESCs) using CRISPR/Cas9 genome editing to further investigate the roles and genomic targets of these enzymes. Disruption of DNMT3A or DNMT3B individually as well as of both enzymes in tandem results in viable, pluripotent cell lines with distinct effects on the DNA methylation landscape, as assessed by whole-genome bisulfite sequencing. Surprisingly, in contrast to findings in mouse, deletion of DNMT1 resulted in rapid cell death in human ESCs. To overcome this immediate lethality, we generated a doxycycline-responsive tTA-DNMT1* rescue line and readily obtained homozygous DNMT1-mutant lines. However, doxycycline-mediated repression of exogenous DNMT1* initiates rapid, global loss of DNA methylation, followed by extensive cell death. Our data provide a comprehensive characterization of DNMT-mutant ESCs, including single-base genome-wide maps of the targets of these enzymes. C1 [Liao, Jing; Karnik, Rahul; Gu, Hongcang; Ziller, Michael J.; Clement, Kendell; Tsankov, Alexander M.; Akopian, Veronika; Gifford, Casey A.; Donaghey, Julie; Galonska, Christina; Pop, Ramona; Mallard, William; Rinn, John L.; Gnirke, Andreas; Meissner, Alexander] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Liao, Jing; Karnik, Rahul; Ziller, Michael J.; Clement, Kendell; Tsankov, Alexander M.; Akopian, Veronika; Gifford, Casey A.; Donaghey, Julie; Galonska, Christina; Pop, Ramona; Mallard, William; Rinn, John L.; Meissner, Alexander] Harvard Stem Cell Inst, Cambridge, MA USA. [Liao, Jing; Karnik, Rahul; Ziller, Michael J.; Clement, Kendell; Tsankov, Alexander M.; Akopian, Veronika; Gifford, Casey A.; Donaghey, Julie; Galonska, Christina; Pop, Ramona; Mallard, William; Rinn, John L.; Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Reyon, Deepak; Tsai, Shengdar Q.; Joung, J. Keith] Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA USA. RP Meissner, A (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM alexander_meissner@harvard.edu OI Karnik, Rahul/0000-0002-0400-635X FU Human Frontiers Science Program; US NIH Director's Pioneer Award [DP1 GM105378]; US NIH (National Institute of General Medical Sciences) [P01GM099117]; New York Stem Cell Foundation FX We thank all members of the Meissner laboratory, in particular C. Sindhu for helpful discussion and Z.D. Smith for critical feedback on the manuscript. We thank K. Musunuru (Harvard University) for providing the CRIPSR/Cas9 plasmids and thank Q. Ding from the Musunuru laboratory for technical support. J.L. was supported by a postdoctoral fellowship from the Human Frontiers Science Program. J.K.J. is supported by US NIH Director's Pioneer Award DP1 GM105378. A.M. is a New York Stem Cell Foundation Robertson Investigator. The work was funded by a US NIH (National Institute of General Medical Sciences) grant (P01GM099117) and the New York Stem Cell Foundation. NR 66 TC 63 Z9 66 U1 14 U2 43 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 MAY PY 2015 VL 47 IS 5 BP 469 EP U64 DI 10.1038/ng.3258 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA CG9LE UT WOS:000353635800009 PM 25822089 ER PT J AU Lin, L Liu, L Zhao, B Xie, R Lin, W Li, H Li, YY Shi, ML Chen, YG Springer, TA Chen, X AF Lin, Liang Liu, Ling Zhao, Bing Xie, Ran Lin, Wei Li, He Li, Yaya Shi, Minlong Chen, Ye-Guang Springer, Timothy A. Chen, Xing TI Carbon nanotube-assisted optical activation of TGF-beta signalling by near-infrared light SO NATURE NANOTECHNOLOGY LA English DT Article ID 2-PHOTON EXCITATION; PHOTOTHERMAL THERAPY; NANOPARTICLES; CHANNELRHODOPSIN-2; TRANSPORTERS; INHIBITION; MECHANISM; GRAPHENE; BIOLOGY; BINDING AB Receptor-mediated signal transduction modulates complex cellular behaviours such as cell growth, migration and differentiation. Although photoactivatable proteins have emerged as a powerful tool for controlling molecular interactions and signalling cascades at precise times and spaces using light, many of these light-sensitive proteins are activated by ultraviolent or visible light, which has limited tissue penetration. Here, we report a single-walled carbon nanotube (SWCNT)-assisted approach that enables near-infrared light-triggered activation of transforming growth factor beta (TGF-beta) signal transduction, an important signalling pathway in embryonic development and cancer progression. The protein complex of TGF-beta and its latency-associated peptide is conjugated onto SWCNTs, where TGF-beta is inactive. Upon nearinfrared irradiation, TGF-beta is released through the photothermal effect of SWCNTs and becomes active. The released TGF-beta activates downstream signal transduction in live cells and modulates cellular behaviours. Furthermore, preliminary studies show that the method can be used to mediate TGF-beta signalling in living mice. C1 [Lin, Liang; Liu, Ling; Xie, Ran; Lin, Wei; Li, He; Li, Yaya; Chen, Xing] Peking Univ, Coll Chem & Mol Engn, Synthet & Funct Biomolecules Ctr,Minist Educ, Beijing Natl Lab Mol Sci,Key Lab Bioorgan Chem &, Beijing 100871, Peoples R China. [Lin, Liang; Liu, Ling; Xie, Ran; Lin, Wei; Li, He; Li, Yaya; Chen, Xing] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China. [Zhao, Bing; Chen, Ye-Guang] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. [Shi, Minlong; Springer, Timothy A.] Harvard Univ, Childrens Hosp Boston, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Shi, Minlong; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Chen, X (reprint author), Peking Univ, Coll Chem & Mol Engn, Synthet & Funct Biomolecules Ctr,Minist Educ, Beijing Natl Lab Mol Sci,Key Lab Bioorgan Chem &, Beijing 100871, Peoples R China. EM xingchen@pku.edu.cn FU National Basic Research Program of China (973 program) [2012CB917303]; National Natural Science Foundation of China [91313301, 21425204, 91127034] FX This work was supported by the National Basic Research Program of China (973 program; 2012CB917303) and the National Natural Science Foundation of China (nos. 91313301, 21425204 and 91127034). NR 40 TC 12 Z9 12 U1 9 U2 86 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 EI 1748-3395 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD MAY PY 2015 VL 10 IS 5 BP 465 EP 471 DI 10.1038/NNANO.2015.28 PG 7 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA CH5SF UT WOS:000354094900017 PM 25775150 ER PT J AU Rost, NS AF Rost, Natalia S. TI STROKE More than meets the eye-big consequences of small strokes SO NATURE REVIEWS NEUROLOGY LA English DT Editorial Material ID SMALL VESSEL DISEASE AB A long-term outcome analysis in patients with lacunar stroke enrolled in the Secondary Prevention of Small Subcortical Strokes trial highlights the relevance of functional disability after small-vessel strokes. These data support the emerging ` burden of disease' concept in individuals with cerebral microangiopathy, and the role of MRI in outcome prediction. C1 Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org NR 10 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 1759-4758 EI 1759-4766 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD MAY PY 2015 VL 11 IS 5 BP 249 EP 250 DI 10.1038/nrneurol.2015.52 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CH5IU UT WOS:000354069700002 PM 25848922 ER PT J AU Brown, K Poppe, A Kaminetzky, C Wipf, J Woods, NF AF Brown, Kameka Poppe, Anne Kaminetzky, Catherine Wipf, Joyce Woods, Nancy Fugate TI Recommendations for Nurse Practitioner Residency Programs SO NURSE EDUCATOR LA English DT Article DE graduate nursing education; nurse practitioner program; nursing practitioner residency; residencies AB The purpose of this study was to identify and prioritize critical aspects needed in the design and execution of new nurse practitioner (NP) residency programs. Subjects answered a series of questions on formulating residency programs and on key outcomes and cost measures related to their sustainability. These results serve as potential guideposts for future work in NP residency standardization and sustainability development. C1 [Brown, Kameka; Poppe, Anne; Wipf, Joyce] Ctr Excellence Primary Care Educ, Seattle, WA USA. [Kaminetzky, Catherine] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Brown, Kameka; Poppe, Anne; Woods, Nancy Fugate] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Kaminetzky, Catherine; Wipf, Joyce] Univ Washington, Sch Med, Seattle, WA USA. RP Brown, K (reprint author), 1660 S Columbian Way,S 123 COE, Seattle, WA 98108 USA. EM kameka.brown2@va.gov FU Veteran Affairs Office of Academic Affiliations FX This study was funded by a grant from Veteran Affairs Office of Academic Affiliations. NR 16 TC 1 Z9 1 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-3624 EI 1538-9855 J9 NURS EDUC JI Nurs. Educ. PD MAY-JUN PY 2015 VL 40 IS 3 BP 148 EP 151 DI 10.1097/NNE.0000000000000117 PG 4 WC Nursing SC Nursing GA CH5ZU UT WOS:000354115700013 PM 25501654 ER PT J AU Lawson, EA Marengi, DA DeSanti, RL Holmes, TM Schoenfeld, DA Tolley, CJ AF Lawson, Elizabeth A. Marengi, Dean A. DeSanti, Rebecca L. Holmes, Tara M. Schoenfeld, David A. Tolley, Christiane J. TI Oxytocin Reduces Caloric Intake in Men SO OBESITY LA English DT Article ID FOOD-INTAKE; DEFICIENT MICE; GENE-EXPRESSION; COLD-EXPOSURE; OBESITY; RATS; NEURONS; RECEPTOR; NUCLEUS; BRAIN AB ObjectivePreclinical studies indicate that oxytocin is anorexigenic and has beneficial metabolic effects. Oxytocin effects on nutrition and metabolism in humans are not well defined. It was hypothesized that oxytocin would reduce caloric intake and appetite and alter levels of appetite-regulating hormones. Metabolic effects of oxytocin were also explored. MethodsA randomized, placebo-controlled crossover study of single-dose intranasal oxytocin (24 IU) in 25 fasting healthy men was performed. After oxytocin/placebo, subjects selected breakfast from a menu and were given double portions. Caloric content of food consumed was measured. Visual analog scales were used to assess appetite, and blood was drawn for appetite-regulating hormones, insulin, and glucose before and after oxytocin/placebo. Indirect calorimetry assessed resting energy expenditure (REE) and substrate utilization. ResultsOxytocin reduced caloric intake with a preferential effect on fat intake and increased levels of the anorexigenic hormone cholecystokinin without affecting appetite or other appetite-regulating hormones. There was no effect of oxytocin on REE. Oxytocin resulted in a shift from carbohydrate to fat utilization and improved insulin sensitivity. ConclusionsIntranasal oxytocin reduces caloric intake and has beneficial metabolic effects in men without concerning side effects. The efficacy and safety of sustained oxytocin administration in the treatment of obesity warrants investigation. C1 [Lawson, Elizabeth A.; Marengi, Dean A.; DeSanti, Rebecca L.; Tolley, Christiane J.] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Lawson, Elizabeth A.; Marengi, Dean A.; DeSanti, Rebecca L.; Holmes, Tara M.; Schoenfeld, David A.; Tolley, Christiane J.] Harvard Univ, Sch Med, Boston, MA USA. [Holmes, Tara M.] Massachusetts Gen Hosp, Harvard Catalyst Clin Res Ctr, Boston, MA 02114 USA. [Schoenfeld, David A.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Lawson, EA (reprint author), Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. EM ealawson@partners.org FU NIH [K23 MH092560, 1UL1 TR001102-01, 2P30DK046200]; MGH Claflin Distinguished Scholar Award FX Funding agencies: NIH K23 MH092560, 1UL1 TR001102-01, 2P30DK046200; MGH Claflin Distinguished Scholar Award. NR 40 TC 20 Z9 20 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD MAY PY 2015 VL 23 IS 5 BP 950 EP 956 DI 10.1002/oby.21069 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CH3XL UT WOS:000353964200008 PM 25865294 ER PT J AU Palma, E Deatrick, JA Hobbie, WL Ogle, SK Kobayashi, K Maldonado, L AF Palma, Erica Deatrick, Janet A. Hobbie, Wendy L. Ogle, Sue K. Kobayashi, Kyoko Maldonado, Linda TI Maternal Caregiving Demands for Adolescent and Young Adult Survivors of Pediatric Brain Tumors SO ONCOLOGY NURSING FORUM LA English DT Article DE caregiver tasks; pediatric brain tumors; caregiving demands; caregiving burden; parents; qualitative research ID QUALITY-OF-LIFE; HEALTH-RELATED QUALITY; CHILDHOOD-CANCER; CEREBRAL-PALSY; FAMILY CAREGIVERS; CHILDREN; PARENTS; BURDEN; IMPACT; MOTHERS AB Purpose/Objectives: To examine the daily maternal caregiving demands for adolescent and young adult survivors of pediatric brain tumors who live with their families. Design: A secondary analysis was conducted on interview data gathered during a large mixed-methods study that focused on perceived maternal caregiver competency and survivor health-related quality of life. Setting: Home interviews. Sample: A purposive sample of 46 maternal caregivers was selected from participants in the larger study. Methods: Semistructured interviews were conducted with mothers. A directed content analysis was informed by Sullivan-Bolyai's framework describing the components of primary caregiving. Main Research Variables: Caregiving demands. Findings: Data regarding four main categories of maternal daily caregiving demands were identified from 25 of the 46 interviews: managing the illness; identifying, accessing, and coordinating resources; assisting with everyday responsibilities; and fostering psychosocial health. Conclusions: Potential day-to-day management tasks or demands of mothers of adolescent and young adult survivors of pediatric brain tumors were identified. Implications for Nursing: The major demands of caregiving are similar to those for children with other chronic conditions, with the addition of assisting with everyday responsibilities and fostering psychosocial health. C1 [Palma, Erica; Hobbie, Wendy L.; Maldonado, Linda] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Palma, Erica] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Deatrick, Janet A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Hobbie, Wendy L.] Childrens Hosp Philadelphia, Canc Survivorship Program, Philadelphia, PA USA. [Ogle, Sue K.] Childrens Hosp Philadelphia, Med & Med Subspecialty Nursing, Philadelphia, PA USA. [Ogle, Sue K.] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Kobayashi, Kyoko] St Lukes Int Univ, Sch Nursing, Dept Child & Family Nursing, Tokyo, Japan. [Maldonado, Linda] Univ Penn, Ctr Global Womens Hlth, Philadelphia, PA 19104 USA. [Maldonado, Linda] Univ Penn, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. RP Palma, E (reprint author), Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. EM deatrick@nursing.upenn.edu FU National Institutes of Nursing Research [R01 NR009651, 3-T32-NR007100]; National Institutes of Health; ONS Foundation through American Brain Tumor Association FX Erica Palma, BSN, RN, OCN (R), is a graduate student in the School of Nursing at the University of Pennsylvania in Philadelphia and a clinical nurse at Memorial Sloan-Kettering Cancer Center in New York, NY; Janet A. Deatrick, PhD, RN, FAAN, is a professor, a Shearer Endowed Term Chair in Healthy Community Practices, and a director of the Center for Health Equity Research, all in the School of Nursing at the University of Pennsylvania; Wendy L. Hobbie, MSN, CRNP, FAAN, is the associate director for the Cancer Survivorship Program at the Children's Hospital of Philadelphia and the director of the Pediatric Oncology Nurse Practitioner Concentration in the School of Nursing at the University of Pennsylvania; Sue K. Ogle, MSN, CRNP, is an advanced practice nurse manager for Medical and Medical Subspecialty Nursing and a cancer survivorship nurse practitioner at the Children's Hospital of Philadelphia; Kyoko Kobayashi, PhD, RN, PHN, is an associate professor in the Department of Child and Family Nursing at St. Luke's International University School of Nursing in Tokyo, Japan; and Linda Maldonado, PhD, RN, is a Ruth L. Kirschstein National Research Service Award Postdoctoral Fellow in the School of Nursing and the Centers for Global Women's Health and Health Equity Research, both at the University of Pennsylvania. This study was supported, in part, by grants (R01 NR009651 and 3-T32-NR007100) from the National Institutes of Nursing Research and National Institutes of Health, and funding from the ONS Foundation through a grant from the American Brain Tumor Association. Deatrick can be reached at deatrick@nursing.upenn.edu, with copy to editor at ONFEditor@ons.org. (Submitted August 2014. Accepted for publication November 13, 2014.) NR 42 TC 2 Z9 2 U1 2 U2 12 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2015 VL 42 IS 3 BP 222 EP 229 DI 10.1188/15.ONF.222-229 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA CH7QZ UT WOS:000354233000005 PM 25901374 ER PT J AU Chen, X Jakobiec, FA Yadav, P Werdich, XQ Fay, A AF Chen, Xi Jakobiec, Frederick A. Yadav, Prashant Werdich, Xiang Q. Fay, Aaron TI Melkersson-Rosenthal Syndrome with Isolated Unilateral Eyelid Edema: An Immunopathologic Study SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ANGIOEDEMA; ROSACEA; DISEASE AB Lymphedema is caused by defective drainage of the lymphatic system. In Melkersson-Rosenthal syndrome, involvement is predominantly of the lumens with blockage of lymphatic channels by histiocytic-epithelioid cell clusters accompanied by dermal granulomas and lymphocytes. It is a localized, painless, nonitching, and nonpitting form of lymphedema. Besides the eyelids, the disease can cause lip edema, facial palsy, and/or fissured tongue. It is rare and has received little attention in the ophthalmic literature, either in its complete triadic form, or more frequently, in its monosymptomatic forms. Pathogenesis is not well understood, and there is no effective therapy. The authors describe a case of Melkesson-Rosenthal syndrome in a 45-year-old Hispanic man with isolated unilateral upper eyelid edema. Histopathological and immunohistochemical evaluations of an eyelid biopsy specimen revealed intravascular and extravascular clusters of histiocytic-epithelioid cells that were CD68/163-positive. Variable numbers of mostly T-lymphocytes were found in the epidermis, dermis, and orbicularis muscle and by virtue of the associated granulomas established the diagnosis of Melkersson-Rosenthal syndrome. CD4 helper and CD8 suppressor T-lymphocytes were equally represented. CD20 B-lymphocytes were exceedingly sparse. Conspicuous CD1a-positive Langerhans' cells were present in the epidermis, sometimes formed subepithelial loose aggregates and were also incorporated in the granulomas. The differential diagnosis includes the far more common condition of acne rosacea. Management of Melkersson-Rosenthal syndrome, and of angioedema in general, is reviewed. C1 [Chen, Xi; Jakobiec, Frederick A.; Werdich, Xiang Q.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Dept Ophthalmol, Boston, MA 02114 USA. [Yadav, Prashant; Fay, Aaron] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Eye Plast Orbital & Cosmet Surg Serv, Boston, MA 02114 USA. [Chen, Xi; Jakobiec, Frederick A.; Yadav, Prashant; Werdich, Xiang Q.; Fay, Aaron] Harvard Univ, Sch Med, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 29 TC 0 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAY-JUN PY 2015 VL 31 IS 3 BP E70 EP E77 DI 10.1097/IOP.0000000000000088 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA CH7MZ UT WOS:000354222200011 PM 24853119 ER PT J AU Lippok, N Villiger, M Jun, CS Bouma, BE AF Lippok, Norman Villiger, Martin Jun, Changsu Bouma, Brett E. TI Single input state, single-mode fiber-based polarization-sensitive optical frequency domain imaging by eigenpolarization referencing SO OPTICS LETTERS LA English DT Article ID LOW-COHERENCE REFLECTOMETER; TOMOGRAPHY; BIREFRINGENCE; COMPONENTS; PHASE AB Fiber-based polarization-sensitive optical frequency domain imaging is more challenging than free-space implementations. Using multiple input states, fiber-based systems provide sample birefringence information with the benefit of a flexible sample arm but come at the cost of increased system and acquisition complexity, and either reduce acquisition speed or require increased acquisition bandwidth. Here we show that with the calibration of a single polarization state, fiber-based configurations can approach the conceptual simplicity of traditional free-space configurations. We remotely control the polarization state of the light incident at the sample using the eigen-polarization states of a wave plate as a reference, and determine the Jones matrix of the output fiber. We demonstrate this method for polarization-sensitive imaging of biological samples. (C) 2015 Optical Society of America C1 [Lippok, Norman; Villiger, Martin; Jun, Changsu; Bouma, Brett E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lippok, Norman; Villiger, Martin; Jun, Changsu; Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Bouma, Brett E.] Harvard Massachusetts Inst Technol, Program Hlth Sci & Technol, Cambridge, MA 02142 USA. RP Lippok, N (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM nlippok@mgh.harvard.edu FU National Institute of Health [P41 EB015903]; Terumo Corporation FX This work was supported in part by the National Institute of Health (Grant No. P41 EB015903) and by the Terumo Corporation. NR 18 TC 4 Z9 4 U1 1 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD MAY 1 PY 2015 VL 40 IS 9 BP 2025 EP 2028 DI 10.1364/OL.40.002025 PG 4 WC Optics SC Optics GA CH3IQ UT WOS:000353924600037 PM 25927775 ER PT J AU Peng, KA Kuan, EC Unger, L Lorentz, WC Wang, MB Long, JL AF Peng, Kevin A. Kuan, Edward C. Unger, Lindsey Lorentz, William C. Wang, Marilene B. Long, Jennifer L. TI A Swallow Preservation Protocol Improves Function for Veterans Receiving Chemoradiation for Head and Neck Cancer SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE dysphagia; head and neck cancer; chemoradiation; swallow preservation ID QUALITY-OF-LIFE; LOCALLY ADVANCED HEAD; LONG-TERM DYSPHAGIA; OROPHARYNGEAL DYSPHAGIA; DEFINITIVE RADIOTHERAPY; ASPIRATION; CHEMORADIOTHERAPY; REHABILITATION; THERAPY; IMPACT AB Objective Determine the efficacy of a swallow preservation protocol (SPP) on maintaining swallow function in patients undergoing chemoradiation (CRT) or radiation therapy alone (RT) for head and neck squamous cell carcinoma (HNSCC). Study design Retrospective case series. Setting Veterans Affairs medical center. Subjects and Methods Patients treated with CRT or RT for HNSCC between February 2006 and November 2013 were studied. Those enrolled in the SPP participated in swallowing, jaw, and tongue exercises during cancer therapy. The comparator group received no swallowing intervention during CRT. A previously described functional outcome swallowing scale (FOSS; 0 = no symptoms and 5 = nonoral feeding for all nutrition) was used to quantify dysphagia prior to and at the completion of cancer therapy, and an analysis was performed to compare swallowing function. Results Forty-one (all male; mean age, 66 years) and 66 patients (all male; mean age, 61 years) were included in the SPP and comparator groups, respectively. In the SPP group, mean pre- and posttreatment FOSS scores were 2.2 and 2.2, respectively, while the corresponding scores in the comparator group were 1.8 and 2.7, respectively, with posttreatment FOSS scores being significantly worse than pretreatment FOSS scores in the comparator group only. Conclusion Patients enrolled in the SPP demonstrated preserved swallowing function over the course of cancer treatment compared with a comparator group. This confirms the importance of early evaluation and intervention for dysphagia prior to and during CRT or RT alone. C1 [Peng, Kevin A.; Kuan, Edward C.; Wang, Marilene B.; Long, Jennifer L.] Univ Calif Los Angeles, Dept Head & Neck Surg, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Unger, Lindsey] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Audiol & Speech Pathol, Los Angeles, CA USA. [Lorentz, William C.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Radiat Oncol, Los Angeles, CA USA. [Wang, Marilene B.; Long, Jennifer L.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Long, Jennifer L.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. RP Peng, KA (reprint author), Univ Calif Los Angeles, Head & Neck Surg, 10833 Le Conte Ave,CHS 62-132, Los Angeles, CA 90095 USA. EM kap@ucla.edu OI Long, Jennifer/0000-0002-4185-2328; Kuan, Edward/0000-0003-3475-0718 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, Career Development Award [IK2BX001944] FX Funding source: 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, Career Development Award IK2BX001944 (Dr Jennifer L. Long). This work was supported with resources and facilities at the Greater Los Angeles VA Healthcare System. NR 25 TC 4 Z9 4 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 MAY PY 2015 VL 152 IS 5 BP 863 EP 867 DI 10.1177/0194599815575508 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CH8BR UT WOS:000354261400017 PM 25829388 ER PT J AU Shalaby, AA Abraham, WT Fonarow, GC Bersohn, MM Gorcsan, J Lee, LY Halilovic, J Saba, S Maisel, A Singh, JP Sonel, A Kadish, A AF Shalaby, Alaa A. Abraham, William T. Fonarow, Gregg C. Bersohn, Malcolm M. Gorcsan, John, III Lee, Li-Yin Halilovic, Jasmina Saba, Samir Maisel, Alan Singh, Jagmeet P. Sonel, Ali Kadish, Alan TI Association of BNP and Troponin Levels with Outcome among Cardiac Resynchronization Therapy Recipients SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE biomarkers; BNP; cardiac resynchronization therapy; congestive heart failure; troponin ID BRAIN NATRIURETIC PEPTIDE; LEFT-VENTRICULAR DYSFUNCTION; CHRONIC HEART-FAILURE; RISK STRATIFICATION; PROGNOSTIC VALUE; TRIAL; DEFIBRILLATOR; DYSSYNCHRONY; PREVENTION; MORTALITY AB BackgroundWe conducted a prospective multicenter study to assess the prognostic value of combined baseline preimplant plasma levels of the biomarkers cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) among cardiac resynchronization therapy (CRT) with or without defibrillator capability (CRT-D) recipients. MethodsAt CRT-D implant, patients were stratified based on detectable TnT (0.01 ng/mL) and elevated BNP (predefined as >440 pg/mL) levels. Patients were classified into three groups: high (both detectable TnT and high BNP), intermediate (either detectable TnT or high BNP), or low (nondetectable TnT and low BNP). Patients were followed for 12 months. Survival curves free from mortality or heart failure hospitalizations (HFH) were assessed. To assess the predictive value of biomarker category, we constructed a multivariate Cox regression model, including the covariates of age, New York Heart Association class, left ventricular ejection fraction (LVEF), and QRS duration. ResultsA total of 267 patients (age 66 12 years, males 80%, LVEF 25% +/- 8%, ischemic cardiomyopathy 52%, QRSd 155 +/- 26 ms) were studied. After 1 year, there were 13 deaths and 25 HFH events. A significant difference in event-free survival among the three groups was observed, with high and intermediate categories having worse survival than low (log-rank test, P < 0.001). In the multivariate model, risk category was a significant predictor of outcome: hazard ratios were 7.34 (95% confidence interval [CI]: 2.48-21.69) and 2.50 (95% confidence interval [CI]: 1.04-6.04) for high-risk and intermediate-risk groups, respectively (P < 0.0001). ConclusionAmong CRT-D recipients, baseline TnT and BNP values alone or in combination provide significant prognostic value for the outcome of mortality or HFH. C1 [Shalaby, Alaa A.; Gorcsan, John, III; Saba, Samir; Sonel, Ali] Univ Pittsburgh, Pittsburgh, PA USA. [Shalaby, Alaa A.; Sonel, Ali] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Abraham, William T.] Ohio State Univ, Columbus, OH 43210 USA. [Fonarow, Gregg C.; Bersohn, Malcolm M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bersohn, Malcolm M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lee, Li-Yin; Halilovic, Jasmina] St Jude Med, Sylmar, CA USA. [Maisel, Alan] Univ Calif San Diego, San Diego, CA 92103 USA. [Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kadish, Alan] New York Med Coll, Valhalla, NY 10595 USA. RP Shalaby, AA (reprint author), 111C Univ Dr, Pittsburgh, PA 15240 USA. EM Alaa.Shalaby@va.gov FU St. Jude Medical, CRM FX Study sponsored by St. Jude Medical, CRM. NR 28 TC 2 Z9 2 U1 0 U2 0 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 MAY PY 2015 VL 38 IS 5 BP 581 EP 590 DI 10.1111/pace.12610 PG 10 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA CH4EY UT WOS:000353987200007 PM 25677851 ER PT J AU Lam, DK Dang, DM Flynn, AN Hardt, M Schmidt, BL AF Lam, David K. Dang, Dongmin Flynn, Andrea N. Hardt, Markus Schmidt, Brian L. TI TMPRSS2, a novel membrane-anchored mediator in cancer pain SO PAIN LA English DT Article DE Cancer pain; Head and neck cancer; PAR2; Proteases ID PROTEINASE-ACTIVATED RECEPTOR-2; TRANSMEMBRANE SERINE PROTEASES; SURFACE PROTEOLYTIC-ENZYMES; PROSTATE-CANCER; PANCREATIC PAIN; ANIMAL-MODELS; GENE; NOCICEPTION; EXPRESSION; CARCINOMA AB More than half of all-cancer patients have significant pain during the course of their disease. The strategic localization Of TMPRSS2, a membrane-bound serine protease, on the cancer cell surface may allow it to mediate signal-transduction between the cancer cell and its extracellular environment. We show that TMPRSS2 expression is not only dramatically increased in the primary cancers of patients but TMPRSS2 immunopositivity is also directly correlated with cancer pain severity in these patients. TMPRSS2 induced proteolytic activity, activated trigeminal neurons, and produced marked, mechanical hyperalgesia when administered into the hind paw of wild-type mice but not PAR2-deficient mice. Coculture of human cancer cells with murine trigeminal neurons demonstrated colocalization of TMPRSS2 with PAR2. These results point to a novel role for a cell membrane anchored mediator in cancer pain, as well as pain in general. C1 [Lam, David K.] Univ Toronto, Discipline Oral & Maxillofacial Surg, Toronto, ON, Canada. [Lam, David K.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Dang, Dongmin; Schmidt, Brian L.] NYU, Dept Oral & Maxillofacial Surg, New York, NY USA. [Flynn, Andrea N.; Schmidt, Brian L.] NYU, Bluestone Ctr Clin Res, New York, NY USA. [Hardt, Markus] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. RP Schmidt, BL (reprint author), NYU, Coll Dent, Bluestone Ctr Clin Res, 345 East 24th St,Clin 2W, New York, NY 10010 USA. EM bls322@nyu.edu FU NIH/NIDCR [R21 DE018561, R01 DE019796] FX This work was supported by a grant from the NIH/NIDCR R21 DE018561 and R01 DE019796. NR 29 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD MAY PY 2015 VL 156 IS 5 BP 923 EP 930 DI 10.1097/j.pain.0000000000000130 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA CH4MO UT WOS:000354007800019 PM 25734995 ER PT J AU Fisch, MJ Zhao, FM Manola, J Miller, AH Pirl, WF Wagner, LI AF Fisch, Michael J. Zhao, Fengmin Manola, Judith Miller, Andrew H. Pirl, William F. Wagner, Lynne I. TI Patterns and predictors of antidepressant use in ambulatory cancer patients with common solid tumors SO PSYCHO-ONCOLOGY LA English DT Article ID DEPRESSIVE SYMPTOMS; PSYCHOSOCIAL CARE; PALLIATIVE CARE; SCREENING TOOLS; METAANALYSIS; DISTRESS; ADULTS; ONCOLOGISTS; RECOGNITION; PREVALENCE AB Purpose: Depressive symptoms and antidepressant use are prevalent among cancer patients. We sought to identify determinants of prescribing commonly used antidepressants. Patients and methods: This multi-institutional study enrolled 3106 ambulatory patients with cancer of the breast, prostate, colon/rectum, or lung. Five case-finding methods were used to identify patients with depressive symptoms. Logistic models were used to examine factors that impact antidepressant use. Results: Approximately, 47% of patients were defined as having depressive symptoms. Clinicians rated being sad/depressed as one of the top three priority problems for 10.5% of patients. Antidepressants were prescribed in 19% of all patients, 25% with depressive symptoms and 14% nondepressed patients. After adjusting for other covariates, these variable categories were significantly associated with greater use of antidepressants: depressive symptoms, family history of depression, concurrent-medication use, cancer treatment status, and certain other clinical and demographic variables. The strongest individual predictors were concurrent use of more than 10 medications (odds ratio [OR] = 3.3), a family history of depression (OR= 2.2), sedative use (OR= 2.1), non-Hispanic white race (OR= 2.0), and anxiolytics use (OR= 2.0). Conclusions: Depressive symptoms are found in nearly half of outpatients with cancer, and one-fourth of patients with depressive symptoms are taking an antidepressant. Patients receiving antidepressants are more often those taking multiple medications, those with a depression diathesis, and those with more extensive cancer treatment. Patients who were younger, white, and female were also more likely to be taking antidepressants. Copyright (C) 2014 John Wiley & Sons, Ltd. C1 [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zhao, Fengmin; Manola, Judith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miller, Andrew H.] Emory Univ, Sch Med, Atlanta, GA USA. [Pirl, William F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wagner, Lynne I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Fisch, MJ (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Unit 0462 1515 Holcombe Blvd, Houston, TX 77030 USA. EM mfisch@mdanderson.org FU Public Health Service [CA37604, CA17145]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was supported in part by Public Health Service Grants CA37604 and CA17145 and grants from the National Cancer Institute, National Institutes of Health, and Department of Health and Human Services. This study's contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 44 TC 6 Z9 6 U1 4 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD MAY PY 2015 VL 24 IS 5 BP 523 EP 532 DI 10.1002/pon.3606 PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CH3YA UT WOS:000353965900004 PM 24930693 ER PT J AU Tucker-Seeley, RD Abel, GA Uno, H Prigerson, H AF Tucker-Seeley, Reginald D. Abel, Gregory A. Uno, Hajime Prigerson, Holly TI Financial hardship and the intensity of medical care received near death SO PSYCHO-ONCOLOGY LA English DT Article ID OF-LIFE CARE; FAMILY-MEMBERS; CANCER-PATIENTS; UNIT PATIENTS; POSTTRAUMATIC STRESS; TREATMENT PREFERENCES; SERIOUS ILLNESS; ODDS RATIOS; HIGH-RISK; END AB Background: Although end-of-life (EOL) care can present a substantial financial burden for the household, the influence of this burden on the intensity of care received at the EOL remains unknown. The goal of this study was to determine the association between financial hardship and intensive care in the last week of life. Methods: The Coping with Cancer (CwC) Study is a longitudinal, multisite cohort study of terminally ill cancer patients and their informal caregivers, September 2002-February 2008. Patients (N = 281) were followed from baseline to death, a median of 4.4 months after baseline assessment. Intensive care was defined as the use of resuscitation and/or ventilation in the patient's last week of life. Financial hardship was measured at study baseline as a positive response to whether the household had to use all or most of their savings because of the family member's illness. Results: Twenty-nine percent reported financial hardship, and 9% received intensive EOL care. Patients reporting financial hardship had a 3.22 (95% CI: 1.38, 7.53) higher likelihood of receiving intensive EOL care compared with patients not reporting financial hardship. After adjusting for sociodemographic characteristics and patient preferences, patients reporting financial hardship had a 3.05 (95% CI: 1.22, 7.62) higher likelihood of receiving intensive EOL care. Conclusion: The depletion of a family's financial resources is a significant predictor of intensive EOL care, over and above the influence of sociodemographic characteristics and patient preferences. Copyright (C) 2014 John Wiley & Sons, Ltd. C1 [Tucker-Seeley, Reginald D.; Abel, Gregory A.; Uno, Hajime] Dana Farber Canc Inst, Boston, MA 02215 USA. [Tucker-Seeley, Reginald D.; Uno, Hajime] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Abel, Gregory A.] Harvard Univ, Sch Med, Boston, MA USA. [Prigerson, Holly] Weill Cornell Med Coll, New York, NY USA. RP Tucker-Seeley, RD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW 666A, Boston, MA 02215 USA. EM retucker@hsph.harvard.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA 106370, CA 156732, 1 U54 (CA156732-01), 1K01CA169041-01] FX This research was supported in part by grant MH63892 from the National Institute of Mental Health and grants CA 106370 and CA 156732 from the National Cancer Institute to Dr. Prigerson and grants from the National Cancer Institute Research Supplement to 1 U54 (CA156732-01) and the National Cancer Institute (1K01CA169041-01) to Dr. Tucker-Seeley. NR 46 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD MAY PY 2015 VL 24 IS 5 BP 572 EP 578 DI 10.1002/pon.3624 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CH3YA UT WOS:000353965900010 PM 25052138 ER PT J AU Wang, EA McGinms, KA Goulet, J Bryant, K Gibert, C Leaf, DA Mattocks, K Fiellin, LE Vogenthaler, N Justice, AC Fiellin, DA AF Wang, Emily A. McGinms, Kathleen A. Goulet, Joseph Bryant, Kendall Gibert, Cynthia Leaf, David A. Mattocks, Kristin Fiellin, Lynn E. Vogenthaler, Nicholas Justice, Amy C. Fiellin, David A. CA Vet Aging Cohort Study Project Tea TI Food Insecurity and Health: Data from the Veterans Aging Cohort Study SO PUBLIC HEALTH REPORTS LA English DT Article ID HIV-INFECTED INDIVIDUALS; MENTAL-HEALTH; HOUSING INSTABILITY; WELFARE RECIPIENTS; INSUFFICIENCY; CARE; MORTALITY; ADULTS; CHILDREN; DISEASE AB Objective. Food insecurity may be a modifiable and independent risk factor for worse control of medical conditions, but it has not been explored among veterans. We determined the prevalence of, and factors independently associated with, food insecurity among veterans in the Veterans Aging Cohort Study (VACS). Methods. Using data from VACS from 2002-2008, we determined the prevalence of food insecurity among veterans who have accessed health care in the Veterans Health Administration (VA) as defined by "concern about having enough food for you or your family in the past month." We used multivariable logistic regression to determine factors independently associated with food insecurity and tests of trend to measure the association between food insecurity and control of hypertension, diabetes, HIV, and depression. Results. Of the 6,709 veterans enrolled in VACS, 1,624 (24%) reported being food insecure. Food insecurity was independently associated with being African American, earning <$25,000/year, recent homelessness, marijuana use, and depression. Being food insecure was also associated with worse control of hypertension, diabetes, HIV and depression (p<0.001). Conclusion. Food insecurity is prevalent and associated with worse control of medical conditions among veterans who have accessed care in the VA. C1 [Wang, Emily A.; Goulet, Joseph; Fiellin, Lynn E.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [McGinms, Kathleen A.; Goulet, Joseph; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Bryant, Kendall] NIAAA, NIH, Rockville, MD 20852 USA. [Gibert, Cynthia] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Mattocks, Kristin] VA Cent Western Massachusetts, Northampton, MA USA. [Mattocks, Kristin] Univ Massachusetts, Sch Med, Worcester, MA USA. [Vogenthaler, Nicholas] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT 06510 USA. RP Wang, EA (reprint author), Yale Univ, Sch Med, Gen Internal Med, Harkness Hall Bldg A,367 Cedar St,Ste 410A, New Haven, CT 06510 USA. EM emily.wang@yale.edu OI Fiellin, David/0000-0002-4006-010X; Goulet, Joseph/0000-0002-0842-804X FU National Institute on Alcohol Abuse and Alcoholism [U01-AA-13566, U10-AA-13566]; National Institute on Aging (NIA) [K23-AG00826]; Robert Wood Johnson Generalist Faculty Scholar Award; NIA, National Institute of Mental Health; Veterans Health Administration Health Services Research & Development Research Enhancement Award Program (REAP) PRIME Project [REA-08-266]; National Heart, Lung, and Blood Institute [K23-HL103720]; Yale Clinical Center of Investigation's Clinical & Translations Science Awards Grant [UL1 RR024139] FX The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The Veterans Aging Cohort Study (VACS) is funded by the National Institute on Alcohol Abuse and Alcoholism (#U01-AA-13566 and #U10-AA-13566); the National Institute on Aging (NIA) (#K23-AG00826); and the Robert Wood Johnson Generalist Faculty Scholar Award, an interagency agreement among the NIA, National Institute of Mental Health, and Veterans Health Administration Health Services Research & Development Research Enhancement Award Program (REAP) PRIME Project (#REA-08-266). Emily Wang receives salary support from a career development award from the National Heart, Lung, and Blood Institute (#K23-HL103720) and the Yale Clinical Center of Investigation's Clinical & Translations Science Awards Grant (#UL1 RR024139). The Institutional Review Boards at the Veterans Health Administrations in Atlanta, Georgia; Baltimore, Maryland; Bronx, New York; Manhattan/Brooklyn, New York; Houston, Texas; Los Angeles, California; Pittsburgh, Pennsylvania; and Washington, D.C., approved the study, and all participants provided written informed consent prior to enrollment. NR 33 TC 7 Z9 7 U1 3 U2 11 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 MAY-JUN PY 2015 VL 130 IS 3 BP 261 EP 268 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH5JJ UT WOS:000354071600013 PM 25931630 ER PT J AU Pettersson, S Lundberg, IE Liang, MH Pouchot, J Henriksson, EW AF Pettersson, S. Lundberg, I. E. Liang, M. H. Pouchot, J. Henriksson, E. Welin TI Determination of the minimal clinically important difference for seven measures of fatigue in Swedish patients with systemic lupus erythematosus SO SCANDINAVIAN JOURNAL OF RHEUMATOLOGY LA English DT Article ID QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS; HEALTH-STATUS AB Objective: To estimate the minimal clinically important difference (MCID) in seven self-administered measures assessing fatigue in Swedish patients with systemic lupus erythematosus (SLE). Method: The participants (n = 51, women 98%, age 52.8 +/- 12.1 years, disease duration 18.7 +/- 13.6 years) met in groups of six to nine persons. After completing seven fatigue questionnaires [the Fatigue Severity Scale (FSS); the Multidimensional Assessment of Fatigue (MAF) scale; the 20-item Multidimensional Fatigue Inventory (MFI); the Chalder Fatigue Scale (CFS); the Short Form-36 Vitality subscale (VT); the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) scale; and the Numeric Rating Scale (NRS)], each respondent had a minimum of five face-to-face discussions, followed by an individual comparative assessment of their own level of fatigue (seven-grade scale). This method resulted in 260 contrasting assessments; MCIDs were first calculated using the paired differences and then established by a regression approach. Patients were asked to comment on their experience with the questionnaires and whether they captured their fatigue adequately. Results: The paired approach (using 'little more fatigue' as an anchor for MCID during the face-to-face comparative assessments) provided estimates of 4.6-17.0; the regression approach provided estimates of 4.3-10.8. Estimates using the regression approach were consistently lower than those using the paired model. The MCID estimates were least favourable and fewer respondents supported the use of the NRS compared to the other self-reported questionnaires. Conclusions: All seven instruments detect MCIDs for fatigue in Swedish patients with SLE. However, the single-question measure was not supported by the MCID estimates or by comments from the respondents. C1 [Pettersson, S.; Lundberg, I. E.; Henriksson, E. Welin] Karolinska Univ Hosp, Rheumatol Clin, SE-17176 Stockholm, Sweden. [Pettersson, S.; Henriksson, E. Welin] Karolinska Inst, Div Nursing, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden. [Lundberg, I. E.] Karolinska Inst, Rheumatol Unit, Dept Med, Karolinska Univ Hosp, Stockholm, Sweden. [Liang, M. H.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Liang, M. H.] VA Boston Healthcare Syst, Rheumatol Sect, Boston, MA USA. [Pouchot, J.] Paris Descartes Univ, Fac Med, Georges Pompidou European Hosp, Publ Assistance Hosp Paris AH HP, Paris, France. RP Pettersson, S (reprint author), Karolinska Univ Hosp, Rheumatol Unit, SE-17176 Stockholm, Sweden. EM susanne.pettersson@karolinska.se OI pettersson, susanne/0000-0001-7432-2756; Lundberg, Ingrid/0000-0002-6068-9212 FU Swedish Rheumatism Association; King Gustaf V 80th Birthday Fund; Swedish Heart Lung Foundation; Swedish Society of Medicine; Ake Wiberg Foundation; Alex and Eva Wallstroms Foundation; Foundation in memory of Clas Groschinsky; Karolinska Institutet's Foundations; Stockholm County Council; Karolinska Institutet FX This work was supported by the Swedish Rheumatism Association, a grant from the King Gustaf V 80th Birthday Fund, the Swedish Heart Lung Foundation, the Swedish Society of Medicine, the Ake Wiberg Foundation, the Alex and Eva Wallstroms Foundation, the Foundation in memory of Clas Groschinsky, the Karolinska Institutet's Foundations, and funding through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet. NR 15 TC 2 Z9 2 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-9742 EI 1502-7732 J9 SCAND J RHEUMATOL JI Scand. J. Rheumatol. PD MAY PY 2015 VL 44 IS 3 BP 206 EP 210 DI 10.3109/03009742.2014.988173 PG 5 WC Rheumatology SC Rheumatology GA CH9YO UT WOS:000354392800005 PM 25656604 ER PT J AU Bao, YR Johansen, KL AF Bao, Yeran Johansen, Kirsten L. TI Diagnosis and Treatment of Low Testosterone among Patients with End-Stage Renal Disease SO SEMINARS IN DIALYSIS LA English DT Review ID TANDEM MASS-SPECTROMETRY; PLACEBO-CONTROLLED TRIALS; LATE-ONSET HYPOGONADISM; LOW SERUM TESTOSTERONE; BONE-MINERAL DENSITY; OLDER MEN; TRANSDERMAL TESTOSTERONE; MOBILITY LIMITATION; REFERENCE RANGES; MAINTENANCE HEMODIALYSIS AB The prevalence of low testosterone level is particularly high among patients with end-stage renal disease (ESRD) and has been associated with mortality. In populations without ESRD, low testosterone level has also been associated with a number of morbidities including cardiovascular disease, diabetes mellitus, low muscle mass, low bone mass, low physical performance, and frailty. However, there is controversy regarding what constitutes low testosterone level in the aging population and at what level replacement therapy with testosterone is indicated. There are no randomized controlled trials investigating long-term outcomes of testosterone replacement therapy in populations with or without ESRD. Available trial results suggest equivocal improvements in sexual function. Muscle mass and bone mineral density appear to improve, but results in physical function and performance are mixed and there are no data on fracture prevention. Some recent data suggest harm when testosterone was given to men with limited mobility. Finally, there is little evidence that testosterone adds to existing erythropoietin agents in the treatment of anemia in ESRD. Due to lack of evidence supporting long-term use of testosterone, the authors recommend against the routine use of testosterone in ESRD patients with low testosterone levels. Testosterone treatment can be considered in those with low bone mass and total testosterone level <200ng/dl, or in younger patients with sexual complaints with total testosterone level lower than the reference range. It is important to engage patients in discussion of risks and benefits before initiating testosterone therapy; testosterone therapy should be discontinued if the intended treatment effect is not observed after short-term use. C1 [Bao, Yeran] John Muir Med Grp, Walnut Creek, CA USA. [Johansen, Kirsten L.] San Francisco Gen Hosp, Div Nephrol, San Francisco, CA 94110 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94143 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 NIDDK NIH HHS [K24 DK085153] NR 47 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 EI 1525-139X J9 SEMIN DIALYSIS JI Semin. Dial. PD MAY-JUN PY 2015 VL 28 IS 3 BP 259 EP 265 DI 10.1111/sdi.12318 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CH4BO UT WOS:000353976200012 PM 25376701 ER PT J AU Manoach, DS Stickgold, R AF Manoach, Dara S. Stickgold, Robert TI Sleep, memory and schizophrenia SO SLEEP MEDICINE LA English DT Editorial Material ID CONSOLIDATION; SPINDLES; SLOW C1 [Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Stickgold, Robert] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Manoach, Dara S.; Stickgold, Robert] Harvard Univ, Sch Med, Boston, MA USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM dara@nmr.mgh.harvard.edu OI Manoach, Dara/0000-0001-9208-1167 FU NIMH NIH HHS [R01 MH092638] NR 21 TC 1 Z9 1 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 EI 1878-5506 J9 SLEEP MED JI Sleep Med. PD MAY PY 2015 VL 16 IS 5 BP 553 EP 554 DI 10.1016/j.sleep.2015.01.009 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CH2YV UT WOS:000353892800001 PM 25747334 ER PT J AU Pelton, D Wangelin, B Tuerk, P AF Pelton, Dan Wangelin, Bethany Tuerk, Peter TI Utilizing Telehealth to Support Treatment of Acute Stress Disorder in a Theater of War: Prolonged Exposure via Clinical Videoconferencing SO TELEMEDICINE AND E-HEALTH LA English DT Article DE behavioral health; telepsychiatry; disaster medicine; military medicine ID THERAPY; TELEPSYCHIATRY; PSYCHOTHERAPY; SYMPTOMS; VETERANS; AFGHANISTAN; DEPRESSION; OUTCOMES; INJURY; TRIAL AB Background: Posttraumatic stress disorder (PTSD) and acute stress disorder are prevalent mental health diagnoses associated with the military operations in Iraq and Afghanistan and are especially significant in service members returning from combat. Prolonged exposure (PE) therapy is a highly effective behavioral treatment for these symptoms, and providing this treatment as soon as possible, even in the midst of a soldier's combat deployment, has strong potential benefits. Materials and Methods: In the current case study, telehealth technology was used to support the delivery of PE therapy to treat a service member diagnosed with acute stress disorder in a war zone. PE was conducted face-to-face on the relatively secure Forward Operating Base for the first half of therapy and via clinical videoconferencing (CV) to the service member's remote combat outpost during the later stages of therapy. The service member exhibited marked improvements in symptoms over 10 sessions. Results: Results are consistent with previous empirical findings and highlight the potential benefits of using telehealth to deliver evidenced-based treatment for traumatic stress disorders in a war zone. This case study provides a preliminary working model for delivering PE in a combat environment using multiple delivery systems. Conclusions: Benefits and clinical utility of CV-delivered exposure therapy are discussed, particularly for providers pending future operational deployments (e.g., including members of the military, independent government agencies, and first responders) and for those treating patients in remote locations. C1 [Pelton, Dan] Anxiety Solut LLC, Mclean, VA 22101 USA. [Wangelin, Bethany; Tuerk, Peter] Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv Line, Charleston, SC USA. [Wangelin, Bethany; Tuerk, Peter] Med Univ S Carolina, Dept Psychiat & Behav Sci, Mil Sci Div, Charleston, SC 29425 USA. RP Pelton, D (reprint author), Anxiety Solut LLC, 1499 Chain Bridge Rd,Suite 201, Mclean, VA 22101 USA. EM dpelton@anxiety-solutions.com NR 39 TC 1 Z9 1 U1 3 U2 11 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD MAY 1 PY 2015 VL 21 IS 5 BP 382 EP 387 DI 10.1089/tmj.2014.0111 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CH5UA UT WOS:000354099600006 PM 25764266 ER PT J AU Geltman, PL Fried, LE Arsenault, LN Knowles, AM Link, DA Goldstein, JN Perrin, JM Hacker, KA AF Geltman, Paul L. Fried, Lise E. Arsenault, Lisa N. Knowles, Alice M. Link, David A. Goldstein, Joel N. Perrin, James M. Hacker, Karen A. TI A Planned Care Approach and Patient Registry to Improve Adherence to Clinical Guidelines for the Diagnosis and Management of Attention-Deficit/Hyperactivity Disorder SO ACADEMIC PEDIATRICS LA English DT Article DE AMID; planned care; primary care; quality improvement; registry ID DEFICIT-HYPERACTIVITY DISORDER; SHARED DECISION-MAKING; NATIONAL PERSPECTIVE; US CHILDREN; ADHD; SETTINGS; STIMULANTS; PREVALENCE; PEDIATRICS; PATTERNS AB BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) affects almost 2.4 million US children. Because American Academy of Pediatrics guidelines for ADHD recommend use of standardized diagnostic instruments, regular follow-up and the chronic care model, this pilot project sought to implement and assess an electronic registry of patients with AMID combined with care coordination by a planned care team. METHODS: This quality improvement project was structured with 2 intervention and 2 control clinics to facilitate evaluation of the use of a planned care system for management of ADHD. Care teams included a pediatrician, nurse, medical assistant, and care coordinator and tracked patients using an electronic registry with data drawn from the EMR. Clinical work flows were pilot tested to facilitate use of the Vanderbilt scales and their incorporation into the EMR at intervention sites. Outcome measures included 2 recommended clinical follow-ups based on HEDIS measures as well as use of the Vanderbilt rating scales. Initiation phase measure was for follow-up after initiating medication, while the continuation phase measure was for subsequent follow-up during the first year of treatment. Measures were monitored during the project year and then also in the ensuing period of spread of the intervention to other sites. RESULTS: Although the modified HEDIS initiation phase measure for patients newly on medication remained static at approximately 50% throughout the project period, the continuation phase measure showed improvement from 35% at baseline to 45% at the end of the project assessment year, a 29% increase. Follow-up for patients stable on medications also remained unchanged during the project period, but during subsequent spreading of the intervention to nonproject sites, follow-up of these patients improved to over 90%. In adjusted analyses, patients with ADHD at intervention sites were over 2 times more likely than patients at control sites to have had a Vanderbilt score documented in their records. CONCLUSIONS: The project achieved modest improvements in the diagnostic and treatment process for patients with ADHD. The use of a planned care system and electronic patient registry shows promise for improving the diagnosis and treatment process for patients with AMID. C1 [Geltman, Paul L.; Link, David A.] Cambridge Hlth Alliance, Dept Pediat, Cambridge, MA USA. [Fried, Lise E.; Arsenault, Lisa N.; Knowles, Alice M.] Cambridge Hlth Alliance, Inst Community Hlth, Cambridge, MA USA. [Goldstein, Joel N.] Cambridge Hlth Alliance, Div Child Psychiat, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA USA. [Perrin, James M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Perrin, James M.] Harvard Univ, Sch Med, Boston, MA USA. [Hacker, Karen A.] Allegheny Cty Hlth Dept, Pittsburgh, PA USA. [Hacker, Karen A.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. RP Geltman, PL (reprint author), 1493 Cambridge St,Macht 317C, Cambridge, MA 02139 USA. EM pgeltman@challiance.org FU Harvard Catalyst, The Harvard Clinical and Translational Science Center FX This project was funded by a pilot grant from the Harvard Catalyst, The Harvard Clinical and Translational Science Center (DA Link, PI). The funder had no role in the design and conduct of the project or preparation of this document. NR 31 TC 3 Z9 3 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2015 VL 15 IS 3 BP 289 EP 296 PG 8 WC Pediatrics SC Pediatrics GA CH2MQ UT WOS:000353859700007 PM 25906699 ER PT J AU Perrin, JM Hall, R AF Perrin, James M. Hall, Robert TI The Children's Health Insurance Program Strengthens Children's Health Care SO ACADEMIC PEDIATRICS LA English DT Editorial Material C1 [Perrin, James M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Perrin, James M.] MassGen Hosp Children, Boston, MA USA. [Hall, Robert] Amer Acad Pediat, Washington, DC USA. RP Perrin, JM (reprint author), 100 Cambridge St 1542, Boston, MA 02114 USA. EM jperrin@mgh.harvard.edu NR 9 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 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2015 VL 15 IS 3 SU S BP S11 EP S12 PG 2 WC Pediatrics SC Pediatrics GA CH2MT UT WOS:000353860000004 PM 25906954 ER PT J AU Ludwig, LS Cho, H Wakabayashi, A Eng, JC Ulirsch, JC Fleming, MD Lodish, HF Sankaran, VG AF Ludwig, Leif S. Cho, Hyunjii Wakabayashi, Aoi Eng, Jennifer C. Ulirsch, Jacob C. Fleming, Mark D. Lodish, Harvey F. Sankaran, Vijay G. TI Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ERYTHROID-DIFFERENTIATION; HUMAN HEMATOPOIESIS; CELL-CYCLE; LIVER; GATA1; LOCI AB Genome-wide association studies (GWAS) hold tremendous promise to improve our understanding of human biology. Recent GWAS have revealed over 75 loci associated with erythroid traits, including the 4q27 locus that is associated with red blood cell size (mean corpuscular volume). The close linkage disequilibrium block at this locus harbors the CCNA2 gene that encodes cyclin A2. CCNA2 mRNA is highly expressed in human and murine erythroid progenitor cells and regulated by the essential erythroid transcription factor GATA1. To understand the role of cyclin A2 in erythropoiesis, we have reduced expression of this gene using short hairpin RNAs in a primary murine erythroid culture system. We demonstrate that cyclin A2 levels affect erythroid cell size by regulating the passage through cytokinesis during the final cell division of terminal erythropoiesis. Our study provides new insight into cell cycle regulation during terminal erythropoiesis and more generally illustrates the value of functional GWAS follow-up to gain mechanistic insight into hematopoiesis.Am. J. Hematol. 90:386-391, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Ludwig, Leif S.; Wakabayashi, Aoi; Ulirsch, Jacob C.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Ludwig, Leif S.; Wakabayashi, Aoi; Ulirsch, Jacob C.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Ludwig, Leif S.; Wakabayashi, Aoi; Ulirsch, Jacob C.; Sankaran, Vijay G.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Ludwig, Leif S.; Cho, Hyunjii; Eng, Jennifer C.; Lodish, Harvey F.; Sankaran, Vijay G.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Ludwig, Leif S.] Free Univ Berlin, Inst Chem & Biochem, Berlin, Germany. [Ludwig, Leif S.] Charite, D-13353 Berlin, Germany. [Cho, Hyunjii; Lodish, Harvey F.] MIT, Dept Biol, Cambridge, MA USA. [Fleming, Mark D.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Sankaran, VG (reprint author), Boston Childrens Hosp, 3 Blackfan Circle,CLS 03001, Boston, MA 02115 USA. EM sankaran@broadinstitute.org OI Ludwig, Leif/0000-0002-2916-2164 FU German National Academic Foundation; National Institutes of Health [P01 HL032262, R21 HL120791, R01 DK103794] FX Contract grant sponsor: German National Academic Foundation (to L.S.L.); Contract grant sponsor: National Institutes of Health; Contract grant numbers: P01 HL032262 (to H.F.L.), R21 HL120791, and R01 DK103794 (to V.G.S.). NR 26 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2015 VL 90 IS 5 BP 386 EP 391 DI 10.1002/ajh.23952 PG 6 WC Hematology SC Hematology GA CG6FS UT WOS:000353393300015 PM 25615569 ER PT J AU Patel, HH Patel, HR Higgins, JM AF Patel, Harsh H. Patel, Hasmukh R. Higgins, John M. TI Modulation of red blood cell population dynamics is a fundamental homeostatic response to disease SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID DISTRIBUTION WIDTH; DIABETES-MELLITUS; IN-VIVO; PROGNOSTIC MARKER; IRON-DEFICIENCY; HEART-FAILURE; HEMOGLOBIN; RISK; ERYTHROCYTES; RETICULOCYTE AB Increased red blood cell (RBC) volume variation (RDW) has recently been shown to predict a wide range of mortality and morbidity: death due to cardiovascular disease, cancer, infection, renal disease, and more; complications in heart failure and coronary artery disease, advanced stage and worse prognosis in many cancers, poor outcomes in autoimmune disease, and many more. The mechanisms by which all of these diseases lead to increased RDW are unknown. Here we use a semi-mechanistic mathematical model of in vivo RBC population dynamics to dissect the factors controlling RDW and show that elevated RDW results largely from a slight reduction in the in vivo rate of RBC turnover. RBCs become smaller as they age, and a slight reduction in the rate of RBC turnover allows smaller cells to continue circulating, expanding the low-volume tail of the RBC population's volume distribution, and thereby increasing RDW. Our results show that mildly extended RBC lifespan is a previously unrecognized homeostatic adaptation common to a very wide range of pathologic states, likely compensating for subtle reductions in erythropoietic output. A mathematical model-based estimate of the clearance rate may provide a novel early-warning biomarker for a wide range of morbidity and mortality.Am. J. Hematol. 90:422-428, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Patel, Harsh H.; Patel, Hasmukh R.; Higgins, John M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Patel, Harsh H.; Patel, Hasmukh R.; Higgins, John M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Higgins, John M.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Higgins, JM (reprint author), MGH Ctr Syst Biol, Simches 5-222,185 Cambridge St, Boston, MA 02114 USA. EM john_hig-gins@hms.harvard.edu FU NIDDK [K08DK083242]; NIH [DP2DK098087]; Abbott Hematology FX Contract grant sponsor: NIDDK; Contract grant number: K08DK083242.; Contract grant sponsor: NIH Director's New Innovator Award; Contract grant number: DP2DK098087.; Contract grant sponsor: Abbott Hematology. NR 34 TC 10 Z9 10 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2015 VL 90 IS 5 BP 422 EP 428 DI 10.1002/ajh.23982 PG 7 WC Hematology SC Hematology GA CG6FS UT WOS:000353393300021 PM 25691355 ER PT J AU Ramanathan, S Hill, JN Cameron, KA Safdar, N Guihan, M Evans, CT AF Ramanathan, Swetha Hill, Jennifer N. Cameron, Kenzie A. Safdar, Nasia Guihan, Marylou Evans, Charlesnika T. TI Relationship between knowledge and attitudes of methicillin-resistant Staphylococcus aureus and hand hygiene behavior in Veterans with spinal cord injury and disorder SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Methicillin-resistant Staphylococcus aureus; Veterans; Spinal cord injury; Knowledge; Attitudes; Hand hygiene behavior ID PERCEPTIONS; PATIENT AB The objective of this analysis was to understand the relationship between knowledge and attitudes regarding methicillin-resistant Staphylococcus aureus and hand hygiene behavior based on a baseline survey administered to Veterans with spinal cord injuries and disorders. Higher knowledge was associated with higher attitude scores (r = 0.35, P = .003), but knowledge and attitudes were not associated with behavior. Also, those with quadriplegia had higher knowledge scores (P = .03). Knowledge and attitudes, although related, do not appear to fully explain patients' hand hygiene behavior. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Ramanathan, Swetha; Hill, Jennifer N.; Guihan, Marylou; Evans, Charlesnika T.] Edward Hines Jr VA Hosp, Ctr Innovat Complex Chron Healthcare, Dept Vet Affairs, Hines, IL 60141 USA. [Ramanathan, Swetha; Hill, Jennifer N.; Guihan, Marylou; Evans, Charlesnika T.] Edward Hines Jr VA Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL 60141 USA. [Cameron, Kenzie A.] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Gen Internal Med & Geriatr, Chicago, IL 60611 USA. [Cameron, Kenzie A.; Evans, Charlesnika T.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Cameron, Kenzie A.; Evans, Charlesnika T.] Northwestern Univ, Feinberg Sch Med, Ctr Healthcare Studies, Chicago, IL 60611 USA. [Safdar, Nasia] Univ Wisconsin, Univ Wisconsin Hosp & Clin, Dept Med, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Univ Wisconsin Hosp & Clin, Dept Populat Hlth Sci, Madison, WI USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Ramanathan, S (reprint author), Edward Hines Jr VA Hosp, 5th & Roosevelt Rd 151H,Room C306, Hines, IL 60141 USA. EM Swetha.Ramanathan@va.gov OI Cameron, Kenzie/0000-0002-3535-6459 FU Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Services, Quality Enhancement Research Initiative [RRP 09-125] FX This study was supported by the Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Services, Quality Enhancement Research Initiative (RRP 09-125). NR 10 TC 1 Z9 1 U1 0 U2 2 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 MAY 1 PY 2015 VL 43 IS 5 BP 537 EP 539 DI 10.1016/j.ajic.2015.01.030 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CH2XZ UT WOS:000353890100024 PM 25952051 ER PT J AU Villarruel, A Washington, D Lecher, WT Carver, NA AF Villarruel, Antonia Washington, Deborah Lecher, William T. Carver, Nefertari A. TI A More Diverse Nursing Workforce SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 [Villarruel, Antonia] Univ Penn, Sch Nursing, Nursing, Philadelphia, PA 19104 USA. [Villarruel, Antonia; Washington, Deborah] Future Nursing Campaign Act Divers Steering Comm, New York, NY USA. [Washington, Deborah] Massachusetts Gen Hosp, Divers Patient Care Serv, Boston, MA 02114 USA. [Lecher, William T.] Cincinnati Childrens Hosp Med Ctr, Specialty Resource Unit, Cincinnati, OH 45229 USA. [Lecher, William T.] Amer Assembly Men Nursing, Philadelphia, PA USA. [Carver, Nefertari A.] Ctr Champ Nursing Amer, Washington, DC 20049 USA. RP Carver, NA (reprint author), Ctr Champ Nursing Amer, Washington, DC 20049 USA. EM ncarver@aarp.org NR 13 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-936X EI 1538-7488 J9 AM J NURS JI Am. J. Nurs. PD MAY PY 2015 VL 115 IS 5 BP 57 EP 62 PG 6 WC Nursing SC Nursing GA CG8WN UT WOS:000353596500017 PM 25906230 ER PT J AU Berk, M Nierenberg, AA AF Berk, Michael Nierenberg, Andrew A. TI Three Paths to Drug Discovery in Psychiatry SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID NETWORK MEDICINE; N-ACETYLCYSTEINE; HUMAN-DISEASE; DEPRESSION C1 [Berk, Michael] Deakin Univ, Sch Med, IMPACT Strateg Res Ctr, Geelong, Vic 3217, Australia. Univ Melbourne, Ctr Youth Mental Hlth, Orygen Youth Hlth Res Ctr, Parkville, Vic 3052, Australia. Barwon Hlth & Geelong Clin, Geelong, Vic, Australia. Ftorey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia. Univ Melbourne, Dept Psychiat, Parkville, Vic 3052, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin & Res Program, Boston, MA USA. RP Berk, M (reprint author), Deakin Univ, Sch Med, IMPACT Strateg Res Ctr, Geelong, Vic 3217, Australia. EM mikebe@barwonhealth.org.au FU AstraZeneca; Beyond Blue; Bioadvantex; Bristol-Myers Squibb; Cancer Council of Victoria; Cooperative Research Centre; Eli Lilly; Geelong Medical Research Foundation; GlaxoSmithKline; Janssen-Cilag; Lundbeck; MBF; Mayne Pharma; Meat and Livestock Board; Merck; NIH; Organon; Novartis; Pfizer; Rotary Health; Servier; Sanofi Synthelabo; Simons Autism Foundation; Solvay; Stanley Medical Research Foundation; Woolworths; Wyeth; National Health and Medical Research Council [1059660]; Agency for Healthcare Research and Quality; American Foundation for Suicide Prevention; Belvoir Publications; Brain and Behavior Research Foundation; Brain Cells; Corcept; Forest; Genentech; Hoffman LaRoche; Marriott Foundation; MedAvante; Methylation Sciences; Naurex; NIMH; Pamlab; Patient-Centered Outcomes Research Institute; Ridge Diagnostics; Slack Publications; Sunovion; Takeda/Lundbeck; Teva FX Professor Berk has received research support from or served as a speaker or consultant for AstraZeneca, Beyond Blue, Bioadvantex, Bristol-Myers Squibb, Cancer Council of Victoria, Cooperative Research Centre, Eli Lilly, Geelong Medical Research Foundation, GlaxoSmithKline, Janssen-Cilag, Lundbeck, MBF, Mayne Pharma, Meat and Livestock Board, Merck, National Health and Medical Research Council, NIH, Organon, Novartis, Pfizer, Rotary Health, Servier, Sanofi Synthelabo, Servier, Simons Autism Foundation, Solvay, Stanley Medical Research Foundation, Woolworths, and Wyeth; he is supported by National Health and Medical Research Council Senior Principal Research Fellowship 1059660.; Dr. Nierenberg has received grant support or honoraria from or served as a consultant to Agency for Healthcare Research and Quality, American Foundation for Suicide Prevention, AstraZeneca, Belvoir Publications, Brain and Behavior Research Foundation, Brain Cells, Bristol-Myers Squibb, Corcept, Eli Lilly, Forest, Genentech, GlaxoSmithKline, Hoffman LaRoche, Marriott Foundation, MedAvante, Merck, Methylation Sciences, Naurex, NIMH, Pamlab, Patient-Centered Outcomes Research Institute, Pfizer, Ridge Diagnostics, Slack Publications, Sunovion, Takeda/Lundbeck, and Teva; he owns stock options in Appliance Computing (Mindsite), Brain Cells, and MedAvante; income is possible from Infomedic.com, but no revenue has been received to date; through Massachusetts General Hospital (MGH), he is named for copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery-Asberg Depression Rating Scale, exclusively licensed to the MGH Clinical Trials Network and Institute NR 20 TC 6 Z9 6 U1 0 U2 1 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 MAY PY 2015 VL 172 IS 5 BP 412 EP 414 DI 10.1176/appi.ajp.2014.14070858 PG 3 WC Psychiatry SC Psychiatry GA CH2FM UT WOS:000353841100005 PM 25930130 ER PT J AU Ptaszek, LM Kim, K Spooner, AE MacGillivray, TE Cambria, RP Lindsay, ME Isselbacher, EM AF Ptaszek, Leon M. Kim, Kibeom Spooner, Amy E. MacGillivray, Thomas E. Cambria, Richard P. Lindsay, Mark E. Isselbacher, Eric M. TI Marfan Syndrome Is Associated With Recurrent Dissection of the Dissected Aorta SO ANNALS OF THORACIC SURGERY LA English DT Article ID LONG-TERM SURVIVAL; INTERNATIONAL REGISTRY; FALSE LUMEN; REPAIR; FATE; DETERMINES; ANEURYSM; SURGERY; DISTAL AB Background. Recurrent dissection of a previously dissected aortic segment has been reported as a rare, late complication in single case reports. The infrequency of this event makes informed risk assessment in an individual patient challenging. Methods. To investigate this issue we examined the database of the Massachusetts General Hospital Thoracic Aortic Center between January 1, 2003 and December 31, 2012. A retrospective review was performed to identify patients with both (1) an acute aortic dissection after a prior aortic dissection and (2) evidence of a new dissection within a previously dissected aortic segment creating a triple lumen aorta. Data were reviewed to identify factors predisposing to dissection of a previously dissected aortic segment. Results. Over a 10-year period we identified 5 cases of aortic dissection within a previously dissected aortic segment presenting as a new acute aortic syndrome. On average, the recurrent dissection occurred 1 decade after the first aortic dissection (mean [9.8 +/- 1.9 years). Patients identified in this series were significantly younger at first dissection and more likely to carry the diagnosis of Marfan syndrome. Aortic aneurysm diameter was quantified before and after the new dissection event and demonstrated a marked increase in aneurysmal size (mean increase [1.6 +/- 0.3 cm). Conclusions. We conclude that medial degeneration, as seen in the Marfan aorta, represents a predisposing factor for recurrent dissection of the dissected aorta. Our data indicate that double aortic dissections cause significant arterial destabilization and a low threshold for surgical intervention is appropriate. (C) 2015 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,MGH Cardiovasc Res Ctr, MGH Thorac Aort Ctr,Div Cardiac Surg,Div Cardiol, MGH Heart Ctr,Div Vasc & Endovasc Surg,Dept Med, Boston, MA 02114 USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, 55 Fruit St,Yawkey 5B, Boston, MA 02114 USA. EM eisselbacher@mgh.harvard.edu NR 25 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2015 VL 99 IS 5 BP 1616 EP 1623 DI 10.1016/j.athoracsur.2014.12.066 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CH2TP UT WOS:000353877900033 PM 25818572 ER PT J AU Zhao, GF Seng, JJ Beagle, J Syrkina, O Hales, CA AF Zhao, Gaofeng Seng, Jingjing Beagle, John Syrkina, Olga Hales, Charles A. TI Heparin Reduces Overcirculation-Induced Pulmonary Artery Remodeling Through P38 MAPK in Piglet SO ANNALS OF THORACIC SURGERY LA English DT Article ID SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR; RAT MODEL; INHIBITION; PROLIFERATION; HYPERTENSION; MIGRATION; MECHANISMS; COLLAGEN; BINDING AB Background. Artery remodeling is the principal change of pulmonary artery hypertension. Heparin has been shown to inhibit vascular smooth muscle cell proliferation. We hypothesized that heparin may modulate vascular remodeling in pulmonary artery hypertension, and explored the mechanism. Methods. A localized overcirculation-induced artery remodeling was created in piglets by anastomosing the left lower lobe pulmonary artery (LLLPA) to the thoracic aortic artery. Piglets were treated with heparinor saline for 4 weeks. Hemodynamic data were collected, and histology of the lung was assessed. We investigated the expressions of several candidate genes in lung and further observed the involvement of P3W8 mitogen-activated protein kinases (MAPK). The effects of heparin on the growth of cultured pulmonary arterial vascular smooth muscle cell and P38 MAPK expression were further determined under various conditions. Results. Four weeks after the shunt setup, over-circulation caused significant LLLPA remodeling, pressure increase, and pulmonary vascular resistance increase, and LLLPA flow reduction compared with that immediately after the shunt setup. Heparin reduced the LLLPA remodeling, pressure, and pulmonary vascular resistance, and increased the LLLPA flow compared with that not heparin treated. Shunt and heparin treatment did not change the piglet's systemic hemodynamics. Shunt increased the expression of P38 MAPK and heparin decreased its expression in the shunted LLLPA. Both heparin and P38 MAPK inhibitor suppressed VSMC growth and P38 MAPK expression in the cultured VSMC, but they did not present additive effects when the two treatments were combined. Conclusions. Heparin reduces overcirculation-induced pulmonary artery remodeling through a P38 MAPK dependent pathway. (C) 2015 by The Society of Thoracic Surgeons C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm Crit Care Unit, Boston, MA 02114 USA. Zhengzhou Univ, Affiliated Hosp 1, Dept Surg, Zhengzhou 450052, Henan, Peoples R China. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Hales, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit, 55 Fruit St, Boston, MA 02114 USA. EM chales@partners.org FU National Institutes of Health [HL039150] FX This work was supported by National Institutes of Health Grant HL039150 to Dr Hales. NR 20 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2015 VL 99 IS 5 BP 1677 EP 1684 DI 10.1016/j.athoracsur.2014.12.061 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CH2TP UT WOS:000353877900043 PM 25818573 ER PT J AU Paulson, D Horner, MD Bachman, D AF Paulson, Daniel Horner, Michael David Bachman, David TI A Comparison of Four Embedded Validity Indices for the RBANS in a Memory Disorders Clinic SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Assessment; Response validity; Effort testing; Aging; Malingering; Index validation; Cognitive evaluation ID TRAUMATIC BRAIN-INJURY; MALINGERED NEUROCOGNITIVE DYSFUNCTION; NEUROPSYCHOLOGICAL STATUS RBANS; POSTTRAUMATIC-STRESS-DISORDER; REPEATABLE BATTERY; COGNITIVELY INTACT; GERIATRIC SAMPLE; TEST-PERFORMANCE; NORMATIVE DATA; OLDER-ADULTS AB This examination of four embedded validity indices for the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) explores the potential utility of integrating cognitive and self-reported depressive measures. Examined indices include the proposed RBANS Performance Validity Index (RBANS PVI) and the Charleston Revised Index of Effort for the RBANS (CRIER). The CRIER represented the novel integration of cognitive test performance and depression self-report information. The sample included 234 patients without dementia who could be identified as having demonstrated either valid or invalid responding, based on standardized criteria. Sensitivity and specificity for invalid responding varied widely, with the CRIER emerging as the best all-around index (sensitivity = 0.84, specificity = 0.90, AUC = 0.94). Findings support the use of embedded response validity indices, and suggest that the integration of cognitive and self-report depression data may optimize detection of invalid responding among older Veterans. C1 [Paulson, Daniel] Univ Cent Florida, Dept Psychol, Orlando, FL 32816 USA. [Paulson, Daniel; Horner, Michael David; Bachman, David] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [Horner, Michael David; Bachman, David] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Bachman, David] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. RP Paulson, D (reprint author), Univ Cent Florida, Dept Psychol, Orlando, FL 32816 USA. EM daniel.paulson2@ucf.edu NR 40 TC 1 Z9 1 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAY PY 2015 VL 30 IS 3 BP 207 EP 216 DI 10.1093/arclin/acv009 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA CH1ZO UT WOS:000353822600005 PM 25783523 ER PT J AU Kozhemyakina, E Zhang, MJ Ionescu, A Ayturk, UM Ono, N Kobayashi, A Kronenberg, H Warman, ML Lassar, AB AF Kozhemyakina, Elena Zhang, Minjie Ionescu, Andreia Ayturk, Ugur M. Ono, Noriaki Kobayashi, Akio Kronenberg, Henry Warman, Matthew L. Lassar, Andrew B. TI Identification of a Prg4-Expressing Articular Cartilage Progenitor Cell Population in Mice SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID VARA-PERICARDITIS SYNDROME; SYNOVIAL JOINT; GROWTH-PLATE; EXPRESSION; DIFFERENTIATION; SKELETOGENESIS; PROLIFERATION; MAINTENANCE; LUBRICIN; HEDGEHOG AB Objective. To generate knockin mice that express a tamoxifen-inducible Cre recombinase from the Prg4 locus (Prg4(GFPCreERt2) mice) and to use these animals to fate-map the progeny of Prg4-positive articular cartilage cells at various ages. Methods. We crossed Prg4(GFPCreERt2) mice with Rosa26(floxlacZ) or Rosa26(mTmG) reporter strains, administered tamoxifen to the double heterozygous offspring at different ages, and assayed Cre-mediated recombination by histochemistry and/or fluorescence microscopy. Results. In 1-month-old mice, the expression of the Prg4(GFPCreERt2) allele mirrored the expression of endogenous Prg4 and, when tamoxifen was administered for 10 days, caused Cre-mediated recombination in similar to 70% of the superficial-most chondrocytes. Prg4(GFPCreERt2) -expressing cells were mostly confined to the top 3 cell layers of the articular cartilage in 1-month-old mice, but descendants of these cells were located in deeper regions of the articular cartilage in aged mice. On embryonic day 17.5, Prg4(GFPCreERt2)-expressing cells were largely restricted to the superficial-most cell layer of the forming joint, yet at similar to 1 year, the progeny of these cells spanned the depth of the articular cartilage. Conclusion. Our results suggest that Prg4-expressing cells located at the joint surface in the embryo serve as a progenitor population for all deeper layers of the mature articular cartilage. Also, our findings indicate that Prg4(GFPCreERt2) is expressed by superficial chondrocytes in young mice, but expands into deeper regions of the articular cartilage as the animals age. The Prg4(GFPCreERt2) allele should be a useful tool for inducing efficient Cre-mediated recombination of loxP-flanked alleles at sites of Prg4 expression. C1 [Kozhemyakina, Elena; Zhang, Minjie; Ionescu, Andreia; Ayturk, Ugur M.; Warman, Matthew L.] Harvard Univ, Sch Med, Boston, MA USA. [Zhang, Minjie; Ayturk, Ugur M.; Warman, Matthew L.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA USA. [Kronenberg, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kobayashi, Akio] Univ Washington, Seattle, WA 98195 USA. RP Warman, ML (reprint author), Boston Childrens Hosp, Dept Orthopaed Surg, 320 Longwood Ave,Room EN250, Boston, MA 02115 USA. EM matthew.warman@childrens.harvard.edu; andrew_lassar@hms.harvard.edu FU NIH (National Institute of Dental and Craniofacial Research) [K99-DE-022564]; NIH (National Institute of Diabetes and Digestive and Kidney Diseases) [R01-DK-094933]; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [P01-DK-56246, R01-AR-050180, R21-AR-055148, R01-AR-055552]; Battelle Japan FX Supported by the NIH (National Institute of Dental and Craniofacial Research grant K99-DE-022564 to Dr. Ono, National Institute of Diabetes and Digestive and Kidney Diseases grant R01-DK-094933 to Dr. Kobayashi, and National Institute of Arthritis and Musculoskeletal and Skin Diseases grants P01-DK-56246 to Dr. Kronenberg, R01-AR-050180 to Dr. Warman, and R21-AR-055148 and R01-AR-055552 to Dr. Lassar).; Dr. Kobayashi has received consulting fees, speaking fees, and/or honoraria from Battelle Japan (less than $10,000). NR 29 TC 23 Z9 23 U1 2 U2 7 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 MAY PY 2015 VL 67 IS 5 BP 1261 EP 1273 DI 10.1002/art.39030 PG 13 WC Rheumatology SC Rheumatology GA CH1IV UT WOS:000353775900016 PM 25603997 ER PT J AU Kim, J Loggia, ML Cahalan, CM Harris, RE Beissner, F Garcia, RG Kim, H Barbieri, R Wasan, AD Edwards, RR Napadow, V AF Kim, Jieun Loggia, Marco L. Cahalan, Christine M. Harris, Richard E. Beissner, Florian Garcia, Ronald G. Kim, Hyungjun Barbieri, Riccardo Wasan, Ajay D. Edwards, Robert R. Napadow, Vitaly TI The Somatosensory Link in Fibromyalgia Functional Connectivity of the Primary Somatosensory Cortex Is Altered by Sustained Pain and Is Associated With Clinical/Autonomic Dysfunction SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID HEART-RATE-VARIABILITY; INTRINSIC BRAIN CONNECTIVITY; CLINICAL PAIN; TEMPORAL SUMMATION; ANTERIOR INSULA; CUFF ALGOMETRY; BACK-PAIN; NETWORK; VALIDATION; INVENTORY AB Objective. Fibromyalgia (FM) is a chronic functional pain syndrome characterized by widespread pain, significant pain catastrophizing, sympathovagal dysfunction, and amplified temporal summation for evoked pain. While several studies have demonstrated altered resting brain connectivity in FM, studies have not specifically probed the somatosensory system and its role in both somatic and nonsomatic FM symptoms. Our objective was to evaluate resting primary somatosensory cortex (S1) connectivity and to explore how sustained, evoked deep tissue pain modulates this connectivity. Methods. We acquired functional magnetic resonance imaging and electrocardiography data on FM patients and healthy controls during rest (the rest phase) and during sustained mechanical pressure-induced pain over the lower leg (the pain phase). Functional connectivity associated with different S1 subregions was calculated, while S1(leg) connectivity (representation of the leg in the primary somatosensory cortex) was contrasted between the rest phase and the pain phase and was correlated with clinically relevant measures in FM. Results. During the rest phase, FM patients showed decreased connectivity between multiple ipsilateral and cross-hemispheric S1 subregions, which was correlated with clinical pain severity. Compared to the rest phase, the pain phase produced increased S1(leg) connectivity to the bilateral anterior insula in FM patients, but not in healthy controls. Moreover, in FM patients, sustained pain-altered S1(leg) connectivity to the anterior insula was correlated with clinical/behavioral pain measures and autonomic responses. Conclusion. Our study demonstrates that both somatic and nonsomatic dysfunction in FM, including clinical pain, pain catastrophizing, autonomic dysfunction, and amplified temporal summation, are closely linked with the degree to which evoked deep tissue pain alters S1 connectivity to salience/affective pain-processing regions. Additionally, diminished connectivity between S1 subregions during the rest phase in FM may result from ongoing widespread clinical pain. C1 [Kim, Jieun; Beissner, Florian; Garcia, Ronald G.; Kim, Hyungjun; Barbieri, Riccardo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kim, Jieun; Loggia, Marco L.; Cahalan, Christine M.; Beissner, Florian; Garcia, Ronald G.; Barbieri, Riccardo; Edwards, Robert R.; Napadow, Vitaly] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Jieun; Kim, Hyungjun] Korea Inst Oriental Med, Taejon, South Korea. [Loggia, Marco L.; Napadow, Vitaly] Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA USA. [Cahalan, Christine M.; Edwards, Robert R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Harris, Richard E.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Beissner, Florian] Hannover Med Sch, Hannover, Germany. [Garcia, Ronald G.] Univ Santander, Sch Med, Bucaramanga, Colombia. [Wasan, Ajay D.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Napadow, Vitaly] Kyung Hee Univ, Yongin, South Korea. RP Kim, J (reprint author), Martinos Ctr Biomed Imaging, 149 13th St,Bldg 149,Suite 2301, Charlestown, MA 02129 USA. EM seesawu@gmail.com OI Barbieri, Riccardo/0000-0001-9381-3833; Garcia, Ronald Gerardo/0000-0002-8325-9944 FU National Center for Complementary and Alternative Medicine, NIH [P01-AT-006663, R01-AT-007550, R01-AR-064367, R21-AR-057920]; Korea Institute of Oriental Medicine [K15050, K15070]; German Research Foundation [BE4677/1-1]; Arthritis Foundation; Rheumatology Research Foundation; Pfizer; Analgesic Solutions; Zogenix FX Supported by the National Center for Complementary and Alternative Medicine, NIH (grants P01-AT-006663, R01-AT-007550, R01-AR-064367, and R21-AR-057920), the Korea Institute of Oriental Medicine (grants K15050 and K15070), the German Research Foundation (grant BE4677/1-1), and in part by the Arthritis Foundation and the Rheumatology Research Foundation through grants to Dr. Edwards.; Dr. Harris has received consulting fees and honoraria from Pfizer (less than $10,000) and grant support from Pfizer. Dr. Wasan has received consulting fees, speaking fees, and/or honoraria from Analgesic Solutions and Zogenix (less than $10,000 each). NR 53 TC 14 Z9 14 U1 2 U2 11 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 MAY PY 2015 VL 67 IS 5 BP 1395 EP 1405 DI 10.1002/art.39043 PG 11 WC Rheumatology SC Rheumatology GA CH1IV UT WOS:000353775900031 PM 25622796 ER PT J AU Holstein, SA Richardson, PG Laubach, JP McCarthy, PL AF Holstein, Sarah A. Richardson, Paul G. Laubach, Jacob P. McCarthy, Philip L. TI Management of Relapsed Multiple Myeloma after Autologous Stem Cell Transplant SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Multiple myeloma salvage autologous stem cell transplant; Salvage allogenic stem cell transplant; Monoclonal antibody; Relapsed/refractory ID HIGH-DOSE MELPHALAN; ALLOGENEIC TRANSPLANTATION; 1ST AUTOGRAFT; PHASE-3 TRIAL; OPEN-LABEL; AUTO-SCT; BORTEZOMIB; THERAPY; MULTICENTER; MAINTENANCE AB Autologous stem cell transplantation (ASCT) remains a standard of care for multiple myeloma patients who are eligible to receive high-dose therapy, recognizing that the optimal timing and integration of this approach is now under study in a number of randomized trials. Despite the improved response rates with induction therapy consisting of immunomodulatory drugs and/or proteasome inhibitors, as well as the increasing use of post-ASCT maintenance therapy, most myeloma patients relapse and die of their disease. Here we discuss the options for managing post-ASCT relapse, including the role of various salvage regimens in the setting of relapsed and refractory myeloma, salvage ASCT, and salvage allogeneic SCT. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Holstein, Sarah A.; McCarthy, Philip L.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Richardson, Paul G.; Laubach, Jacob P.] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. RP McCarthy, PL (reprint author), Roswell Pk Canc Inst, Blood & Marrow Transplant Program, Buffalo, NY 14263 USA. EM plmcc54@gmail.com FU Onyx; Novartis; Celgene; Millennium FX S.A.H. has served on advisory boards and received honoraria from Celgene and Millennium. P.G.R. has served on advisory boards and received honoraria from Celgene, Johnson & Johnson, Millennium, Novartis, and Bristol Myers Squibb. J.P.L. ha S received research funding from Onyx, Novartis, Celgene, and Millennium. P.L.M. has served on advisory boards and received honoraria from Celgene, Millennium, Sanofi, Onyx, and Janssen. NR 45 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2015 VL 21 IS 5 BP 793 EP 798 DI 10.1016/j.bbmt.2014.12.026 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CH2LM UT WOS:000353856700003 PM 25652690 ER PT J AU Au, BKC Gooley, TA Armand, P Fang, M Madtes, DK Sorror, ML Boeckh, MJ Gibson, CJ Deeg, HJ Storb, R Appelbaum, FR Chien, JW Martin, PJ AF Au, Brandon K. C. Gooley, Ted A. Armand, Philippe Fang, Min Madtes, David K. Sorror, Mohamed L. Boeckh, Michael J. Gibson, Christopher J. Deeg, Hans Joachim Storb, Rainer Appelbaum, Frederick R. Chien, Jason W. Martin, Paul J. TI Reevaluation of the Pretransplant Assessment of Mortality Score after Allogeneic Hematopoietic Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic hematopoietic cell transplantation; Survival; Comorbidity; Risk assessment ID INTERNATIONAL PROGNOSTIC INDEX; STEM-CELL TRANSPLANTATION; RISK-ASSESSMENT; LYMPHOMA; PREDICTOR; DISEASE; MODELS; VALUES; OLDER; HCT AB The Pretransplant Assessment of Mortality (PAM) score was developed in 2006 to predict risk of mortality after allogeneic hematopoietic cell transplantation (HCT). Transplant practices have evolved during the past decade, suggesting the need to reevaluate the performance of the PAM score. We used statistical modeling to analyze and recalibrate mortality based on overall PAM scores, its components, and conditioning regimen in a retrospective cohort of 1549 patients who had HCT from 2003 through 2009. PAM scores correlated with mortality, but the effect size was smaller in the current study than in previous studies. PAM scores also demonstrated a stronger association with mortality in patients who received myeloablative conditioning than in those who received reduced-intensity conditioning. In contrast to the original study, carbon monoxide diffusing capacity, serum alanine aminotransferase, and serum creatinine concentrations were no longer significantly associated with 2-year mortality, whereas patient and donor cytomegalovirus serology was associated with mortality in the current cohort. Based on our findings, we developed and tested a revised PAM score for clinicians to estimate survival after allogeneic HCT with myeloablative conditioning regimens for patients with hematologic malignancy. Prognostic models such as the PAM score should be updated and recalibrated periodically to accommodate changes in clinical practice. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Au, Brandon K. C.] Univ Washington, Dept Med, Seattle, WA USA. [Gooley, Ted A.; Fang, Min; Chien, Jason W.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Armand, Philippe] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Madtes, David K.; Sorror, Mohamed L.; Boeckh, Michael J.; Deeg, Hans Joachim; Storb, Rainer; Appelbaum, Frederick R.; Martin, Paul J.] Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Med, Div Clin Res, Seattle, WA 98195 USA. [Gibson, Christopher J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Martin, PJ (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024,1100 Fairview Ave N, Seattle, WA 98109 USA. EM pmartin@fhcrc.org FU National Cancer Institute [CA18029, CA78902, CA15704] FX Supported by grants CA18029, CA78902, and CA15704 from the National Cancer Institute. NR 27 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2015 VL 21 IS 5 BP 848 EP 854 DI 10.1016/j.bbmt.2015.01.011 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CH2LM UT WOS:000353856700009 PM 25644959 ER PT J AU Kim, HT Armand, P Frederick, D Andler, E Cutler, C Koreth, J Alyea, EP Antin, JH Soiffer, RJ Ritz, J Ho, VT AF Kim, Haesook T. Armand, Philippe Frederick, David Andler, Emily Cutler, Corey Koreth, John Alyea, Edwin P., III Antin, Joseph H. Soiffer, Robert J. Ritz, Jerome Ho, Vincent T. TI Absolute Lymphocyte Count Recovery after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Clinical Outcome SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Lymphocyte; Absolute lymphocyte count (ALC); Hematopoietic stem cell transplantation (HSCT) ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MONOCYTE RECOVERY; RISK; MALIGNANCIES; RELAPSE; DISEASE; IMPACT; INDEX AB Immune reconstitution is critical for clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). To determine the impact of absolute lymphocyte count (ALC) recovery on clinical outcomes, we conducted a retrospective study of 1109 adult patients who underwent a first allogeneic HSCT from 2003 through 2009, excluding patients who died or relapsed before day 30. The median age was 51 years (range, 18 to 74) with 52% undergoing reduced-intensity conditioning and 48% undergoing myeloablative conditioning HSCT with T cell-replete peripheral blood stem cells (93.7%) or marrow (6.4%) grafts. The median follow-up time was 6 years. To determine the threshold value of ALC for survival, the entire cohort was randomly split into a training set and a validation set in a 1:1 ratio, and then a restricted cubic spline smoothing method was applied to obtain relative hazard estimates of the relationship between ALC at 1 month and log hazard of progression-free survival (PFS). Based on this approach, ALC was categorized as <=.2 x 10(9) cells/L (low) or >.2 x 10(9) cells/L. For patients with low ALC at 1, 2, or 3 months after HSCT, the overall survival (OS) (P <= .0001) and PFS (P <= .0002) were significantly lower and nonrelapse mortality (NRM) (P <= .002) was significantly higher compared with patients with ALC > .2 x 10(9) cells/L at each time point. When patients who had low ALC at 1, 2, or 3 months after HSCT were grouped together and compared, their outcomes were inferior to those of patients who had ALC > .2 x 10(9) cells/L at 1, 2, and 3 months after HSCT: the 5-year OS for patients with low ALC was 28% versus 46% for patients with ALC > .2 x 10(9) cells/L, P < .0001; the 5-year PFS was 21% versus 39%, P < .0001, respectively and 5-year NRM was 40% versus 18%, P < .0001, respectively. This result remained consistent when other prognostic factors, including occurrence of grade II to IV acute graft-versus-host disease (GVHD), were adjusted for in multivariable Cox models stratified by conditioning intensity: hazard ratio (HR) for OS: 1.52; P <= .0001; for PFS: 1.42; P = .0008; and for NRM: 2.4 P < .0001 for patients with low ALC. Low ALC was not significantly associated with relapse (HR, 1.01; P = .92) in the multivariable model. Low ALC early after HSCT is an independent risk factor for increased NRM and poor survival independent of grade II to IV acute GVHD. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Armand, Philippe; Frederick, David; Andler, Emily; Cutler, Corey; Koreth, John; Alyea, Edwin P., III; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome; Ho, Vincent T.] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02215 USA. RP Kim, HT (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM kim.haesook@jimmy.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU National Institutes of Health/National Cancer Institute [P01 CA142106-10, R01 CA183559-01] FX This study was supported in part by the National Institutes of Health/National Cancer Institute (P01 CA142106-10, R01 CA183559-01). NR 16 TC 8 Z9 8 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2015 VL 21 IS 5 BP 873 EP 880 DI 10.1016/j.bbmt.2015.01.019 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CH2LM UT WOS:000353856700013 PM 25623931 ER PT J AU Shulman, DS London, WB Guo, DJ Duncan, CN Lehmann, LE AF Shulman, David Stephen London, Wendy B. Guo, Dongjing Duncan, Christine N. Lehmann, Leslie E. TI Incidence and Causes of Hospital Readmission in Pediatric Patients after Hematopoietic Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Bone marrow transplantation; Stem cell transplantation; Readmission; Quality improvement ID CORD BLOOD TRANSPLANTATION; IMMUNE RECONSTITUTION; RISK-FACTORS; INFANTS AB Allogeneic (allo) and autologous (auto) hematopoietic cell transplantation (HCT) provide the potential to cure otherwise fatal diseases but they are resource-intense therapies. There is scant literature describing the burden of hospital readmission in the critical 6-month period of immunosuppression after HCT. We report the incidence, causes, and outcomes of readmission in the 6 months after day 0 of HCT and in the 30 days after hospital discharge. This study is an institutional review board approved retrospective medical record review of children who underwent HCT at a single institution. Between January 1, 2008 and December 31, 2011, 291 children underwent HCT at our institute. Of these, 140 patients were excluded because they were not followed primarily at our institute for the first 6 months after transplantation, 14 patients were excluded because they died during their initial hospitalization, and 1 patient was excluded because the initial hospitalization was longer than 6 months. Of the remaining 136 patients, 63% had at least 1 readmission. Of the patients who underwent allo-HCT, 78% were readmitted, in contrast to 38% of auto-HCT patients (P < .001). For the 206 readmissions, the mean length of hospital stay was 10.7 days (range, 1 to 129). Seventy-two percent of auto-HCT patients were initially readmitted for fever, and 46% ultimately had a source identified. No risk factors for readmission were found in the auto-HCT group. Fifty-two percent of allo-HCT patients were readmitted for fever and 28% of these patients ultimately had an identified source. Gastrointestinal-related problems accounted for 30% of primary readmissions among allo-HCT patients. Patients with an unrelated donor had a trend towards increased rates of 30-day readmission (P = .06) and were more likely to have a second readmission (P = .002). Patients who were cytomegalovirus (CMV) positive before transplantation were more likely to be readmitted (P = .02). The majority of children who undergo HCT are readmitted during the critical 180 days after transplantation. Readmission is much more common among allo-Ha patients, in particular those with unrelated donors and CMV-positive serologies before transplantation. Fever is the most common cause of readmission in these patients, and serious infections are identified in a significant portion of patients. These findings and future research in this area will help improve both patient education and resource utilization. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Shulman, David Stephen] Boston Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. [London, Wendy B.; Duncan, Christine N.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Guo, Dongjing] Boston Childrens Hosp, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Lehmann, Leslie E.] Boston Childrens Hosp, Dana Farber Canc Inst, Pediat Stem Cell Transplantat Ctr, Boston, MA 02115 USA. RP Shulman, DS (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM davidsshulman@gmail.com NR 15 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2015 VL 21 IS 5 BP 913 EP 919 DI 10.1016/j.bbmt.2015.01.027 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CH2LM UT WOS:000353856700019 PM 25667988 ER PT J AU Khan, S Michmizos, K Tommerdahl, M Ganesan, S Kitzbichler, MG Zetino, M Garel, KLA Herbert, MR Hamalainen, MS Kenet, T AF Khan, Sheraz Michmizos, Konstantinos Tommerdahl, Mark Ganesan, Santosh Kitzbichler, Manfred G. Zetino, Manuel Garel, Keri-Lee A. Herbert, Martha R. Hamalainen, Matti S. Kenet, Tal TI Somatosensory cortex functional connectivity abnormalities in autism show opposite trends, depending on direction and spatial scale SO BRAIN LA English DT Article DE magnetoencephalography; coherence; biomarker; steady-state; vibrotactile; mu-rhythm; autism spectrum disorder ID SPACE SEPARATION METHOD; SURFACE-BASED ANALYSIS; TOP-DOWN MODULATION; SPECTRUM DISORDERS; BRAIN CONNECTIVITY; EVOKED-RESPONSES; CORTICAL SURFACE; EEG-DATA; COORDINATE SYSTEM; MU RHYTHM AB Functional connectivity is abnormal in autism, but the nature of these abnormalities remains elusive. Different studies, mostly using functional magnetic resonance imaging, have found increased, decreased, or even mixed pattern functional connectivity abnormalities in autism, but no unifying framework has emerged to date. We measured functional connectivity in individuals with autism and in controls using magnetoencephalography, which allowed us to resolve both the directionality (feedforward versus feedback) and spatial scale (local or long-range) of functional connectivity. Specifically, we measured the cortical response and functional connectivity during a passive 25-Hz vibrotactile stimulation in the somatosensory cortex of 20 typically developing individuals and 15 individuals with autism, all males and right-handed, aged 8-18, and the mu-rhythm during resting state in a subset of these participants (12 per group, same age range). Two major significant group differences emerged in the response to the vibrotactile stimulus. First, the 50-Hz phase locking component of the cortical response, generated locally in the primary (S1) and secondary (S2) somatosensory cortex, was reduced in the autism group (P < 0.003, corrected). Second, feedforward functional connectivity between S1 and S2 was increased in the autism group (P < 0.004, corrected). During resting state, there was no group difference in the mu-a rhythm. In contrast, the mu-beta rhythm, which has been associated with feedback connectivity, was significantly reduced in the autism group (P < 0.04, corrected). Furthermore, the strength of the mu-beta was correlated to the relative strength of 50 Hz component of the response to the vibrotactile stimulus (r = 0.78, P < 0.00005), indicating a shared aetiology for these seemingly unrelated abnormalities. These magnetoencephalography-derived measures were correlated with two different behavioural sensory processing scores (P < 0.01 and P < 0.02 for the autism group, P < 0.01 and P < 0.0001 for the typical group), with autism severity (P < 0.03), and with diagnosis (89% accuracy). A biophysically realistic computational model using data driven feedforward and feedback parameters replicated the magnetoencephalography data faithfully. The direct observation of both abnormally increased and abnormally decreased functional connectivity in autism occurring simultaneously in different functional connectivity streams, offers a potential unifying framework for the unexplained discrepancies in current findings. Given that cortical feedback, whether local or long-range, is intrinsically non-linear, while cortical feedforward is generally linear relative to the stimulus, the present results suggest decreased non-linearity alongside an increased veridical component of the cortical response in autism. C1 [Khan, Sheraz; Michmizos, Konstantinos; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Garel, Keri-Lee A.; Herbert, Martha R.; Kenet, Tal] Harvard Univ, Sch Med, Dept Neurol, MGH, Boston, MA 02115 USA. [Khan, Sheraz; Michmizos, Konstantinos; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Garel, Keri-Lee A.; Herbert, Martha R.; Hamalainen, Matti S.; Kenet, Tal] MGH MIT Harvard, AA Martinos Ctr Biomed Imaging, Boston, MA USA. [Tommerdahl, Mark] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC USA. [Hamalainen, Matti S.] Harvard Univ, Sch Med, Dept Radiol, MGH, Boston, MA 02115 USA. [Hamalainen, Matti S.] Aalto Univ, Sch Sci, Dept Neurosci & Biomed Engn, Espoo, Finland. RP Kenet, T (reprint author), Massachusetts Gen Hosp, 149 13th St CNY 2275, Charlestown, MA 02129 USA. EM tal@nmr.mgh.harvard.edu OI Garel, Keri-Lee/0000-0002-9198-6535; Khan, Sheraz/0000-0002-6792-3577 FU Nancy Lurie Marks Family Foundation; Autism Speaks; Simons Foundation [SFARI 239395]; National Institute of Child Health and Development [R01HD073254]; National Centre for Research Resources [P41EB015896]; National Institute for Biomedical Imaging and Bioengineering [5R01EB009048]; Cognitive Rhythms Collaborative: A Discovery Network [NFS 1042134] FX This work was supported by grants from the Nancy Lurie Marks Family Foundation (T.K., S.K.), Autism Speaks (T.K.), The Simons Foundation (SFARI 239395, T.K.), The National Institute of Child Health and Development (R01HD073254, T.K.), The National Centre for Research Resources (P41EB015896, M.S.H.), National Institute for Biomedical Imaging and Bioengineering (5R01EB009048, M.S.H.), and the Cognitive Rhythms Collaborative: A Discovery Network (NFS 1042134, M.S.H.). Article needs to be deposited in PMC. NR 79 TC 9 Z9 9 U1 1 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD MAY 1 PY 2015 VL 138 BP 1394 EP 1409 DI 10.1093/brain/awv043 PN 5 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH2DB UT WOS:000353834100032 PM 25765326 ER PT J AU Fling, BW Nutt, JG Horak, FB AF Fling, Brett W. Nutt, John G. Horak, Fay B. TI Reply: Does dominant pedunculopontine nucleus exist? Probably not SO BRAIN LA English DT Letter ID MULTIPLE SYSTEM ATROPHY; PARKINSONS-DISEASE; HEMIPARKINSONS-DISEASE; GAIT; DISTURBANCES; INHIBITION C1 [Fling, Brett W.; Nutt, John G.; Horak, Fay B.] Oregon Hlth & Sci Univ, Sch Med, Dept Neurol, Portland, OR 97239 USA. [Fling, Brett W.; Horak, Fay B.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Fling, BW (reprint author), Oregon Hlth & Sci Univ, Sch Med, Dept Neurol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM fling@ohsu.edu FU NIA NIH HHS [R01 AG006457]; RRD VA [I01 RX001075] NR 22 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD MAY 1 PY 2015 VL 138 BP E347 EP U7 DI 10.1093/brain/awu317 PN 5 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH2DB UT WOS:000353834100002 PM 25367026 ER PT J AU Reichardt, P Kang, YK Rutkowski, P Schuette, J Rosen, LS Seddon, B Yalcin, S Gelderblom, H Williams, CC Fumagalli, E Biasco, G Hurwitz, HI Kaiser, PE Fly, K Matczak, E Chen, L Lechuga, MJ Demetri, GD AF Reichardt, Peter Kang, Yoon-Koo Rutkowski, Piotr Schuette, Jochen Rosen, Lee S. Seddon, Beatrice Yalcin, Suayib Gelderblom, Hans Williams, Charles C., Jr. Fumagalli, Elena Biasco, Guido Hurwitz, Herbert I. Kaiser, Pamela E. Fly, Kolette Matczak, Ewa Chen, Liang Lechuga, Maria Jose Demetri, George D. TI Clinical Outcomes of Patients With Advanced Gastrointestinal Stromal Tumors: Safety and Efficacy in a Worldwide Treatment-Use Trial of Sunitinib SO CANCER LA English DT Article DE sunitinib; gastrointestinal stromal tumor; treatment-use trial; long-term safety; efficacy; worldwide ID IMATINIB; MUTATIONS; PLACEBO AB BACKGROUNDThe objectives of this study were to provide sunitinib to patients with gastrointestinal stromal tumor (GIST) who were otherwise unable to obtain it and to collect broad safety and efficacy data from a large population of patients with advanced GIST after imatinib failure. METHODSImatinib-resistant/intolerant patients with advanced GIST received sunitinib on an initial dosing schedule of 50 mg daily in 6-week cycles (4 weeks on treatment, 2 weeks off treatment). Tumor assessment frequency was according to local practice, and response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors version 1.0. Overall survival (OS) and safety were assessed regularly. Post hoc analyses evaluated different patterns of treatment management. RESULTSAt final data cutoff, 1124 patients comprised the intent-to-treat population, and 15% of these patients had a baseline Eastern Cooperative Oncology Group performance status 2. The median treatment duration was 7.0 months. The median time to tumor progression was 8.3 months (95% confidence interval [CI], 8.0-9.4 months), the median OS was 16.6 months (95% CI, 14.9-18.0 months), and 36% of patients were alive at the time of analysis. Patients for whom the initial dosing schedule was modified exhibited longer median OS (23.5 months) than those who were treated strictly according to the initial dosing schedule (11.1 months). The most common treatment-related grade 3 and 4 adverse events were hand-foot syndrome (11%), fatigue (9%), neutropenia (8%), hypertension (7%), and thrombocytopenia (6%). Treatment-related adverse events associated with cardiac function (eg, congestive heart failure and myocardial infarction) were reported at frequencies of 1% each. CONCLUSIONSThis treatment-use study confirms the long-term safety and efficacy of sunitinib in a large international population of patients with advanced GIST after imatinib failure. Cancer 2015;121:1405-1413. (c) 2015 American Cancer Society. Final results from a worldwide treatment-use study of sunitinib in gastrointestinal stromal tumor (GIST) add to the existing body of evidence supporting the long-term safety and efficacy of sunitinib in an international population of patients with advanced GIST after failure on first-line imatinib who were ineligible for other sunitinib clinical trials. These data expand results reported in the more restricted and selected population of patients accrued to the phase 3 study of sunitinib in GIST. C1 [Reichardt, Peter] HELIOS Clin Berlin Buch, Dept Interdisciplinary Oncol, Berlin, Germany. [Kang, Yoon-Koo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Rutkowski, Piotr] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Rutkowski, Piotr] Inst Oncol, Warsaw, Poland. [Rosen, Lee S.] Univ Calif Los Angeles, Div Hematol Oncol, Santa Monica, CA USA. [Seddon, Beatrice] Univ Coll London Hosp, Dept Oncol, London, England. [Yalcin, Suayib] Hacettepe Univ, Inst Canc, Dept Med Oncol, Ankara, Turkey. [Gelderblom, Hans] Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. [Williams, Charles C., Jr.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Fumagalli, Elena] Inst Res & Treatment Canc, Milan Canc Inst, Dept Canc Med, Milan, Italy. [Biasco, Guido] Univ Bologna, Dept Hematol & Oncol Sci, Bologna, Italy. [Hurwitz, Herbert I.] Duke Univ, Med Ctr, Div Med Oncol, Durham, NC USA. [Kaiser, Pamela E.] Lutheran Gen Canc Care Ctr, Oncol Specialists SC, Park Ridge, IL USA. [Fly, Kolette] Pfizer Oncol, Groton, CT USA. [Matczak, Ewa; Chen, Liang] Pfizer Oncol, New York, NY USA. [Lechuga, Maria Jose] Pfizer Oncol, Milan, Italy. [Demetri, George D.] Ludwig Ctr Harvard, Boston, MA USA. [Demetri, George D.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Dept Med Oncol, Boston, MA 02115 USA. RP Reichardt, P (reprint author), HELIOS Klinikum Berlin Buch, Dept Interdisciplinary Oncol, Schwanebecker Chaussee 50, D-13125 Berlin, Germany. EM peter.reichardt@helios-kliniken.de RI Fumagalli, Elena Rosa/E-2065-2017; OI Fumagalli, Elena Rosa/0000-0003-4814-7637; Rutkowski, Piotr/0000-0002-8920-5429 FU Pfizer; Virginia and Daniel K. Ludwig Trust for Cancer Research; Paul's Posse of the Pan Mass Challenge; Team Russo; US National Cancer Institute [CA127003]; Pfizer Inc FX This study was sponsored by Pfizer. Additional support to Dr. Demetri was provided by the Virginia and Daniel K. Ludwig Trust for Cancer Research, Paul's Posse of the Pan Mass Challenge, Team Russo, and Specialized Programs of Research Excellence (SPOREs) grant CA127003 from the US National Cancer Institute. Medical writing support was provided by Wendy Sacks at ACUMED (New York, NY), which was funded by Pfizer Inc; the authors maintained complete control of the manuscript as submitted. NR 17 TC 12 Z9 14 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAY 1 PY 2015 VL 121 IS 9 BP 1405 EP 1413 DI 10.1002/cncr.29220 PG 9 WC Oncology SC Oncology GA CG5TE UT WOS:000353357000010 PM 25641662 ER PT J AU Klaassen, Z Singh, AA Howard, LE Feng, ZY Trock, B Terris, MK Aronson, WJ Cooperberg, MR Amling, CL Kane, CJ Partin, A Han, M Freedland, SJ AF Klaassen, Zachary Singh, Abhay A. Howard, Lauren E. Feng, Zhaoyong Trock, Bruce Terris, Martha K. Aronson, William J. Cooperberg, Matthew R. Amling, Christopher L. Kane, Christopher J. Partin, Alan Han, Misop Freedland, Stephen J. TI Is Clinical Stage T2c Prostate Cancer an Intermediate- or High-Risk Disease? SO CANCER LA English DT Article DE biochemical recurrence; clinical staging; D'Amico risk stratification; Gleason score; prostate cancer; prostate-specific antigen; radical prostatectomy ID ANDROGEN DEPRIVATION THERAPY; BEAM RADIATION-THERAPY; GROUP PROTOCOL 92-02; PHASE-III TRIAL; RADICAL PROSTATECTOMY; PREOPERATIVE NOMOGRAM; RANDOMIZED-TRIAL; RECURRENCE; VALIDATION; PROBABILITY AB BACKGROUNDClinical stage T2c (cT2c) is an indeterminate factor in prostate cancer (PC) risk stratification. According to the D'Amico grouping and American Urological Association guidelines, cT2c is a high risk, whereas the National Comprehensive Cancer Network and the European Urological Association classify cT2c as an intermediate risk. This study assessed whether cT2c tumors without other high-risk factors (clinical stage T2c, not otherwise specified [cT2c-NOS]) behaved as an intermediate or high risk through an analysis of biochemical recurrence (BCR) after radical prostatectomy. METHODSTwo thousand seven hundred fifty-nine men from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database and 12,900 men from Johns Hopkins Hospital (JHH) from 1988-2011 and 1982-2012, respectively, were analyzed. Patients were grouped into low-risk (prostate-specific antigen [PSA] < 10 ng/mL, Gleason sum 6, and cT1-T2a), intermediate-risk (PSA = 10-20 ng/mL, Gleason sum = 7, or cT2b), and high-risk PC categories (PSA > 20 ng/mL, Gleason sum = 8-10, or cT3). Men with cT2c tumors who were not otherwise at high risk (ie, PSA< 20 ng/mL and Gleason sum < 8) were placed into a separate category termed cT2c-NOS. Associations between cT2c-NOS and intermediate- and high-risk patients and BCR were tested with the log-rank test and Cox proportional analysis models. RESULTSNinety-nine men (4%) from SEARCH and 202 men (2%) from JHH had tumors classified as cT2c-NOS. The cT2c-NOS patients had a BCR risk similar to that of the intermediate-risk patients (SEARCH, P = .27; JHH, P = .23) but a significantly lower BCR risk in comparison with the high-risk patients (SEARCH, P < .001; JHH, P < .001). When they were specifically compared with intermediate- and high-risk patients, after adjustments for year and center, cT2c-NOS patients had outcomes comparable to those of intermediate-risk patients (SEARCH, P = .53; JHH, P = .54) but significantly better than those of high-risk patients (SEARCH, P = .003; JHH, P < .001). CONCLUSIONSPatients with cT2c disease without other high-risk features had outcomes similar to the outcomes of patients with intermediate-risk PC and significantly better than the outcomes of patients with high-risk PC. These findings suggest that men with cT2c disease should be considered to be at intermediate risk. Cancer 2015;121:1414-1421. (c) 2014 American Cancer Society. The risk of biochemical recurrence for patients with clinical stage T2c disease without other high-risk features is comparable to the risk for men with intermediate-risk prostate cancer and significantly better than the risk for men with high-risk prostate cancer. Men with clinical stage T2c prostate cancer should be offered treatment options for intermediate-risk disease. C1 [Klaassen, Zachary; Terris, Martha K.] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA. [Singh, Abhay A.; Howard, Lauren E.; Freedland, Stephen J.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Howard, Lauren E.; Freedland, Stephen J.] Durham Vet Affairs Med Ctr, Durham, NC USA. [Feng, Zhaoyong; Trock, Bruce; Partin, Alan; Han, Misop] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Terris, Martha K.] Augusta Vet Affairs Med Ctr, Augusta, GA USA. [Aronson, William J.] West Los Angeles Vet Affairs Med Ctr, West Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Cooperberg, Matthew R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cooperberg, Matthew R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kane, Christopher J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Kane, Christopher J.] San Diego Vet Affairs Med Ctr, San Diego, CA USA. RP Freedland, SJ (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 2626, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU Department of Veterans Affairs; Georgia Cancer Coalition; National Institutes of Health [R01CA100938, K24CA160653]; Specialized Programs of Research Excellence (National Institutes of Health) [P50 CA92131-01A1] FX Research support was received from the Department of Veterans Affairs. Martha K. Terris reports a grant from the Georgia Cancer Coalition. William J. Aronson reports grant R01CA100938 from the National Institutes of Health and grant P50 CA92131-01A1 from the Specialized Programs of Research Excellence (National Institutes of Health). Stephen J. Freedland reports grant K24CA160653 from the National Institutes of Health. NR 30 TC 3 Z9 3 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAY 1 PY 2015 VL 121 IS 9 BP 1414 EP 1421 DI 10.1002/cncr.29147 PG 8 WC Oncology SC Oncology GA CG5TE UT WOS:000353357000011 PM 25492369 ER PT J AU Hata, AN Engelman, JA Faber, AC AF Hata, Aaron N. Engelman, Jeffrey A. Faber, Anthony C. TI The BCL2 Family: Key Mediators of the Apoptotic Response to Targeted Anticancer Therapeutics SO CANCER DISCOVERY LA English DT Review ID CELL LUNG-CANCER; BIM DELETION POLYMORPHISM; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; OBATOCLAX MESYLATE GX15-070; MOLECULE MCL-1 INHIBITORS; PROAPOPTOTIC GENE BIM; BH3 MIMETIC ABT-737; ABL TYROSINE KINASE AB The ability of cancer cells to suppress apoptosis is critical for carcinogenesis. The BCL2 family proteins comprise the sentinel network that regulates the mitochondrial or intrinsic apoptotic response. Recent advances in our understanding of apoptotic signaling pathways have enabled methods to identify cancers that are "primed" to undergo apoptosis, and have revealed potential biomarkers that may predict which cancers will undergo apoptosis in response to specific therapies. Complementary efforts have focused on developing novel drugs that directly target antiapoptotic BCL2 family proteins. In this review, we summarize the current knowledge of the role of BCL2 family members in cancer development and response to therapy, focusing on targeted therapeutics, recent progress in the development of apoptotic biomarkers, and therapeutic strategies designed to overcome deficiencies in apoptosis. Significance: Apoptosis, long known to be important for response to conventional cytotoxic chemotherapy, has more recently been shown to be essential for the efficacy of targeted therapies. Approaches that increase the likelihood of a cancer to undergo apoptosis following therapy may help improve targeted treatment strategies. (C) 2015 AACR. C1 [Hata, Aaron N.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Hata, Aaron N.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Faber, Anthony C.] Virginia Commonwealth Univ, Philips Inst Oral Hlth Res, Sch Dent, Richmond, VA USA. [Faber, Anthony C.] Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Boston, MA 02129 USA. EM jengelman@partners.org; acfaber@vcu.edu FU NIH-NCI [R01CA164273, 2RO1CA140594, 2P50CA127003, R01CA137008] FX J.A. Engelman is supported by NIH-NCI R01CA164273, NIH-NCI 2RO1CA140594, NIH-NCI 2P50CA127003, and NIH-NCI R01CA137008. NR 181 TC 39 Z9 41 U1 7 U2 36 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAY PY 2015 VL 5 IS 5 BP 475 EP 487 DI 10.1158/2159-8290.CD-15-0011 PG 13 WC Oncology SC Oncology GA CH0HI UT WOS:000353700000021 PM 25895919 ER PT J AU Lunardi, A Varmeh, S Chen, M Taulli, R Guarnerio, J Ala, U Seitzer, N Ishikawa, T Carver, BS Hobbs, RM Quarantotti, V Ng, C Berger, AH Nardella, C Poliseno, L Montironi, R Castillo-Martin, M Cordon-Cardo, C Signoretti, S Pandolfi, PP AF Lunardi, Andrea Varmeh, Shohreh Chen, Ming Taulli, Riccardo Guarnerio, Jlenia Ala, Ugo Seitzer, Nina Ishikawa, Tomoki Carver, Brett S. Hobbs, Robin M. Quarantotti, Valentina Ng, Christopher Berger, Alice H. Nardella, Caterina Poliseno, Laura Montironi, Rodolfo Castillo-Martin, Mireia Cordon-Cardo, Carlos Signoretti, Sabina Pandolfi, Pier Paolo TI Suppression of CHK1 by ETS Family Members Promotes DNA Damage Response Bypass and Tumorigenesis SO CANCER DISCOVERY LA English DT Article ID PROSTATE-CANCER PROGRESSION; CELL-CYCLE CHECKPOINTS; ANDROGEN RECEPTOR; TUMOR SUPPRESSION; MICROSATELLITE INSTABILITY; ENDOMETRIAL CANCERS; GENE FUSIONS; IN-VITRO; REPLICATION; P53 AB The ETS family of transcription factors has been repeatedly implicated in tumorigenesis. In prostate cancer, ETS family members, such as ERG, ETV1, ETV4, and ETV5, are frequently overexpressed due to chromosomal translocations, but the molecular mechanisms by which they promote prostate tumorigenesis remain largely undefined. Here, we show that ETS family members, such as ERG and ETV1, directly repress the expression of the checkpoint kinase 1 (CHK1), a key DNA damage response cell-cycle regulator essential for the maintenance of genome integrity. Critically, we find that ERG expression correlates with CHK1 downregulation in human patients and demonstrate that Chk1 heterozygosity promotes the progression of high-grade prostatic intraepithelial neoplasia into prostatic invasive carcinoma in Pten(+/-) mice. Importantly, CHK1 downregulation sensitizes prostate tumor cells to etoposide but not to docetaxel treatment. Thus, we identify CHK1 as a key functional target of the ETS proto-oncogenic family with important therapeutic implications. SIGNIFICANCE: Genetic translocation and aberrant expression of ETS family members is a common event in different types of human tumors. Here, we show that through the transcriptional repression of CHK1, ETS factors may favor DNA damage accumulation and consequent genetic instability in proliferating cells. Importantly, our findings provide a rationale for testing DNA replication inhibitor agents in ETS-positive TP53-proficient tumors. (C) 2015 AACR. C1 [Lunardi, Andrea; Varmeh, Shohreh; Chen, Ming; Taulli, Riccardo; Guarnerio, Jlenia; Ala, Ugo; Seitzer, Nina; Ishikawa, Tomoki; Hobbs, Robin M.; Quarantotti, Valentina; Ng, Christopher; Berger, Alice H.; Nardella, Caterina; Poliseno, Laura; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Canc Ctr, Beth Israel Deaconess Med Ctr, Canc Res Inst,Dept Med & Pathol,Med Sch, Boston, MA 02215 USA. [Carver, Brett S.] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Div Urol, Canc Biol & Genet Program,Dept Surg, New York, NY 10021 USA. [Montironi, Rodolfo] Polytech Univ Marche Reg Ancona, United Hosp, Inst Pathol Anat & Histopathol, Ancona, Italy. [Castillo-Martin, Mireia; Cordon-Cardo, Carlos] Mt Sinai Sch Med, Dept Pathol, New York, NY USA. [Signoretti, Sabina] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Signoretti, Sabina] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. RP Pandolfi, PP (reprint author), Harvard Univ, Canc Res Inst, Beth Israel Deaconess Canc Ctr, Dept Med,Med Sch, 330 Brookline, Boston, MA 02215 USA. EM ppandolf@bidmc.harvard.edu RI Castillo-Martin, Mireia/H-6152-2013; Poliseno, Laura/B-5711-2012; Ala, Ugo/K-2029-2016 OI Poliseno, Laura/0000-0001-6557-955X; Ala, Ugo/0000-0001-5408-6397 FU NIH [R01 CA082328]; Istituto Toscano Tumori (ITT; Italy) FX This work was supported by the NIH grant R01 CA082328 (to P.P. Pandolfi). A. Lunardi has been supported in part by a fellowship from the Istituto Toscano Tumori (ITT; Italy). NR 69 TC 4 Z9 5 U1 3 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAY PY 2015 VL 5 IS 5 BP 550 EP 563 DI 10.1158/2159-8290.CD-13-1050 PG 14 WC Oncology SC Oncology GA CH0HI UT WOS:000353700000026 PM 25653093 ER PT J AU Eisele, SC Gill, CM Shankar, GM Brastianos, PK AF Eisele, Sylvia C. Gill, Corey M. Shankar, Ganesh M. Brastianos, Priscilla K. TI PLEKHA5: A Key to Unlock the Blood-Brain Barrier? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID PLECKSTRIN HOMOLOGY DOMAINS; PI3K PATHWAY; MELANOMA; METASTASIS; IDENTIFICATION; MUTATIONS; MEMBRANE; SURVIVAL; PROTEIN AB Brain metastases represent a devastating complication of melanoma. Our understanding of the mechanisms driving metastasis to the brain is limited. PLEKHA5 functions as a regulator of brain metastasis in melanoma, and further investigation is warranted to explore the use of PLEKHA5 as a potential therapeutic target. (C) 2015 AACR. C1 [Eisele, Sylvia C.; Gill, Corey M.; Brastianos, Priscilla K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuro Oncol, Boston, MA 02115 USA. [Shankar, Ganesh M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Brastianos, Priscilla K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Hematol Oncol, Boston, MA 02115 USA. RP Brastianos, PK (reprint author), Massachusetts Gen Hosp, Cent Nervous Syst Metastasis Program, Div Neuro Oncol, 55 Fruit St,Yawkey 9E, Boston, MA 02115 USA. EM pbrastianos@mgh.harvard.edu OI Brastianos, Priscilla/0000-0003-4470-8425 FU Brain Science Foundation; Susan G. Komen for the Cure; Terri Brodeur Breast Cancer Foundation; Conquer Cancer Foundation; American Brain Tumor Association; Breast Cancer Research Foundation; NIH [K12CA090354] FX P.K. Brastianos was supported by grants from the Brain Science Foundation, Susan G. Komen for the Cure, the Terri Brodeur Breast Cancer Foundation, the Conquer Cancer Foundation, the American Brain Tumor Association, the Breast Cancer Research Foundation, and the NIH under award number K12CA090354. NR 12 TC 2 Z9 2 U1 1 U2 3 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 MAY 1 PY 2015 VL 21 IS 9 BP 1978 EP 1980 DI 10.1158/1078-0432.CCR-14-2604 PG 3 WC Oncology SC Oncology GA CH0KK UT WOS:000353708200002 PM 25779946 ER PT J AU Rusan, M Li, YY Hammerman, PS AF Rusan, Maria Li, Yvonne Y. Hammerman, Peter S. TI Genomic Landscape of Human Papillomavirus-Associated Cancers SO CLINICAL CANCER RESEARCH LA English DT Review ID SQUAMOUS-CELL CARCINOMA; CERVICAL INTRAEPITHELIAL NEOPLASIA; HPV-ASSOCIATED P16-EXPRESSION; NECK-CANCER; PROGNOSTIC-SIGNIFICANCE; PHYSICAL STATE; LUNG-CANCER; E7 PROTEIN; LIFE-CYCLE; HEAD AB Recent next-generation sequencing studies have generated a comprehensive overview of the genomic landscape of human papillomavirus (HPV)-associated cancers. This review summarizes these findings to provide insight into the tumor biology of these cancers and potential therapeutic opportunities for HPV-driven malignancies. In addition to the tumorigenic properties of the HPV oncoproteins, integration of HPV DNA into the host genome is suggested to be a driver of the neoplastic process. Integration may confer a growth and survival advantage via enhanced expression of viral oncoproteins, alteration of critical cellular genes, and changes in global promoter methylation and transcription. Alteration of cellular genes may lead to loss of function of tumor suppressor genes, enhanced oncogene expression, loss of function of DNA repair genes, or other vital cellular functions. Recurrent integrations in RAD51B, NR4A2, and TP63, leading to aberrant forms of these proteins, are observed in both HPV-positive head and neck squamous cell carcinoma (HNSCC) and cervical carcinoma. Additional genomic alterations, independent of integration events, include recurrent PIK3CA mutations (and aberrations in other members of the PI3K pathway), alterations in receptor tyrosine kinases (primarily FGFR2 and FGFR3 in HPV-positive HNSCC, and ERBB2 in cervical squamous cell carcinoma), and genes in pathways related to squamous cell differentiation and immune responses. A number of the alterations identified are potentially targetable, which may lead to advances in the treatment of HPV-associated cancers. (C) 2015 AACR. C1 [Rusan, Maria] Aarhus Univ, Dept Clin Med, DK-8000 Aarhus C, Denmark. [Rusan, Maria] Aarhus Univ, Dept Otorhinolaryngol, DK-8000 Aarhus C, Denmark. [Rusan, Maria; Li, Yvonne Y.; Hammerman, Peter S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rusan, Maria; Li, Yvonne Y.; Hammerman, Peter S.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. RP Hammerman, PS (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM phammerman@partners.org FU Danish Council for Independent Research; Aarhus University; NCI of the NIH [K08CA163677] FX M. Rusan was supported by an EliteForsk Travel scholarship (Danish Council for Independent Research) and a PhD scholarship from Aarhus University. P. S. Hammerman was supported by the NCI of the NIH under award number K08CA163677. NR 94 TC 20 Z9 20 U1 1 U2 16 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 MAY 1 PY 2015 VL 21 IS 9 BP 2009 EP 2019 DI 10.1158/1078-0432.CCR-14-1101 PG 11 WC Oncology SC Oncology GA CH0KK UT WOS:000353708200008 PM 25779941 ER PT J AU Boyiadzis, M Arora, M Klein, JP Hassebroek, A Hemmer, M Urbano-Ispizua, A Antin, JH Bolwell, BJ Cahn, JYY Cairo, MS Cutler, CS Flowers, ME Gale, RP Herzig, R Isola, LM Jacobsohn, DA Jagasia, MH Klumpp, TR Lee, SJ Petersdorf, EW Santarone, S Spellman, SR Schouten, HC Verdonck, LF Wingard, JR Weisdorf, DJ Horowitz, MM Pavletic, SZ AF Boyiadzis, Michael Arora, Mukta Klein, John P. Hassebroek, Anna Hemmer, Michael Urbano-Ispizua, Alvaro Antin, Joseph H. Bolwell, Brian J. Cahn, Jean-Yves Y. Cairo, Mitchell S. Cutler, Corey S. Flowers, Mary E. Gale, Robert P. Herzig, Roger Isola, Luis M. Jacobsohn, David A. Jagasia, Madan H. Klumpp, Thomas R. Lee, Stephanie J. Petersdorf, Effie W. Santarone, Stella Spellman, Stephen R. Schouten, Harry C. Verdonck, Leo F. Wingard, John R. Weisdorf, Daniel J. Horowitz, Mary M. Pavletic, Steven Z. TI Impact of Chronic Graft-versus-Host Disease on Late Relapse and Survival on 7,489 Patients after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID BONE-MARROW-TRANSPLANTATION; UNRELATED DONOR TRANSPLANTATION; HLA-IDENTICAL SIBLINGS; LEUKOCYTE INFUSIONS; MYELOID-LEUKEMIA; EUROPEAN GROUP; MORTALITY; BLOOD AB Purpose: Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse, it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year after transplant at the time when acute GVHD is still active. Experimental Design: This study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7,489 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndromes (MDS), who were leukemia free at 12 months after myeloablative allogeneic HCT. Results: Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on late relapse was present only in patients with CML [RR, 0.47; 95% confidence interval (CI), 0.37-0.59; P < 0.0001). cGVHD was significantly associated with higher risk of treatment-related mortality (TRM; RR, 2.43; 95% CI, 2.09-2.82; P < 0.0001) and inferior overall survival (RR, 1.56; 95% CI, 1.41-1.73; P < 0.0001) for all diseases. In patients with CML, all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse. Conclusions: These results indicate that clinically relevant antileukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL, or MDS. Chronic GVHD in patients who are 1-year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival. (C) 2014 AACR. C1 [Boyiadzis, Michael] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15232 USA. [Arora, Mukta; Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Klein, John P.; Hemmer, Michael; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Hassebroek, Anna; Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Urbano-Ispizua, Alvaro] Hosp Clinic, Inst Hematol & Oncol, Boston, MA USA. [Antin, Joseph H.; Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bolwell, Brian J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Cahn, Jean-Yves Y.] CHU Grenoble, Hop Michallon, F-38043 Grenoble, France. [Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA. [Flowers, Mary E.; Lee, Stephanie J.; Petersdorf, Effie W.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Gale, Robert P.] Univ London Imperial Coll Sci Technol & Med, London, England. [Herzig, Roger] Univ Louisville, Hosp James Brown Canc Ctr, Louisville, KY 40292 USA. [Isola, Luis M.] Mt Sinai Med Ctr, Miami, FL USA. [Jacobsohn, David A.] Childrens Hosp, Natl Med Ctr, Washington, DC 20010 USA. [Jagasia, Madan H.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Klumpp, Thomas R.] Temple Bone Marrow Transplant Program, Philadelphia, PA USA. [Santarone, Stella] Osped Civile BMT Ctr, Pescara, Italy. [Schouten, Harry C.] Acad Ziekenhuis Maastricht, Maastricht, Netherlands. [Verdonck, Leo F.] Isala Clin, Zwolle, Netherlands. [Wingard, John R.] Shands HealthCare, Gainesville, FL USA. [Wingard, John R.] Univ Florida, Gainesville, FL USA. [Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA. RP Boyiadzis, M (reprint author), Univ Pittsburgh, Inst Canc, UPMC Canc Pavil,5150 Ctr Ave,Suite 564, Pittsburgh, PA 15232 USA. EM boyiadzism@upmc.edu FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service grant/cooperative agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a grant/cooperative agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. NR 22 TC 15 Z9 15 U1 0 U2 1 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 MAY 1 PY 2015 VL 21 IS 9 BP 2020 EP 2028 DI 10.1158/1078-0432.CCR-14-0586 PG 9 WC Oncology SC Oncology GA CH0KK UT WOS:000353708200009 PM 25348512 ER PT J AU An, G Li, ZJ Tai, YT Acharya, C Li, Q Qin, XQ Yi, SH Xu, Y Feng, XY Li, CW Zhao, JW Shi, LH Zang, MR Deng, SH Sui, WW Hao, M Zou, DH Zhao, YZ Qi, JY Cheng, T Ru, K Wang, JX Anderson, KC Qiu, LG AF An, Gang Li, Zengjun Tai, Yu-Tzu Acharya, Chirag Li, Qian Qin, Xiaoqi Yi, Shuhua Xu, Yan Feng, Xiaoyan Li, Chengwen Zhao, Jiawei Shi, Lihui Zang, Meirong Deng, Shuhui Sui, Weiwei Hao, Mu Zou, Dehui Zhao, Yaozhong Qi, Junyuan Cheng, Tao Ru, Kun Wang, Jianxiang Anderson, Kenneth C. Qiu, Lugui TI The Impact of Clone Size on the Prognostic Value of Chromosome Aberrations by Fluorescence In Situ Hybridization in Multiple Myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID STEM-CELL TRANSPLANTATION; LENALIDOMIDE PLUS DEXAMETHASONE; INTERPHASE FISH; DOSE CHEMOTHERAPY; WORKING GROUP; P53 DELETION; 1Q21 GAINS; SURVIVAL; ABNORMALITIES; CLASSIFICATION AB Purpose: Accumulating evidence indicates that intratumor heterogeneity is prevalent in multiple myeloma and that a collection of multiple, genetically distinct subclones are present within the myeloma cell population. It is not clear whether the size of clonal myeloma populations harboring unique cytogenetic abnormalities carry any additional prognostic value. Experimental Design: We analyzed the prognostic impact of cytogenetic aberrations by fluorescence in situ hybridization at different cutoff values in a cohort of 333 patients with newly diagnosed myeloma and 92 patients with relapsed myeloma. Results: We found that nearly all IgH-related arrangements were observed in a large majority of the purified plasma cells; however, 13q deletion, 17p deletion, and 1q21 amplification appeared in different percentages within the malignant plasma cell population. Based on the size of subclones carrying these cytogenetic aberrations, the patients were divided into four groups: 0%-10%, 10.5%-20%, 20.5%-50%, and >50%. Receiver-operating characteristics analysis was applied to determine the optimal cutoff value with the greatest differential survival and showed that the most powerful clone sizes were 10% for 13q deletion, 50% for 17p deletion, and 20% for 1q21 gains, which provided the best possible cutoffs for predicting poor outcomes. Conclusions: Our study indicated that the impact of clone size on prognostic value varies between specific genetic abnormalities. Prognostic value was observed for even a subgroup of plasma cells harboring the cytogenetic aberration of 13q deletion and 1q21 gains; however, 17p deletion displayed the most powerful cutoff for predicting survival only if the predominant clones harbored the abnormality. (C) 2015 AACR. C1 [An, Gang; Li, Zengjun; Qin, Xiaoqi; Yi, Shuhua; Xu, Yan; Feng, Xiaoyan; Li, Chengwen; Zhao, Jiawei; Shi, Lihui; Zang, Meirong; Deng, Shuhui; Sui, Weiwei; Hao, Mu; Zou, Dehui; Zhao, Yaozhong; Qi, Junyuan; Cheng, Tao; Ru, Kun; Wang, Jianxiang; Qiu, Lugui] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China. [An, Gang; Li, Zengjun; Qin, Xiaoqi; Yi, Shuhua; Xu, Yan; Feng, Xiaoyan; Li, Chengwen; Zhao, Jiawei; Shi, Lihui; Zang, Meirong; Deng, Shuhui; Sui, Weiwei; Hao, Mu; Zou, Dehui; Zhao, Yaozhong; Qi, Junyuan; Cheng, Tao; Ru, Kun; Wang, Jianxiang; Qiu, Lugui] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China. [An, Gang; Li, Zengjun; Qin, Xiaoqi; Yi, Shuhua; Xu, Yan; Feng, Xiaoyan; Li, Chengwen; Zhao, Jiawei; Shi, Lihui; Zang, Meirong; Deng, Shuhui; Sui, Weiwei; Hao, Mu; Zou, Dehui; Zhao, Yaozhong; Qi, Junyuan; Cheng, Tao; Ru, Kun; Wang, Jianxiang; Qiu, Lugui] Peking Union Med Coll, Tianjin, Peoples R China. [An, Gang; Tai, Yu-Tzu; Acharya, Chirag; Feng, Xiaoyan; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [An, Gang; Tai, Yu-Tzu; Acharya, Chirag; Feng, Xiaoyan; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Ctr, Boston, MA 02115 USA. [Li, Qian] Tianjin Med Univ, Canc Inst & Hosp, Tianjin, Peoples R China. RP Qiu, LG (reprint author), Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China. EM kenneth_anderson@dfci.harvard.edu; qiulg@ihcams.ac.cn FU National Natural Science Fund [81400175, 81172255, 81370632]; Special Key Anticancer Research and Development Program of Tianjin Municipality [12ZCDZSY17600]; Ministry of Health, China; Union Youth Research Fund of Peking Union Medical College; Doctoral Foundation [20131106120037] FX The present study was supported by the National Natural Science Fund (81400175, 81172255, 81370632), the Special Key Anticancer Research and Development Program of Tianjin Municipality (12ZCDZSY17600), the Clinical Research Program from Ministry of Health, China (Key project 2010 to 2012), the Union Youth Research Fund of Peking Union Medical College (2012-2013), the Doctoral Foundation (20131106120037). NR 43 TC 12 Z9 13 U1 2 U2 3 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 MAY 1 PY 2015 VL 21 IS 9 BP 2148 EP 2156 DI 10.1158/1078-0432.CCR-14-2576 PG 9 WC Oncology SC Oncology GA CH0KK UT WOS:000353708200022 PM 25652456 ER PT J AU Heller, MT Shah, AB Bhargava, P Srivastava, U Sun, XM AF Heller, Matthew T. Shah, Amar B. Bhargava, Puneet Srivastava, Udayan Sun, Xiameng TI MDCT of endoleaks following endovascular repair of abdominal aortic aneurysms SO CLINICAL IMAGING LA English DT Article DE EVAR; AAA; MDCT; Aneurysm; Endoleak ID CT ANGIOGRAPHY; STENT-GRAFT; HELICAL CT; SURVEILLANCE; ENDOTENSION; MORTALITY; THERAPY; RUPTURE; DISEASE AB Endovascular aneurysm repair has been used to repair abdominal aortic aneurysms but necessitates surveillance to diagnose the delayed possibility of endoleak formation. Multi-detector computer tomography (MDCT) of the abdomen is one imaging technique used to diagnose enlargement of the aneurysm sac that may be indicative of endoleaks. MDCT has a role in identifying the initial endoleak formation and providing signs suggestive of the specific endoleak subtype; thus it is necessary for radiologists to be familiar with the findings of endoleak seen on MDCT. In this pictorial review, we explore the various types of endoleaks and their appearance on MDCT. (C) 2015 Elsevier Inc. All rights reserved. C1 [Heller, Matthew T.; Srivastava, Udayan; Sun, Xiameng] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15213 USA. [Shah, Amar B.] Westchester Cty Med Ctr, Dept Radiol, Valhalla, NY 10595 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Radiol S114, Seattle, WA 98108 USA. RP Srivastava, U (reprint author), Univ Pittsburgh, Sch Med, Dept Radiol, 200 Lothrop St,Suite 3950,PUH S Tower, Pittsburgh, PA 15213 USA. EM uds4@pitt.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 43 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 EI 1873-4499 J9 CLIN IMAG JI Clin. Imaging PD MAY-JUN PY 2015 VL 39 IS 3 BP 367 EP 373 DI 10.1016/j.clinimag.2015.01.004 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CG9VT UT WOS:000353668900005 PM 25660322 ER PT J AU Metlay, JP AF Metlay, Joshua P. TI Setting National Targets for Antibiotic Use SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE antibiotic use; national; prescribing C1 Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Metlay, JP (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. EM jmetlay@partners.org NR 4 TC 3 Z9 3 U1 0 U2 2 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 MAY 1 PY 2015 VL 60 IS 9 BP 1317 EP 1318 DI 10.1093/cid/civ081 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CH0NS UT WOS:000353718400005 PM 25747408 ER PT J AU Aran, S Shaqdan, KW Abujudeh, HH AF Aran, S. Shaqdan, K. W. Abujudeh, H. H. TI Adverse allergic reactions to linear ionic gadolinium-based contrast agents: experience with 194, 400 injections SO CLINICAL RADIOLOGY LA English DT Article ID NEPHROGENIC SYSTEMIC FIBROSIS; GADOBENATE DIMEGLUMINE; GADOPENTETATE DIMEGLUMINE; CLINICAL SAFETY; MEDIA; FREQUENCY; SEVERITY AB AIM: To report the authors' experience with the administration of four gadolinium-based contrast agents (GBCA; gadopentetate dimeglumine, gadofosveset trisodium, gadoxetate disodium and gadobenate dimeglumine) in a large study population at a single, large academic medical centre. MATERIALS AND METHODS: The institutional review board approved this retrospective study in which data in the electronic incident reporting system were searched. A total of 194, 400 intravenous administrations of linear ionic GBCAs were assessed for the incidence of adverse reactions and risk factors from 1 January 2007 to 14 January 2014. The severity of reactions (mild, moderate, and severe), patient type (outpatients, inpatients, and emergency), examination type, and treatment options were also investigated. RESULTS: In total, 204/194400 (0.1%) patients (mean age 45.7 +/- 14.9) showed adverse reactions, consisting of 6/746 (0.80%), 10/3200 (0.31%), 14/6236 (0.22%) and 174/184218 (0.09%), for gadofosveset trisodium, gadoxetate disodium, gadobenate dimeglumine, and gadopentetate dimeglumine, respectively. An overall significant difference was found between different GBCAs regarding the total number of reactions (p < 0.0001). When comparing the GBCAs together, significant differences were found between gadofosveset trisodium versus gadopentetate dimeglumine (p < 0.0001), gadofosveset trisodium versus gadobenate dimeglumine (p = 0.0051), gadoxetate disodium versus gadopentetate dimeglumine (p < 0.0001) and gadopentetate dimeglumine versus gadobenate dimeglumine (p = 0.0013). Rate of reaction was higher in females (F: 146/113187, 0.13%/M: 58/81213, 0.07%; p < 0.0001). Rate of reactions was higher in outpatient (180/158885, 0.11%), emergency (10/10413, 0.10%), and inpatients (14/25102, 0.05%), respectively (p < 0.0001). Most of the patients had mild symptoms 171/204 (83.8%). Abdomen-pelvis, liver, and thoracic examinations had highest rates of reactions (0.17 versus 0.16 versus 0.15). CONCLUSION: The overall rate of adverse reaction to GBCAs was 0.1%. The rates of reactions were highest in gadofosveset trisodium with (0.80%), followed by gadoxetate disodium (0.31%), gadobenate dimeglumine (0.22%) and gadopentetate dimeglumine (0.09%). (C) 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Aran, S.; Shaqdan, K. W.; Abujudeh, H. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Founders Bldg,Room 210, Boston, MA 02114 USA. EM Abujudeh.Hani@mgh.harvard.edu NR 22 TC 8 Z9 10 U1 1 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 EI 1365-229X J9 CLIN RADIOL JI Clin. Radiol. PD MAY PY 2015 VL 70 IS 5 BP 466 EP 475 DI 10.1016/j.crad.2014.12.011 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CH0SG UT WOS:000353732100002 PM 25626627 ER PT J AU Rochau, U Jahn, B Qerimi, V Burger, EA Kurzthaler, C Kluibenschaedl, M Willenbacher, E Gastl, G Willenbacher, W Siebert, U AF Rochau, U. Jahn, B. Qerimi, V. Burger, E. A. Kurzthaler, C. Kluibenschaedl, M. Willenbacher, E. Gastl, G. Willenbacher, W. Siebert, U. TI Decision-analytic modeling studies: An overview for clinicians using multiple myeloma as an example SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Decision-analytic modeling; Multiple myeloma; Systematic overview; Cost effectiveness analysis; Health economic modeling ID PRACTICES TASK-FORCE; COST-EFFECTIVENESS; ECONOMIC-EVALUATION; ZOLEDRONIC ACID; HEALTH; BORTEZOMIB; LENALIDOMIDE; PERSPECTIVE; THALIDOMIDE; PREDNISONE AB Purpose: The purpose of this study was to provide a clinician-friendly overview of decision-analytic models evaluating different treatment strategies for multiple myeloma (MM). Methods: We performed a systematic literature search to identify studies evaluating MM treatment strategies using mathematical decision-analytic models. We included studies that were published as full-text articles in English, and assessed relevant clinical endpoints, and summarized methodological characteristics (e.g., modeling approaches, simulation techniques, health outcomes, perspectives). Results: Eleven decision-analytic modeling studies met our inclusion criteria. Five different modeling approaches were adopted: decision-tree modeling, Markov state-transition modeling, discrete event simulation, partitioned-survival analysis and area-under-the-curve modeling. Health outcomes included survival, number-needed-to-treat, life expectancy, and quality-adjusted life years. Evaluated treatment strategies included novel agent-based combination therapies, stem cell transplantation and supportive measures. Conclusion: Overall, our review provides a comprehensive summary of modeling studies assessing treatment of MM and highlights decision-analytic modeling as an important tool for health policy decision making. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Rochau, U.; Jahn, B.; Qerimi, V.; Kurzthaler, C.; Kluibenschaedl, M.; Siebert, U.] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth & Hlth Technol Assessment, Inst Publ Hlth Med Decis Making & Hlth Technol As, Hall In Tirol, Austria. [Rochau, U.; Willenbacher, E.; Gastl, G.; Willenbacher, W.; Siebert, U.] ONCOTYROL Ctr Personalized Canc Med, Area Hlth Technol Assessment & Bioinformat 4, A-6020 Innsbruck, Austria. [Qerimi, V.] Ss Cyril & Methodius Univ Skopje, Sch PhD Studies, Fac Pharm, Skopje, Macedonia. [Burger, E. A.] Univ Oslo, Dept Hlth Management & Hlth Econ, N-0316 Oslo, Norway. [Willenbacher, E.; Gastl, G.; Willenbacher, W.] Med Univ Innsbruck, Internal Med Hematol & Oncol 5, A-6020 Innsbruck, Austria. [Burger, E. A.; Siebert, U.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, U.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Siebert, U (reprint author), ONCOTYROL Ctr Personalized Canc Med, Area Hlth Technol Assessment & Bioinformat 4, Innrain 66a, A-6020 Innsbruck, Austria. EM ursula.rochau@umit.at; beate.jahn@umit.at; vjollca.qerimi@umit.at; emily.burger@medisin.uio.no; christina.kurzthaler@umit.at; martina.kluibenschaedl@umit.at; ella.willenbacher@i-med.ac.at; guenther.gastl@i-med.ac.at; wolfgang.willenbacher@uki.at; uwe.siebert@umit.at FU COMET ONCOTYROL - Center for Personalized Cancer Medicine - Austrian Federal Ministries for Transport Innovation and Technology (BMVIT) and Economy, Family and Youth (BMWFJ) (via the Austrian Research Promotion Agency FFG) [2073085]; Tyrolean Future Foundation/Standortagentur Tirol (SAT); Erasmus Mundus Western Balkans (ERAWEB) - European Commission FX This work was supported by the COMET ONCOTYROL (Grant no. 2073085) - Center for Personalized Cancer Medicine, which is funded by the Austrian Federal Ministries for Transport Innovation and Technology (BMVIT) and Economy, Family and Youth (BMWFJ) (via the Austrian Research Promotion Agency FFG) and the Tyrolean Future Foundation/Standortagentur Tirol (SAT), and has been financially supported through Erasmus Mundus Western Balkans (ERAWEB), a project funded by the European Commission. The funding source had no influence on study design, analysis and interpretation of data, in the writing of the manuscript and the decision to submit the manuscript for publication. NR 53 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 EI 1879-0461 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD MAY PY 2015 VL 94 IS 2 BP 164 EP 178 DI 10.1016/j.critrevonc.2014.12.017 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA CG9AA UT WOS:000353605600002 PM 25620327 ER PT J AU Ghatalia, P Morgan, CJ Je, Y Nguyen, PL Trinh, QD Choueiri, TK Sonpavde, G AF Ghatalia, Pooja Morgan, Charity J. Je, Youjin Nguyen, Paul L. Quoc-Dien Trinh Choueiri, Toni K. Sonpavde, Guru TI Congestive heart failure with vascular endothelial growth factor receptor tyrosine kinase inhibitors SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Vascular endothelial growth factor receptor; Tyrosine kinase inhibitors; Approved; Congestive heart failure; Meta-analysis ID PHASE-III TRIAL; RENAL-CELL CARCINOMA; ADVANCED HEPATOCELLULAR-CARCINOMA; RANDOMIZED CONTROLLED-TRIALS; METASTATIC BREAST-CANCER; DOUBLE-BLIND; CLINICAL-TRIALS; 1ST-LINE TREATMENT; SUNITINIB; METAANALYSIS AB A systematic review and meta-analysis was conducted to determine the relative risk (RR) of congestive heart failure (CHIP) associated with approved multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized trials comparing arms with and without an FDA-approved VEGFR TKI. Statistical analyses calculated the relative risk (RR) and 95% confidence intervals (CI). A total of 10,647 patients from 16 phase III trials and 5 phase II trials were selected. All grade CHIP occurred in 138 of 5752 (2.39%) patients receiving VEGFR TKIs and 37 of 4895 (0.75%) patients in the non-TKI group. High-grade CHF occurred in 17 of 1426(1.19%) patients receiving VEGFR TKIs and 8 of 1232(0.65%) patients in the non-TKI group. The RR of all grade and high-grade CHF for the TKI vs. no TKI arms was 2.69 (p<0.001; 95% CI: 1.86 to 3.87) and 1.65 (p=0.227, 95% CI: 0.73 to 3.70), respectively. The RR of relatively specific TKIs (axitinib) was similar to relatively non-specific TKIs (sunitinib, sorafenib, vandetanib, pazopanib). (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Ghatalia, Pooja] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL USA. [Morgan, Charity J.] Kyung Hee Univ, UAB Sch Publ Hlth, Dept Biostat, Seoul, South Korea. [Je, Youjin] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea. [Nguyen, Paul L.; Quoc-Dien Trinh; Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Nguyen, Paul L.; Quoc-Dien Trinh; Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA. [Sonpavde, Guru] UAB Med Ctr, Sect Med Oncol, Dept Internal Med, Birmingham, AL 35233 USA. RP Sonpavde, G (reprint author), UAB Med Ctr, Sect Med Oncol, Dept Internal Med, Birmingham, AL 35233 USA. EM gsonpavde@uabmc.edu FU Onyx FX Toni K. Choueiri, MD: Advisory board: Bayer, Pfizer, GSK, Novartis, Aveo. Guru Sonpavde, MD: Research support and advisory board for Novartis; Advisory board for GSK; Research support from Onyx. NR 39 TC 11 Z9 11 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 EI 1879-0461 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD MAY PY 2015 VL 94 IS 2 BP 228 EP 237 DI 10.1016/j.critrevonc.2014.12.008 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA CG9AA UT WOS:000353605600007 PM 25577572 ER PT J AU Murray, DE Durazzo, TC Mon, A Schmidt, TP Meyerhoff, DJ AF Murray, Donna E. Durazzo, Timothy C. Mon, Anderson Schmidt, Thomas P. Meyerhoff, Dieter J. TI Brain perfusion in polysubstance users: Relationship to substance and tobacco use, cognition, and self-regulation SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE MRI; Perfusion; Blood flow; Polysubstance; Alcohol; Smoking ID CEREBRAL-BLOOD-FLOW; ALCOHOL-DEPENDENT INDIVIDUALS; CHRONIC CIGARETTE-SMOKING; EMISSION COMPUTERIZED-TOMOGRAPHY; NATIONAL EPIDEMIOLOGIC SURVEY; BARRATT IMPULSIVENESS SCALE; TERM ABSTINENT ALCOHOLICS; DSM-IV ALCOHOL; DECISION-MAKING; PREFRONTAL CORTEX AB Background: Brain perfusion is altered in both alcohol dependence and stimulant dependence. Although most substance users also abuse/depend on alcohol concurrently (polysubstance users; PSU), rigorous perfusion research in PSU is limited. Also, the relationships of perfusion abnormalities with cognition, impulsivity, or decision making are not well known. Methods: Arterial spin labeling MRI and neuropsychological measures assessed perfusion levels and neurocognition in 20 alcohol-dependent individuals with comorbid-stimulant dependence (PSU), 26 individuals dependent on alcohol only (ALC), and 31 light/non-drinking controls (LD). The patient groups included smokers and non-smokers. Results: ALC had lower perfusion than LD in subcortical and cortical brain regions including the brain reward/executive oversight system (BREOS). Contrary to our hypothesis, regional perfusion was generally not lower in PSU than ALC. However, smoking PSU had lower perfusion than smoking ALC in several regions, including BREOS. Lower BREOS perfusion related to greater drinking severity in smoking substance users and to greater smoking severity in smoking ALC. Lower regional perfusion in ALC and PSU correlated with worse performance in different cognitive domains; smoking status affected perfusion-cognition relationships in ALC only. Lower BREOS perfusion in both substance using groups related to higher impulsivity. Conclusion: Although regional perfusion was not decreased in PSU as a group, the combination of cigarette smoking and polysubstance use is strongly related to hypoperfusion in important cortical and subcortical regions. As lower perfusion relates to greater smoking severity, worse cognition and higher impulsivity, smoking cessation is warranted for treatment-seeking PSU and ALC. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Murray, Donna E.; Durazzo, Timothy C.; Schmidt, Thomas P.; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Murray, Donna E.; Durazzo, Timothy C.; Schmidt, Thomas P.; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Mon, Anderson] Koforidua Polytech, Sch Appl Sci & Stat, Koforidua, Ghana. RP Murray, DE (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM donna.murray@ucsf.edu FU National Institutes of Health [AA10788, DA025202, DA24136] FX This work was supported by grants AA10788, DA025202 (both to DJM) and DA24136 (to TCD) from the National Institutes of Health and by the use of resources at the SFVA Medical Center. The research has been administered by the Northern California Institute for Research and Education. Apart from funding, the centers did not contribute to this research or to the manuscript preparation. NR 80 TC 2 Z9 2 U1 2 U2 5 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 MAY 1 PY 2015 VL 150 BP 120 EP 128 DI 10.1016/j.drugalcdep.2015.02.022 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CG8YF UT WOS:000353600900016 PM 25772434 ER PT J AU Herrmann, BS Brown, MC Eddington, DK Hancock, KE Lee, DJ AF Herrmann, Barbara S. Brown, M. Christian Eddington, Donald K. Hancock, Kenneth E. Lee, Daniel J. TI Auditory Brainstem Implant: Electrophysiologic Responses and Subject Perception SO EAR AND HEARING LA English DT Article DE Auditory brainstem response; Cochlear nucleus; Middle-latency response; Neural prosthesis ID COCHLEAR NUCLEUS; ELECTRICAL-STIMULATION; NEUROFIBROMATOSIS TYPE-2 AB Objectives: The primary aim of this study was to compare the perceptual sensation produced by bipolar electrical stimulation of auditory brainstem implant (ABI) electrodes with the morphology of electrically evoked responses elicited by the same bipolar stimulus in the same unanesthetized, postsurgical state. Secondary aims were to (1) examine the relationships between sensations elicited by the bipolar stimulation used for evoked potential recording and the sensations elicited by the monopolar pulse-train stimulation used by the implant processor, and (2) examine the relationships between evoked potential morphology (elicited by bipolar stimulation) to the sensations elicited by monopolar stimulation. Design: Electrically evoked early-latency and middle-latency responses to bipolar, biphasic low-rate pulses were recorded postoperatively in four adults with ABIs. Before recording, the perceptual sensations elicited by these bipolar stimuli were obtained and categorized as (1) auditory sensations only, (2) mixed sensations (both auditory and nonauditory), (3) side effect (nonauditory sensations), or (4) no sensation. In addition, the sensations elicited by monopolar higher-rate pulse-train stimuli similar to that used in processor programming were measured for all electrodes in the ABI array and classified using the same categories. Comparisons were made between evoked response morphology, bipolar stimulation sensation, and monopolar stimulation sensation. Results: Sensations were classified for 33 bipolar pairs as follows: 21 pairs were auditory, 6 were mixed, 5 were side effect, and 1 was no sensation. When these sensations were compared with the electrically evoked response morphology for these signals, P3 of the electrically evoked auditory brainstem response (eABR) and the presence of a middle-latency positive wave, usually between 15 and 25 msec (electrical early middle-latency response [eMLR]), were only present when the perceptual sensation had an auditory component (either auditory or mixed pairs). The presence of other waves in the early-latency response such as N1 or P2 or a positive wave after 4 msec did not distinguish between only auditory or only nonauditory sensations. For monopolar stimulation, 42 were classified as auditory, 16 were mixed, and 26 were classified as side effect or no sensation. When bipolar sensations were compared with monopolar sensations for the 21 bipolar pairs categorized as auditory, 7 pairs had monopolar sensations of auditory for both electrodes, 9 pairs had only one electrode with a monopolar sensation of auditory, with the remainder having neither electrode as auditory. Of 6 bipolar pairs categorized as mixed, 3 had monopolar auditory sensations for one of the electrodes. When monopolar stimulation was compared with evoked potential morphology elicited by bipolar stimulation, P3 and the eMLR were more likely to be present when one or both of the electrodes in the bipolar pair elicited an auditory or mixed sensation with monopolar stimulation and were less likely to occur when neither of the electrodes had an auditory monopolar sensation. Again, other eABR waves did not distinguish between auditory and nonauditory sensations. Conclusions: ABI electrodes that are associated with auditory sensations elicited by bipolar stimulation are more likely to elicit evoked responses with a P3 wave or a middle-latency wave. P3 of the eABR and M15-25 of the eMLR are less likely to be present if neither electrode of the bipolar pair evoked an auditory sensation with monopolar stimulation. C1 [Herrmann, Barbara S.; Brown, M. Christian; Eddington, Donald K.; Hancock, Kenneth E.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Herrmann, Barbara S.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Brown, M. Christian; Hancock, Kenneth E.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Eddington, Donald K.] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. [Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Herrmann, BS (reprint author), Massachusetts Eye & Ear Infirm, Dept Audiol, 243 Charles St, Boston, MA 02114 USA. EM Barbara_herrmann@meei.harvard.edu FU Helene and Grant Wilson Auditory Brainstem Implant Program at the Massachusetts Eye and Ear Infirmary; National Institutes of Health (NIH) [DC01089]; Bertarelli Foundation FX This research was funded by the Helene and Grant Wilson Auditory Brainstem Implant Program at the Massachusetts Eye and Ear Infirmary, National Institutes of Health (NIH) grant DC01089 and The Bertarelli Foundation. NR 17 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD MAY-JUN PY 2015 VL 36 IS 3 BP 368 EP 376 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA CG8SC UT WOS:000353581000017 PM 25437141 ER PT J AU Geffrey, AL Belt, OD Paolini, JL Thiele, EA AF Geffrey, Alexandra L. Belt, Olivia D. Paolini, Jan L. Thiele, Elizabeth A. TI Lacosamide use in the treatment of refractory epilepsy in tuberous sclerosis complex SO EPILEPSY RESEARCH LA English DT Article DE Epilepsy; Tuberous sclerosis complex; Adjunctive therapy; Anticonvulsants; LCS ID THERAPY AB Lacosamide (LCS) was approved by the United States Food and Drug Administration (FDA) in 2008 as adjunctive therapy to other anti-epileptic drugs (AEDs) to treat focal-onset seizures, with or without secondary generalization. Its role in the treatment of epilepsy in individuals with tuberous sclerosis complex (TSC) has yet to be determined. This study evaluates LCS treatment of focal-onset refractory epilepsy in patients with TSC. From November 2009 to June 2014, 46 TSC patients followed by a single neurologist were treated with LCS. Forty-eight percent were responders (seizure reduction >= 50%). No significant differences between responders and non-responders in demographic characteristics were found. LCS appears to be an effective and safe treatment of refractory focal onset seizures in TSC. Determining the long-term tolerability and efficacy of LCS in TSC patients requires additional clinical experience. (C) 2015 Elsevier B.V. All rights reserved. C1 [Geffrey, Alexandra L.; Belt, Olivia D.; Paolini, Jan L.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Herscot Ctr Tuberous Sclerosis Complex, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Herscot Ctr Tuberous Sclerosis Complex, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Herscot Center for Tuberous Sclerosis Complex FX The Herscot Center for Tuberous Sclerosis Complex supported this study. NR 14 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2015 VL 112 BP 72 EP 75 DI 10.1016/j.eplepsyres.2015.02.008 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA CH2HD UT WOS:000353845400009 PM 25847341 ER PT J AU Thomas, JJ Eddy, KT Ruscio, J Ng, KL Casale, KE Becker, AE Lee, S AF Thomas, Jennifer J. Eddy, Kamryn T. Ruscio, John Ng, King Lam Casale, Kristen E. Becker, Anne E. Lee, Sing TI Do Recognizable Lifetime Eating Disorder Phenotypes Naturally Occur in a Culturally Asian Population? A Combined Latent Profile and Taxometric Approach SO EUROPEAN EATING DISORDERS REVIEW LA English DT Article DE DSM-5; fat phobia; anorexia nervosa; latent profile analysis; taxometric analysis ID ATYPICAL ANOREXIA-NERVOSA; 2 QUANTITATIVE INDICATORS; BULIMIA-NERVOSA; HONG-KONG; DSM-V; DETECTING TAXONICITY; CHINESE PATIENTS; CLASSIFICATION; FAT; ADOLESCENTS AB BackgroundWe examined whether empirically derived eating disorder (ED) categories in Hong Kong Chinese patients (N=454) would be consistent with recognizable lifetime ED phenotypes derived from latent structure models of European and American samples. MethodWe performed latent profile analysis (LPA) using indicator variables from data collected during routine assessment, and then applied taxometric analysis to determine whether latent classes were qualitatively versus quantitatively distinct. ResultsLatent profile analysis identified four classes: (i) binge/purge (47%); (ii) non-fat-phobic low-weight (34%); (iii) fat-phobic low-weight (12%); and (iv) overweight disordered eating (6%). Taxometric analysis identified qualitative (categorical) distinctions between the binge/purge and non-fat-phobic low-weight classes, and also between the fat-phobic and non-fat-phobic low-weight classes. Distinctions between the fat-phobic low-weight and binge/purge classes were indeterminate. ConclusionEmpirically derived categories in Hong Kong showed recognizable correspondence with recognizable lifetime ED phenotypes. Although taxometric findings support two distinct classes of low weight EDs, LPA findings also support heterogeneity among non-fat-phobic individuals. Copyright (c) 2015 John Wiley & Sons, Ltd and Eating Disorders Association. C1 [Thomas, Jennifer J.; Eddy, Kamryn T.; Becker, Anne E.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Thomas, Jennifer J.; Eddy, Kamryn T.; Casale, Kristen E.; Becker, Anne E.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Ruscio, John] Coll New Jersey, Dept Psychol, Ewing Township, NJ 08618 USA. [Ng, King Lam] Univ Hong Kong, Dept Social Work & Social Adm, Hong Kong, Hong Kong, Peoples R China. [Becker, Anne E.; Lee, Sing] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Cambridge, MA 02138 USA. [Lee, Sing] Chinese Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. RP Thomas, JJ (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA. EM jjthomas@mgh.harvard.edu RI Lee, Sing/O-2136-2015 NR 63 TC 2 Z9 2 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1072-4133 EI 1099-0968 J9 EUR EAT DISORD REV JI Eur. Eat. Disord. Rev. PD MAY PY 2015 VL 23 IS 3 BP 199 EP 209 DI 10.1002/erv.2357 PG 11 WC Psychology, Clinical SC Psychology GA CH3BT UT WOS:000353901900005 PM 25787700 ER PT J AU Kazlauskas, A AF Kazlauskas, Andrius TI Lysophosphatidic acid contributes to angiogenic homeostasis SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE LPA; ATX; Angiogenesis; Blood vessel stability/regression ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR DEVELOPMENT; LYSOPHOSPHOLIPASE-D; EMBRYONIC LETHALITY; CELLULAR-RESPONSES; BINDING PROTEINS; BLOOD-VESSELS; LPA RECEPTORS; AUTOTAXIN; CELLS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Kazlauskas, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM andrius_kazlauskas@meei.harvard.edu FU NIH [EY016385] FX I would like to thank Mohammed Anwar, Sarah Jacobo and Ashley Mackey for constructive input for improving this review article. Funding was provided by NIH Grant EY016385. NR 55 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 2015 VL 333 IS 2 BP 166 EP 170 DI 10.1016/j.yexcr.2014.11.012 PG 5 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CG9UR UT WOS:000353666100002 PM 25433269 ER PT J AU Theivanthiran, B Batra, S Balamayooran, G Cai, S Kobayashi, K Flavell, RA Jeyaseelan, S AF Theivanthiran, Balamayooran Batra, Sanjay Balamayooran, Gayathriy Cai, Shanshan Kobayashi, Koichi Flavell, Richard A. Jeyaseelan, Samithamby TI NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection (Retraction of vol 80, pg 2558, 2012) SO INFECTION AND IMMUNITY LA English DT Correction C1 [Theivanthiran, Balamayooran; Batra, Sanjay; Balamayooran, Gayathriy; Cai, Shanshan; Jeyaseelan, Samithamby] Harvard Univ, Sch Med, Lab Lung Biol, Dept Pathobiol Sci, Boston, MA 02115 USA. [Theivanthiran, Balamayooran; Batra, Sanjay; Balamayooran, Gayathriy; Cai, Shanshan; Jeyaseelan, Samithamby] Harvard Univ, Sch Med, Ctr Expt Infect Dis Res, Boston, MA USA. [Kobayashi, Koichi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Immunobiol, New Haven, CT 06510 USA. [Jeyaseelan, Samithamby] LSU Hlth Sci Ctr, Dept Med, Sect Pulm & Crit Care Med, New Orleans, LA USA. RP Theivanthiran, B (reprint author), Harvard Univ, Sch Med, Lab Lung Biol, Dept Pathobiol Sci, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 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 MAY PY 2015 VL 83 IS 5 BP 2199 EP 2199 DI 10.1128/IAI.00200-15 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CG0TJ UT WOS:000352982600045 ER PT J AU Vogel, J Haddadin, S Jarosiewicz, B Simeral, JD Bacher, D Hochberg, LR Donoghue, JP van der Smagt, P AF Vogel, J. Haddadin, S. Jarosiewicz, B. Simeral, J. D. Bacher, D. Hochberg, L. R. Donoghue, J. P. van der Smagt, P. TI An assistive decision-and-control architecture for force-sensitive hand-arm systems driven by human-machine interfaces SO INTERNATIONAL JOURNAL OF ROBOTICS RESEARCH LA English DT Article DE Service robots; assistive robotics; medical robots and systems; human-centered and life-like robotics; telerobotics ID BRAIN-COMPUTER INTERFACE; SURFACE EMG; SIGNALS; TETRAPLEGIA; ENVIRONMENTS; PROSTHESES; MOVEMENTS; DIRECTION; POSITION; PEOPLE AB Fully autonomous applications of modern robotic systems are still constrained by limitations in sensory data processing, scene interpretation, and automated reasoning. However, their use as assistive devices for people with upper-limb disabilities has become possible with recent advances in soft robotics, that is, interaction control, physical human-robot interaction, and reflex planning. In this context, impedance and reflex-based control has generally been understood to be a promising approach to safe interaction robotics. To create semi-autonomous assistive devices, we propose a decision-and-control architecture for hand-arm systems with soft robotics capabilities, which can then be used via human-machine interfaces (HMIs). We validated the functionality of our approach within the BrainGate2 clinical trial, in which an individual with tetraplegia used our architecture to control a robotic hand-arm system under neural control via a multi-electrode array implanted in the motor cortex. The neuroscience results of this research have previously been published by Hochberg et al. In this paper we present our assistive decision-and-control architecture and demonstrate how the semi-autonomous assistive behavior can help the user. In our framework the robot is controlled through a multi-priority Cartesian impedance controller and its behavior is extended with collision detection and reflex reaction. Furthermore, virtual workspaces are added to ensure safety. On top of this we employ a decision-and-control architecture that uses sensory information available from the robotic system to evaluate the current state of task execution. Based on a set of available assistive skills, our architecture provides support in object interaction and manipulation and thereby enhances the usability of the robotic system for use with HMIs. The goal of our development is to provide an easy-to-use robotic system for people with physical disabilities and thereby enable them to perform simple tasks of daily living. In an exemplary real-world task, the participant was able to serve herself a beverage autonomously for the first time since her brainstem stroke, which she suffered approximately 14 years prior to this research. C1 [Vogel, J.] German Aerosp Ctr DLR, Inst Robot & Mechatron, Robot & Mechatron Ctr, D-82234 Oberpfaffenhofen, Germany. [Haddadin, S.] Leibniz Univ Hannover, Inst Automat Control, Hannover, Germany. [Jarosiewicz, B.; Donoghue, J. P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Jarosiewicz, B.; Donoghue, J. P.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Jarosiewicz, B.; Simeral, J. D.; Hochberg, L. R.; Donoghue, J. P.] US Dept Vet Affairs, Ctr Neurorestorat & Neurotechnol, Providence, RI USA. [Simeral, J. D.; Bacher, D.; Hochberg, L. R.; Donoghue, J. P.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Simeral, J. D.; Bacher, D.; Hochberg, L. R.; Donoghue, J. P.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Simeral, J. D.; Hochberg, L. R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hochberg, L. R.] Harvard Univ, Sch Med, Boston, MA USA. [van der Smagt, P.] Tech Univ Munich, Fortiss, D-80290 Munich, Germany. [van der Smagt, P.] Tech Univ Munich, BRML, Dept Informat, D-80290 Munich, Germany. RP Vogel, J (reprint author), German Aerosp Ctr DLR, Inst Robot & Mechatron, Robot & Mechatron Ctr, D-82234 Oberpfaffenhofen, Germany. EM joern.vogel@dlr.de OI Vogel, Jorn/0000-0002-1987-0028; van der Smagt, Patrick/0000-0003-4418-4916 FU European Commission [287513, 248257] FX This work has been partially funded by the European Commission's Sixth Framework Programme as part of the project SAPHARI (grant number 287513) and by the European Commission's Seventh Framework Programme as part of the Project THE Hand Embodied (grant number 248257). NR 58 TC 5 Z9 6 U1 6 U2 37 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0278-3649 EI 1741-3176 J9 INT J ROBOT RES JI Int. J. Robot. Res. PD MAY PY 2015 VL 34 IS 6 BP 763 EP 780 DI 10.1177/0278364914561535 PG 18 WC Robotics SC Robotics GA CH4DH UT WOS:000353981500003 ER PT J AU Chen, YT Brennan-Minnella, AM Sheth, S El-Benna, J Swanson, RA AF Chen, Yanting Brennan-Minnella, Angela M. Sheth, Sunil El-Benna, Jamel Swanson, Raymond A. TI Tat-NR2B9c prevents excitotoxic neuronal superoxide production SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE DNA damage; glutamate; ischemia; nitric oxide; oxidative stress; stroke ID NMDA RECEPTOR ACTIVATION; NITRIC-OXIDE; NADPH OXIDASE; PROTEIN INTERACTIONS; MICE; NEUROPROTECTION; NEUROTOXICITY AB The Tat-NR2B9c peptide has shown clinical efficacy as a neuroprotective agent in acute stroke. Tat-NR2B9c is designed to prevent nitric oxide (NO) production by preventing postsynaptic density protein 95 (PSD-95) binding to N-methyl-D-aspartate (NMDA) receptors and neuronal nitric oxide synthase; however, PSD-95 is a scaffolding protein that also couples NMDA receptors to other downstream effects. Here, using neuronal cultures, we show that Tat-NR2B9c also prevents NMDA-induced activation of neuronal NADPH oxidase, thereby blocking superoxide production. Given that both superoxide and NO are required for excitotoxic injury, the neuroprotective effect of Tat-NR2B9c may alternatively be attributable to uncoupling neuronal NADPH oxidase from NMDA receptor activation. C1 [Chen, Yanting] Nanjing Univ, Sch Med, Drum Tower Hosp, Dept Neurol, Nanjing 210008, Jiangsu, Peoples R China. [Chen, Yanting; Brennan-Minnella, Angela M.; Sheth, Sunil; Swanson, Raymond A.] Univ Calif San Francisco, Dept Neurol, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [El-Benna, Jamel] CNRS, Ctr Rech Inflammat Paris, INSERM, U1149,ERL8252, Paris, France. [El-Benna, Jamel] Univ Paris Diderot, Lab Excellence Inflamex, Sorbonne Paris Cite, Paris, France. RP Swanson, RA (reprint author), SFVAMC, Neurol 127, 4150 Clement St, San Francisco, CA 94121 USA. EM raymond.swanson@ucsf.edu FU US National Institutes of Health [NS081149]; Department of Veterans Affairs; China Scholarship Council FX This work was supported by the US National Institutes of Health (NS081149, RAS); Department of Veterans Affairs (RAS); and the China Scholarship Council (YC). NR 17 TC 6 Z9 6 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2015 VL 35 IS 5 BP 739 EP 742 DI 10.1038/jcbfm.2015.16 PG 4 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CH1GK UT WOS:000353769100006 PM 25669908 ER PT J AU Press, VG Matthiesen, MI Ranadive, A Hariprasad, SM Meltzer, DO Arora, VM AF Press, Valerie G. Matthiesen, Madeleine I. Ranadive, Alisha Hariprasad, Seenu M. Meltzer, David O. Arora, Vineet M. TI Insights Into Inpatients With Poor Vision: A High Value Proposition SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID RISK-FACTORS; DELIRIUM; MEDICINE; COSTS AB BACKGROUNDVision impairment is an under-recognized risk factor for adverse events among hospitalized patients, yet vision is neither routinely tested nor documented for inpatients. Low-cost ($8 and up) nonprescription readers may be a simple, high-value intervention to improve inpatients' vision. We aimed to study initial feasibility and efficacy of screening and correcting inpatients' vision. METHODSFrom June 2012 through January 2014 we began testing whether participants' vision corrected with nonprescription lenses for eligible participants failing a vision screen (Snellen chart) performed by research assistants (RAs). Descriptive statistics and tests of comparison, including t tests and (2) tests, were used when appropriate. All analyses were performed using Stata version 12 (StataCorp, College Station, TX). RESULTSOver 800 participants' vision was screened (n=853). Older (65 years; 56%) participants were more likely to have insufficient vision than younger (<65 years; 28%; P<0.001). Nonprescription readers corrected the majority of eligible participants' vision (82%, 95/116). DISCUSSIONAmong an easily identified subgroup of inpatients with poor vision, low-cost readers successfully corrected most participants' vision. Hospitalists and other clinicians working in the inpatient setting can play an important role in identifying opportunities to provide high-value care related to patients' vision. Journal of Hospital Medicine 2015;10:311-313. (c) 2015 Society of Hospital Medicine C1 [Press, Valerie G.; Meltzer, David O.] Univ Chicago, Dept Med, Sect Hosp Med, Chicago, IL 60637 USA. [Matthiesen, Madeleine I.] Massachusetts Gen Hosp, Dept Med Pediat, Boston, MA 02114 USA. [Ranadive, Alisha] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Hariprasad, Seenu M.] Univ Chicago, Dept Ophthalmol, Chicago, IL 60637 USA. [Arora, Vineet M.] Univ Chicago, Dept Med, Sect Gen Internal Med, Chicago, IL 60637 USA. RP Press, VG (reprint author), 5841 S Maryland Ave,MC 5000, Chicago, IL 60637 USA. EM vpress@medicine.bsd.uchicago.edu RI Meltzer, David/C-2926-2009; OI Meltzer, David/0000-0003-2790-7393; Arora, Vineet/0000-0002-4745-7599 FU National Heart Lung and Blood Institute [NIH K23HL118151]; Center on the Demography and Economics of Aging (CoA, National Institute of Aging) [P30 AG012857]; Summer Research Program - National Institutes on Aging Short-Term Aging-Related Research Program [T35AG029795]; Calvin Fentress Fellowship Program; National Institutes on Aging Short-Term Aging-Related Research Program [T35AG029795]; Agency for Healthcare Quality and Research through the Hospital Medicine and Economics Center for Education and Research in Therapeutics [U18 HS016967-01]; National Institute of Aging through a Midcareer Career Development Award [K24 AG031326-01]; National Cancer Institute [KM1 CA156717]; National Center for Advancing Translational Science [2UL1TR000430-06]; National Institutes on Aging [K23AG033763] FX Dr. Press is supported by a career development award from the National Heart Lung and Blood Institute (NIH K23HL118151). A pilot award from The Center on the Demography and Economics of Aging (CoA, National Institute of Aging P30 AG012857) supported this project. Dr. Matthiesen and Ms. Ranadive received support from the Summer Research Program funded by the National Institutes on Aging Short-Term Aging-Related Research Program (T35AG029795). Dr. Matthiesen also received funding from the Calvin Fentress Fellowship Program. Dr. Hariprasad reports being a consultant or participating on a speaker's bureau for Alcon, Allergan, Regeneron, Genentech, Optos, OD-OS, Bayer, Clearside Biomedical, and Ocular Therapeutix. Dr. Meltzer received funding from the National Institutes on Aging Short-Term Aging-Related Research Program (T35AG029795), and from the Agency for Healthcare Quality and Research through the Hospital Medicine and Economics Center for Education and Research in Therapeutics (U18 HS016967-01), and from the National Institute of Aging through a Midcareer Career Development Award (K24 AG031326-01), from the National Cancer Institute (KM1 CA156717), and from the National Center for Advancing Translational Science (2UL1TR000430-06). Dr. Arora received funding from the National Institutes on Aging Short-Term Aging-Related Research Program (T35AG029795) and National Institutes on Aging (K23AG033763). NR 11 TC 5 Z9 5 U1 4 U2 6 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 MAY PY 2015 VL 10 IS 5 BP 311 EP 313 DI 10.1002/jhm.2342 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CH3IV UT WOS:000353925100007 PM 25755206 ER PT J AU Wald, HL Leykum, LK Mattison, MLP Vasilevskis, EE Meltzer, DO AF Wald, Heidi L. Leykum, Luci K. Mattison, Melissa L. P. Vasilevskis, Eduard E. Meltzer, David O. TI A Patient-Centered Research Agenda for the Care of the Acutely Ill Older Patient SO JOURNAL OF HOSPITAL MEDICINE LA English DT Review ID MECHANICALLY VENTILATED PATIENTS; INAPPROPRIATE MEDICATION USE; GENERAL-HOSPITAL INPATIENTS; FACULTY-DEVELOPMENT PROGRAM; IMPROVE TRANSITIONAL CARE; DEPRESSIVE SYMPTOMS; COGNITIVE IMPAIRMENT; GERIATRICS EDUCATION; NURSING FACILITIES; MANAGEMENT PROGRAM AB Hospitalists and others acute-care providers are limited by gaps in evidence addressing the needs of the acutely ill older adult population. The Society of Hospital Medicine sponsored the Acute Care of Older Patients Priority Setting Partnership to develop a research agenda focused on bridging this gap. Informed by the Patient-Centered Outcomes Research Institute framework for identification and prioritization of research areas, we adapted a methodology developed by the James Lind Alliance to engage diverse stakeholders in the research agenda setting process. The work of the Partnership proceeded through 4 steps: convening, consulting, collating, and prioritizing. First, the steering committee convened a partnership of 18 stakeholder organizations in May 2013. Next, stakeholder organizations surveyed members to identify important unanswered questions in the acute care of older persons, receiving 1299 responses from 580 individuals. Finally, an extensive and structured process of collation and prioritization resulted in a final list of 10 research questions in the following areas: advanced-care planning, care transitions, delirium, dementia, depression, medications, models of care, physical function, surgery, and training. With the changing demographics of the hospitalized population, a workforce with limited geriatrics training, and gaps in evidence to inform clinical decision making for acutely ill older patients, the identified research questions deserve the highest priority in directing future research efforts to improve care for the older hospitalized patient and enrich training. Journal of Hospital Medicine 2015;10:318-327. (c) 2015 Society of Hospital Medicine C1 [Wald, Heidi L.] Univ Colorado, Sch Med, Div Hlth Care Policy & Res, Aurora, CO USA. [Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Mattison, Melissa L. P.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Sect Hosp Med, Boston, MA 02215 USA. [Vasilevskis, Eduard E.] Vanderbilt Univ, Sch Med, Sect Hosp Med, Div Gen Internal Med & Publ Hlth, Nashville, TN 37212 USA. [Vasilevskis, Eduard E.] Vanderbilt Univ, Sch Med, Ctr Qual Aging, Nashville, TN 37212 USA. [Vasilevskis, Eduard E.] VA Tennessee Valley Healthcare Syst, Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Meltzer, David O.] Univ Chicago, Dept Med, Sect Hosp Med, Chicago, IL 60637 USA. RP Wald, HL (reprint author), 13199 E Montview Blvd,Suite 400, Aurora, CO 80045 USA. EM heidi.wald@ucdenver.edu RI Meltzer, David/C-2926-2009 OI Meltzer, David/0000-0003-2790-7393 FU Association of Specialty Professors/American Society of Internal Medicine; John A. Hartford Foundation; National Institute on Aging of the National Institutes of Health [K23AG040157]; Veterans Affairs Clinical Research Center of Excellence; Geriatric Research, Education and Clinical Center (GRECC) FX This work was supported by the Association of Specialty Professors/American Society of Internal Medicine and the John A. Hartford Foundation. Dr. Vasilevskis was supported by the National Institute on Aging of the National Institutes of Health under award number K23AG040157 and the Veterans Affairs Clinical Research Center of Excellence, and the Geriatric Research, Education and Clinical Center (GRECC). Dr. Vasilevskis' institution receives grant funding for an aspect of submitted work. Dr. Meltzer is a PCORI Methodology Committee member. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans' Affairs. The authors report no conflicts of interest. NR 106 TC 1 Z9 1 U1 9 U2 15 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 MAY PY 2015 VL 10 IS 5 BP 318 EP 327 DI 10.1002/jhm.2356 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CH3IV UT WOS:000353925100009 PM 25877486 ER PT J AU Alhamud, A Taylor, PA Laughton, B van der Kouwe, AJW Meintjes, EM AF Alhamud, A. Taylor, Paul A. Laughton, Barbara van der Kouwe, Andre J. W. Meintjes, Ernesta M. TI Motion Artifact Reduction in Pediatric Diffusion Tensor Imaging Using Fast Prospective Correction SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE diffusion tensor imaging (DTI); prospective motion correction; navigated diffusion sequence (vNav); retrospective motion correction; tractography ID NORMAL BRAIN MATURATION; FRACTIONAL ANISOTROPY; NAVIGATOR ECHOES; HEAD MOTION; MRI; CHILDHOOD; CHILDREN; ARCHITECTURE; DISTORTION; IMAGES AB PurposeTo evaluate the patterns of head motion in scans of young children and to examine the influence of corrective techniques, both qualitatively and quantitatively. We investigate changes that both retrospective (with and without diffusion table reorientation) and prospective (implemented with a short navigator sequence) motion correction induce in the resulting diffusion tensor measures. Materials and MethodsEighteen pediatric subjects (aged 5-6 years) were scanned using 1) a twice-refocused, 2D diffusion pulse sequence, 2) a prospectively motion-corrected, navigated diffusion sequence with reacquisition of a maximum of five corrupted diffusion volumes, and 3) a T-1-weighted structural image. Mean fractional anisotropy (FA) values in white and gray matter regions, as well as tractography in the brainstem and projection fibers, were evaluated to assess differences arising from retrospective (via FLIRT in FSL) and prospective motion correction. In addition to human scans, a stationary phantom was also used for further evaluation. ResultsIn several white and gray matter regions retrospective correction led to significantly (P<0.05) reduced FA means and altered distributions compared to the navigated sequence. Spurious tractographic changes in the retrospectively corrected data were also observed in subject data, as well as in phantom and simulated data. ConclusionDue to the heterogeneity of brain structures and the comparatively low resolution (approximate to 2 mm) of diffusion data using 2D single shot sequencing, retrospective motion correction is susceptible to distortion from partial voluming. These changes often negatively bias diffusion tensor imaging parameters. Prospective motion correction was shown to produce smaller changes.J. Magn. Reson. Imaging 2014. (c) 2014 Wiley Periodicals, Inc. J. Magn. Reson. Imaging 2015;41:1353-1364. (c) 2014 Wiley Periodicals, Inc. C1 [Alhamud, A.; Taylor, Paul A.; Meintjes, Ernesta M.] Univ Cape Town, Fac Hlth Sci, Dept Human Biol, MRC UCT Med Imaging Res Unit, ZA-7925 Cape Town, South Africa. [Taylor, Paul A.] African Inst Math Sci, Western Cape, South Africa. [Laughton, Barbara] Univ Stellenbosch, Dept Pediat & Child Hlth, Childrens Infect Dis Clin Res Unit, Cape Town, South Africa. [Laughton, Barbara] Tygerberg Hosp, Cape Town, South Africa. [van der Kouwe, Andre J. W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. RP Alhamud, A (reprint author), Univ Cape Town Observ, Fac Hlth Sci, Dept Human Biol, ZA-7925 Cape Town, South Africa. EM alkk1973@gmail.com RI Laughton, Barbara/Q-3496-2016 OI Laughton, Barbara/0000-0001-7260-7723 FU NIH [R21AA017410, R01HD071664, R21MH096559, R21EB008547, P41RR014075, U19 AI53217]; NRF [CPRR78737] FX Contract grant sponsor: NIH; Contract grant numbers: R21AA017410, R01HD071664, R21MH096559, R21EB008547, P41RR014075, U19 AI53217; Contract grant sponsor: NRF; Contract grant number: CPRR78737. NR 41 TC 3 Z9 3 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAY PY 2015 VL 41 IS 5 BP 1353 EP 1364 DI 10.1002/jmri.24678 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CG9ND UT WOS:000353641600023 PM 24935904 ER PT J AU Castellanos-Rizaldos, E Paweletz, C Song, C Oxnard, GR Mamon, H Janne, PA Makrigiorgos, GM AF Castellanos-Rizaldos, Elena Paweletz, Cloud Song, Chen Oxnard, Geoffrey R. Mamon, Harvey Jaenne, Pasi A. Makrigiorgos, G. Mike TI Enhanced Ratio of Signals Enables Digital Mutation Scanning for Rare Allele Detection SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID REAL-TIME PCR; UNKNOWN DNA MUTATIONS; COLD-PCR; MELTING ANALYSIS; KRAS MUTATIONS; NONINVASIVE DETECTION; COLORECTAL-CANCER; LUNG-CANCER; ENRICHMENT; QUANTIFICATION AB The use of droplet digital PCR (ddPCR) for low-Level DNA mutation detection in cancer, prenatal diagnosis, and infectious diseases is growing rapidly. However, although ddPCR has been implemented successfully for detection of rare mutations at pre-determined positions, no ddPCR adaptation for mutation scanning exists. Yet, frequently, clinically relevant mutations reside on multiple sequence positions in tumor suppressor genes or complex hotspot mutations in oncogenes. Here, we describe a combination of coamplification at Lower denaturation temperature PCR (COLD-PCR) with ddPCR that enables digital mutation scanning within approximately 50-bp sections of a target amplicon. Two FAM/HEX-labeled hydrolysis probes matching the wild-type sequence are used during ddPCR. The ratio of FAM/HEX-positive droplets is constant when wild-type amplicons are amplified but deviates when mutations anywhere under the FAM or HEX probes are present. To enhance the change in FAM/HEX ratio, we employed COLD-PCR cycling conditions that enrich mutation-containing amplicons anywhere on the sequence. We validated COLD-ddPCR on multiple mutations in TP53 and in EGFR using serial mutation dilutions and cell-free circulating DNA samples, and demonstrate detection down to approximately 0.2% to 1.2% mutation abundance. COLD-ddPCR enables a simple, rapid, and robust two-fluorophore detection method for the identification of multiple mutations during ddPCR and potentially can identify unknown DNA variants present in the target sequence. C1 [Castellanos-Rizaldos, Elena; Song, Chen; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Div DNA Repair & Genome Stabil, Boston, MA USA. [Paweletz, Cloud; Oxnard, Geoffrey R.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dept Med Oncol, Boston, MA USA. [Paweletz, Cloud; Jaenne, Pasi A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Boston, MA USA. [Oxnard, Geoffrey R.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA USA. [Mamon, Harvey; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Mamon, Harvey; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Canc Ctr, Boston, MA USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Radiat Therapy, Level L2,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@lroc.harvard.edu RI Song, Chen/H-6615-2015 OI Song, Chen/0000-0002-4439-4377 FU National Cancer Institute [R21CA-155615, R21CA-175542, R01CA135257] FX Supported by National Cancer Institute grant numbers R21CA-155615 (G.M.M.), R21CA-175542 (G.M.M.), and R01CA135257 (P.A.J.). NR 37 TC 7 Z9 9 U1 5 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAY PY 2015 VL 17 IS 3 BP 284 EP 292 DI 10.1016/j.jmoldx.2014.12.003 PG 9 WC Pathology SC Pathology GA CH2GO UT WOS:000353843900008 PM 25772705 ER PT J AU Addington, J Liu, L Buchy, L Cadenhead, KS Cannon, TD Cornblatt, BA Perkins, DO Seidman, LJ Tsuang, MT Walker, EF Woods, SW Bearden, CE Mathalon, DH McGlashan, TH AF Addington, Jean Liu, Lu Buchy, Lisa Cadenhead, Kristin S. Cannon, Tyrone D. Cornblatt, Barbara A. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming T. Walker, Elaine F. Woods, Scott W. Bearden, Carrie E. Mathalon, Daniel H. McGlashan, Thomas H. TI North American Prodrome Longitudinal Study (NAPLS 2) The Prodromal Symptoms SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Prodromal; psychosis; symptoms; at-risk; youth ID CLINICAL HIGH-RISK; EPISODE SCHIZOPHRENIA; 1ST EPISODE; PSYCHOSIS; INDIVIDUALS; PREDICTION; TRANSITION; YOUTH AB In studies describing the long-term follow-up up of youth at clinical high risk (CHR) of psychosis, little attention has been given to details of specific prodromal symptoms. In this paper, we describe the prodromal symptoms of 764 CHR participants recruited in the multi-site North American Prodrome Longitudinal Study (NAPLS). Symptoms were rated on the Scale of Prodromal Symptoms (SOPS) at baseline and 6-, 12-, 18-, and 24-month follow-ups. Clinical outcome at the 2-year assessment was categorized as psychotic, prodromal progression, symptomatic or in remission. Most of the CHR sample (92%) met criteria for the attenuated positive symptoms syndrome (APSS). Significant improvements in SOPS symptoms were observed over time. Unusual thought content, disorganized communication, and overall ratings on disorganized symptoms differentiated those who transitioned to psychosis from the other clinical outcome groups. Suspiciousness and total positive symptoms differentiated those in remission from the other clinical outcome groups. C1 [Addington, Jean; Liu, Lu; Buchy, Lisa] Univ Calgary, Dept Psychiat, Calgary, AB T2N 4Z6, Canada. [Cadenhead, Kristin S.; Tsuang, Ming T.] UCSD, Dept Psychiat, La Jolla, CA USA. [Cannon, Tyrone D.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Woods, Scott W.; McGlashan, Thomas H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Mathalon, Daniel H.] UCSF, Dept Psychiat, San Francisco, CA USA. [Mathalon, Daniel H.] SFVA Med Ctr, San Francisco, CA USA. RP Addington, J (reprint author), Univ Calgary, Ctr Mental Hlth Res & Educ, 3280 Hosp Dr NW, Calgary, AB T2N 4Z6, Canada. EM jmadding@ucalgary.ca FU National Institute of Mental Health [U01MH081984]; Commonwealth of Massachusetts [SCDMH82101008006]; [U01 MH081928]; [P50 MH080272]; [R01 MH60720]; [U01 MH082022]; [K24 MH76191]; [U01MH081902]; [P50MH066286]; [U01MH082004]; [U01MH081988]; [U01MH082022]; [UO1 MH081857-05] FX This study was supported by the National Institute of Mental Health (grant U01MH081984 to Dr Addington; grants U01 MH081928; P50 MH080272; Commonwealth of Massachusetts SCDMH82101008006 to Dr Seidman; grants R01 MH60720, U01 MH082022, and K24 MH76191 to Dr Cadenhead; grant U01MH081902 to Dr Cannon; P50MH066286 (Prodromal Core) to Dr Bearden; grant U01MH082004 to Dr Perkins; grant U01MH081988 to Dr Walker; grant U01MH082022 to Dr Woods; and UO1 MH081857-05 grant to Dr Cornblatt. The NIMH had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 23 TC 13 Z9 13 U1 3 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAY PY 2015 VL 203 IS 5 BP 328 EP 335 DI 10.1097/NMD.0000000000000290 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CH0CO UT WOS:000353686800005 PM 25919383 ER PT J AU Zollfrank, AA Trevino, KM Cadge, W Balboni, MJ Thiel, MM Fitchett, G Gallivan, K VanderWeele, T Balboni, TA AF Zollfrank, Angelika A. Trevino, Kelly M. Cadge, Wendy Balboni, Michael J. Thiel, Mary Martha Fitchett, George Gallivan, Kathleen VanderWeele, Tyler Balboni, Tracy A. TI Teaching Health Care Providers To Provide Spiritual Care: A Pilot Study SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID QUALITY-OF-LIFE; CANCER-PATIENTS; MEDICAL-SCHOOL; END; SUPPORT; ASSOCIATIONS; PHYSICIANS; ILL; PERCEPTIONS; GUIDELINES AB Background: Health care providers' lack of education on spiritual care is a significant barrier to the integration of spiritual care into health care services. Objective: The study objective was to describe the training program, Clinical Pastoral Education for Healthcare Providers (CPE-HP) and evaluate its impact on providers' spiritual care skills. Methods: Fifty CPE-HP participants completed self-report surveys at baseline and posttraining measuring frequency of and confidence in providing religious/spiritual (R/S) care. Four domains were assessed: (1) ability and (2) frequency of R/S care provision; (3) comfort using religious language; and (4) confidence in providing R/S care. Results: At baseline, participants rated their ability to provide R/S care and comfort with religious language as "fair." In the previous two weeks, they reported approximately two R/S patient conversations, initiated R/S conversations less than twice, and prayed with patients less than once. Posttraining participants' reported ability to provide spiritual care increased by 33% (p<0.001). Their comfort using religious language improved by 29% (p<0.001), and frequency of R/S care increased 75% (p<0.001). Participants reported having 61% more (p<0.001) R/S conversations and more frequent prayer with patients (95% increase; p<0.001). Confidence in providing spiritual care improved by 36% overall, by 20% (p<0.001) with religiously concordant patients, and by 43% (p<0.001) with religiously discordant patients. Conclusions: This study suggests that CPE-HP is an effective approach for training health care providers in spiritual care. Dissemination of this training may improve integration of spiritual care into health care, thereby strengthening comprehensive patient-centered care. C1 [Zollfrank, Angelika A.] Yale New Haven Med Ctr, Dept Spiritual Care, New Haven, CT 06511 USA. [Trevino, Kelly M.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Cadge, Wendy] Brandeis Univ, Dept Sociol, Waltham, MA USA. [Balboni, Michael J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Thiel, Mary Martha] HebrewSenior Life, Boston, MA USA. [Fitchett, George] Rush Univ, Med Ctr, Dept Relig Hlth & Human Values, Chicago, IL 60612 USA. [Gallivan, Kathleen] Brigham & Womens Hosp, Boston, MA 02115 USA. [VanderWeele, Tyler] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Zollfrank, AA (reprint author), Yale New Haven Med Ctr, Dept Spiritual Care, 20 York St,Hunter 5, New Haven, CT 06511 USA. EM Angelika.Zollfrank@ynhh.org FU NCI NIH HHS [U54 CA156732] NR 36 TC 2 Z9 2 U1 0 U2 7 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 MAY 1 PY 2015 VL 18 IS 5 BP 408 EP 414 DI 10.1089/jpm.2014.0306 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CH0LC UT WOS:000353710300006 PM 25871494 ER PT J AU Bath, E Pope, K Ijadi-Maghsoodi, R Thomas, C AF Bath, Eraka Pope, Kayla Ijadi-Maghsoodi, Roya Thomas, Christopher TI Juvenile Life Without Parole: Updates on Legislative and Judicial Trends and on Facilitating Fair Sentencing SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 [Bath, Eraka] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Pope, Kayla] Creighton Univ, Med Ctr, CHI Hlth, Boys Town Natl Res Hosp, Omaha, NE USA. [Pope, Kayla] Univ Nebraska Med Ctr, Omaha, NE USA. [Ijadi-Maghsoodi, Roya] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Thomas, Christopher] Univ Texas Med Branch, Galveston, TX 77555 USA. RP Bath, E (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Child Forens Serv, 300 Med Plaza,Room 1243, Los Angeles, CA 90024 USA. EM ebath@mednet.ucla.edu FU Office of Academic Affiliations through the VA Advanced Fellowship Program in Women's Health FX Dr Ijadi-Maghsoodi is supported by the Office of Academic Affiliations through the VA Advanced Fellowship Program in Women's Health. NR 5 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2015 VL 54 IS 5 BP 343 EP 347 DI 10.1016/j.jaac.2015.02.011 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CG9WE UT WOS:000353670000002 PM 25901768 ER PT J AU Tan, TC Bouras, S Sawaya, H Sebag, IA Cohen, V Picard, MH Passeri, J Kuter, I Scherrer-Crosbie, M AF Tan, Timothy C. Bouras, Souhila Sawaya, Heloisa Sebag, Igal A. Cohen, Victor Picard, Michael H. Passeri, Jonathan Kuter, Irene Scherrer-Crosbie, Marielle TI Time Trends of Left Ventricular Ejection Fraction and Myocardial Deformation Indices in a Cohort of Women with Breast Cancer Treated with Anthracyclines, Taxanes, and Trastuzumab SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Cardiotoxicity; Breast cancer; Echocardiography; Strain; Strain rate; LVEF ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TRIAL COMPARING DOXORUBICIN; CONGESTIVE-HEART-FAILURE; INDUCED CARDIOMYOPATHY; INDUCED CARDIOTOXICITY; EUROPEAN-ASSOCIATION; CARDIAC DYSFUNCTION; AMERICAN-SOCIETY; RANDOMIZED-TRIAL; ADJUVANT THERAPY AB Background: Trastuzumab, a HER2 monoclonal antibody, has transformed the prognosis of patients with the aggressive HER2-positive breast cancer type. Trastuzumab augments the cardiotoxic effects of anthracyclines, but its effect is thought to be at least partially reversible. The objective of this study was to examine the time trends of left ventricular (LV) size and function in a cohort of women treated with anthracyclines and trastuzumab. Methods: Twenty-nine patients >18 years of age with first-time breast cancer treated with anthracyclines and trastuzumab were monitored using echocardiography before, at the completion of, and at a median follow-up of 24.7 months (interquartile range, 15.9-34 months) after the end of their cancer treatment. LV volume, LV ejection fraction, and global peak systolic longitudinal strain and strain rate were measured in the apical four-and two chamber views. Left ventricular ejection fraction was measured using a modified Simpson's biplane method. Results: LV end-diastolic and end-systolic volumes increased at the end of treatment compared with baseline and did not recover during follow-up. Left ventricular ejection fraction, strain, and strain rate decreased at the end of treatment compared with baseline (from 64 +/- 6% to 59 +/- 8%, from -20.0 +/- 2.5% to -17.6 +/- 2.6%, and from -1.26 +/- 0.23 to -1.13 +/- 0.16 sec(-1), respectively; P < .05 for all parameters) and remained decreased at follow-up. Conclusions: LV dilation and subclinical impairment in cardiac function persists >2 years after the end of anthracycline and trastuzumab treatment, without significant recovery after trastuzumab cessation, suggestive of long-term underlying cardiac damage and remodeling. C1 [Tan, Timothy C.; Bouras, Souhila; Sawaya, Heloisa; Picard, Michael H.; Passeri, Jonathan; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Tan, Timothy C.; Bouras, Souhila; Sawaya, Heloisa; Picard, Michael H.; Passeri, Jonathan; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kuter, Irene] Massachusetts Gen Hosp, MGH Ctr Breast Canc, Boston, MA 02114 USA. [Kuter, Irene] Harvard Univ, Sch Med, Boston, MA USA. [Sebag, Igal A.] Sir Mortimer B Davis Jewish Hosp, Echocardiog Lab, Montreal, PQ, Canada. [Sebag, Igal A.] Sir Mortimer B Davis Jewish Hosp, Div Cardiol, Montreal, PQ, Canada. [Cohen, Victor] Sir Mortimer B Davis Jewish Hosp, Dept Oncol, Montreal, PQ, Canada. [Cohen, Victor] McGill Univ, Montreal, PQ, Canada. [Cohen, Victor] Segal Canc Ctr, Dept Med, Montreal, PQ, Canada. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Blake 254, Boston, MA 02114 USA. EM marielle@crosbie.com OI Picard, Michael/0000-0002-9264-3243 FU American Society for Echocardiography Career Development Award; Robert and Elizabeth Albert Study Grant (Royal Australasian College of Physicians); Susan G. Komen for the Cure Foundation; Claflin Distinguished Scholar Award; Clinical Innovation Award from MGH FX Dr Tan was supported by an American Society for Echocardiography Career Development Award and a Robert and Elizabeth Albert Study Grant (Royal Australasian College of Physicians). Dr Scherrer-Crosbie was funded by an investigator-initiated grant from Susan G. Komen for the Cure Foundation, Claflin Distinguished Scholar Award and a Clinical Innovation Award from MGH. NR 51 TC 10 Z9 10 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAY PY 2015 VL 28 IS 5 BP 509 EP 514 DI 10.1016/j.echo.2015.02.001 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH2ZJ UT WOS:000353894400002 PM 25772019 ER PT J AU Tardif, S Ross, C Bergman, P Fernandez, E Javors, M Salmon, A Spross, J Strong, R Richardson, A AF Tardif, Suzette Ross, Corinna Bergman, Phillip Fernandez, Elizabeth Javors, Marty Salmon, Adam Spross, Jennifer Strong, Randy Richardson, Arlan TI Testing Efficacy of Administration of the Antiaging Drug Rapamycin in a Nonhuman Primate, the Common Marmoset SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Rapamycin; mTOR; Marmoset; Nonhuman primate ID GENETICALLY HETEROGENEOUS MICE; EXTENDS LIFE-SPAN AB This report is the first description of dosing procedures, pharmacokinetics, biochemical action, and general tolerability of the antiaging drug rapamycin in the common marmoset, a small and short-lived monkey. Eudragit-encapsulated rapamycin was given orally to trained marmosets in a short-term (3 weeks) and a long-term (14 months) study. Circulating trough rapamycin levels (mean = 5.2 ng/mL; 1.93-10.73 ng/mL) achieved at roughly 1.0 mg/kg/day was comparable to those reported in studies of rodents and within the therapeutic range for humans. Long-term treated animals (6/8) indicated a reduction in mammalian target of rapamycin complex 1 signaling as noted by a decrease in the phospho rpS6 to total rpS6 ratio after 2 weeks of treatment. All long-term treated subjects had detectable concentrations of rapamycin in liver (4.7-19.9 pg/mg) and adipose tissue (2.2-32.8 pg/mg) with reduced mammalian target of rapamycin signaling in these tissues. There was no evidence of clinical anemia, fibrotic lung changes, or mouth ulcers. The observed death rate in the long-term study was as expected given the animals' ages. The ability to rapidly and reliably dose socially housed marmosets with an oral form of rapamycin that is well tolerated and that demonstrates a suppression of the mammalian target of rapamycin pathway leads us to conclude that this species offers a viable model for rapamycin testing to establish safety and efficacy for long-term antiaging intervention. C1 [Tardif, Suzette; Ross, Corinna; Bergman, Phillip; Fernandez, Elizabeth; Javors, Marty; Salmon, Adam; Spross, Jennifer; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Tardif, Suzette] Texas Biomed Res Inst, Southwest Natl Primate Res Ctr, San Antonio, TX USA. [Ross, Corinna; Strong, Randy] Texas A&M San Antonio, Dept Arts & Sci, San Antonio, TX USA. [Fernandez, Elizabeth; Salmon, Adam] South Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. [Richardson, Arlan] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Richardson, Arlan] Oklahoma City VA Med Ctr, Oklahoma City, OK USA. RP Tardif, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM tardif@uthscsa.edu FU Barshop Institute for Longevity Aging Studies; Glenn Foundation; San Antonio Nathan Shock Center of Excellence in the Basic Biology of Aging FX This research was financially supported by the Barshop Institute for Longevity & Aging Studies, the Glenn Foundation, and the San Antonio Nathan Shock Center of Excellence in the Basic Biology of Aging. NR 19 TC 9 Z9 9 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2015 VL 70 IS 5 BP 577 EP 587 DI 10.1093/gerona/glu101 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CH3AX UT WOS:000353899100005 PM 25038772 ER PT J AU Chen, DS Betz, J Yaffe, K Ayonayon, HN Kritchevsky, S Martin, KR Harris, TB Purchase-Helzner, E Satterfield, S Xue, QL Pratt, S Simonsick, EM Lin, FR AF Chen, David S. Betz, Joshua Yaffe, Kristine Ayonayon, Hilsa N. Kritchevsky, Stephen Martin, Kathryn R. Harris, Tamara B. Purchase-Helzner, Elizabeth Satterfield, Suzanne Xue, Qian-Li Pratt, Sheila Simonsick, Eleanor M. Lin, Frank R. CA Hlth ABC Study TI Association of Hearing Impairment with Declines in Physical Functioning and the Risk of Disability in Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Physical function; Physical performance; Epidemiology ID LOWER-EXTREMITY FUNCTION; GAIT SPEED DECLINE; PERFORMANCE BATTERY; BODY-COMPOSITION; UNITED-STATES; SUBSEQUENT DISABILITY; VESTIBULAR FUNCTION; PROGNOSTIC VALUE; HEALTH; SURVIVAL AB Background: Identifying factors associated with functional declines in older adults is important given the aging of the population. We investigated if hearing impairment is independently associated with objectively measured declines in physical functioning in a community-based sample of older adults. Methods: Prospective observational study of 2,190 individuals from the Health, Aging, and Body Composition study. Participants were followed annually for up to 11 visits. Hearing was measured with pure-tone audiometry. Physical functioning and gait speed were measured with the Short Physical Performance Battery (SPPB). Incident disability and requirement for nursing care were assessed semiannually through self-report. Results: In a mixed-effects model, greater hearing impairment was associated with poorer physical functioning. At both Visit 1 and Visit 11, SPPB scores were lower in individuals with mild (10.14 [95% CI 10.04-10.25], p < .01; 7.35 [95% CI 7.12-7.58], p < .05) and moderate or greater hearing impairment (10.04 [95% CI 9.90-10.19], p < .01; 7.00 [95% CI 6.69-7.32], p < .01) than scores in normal hearing individuals (10.36 [95% CI 10.26-10.46]; 7.71 [95% CI 7.49-7.92]). We observed that women with moderate or greater hearing impairment had a 31% increased risk of incident disability (Hazard ratio [HR] = 1.31 [95% CI 1.08-1.60], p < .01) and a 31% increased risk of incident nursing care requirement (HR = 1.31 [95% CI 1.05-1.62], p = .02) compared to women with normal hearing. Conclusions: Hearing impairment is independently associated with poorer objective physical functioning in older adults, and a 31% increased risk for incident disability and need for nursing care in women. C1 [Chen, David S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Chen, David S.; Betz, Joshua; Xue, Qian-Li; Lin, Frank R.] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. [Yaffe, Kristine; Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kritchevsky, Stephen] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Martin, Kathryn R.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Martin, Kathryn R.; Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Martin, Kathryn R.] Univ Aberdeen, Sch Med & Dent, Epidemiol Grp, Aberdeen, Scotland. [Purchase-Helzner, Elizabeth] Suny Downstate Med Ctr, Dept Epidemiol & Biostat, Brooklyn, NY 11203 USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Xue, Qian-Li] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Pratt, Sheila] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Pratt, Sheila] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Lin, Frank R.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Lin, FR (reprint author), Johns Hopkins Ctr Aging & Hlth, 2024 Monument St,Suite 2-700, Baltimore, MD 21287 USA. EM flin1@jhmi.edu OI Betz, Joshua/0000-0003-4488-9799 FU NIH [K23DC011279]; Eleanor Schwartz Charitable Foundation; Triological Society/American College of Surgeons; National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050]; NINR [R01NR012459]; NIH, National Institute on Aging FX This manuscript was supported in part by NIH K23DC011279, the Eleanor Schwartz Charitable Foundation, and a Triological Society/American College of Surgeons Clinician Scientist Award, as well as National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, NINR grant R01NR012459, and the Intramural Research Program of the NIH, National Institute on Aging. NR 44 TC 14 Z9 15 U1 4 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2015 VL 70 IS 5 BP 654 EP 661 DI 10.1093/gerona/glu207 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CH3AX UT WOS:000353899100016 PM 25477427 ER PT J AU Wipf, JE AF Wipf, Joyce E. TI Women's Health Preface SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle VA Ctr Excellence Primary Care Educ, Seattle, WA 98108 USA. RP Wipf, JE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Seattle VA Ctr Excellence Primary Care Educ, 1660 South Columbian Way Mailstop S-123-COE, Seattle, WA 98108 USA. EM jwipf@uw.edu NR 0 TC 0 Z9 0 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 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2015 VL 99 IS 3 BP XVII EP XVIII DI 10.1016/j.mcna.2015.03.001 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CG9VH UT WOS:000353667700002 PM 25841608 ER PT J AU Evans, G Sutton, EL AF Evans, Ginger Sutton, Eliza L. TI Oral Contraception SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Oral contraception; Ethinyl estradiol; Levonorgestrel; Venous thromboembolism; Medical eligibility criteria ID COMBINED HORMONAL CONTRACEPTIVES; RANDOMIZED-CONTROLLED-TRIAL; POLYCYSTIC-OVARY-SYNDROME; UNITED-STATES; VENOUS THROMBOEMBOLISM; DOUBLE-BLIND; POSTPARTUM CONTRACEPTION; ETHINYL ESTRADIOL; FAMILY-HISTORY; BREAST-CANCER AB Oral contraception (OC) remains a popular noninvasive, readily reversible approach for pregnancy prevention and, largely off label, for control of acne, hirsutism, dysmenorrhea, irregular menstruation, menorrhagia, and other menstrual-related symptoms. Many OC formulations exist, with generics offering lower cost and comparable efficacy. Certain medical conditions, including hypertension, migraine, breast cancer, and risk of venous thromboembolism (VTE), present contraindications. Blood pressure measurement is the only physical examination or testing needed before prescription. Although no 00 is clearly superior to others, OCs containing the second-generation progestin levonorgestrel have been associated with lower VTE risk than those containing other progestins. C1 [Evans, Ginger] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Sutton, Eliza L.] Univ Washington, Womens Hlth Care Ctr, Seattle, WA 98105 USA. RP Evans, G (reprint author), VA Puget Sound Hlth Care Syst, 1660 South Columbian Way,S-123 PCC, Seattle, WA 98108 USA. EM gingere@u.washington.edu NR 121 TC 5 Z9 6 U1 4 U2 17 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 MAY PY 2015 VL 99 IS 3 BP 479 EP + DI 10.1016/j.mcna.2015.01.004 PG 26 WC Medicine, General & Internal SC General & Internal Medicine GA CG9VH UT WOS:000353667700005 PM 25841596 ER PT J AU Allen, C Kolehmainen, C AF Allen, Caitlin Kolehmainen, Christine TI Intrauterine Devices and Other Forms of Contraception: Thinking Outside the Pack SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Contraception; Intrauterine devices; Subcutaneous implants; Barrier methods; Emergency contraception ID ACTING REVERSIBLE CONTRACEPTION; EMERGENCY CONTRACEPTION; ULIPRISTAL ACETATE; SEXUAL-BEHAVIOR; TUBAL-LIGATION; UNITED-STATES; VAGINAL RING; WOMEN; RISK; LEVONORGESTREL AB A variety of contraception options are available in addition to traditional combined oral contraceptive pills. Newer long-acting reversible contraceptive (LARC) methods such as intrauterine devices and subcutaneous implants are preferred because they do not depend on patient compliance. They are highly effective and appropriate for most women. Female and male sterilization are other effective but they are irreversible and require counseling to minimize regret. The contraceptive injection, patch, and ring do not require daily administration, but their typical efficacy rates are lower than LARC methods and similar to those for combined oral contraceptive pills. C1 [Allen, Caitlin] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53705 USA. [Kolehmainen, Christine] Univ Wisconsin, Sch Med & Publ Hlth, William S Middleton Mem Vet Hosp, Madison, WI 53703 USA. RP Allen, C (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, 5120 MFCB,1685 Highland Ave, Madison, WI 53705 USA. EM callen@uwhealth.org NR 64 TC 0 Z9 0 U1 1 U2 14 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 MAY PY 2015 VL 99 IS 3 BP 505 EP + DI 10.1016/j.mcna.2015.01.005 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA CG9VH UT WOS:000353667700006 PM 25841597 ER PT J AU Takahashi, TA Johnson, KM AF Takahashi, Traci A. Johnson, Kay M. TI Menopause SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Menopause; Hot flashes; Vulvovaginal atrophy; Vasomotor symptoms; Hormone therapy; Estrogen ID CONJUGATED EQUINE ESTROGENS; HEALTH INITIATIVE MEMORY; HYSTERECTOMIZED POSTMENOPAUSAL WOMEN; GLOBAL COGNITIVE FUNCTION; VULVO-VAGINAL ATROPHY; HORMONE-THERAPY; VASOMOTOR SYMPTOMS; MIDLIFE WOMEN; VENOUS THROMBOEMBOLISM; TRANSITION AB Women generally spend the last third of their lifetime in menopause, after their reproductive years have ended. During menopause, women experience a variety of predictable symptoms and conditions related to changes in sex hormone levels and aging. The menopausal transition precedes menopause by several years and is usually characterized by irregularity of the menstrual cycle and by hot flashes and night sweats. After menopause, genitourinary symptoms predominate, including vulvovaginal atrophy and dryness and lower urinary tract symptoms, including urinary frequency, urgency, and nocturia. Hormonal treatment is effective for vasomotor and genitourinary symptoms, but the understanding of its impact on cardiovascular disease, cognitive dysfunction, and depression continues to evolve. C1 [Takahashi, Traci A.; Johnson, Kay M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98108 USA. [Takahashi, Traci A.; Johnson, Kay M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Takahashi, TA (reprint author), Univ Washington, Sch Med, Dept Med, 1660 South Columbian Way,S-123 PCC, Seattle, WA 98108 USA. EM traci@u.washington.edu NR 51 TC 9 Z9 12 U1 6 U2 15 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 MAY PY 2015 VL 99 IS 3 BP 521 EP + DI 10.1016/j.mcna.2015.01.006 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA CG9VH UT WOS:000353667700007 PM 25841598 ER PT J AU Gill, SK AF Gill, Sharon K. TI Cardiovascular Risk Factors and Disease in Women SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE ASCVD; Heart disease; Stroke; Risk factors; Women; Prevention ID POLYCYSTIC-OVARY-SYNDROME; DENSITY-LIPOPROTEIN CHOLESTEROL; FORCE RECOMMENDATION STATEMENT; AMERICAN-HEART-ASSOCIATION; EXTENDED-RELEASE NIACIN; BLOOD-PRESSURE; PHYSICAL-ACTIVITY; STATIN THERAPY; ORAL-CONTRACEPTIVES; ATRIAL-FIBRILLATION AB Coronary artery disease and stroke predominantly affect older women as opposed to younger women, but the risk factors that contribute to atherosclerotic cardiovascular disease risk often start in young women. Young women with polycystic ovary syndrome (PCOS), with migraine, and who use oral contraceptive pills (OCPs) have short-term increases in thrombotic complications that can result in coronary events or stroke. Attention should be focused on risk reduction in women of all ages. Screening for and discussing diabetes, hypertension, obesity, smoking, migraine, PCOS, and pregnancy complication history and discussing the pros and cons of hormone and statin medications are part of reducing cardiovascular risk for women. C1 VA Puget Sound, Womens Hlth Program, Seattle, WA 98108 USA. RP Gill, SK (reprint author), VA Puget Sound, Womens Hlth Program, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Sharon.gill@va.gov NR 77 TC 3 Z9 3 U1 1 U2 15 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 MAY PY 2015 VL 99 IS 3 BP 535 EP + DI 10.1016/j.mcna.2015.01.007 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA CG9VH UT WOS:000353667700008 PM 25841599 ER PT J AU Beste, LA Bondurant, HC Ioannou, GN AF Beste, Lauren A. Bondurant, Hollye C. Ioannou, George N. TI Prevalence and Management of Chronic Hepatitis C Virus Infection in Women SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Viral hepatitis; Women; Pregnancy; Antiviral therapy ID GENOTYPE 1 INFECTION; TREATMENT-NAIVE PATIENTS; INTERFERON-ALPHA 2A; PEGYLATED INTERFERON; NATURAL-HISTORY; PLUS RIBAVIRIN; UNITED-STATES; RISK-FACTORS; PERINATAL TRANSMISSION; FIBROSIS PROGRESSION AB Hepatitis C virus (HCV) is the most common blood-borne pathogen in the United States and is a leading cause of cirrhosis, need for liver transplantation, and liver-related mortality in women. Women should be offered testing if they fall in a high-risk group for exposure. Compared to men, women have higher rates of spontaneous HCV clearance after exposure and slower progression to cirrhosis but are more susceptible to liver damage from comorbid alcohol use. Premenopausal women with HCV should be counseled about the risks of antiviral treatment during pregnancy and the potential for vertical transmission of HCV to their offspring. C1 [Beste, Lauren A.] VA Puget Sound Hlth Care Syst, Primary Care Serv, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Beste, Lauren A.] Univ Washington, Dept Internal Med, Div Gen Internal Med, Seattle, WA 98195 USA. [Bondurant, Hollye C.] VA Puget Sound Hlth Care Syst, Serv Pharm, Seattle, WA 98108 USA. [Ioannou, George N.] VA Puget Sound Hlth Care Syst, Hosp & Specialty Med Serv, Seattle, WA 98108 USA. [Ioannou, George N.] Univ Washington, Dept Internal Med, Div Gastroenterol, Seattle, WA 98195 USA. RP Beste, LA (reprint author), VA Puget Sound Hlth Care Syst, Primary Care Serv, Hlth Serv Res & Dev, 1660 South Columbian Way,5-111 GI, Seattle, WA 98108 USA. EM Lauren.beste@va.gov NR 49 TC 2 Z9 2 U1 1 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 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2015 VL 99 IS 3 BP 575 EP + DI 10.1016/j.mcna.2015.01.009 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA CG9VH UT WOS:000353667700010 PM 25841601 ER PT J AU Golob, AL Laya, MB AF Golob, Anna L. Laya, Mary B. TI Osteoporosis Screening, Prevention, and Management SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Osteoporosis; Osteopenia; Fragility fractures; Prevention; Screening; Management ID SERVICES TASK-FORCE; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; VITAMIN-D; RANDOMIZED-TRIAL; RECOMMENDATION STATEMENT; CALCIUM SUPPLEMENTATION; VERTEBRAL FRACTURE; SALMON-CALCITONIN; RISK AB Osteoporosis is characterized by low bone mineral density (BMD) and abnormal bone architecture. Common fracture sites are vertebrae, proximal femur, and distal forearm. Osteoporosis is underdiagnosed and undertreated. All women 65 and older should be screened. Consider screening younger postmenopausal women with elevated risk. Osteoporosis is diagnosed based on T score or a fragility fracture. Women with osteoporosis or who have a 10-year risk of any major fracture of 20% or hip fracture of 3% should be evaluated for causes of low bone density and treated with an osteoporosis-specific medication, lifestyle interventions, and calcium and vitamin D intake. C1 [Golob, Anna L.] Univ Washington, Dept Med, Div Gen Internal Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Laya, Mary B.] Univ Washington, Gen Internal Med Ctr, UW Med Ctr, Div Gen Internal Med,Dept Med, Seattle, WA 98105 USA. RP Golob, AL (reprint author), Univ Washington, Dept Med, Div Gen Internal Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Anna.Golob@va.gov NR 49 TC 24 Z9 29 U1 5 U2 37 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 MAY PY 2015 VL 99 IS 3 BP 587 EP + DI 10.1016/j.mcna.2015.01.010 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA CG9VH UT WOS:000353667700011 PM 25841602 ER PT J AU Levander, XA Overland, MK AF Levander, Ximena A. Overland, Maryann K. TI Care of Women Veterans SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Women veterans; Military cultural competency; Functional gastrointestinal disorders; Chronic pain syndromes; Post-traumatic stress disorder; Military sexual trauma; Veteran homelessness ID POSTTRAUMATIC-STRESS-DISORDER; IRRITABLE-BOWEL-SYNDROME; MILITARY SEXUAL TRAUMA; HEALTH-STATUS; PREVALENCE; RISK; FEMALE; HOMELESSNESS; ASSOCIATION; SYMPTOMS AB As more women have joined the US military, there has been a shift in the overall veteran population. Those who served in the US military, especially women, have undergone experiences that will impact their overall health and wellbeing. It is therefore critical for providers to better understand US military culture and be prepared on how to ask patients about their military experience. Health care providers need to be aware of the unique medical, psychiatric, and psychosocial needs of women veterans in order to best serve this patient population. C1 [Levander, Ximena A.; Overland, Maryann K.] Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Levander, XA (reprint author), 1959 Northeast Pacific St,Box 356421, Seattle, WA 98195 USA. EM Ximena@u.washington.edu NR 36 TC 4 Z9 4 U1 1 U2 8 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 MAY PY 2015 VL 99 IS 3 BP 651 EP + DI 10.1016/j.mcna.2015.01.013 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA CG9VH UT WOS:000353667700014 PM 25841605 ER PT J AU Callegari, LS Ma, EW Schwarz, EB AF Callegari, Lisa S. Ma, Erica W. Schwarz, Eleanor Bimla TI Preconception Care and Reproductive Planning in Primary Care SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Preconception care; Reproductive life plan; Reproductive planning; Reproductive-aged women; Primary care ID GESTATIONAL DIABETES-MELLITUS; LIFE-STYLE INTERVENTIONS; LOW-BIRTH-WEIGHT; BODY-MASS INDEX; HEALTH-CARE; CLINICAL CONTENT; UNITED-STATES; SPONTANEOUS-ABORTIONS; CONGENITAL-ANOMALIES; BARIATRIC SURGERY AB Preconception care is designed to identify and reduce biomedical, behavioral, and social risks to the health of a woman or her baby before pregnancy occurs. Few women present requesting preconception care; however, 1 in 10 US women of childbearing age will become pregnant each year. As primary care physicians (PCPs) care for reproductive-aged women before, between, and after their pregnancies, they are ideally positioned to help women address health risks before conception, including optimizing chronic conditions, to prevent adverse pregnancy and longer-term health outcomes. PCPs can help women make informed decisions both about preparing for pregnancy and about using effective contraception when pregnancy is not desired. C1 [Callegari, Lisa S.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Callegari, Lisa S.; Ma, Erica W.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev HSR&D, Seattle, WA 98108 USA. [Schwarz, Eleanor Bimla] Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. RP Callegari, LS (reprint author), Univ Washington, Dept Vet Affairs, Hlth Serv Res & Dev HSR&D, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way S-152, Seattle, WA 98108 USA. EM lcallega@uw.edu FU VA Health Services Research and Development Postdoctoral Fellowship [TPM 61-041] FX L.S. Callegari was supported by a VA Health Services Research and Development Postdoctoral Fellowship (TPM 61-041). NR 97 TC 2 Z9 2 U1 2 U2 8 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 MAY PY 2015 VL 99 IS 3 BP 663 EP + DI 10.1016/j.mcna.2015.01.014 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA CG9VH UT WOS:000353667700015 PM 25841606 ER PT J AU Brown, DN AF Brown, Douglas N. TI Pelvic organ prolapse: a consequence of nature or nurture? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID UNITED-STATES; RISK-FACTORS; WOMEN; HYSTERECTOMY; EPIDEMIOLOGY; PREVALENCE; WALL C1 Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Ctr Minimally Invas Gynecol Surg, Boston, MA 02114 USA. RP Brown, DN (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Ctr Minimally Invas Gynecol Surg, Boston, MA 02114 USA. NR 21 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAY PY 2015 VL 22 IS 5 BP 477 EP 479 DI 10.1097/gme.0000000000000456 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CG9ZB UT WOS:000353677500001 PM 25871001 ER PT J AU Amin, MB Smith, SC Reuter, VE Epstein, JI Grignon, DJ Hansel, DE Lin, O McKenney, JK Montironi, R Paner, GP Al-Ahmadie, HA Algaba, F Ali, S Alvarado-Cabrero, I Bubendorf, L Cheng, L Cheville, JC Kristiansen, G Cote, RJ Delahunt, B Eble, JN Genega, EM Gulmann, C Hartmann, A Langner, C Lopez-Beltran, A Magi-Galluzzi, C Merce, J Netto, GJ Oliva, E Rao, P Ro, JY Srigley, JR Tickoo, SK Tsuzuki, T Umar, SA Van der Kwast, T Young, RH Soloway, MS AF Amin, Mahul B. Smith, Steven C. Reuter, Victor E. Epstein, Jonathan I. Grignon, David J. Hansel, Donna E. Lin, Oscar McKenney, Jesse K. Montironi, Rodolfo Paner, Gladell P. Al-Ahmadie, Hikmat A. Algaba, Ferran Ali, Syed Alvarado-Cabrero, Isabel Bubendorf, Lukas Cheng, Liang Cheville, John C. Kristiansen, Glen Cote, Richard J. Delahunt, Brett Eble, John N. Genega, Elizabeth M. Gulmann, Christian Hartmann, Arndt Langner, Cord Lopez-Beltran, Antonio Magi-Galluzzi, Cristina Merce, Jorda Netto, George J. Oliva, Esther Rao, Priya Ro, Jae Y. Srigley, John R. Tickoo, Satish K. Tsuzuki, Toyonori Umar, Saleem A. Van der Kwast, Theo Young, Robert H. Soloway, Mark S. TI Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer SO MODERN PATHOLOGY LA English DT Review ID MICROPAPILLARY UROTHELIAL CARCINOMA; TRANSITIONAL-CELL-CARCINOMA; HEALTH-ORGANIZATION/INTERNATIONAL-SOCIETY; DIVERGENT HISTOLOGIC DIFFERENTIATION; INVERTED GROWTH-PATTERN; IN-SITU HYBRIDIZATION; VON BRUNN NESTS; URINARY-BLADDER; TRANSURETHRAL RESECTION; CLINICOPATHOLOGICAL ANALYSIS AB The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting. C1 [Amin, Mahul B.; Smith, Steven C.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Reuter, Victor E.; Lin, Oscar; Al-Ahmadie, Hikmat A.; Tickoo, Satish K.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Epstein, Jonathan I.; Ali, Syed; Netto, George J.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. [Grignon, David J.; Cheng, Liang; Eble, John N.] Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46204 USA. [Hansel, Donna E.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [McKenney, Jesse K.; Magi-Galluzzi, Cristina] Cleveland Clin Fdn, Dept Pathol, Cleveland, OH 44195 USA. [Montironi, Rodolfo] United Hosp, Polytech Univ Med, Sect Pathol Anat, Ancona, Italy. [Paner, Gladell P.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Algaba, Ferran] Univ Autonoma Barcelona, Fundacio Puigvert, Pathol Sect, E-08193 Barcelona, Spain. [Alvarado-Cabrero, Isabel] Mexican Oncol Hosp, Dept Pathol, Mexico City, DF, Mexico. [Bubendorf, Lukas] Univ Basel Hosp, Inst Pathol, CH-4031 Basel, Switzerland. [Cheville, John C.] Mayo Clin, Div Anat Pathol, Rochester, MN USA. [Kristiansen, Glen] Univ Hosp Bonn, Inst Pathol, Bonn, Germany. [Cote, Richard J.; Merce, Jorda; Umar, Saleem A.; Soloway, Mark S.] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA. [Delahunt, Brett] Univ Otago, Wellington Sch Med & Hlth Sci, Dept Pathol, Wellington, New Zealand. [Genega, Elizabeth M.] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA USA. [Gulmann, Christian] Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. [Hartmann, Arndt] Univ Erlangen Nurnberg, Inst Pathol, D-91054 Erlangen, Germany. [Langner, Cord] Med Univ Graz, Inst Pathol, Graz, Austria. [Lopez-Beltran, Antonio] Univ Cordoba, Fac Med, Anat Pathol Unit, Sch Med, E-14071 Cordoba, Spain. [Oliva, Esther; Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02115 USA. [Rao, Priya] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Ro, Jae Y.] Cornell Univ, Weill Cornell Med Coll, Methodist Hosp Phys Org, Dept Pathol & Genom Med, Houston, TX USA. [Srigley, John R.] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Tsuzuki, Toyonori] Japanese Red Cross Nagoya Daini Hosp, Dept Pathol, Nagoya, Aichi, Japan. [Van der Kwast, Theo] Univ Miami, Miller Sch Med, Dept Urol, Miami, FL 33136 USA. RP Amin, MB (reprint author), Cedars Sinai Med Ctr, Dept Pathol & Lab Med, 8700 Beverly Blvd,S Tower,Rm 8707, Los Angeles, CA 90048 USA. EM aminm@cshs.org OI Al-Ahmadie, Hikmat/0000-0002-2938-6627 FU NCI NIH HHS [P30 CA008748] NR 82 TC 15 Z9 16 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 2015 VL 28 IS 5 BP 612 EP 630 DI 10.1038/modpathol.2014.158 PG 19 WC Pathology SC Pathology GA CH1IE UT WOS:000353774200002 PM 25412849 ER PT J AU Bhang, HEC Ruddy, DA Radhakrishna, VK Caushi, JX Zhao, R Hims, MM Singh, AP Kao, I Rakiec, D Shaw, P Balak, M Raza, A Ackley, E Keen, N Schlabach, MR Palmer, M Leary, RJ Chiang, DY Sellers, WR Michor, F Cooke, VG Korn, JM Stegmeier, F AF Bhang, Hyo-eun C. Ruddy, David A. Radhakrishna, Viveksagar Krishnamurthy Caushi, Justina X. Zhao, Rui Hims, Matthew M. Singh, Angad P. Kao, Iris Rakiec, Daniel Shaw, Pamela Balak, Marissa Raza, Alina Ackley, Elizabeth Keen, Nicholas Schlabach, Michael R. Palmer, Michael Leary, Rebecca J. Chiang, Derek Y. Sellers, William R. Michor, Franziska Cooke, Vesselina G. Korn, Joshua M. Stegmeier, Frank TI Studying clonal dynamics in response to cancer therapy using high-complexity barcoding SO NATURE MEDICINE LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; ABL KINASE DOMAIN; BCR-ABL; ACQUIRED-RESISTANCE; LUNG-CANCER; MET AMPLIFICATION; EGFR INHIBITORS; DRUG-SENSITIVITY; RARE MUTATIONS; GENE-MUTATIONS AB Resistance to cancer therapies presents a significant clinical challenge. Recent studies have revealed intratumoral heterogeneity as a source of therapeutic resistance. However, it is unclear whether resistance is driven predominantly by pre-existing or de novo alterations, in part because of the resolution limits of next-generation sequencing. To address this, we developed a high-complexity barcode library, ClonTracer, which enables the high-resolution tracking of more than 1 million cancer cells under drug treatment. In two clinically relevant models, ClonTracer studies showed that the majority of resistant clones were part of small, pre-existing subpopulations that selectively escaped under therapeutic challenge. Moreover, the ClonTracer approach enabled quantitative assessment of the ability of combination treatments to suppress resistant clones. These findings suggest that resistant clones are present before treatment, which would make up-front therapeutic combinations that target non-overlapping resistance a preferred approach. Thus, ClonTracer barcoding may be a valuable tool for optimizing therapeutic regimens with the goal of curative combination therapies for cancer. C1 [Bhang, Hyo-eun C.; Radhakrishna, Viveksagar Krishnamurthy; Caushi, Justina X.; Hims, Matthew M.; Singh, Angad P.; Raza, Alina; Keen, Nicholas; Schlabach, Michael R.; Leary, Rebecca J.; Chiang, Derek Y.; Sellers, William R.; Cooke, Vesselina G.; Korn, Joshua M.; Stegmeier, Frank] Novartis Inst Biomed Res, Oncol Dis Area, Cambridge, MA 02139 USA. [Ruddy, David A.; Kao, Iris; Rakiec, Daniel; Shaw, Pamela; Balak, Marissa; Ackley, Elizabeth; Palmer, Michael] Novartis Inst Biomed Res, Translat Clin Oncol, Cambridge, MA USA. [Zhao, Rui; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zhao, Rui; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Stegmeier, F (reprint author), Novartis Inst Biomed Res, Oncol Dis Area, Cambridge, MA 02139 USA. EM frank.stegmeier@novartis.com OI Chiang, Derek/0000-0002-1131-6065 FU Dana-Farber Cancer Institute Physical Sciences-Oncology Center [U54CA143798] FX We thank A. Wylie, J. Donovan, S. Zhu, E. R. McDonald, Z. Jagani and B. Firestone for helpful discussion. We also thank J. Brugge, K. Polyak, J. Williams and J. Kuiken for critical reading of the manuscript and K. Yu for technical assistance. R.Z. and F.M. gratefully acknowledge support from the Dana-Farber Cancer Institute Physical Sciences-Oncology Center (U54CA143798). NR 57 TC 50 Z9 52 U1 3 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD MAY PY 2015 VL 21 IS 5 BP 440 EP U207 DI 10.1038/nm.3841 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CH5IL UT WOS:000354068800010 PM 25849130 ER PT J AU Caruana, I Savoldo, B Hoyos, V Weber, G Liu, H Kim, ES Ittmann, MM Marchetti, D Dotti, G AF Caruana, Ignazio Savoldo, Barbara Hoyos, Valentina Weber, Gerrit Liu, Hao Kim, Eugene S. Ittmann, Michael M. Marchetti, Dario Dotti, Gianpietro TI Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes SO NATURE MEDICINE LA English DT Article ID METASTATIC BREAST-CANCER; ANTIGEN RECEPTOR; GENE-EXPRESSION; SULFATE; CELLS; GROWTH; MATRIX; ENDOGLYCOSIDASE; PROTEOGLYCANS; TRANSCRIPTION AB Adoptive transfer of chimeric antigen receptor (CAR)-redirected T lymphocytes (CAR-T cells) has had less striking therapeutic effects in solid tumors(1-3) than in lymphoid malignancies(4,5). Although active tumor-mediated immunosuppression may have a role in limiting the efficacy of CAR-T cells(6), functional changes in T lymphocytes after their ex vivo manipulation may also account for the reduced ability of cultured CAR-T cells to penetrate stroma-rich solid tumors compared with lymphoid tissues. We therefore studied the capacity of human in vitro-cultured CAR-T cells to degrade components of the extracellular matrix (ECM). In contrast to freshly isolated T lymphocytes, we found that in vitro-cultured T lymphocytes lack expression of the enzyme heparanase (HPSE), which degrades heparan sulfate proteoglycans, the main components of ECM. We found that HPSE mRNA is downregulated in in vitro-expanded T cells, which may be a consequence of p53 (officially known as TP53, encoding tumor protein 53) binding to the HPSE gene promoter. We therefore engineered CAR-T cells to express HPSE and showed their improved capacity to degrade the ECM, which promoted tumor T cell infiltration and antitumor activity. The use of this strategy may enhance the activity of CAR-T cells in individuals with stroma-rich solid tumors. C1 [Caruana, Ignazio; Savoldo, Barbara; Hoyos, Valentina; Weber, Gerrit; Dotti, Gianpietro] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Caruana, Ignazio; Savoldo, Barbara; Hoyos, Valentina; Weber, Gerrit; Dotti, Gianpietro] Houston Methodist Hosp, Houston, TX USA. [Savoldo, Barbara] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Liu, Hao] Baylor Coll Med, Biostat Shared Resource, Houston, TX 77030 USA. [Kim, Eugene S.] Texas Childrens Hosp, Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. [Ittmann, Michael M.; Marchetti, Dario; Dotti, Gianpietro] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Ittmann, Michael M.] Baylor Coll Med, Interdept Program Translat Biol & Mol Med, Houston, TX 77030 USA. [Ittmann, Michael M.] Michael E DeBakey Dept Vet Affairs Med Ctr, Dan L Duncan Canc Ctr, Houston, TX USA. [Dotti, Gianpietro] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Dotti, G (reprint author), Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. EM gdotti@bcm.edu OI Caruana, Ignazio/0000-0002-9250-0605 FU US National Institutes of Health-National Cancer Institute [R01 CA142636]; Department of Defense; Technology and Therapeutic Development Award [W81XWH-10-10425] FX The authors would like to thank I. Vlodavsky and M. Brenner for the critical review of the manuscript and C. Gillespie for editing. This work was supported in part by the US National Institutes of Health-National Cancer Institute (G.D., no. R01 CA142636) and by a Department of Defense and Technology and Therapeutic Development Award (G.D., no. W81XWH-10-10425). L. Metelitsa kindly provided the CHLA-255 human NB cell line. NR 37 TC 35 Z9 38 U1 6 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD MAY PY 2015 VL 21 IS 5 BP 524 EP U158 DI 10.1038/nm.3833 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CH5IL UT WOS:000354068800022 PM 25849134 ER PT J AU Williams, ZM AF Williams, Ziv M. TI Good vibrations with deep brain stimulation SO NATURE NEUROSCIENCE LA English DT Editorial Material ID PARKINSONS-DISEASE C1 [Williams, Ziv M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Williams, Ziv M.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Williams, Ziv M.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. RP Williams, ZM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. EM zwilliams@mgh.harvard.edu NR 7 TC 6 Z9 6 U1 1 U2 3 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 MAY PY 2015 VL 18 IS 5 BP 618 EP 619 PG 3 WC Neurosciences SC Neurosciences & Neurology GA CG9LN UT WOS:000353636900005 PM 25919960 ER PT J AU Srinivasan, R Huang, BS Venugopal, S Johnston, AD Chai, H Zeng, HK Golshani, P Khakh, BS AF Srinivasan, Rahul Huang, Ben S. Venugopal, Sharmila Johnston, April D. Chai, Hua Zeng, Hongkui Golshani, Peyman Khakh, Baljit S. TI Ca2+ signaling in astrocytes from Ip3r2(-/-) mice in brain slices and during startle responses in vivo SO NATURE NEUROSCIENCE LA English DT Article ID NEURONAL-ACTIVITY; VISUAL-CORTEX; HIPPOCAMPAL ASTROCYTES; RECEPTOR ACTIVATION; CORTICAL ASTROCYTES; SYNAPTIC ACTIVITY; BEHAVIOR; MODULATION; PLASTICITY; GLIA AB Intracellular Ca2+ signaling is considered to be important for multiple astrocyte functions in neural circuits. However, mice devoid of inositol triphosphate type 2 receptors (IP3R2) reportedly lack all astrocyte Ca2+ signaling, but display no neuronal or neurovascular deficits, implying that astrocyte Ca2+ fluctuations are not involved in these functions. An assumption has been that the loss of somatic Ca2+ fluctuations also reflects a similar loss in astrocyte processes. We tested this assumption and found diverse types of Ca2+ fluctuations in astrocytes, with most occurring in processes rather than in somata. These fluctuations were preserved in Ip3r2(-/-) (also known as Itpr2(-/-)) mice in brain slices and in vivo, occurred in end feet, and were increased by G protein-coupled receptor activation and by startle-induced neuromodulatory responses. Our data reveal previously unknown Ca2+ fluctuations in astrocytes and highlight limitations of studies that used Ip3r2(-/-) mice to evaluate astrocyte contributions to neural circuit function and mouse behavior. C1 [Srinivasan, Rahul; Venugopal, Sharmila; Johnston, April D.; Chai, Hua; Khakh, Baljit S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Huang, Ben S.; Golshani, Peyman] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Zeng, Hongkui] Allen Inst Brain Sci, Seattle, WA USA. [Golshani, Peyman] Univ Calif Los Angeles, David Geffen Sch Med, Integrat Ctr Learning & Memory, Los Angeles, CA 90095 USA. [Golshani, Peyman] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. [Khakh, Baljit S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. RP Khakh, BS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. EM bkhakh@mednet.ucla.edu OI Huang, Ben/0000-0003-2838-6315 FU US National Institutes of Health (NIH) [NS060677]; NIH [MH099559A, MH104069, MH101198-1]; CHDI Foundation; Simon's Foundation Circuits Grant FX The authors are grateful to current and past members of the laboratories for discussions and comments. Thanks also to M.V. Sofroniew for sharing equipment and to J. Chen for sharing mice. Special thanks to M.D. Haustein who helped with the initial testing of GECIquant and made valuable suggestions on its development. We thank C. Octeau for comments on the paper. Most of the work was supported by the US National Institutes of Health (NIH, NS060677). B.S.K., R.S. and S.V. were also supported by NIH grants (MH099559A, MH104069) and the CHDI Foundation. P.G. and B.S.H. were supported by NIH MH101198-1 and a Simon's Foundation Circuits Grant. NR 48 TC 49 Z9 50 U1 6 U2 26 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 MAY PY 2015 VL 18 IS 5 BP 708 EP + DI 10.1038/nn.4001 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CG9LN UT WOS:000353636900018 PM 25894291 ER PT J AU Noble, KG Houston, SM Brito, NH Bartsch, H Kan, E Kuperman, JM Akshoomoff, N Amaral, DG Bloss, CS Libiger, O Schork, NJ Murray, SS Casey, BJ Chang, LD Ernst, TM Frazier, JA Gruen, JR Kennedy, DN Van Zijl, P Mostofsky, S Kaufmann, WE Kenet, T Dale, AM Jernigan, TL Sowell, ER AF Noble, Kimberly G. Houston, Suzanne M. Brito, Natalie H. Bartsch, Hauke Kan, Eric Kuperman, Joshua M. Akshoomoff, Natacha Amaral, David G. Bloss, Cinnamon S. Libiger, Ondrej Schork, Nicholas J. Murray, Sarah S. Casey, B. J. Chang, Linda Ernst, Thomas M. Frazier, Jean A. Gruen, Jeffrey R. Kennedy, David N. Van Zijl, Peter Mostofsky, Stewart Kaufmann, Walter E. Kenet, Tal Dale, Anders M. Jernigan, Terry L. Sowell, Elizabeth R. TI Family income, parental education and brain structure in children and adolescents SO NATURE NEUROSCIENCE LA English DT Article ID SOCIOECONOMIC-STATUS; CORTICAL THICKNESS; CHILDHOOD POVERTY; WORKING-MEMORY; FUNCTIONAL MRI; ASSOCIATIONS; CORTEX; NETWORKS; BEHAVIOR; INFANCY AB Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. We investigated relationships between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1,099 typically developing individuals between 3 and 20 years of age. Income was logarithmically associated with brain surface area. Among children from lower income families, small differences in income were associated with relatively large differences in surface area, whereas, among children from higher income families, similar income increments were associated with smaller differences in surface area. These relationships were most prominent in regions supporting language, reading, executive functions and spatial skills; surface area mediated socioeconomic differences in certain neurocognitive abilities. These data imply that income relates most strongly to brain structure among the most disadvantaged children. C1 [Noble, Kimberly G.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Noble, Kimberly G.] Columbia Univ, Teachers Coll, New York, NY 10027 USA. [Houston, Suzanne M.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Houston, Suzanne M.; Kan, Eric; Sowell, Elizabeth R.] Childrens Hosp, Saban Res Inst, Los Angeles, CA 90027 USA. [Houston, Suzanne M.; Kan, Eric; Sowell, Elizabeth R.] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. [Brito, Natalie H.] Columbia Univ, Robert Wood Johnson Hlth & Soc Scholar Program, New York, NY 10027 USA. [Bartsch, Hauke] Univ Calif San Diego, Stein Inst Res Aging, San Diego, CA 92103 USA. [Kuperman, Joshua M.; Dale, Anders M.] Univ Calif San Diego, Multimodal Imaging Lab, San Diego, CA 92103 USA. [Kuperman, Joshua M.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. [Kuperman, Joshua M.; Akshoomoff, Natacha; Amaral, David G.; Bloss, Cinnamon S.; Murray, Sarah S.; Casey, B. J.; Chang, Linda; Ernst, Thomas M.; Frazier, Jean A.; Gruen, Jeffrey R.; Kennedy, David N.; Van Zijl, Peter; Mostofsky, Stewart; Kaufmann, Walter E.; Kenet, Tal; Dale, Anders M.; Jernigan, Terry L.; Sowell, Elizabeth R.] Pediat Imaging Neurocognit & Genet Study, San Diego, CA USA. [Akshoomoff, Natacha; Jernigan, Terry L.] Univ Calif San Diego, Ctr Human Dev, San Diego, CA 92103 USA. [Akshoomoff, Natacha; Jernigan, Terry L.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Amaral, David G.] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Bloss, Cinnamon S.] Univ Calif San Diego, Qualcomm Inst, San Diego, CA 92103 USA. [Libiger, Ondrej] MD Revolut Inc, La Jolla, CA USA. [Schork, Nicholas J.] Univ Calif San Diego, J Craig Venter Inst, Human Biol, San Diego, CA 92103 USA. [Murray, Sarah S.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Casey, B. J.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Chang, Linda; Ernst, Thomas M.] Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. [Frazier, Jean A.; Kennedy, David N.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Gruen, Jeffrey R.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Gruen, Jeffrey R.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gruen, Jeffrey R.] Yale Univ, Sch Med, Dept Investigat Med, New Haven, CT 06510 USA. [Van Zijl, Peter] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Van Zijl, Peter; Mostofsky, Stewart] Kennedy Krieger Inst, Baltimore, MD USA. [Kaufmann, Walter E.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Kaufmann, Walter E.; Kenet, Tal] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kenet, Tal] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dale, Anders M.; Jernigan, Terry L.] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92103 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, Dept Neurol, San Diego, CA 92103 USA. [Dale, Anders M.] Univ Calif San Diego, Ctr Translat Imaging & Personalized Med, La Jolla, CA 92093 USA. RP Sowell, ER (reprint author), Childrens Hosp, Saban Res Inst, Los Angeles, CA 90027 USA. EM kgn2106@columbia.edu; esowell@chla.usc.edu FU Annie E. Casey Foundation; GH Sergievsky Center; [RC2 DA029475]; [R01 HD053893]; [R01 MH087563]; [R01 HD061414] FX This work was funded by the Annie E. Casey Foundation and the GH Sergievsky Center (K.G.N.) and by the following grants: RC2 DA029475 to T.L.J., L.C., T.M.E., A.M.D. and S.S.M. R01 HD053893 to E.R.S., R01 MH087563 to E.R.S. and R01 HD061414 to T.L.J. NR 49 TC 83 Z9 87 U1 19 U2 94 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 MAY PY 2015 VL 18 IS 5 BP 773 EP + DI 10.1038/nn.3983 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CG9LN UT WOS:000353636900026 PM 25821911 ER PT J AU Zhang, HJ Abraham, N Khan, LA Gobel, V AF Zhang, Hongjie Abraham, Nessy Khan, Liakot A. Gobel, Verena TI RNAi-based biosynthetic pathway screens to identify in vivo functions of non-nucleic acid-based metabolites such as lipids SO NATURE PROTOCOLS LA English DT Article ID IONIZATION-MASS-SPECTROMETRY; CAENORHABDITIS-ELEGANS; BRANCHED-CHAIN; FATTY-ACIDS; CELLS; QUANTITATION; LIPIDOMICS; MEMBRANES; ENZYMES; GROWTH AB The field of metabolomics continues to catalog new compounds, but their functional analysis remains technically challenging, and roles beyond metabolism are largely unknown. Unbiased genetic/RNAi screens are powerful tools to identify the in vivo functions of protein-encoding genes, but not of nonproteinaceous compounds such as lipids. They can, however, identify the biosynthetic enzymes of these compounds-findings that are usually dismissed, as these typically synthesize multiple products. Here, we provide a method using follow-on biosynthetic pathway screens to identify the endpoint biosynthetic enzyme and thus the compound through which they act. The approach is based on the principle that all subsequently identified downstream biosynthetic enzymes contribute to the synthesis of at least this one end product. We describe how to systematically target lipid biosynthetic pathways; optimize targeting conditions; take advantage of pathway branchpoints; and validate results by genetic assays and biochemical analyses. This approach extends the power of unbiased genetic/RNAi screens to identify in vivo functions of non-nucleic acid-based metabolites beyond their metabolic roles. It will typically require several months to identify a metabolic end product by biosynthetic pathway screens, but this time will vary widely depending, among other factors, on the end product's location in the pathway, which determines the number of screens required for its identification. C1 [Zhang, Hongjie; Abraham, Nessy; Khan, Liakot A.; Gobel, Verena] Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA. [Zhang, Hongjie; Abraham, Nessy; Khan, Liakot A.; Gobel, Verena] Harvard Univ, Sch Med, Boston, MA USA. RP Gobel, V (reprint author), Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA. EM vgobel@mgh.harvard.edu FU US National Institutes of Health [GM078653]; Massachusetts General Hospital IS Funding; Mattina R. Proctor Award FX C. elegans strains were provided by G. Ruvkun (Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA), S. Mitani (National Bioresource Project Japan) and the Caenorhabditis Genetics Center (NIH Center for Research Resources). We thank J. Moore (Avanti Polar Lipids) and E. Membreno for contributions to LC/MS and C. elegans maintenance, respectively. We thank H. Weinstein and R. Kleinman for ongoing support. This work was supported by US National Institutes of Health grant GM078653, Massachusetts General Hospital IS Funding and a Mattina R. Proctor Award to V.G. NR 36 TC 1 Z9 1 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD MAY PY 2015 VL 10 IS 5 BP 681 EP 700 DI 10.1038/nprot.2015.031 PG 20 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CH1KJ UT WOS:000353780000003 PM 25837419 ER PT J AU Naxerova, K Jain, RK AF Naxerova, Kamila Jain, Rakesh K. TI Using tumour phylogenetics to identify the roots of metastasis in humans SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID BREAST-CANCER METASTASIS; LYMPH-NODE METASTASES; CELL LINEAGE ANALYSIS; PROSTATE-CANCER; COLORECTAL CANCERS; SOMATIC MUTATIONS; COLON-CANCER; MICROSATELLITE INSTABILITY; INTRATUMOR HETEROGENEITY; GENETIC-HETEROGENEITY AB In cancer, much uncertainty remains regarding the origins of metastatic disease. Models of metastatic progression offer competing views on when dissemination occurs (at an early or late stage of tumour development), whether metastases at different sites arise independently and directly from the primary tumour or give rise to each other, and whether dynamic cell exchange occurs between synchronously growing lesions. Although it is probable that many routes can lead to the establishment of systemic disease, clinical observations suggest that distinct modes of metastasis might prevail in different tumour types. Gaining a more-comprehensive understanding of the evolutionary processes that underlie metastasis is not only relevant from a basic biological perspective, but also has profound clinical implications. The 'tree of life' of metastatic cancer contains answers to many outstanding questions about the development of systemic disease, but has only been reconstructed in a limited number of patients. Here we review available data on the phylogenetic relationships between primary solid tumours and their metastases, and examine to what degree they support different models of metastatic progression. We provide a description of experimental methods for lineage tracing in human cancer, ranging from broad DNA-sequencing approaches to more-targeted techniques, and discuss their respective benefits and caveats. Finally, we propose future research questions in the area of cancer phylogenetics. C1 [Naxerova, Kamila; Jain, Rakesh K.] Massachusetts Gen Hosp, Edwin L Steele Lab Tumour Biol, Boston, MA 02114 USA. [Naxerova, Kamila; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. RP Naxerova, K (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab Tumour Biol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM knaxerova@partners.org OI Naxerova, Kamila/0000-0001-7744-5110 FU US Department of Defence [W81XWH-11-1-0146]; Breast Cancer Innovator Award [W81XWH-10-1-0016]; US National Institutes of Health [P01CA080124, R01CA163815]; Proton Beam/Federal Share Program; National Foundation for Cancer Research FX The work of the authors is supported in part by funding from the US Department of Defence (grant W81XWH-11-1-0146 to K.N.), the Breast Cancer Innovator Award (grant W81XWH-10-1-0016 to R.K.J.), the US National Institutes of Health (grants P01CA080124 and R01CA163815 to R.K.J.), the Proton Beam/Federal Share Program (R.K.J.), and the National Foundation for Cancer Research (R.K.J.). NR 119 TC 21 Z9 21 U1 6 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAY PY 2015 VL 12 IS 5 BP 258 EP 272 DI 10.1038/nrclinonc.2014.238 PG 15 WC Oncology SC Oncology GA CH1LP UT WOS:000353783400005 PM 25601447 ER PT J AU Zurcher, NR Bhanot, A McDougle, CJ Hooker, JM AF Zuercher, Nicole R. Bhanot, Anisha McDougle, Christopher J. Hooker, Jacob M. TI A systematic review of molecular imaging (PET and SPECT) in autism spectrum disorder: Current state and future research opportunities SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Positron emission tomography (PET); Single-photon emission computed tomography (SPECT); Neuroimaging; Molecular imaging; Autism spectrum disorder ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; PERVASIVE DEVELOPMENTAL DISORDERS; SEROTONIN TRANSPORTER BINDING; CHILDHOOD AUTISM; GLUCOSE-METABOLISM; ASPERGER-SYNDROME; INFANTILE-AUTISM; BRAIN SPECT; MICROGLIAL ACTIVATION AB Non-invasive positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are techniques used to quantify molecular interactions, biological processes and protein concentration and distribution. In the central nervous system, these molecular imaging techniques can provide critical insights into neurotransmitter receptors and their occupancy by neurotransmitters or drugs. In recent years, there has been an increase in the number of studies that have investigated neurotransmitters in autism spectrum disorder (ASD), while earlier studies mostly focused on cerebral blood flow and glucose metabolism. The underlying and contributing mechanisms of ASD are largely undetermined and ASD diagnosis relies on the behavioral phenotype. Discovery of biochemical endophenotypes would represent a milestone in autism research that could potentially lead to ASD subtype stratification and the development of novel therapeutic drugs. This review characterizes the prior use of molecular imaging by PET and SPECT in ASD, addresses methodological challenges and highlights areas of future opportunity for contributions from molecular imaging to understand ASD pathophysiology. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Zuercher, Nicole R.; Bhanot, Anisha; Hooker, Jacob M.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Zuercher, Nicole R.; Hooker, Jacob M.] Harvard Univ, Sch Med, Boston, MA USA. [McDougle, Christopher J.] MassGen Hosp Children, Dept Pediat, Lurie Ctr Autism, Lexington, MA USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Hooker, JM (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Suite 2301, Charlestown, MA 02129 USA. EM hooker@martinos.org FU Robert E. and Donna Landreth Fund for the Study of Neuroinflammation in Autism; Autism Speaks Meixner Translational Postdoctoral Fellowship [9258] FX The authors acknowledge support from the Robert E. and Donna Landreth Fund for the Study of Neuroinflammation in Autism. Nicole R. Zurcher was funded by an Autism Speaks Meixner Translational Postdoctoral Fellowship (#9258). The authors would like to thank Nouchine Hadjikhani for helpful comments on an earlier version of the manuscript and Regan Butterfield for discussions regarding Fig. 1. NR 131 TC 7 Z9 7 U1 12 U2 40 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 EI 1873-7528 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD MAY PY 2015 VL 52 BP 56 EP 73 DI 10.1016/j.neubiorev.2015.02.002 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CG8YJ UT WOS:000353601300005 PM 25684726 ER PT J AU AhnAllen, CG Bidwell, LC Tidey, JW AF AhnAllen, Christopher G. Bidwell, L. Cinnamon Tidey, Jennifer W. TI Cognitive Effects of Very Low Nicotine Content Cigarettes, With and Without Nicotine Replacement, in Smokers With Schizophrenia and Controls SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SMOKING ABSTINENCE; WORKING-MEMORY; NASAL SPRAY; TOBACCO; DEPENDENCE; DEFICITS AB Introduction: Beneficial effects of nicotine on cognitive functioning may contribute to the markedly high rates of smoking among people with schizophrenia. A reduction in the nicotine content of cigarettes to non-addictive levels is being considered as a regulatory strategy for reducing tobacco dependence in the United States. We examined whether switching to very low nicotine content (VLNC) cigarettes impairs cognitive functioning in smokers with and without schizophrenia, and-whether nicotine replacement reverses these effects. Methods: Smokers with schizophrenia (SS, n = 29) and control smokers matched on smoking rate but without psychiatric illness (CS, n = 28) smoked usual-brand cigarettes, VLNC cigarettes while wearing 2 placebo patches (PLA), or VLNC cigarettes while wearing 2 nicotine patches totaling 42 mg (NIC) for 5 hr, and then completed computerized assessments of visual sustained attention, motor speed, visual working memory, processing speed, inhibitory control, and response variability. Results: Across conditions, SS were slower than CS in tasks of motor speed and visual working memory, and had poorer target detectability on a visual sustained attention task. Across groups, functioning in domains of visual sustained attention, inhibitory control, processing speed, and response variability was impaired in the VLNC + PLA condition relative to the usual-brand and VLNC + NIC conditions. Conclusions: Dramatically reducing the nicotine content of cigarettes may impair cognitive functioning in heavy smokers with and without schizophrenia, but the use of nicotine replacement while smoking VLNC cigarettes may preserve cognitive functioning in these smokers. C1 [AhnAllen, Christopher G.] VA Boston Healthcare Syst, Mental Hlth Serv, Brockton, MA USA. [AhnAllen, Christopher G.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Bidwell, L. Cinnamon; Tidey, Jennifer W.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. RP Tidey, JW (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Box S121-5, Providence, RI 02912 USA. EM jennifer_tidey@brown.edu FU National Institute on Drug Abuse [R01DA14002, U54DA031659, P50DA036114, T32DA016184, K23DA033302]; FDA Center for Tobacco Products (CTP) FX This research was supported by grant number R01DA14002 to JWT from the National Institute on Drug Abuse and conducted at the Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA. Salary support for this secondary analysis and manuscript were provided by grants U54DA031659 and P50DA036114 (JWT) from the National Institute on Drug Abuse and FDA Center for Tobacco Products (CTP), and grants T32DA016184 (CGA) and K23DA033302 (LCB) from the National Institute on Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. Portions of these data were presented at annual meetings of the College on Problems of Drug Dependence and the Society for Research on Nicotine and Tobacco. NR 28 TC 5 Z9 5 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAY PY 2015 VL 17 IS 5 BP 510 EP 514 DI 10.1093/ntr/ntu163 PG 5 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA CH3CL UT WOS:000353904000002 PM 25143294 ER PT J AU Barnett, PG Hamlett-Berry, K Sung, HY Max, W AF Barnett, Paul G. Hamlett-Berry, Kim Sung, Hai-Yen Max, Wendy TI Health Care Expenditures Attributable to Smoking in Military Veterans SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID CIGARETTE-SMOKING; UNITED-STATES; US MILITARY; TOBACCO USE; COSTS; PREVALENCE; BEHAVIOR; CALIFORNIA; SERVICE; IRAQ AB Introduction: The health effects of cigarette smoking have been estimated to account for between 6%-8% of U.S. health care expenditures. We estimated Veterans Health Administration (VHA) health care costs attributable to cigarette smoking. Methods: VHA survey and administrative data provided the number of Veteran enrollees, current and former smoking prevalence, and the cost of 4 types of care for groups defined by age, gender, and region. Cost and smoking status could not be linked at the enrollee level, so we used smoking attributable fractions estimated in sample of U.S. residents where the linkage could be made. Results: The 7.7 million Veterans enrolled in VHA received $40.2 billion in VHA provided health services in 2010. We estimated that $2.7 billion in VHA costs were attributable to the health effects of smoking. This was 7.6% of the $35.3 billion spent on the types of care for which smoking-attributable fractions could be determined. The fraction of inpatient costs that was attributable to smoking (11.4%) was greater than the fraction of ambulatory care cost attributable to smoking (5.3%). More cost was attributable to current smokers ($1.7 billion) than to former smokers ($ 983 million). Conclusions: The fraction of VHA costs attributable to smoking is similar to that of other health care systems. Smoking among Veterans is slowly decreasing, but prevalence remains high in Veterans with psychiatric and substance use disorders, and in younger and female Veterans. VHA has adopted a number of smoking cessation programs that have the potential for reducing future smoking-attributable costs. C1 [Barnett, Paul G.] US Dept Vet Affairs, Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Hamlett-Berry, Kim] US Dept Vet Affairs, Publ Hlth Strateg Hlth Care Grp, Washington, DC USA. [Barnett, Paul G.] Univ Calif San Francisco, Treatment Res Ctr, San Francisco, CA 94143 USA. [Sung, Hai-Yen; Max, Wendy] Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA USA. RP Barnett, PG (reprint author), VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, 795 Willow Rd 152, Menlo Pk, CA 94025 USA. EM paul.barnett@va.gov FU Public Health Strategic Health Care Group; Health Services Research and Development Service of the U.S. Department of Veterans Affairs [ECN 99-017, RRP 11-266] FX This work was supported by funding from the Public Health Strategic Health Care Group and the Health Services Research and Development Service of the U.S. Department of Veterans Affairs, projects ECN 99-017 and RRP 11-266. NR 40 TC 5 Z9 5 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAY PY 2015 VL 17 IS 5 BP 586 EP 591 DI 10.1093/ntr/ntu187 PG 6 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA CH3CL UT WOS:000353904000010 PM 25239960 ER PT J AU Saladin, ME Wray, JM Carpenter, MJ McClure, EA LaRowe, SD Upadhyaya, HP Gray, KM AF Saladin, Michael E. Wray, Jennifer M. Carpenter, Matthew J. McClure, Erin A. LaRowe, Steven D. Upadhyaya, Himanshu P. Gray, Kevin M. TI Menstrual Cycle Phase Effects in the Gender Dimorphic Stress Cue Reactivity of Smokers SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SMOKING STATUS; QUIT DATE; WITHDRAWAL; DEPENDENCE; NICOTINE; EMOTION; ADULTS; TRIAL; WOMEN; URGES AB Introduction: We previously reported that female smokers evidence greater subjective craving and stress/emotional reactivity to personalized stress cues than males. The present study employed the same dataset to assess whether females in the follicular versus luteal phase of the menstrual cycle accounted for the gender differences. Methods: Two objective criteria, onset of menses and luteinizing hormone surge (evaluated via home testing kits), were used to determine whether female smokers were in either the follicular (n = 22) or the luteal (n = 15) phase of their menstrual cycle, respectively. The females and a sample of male smokers (n = 53) were then administered a laboratory-based cue reactivity paradigm that involved assessment of craving, stress, and emotional reactivity in response to counterbalanced presentations of both a personalized stress script and neutral/relaxed script. Results: While there were no significant differences between females in the follicular versus luteal phase on any outcome measure, females in the luteal menstrual phase reported greater craving than males whereas females in the follicular phase reported greater stress and arousal than males and perceived the stress cues as more emotionally aversive than males. Conclusions: This preliminary investigation suggests that gender differences in craving versus affective responding to stress cues may, in part, be explained variation by menstrual cycle phase. Study limitations and implications of the findings for future research and treatment are briefly discussed. C1 [Saladin, Michael E.; Wray, Jennifer M.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Saladin, Michael E.; Wray, Jennifer M.; Carpenter, Matthew J.; McClure, Erin A.; LaRowe, Steven D.; Gray, Kevin M.] MUSC, Dept Psychiat & Behav Sci, Clin Neurosci Div, Charleston, SC USA. [Carpenter, Matthew J.] MUSC, Hollings Canc Ctr, Charleston, SC USA. [LaRowe, Steven D.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Subst Abuse Treatment Ctr, Charleston, SC USA. [Upadhyaya, Himanshu P.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Gray, Kevin M.] MUSC, Youth Div, Dept Psychiat & Behav Sci, Charleston, SC USA. RP Saladin, ME (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, Coll Hlth Profess, 77 President St,Room 224,MSC700, Charleston, SC 29425 USA. EM saladinm@musc.edu FU NIDA (Specialized Center of Research (SCOR) on Sex and Gender Factors Affecting Women's Health (SCOR) [P50 DA016511-11]; South Carolina Clinical & Translational Research (SCTR) Institute; NIH [UL1 RR029882, UL1 TR000062]; Pfizer, Inc. FX This research was supported by NIDA grants P50 DA016511-11 Specialized Center of Research (SCOR) on Sex and Gender Factors Affecting Women's Health (SCOR PI: K. T. Brady, and SCOR Component 4 PI's: MES and KMG), South Carolina Clinical & Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina, through NIH Grant Numbers UL1 RR029882 and UL1 TR000062. Dr. KMG has received research support from Pfizer, Inc. (medication and placebo supply for NIH-funded research). NR 24 TC 2 Z9 2 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAY PY 2015 VL 17 IS 5 BP 607 EP 611 DI 10.1093/ntr/ntu203 PG 5 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA CH3CL UT WOS:000353904000013 PM 25324432 ER PT J AU Djousse, L Petrone, AB Blackshear, C Griswold, M Harman, JL Clark, CR Talegawkar, S Hickson, DA Gaziano, JM Dubbert, PM Correa, A Tucker, KL Taylor, HA AF Djousse, Luc Petrone, Andrew B. Blackshear, Chad Griswold, Michael Harman, Jane L. Clark, Cheryl R. Talegawkar, Sameera Hickson, DeMarc A. Gaziano, J. Michael Dubbert, Patricia M. Correa, Adolfo Tucker, Katherine L. Taylor, Herman A. TI Prevalence and changes over time of ideal cardiovascular health metrics among African-Americans: The Jackson Heart Study SO PREVENTIVE MEDICINE LA English DT Article DE Epidemiology; Cardiovascular disease; Risk factors; Diet ID ATHEROSCLEROSIS RISK; PHYSICAL-ACTIVITY; DISEASE INCIDENCE; US ADULTS; ASSOCIATION; MORTALITY; COMMUNITIES; WOMEN; POPULATION; UPDATE AB Objectives. The aim of this study is to assess the prevalence and changes over time of ideal Life's Simple Seven (LSS) in African-Americans. Methods. Prospective cohort of 5301 African-Americans from the Jackson Heart Study OHS) from 2000 to 2013. Each of the LSS metrics was categorized as poor, intermediate, or ideal. Results. Among men, the prevalence of having 0, 1, 2, 3, 4, 5, 6, and 7 ideal LSS was 3.3%, 23.0%, 33.5%, 24.7%, 11.6%, 3.6%, 0.3%, and 0%, respectively. Corresponding values for women were 1.7%, 26.3%, 33.1%, 22.8%, 11.9%, 3.7%, 0.6%, and 0%. Prevalence of ideal diet was 0.9%. The proportions of those meeting LSS ideal recommendations for cholesterol and fasting glucose declined from the first through third JHS visits across all age groups, whereas prevalence of ideal BMI declined only in participants <40 years at a given visit. Prevalence of ideal blood pressure did not change over time and being ideal on physical activity improved from the first [18.3% (95% CI: 17.3% to 19.3%)] to third visit [24.8% (95% CI: 23.3% to 26.3%)]. Conclusions. Our data show a low prevalence of ideal LSS (especially diet, physical activity, and obesity) in the JHS and a slight improvement in adherence to physical activity recommendations over time. (C) 2015 Elsevier Inc. All rights reserved. C1 [Djousse, Luc; Petrone, Andrew B.; Clark, Cheryl R.; Gaziano, J. Michael] Brigham & Womens Hosp, Boston, MA 02120 USA. [Djousse, Luc; Gaziano, J. Michael] Boston VA Healthcare Syst, Boston, MA USA. [Djousse, Luc; Clark, Cheryl R.; Gaziano, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. [Blackshear, Chad; Griswold, Michael; Hickson, DeMarc A.; Correa, Adolfo; Taylor, Herman A.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Harman, Jane L.] NHLBI, Bethesda, MD 20892 USA. [Talegawkar, Sameera] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Dubbert, Patricia M.] South Cent VA MIRECC, Little Rock, AR USA. [Dubbert, Patricia M.] Little Rock GRECC, Little Rock, AR USA. [Tucker, Katherine L.] Univ Massachusetts Lowell, Lowell, MA USA. [Taylor, Herman A.] Jackson State Univ, Jackson, MS USA. [Taylor, Herman A.] Tougaloo Coll, Jackson, MS USA. RP Djousse, L (reprint author), Brigham & Womens Hosp, Div Aging, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM ldjousse@rics.bwh.harvard.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities; National Health Institutes [R21 NR013231]; American Diabetes Association [13BGIA17080036] FX The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, and HHSN268201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. This project was also supported by grant R21 NR013231 from the National Health Institutes. Dr. Talegawkar was supported by grant 13BGIA17080036 from the American Diabetes Association. NR 35 TC 6 Z9 6 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD MAY PY 2015 VL 74 BP 111 EP 116 DI 10.1016/j.ypmed.2015.02.006 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CH1AX UT WOS:000353754600018 PM 25712326 ER PT J AU Bishwakarma, R Kinney, WH Honda, JR Mya, J Strand, MJ Gangavelli, A Bai, XY Ordway, DJ Iseman, MD Chan, ED AF Bishwakarma, Raju Kinney, William H. Honda, Jennifer R. Mya, Jenny Strand, Matthew J. Gangavelli, Avani Bai, Xiyuan Ordway, Diane J. Iseman, Michael D. Chan, Edward D. TI Epidemiologic link between tuberculosis and cigarette/biomass smoke exposure: Limitations despite the vast literature SO RESPIROLOGY LA English DT Review DE biomass fuel smoke; latent tuberculosis infection; Mycobacterium tuberculosis; tobacco smoke ID INDOOR AIR-POLLUTION; RISK-FACTORS; PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; SOLID-FUEL; ACTIVE TUBERCULOSIS; TOBACCO SMOKING; BIOMASS FUEL; HONG-KONG; ANTITUBERCULOSIS TREATMENT AB The geographic overlap between the prevalence of cigarette smoke (CS) exposure and tuberculosis (TB) in the world is striking. In recent years, relatively large number of studies has linked cigarette or biomass fuel smoke exposure and various aspects of TB. Our goals are to summarize the significance of the known published studies, graphically represent reports that quantified the association and discuss their potential limitations. PubMed searches were performed using the key words tuberculosis' with cigarette', tobacco', smoke' or biomass fuel smoke.' The references of relevant articles were examined for additional pertinent papers. A large number of mostly case-control and cross-sectional studies significantly associate both direct and second-hand smoke exposure with tuberculous infection, active TB, and/or more severe and lethal TB. Fewer link biomass fuel smoke exposure and TB. While a number of studies interpreted the association with multivariate analysis, other confounders are often not accounted for in these analyses. It is also important to emphasize that these retrospective studies can only show an association and not any causal link. We further explored the possibility that even if CS exposure is a risk factor for TB, several mechanisms may be responsible. Numerous studies associate cigarette and biomass smoke exposure with TB but the mechanism(s) remains largely unknown. While the associative link of these two health maladies is well established, more definitive, mechanistic studies are needed to cement the effect of smoke exposure on TB pathogenesis and to utilize this knowledge in empowering public health policies. C1 [Bishwakarma, Raju; Kinney, William H.; Mya, Jenny; Strand, Matthew J.; Gangavelli, Avani; Bai, Xiyuan; Iseman, Michael D.; Chan, Edward D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Bishwakarma, Raju; Kinney, William H.; Mya, Jenny; Strand, Matthew J.; Gangavelli, Avani; Bai, Xiyuan; Iseman, Michael D.; Chan, Edward D.] Natl Jewish Hlth, Dept Acad Affairs, Denver, CO 80206 USA. [Honda, Jennifer R.; Iseman, Michael D.; Chan, Edward D.] Univ Colorado, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. [Ordway, Diane J.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. [Bishwakarma, Raju] Univ Texas Med Branch, Dept Med, Galveston, TX 77555 USA. RP Chan, ED (reprint author), Natl Jewish Hlth, Dept Med, D509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org NR 93 TC 3 Z9 3 U1 3 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-7799 EI 1440-1843 J9 RESPIROLOGY JI Respirology PD MAY PY 2015 VL 20 IS 4 BP 556 EP 568 DI 10.1111/resp.12515 PG 13 WC Respiratory System SC Respiratory System GA CH2XW UT WOS:000353889700008 PM 25808744 ER PT J AU Sibila, O Laserna, E Maselli, DJ Fernandez, JF Mortensen, EM Anzueto, A Waterer, G Restrepo, MI AF Sibila, Oriol Laserna, Elena Maselli, Diego Jose Fernandez, Juan Felipe Mortensen, Eric M. Anzueto, Antonio Waterer, Grant Restrepo, Marcos I. TI Risk factors and antibiotic therapy in P. aeruginosa community-acquired pneumonia SO RESPIROLOGY LA English DT Article DE antibiotic treatment; community-acquired pneumonia; Pseudomonas aeruginosa; risk factor ID VENTILATOR-ASSOCIATED PNEUMONIA; OBSTRUCTIVE PULMONARY-DISEASE; CARE-ASSOCIATED PNEUMONIA; GRAM-NEGATIVE BACILLI; PSEUDOMONAS-AERUGINOSA; OUTCOMES; SEVERITY; EXACERBATIONS; METAANALYSIS; MULTICENTER AB Background and objectiveCurrent guidelines recommend empirical treatment against Pseudomonas aeruginosa in community-acquired pneumonia (CAP) patients with specific risk factors. However, evidence to support these recommendations is limited. We evaluate the risk factors and the impact of antimicrobial therapy in patients hospitalized with CAP due to P.aeruginosa. MethodsWe performed a retrospective population-based study of >150 hospitals. Patients were included if they had a diagnosis of CAP and P.aeruginosa was identified as the causative pathogen. Univariate and multivariate analyses were performed using the presence of risk factors and 30-day mortality as the dependent measures. ResultsSeven hundred eighty-one patients with P.aeruginosa pneumonia were identified in a cohort of 62689 patients with pneumonia (1.1%). Of these, 402 patients (0.6%) were included in the study and 379 (0.5%) were excluded due to health care-associated pneumonia or immunosuppression. In patients with CAP due to P.aeruginosa, 272 (67.8%) had no documented risk factors. These patients had higher rates of dementia and cerebrovascular disease. Empirical antibiotic therapy against P.aeruginosa within the first 48h of presentation was independently associated with lower 30-day mortality in patients with CAP due to P.aeruginosa (hazard ratio (HR) 0.42, 95% confidence interval (CI): 0.23-0.76) and in patients without risk factors for P.aeruginosaCAP (HR 0.40, 95% CI: 0.21-0.76). ConclusionsRisk factor recommended by current guidelines only detect one third of the patients admitted with CAP due to P.aeruginosa. Risk factors did not define the whole benefit observed due to empirical therapy covering P.aeruginosa. Risk factors recommended by current guidelines only detect one third of the patients admitted with CAP due to P.aeruginosa.Not administrating antibiotics active against P.aeruginosa in the first 48h increases 30-day mortality. C1 [Sibila, Oriol] Hosp Santa Creu & Sant Pau, Resp Dept, Barcelona, Spain. [Sibila, Oriol] St Pau Biomed Res Inst IIB St Pau, Barcelona, Spain. [Laserna, Elena] Hosp Comarcal Mollet, Mollet Del Valles, Spain. [Sibila, Oriol; Laserna, Elena; Maselli, Diego Jose; Fernandez, Juan Felipe; Anzueto, Antonio; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care, San Antonio, TX 78229 USA. [Maselli, Diego Jose; Fernandez, Juan Felipe; Anzueto, Antonio; Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] Vet Evidence Based Res Disseminat & Implementat C, Med, 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. [Waterer, Grant] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Waterer, Grant] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. RP Restrepo, MI (reprint author), South Texas Vet Hlth Care Syst ALMD, Vet Evidence Based Res Disseminat & Implementat C, Med, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu OI Mortensen, Eric/0000-0002-3880-5563 FU National Institute of Nursing Research [R01NR010828]; Instituto de Salud Carlos III [BAE11/00102]; Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR); Societat Catalana de Pneumologia (SOCAP); Fundacio Catalana de Pneumologia (FUCAP); National Heart, Lung, and Blood Institute [K23HL096054] FX The project described was supported by Grant Number R01NR010828 from the National Institute of Nursing Research. Dr Sibila is supported by Instituto de Salud Carlos III (BAE11/00102). Dr Sibila and Dr Laserna are supported by Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), Societat Catalana de Pneumologia (SOCAP) and Fundacio Catalana de Pneumologia (FUCAP). Dr Restrepo's time is partially protected by Award Number K23HL096054 from the National Heart, Lung, and Blood Institute. NR 32 TC 9 Z9 10 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-7799 EI 1440-1843 J9 RESPIROLOGY JI Respirology PD MAY PY 2015 VL 20 IS 4 BP 660 EP 666 DI 10.1111/resp.12506 PG 7 WC Respiratory System SC Respiratory System GA CH2XW UT WOS:000353889700021 PM 25776134 ER PT J AU Papas, AS Singh, ML Teles, R Haffajee, AD Socransky, SS AF Papas, A. S. Singh, M. L. Teles, R. Haffajee, A. D. Socransky, S. S. TI A Potential Microbiomic Biomarker for Sjogren's from Oral Tissues SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Sjogren's Syndrome CY MAY 19-22, 2015 CL Bergen, NORWAY C1 [Papas, A. S.; Singh, M. L.] Tufts Univ, Sch Dent Med Boston, Oral Med, Medford, MA 02155 USA. [Teles, R.] UNC Sch Dent, Dept Periodontol, Chapel Hill, NC USA. [Haffajee, A. D.; Socransky, S. S.] Forsyth Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-9475 EI 1365-3083 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2015 VL 81 IS 5 MA S3.15 BP 351 EP 352 PG 2 WC Immunology SC Immunology GA CG6HV UT WOS:000353401300050 ER PT J AU Faustman, DL Alevizos, I AF Faustman, D. L. Alevizos, I. TI Investigation of Repeat BCG Vaccinations in Autoimmunity: Rationale and Phase I Trial in Sjogren's Syndrome SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Sjogren's Syndrome CY MAY 19-22, 2015 CL Bergen, NORWAY C1 [Faustman, D. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunobiol Lab, Boston, MA USA. [Alevizos, I.] NIDCR, Sjogrens Syndrome Clin, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-9475 EI 1365-3083 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2015 VL 81 IS 5 MA S13.3 BP 428 EP 429 PG 2 WC Immunology SC Immunology GA CG6HV UT WOS:000353401300198 ER PT J AU Hertzberg, L Katsel, P Roussos, P Haroutunian, V Domany, E AF Hertzberg, L. Katsel, P. Roussos, P. Haroutunian, V. Domany, E. TI Integration of gene expression and GWAS results supports involvement of calcium signaling in Schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE GWAS; Gene expression; Pathway analysis ID GENOME-WIDE ASSOCIATION; MULTIPLE BRAIN-REGIONS; RISK LOCI; IDENTIFICATION; METAANALYSIS; DATABASE AB The number of Genome Wide Association Studies (GWAS) of schizophrenia is rapidly growing. However, the small effect of individual genes limits the number of reliably implicated genes, which are too few and too diverse to perform reliable pathway analysis; hence the biological roles of the genes implicated in schizophrenia are unclear. To overcome these limitations we combine GWAS with genome-wide expression data from human post-mortem brain samples of schizophrenia patients and controls, taking these steps: 1) Identify 36 GWAS-based genes which are expressed in our dataset. 2) Find a cluster of 19 genes with highly correlated expression. We show that this correlation pattern is robust and statistically significant. 3) GO-enrichment analysis of these 19 genes reveals significant enrichment of ion channels and calcium-related processes. This finding (based on analyzing a small number of coherently expressed genes) is validated and enhanced in two ways: First, the emergence of calcium channels and calcium signaling is corroborated by identifying proteins that interact with those encoded by the cluster of 19. Second, extend the 19 cluster genes into 1028 genes, whose expression is highly correlated with the cluster's average profile. When GO-enrichment analysis is performed on this extended set, many schizophrenia related pathways appear, with calcium-related processes enriched with high statistical significance. Our results give further, expression-based validation to GWAS results, support a central role of calcium-signaling in the pathogenesis of schizophrenia, and point to additional pathways potentially related to the disease. (C) 2015 Elsevier B.V. All rights reserved. C1 [Hertzberg, L.; Domany, E.] Weizmann Inst Sci, Dept Phys Complex Syst, IL-7610001 Rehovot, Israel. [Hertzberg, L.] Tel Aviv Univ, Sackler Fac Med, Shalvata Mental Hlth Ctr, Emot Cognit Res Ctr, IL-69978 Tel Aviv, Israel. [Katsel, P.; Roussos, P.; Haroutunian, V.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Haroutunian, V.] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY USA. RP Domany, E (reprint author), Weizmann Inst Sci, Dept Phys Complex Syst, 234 Herzl St, IL-7610001 Rehovot, Israel. EM Eytan.domany@weizmann.ac.il RI Roussos, Panos/J-7090-2013 OI Roussos, Panos/0000-0002-4640-6239 FU VA-MIRECC; NIH [MH066392, MH064673]; Leir Charitable Foundation FX The study was funded by VA-MIRECC, NIH MH066392 and MH064673 and the Leir Charitable Foundation. NR 33 TC 6 Z9 6 U1 0 U2 6 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 MAY PY 2015 VL 164 IS 1-3 BP 92 EP 99 DI 10.1016/j.schres.2015.02.001 PG 8 WC Psychiatry SC Psychiatry GA CG5MX UT WOS:000353337100014 PM 25702973 ER PT J AU Vaez-Azizi, LM Ruby, E Dracxler, R Rothman, K Perrin, M Walsh-Messinger, J Antonius, D Goetz, RR Goetz, DM Keefe, DL Malaspina, D AF Vaez-Azizi, Leila M. Ruby, Eugene Dracxler, Roberta Rothman, Karen Perrin, Mary Walsh-Messinger, Julie Antonius, Daniel Goetz, Raymond R. Goetz, Deborah M. Keefe, David L. Malaspina, Dolores TI Telomere length variability is related to symptoms and cognition in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Letter ID AGE C1 [Vaez-Azizi, Leila M.; Ruby, Eugene; Dracxler, Roberta; Rothman, Karen; Antonius, Daniel; Goetz, Raymond R.; Keefe, David L.; Malaspina, Dolores] NYU, Sch Med, Dept Psychiat, Inst Social & Psychiat Initiat InSPIRES, New York, NY USA. [Dracxler, Roberta; Keefe, David L.] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. [Perrin, Mary; Malaspina, Dolores] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. [Walsh-Messinger, Julie] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC, Bronx, NY USA. [Walsh-Messinger, Julie] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Antonius, Daniel] SUNY Buffalo, Erie Cty Forens Mental Hlth Serv, Buffalo, NY 14260 USA. [Goetz, Raymond R.] New York State Psychiat Inst & Hosp, Div Clin Phenomenolgy, New York, NY 10032 USA. [Goetz, Deborah M.] New York State Off Mental Hlth, Nathan Kline Inst Psychiat Res, Orangeburg, NY USA. [Malaspina, Dolores] NY State Off Mental Hlth, Creedmoor Psychiat Ctr, Queens Village, NY 11427 USA. RP Vaez-Azizi, LM (reprint author), NYU, Sch Med, Dept Psychiat, 1 Pk Ave,8th Floor,Room 222, New York, NY 10016 USA. EM leila.vaez-azizi@med.nyu.edu; gene12586@gmail.com; roberta.dracxler@nyumc.org; Karen.rothman@nyumc.org; mary.perrin@nyumc.org; juliewmessinger@gmail.com; danantonius@gmail.com; goetzra@nyspi.columbia.edu; dgoetz@nki.rfmh.org; david.keefe@nyumc.org; dolores.malaspina@nyumc.org OI Goetz, Raymond/0000-0002-6797-2547 NR 10 TC 0 Z9 0 U1 1 U2 2 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 MAY PY 2015 VL 164 IS 1-3 BP 268 EP 269 DI 10.1016/j.schres.2015.03.011 PG 2 WC Psychiatry SC Psychiatry GA CG5MX UT WOS:000353337100040 PM 25841297 ER PT J AU Gottlieb, DJ AF Gottlieb, Daniel J. TI Obstructive Sleep Apnea: How Much Is Too Much? SO SLEEP LA English DT Editorial Material ID POSITIVE AIRWAY PRESSURE; CORONARY-ARTERY-DISEASE; BLOOD-PRESSURE; HEART-DISEASE; HYPERTENSION; CPAP; ADULTS; TRIAL C1 [Gottlieb, Daniel J.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Gottlieb, Daniel J.] Harvard Univ, Sch Med, Boston, MA USA. RP Gottlieb, DJ (reprint author), Brigham & Womens Hosp, Div Sleep Med, 221 Longwood Ave,BLI 225E, Boston, MA 02115 USA. EM djgottlieb@partners.org NR 19 TC 0 Z9 0 U1 1 U2 7 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 MAY 1 PY 2015 VL 38 IS 5 BP 659 EP 660 DI 10.5665/sleep.4644 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH2TD UT WOS:000353876600001 PM 25845683 ER PT J AU Janssen, SJ Braun, Y Wood, KB Cha, TD Schwab, JH AF Janssen, Stein J. Braun, Yvonne Wood, Kirkham B. Cha, Thomas D. Schwab, Joseph H. TI Allogeneic blood transfusions and postoperative infections after lumbar spine surgery SO SPINE JOURNAL LA English DT Article DE Transfusion; Infection; Lumbar; Surgery; Guideline; Policy; Immunomodulation ID SURGICAL SITE INFECTION; CHARLSON COMORBIDITY INDEX; COLORECTAL-CANCER SURGERY; BACTERIAL-INFECTION; CELL TRANSFUSION; FUSION SURGERY; RISK-FACTORS; METAANALYSIS; COMPLICATIONS; VALIDATION AB BACKGROUND CONTEXT: Allogeneic blood transfusions have an immunomodulating effect, and the previous studies in other fields of medicine demonstrated an increased risk of infections after administration of allogeneic blood transfusions. PURPOSE: Our primary null hypothesis is that exposure to allogeneic blood transfusion in patients undergoing lumbar spine surgery is not associated with postoperative infections after controlling for patient and treatment characteristics. Second, we assessed if there was a dose-response relationship per unit of blood transfused. STUDY DESIGN/SETTING: This is a retrospective cohort study from a tertiary care spine referral center. PATIENT SAMPLE: A total of 3,721 patients underwent laminectomy and/or arthrodesis of the lumbar spine. OUTCOMES MEASURES: Postoperative infections, pneumonia, endocarditis, meningitis, urinary tract infection, central venous line infection, surgical site infection, and sepsis, within 90 days after lumbar spine surgery were included. METHODS: Multivariable logistic regression analyses were used to assess the relationship of perioperative allogeneic blood transfusion with specific and overall postoperative infections accounting for age, duration of surgery, duration of hospital stay, comorbidity status, preoperative hemoglobin, sex, type of operation, multilevel treatment, operative approach, and year of surgery. RESULTS: The adjusted odds ratio for exposure to allogeneic blood transfusion from multivariable logistic regression analysis was 2.6 for any postoperative infection (95% confidence interval [CI]: 1.7 3.9, p<.001); 2.2 for urinary tract infections (95% CI: 1.3 3.9, p=.004); 2.3 for pneumonia (95% CI: 0.96-5.3, p=.062); and 2.6 for surgical site infection requiring incision and drainage (95% CI: 1.3-5.3, p=.007). Secondary analyses demonstrated no dose-response relationship between the number of blood units transfused and any of the postoperative infections. Because of the low number of endocarditis (1 case, 0.031%), meningitis (1 case, 0.031%), central venous line infection (1 case, 0.031%), and sepsis (14 cases, 0.43%), we abstained from multivariable analysis. CONCLUSIONS: Conscious of the limitations of this retrospective study, our data suggest an increased risk of surgical site infection, urinary tract infection, and overall postoperative infections, but not pneumonia, after exposure to allogeneic blood transfusion in patients undergoing lumbar spine surgery. These findings should be taken into account when considering blood transfusion and developing transfusion policies for patients undergoing lumbar spine procedures. (C) 2015 Elsevier Inc. All rights reserved. C1 [Janssen, Stein J.; Braun, Yvonne; Wood, Kirkham B.; Cha, Thomas D.; Schwab, Joseph H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Spine Serv, Boston, MA 02114 USA. RP Janssen, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Spine Serv, Rm 3-946,Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA. EM steinjanssen@gmail.com OI Braun, Yvonne/0000-0002-8193-5777 FU Anna Foundation; Michael van Vloten Foundation; De Drie Lichten Foundation; KWF Kankerbestrijding; OREF; AO Spine NA; Depuy Spine; K2M, Inc.; TranS1; North American Spine Society; Gordon and Betty Moore Foundation; Bio2; K2M; AO Spine; Stryker; Biom'up FX SJJ: Grant: Anna Foundation (B), Michael van Vloten Foundation (B), De Drie Lichten Foundation (B), KWF Kankerbestrijding (B). YB: Nothing to disclose. KBW: Other: OREF (E, Fellowship Support), AO Spine NA (E, Fellowship Support), Depuy Spine (E, Fellowship Support), K2M, Inc.: (C, Fellowship Support), TranS1 (C, Stock Options). TDC: Grant: North American Spine Society (D), Gordon and Betty Moore Foundation (B); Personnel Fees: Bio2 (B); Other: OREF (E, Institutional Fellowship Support), K2M (E, Institutional Fellowship Support), AO Spine (E, Institutional Fellowship Support). JHS: Other: Stryker (B, Consulting fees), Biom'up (B, Consulting fees). NR 33 TC 13 Z9 13 U1 1 U2 4 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 MAY 1 PY 2015 VL 15 IS 5 BP 901 EP 909 DI 10.1016/j.spinee.2015.02.010 PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA CG9HQ UT WOS:000353626100018 PM 25681582 ER PT J AU Llombart, V Antolin-Fontes, A Bustamante, A Giralt, D Rost, NS Furie, K Shibazaki, K Biteker, M Castillo, J Rodriguez-Yanez, M Fonseca, AC Watanabe, T Purroy, F Wu, ZX Etgen, T Hosomi, N Kerman, SRJ Sharma, JC Knauer, C Santamarina, E Giannakoulas, G Garcia-Berrocoso, T Montaner, J AF Llombart, Victor Antolin-Fontes, Albert Bustamante, Alejandro Giralt, Dolors Rost, Natalia S. Furie, Karen Shibazaki, Kensaku Biteker, Murat Castillo, Jose Rodriguez-Yanez, Manuel Fonseca, Ana Catarina Watanabe, Tetsu Purroy, Francisco Wu Zhixin Etgen, Thorleif Hosomi, Naohisa Kerman, Scott Reza Jafarian Sharma, Jagdish C. Knauer, Carolin Santamarina, Estevo Giannakoulas, George Garcia-Berrocoso, Teresa Montaner, Joan TI B-Type Natriuretic Peptides Help in Cardioembolic Stroke Diagnosis Pooled Data Meta-Analysis SO STROKE LA English DT Article DE biomarker; etiology ID ACUTE ISCHEMIC-STROKE; ATRIAL-FIBRILLATION; CRYPTOGENIC STROKE; UNDETERMINED SOURCE; EMBOLIC STROKES; ATTACK PATIENTS; INCREASED RISK; LEVELS PREDICT; HEART-DISEASE; MORTALITY AB Background and Purpose-Determining the underlying cause of stroke is important to optimize secondary prevention treatment. Increased blood levels of natriuretic peptides (B-type natriuretic peptide/N-terminal pro-BNP [BNP/NT-proBNP]) have been repeatedly associated with cardioembolic stroke. Here, we evaluate their clinical value as pathogenic biomarkers for stroke through a literature systematic review and individual participants' data meta-analysis. Methods-We searched publications in PubMed database until November 2013 that compared BNP and NT-proBNP circulating levels among stroke causes. Standardized individual participants' data were collected to estimate predictive values of BNP/NT-proBNP for cardioembolic stroke. Dichotomized BNP/NT-proBNP levels were included in logistic regression models together with clinical variables to assess the sensitivity and specificity to identify cardioembolic strokes and the additional value of biomarkers using area under the curve and integrated discrimination improvement index. Results-From 23 selected articles, we collected information of 2834 patients with a defined cause. BNP/NT-proBNP levels were significantly elevated in cardioembolic stroke until 72 hours from symptoms onset. Predictive models showed a sensitivity >90% and specificity >80% when BNP/NT-proBNP were added considering the lowest and the highest quartile, respectively. Both peptides also increased significantly the area under the curve and integrated discrimination improvement index compared with clinical models. Sensitivity, specificity, and precision of the models were validated in 197 patients with initially undetermined stroke with final pathogenic diagnosis after ancillary follow-up. Conclusions-Natriuretic peptides are strongly increased in cardioembolic strokes. Future multicentre prospective studies comparing BNP and NT-proBNP might aid in finding the optimal biomarker, the best time point, and the optimal cutoff points for cardioembolic stroke identification. C1 [Llombart, Victor; Antolin-Fontes, Albert; Bustamante, Alejandro; Giralt, Dolors; Garcia-Berrocoso, Teresa; Montaner, Joan] Univ Autonoma Barcelona, Inst Recerca Vall Hebron, Dept Neurol, Neurovasc Unit,Neurovasc Res Lab, E-08193 Barcelona, Spain. [Rost, Natalia S.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Acute Stroke Serv, Boston, MA 02114 USA. [Furie, Karen] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Dept Neurol, Providence, RI 02903 USA. [Shibazaki, Kensaku] Kawasaki Med Univ, Dept Stroke Med, Kurashiki, Okayama, Japan. [Biteker, Murat] Haydarpasa Numune Educ & Res Hosp, Dept Cardiol, Istanbul, Turkey. [Castillo, Jose; Rodriguez-Yanez, Manuel] Clin Univ, Hosp Univ Santiago Compostela, Hlth Res Inst Santiago Compostela IDIS, Dept Neurol, Santiago De Compostela, Spain. [Fonseca, Ana Catarina] Univ Lisbon, Hosp Santa Maria, Dept Neurosci Neurol, P-1699 Lisbon, Portugal. [Watanabe, Tetsu] Yamagata Univ, Sch Med, Dept Cardiol Pulmonol & Nephrol, Yamagata 990, Japan. [Purroy, Francisco] Hosp Arnau Vilanova, Dept Neurol, Stroke Unit, Grp Neurociencies Clin IRBLleida, Lleida, Spain. [Wu Zhixin] Foshan Hosp Tradit Chinese Med, Dept Emergency Med, Foshan, Guangdong, Peoples R China. [Etgen, Thorleif] Kliniken Sudostbayern Klinikum Traunstein, Dept Neurol, Traunstein, Germany. [Etgen, Thorleif] Tech Univ Munich, Dept Psychiat & Psychotherapy, D-80290 Munich, Germany. [Hosomi, Naohisa] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Clin Neurosci & Therapeut, Hiroshima, Japan. [Kerman, Scott Reza Jafarian] Univ Tehran Med Sci, Tehran, Iran. [Kerman, Scott Reza Jafarian] Hlth Serv, Tehran, Iran. [Sharma, Jagdish C.] Univ Nottingham, Lincoln Cty Hosp, Stroke & Parkinsons Dis Serv, Nottingham NG7 2RD, England. [Knauer, Carolin] Univ Ulm, Dept Neurol, D-89069 Ulm, Germany. [Santamarina, Estevo] Hosp Valle De Hebron, Dept Neurol, Stroke Unit, Barcelona, Spain. [Giannakoulas, George] AHEPA Univ Hosp, Dept Cardiol, Thessaloniki, Greece. RP Montaner, J (reprint author), Vall Hebron Univ Hosp, VHIR, Neurovasc Res Lab, Pg Vall Hebron 119-129, Barcelona 08035, Spain. EM 31862jmv@comb.es RI Jafarian Kerman, Scott/H-6329-2015; IBIS, NEUROVASCULAR/O-1855-2015; Fonseca, Ana Catarina/J-3127-2013; Montaner, Joan/D-3063-2015; OI Jafarian Kerman, Scott/0000-0003-0256-5251; Llombart, Victor/0000-0002-9981-7912 FU Fondo de Investigaciones Sanitarias [PI11/00176]; Vall Hebron Institute of Research; Instituto de Salud Carlos III [CM/00265]; Smoking Research Foundation FX Neurovascular Research Laboratory takes part into the Spanish stroke research network INVICTUS (RD12/0014/0005) and is partially funded by grants from the Fondo de Investigaciones Sanitarias PI11/00176). V. Llombart is supported by a predoctoral fellowship from Vall Hebron Institute of Research. Dr Bustamante is supported by a Rio Hortega contract CM/00265 from the Instituto de Salud Carlos III. Dr Hosomi is supported by the Smoking Research Foundation. NR 53 TC 10 Z9 10 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAY PY 2015 VL 46 IS 5 BP 1187 EP 1195 DI 10.1161/STROKEAHA.114.008311 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CG8LR UT WOS:000353559800023 PM 25765726 ER PT J AU Zhang, BX Zhang, ZL Lin, AL Wang, HZ Pilia, M Ong, JL Dean, DD Chen, XD Yeh, CK AF Zhang, Bin-Xian Zhang, Zhi-Liang Lin, Alan L. Wang, Hanzhou Pilia, Marcello Ong, Joo L. Dean, David D. Chen, Xiao-Dong Yeh, Chih-Ko TI Silk Fibroin Scaffolds Promote Formation of the Ex Vivo Niche for Salivary Gland Epithelial Cell Growth, Matrix Formation, and Retention of Differentiated Function SO TISSUE ENGINEERING PART A LA English DT Article ID MESENCHYMAL STEM-CELLS; PAROTID ACINAR-CELLS; EXTRACELLULAR-MATRIX; BIOMEDICAL APPLICATIONS; STERILIZATION METHODS; BONE-MARROW; SECRETION; CULTURE; MORPHOGENESIS; FATE AB Salivary gland hypofunction often results from a number of causes, including the use of various medications, radiation for head and neck tumors, autoimmune diseases, diabetes, and aging. Since treatments for this condition are lacking and adult salivary glands have little regenerative capacity, there is a need for cell-based therapies to restore salivary gland function. Development of these treatment strategies requires the establishment of a system that is capable of replicating the salivary gland cell "niche" to support the proliferation and differentiation of salivary gland progenitor cells. In this study, a culture system using three-dimensional silk fibroin scaffolds (SFS) and primary salivary gland epithelial cells (pSGECs) from rat submandibular (SM) gland and parotid gland (PG) was established and characterized. pSGECs grown on SFS, but not tissue culture plastic (TCP), formed aggregates of cells with morphological features resembling secretory acini. High levels of amylase were released into the media by both cell types after extended periods in culture on SFS. Remarkably, cultures of PG-derived cells on SFS, but not SM cells, responded to isoproterenol, a beta-adrenergic receptor agonist, with increased enzyme release. This behavior mimics that of the salivary glands in vivo. Decellularized extracellular matrix (ECM) formed by pSGECs in culture on SFS contained type IV collagen, a major component of the basement membrane. These results demonstrate that pSGECs grown on SFS, but not TCP, retain important functional and structural features of differentiated salivary glands and produce an ECM that mimics the native salivary gland cell niche. These results demonstrate that SFS has potential as a scaffold for creating the salivary gland cell niche in vitro and may provide an approach for inducing multipotent stem cells to provide therapeutically meaningful numbers of salivary gland progenitor cells for regenerating these tissues in patients. C1 [Zhang, Bin-Xian; Yeh, Chih-Ko] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Audie L Murphy Div, San Antonio, TX 78229 USA. [Zhang, Bin-Xian; Chen, Xiao-Dong] South Texas Vet Hlth Care Syst, Res Serv, Audie L Murphy Div, San Antonio, TX 78229 USA. [Zhang, Bin-Xian; Zhang, Zhi-Liang; Lin, Alan L.; Wang, Hanzhou; Dean, David D.; Chen, Xiao-Dong; Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Pilia, Marcello; Ong, Joo L.] Univ Texas San Antonio, Dept Biomed Engn, San Antonio, TX USA. RP Yeh, CK (reprint author), South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182, Audie L Murphy Div, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM chenx4@uthscsa.edu; yeh@uthscsa.edu OI Dean, David/0000-0002-4512-9065 FU NIH/NIDCR [R01 DE021084]; VA Merit Review grants [1I01BX001103, 1I01BX002145-01] FX This research was supported by grant R01 DE021084 from the NIH/NIDCR (Y. Sun and C.-K.Y.) and VA Merit Review grants 1I01BX001103 (C.-K.Y.) and 1I01BX002145-01 (X.-D.C.). The authors gratefully acknowledge the support from these organizations. NR 37 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 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD MAY 1 PY 2015 VL 21 IS 9-10 BP 1611 EP 1620 DI 10.1089/ten.tea.2014.0411 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CH3TD UT WOS:000353952300013 PM 25625623 ER PT J AU Fedorov, A Penzkofer, T Hirsch, MS Flood, TA Vangel, MG Masry, P Tempany, CM Mulkern, RV Fennessy, FM AF Fedorov, Andriy Penzkofer, Tobias Hirsch, Michelle S. Flood, Trevor A. Vangel, Mark G. Masry, Paul Tempany, Clare M. Mulkern, Robert V. Fennessy, Fiona M. TI The Role of Pathology Correlation Approach in Prostate Cancer Index Lesion Detection and Quantitative Analysis with Multiparametric MRI SO ACADEMIC RADIOLOGY LA English DT Article DE Prostate cancer; magnetic resonance imaging; pathology correlation; quantitative imaging ID CONTRAST-ENHANCED MRI; RADICAL PROSTATECTOMY; TUMOR VOLUME; CLINICAL-SIGNIFICANCE; REPEAT SEXTANT; IN-VIVO; SPECIMENS; HISTOPATHOLOGY; VALIDATION; REGISTRATION AB Rationale and Objectives: Development of imaging biomarkers often relies on their correlation with histopathology. Our aim was to compare two approaches for correlating pathology to multiparametric magnetic resonance (MR) imaging (mpMRI) for localization and quantitative assessment of prostate cancer (PCa) index tumor using whole mount (WM) pathology (WMP) as the reference. Materials and Methods: Patients (N = 30) underwent mpMRI that included diffusion-weighted imaging and dynamic contrast-enhanced (DOE) MRI at 3 T before radical prostatectomy (RP). RP specimens were processed using WM technique (WMP) and findings summarized in a standard surgical pathology report (SPR). Histology index tumor volumes (HTVs) were compared to MR tumor volumes (MRTVs) using two approaches for index lesion identification on mpMRI using annotated WMP slides as the reference (WMP) and using routine SPR as the reference. Consistency of index tumor localization, tumor volume, and mean values of the derived quantitative parameters (mean apparent diffusion coefficient [ADC], K-trans, and v(e)) were compared. Results: Index lesions from 16 of 30 patients met the selection criteria. There was WMP/SRP agreement in index tumor in 13 of 16 patients. ADC-based MRTVs were larger (P < .05) than DOE-based MRTVs. ADC MRTVs were smaller than HTV (P < .005). There was a strong correlation between HTV and MRTV (Pearson rho > 0.8; P < .05). No significant differences were observed in the mean values of K-trans and ADC between the WMP and SPR. Conclusions: WMP correlation is superior to SPR for accurate localization of all index lesions. The use of WMP is however not required to distinguish significant differences of mean values of quantitative MRI parameters within tumor volume. C1 [Fedorov, Andriy; Penzkofer, Tobias; Tempany, Clare M.; Fennessy, Fiona M.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Penzkofer, Tobias] RWTH Aachen Univ Hosp, Dept Radiol, Aachen, Germany. [Hirsch, Michelle S.; Flood, Trevor A.; Masry, Paul] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Vangel, Mark G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mulkern, Robert V.] Boston Childrens Hosp, Dept Radiol, Boston, MA USA. [Fennessy, Fiona M.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Fennessy, FM (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM ffennessy@partners.org OI Fedorov, Andrey/0000-0003-4806-9413 FU National Institutes of Health [U01CA151261, P41EB015898, R01CA111288]; RWTH Aachen University Hospital FX This work was supported by National Institutes of Health through grants U01CA151261, P41EB015898, R01CA111288. T.P. received a grant from RWTH Aachen University Hospital. The authors thank Louise Greenberg, M.Ed., and Sebastian Valentin for coordination of this study, and Sandeep Gupta and Ming-Ching Chang from GE Global Research for providing the OncoQuant research software prototype for use in this study. NR 39 TC 5 Z9 5 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 2015 VL 22 IS 5 BP 548 EP 555 DI 10.1016/j.acra.2014.12.022 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CG2AZ UT WOS:000353078600002 PM 25683501 ER PT J AU Elliott, JT Samkoe, KS Gunn, JR Stewart, EE Gardner, TB Tichauer, KM Lee, TY Hoopes, PJ Pereira, SP Hasan, T Pogue, BW AF Elliott, Jonathan T. Samkoe, Kimberley S. Gunn, Jason R. Stewart, Errol E. Gardner, Timothy B. Tichauer, Kenneth M. Lee, Ting-Yim Hoopes, P. Jack Pereira, Stephen P. Hasan, Tayyaba Pogue, Brian W. TI Perfusion CT Estimates Photosensitizer Uptake and Biodistribution in a Rabbit Orthotopic Pancreatic Cancer Model: A Pilot Study SO ACADEMIC RADIOLOGY LA English DT Article DE Pancreatic cancer; CT perfusion; drug delivery; photodynamic therapy; dosimetry; pharmacokinetics ID PHOTODYNAMIC THERAPY; COMPUTED-TOMOGRAPHY; TUMOR; ADENOCARCINOMA; IDENTIFICATION; CARCINOMA; AGENT; MRI AB Rationale and Objectives: It was hypothesized that perfusion computed tomography (CT), blood flow (BF), blood volume (BV), and vascular permeability surface area (PS) product parameters would be predictive of therapeutic anticancer agent uptake in pancreatic cancer, facilitating image-guided interpretation of human treatments. The hypothesis was tested in an orthotopic rabbit model of pancreatic cancer, by establishing-the model, imaging with endoscopic ultrasound (EUS) and contrast CT, and spatially comparing the perfusion maps to the ex vivo uptake values of the injected photosensitizer, verteporfin. Materials and Methods: Nine New Zealand white rabbits underwent direct pancreas implantation of VX2 tumors, and CT perfusion or EUS was performed 10 days postimplantation. Verteporfin was injected during CT imaging, and the tissue was removed 1 hour post-injection for frozen tissue fluorescence scanning. Region-of-interest-comparisons of CT data with ex vivo fluorescence and histopathologic staining were performed. Results: Dynamic contrast-enhanced CT showed enhanced BF, BV, and PS in the tumor rim and decreased BF, BV, and PS in the tumor core. Significant correlations were found between ex vivo verteporfin concentration and each of BF, BV, and PS. Conclusions: The efficacy of verteporfin delivery in tumors is estimated by perfusion CT, providing a noninvasive method of mapping photosensitizer dose. C1 [Elliott, Jonathan T.; Samkoe, Kimberley S.; Gunn, Jason R.; Hoopes, P. Jack; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Samkoe, Kimberley S.; Gardner, Timothy B.; Hoopes, P. Jack; Pogue, Brian W.] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. [Stewart, Errol E.; Lee, Ting-Yim] Univ Western Ontario, Dept Med Biophys, London, ON, Canada. [Tichauer, Kenneth M.] IIT, Dept Biomed Engn, Chicago, IL 60616 USA. [Pereira, Stephen P.] UCL, Inst Liver & Digest Hlth, London, England. [Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Elliott, JT (reprint author), Dartmouth Coll, Thayer Sch Engn, 14 Engn Dr, Hanover, NH 03755 USA. EM Jonathan.T.Elliott@dartmouth.edu RI Lee, Ting-Yim/M-1721-2013 FU National Institutes of Health [P01 CA84203/CA/NCI] FX This work was funded by a National Institutes of Health grant (P01 CA84203/CA/NCI). NR 26 TC 3 Z9 3 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 2015 VL 22 IS 5 BP 572 EP 579 DI 10.1016/j.acra.2014.12.014 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CG2AZ UT WOS:000353078600005 PM 25683500 ER PT J AU Kanayama, G Hudson, JI DeLuca, J Isaacs, S Baggish, A Weiner, R Bhasin, S Pope, HG AF Kanayama, Gen Hudson, James I. DeLuca, James Isaacs, Stephanie Baggish, Aaron Weiner, Rory Bhasin, Shalender Pope, Harrison G., Jr. TI Prolonged hypogonadism in males following withdrawal from anabolic-androgenic steroids: an under-recognized problem SO ADDICTION LA English DT Article DE Anabolic-androgenic steroids; drug withdrawal; erectile function; hypogonadism; libido; men; testosterone ID HUMAN CHORIONIC-GONADOTROPIN; PERFORMANCE-ENHANCING DRUGS; FAT-FREE MASS; HYPOGONADOTROPIC HYPOGONADISM; ERECTILE DYSFUNCTION; RISK-FACTORS; YOUNG MEN; AZOOSPERMIA; TESTOSTERONE; DEPENDENCE AB AimsTo assess the frequency and severity of hypogonadal symptoms in male long-term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use. DesignCross-sectional, naturalistic. SettingOut-patient facility. ParticipantsTwenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiological testosterone replacement, leaving 19 untreated users for the numerical comparisons below. MeasurementsThe Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations and the International Index of Erectile Function (IIEF). FindingsCompared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes [estimated difference, 95% confidence interval (CI)=2.3 (0.1, 4.5) ml; P=0.042] and lower serum testosterone levels [estimated difference: 95% CI=131 (25, 227) dl; P=0.009], with five users showing testosterone levels below 200ng/dl despite abstinence from AAS for 3-26 months. Untreated former users also displayed significantly lower scores on the IIEF sexual desire subscale [estimated difference: 95% CI=2.4 (1.3, 3.4) points on a 10-point scale; P < 0.001]. In the overall group of 24 treated plus untreated former users, seven (29%) had experienced major depressive episodes during AAS withdrawal; four of these had not experienced major depressive episodes at any other time. Two men (8%) had failed to regain normal libidinal or erectile function despite adequate replacement testosterone treatment. ConclusionsAmong long-term anabolic-androgenic steroid misusers, anabolic-androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged and associated with substantial morbidity. C1 [Kanayama, Gen; Hudson, James I.; Pope, Harrison G., Jr.] McLean Hosp, Biol Psychiat Lab, Belmont, MA 02478 USA. [Kanayama, Gen; Hudson, James I.; Pope, Harrison G., Jr.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bhasin, Shalender] Brigham & Womens Hosp, Res Program Mens Hlth Aging & Metab, Boston, MA USA. [Bhasin, Shalender] Harvard Univ, Sch Med, Boston, MA USA. RP Kanayama, G (reprint author), McLean Hosp, Belmont, MA 02478 USA. EM hpope@mclean.harvard.edu FU United States National Institutes on Drug Abuse (NIDA) [R01 DA029141] FX This research was supported in part by grant R01 DA029141 from the United States National Institutes on Drug Abuse (NIDA) (G.K., R.W., A.B., H.G.P., J.DeL. and S.I.). NIDA had no further role in study design; collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 51 TC 4 Z9 4 U1 1 U2 6 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 MAY PY 2015 VL 110 IS 5 BP 823 EP 831 DI 10.1111/add.12850 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CG1KJ UT WOS:000353031200019 PM 25598171 ER PT J AU Santen, SA Petrusa, E Gruppen, LD AF Santen, Sally A. Petrusa, Emil Gruppen, Larry D. TI The relationship between promotions committees' identification of problem medical students and subsequent state medical board actions SO ADVANCES IN HEALTH SCIENCES EDUCATION LA English DT Article DE Medical student; Professionalism; Assessment; State medical boards ID UNPROFESSIONAL BEHAVIOR; DISCIPLINARY ACTION; PROFESSIONAL BEHAVIOR; SCHOOL; PERFORMANCE AB Studies have found unprofessional behavior in medical school was associated with disciplinary action by state medical boards. For medical schools, promotions committees are responsible for identifying which students do not demonstrate academic performance and professional behavior acceptable for promotion and graduation. The objective of this study was to determine if student identification by promotions committees during medical school was associated with disciplinary actions by state medical boards later in practice. We reviewed 20 years of promotions committees' records from a single institution and noted students identified by promotions committees for performance or behavioral issues. These were compared with disciplinary action reports from the Federation of State Medical Boards (FSMB) for graduates. Over the two decades, 2,131 students matriculated and 2,078 of these graduated. The promotions committees identified 140 students for poor academic performance or behavioral problems (140/2,078, 6.7 %). Of these, 108 students graduated. FSMB records showed 29 of the 2,078 graduates had sanctions by state boards (29/2,078, 1.4 %). Only four students that had actions by state medical boards were among the 108 graduated students identified by medical school promotions committees (4/108, 3.7 %). Of the students not identified by promotions committees, 25 eventually had disciplinary actions (25/1,970, 1.3 %). The odds of having state medical board action if identified by promotions committees was 3.0 (CI 1.02-8.8, p < 0.05). In conclusion, identification of students by medical school promotions committees was later associated with state medical board actions. However, most graduates with state medical board actions were not identified by medical school promotions committees. C1 [Santen, Sally A.; Gruppen, Larry D.] Univ Michigan, Dept Learning Hlth Sci, Sch Med, Ann Arbor, MI 48109 USA. [Santen, Sally A.] Univ Michigan, Dept Emergency Med, Sch Med, Ann Arbor, MI 48109 USA. [Santen, Sally A.; Petrusa, Emil] Vanderbilt Univ Sch Med, Off Teaching & Learning Med, Nashville, TN USA. [Petrusa, Emil] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Santen, SA (reprint author), Univ Michigan, Dept Emergency Med, Sch Med, 5121 Med Sci Bldg 1,1301 Catherine St, Ann Arbor, MI 48109 USA. EM ssanten@umich.edu OI Gruppen, Larry/0000-0002-2107-0126 NR 20 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4996 EI 1573-1677 J9 ADV HEALTH SCI EDUC JI Adv. Health Sci. Educ. PD MAY PY 2015 VL 20 IS 2 BP 421 EP 430 DI 10.1007/s10459-014-9536-2 PG 10 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CG0OQ UT WOS:000352966300010 PM 25134665 ER PT J AU Simpson, TL Malte, CA Dietel, B Tell, D Pocock, I Lyons, R Varon, D Raskind, M Saxon, AJ AF Simpson, Tracy L. Malte, Carol A. Dietel, Bergetta Tell, Dana Pocock, Ian Lyons, Robert Varon, Dana Raskind, Murray Saxon, Andrew J. TI A Pilot Trial of Prazosin, an Alpha-1 Adrenergic Antagonist, for Comorbid Alcohol Dependence and Posttraumatic Stress Disorder SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Noradrenergic; Prazosin; Alcohol Dependence; Posttraumatic Stress Disorder; Human Clinical Trial ID RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE USE DISORDER; PHARMACOLOGICAL-TREATMENT; PREFRONTAL CORTEX; RECENT PROGRESS; PTSD; NOREPINEPHRINE; INDIVIDUALS; NALTREXONE; VETERANS AB BackgroundPosttraumatic stress disorder (PTSD) and alcohol dependence (AD) commonly co-occur and are associated with greater symptom severity and costs than either disorder alone. No pharmacologic interventions have been found to decrease both alcohol use and PTSD symptom severity relative to matched placebo. Prazosin, an alpha-1 adrenoreceptor antagonist, has demonstrated the efficacy of reducing PTSD and AD symptoms among individuals with one or the other disorder and may be useful in addressing comorbid PTSD/AD. MethodsPrazosin and matched placebo were compared in the context of an outpatient 6-week double-blind randomized controlled pilot trial involving 30 individuals with comorbid PTSD/AD. Medication was titrated to 4mgqam, 4mgqpm and 8mg qhs by the end of week 2. Participants in both conditions received 5 medical management sessions. Information regarding alcohol use, craving, and PTSD was gathered daily using a telephone interactive voice response system. ResultsParticipants randomized to prazosin had a greater reduction in percent days drinking per week and percent days heavy drinking per week between baseline and week 6 than did placebo participants. No significant differences were detected within or between groups in change from weeks 1 to 6 in total PTSD symptoms. Participants in the prazosin condition reported drowsiness on significantly more days than those in the placebo condition. ConclusionsConsistent with the extant research evaluating medications for comorbid PTSD/AD, the current evaluation of prazosin also found decreased alcohol consumption but no medication effect on PTSD symptomatology. C1 [Simpson, Tracy L.; Malte, Carol A.; Dietel, Bergetta; Tell, Dana; Pocock, Ian; Lyons, Robert; Varon, Dana; Saxon, Andrew J.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Simpson, Tracy L.; Raskind, Murray] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Simpson, Tracy L.; Raskind, Murray; Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Dietel, Bergetta; Tell, Dana; Pocock, Ian; Lyons, Robert; Varon, Dana] Seattle Inst Biomed & Clin Res, Seattle, WA USA. RP Simpson, TL (reprint author), 1660 S Columbian Way,116 ATC S, Seattle, WA 98108 USA. EM Tracy.Simpson@va.gov FU VA Puget Sound Health Care System, Seattle, Washington Center of Excellence in Substance Abuse Treatment and Education; [NIAAA P20 1 P20 AA017839-01] FX Funding for this study was provided by a grant awarded to AJS (NIAAA P20 1 P20 AA017839-01) and the VA Puget Sound Health Care System, Seattle, Washington Center of Excellence in Substance Abuse Treatment and Education. NR 49 TC 11 Z9 11 U1 1 U2 6 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 MAY PY 2015 VL 39 IS 5 BP 808 EP 817 DI 10.1111/acer.12703 PG 10 WC Substance Abuse SC Substance Abuse GA CG1QX UT WOS:000353049600006 PM 25827659 ER PT J AU Rajbhandari, R Danford, CJ Chung, RT Ananthakrishnan, AN AF Rajbhandari, R. Danford, C. J. Chung, R. T. Ananthakrishnan, A. N. TI HBV infection is associated with greater mortality in hospitalised patients compared to HCV infection or alcoholic liver disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CHRONIC HEPATITIS-B; UNITED-STATES; NATURAL-HISTORY; REACTIVATION; VIRUS; THERAPY; CANCER; BURDEN; COHORT; RISK AB BackgroundLittle is known about outcomes of Hepatitis B virus (HBV)-related hospitalisations. AimTo compare the characteristics and outcomes of hospitalised HBV patients to those with Hepatitis C virus (HCV) infection and alcoholic liver disease (ALD), and to examine variables associated with poor outcomes. MethodsUsing the 2011 US Nationwide Inpatient Sample, we identified hospitalised patients with HBV, HCV or ALD-related admissions using ICD-9-CM codes. We compared liver-related complications between the three groups. Multivariable regression was performed to identify factors associated with in-hospital mortality and length of stay. ResultsA total of 22843 HBV, 203300 HCV and 244383 ALD-related discharges were included. Cirrhosis was noted less commonly in those with HBV (69.1%) compared to HCV (83.9%) or ALD (80.9%) (P<0.001). In contrast, hepatocellular cancer and acute liver failure were more common with HBV (16.5% and 5.2%) compared to HCV (10.4% and 2.8%) or ALD (2.5% and 4.9%) respectively (P<0.0001). On multivariable analysis, adjusting for demographics, liver and nonliver comorbidity, HBV infection was associated with higher mortality compared to HCV infection [Odds ratio (OR) 1.21, 95% CI: 1.04-1.39) or ALD (OR: 1.21, 95% CI: 1.05-1.40). Length of hospital stay was greater with HBV compared to HCV (+0.54days) or ALD (+0.36days). Among those with HBV, significant factors associated with mortality included renal failure, hepatocellular cancer, respiratory failure, ascites, coagulopathy and acute liver failure. ConclusionPatients hospitalised with HBV infection represent a particularly high-risk group with poor in-hospital outcomes and increased mortality compared to HCV infection or alcoholic liver disease. C1 [Rajbhandari, R.; Chung, R. T.; Ananthakrishnan, A. N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Rajbhandari, R.; Chung, R. T.; Ananthakrishnan, A. N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Rajbhandari, R.; Danford, C. J.; Chung, R. T.; Ananthakrishnan, A. N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. EM rtchung@partners.org; aananthakrishnan@mgh.harvard.edu FU Gilead; Bristol Myers Squibb; National Institutes of Health [T32 DK007191, K24 DK078772, K23 DK097142] FX Declaration of personal interests: Dr Ananthakrishnan has participated in scientific advisory boards of Abbvie and Cubist pharmaceuticals. Dr. Raymond Chung has received research funding from Gilead and Bristol Myers Squibb. Dr. Ruma Rajbhandari and Dr. Christopher Danford have no conflicts of interest to disclose.; Declaration of funding interests: Dr Ruma Rajbhandari is supported by a grant from the National Institutes of Health (T32 DK007191). Dr Raymond Chung is supported in part by a grant from the National Institutes of Health (K24 DK078772). Dr Ananthakrishnan is supported in part by a grant from the National Institutes of Health (K23 DK097142). NR 21 TC 4 Z9 4 U1 0 U2 1 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 MAY PY 2015 VL 41 IS 10 BP 928 EP 938 DI 10.1111/apt.13162 PG 11 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA CG1RG UT WOS:000353050600002 PM 25786514 ER PT J AU Shelton, E Chaudrey, K Sauk, J Khalili, H Masia, R Nguyen, DD Yajnik, V Ananthakrishnan, AN AF Shelton, E. Chaudrey, K. Sauk, J. Khalili, H. Masia, R. Nguyen, D. D. Yajnik, V. Ananthakrishnan, A. N. TI New onset idiosyncratic liver enzyme elevations with biological therapy in inflammatory bowel disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID QUALITY-OF-LIFE; CROHNS-DISEASE; AUTOIMMUNE HEPATITIS; INFLIXIMAB THERAPY; RHEUMATOID-ARTHRITIS; MAINTENANCE THERAPY; ULCERATIVE-COLITIS; METAANALYSIS; ANTAGONISTS; ETANERCEPT AB BackgroundAnti-tumour necrosis factor (anti-TNF) agents have been implicated in drug-induced liver injury. There is minimal data on this occurrence in inflammatory bowel disease (IBD) patients. AimTo identify the characteristics of liver enzyme elevations following anti-TNF therapy initiation in IBD. MethodsA retrospective cohort of patients initiating anti-TNF therapy were analysed for new onset alanine transaminase (ALT) elevation (60U/L). We collected data on natural history, outcomes and patient characteristics compared with controls with persistent normal liver enzymes. Likelihood of causal association was assessed using the RUCAM score. ResultsFrom 1753 patients initiating an anti-TNF (1170 infliximab, 575 adalimumab, 8 certolizumab), 102 (6%) developed new onset ALT elevation. In 54 (53%), this could be linked to an alternate aetiology. Among those with idiopathic ALT elevations, the median time to ALT elevation from anti-TNF initiation was 18weeks and median peak ALT was 96U/L. Six underwent liver biopsy, all demonstrating hepatitis with autoimmune features. Compared to controls, cases were on a lower dose of infliximab (5.7 vs. 6.7mg/kg, P=0.02) but were otherwise similar in body mass index, sex and age. On follow-up, 34 continued the anti-TNF, 14 stopped therapy and 4 initiated steroids. Most (85%) normalised their LFTs after a median of 17weeks including 28 (82%) of those who continued anti-TNF therapy. Ten patients were transitioned to a second anti-TNF without recurrence. ConclusionsALT elevations occurred in 6% of IBD patients initiating anti-TNF therapy. Most idiopathic elevations were mild, transient and resolved despite therapy continuation. C1 [Shelton, E.; Chaudrey, K.; Sauk, J.; Khalili, H.; Nguyen, D. D.; Yajnik, V.; Ananthakrishnan, A. N.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Shelton, E.; Sauk, J.; Khalili, H.; Masia, R.; Nguyen, D. D.; Yajnik, V.; Ananthakrishnan, A. N.] Harvard Univ, Sch Med, Boston, MA USA. [Masia, R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU US National Institutes of Health [K23 DK097142] FX Declaration of funding interests: Ananthakrishnan is supported by funding from the US National Institutes of Health (K23 DK097142). NR 32 TC 7 Z9 7 U1 0 U2 2 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 MAY PY 2015 VL 41 IS 10 BP 972 EP 979 DI 10.1111/apt.13159 PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA CG1RG UT WOS:000353050600006 PM 25756190 ER PT J AU Cheng, R Chan, AP Ehdaie, A Bersohn, MM AF Cheng, Richard Chan, Amy P. Ehdaie, Ashkan Bersohn, Malcolm M. TI Heeding the Sign: Macroscopic T-Wave Alternans SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Cheng, Richard; Chan, Amy P.; Ehdaie, Ashkan] Cedars Sinai Heart Inst, Los Angeles, CA USA. [Chan, Amy P.; Ehdaie, Ashkan; Bersohn, Malcolm M.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA 90073 USA. [Bersohn, Malcolm M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Bersohn, MM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Cardiol 111E,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mbersohn@ucla.edu OI Cheng, Richard/0000-0003-2552-6773 NR 5 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 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD MAY PY 2015 VL 128 IS 5 BP 480 EP 483 DI 10.1016/j.amjmed.2015.01.006 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CG7XK UT WOS:000353520500025 PM 25637757 ER PT J AU Slocum, CS Goldstein, R DiVita, MA Mix, J Niewczyk, P Gerrard, P Sheridan, R Kowalske, KJ Zafonte, R Ryan, CM Schneider, JC AF Slocum, Chloe S. Goldstein, Richard DiVita, Margaret A. Mix, Jacqueline Niewczyk, Paulette Gerrard, Paul Sheridan, Robert Kowalske, Karen J. Zafonte, Ross Ryan, Colleen M. Schneider, Jeffrey C. TI Assessing the Ability of Comorbidity Indexes to Capture Comorbid Disease in the Inpatient Rehabilitation Burn Injury Population SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Burns; Comorbidities; Inpatient Rehabilitation; Comorbidity Indexes ID TRAUMATIC BRAIN-INJURY; SPINAL-CORD-INJURY; RISK-FACTORS; ACUTE-CARE; STROKE REHABILITATION; CANCER-PATIENTS; ADULT PATIENTS; OUTCOMES; MORTALITY; PREDICTORS AB Objective: Burn patients exhibit comorbidities that influence outcomes. This study examines whether existing comorbidity measures capture comorbidities in the burn inpatient rehabilitation population. Design: Data were obtained from the Uniform Data System for Medical Rehabilitation from 2002 to 2011 for adults with burn injury. International Classification of Diseases, 9th Revision, codes were used to assess three comorbidity measures (Charlson Comorbidity Index, Elixhauser Comorbidity Index, Centers for Medicare and Medicaid Services Comorbidity Tiers). The number of subjects and unique comorbidity codes (>1% of frequency) captured by each comorbidity measure was calculated. Results: The study included 5347 patients with a median total body surface area burn decile of 20%-29%, mean age of 51.6 yrs, and mean number of comorbidities of 7.6. There were 2809 unique International Classification of Diseases, 9th Revision, comorbidity codes. The Charlson Comorbidity Index, Elixhauser Comorbidity Index, and Centers for Medicare and Medicaid Services Comorbidity Tiers did not capture 67%, 27%, and 58% of the subjects, respectively. There were 107 unique comorbidities that occurred with a frequency of greater than 1%. Of these, 67% were not captured in all three comorbidity measures. Conclusions: Commonly used comorbidity indexes do not reflect the extent of comorbid disease in the burn rehabilitation population. Future work is needed to assess the need for comorbidity indexes specific to the inpatient rehabilitation setting. C1 [Slocum, Chloe S.; Goldstein, Richard; Gerrard, Paul; Zafonte, Ross; Schneider, Jeffrey C.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Charlestown, MA 02129 USA. [DiVita, Margaret A.; Mix, Jacqueline; Niewczyk, Paulette] Uniform Data Syst Med Rehabil, Amherst, NY USA. [Niewczyk, Paulette] Daemen Coll, Hlth Care Studies Dept, Amherst, NY USA. [Sheridan, Robert; Ryan, Colleen M.] Shriners Hosp Children, Dept Surg, Boston, MA USA. [Sheridan, Robert; Ryan, Colleen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv,Sumner Redstone Burn Ctr, Boston, MA USA. [Kowalske, Karen J.] Univ Texas SW Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. RP Schneider, JC (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 300 1st Ave, Charlestown, MA 02129 USA. OI DiVita, Margaret/0000-0002-4878-2959 FU Department of Education, NIDRR [H133A120034] FX Funded by grants from the Department of Education, NIDRR grant number H133A120034. However, these contents do not necessarily represent the policy of the Department of Education, and endorsement by the Federal Government should not be assumed. Presented at the 46th Annual Meeting of the American Burn Association, Boston, Massachusetts, March 25-28, 2014, in Correlative Session V, Session Title: Rehabilitation. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. NR 41 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAY PY 2015 VL 94 IS 5 BP 373 EP 384 DI 10.1097/PHM.0000000000000180 PG 12 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CG3BN UT WOS:000353151700008 PM 25171665 ER PT J AU Williams, CD Chan, AT Elman, MR Kristensen, AH Miser, WF Pignone, MP Stafford, RS McGregor, JC AF Williams, Craig D. Chan, Andrew T. Elman, Miriam R. Kristensen, Alyson H. Miser, W. Fred Pignone, Michael P. Stafford, Randall S. McGregor, Jessina C. TI Aspirin Use Among Adults in the US Results of a National Survey SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID RANDOMIZED-TRIALS; PREVENTION AB Introduction: The use of aspirin in patients without cardiovascular disease remains controversial. Patients' understanding of the risks and benefits of aspirin likely contribute to the decision of whether or not to use aspirin regularly. The purpose of this study is to assess patients' knowledge of aspirin and identify factors contributing to regular use. Methods: A survey of U.S. adults aged 45-75 years was performed to ascertain aspirin use and factors that may be associated with use. Multivariate logistic regression was used to identify predictors of current use of aspirin among those with a primary prevention indication. The survey was completed in 2012 with data analysis performed in 2013. Results: Among 2,509 respondents, 52% reported current aspirin use. Among 2,039 respondents without a history of cardiovascular disease, current use of aspirin was 47%. Regular use of aspirin for primary prevention was associated with the presence of major cardiovascular disease risk factors (OR = 3.0, 95% CI = 2.4, 3.7), high self-assessed knowledge of aspirin (OR = 9.1, 95% CI = 5.2, 15.7), and having discussed aspirin therapy with a provider (OR = 25.9, 95% CI = 19.7, 34.1). Several markers of healthy lifestyle choices were also associated with regular use. After multivariate analysis, the strongest independent predictor of regular aspirin use was having discussed aspirin therapy with a provider (OR = 23.79, 95% CI = 17.8, 31.5). Conclusions: Approximately half of the nationwide survey of U.S. adults reported regular aspirin use. Among those with a primary prevention indication, having discussed aspirin with a provider was the strongest predictor of regular use. (C) 2015 American Journal of Preventive Medicine C1 [Williams, Craig D.; Elman, Miriam R.; McGregor, Jessina C.] Oregon Hlth & Sci Univ, Oregon State Univ, Coll Pharm, Dept Pharm Practice, Portland, OR 97201 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Kristensen, Alyson H.] Partnership Prevent, Washington, DC USA. [Miser, W. Fred] Ohio State Univ, Div Family Med, Columbus, OH 43210 USA. [Pignone, Michael P.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Stafford, Randall S.] Stanford Univ, Dept Med, Palo Alto, CA USA. RP Williams, CD (reprint author), Oregon Hlth & Sci Univ, Oregon State Univ, Coll Pharm, 2730 SW Moody Ave,CL5CP, Portland, OR 97201 USA. EM williacr@ohsu.edu FU Partnership for Prevention and the Council on Aspirin for Health and Prevention; Bayer HealthCare FX The study survey was sponsored by Partnership for Prevention and the Council on Aspirin for Health and Prevention. The Council on Aspirin for Health and Prevention is an initiative of Partnership for Prevention, a nonprofit organization that promotes disease prevention and health policy. Partnership for Prevention receives financial support for the Council through an unrestricted grant from Bayer HealthCare, which has no influence over the programs or activities of the Council. Bayer HealthCare had no role in the decision to conduct this research, design and implementation of the survey, analysis and interpretation of the data, or writing and editing of the manuscript. The authors do not receive any financial support from Bayer HealthCare. ATC reports being a previous consultant for Bayer and Pozen (412 months prior) and a current DSMB member for Pfizer. NR 9 TC 6 Z9 6 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2015 VL 48 IS 5 BP 501 EP 508 DI 10.1016/j.amepre.2014.11.005 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CG1XO UT WOS:000353069300004 PM 25891049 ER PT J AU Huprikar, S Danziger-Isakov, L Ahn, J Naugler, S Blumberg, E Avery, RK Koval, C Lease, ED Pillai, A Doucette, KE Levitsky, J Morris, MI Lu, K McDermott, JK Mone, T Orlowski, JP Dadhania, DM Abbott, K Horslen, S Laskin, BL Mougdil, A Venkat, VL Korenblat, K Kumar, V Grossi, P Bloom, RD Brown, K Kotton, CN Kumar, D AF Huprikar, S. Danziger-Isakov, L. Ahn, J. Naugler, S. Blumberg, E. Avery, R. K. Koval, C. Lease, E. D. Pillai, A. Doucette, K. E. Levitsky, J. Morris, M. I. Lu, K. McDermott, J. K. Mone, T. Orlowski, J. P. Dadhania, D. M. Abbott, K. Horslen, S. Laskin, B. L. Mougdil, A. Venkat, V. L. Korenblat, K. Kumar, V. Grossi, P. Bloom, R. D. Brown, K. Kotton, C. N. Kumar, D. TI Solid Organ Transplantation From Hepatitis B Virus-Positive Donors: Consensus Guidelines for Recipient Management SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID HBSAG-NEGATIVE RECIPIENTS; OF-THE-LITERATURE; SURFACE-ANTIGEN; CORE ANTIBODY; LIVER-TRANSPLANTATION; KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; LUNG TRANSPLANTATION; HEART-TRANSPLANTATION; ENTECAVIR THERAPY AB Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended. C1 [Huprikar, S.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Danziger-Isakov, L.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Ahn, J.; Naugler, S.] Oregon Hlth & Sci Univ, Portland, OR USA. [Blumberg, E.; Bloom, R. D.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Avery, R. K.] Johns Hopkins, Baltimore, MD USA. [Koval, C.] Cleveland Clin, Cleveland, OH 44106 USA. [Lease, E. D.] Univ Washington, Seattle, WA 98195 USA. [Pillai, A.] Emory Univ Hosp, Atlanta, GA 30322 USA. [Doucette, K. E.] Univ Alberta, Edmonton, AB, Canada. [Levitsky, J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Morris, M. I.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Lu, K.] I Shou Univ, Dept Surg, Div Urol, Kaohsiung, Taiwan. [McDermott, J. K.] Spectrum Hlth, Grand Rapids, MI USA. [Mone, T.] OneLegacy, Los Angeles, CA USA. [Orlowski, J. P.] LifeShare Oklahoma, Oklahoma City, OK USA. [Dadhania, D. M.] Cornell Univ, New York, NY 10021 USA. [Abbott, K.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Horslen, S.] Seattle Childrens Hosp, Seattle, WA USA. [Laskin, B. L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Mougdil, A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Venkat, V. L.] UPMC, Pediat Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Korenblat, K.] Washington Univ, St Louis, MO USA. [Kumar, V.] Univ Alabama Birmingham, Birmingham, AL USA. [Grossi, P.] Univ Insubria, Varese, Italy. [Brown, K.] Henry Ford Hosp, Detroit, MI 48202 USA. [Kotton, C. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kumar, D.] Univ Toronto, Toronto, ON, Canada. RP Huprikar, S (reprint author), Icahn Sch Med Mt Sinai, New York, NY 10029 USA. EM shirish.huprikar@mssm.edu OI Doucette, Karen/0000-0002-1660-9166 NR 85 TC 19 Z9 19 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 IS 5 BP 1162 EP 1172 DI 10.1111/ajt.13187 PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA CG5ML UT WOS:000353335900009 PM 25707744 ER PT J AU Aoyama, A Tonsho, M Ng, CY Lee, S Millington, T Nadazdin, O Wain, JC Cosimi, AB Sachs, DH Smith, RN Colvin, RB Kawai, T Madsen, JC Benichou, G Allan, JS AF Aoyama, A. Tonsho, M. Ng, C. Y. Lee, S. Millington, T. Nadazdin, O. Wain, J. C. Cosimi, A. B. Sachs, D. H. Smith, R. N. Colvin, R. B. Kawai, T. Madsen, J. C. Benichou, G. Allan, J. S. TI Long-Term Lung Transplantation in Nonhuman Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID REGULATORY T-CELLS; INDUCED ARTHRITIS; INDUCTION; INTERLEUKIN-6; INFLAMMATION; TOLERABILITY; CYCLOSPORINE; TOLERANCE; REJECTION; RESPONSES AB Despite advances in surgical technique and clinical care, lung transplantation still remains a short-term solution for the treatment of end-stage lung disease. To date, there has been limited experience in experimental lung transplantation using nonhuman primate models. Therefore, we have endeavored to develop a long-term, nonhuman primate model of orthotopic lung transplantation for the ultimate purpose of designing protocols to induce tolerance of lung grafts. Here, we report our initial results in developing this model and our observation that the nonhuman primate lung is particularly prone to rejection. This propensity toward rejection may be a consequence of 1) upregulated nonspecific inflammation, and 2) a larger number of pre-existing alloreactive memory T cells, leading to augmented deleterious immune responses. Our data show that triple-drug immunosuppression mimicking clinical practice is not sufficient to prevent acute rejection in nonhuman primate lung transplantation. The addition of horse-derived anti-thymocyte globulin and a monoclonal antibody to the IL-6 receptor allowed six out of six lung recipients to be free of rejection for over 120 days. C1 [Aoyama, A.; Tonsho, M.; Ng, C. Y.; Lee, S.; Millington, T.; Nadazdin, O.; Wain, J. C.; Cosimi, A. B.; Sachs, D. H.; Smith, R. N.; Colvin, R. B.; Kawai, T.; Madsen, J. C.; Benichou, G.; Allan, J. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Transplant Ctr,Dept Surg, Boston, MA 02163 USA. RP Allan, JS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Transplant Ctr,Dept Surg, Boston, MA 02163 USA. EM jallan@partners.org FU NIH [P01HL67110, U19AI066705, P01HL018646]; American Society of Transplant Surgeons-Wyeth Collaborative Scientist Award; Yoshida Scholarship Foundation FX This work was supported by NIH grants P01HL67110, U19AI066705, P01HL018646, the American Society of Transplant Surgeons-Wyeth Collaborative Scientist Award (J.S.A), and a Scholarship to Study Abroad from the Yoshida Scholarship Foundation (A.A.). NR 23 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 IS 5 BP 1415 EP 1420 DI 10.1111/ajt.13130 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA CG5ML UT WOS:000353335900034 PM 25772308 ER PT J AU Leffert, L AF Leffert, Lisa TI What's New in Obstetric Anesthesia: The 2014 Gerard W. Ostheimer Lecture SO ANESTHESIA AND ANALGESIA LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology CY MAY 05-09, 2014 CL Toronto, CANADA SP Soc Obstet Anesthesia & Perinatol ID POSTCESAREAN DELIVERY ANALGESIA; RANDOMIZED-CONTROLLED-TRIAL; ABDOMINIS PLANE BLOCKS; CESAREAN DELIVERY; UNITED-STATES; RESPIRATORY DEPRESSION; POSTPARTUM HEMORRHAGE; TRACHEAL INTUBATION; ADMINISTRATIVE DATA; MATERNAL MORTALITY C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Leffert, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM lleffert@partners.org NR 79 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2015 VL 120 IS 5 BP 1065 EP 1073 DI 10.1213/ANE.0000000000000686 PG 9 WC Anesthesiology SC Anesthesiology GA CG5OU UT WOS:000353342800024 PM 25811260 ER PT J AU Dutta, P Nahrendorf, M AF Dutta, Partha Nahrendorf, Matthias TI Monocytes in Myocardial Infarction SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE hematopoiesis; macrophages; monocytes; myocardial infarction ID DENDRITIC CELLS; STEADY-STATE; ATHEROSCLEROTIC LESIONS; INFLAMMATORY MONOCYTES; LY-6C(HIGH) MONOCYTES; CARDIAC MACROPHAGES; SPLENIC RESERVOIR; PROGENITOR CELLS; SELF-RENEWAL; STEM-CELLS AB Myocardial infarction (MI) is the leading cause of death in developed countries. Though timely revascularization of the ischemic myocardium and current standard therapy reduce acute mortality after MI, long-term morbidity and mortality remain high. During the first 1 to 2 weeks after MI, tissues in the infarcted myocardium undergo rapid turnover, including digestion of extracellular matrix and fibrosis. Post-MI repair is crucial to survival. Monocytes recruited to the infarcted myocardium remove debris and facilitate the repair process. However, exaggerated inflammation may also impede healing, as demonstrated by the association between elevated white blood cell count and in-hospital mortality after MI. Monocytes produced in the bone marrow and spleen enter the blood after MI and are recruited to the injured myocardium in 2 phases. The first phase is dominated by Ly-6c(high) monocytes and the second phase by Ly-6c(low) monocytes. Yet the number of Ly6C(low) monocytes recruited to the infarct is much lower, and Ly6C(high) monocytes can differentiate to Ly6C(low) macrophages in later healing stages. Understanding the signals regulating monocytosis after MI will help design new therapies to facilitate cardiac healing and limit heart failure. C1 [Dutta, Partha] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Dutta, Partha] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Dutta, P (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM Dutta.Partha@mgh.harvard.edu FU National Institutes of Health [K99HL121076, R01HL096576, R01HL114477, R01HL117829, R01NS084863] FX This work was supported by National Institutes of Health (K99HL121076, R01HL096576, R01HL114477, R01HL117829, and R01NS084863). NR 57 TC 19 Z9 19 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2015 VL 35 IS 5 BP 1066 EP 1070 DI 10.1161/ATVBAHA.114.304652 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CG5MF UT WOS:000353335300005 PM 25792449 ER PT J AU Hasturk, H Abdallah, R Kantarci, A Nguyen, D Giordano, N Hamilton, J Van Dyke, TE AF Hasturk, Hatice Abdallah, Rima Kantarci, Alpdogan Nguyen, Daniel Giordano, Nicholas Hamilton, James Van Dyke, Thomas E. TI Resolvin E1 (RvE1) Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation-Induced Atherogenesis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; inflammation; models, animal ID C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; LIPID MEDIATORS; PERIODONTAL-DISEASE; PORPHYROMONAS-GINGIVALIS; INTERLEUKIN-6 RECEPTOR; VASCULAR INFLAMMATION; RESOLUTION; STATINS; ASPIRIN AB Objective-Epidemiological and recent clinical studies implicate periodontitis as an independent risk factor for cardiovascular disease. Previously, we demonstrated that rabbits with experimental periodontitis and cholesterol diet exhibit more aortic plaque compared with diet alone. We also showed that a proresolution mediator, Resolvin E1 (RvE1), reverses the experimental periodontitis. Here, we determined whether oral/topical application of RvE1 attenuates aortic atherosclerosis induced by both diet and periodontal inflammation. Approach and Results-Thirty-nine rabbits on a 13-week regimen of 0.5% cholesterol diet were included. Periodontitis was induced by Porphyromonas gingivalis in 24 rabbits and 15 rabbits were placed in no-periodontitis groups. Interventions were no-treatment, vehicle, and RvE1 treatment (4 mu g/site or 0.4 mu g/site) topically applied 3x per week. At 13 weeks, both periodontitis and atherosclerosis were quantified. Atherosclerotic plaques were assessed by Sudan IV staining, histology, and ex vivo MRI. Serum levels of C-reactive protein were evaluated as a measure of systemic inflammation. RvE1, used as an oral/topical agent, significantly diminished atherogenesis and prevented periodontitis (P<0.05). In the absence of periodontal inflammation, oral/topical application of RvE1 resulted in significantly less arterial plaque, a lower intima/media ratio, and decreased inflammatory cell infiltration compared with no-treatment (P<0.001). Local oral RvE1 application significantly reduced systemic levels of C-reactive protein (P<0.05). Conclusions-The results suggest that oral/topical RvE1 attenuates enhanced atherogenesis induced by periodontitis and prevents vascular inflammation and atherogenesis in the absence of periodontitis. The inhibition of vascular inflammation with endogenous mediators of resolution of inflammation provides a novel approach in the prevention of atherogenic events. C1 [Hasturk, Hatice; Kantarci, Alpdogan; Nguyen, Daniel; Van Dyke, Thomas E.] Forsyth Inst, Ctr Periodontol, Dept Appl Oral Sci, Cambridge, MA 02142 USA. [Abdallah, Rima] Beirut Arab Univ, Dept Biol & Diagnost Sci, Beirut, Lebanon. [Hamilton, James] Boston Univ, Dept Biophys, Sch Med, Boston, MA 02215 USA. [Giordano, Nicholas] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Hasturk, H (reprint author), Forsyth Inst, 245 First St,Suite 1757, Cambridge, MA 02142 USA. EM hhasturk@forsyth.org; tvandyke@forsyth.org FU USPHS National Institute of Dental and Craniofacial Research grants [DE19938, DE15566, DE18917]; Boston University Nano Medicine grant FX This study was partly supported by USPHS National Institute of Dental and Craniofacial Research grants (DE19938, DE15566 to Dr Van Dyke), (DE18917 to Dr Hasturk) and a Boston University Nano Medicine grant (J. Hamilton). NR 53 TC 19 Z9 19 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2015 VL 35 IS 5 BP 1123 EP 1133 DI 10.1161/ATVBAHA.115.305324 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CG5MF UT WOS:000353335300011 PM 25792445 ER PT J AU Long, MT Wang, N Larson, MG Mitchell, GF Palmisano, J Vasan, RS Hoffmann, U Speliotes, EK Vita, JA Benjamin, EJ Fox, CS Hamburg, NM AF Long, Michelle T. Wang, Na Larson, Martin G. Mitchell, Gary F. Palmisano, Joseph Vasan, Ramachandran S. Hoffmann, Udo Speliotes, Elizabeth K. Vita, Joseph A. Benjamin, Emelia J. Fox, Caroline S. Hamburg, Naomi M. TI Nonalcoholic Fatty Liver Disease and Vascular Function Cross-Sectional Analysis in the Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE multidetector computed tomography; obesity; risk factors; vascular endothelium ID INCREASED ARTERIAL STIFFNESS; FLOW-MEDIATED DILATION; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE; HEPATIC STEATOSIS; RISK-FACTORS; SYSTEMIC INFLAMMATION; METABOLIC SYNDROME; NATURAL-HISTORY; ATHEROSCLEROSIS AB Objective-Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk of cardiovascular disease; however, it is not known whether NAFLD contributes to cardiovascular disease independent of established risk factors. We examined the association between NAFLD and vascular function. Approach and Results-We conducted a cross-sectional study of 2284 Framingham Heart Study participants without overt cardiovascular disease who had liver fat attenuation measured on computed tomography and who had measurements of vascular function and covariates. We evaluated the association between NAFLD and vascular function using multivariable partial correlations adjusting for age, sex, cohort, smoking, diabetes mellitus, hyperlipidemia, hypertension, body mass index, and visceral adipose tissue. The prevalence of NAFLD in our sample (mean age, 52 +/- 12 years; 51.4% women) was 15.3%. In age-, sex-, and cohort-adjusted analyses, greater liver fat was modestly associated with lower flow-mediated dilation (r=-0.05; P=0.02), lower peripheral arterial tonometry ratio (r=-0.20; P<0.0001), higher carotid-femoral pulse wave velocity (r=0.13; P<0.0001), and higher mean arterial pressure (r=0.11; P<0.0001). In multivariable-adjusted models, NAFLD remained associated with higher mean arterial pressure (r=0.06; P=0.005) and lower peripheral arterial tonometry ratio (r=-0.12; P<0.0001). The association between NAFLD and peripheral arterial tonometry ratio persisted after further adjustment for body mass index and visceral adipose tissue. Conclusions-For multiple measures of vascular function, the relationship with NAFLD appeared largely determined by shared cardiometabolic risk factors. The persistent relationship with reduced peripheral arterial tonometry response beyond established risk factors suggests that NAFLD may contribute to microvascular dysfunction. C1 [Long, Michelle T.] Boston Univ, Sch Med, Boston Med Ctr, Div Gastroenterol, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med, Dept Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Evans Dept Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Long, Michelle T.; Larson, Martin G.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA. [Wang, Na; Palmisano, Joseph] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Speliotes, Elizabeth K.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Speliotes, Elizabeth K.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA. RP Hamburg, NM (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, 88 East Newton St,Suite C-818, Boston, MA 02118 USA. EM nhamburg@bu.edu OI Long, Michelle/0000-0001-6131-3981; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Boston University School of Medicine; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Division of Intramural Research of the National Heart, Lung, and Blood Institute; National Institutes of Health (NIH) [R01 AG047645-1, HL102299, 1R01HL60040, HL70100, HL076784, HL077447, HL107385]; Donald W. Reynolds Foundation; Boston University Clinical and Translational Science Institute [UL1-TR000157]; NIH [K23DK08145]; Doris Duke Foundation; Central Society for Clinical Research; Department of Internal Medicine at University of Michigan; BSSP program at University of Michigan FX This work was supported by the Boston University School of Medicine and the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01-HC-25195) and the Division of Intramural Research of the National Heart, Lung, and Blood Institute. The project was supported by National Institutes of Health (NIH) grants R01 AG047645-1, HL102299, 1R01HL60040; HL70100, HL076784, HL077447, HL107385 and the Donald W. Reynolds Foundation. Dr Long was supported in part by the Boston University Clinical and Translational Science Institute (grant UL1-TR000157). E. K. Speliotes was supported by NIH K23DK08145, The Doris Duke Foundation, Central Society for Clinical Research, and the Department of Internal Medicine and BSSP program at University of Michigan. NR 40 TC 13 Z9 13 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2015 VL 35 IS 5 BP 1284 EP 1291 DI 10.1161/ATVBAHA.114.305200 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CG5MF UT WOS:000353335300028 PM 25745056 ER PT J AU Minor, KS Friedman-Yakoobian, M Leung, YJ Meyer, EC Zimmet, SV Caplan, B Monteleone, T Bryant, C Guyer, M Keshavan, MS Seidman, LJ AF Minor, Kyle S. Friedman-Yakoobian, Michelle Leung, Y. Jude Meyer, Eric C. Zimmet, Suzanna V. Caplan, Brina Monteleone, Thomas Bryant, Caitlin Guyer, Margaret Keshavan, Matcheri S. Seidman, Larry J. TI The impact of premorbid adjustment, neurocognition, and depression on social and role functioning in patients in an early psychosis treatment program SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Article DE depression; early psychosis; premorbid adjustment; role functioning; social functioning ID QUALITY-OF-LIFE; 1ST-EPISODE NONAFFECTIVE PSYCHOSIS; 1ST EPISODE PSYCHOSIS; 10-YEAR FOLLOW-UP; NEGATIVE SYMPTOMS; HIGH-RISK; SCHIZOPHRENIA; PREDICTORS; RECOVERY; SCALE AB Objective: Functional impairments are debilitating concomitants of psychotic disorders and are present early in the illness course and, commonly, prior to psychosis onset. The factors affecting social and role functioning in early psychosis (EP) following treatment are unclear. We evaluated whether six months of participation in the PREPR, Boston, EP treatment program, part of a public-academic community mental health center, was related to improvements in social and role functioning and whether premorbid adjustment in adolescence, baseline neurocognition, and depression symptoms predicted functional improvement. Method: The Global Functioning Social and Role scales, MATRICS neurocognitive battery, and Calgary Depression Scale were assessed at baseline and six months during naturalistic treatment, while premorbid adjustment was measured at baseline. All participants were psychotic disorder patients in PREPR (n = 46 with social functioning and 47 with role functioning measures at both time points). Results: Large improvements were observed in role functioning (d = 0.84) and medium to large improvements were observed in social functioning (d = 0.70). Models consisting of adolescent premorbid adjustment and change in depression symptoms predicted social and role functioning change, whereas neuropsychological functioning did not. Conclusions: Substantial improvements in social and role functioning were observed among this sample participating in a recovery-based EP program. The impact of clinical factors on social and role functioning was highlighted. Further studies of premorbid adjustment in adolescence and the treatment of depression in EP programs in controlled treatment trials are needed to confirm these findings. C1 [Minor, Kyle S.] Indiana Univ Purdue Univ, Dept Psychol, Indianapolis, IN 46202 USA. [Friedman-Yakoobian, Michelle; Zimmet, Suzanna V.; Keshavan, Matcheri S.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Friedman-Yakoobian, Michelle; Leung, Y. Jude; Zimmet, Suzanna V.; Monteleone, Thomas; Bryant, Caitlin; Guyer, Margaret; Keshavan, Matcheri S.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA 02215 USA. [Meyer, Eric C.] US Dept Vet Affairs, VISN Ctr Excellence Res Returning War Vet 17, Waco, TX USA. [Meyer, Eric C.] Cent Texas Vet Healthcare Syst, Temple, TX USA. [Monteleone, Thomas; Guyer, Margaret] Massachusetts Mental Hlth Ctr, Dept Mental Hlth, Boston, MA 02115 USA. RP Minor, KS (reprint author), Indiana Univ Purdue Univ, Dept Psychol, 402 N Blackford,LD120C, Indianapolis, IN 46202 USA. EM ksminor@iupui.edu FU Commonwealth of Massachusetts [SCDMH82101008006]; Sidney R. Baer Jr. Foundation FX This work was supported in part by The Commonwealth of Massachusetts (SCDMH82101008006, L.J.S.) and the Sidney R. Baer Jr. Foundation (L.J.S.). NR 50 TC 3 Z9 3 U1 2 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2015 VL 49 IS 5 BP 444 EP 452 DI 10.1177/0004867414565473 PG 9 WC Psychiatry SC Psychiatry GA CG3YC UT WOS:000353214700007 PM 25586755 ER PT J AU Sylvia, LG Thase, ME Reilly-Harrington, NA Salcedo, S Brody, B Kinrys, G Kemp, D Shelton, RC McElroy, SL Kocsis, JH Bobo, WV Kamali, M McInnis, M Friedman, E Tohen, M Bowden, CL Ketter, TA Singh, V Calabrese, J Nierenberg, AA Rabideau, DJ Elson, CM Deckersbach, T AF Sylvia, Louisa G. Thase, Michael E. Reilly-Harrington, Noreen A. Salcedo, Stephanie Brody, Benjamin Kinrys, Gustavo Kemp, David Shelton, Richard C. McElroy, Susan L. Kocsis, James H. Bobo, William V. Kamali, Masoud McInnis, Melvin Friedman, Edward Tohen, Mauricio Bowden, Charles L. Ketter, Terence A. Singh, Vivek Calabrese, Joseph Nierenberg, Andrew A. Rabideau, Dustin J. Elson, Constance M. Deckersbach, Thilo TI Psychotherapy use in bipolar disorder: Association with functioning and illness severity SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Article DE Bipolar disorder; psychotherapy; service utilization; medication use ID SOCIAL RHYTHM THERAPY; HEALTH-SERVICE USE; II DISORDER; MEDICATION; SCALE AB Objective: This study examines characteristics of individuals with bipolar disorder who sought psychotherapy versus those who did not. Methods: Bipolar CHOICE was an 11-site comparative effectiveness study of lithium versus quetiapine in symptomatic outpatients (N = 482) with bipolar disorder. At baseline, participants' psychotherapy use within the past 3 months, mood, functioning, and overall health were assessed. Logistic regressions were used to test whether psychotherapy users and non-users differed on various demographic and clinical variables at baseline. Mixed-effects regression was used to determine whether psychotherapy groups differed on response to treatment over the 6-month study. Kaplan-Meier plots and log-rank tests were employed to test whether there were any differences in time to recovery (CGI-BP 2 for at least 8 weeks) between the groups. Results: Thirty one percent of participants reported using psychotherapy services. Psychotherapy users reported greater medication side effect burden than non-users and were more likely to have moderate to high suicide risk and at least one anxiety disorder. Participants not utilizing medications or psychotherapy had greater mania symptom severity, were younger, and less educated than medication only users. Medication only users were more likely to be married than the other participants. Conclusions: These data suggest that a minority of individuals with bipolar disorder attend psychotherapy services, and those that do have greater illness burden. C1 [Sylvia, Louisa G.; Reilly-Harrington, Noreen A.; Salcedo, Stephanie; Kinrys, Gustavo; Nierenberg, Andrew A.; Deckersbach, Thilo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sylvia, Louisa G.; Reilly-Harrington, Noreen A.; Kinrys, Gustavo; Nierenberg, Andrew A.; Deckersbach, Thilo] Harvard Univ, Sch Med, Boston, MA USA. [Thase, Michael E.] Univ Penn, Philadelphia, PA 19104 USA. [Brody, Benjamin; Kocsis, James H.] Weill Cornell Med Coll, New York, NY USA. [Kemp, David; Calabrese, Joseph] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Shelton, Richard C.] Univ Alabama Birmingham, Birmingham, AL USA. [McElroy, Susan L.] Lindner Ctr HOPE, Mason, OH USA. [McElroy, Susan L.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Bobo, William V.] Mayo Clin, Rochester, MN USA. [Kamali, Masoud; McInnis, Melvin] Univ Michigan, Ann Arbor, MI 48109 USA. [Friedman, Edward] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Tohen, Mauricio] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Bowden, Charles L.; Singh, Vivek] Univ Texas Hlth Sci, San Antonio, TX USA. [Ketter, Terence A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Rabideau, Dustin J.; Elson, Constance M.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Sylvia, LG (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM lsylvia2@mgh.harvard.edu FU Agency for Healthcare Research and Quality (AHRQ) [1R01HS019371-01] FX This study was funded by the Agency for Healthcare Research and Quality (AHRQ), 1R01HS019371-01 NR 27 TC 2 Z9 2 U1 8 U2 12 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2015 VL 49 IS 5 BP 453 EP 461 DI 10.1177/0004867415569803 PG 9 WC Psychiatry SC Psychiatry GA CG3YC UT WOS:000353214700008 PM 25680360 ER PT J AU Melton, DW McManus, LM Gelfond, JAL Shireman, PK AF Melton, David W. McManus, Linda M. Gelfond, Jonathan A. L. Shireman, Paula K. TI Temporal phenotypic features distinguish polarized macrophages in vitro SO AUTOIMMUNITY LA English DT Article DE Chemokine; cytokine; macrophage; polarization; temporal ID ALTERNATIVELY ACTIVATED MACROPHAGES; TUMOR-ASSOCIATED MACROPHAGES; INDUCED MITOGENIC FACTOR; GENE-EXPRESSION; HUMAN MONOCYTES; GM-CSF; INTERFERON-GAMMA; IFN-GAMMA; INFLAMMATORY RESPONSE; CYTOKINE EXPRESSION AB Macrophages are important in vascular inflammation and environmental factors influence macrophage plasticity. Macrophage transitions into pro-inflammatory (M1) or anti-inflammatory (M2) states have been defined predominately by measuring cytokines in culture media (CM). However, temporal relationships between cellular and secreted cytokines have not been established. We measured phenotypic markers and cytokines in cellular and CM of murine bone marrow-derived macrophages at multiple time points following stimulation with IFN-gamma + LPS (M1), IL-4 (M2a) or IL-10 (M2c). Cytokines/proteins in M1-polarized macrophages exhibited two distinct temporal patterns; an early (0.5-3 h), transient increase in cellular cytokines (GM-CSF, KC-GRO, MIP-2, IP-10 and MIP-1 beta) and a delayed (3-6 h) response that was more sustained [IL-3, regulated on activation normal T cell expressed and secreted (RANTES), and tissue inhibitor of metalloproteinases 1 (TIMP-1)]. M2a-related cytokine/cell markers (IGF-1, Fizz1 and Ym1) were progressively (3-24 h) increased post-stimulation. In addition, novel patterns were observed. First, and unexpectedly, cellular pro-inflammatory chemokines, MCP-1 and MCP-3 but not MCP-5, were comparably increased in M1 and M2a macrophages. Second, Vegfr1 mRNA was decreased in M1 and increased in M2a macrophages. Finally, VEGF-A was increased in the CM of M1 cultures and strikingly reduced in M2a coinciding with increased Vegfr1 expression, suggesting decreased VEGF-A in M2a CM was secondary to increased soluble VEGFR1. In conclusion, macrophage cytokine production and marker expression were temporally regulated and relative levels compared across polarizing conditions were highly dependent upon the timing and location (cellular versus CM) of the sample collection. For most cytokines, cellular production preceded increases in the CM suggesting that cellular regulatory pathways should be studied within 6 h of stimulation. The divergent polarization-dependent expression of Vegfr1 may be essential to controlling VEGF potentially regulating angiogenesis and inflammatory cell infiltration in the vascular niche. The current study expands the repertoire of cytokines produced by polarized macrophages and provides insights into the dynamic regulation of macrophage polarization and resulting cytokines, proteins and gene expression that influence vascular inflammation. C1 [Melton, David W.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Melton, David W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Melton, David W.; McManus, Linda M.; Gelfond, Jonathan A. L.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Gelfond, Jonathan A. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biostat & Epidemiol, San Antonio, TX 78229 USA. [Shireman, Paula K.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Shireman, PK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, 7703 Floyd Curl Dr,MC 7741, San Antonio, TX 78229 USA. EM shireman@uthscsa.edu FU UTHSCSA; NIH-NCI [P30CA054174]; National Institutes of Health [HL074236, HL110743]; Veterans Administration Merit Review [1I01BX001186] FX We acknowledge the assistance of the UTHSCSA Genomics Core Shared Resource, which is supported by UTHSCSA and NIH-NCI P30CA054174 (CTRC of UTHSCSA).; The authors have no financial conflict of interest. These studies were supported, in part, by grants from the National Institutes of Health (HL074236 and HL110743), and the Veterans Administration Merit Review (1I01BX001186). NR 120 TC 6 Z9 7 U1 3 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0891-6934 EI 1607-842X J9 AUTOIMMUNITY JI Autoimmunity PD MAY PY 2015 VL 48 IS 3 BP 161 EP 176 DI 10.3109/08916934.2015.1027816 PG 16 WC Immunology SC Immunology GA CG7YN UT WOS:000353523900004 PM 25826285 ER PT J AU Leow, JJ Reese, S Trinh, QD Bellmunt, J Chung, BI Kibel, AS Chang, SL AF Leow, Jeffrey J. Reese, Stephen Quoc-Dien Trinh Bellmunt, Joaquim Chung, Benjamin I. Kibel, Adam S. Chang, Steven L. TI Impact of surgeon volume on the morbidity and costs of radical cystectomy in the USA: a contemporary population-based analysis SO BJU INTERNATIONAL LA English DT Article DE cystectomy; urinary bladder neoplasms; complications; morbidity; costs and cost analysis ID IN-HOSPITAL MORTALITY; BLADDER-CANCER; OPERATIVE MORTALITY; PROSTATECTOMY OUTCOMES; SURGICAL-PROCEDURES; URINARY-DIVERSION; UNITED-STATES; COMPLICATIONS; CARE; LYMPHADENECTOMY AB Objectives To evaluate the relationship between surgeon volume of radical cystectomy (RC) and postoperative morbidity, and to assess the economic burden of bladder cancer in the USA. Methods We captured all patients who underwent RC (International Classification of Diseases, ninth revision, code 57.71) between 2003 and 2010, using a nationwide hospital discharge database. Patient, hospital and surgical characteristics were evaluated. The annual volume of RCs performed by the surgeons was divided into quintiles. Multivariable regression models were developed, adjusting for clustering and survey weighting, to evaluate the outcomes, including 90-day major complications (Clavien grade III-V) and direct patient costs. We adjusted for clustering and weighting to achieve a nationally representative analysis. Results The weighted cohort included 49 792 patients who underwent RC, with an overall 90-day major complication rate of 16.2%. Compared with surgeons performing one RC annually, surgeons performing >= 7 RCs each year had 45% lower odds of major complications (odds ratio [OR] 0.55; P < 0.001) and lower costs by $ 1690 (P = 0.02). Results were consistent when we analysed surgeon volume as a continuous variable and when we examined the surgeons with the highest volumes (= 28 cases annually), which showed markedly lower odds of major complications compared with the surgeons with the lowest volumes (OR 0.45, 95% CI 0.31-0.67; P < 0.001). Compared with patients who did not have any complications, those who had a major complication were associated with significantly higher 90-day median direct hospital costs ($43 965 vs $24 341; P < 0.001). Conclusions We showed that there was an inverse relationship between surgeon volume and the development of postoperative 90-day major complication rates as well as direct hospital costs. Centralisation of RC to surgeons with higher volumes may reduce the development of postoperative major complications, thereby decreasing the burden of bladder cancer on the healthcare system. C1 [Leow, Jeffrey J.; Reese, Stephen; Quoc-Dien Trinh; Chang, Steven L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Leow, Jeffrey J.; Reese, Stephen; Quoc-Dien Trinh; Kibel, Adam S.; Chang, Steven L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol, Boston, MA 02115 USA. [Quoc-Dien Trinh; Bellmunt, Joaquim; Kibel, Adam S.; Chang, Steven L.] Harvard Univ, Dana Farber Brigham & Womens Hosp, Ctr Canc, Sch Med, Boston, MA 02115 USA. [Chung, Benjamin I.] Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA. RP Chang, SL (reprint author), Brigham & Womens Hosp, Div Urol, 45 Francis St, Boston, MA 02115 USA. EM slchang@bics.bwh.harvard.edu NR 52 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD MAY PY 2015 VL 115 IS 5 BP 713 EP 721 DI 10.1111/bju.12749 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CG4CT UT WOS:000353230500011 PM 24674655 ER PT J AU Lucca, I Roupret, M Kluth, L Rink, M Tilki, D Fajkovic, H Kassouf, W Hofbauer, SL de Martino, M Karakiewicz, PI Briganti, A Trinh, QD Seitz, C Fritsche, HM Burger, M Lotan, Y Kramer, G Shariat, SF Klatte, T AF Lucca, Ilaria Roupret, Morgan Kluth, Luis Rink, Michael Tilki, Derya Fajkovic, Harun Kassouf, Wassim Hofbauer, Sebastian L. de Martino, Michela Karakiewicz, Pierre I. Briganti, Alberto Quoc-dien Trinh Seitz, Christian Fritsche, Hans-Martin Burger, Maximilian Lotan, Yair Kramer, Gero Shariat, Shahrokh F. Klatte, Tobias TI Adjuvant cisplatin-based combined chemotherapy for lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a retrospective international study of > 1500 patients SO BJU INTERNATIONAL LA English DT Article DE adjuvant chemotherapy; urothelial carcinoma of bladder; lymph node positive; radical cystectomy; survival ID CANCER-SPECIFIC SURVIVAL; NEOADJUVANT CHEMOTHERAPY; EXTERNAL VALIDATION; RISK STRATIFICATION; URINARY-BLADDER; TRIAL; LYMPHADENECTOMY; METAANALYSIS; RECURRENCE; PREDICTION AB Objective To compare outcomes of patients with lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) treated with or without cisplatin-based combined adjuvant chemotherapy (AC) after radical cystectomy (RC). Patients and Methods We retrospectively analysed 1523 patients with LN-positive UCB, who underwent RC with bilateral pelvic LN dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality. Results Of the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2-and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients aged = 70 years, in women, in pT3-4 disease, and in those with a higher LN density and lymphovascular invasion. This study is limited by its retrospective and non-randomised design, selection bias, the absence of central pathological review and lack in standardisation of LN dissection and cisplatin-based protocols. Conclusion AC seems to reduce UCB-related mortality in patients with LN-positive UCB after RC. Younger patients, women and those with high-risk features such as pT3-4 disease, a higher LN density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomised trials are necessary to confirm these findings. C1 [Lucca, Ilaria; Fajkovic, Harun; Hofbauer, Sebastian L.; de Martino, Michela; Seitz, Christian; Kramer, Gero; Shariat, Shahrokh F.; Klatte, Tobias] Med Univ Vienna, Vienna Gen Hosp, Dept Urol, Ctr Comprehens Canc, A-1090 Vienna, Austria. [Lucca, Ilaria] CHU Vaudois, Dept Urol, CH-1011 Lausanne, Switzerland. [Roupret, Morgan] Univ Paris 06, Grp Hosp Pitie Salpetriere, Fac Med Pierre & Marie Curie, AP HP,Dept Urol,Inst Univ Cancerol GRC5, Paris, France. [Kluth, Luis; Rink, Michael] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Fritsche, Hans-Martin; Burger, Maximilian] Univ Regensburg, Caritas St Josef Med Ctr, Dept Urol, D-93053 Regensburg, Germany. [Tilki, Derya] Univ Calif Davis, Sch Med, Dept Urol, Sacramento, CA 95817 USA. [Quoc-dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg,Div Urol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Lotan, Yair; Shariat, Shahrokh F.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA. [Shariat, Shahrokh F.] Weill Cornell Med Coll, New York Presbyterian Hosp, Dept Urol, New York, NY USA. [Kassouf, Wassim] McGill Univ, Dept Urol, Montreal, PQ, Canada. [Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Briganti, Alberto] Ist Sci San Raffaele, Dept Urol, Urol Res Inst, I-20132 Milan, Italy. RP Shariat, SF (reprint author), Med Univ Vienna, Vienna Gen Hosp, Dept Urol, Ctr Comprehens Canc, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM sfshariat@gmail.com FU CHUV-University Hospital; GEROK research grant of the University of Hamburg; Oesterreichische Nationalbank [15362] FX I.L. was supported by the development fund of the CHUV-University Hospital. M.R. is supported by the GEROK research grant of the University of Hamburg. T.K. is supported by funds of the Oesterreichische Nationalbank (Anniversary Fund, project number: 15362). NR 37 TC 6 Z9 6 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD MAY PY 2015 VL 115 IS 5 BP 722 EP 727 DI 10.1111/bju.12829 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA CG4CT UT WOS:000353230500012 PM 24905084 ER PT J AU Rolfson, O Malchau, H AF Rolfson, O. Malchau, H. TI The use of patient-reported outcomes after routine arthroplasty BEYOND THE WHYS AND IFS SO BONE & JOINT JOURNAL LA English DT Editorial Material ID TOTAL KNEE REPLACEMENT; TOTAL HIP-REPLACEMENT; NATIONAL-JOINT-REGISTRY; MEASURES PROMS; IMPORTANT DIFFERENCE; SATISFACTION; HEALTH; COHORT; THRESHOLDS; VARIABLES AB The limitations and benefits of patient-reported outcome measures, in defining the merits of arthroplasty surgery, are discussed. C1 [Rolfson, O.; Malchau, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Rolfson, O (reprint author), Ctr Registers Vastra Gotaland, SE-41345 Gothenburg, Sweden. EM ola.rolfson@vgregion.se OI Rolfson, Ola/0000-0001-6534-1242 NR 39 TC 7 Z9 7 U1 0 U2 1 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 2049-4394 J9 BONE JOINT J JI Bone Joint J. PD MAY PY 2015 VL 97B IS 5 BP 578 EP 581 DI 10.1302/0301-620X.97B5.35356 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CG8SD UT WOS:000353581100002 PM 25922448 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI An open letter to panels that are deciding guidelines for breast cancer screening SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Review DE Breast; Breast cancer; Screening; Mammography ID DIFFERENT PERSPECTIVE; CARCINOMA MORTALITY; FAULTY SCIENCE; 3 DECADES; MAMMOGRAPHY; WOMEN; REDUCTION; OVERDIAGNOSIS; TRENDS; TRIALS AB Panels are presently reviewing breast cancer screening guidelines. It is critical that they understand which publications are scientifically valid, and which analyses are methodologically flawed and not valid. The scientific evidence clearly supports annual mammography screening beginning at the age of 40. The analyses that suggest that screening leads to overdiagnosis of invasive breast cancers are flawed and incorrect. There is little if any overdiagnosis of these cancers. The vast majority of breast cancers occur in women who are not at elevated risk so that excluding them from screening and only screening high risk women will deny the benefits of early detection to most women who develop breast cancer. Guidelines panels should not make decisions that exclude women from screening. Women should be provided with accurate information so that they can make informed decisions and have unimpeded access to screening if that is their preference. C1 [Kopans, Daniel B.] Harvard Univ, Med Sch Boston, Boston, MA 02115 USA. [Kopans, Daniel B.] Massachusetts Gen Hosp, Breast Imaging Div, Avon Breast Ctr, Wang Ambulatory Care Ctr, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Med Sch Boston, Boston, MA 02115 USA. EM dkopans@partners.org NR 56 TC 5 Z9 5 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 2015 VL 151 IS 1 BP 19 EP 25 DI 10.1007/s10549-015-3373-8 PG 7 WC Oncology SC Oncology GA CG5RU UT WOS:000353352500003 PM 25868866 ER PT J AU Warren, LEG Guo, H Regan, MM Nakhlis, F Yeh, ED Jacene, HA Hirshfield-Bartek, J Overmoyer, BA Bellon, JR AF Warren, Laura E. G. Guo, Hao Regan, Meredith M. Nakhlis, Faina Yeh, Eren D. Jacene, Heather A. Hirshfield-Bartek, Judi Overmoyer, Beth A. Bellon, Jennifer R. TI Inflammatory breast cancer and development of brain metastases: risk factors and outcomes SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Inflammatory breast cancer; Brain metastases; Surveillance ID NERVOUS-SYSTEM METASTASIS; PROGNOSTIC-FACTORS; NATURAL-HISTORY; STEREOTACTIC RADIOSURGERY; SINGLE METASTASES; RANDOMIZED-TRIAL; COMPETING RISK; UNITED-STATES; CARCINOMA; SURVIVAL AB Brain metastases are associated with significant morbidity. Minimal research has been conducted on the risk factors for and incidence of brain metastases in women with inflammatory breast cancer (IBC). 210 women with Stage III or IV IBC diagnosed from 1997-2011 were identified. Competing risk analysis and competing risks regression were used to calculate the incidence of brain metastases and identify significant risk factors. After a median follow-up in surviving patients of 2.8 years (range 0.6-7.6) and 3.3 years (range 0.2-14.5) in the 47 and 163 patients with (MET) and without (non-MET) metastatic disease at diagnosis, 17 (36 %) and 30 (18 %) developed brain metastases, respectively. The cumulative incidence at 1, 2, and 3 years was 17 % [95 % confidence interval (CI), 8-30], 34 % (95 % CI, 20-48), and 37 % (95 % CI, 22-51) for the MET cohort. The corresponding non-MET values were 4 % (95 % CI, 2-8), 8 % (95 % CI 5-13), and 15 % (95 % CI, 10-22). Once non-MET patients developed extracranial distant metastases, the subsequent 1, 2, and 3 years cumulative incidence of brain metastases was 18 % (95 % CI, 10-28), 25 % (95 % CI, 15-36), and 31 % (95 % CI, 20-43). On multivariate analysis, brain metastases were associated with younger age [hazard ratio (HR), 0.73; 95 % CI, 0.53-1.00; P = 0.05] and distant metastases at diagnosis (HR, 2.33; 95 % CI, 1.11-4.89; P = 0.03). The incidence of brain metastases is high in women with IBC. Particularly for patients with extracranial distant metastases, routine screening with magnetic resonance imaging should be considered. C1 [Warren, Laura E. G.] Harvard Radiat Oncol Program, Boston, MA USA. [Guo, Hao; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Nakhlis, Faina] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Nakhlis, Faina; Yeh, Eren D.; Jacene, Heather A.; Hirshfield-Bartek, Judi; Overmoyer, Beth A.; Bellon, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Yeh, Eren D.] Brigham & Womens Hosp, Dept Radiol, Div Breast Imaging, Boston, MA 02115 USA. [Jacene, Heather A.] Brigham & Womens Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02115 USA. [Hirshfield-Bartek, Judi; Overmoyer, Beth A.] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Bellon, Jennifer R.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. RP Bellon, JR (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM lewarren@partners.org; haoguo@jimmy.harvard.edu; mregan@jimmy.harvard.edu; fnahklis1@partners.org; eyeh@partners.org; hjacene@partners.org; judith_hirshfield-bartek@dfci.harvard.edu; beth_overmoyer@dfci.harvard.edu; jbellon@lroc.harvard.edu RI Guo, Hao/E-8921-2015 OI Guo, Hao/0000-0003-1658-0989 NR 38 TC 2 Z9 2 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 2015 VL 151 IS 1 BP 225 EP 232 DI 10.1007/s10549-015-3381-8 PG 8 WC Oncology SC Oncology GA CG5RU UT WOS:000353352500023 PM 25893587 ER PT J AU Singh, V Badheka, AO Patel, NJ Chothani, A Mehta, K Arora, S Patel, N Deshmukh, A Shah, N Savani, GT Rathod, A Manvar, S Thakkar, B Panchal, V Patel, J Palacios, IF Rihal, CS Cohen, MG O'Neill, W De Marchena, E AF Singh, Vikas Badheka, Apurva O. Patel, Nileshkumar J. Chothani, Ankit Mehta, Kathan Arora, Shilpkumar Patel, Nilay Deshmukh, Abhishek Shah, Neeraj Savani, Ghanshyambhai T. Rathod, Ankit Manvar, Sohilkumar Thakkar, Badal Panchal, Vinaykumar Patel, Jay Palacios, Igor F. Rihal, Charanjit S. Cohen, Mauricio G. O'Neill, William De Marchena, Eduardo TI Influence of Hospital Volume on Outcomes of Percutaneous Atrial Septal Defect and Patent Foramen Ovale Closure: A 10-Years US Perspective SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE atrial septal defect; patent foramen ovale; percutaneous; closure complication; length of stay; cost ID CARDIAC INTERVENTIONAL PROCEDURES; CLINICAL COMPETENCE STATEMENT; ACCF/AHA/SCAI 2007 UPDATE; MEDICAL THERAPY; TRANSCATHETER CLOSURE; CRYPTOGENIC STROKE; WRITING COMMITTEE; UNITED-STATES; TASK-FORCE; TRENDS AB Background: Contemporary data regarding percutaneous closure of atrial septal defect/patent foramen ovale (ASD/PFO) are lacking. We evaluated the current trends in utilization of ASD/PFO closure in adults and investigated the effect of annual hospital volume on in-hospital outcomes. Methods: We queried the Nationwide Inpatient Sample between the years 2001 and 2010 using the International Classification of Diseases (ICD-9-CM) procedure code for percutaneous closure of ASD/PFO with device. Hierarchical mixed effects models were generated to identify the independent multivariate predictors of outcomes. Results: A total of 7,107 percutaneous ASD/PFO closure procedures (weighted n=34,992) were available for analysis. A 4.7-fold increase in the utilization of this procedure from 3/million in 2001 to 14/million adults in 2010 in US (P<0.001) was noted. Overall, percutaneous ASD/PFO closure was associated with 0.5% mortality and 12% in-hospital complications. The utilization of intracardiac echocardiography (ICE) increased 15 fold (P<0.001) during the study period. The procedures performed at the high volume hospitals [2nd (14-37 procedures/year) and 3rd (>38 procedures/year) tertile] were associated with significant reduction in complications, length of stay and cost of hospitalization when compared to those performed at lowest volume centers (<13 procedures/year). Majority (70.5%) of the studied hospitals were found to be performing <10 procedures/year hence deviating from the ACC/AHA/SCAI clinical competency guidelines. Conclusions: Low hospital volume is associated with an increased composite (mortality and procedural complications) adverse outcome following ASD/PFO closure. In the interest of patient safety, implementation of the current guidelines for minimum required annual hospital volume to improve clinical outcomes is warranted. (c) 2014 Wiley Periodicals, Inc. C1 [Singh, Vikas] Univ Miami, Miller Sch Med, Cardiol, Miami, FL 33136 USA. [Badheka, Apurva O.] Yale Univ, Dept Intervent Cardiol, Sch Med, New Haven, CT 06520 USA. [Patel, Nileshkumar J.; Shah, Neeraj] Staten Isl Univ Hosp, Dept Internal Med, Staten Isl, NY USA. [Chothani, Ankit] MedStar Washington Hosp Ctr, Dept Internal Med, Washington, DC USA. [Mehta, Kathan] UPMC Shadyside Hosp, Dept Internal Med, Pittsburgh, PA USA. [Arora, Shilpkumar] Mt Sinai St Lukes Roosevelt Hosp Ctr, Dept Internal Med, New York, NY USA. [Patel, Nilay] St Peters Univ Hosp, Dept Internal Med, New Brunswick, NJ USA. [Deshmukh, Abhishek] Mayo Clin, Dept Cardiol, Rochester, MN USA. [Savani, Ghanshyambhai T.] Prince Georges Gen Hosp & Med Ctr, Dept Internal Med, Cheverly, MD USA. [Rathod, Ankit] Cedars Sinai Med Ctr, Dept Cardiol, Los Angeles, CA 90048 USA. [Manvar, Sohilkumar; Patel, Jay] Detroit Med Ctr, Dept Cardiol, Detroit, MI USA. [Thakkar, Badal; Panchal, Vinaykumar] Tulane Sch Publ Hlth & Trop Med, Dept Publ Hlth, New Orleans, LA USA. [Palacios, Igor F.] Henry Ford Hosp, Detroit, MI 48202 USA. [Rihal, Charanjit S.] Mayo Clin, Dept Intervent Cardiol, Rochester, MN USA. [Cohen, Mauricio G.; De Marchena, Eduardo] Univ Miami, Miller Sch Med, Dept Intervent Cardiol, Miami, FL 33136 USA. [O'Neill, William] Massachusetts Gen Hosp, Dept Intervent Cardiol, Boston, MA 02114 USA. RP Badheka, AO (reprint author), Yale Univ, Dept Intervent Cardiol, Sch Med, 333 Cedar St, New Haven, CT 06520 USA. EM apurva.badheka@yale.edu OI Cohen, Mauricio/0000-0003-2038-6070 NR 29 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAY PY 2015 VL 85 IS 6 BP 1073 EP 1081 DI 10.1002/ccd.25794 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG5UG UT WOS:000353360800027 PM 25534392 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Adverse Outcomes: Why Bad Things Happen to Good People SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97239 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 9 TC 2 Z9 2 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 MAY PY 2015 VL 13 IS 5 BP 820 EP U295 DI 10.1016/j.cgh.2014.07.064 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CG1XN UT WOS:000353069000007 PM 25890669 ER PT J AU Singh, H Allen, JI AF Singh, Hardeep Allen, John I. TI Patient Safety Counterpoint: Systems Approaches and Multidisciplinary Strategies at the Centerpiece of Error Prevention SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID COLORECTAL-CANCER DIAGNOSIS C1 [Singh, Hardeep] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Vet Affairs Ctr Innovat Qual Effectivenes, Houston, TX 77030 USA. [Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Allen, John I.] Yale Univ, Sch Med, New Haven, CT USA. RP Singh, H (reprint author), VA Med Ctr, Hlth Policy Qual & Informat Program, 152 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu FU AHRQ HHS [R01HS022087] NR 16 TC 2 Z9 2 U1 1 U2 3 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 MAY PY 2015 VL 13 IS 5 BP 824 EP 826 DI 10.1016/j.cgh.2015.01.005 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CG1XN UT WOS:000353069000008 PM 25890670 ER PT J AU Eshleman, JR Norris, AL Sadakari, Y Debeljak, M Borges, M Harrington, C Lin, E Brant, A Barkley, T Almario, JA Topazian, M Farrell, J Syngal, S Lee, JH Yu, J Hruban, RH Kanda, M Canto, MI Goggins, M AF Eshleman, James R. Norris, Alexis L. Sadakari, Yoshihiko Debeljak, Marija Borges, Michael Harrington, Colleen Lin, Elaine Brant, Aaron Barkley, Thomas Almario, J. Alejandro Topazian, Mark Farrell, James Syngal, Sapna Lee, Jeffrey H. Yu, Jun Hruban, Ralph H. Kanda, Mitsuro Canto, Marcia Irene Goggins, Michael TI KRAS and Guanine Nucleotide-Binding Protein Mutations in Pancreatic Juice Collected From the Duodenum of Patients at High Risk for Neoplasia Undergoing Endoscopic Ultrasound SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Screening; EUS; Early Detection; IPMN; PDAC ID K-RAS MUTATIONS; INTRAEPITHELIAL NEOPLASIA; DUCTAL ADENOCARCINOMA; FAMILY-HISTORY; GENE-MUTATIONS; CANCER; LESIONS; CYSTS; INDIVIDUALS; PREVALENCE AB BACKGROUND & AIMS: Pancreatic imaging can identify neoplastic cysts but not microscopic neoplasms. Mutation analysis of pancreatic fluid after secretin stimulation might identify microscopic neoplasias in the pancreatic duct system. We determined the prevalence of mutations in KRAS and guanine nucleotide-binding protein a-stimulating genes in pancreatic juice from subjects undergoing endoscopic ultrasound for suspected pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms, or pancreatic adenocarcinoma. METHODS: Secretin-stimulated juice samples were collected from the duodenum of 272 subjects enrolled in Cancer of the Pancreas Screening studies; 194 subjects were screened because of a family history of, or genetic predisposition to, pancreatic cancer, and 78 subjects were evaluated for pancreatic cancer (n = 30) or other disorders (controls: pancreatic cysts, pancreatitis, or normal pancreata, n = 48). Mutations were detected by digital high-resolution melt-curve analysis and pyrosequencing. The number of replicates containing a mutation determined the mutation score. RESULTS: KRAS mutations were detected in pancreatic juice from larger percentages of subjects with pancreatic cancer (73%) or undergoing cancer screening (50%) than controls (19%) (P = .0005). A greater proportion of patients with pancreatic cancer had at least 1 KRAS mutation detected 3 or more times (47%) than screened subjects (21%) or controls (6%, P =. 002). Among screened subjects, mutations in KRAS (but not guanine nucleotide-binding protein a-stimulating) were found in similar percentages of patients with or without pancreatic cysts. However, a greater proportion of patients older than age 50 years had KRAS mutations (54.6%) than younger patients (36.3%) (P = .032); the older subjects also had more mutations in KRAS (P = .02). CONCLUSIONS: Mutations in KRAS are detected in pancreatic juice from the duodenum of 73% of patients with pancreatic cancer, and 50% of asymptomatic individuals with a high risk for pancreatic cancer. However, KRAS mutations were detected in pancreatic juice from 19% of controls. Mutations detected in individuals without pancreatic abnormalities, based on imaging analyses, likely arise from small pancreatic intraepithelial neoplasia lesions. C1 [Eshleman, James R.; Norris, Alexis L.; Sadakari, Yoshihiko; Debeljak, Marija; Borges, Michael; Harrington, Colleen; Lin, Elaine; Brant, Aaron; Barkley, Thomas; Almario, J. Alejandro; Yu, Jun; Hruban, Ralph H.; Kanda, Mitsuro; Goggins, Michael] Johns Hopkins Med Inst, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. [Canto, Marcia Irene; Goggins, Michael] Johns Hopkins Med Inst, Dept Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. [Eshleman, James R.; Hruban, Ralph H.; Canto, Marcia Irene; Goggins, Michael] Johns Hopkins Med Inst, Dept Oncol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. [Topazian, Mark] Mayo Clin, Rochester, MN USA. [Farrell, James] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Farrell, James] Harvard Univ, Sch Med, Boston, MA USA. [Syngal, Sapna] Yale Univ, New Haven, CT USA. [Lee, Jeffrey H.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Eshleman, JR (reprint author), Johns Hopkins Med Inst, Dept Pathol, 1550 Orleans St, Baltimore, MD 21231 USA. EM jeshlem@jhmi.edu; mgoggins@jhmi.edu RI Kanda, Mitsuro/M-4891-2014 FU National Institutes of Health [CA62924, R01CA176828]; American Association for Cancer Research; Goldman grant; Lustgarten Foundation for Pancreatic Cancer Research; Jimmy V Foundation; Michael Rolfe Foundation; Karp Family H.H. & M. Metals, Inc, Fund FX Supported by Susan Wojcicki and Dennis Troper, National Institutes of Health grants (CA62924 and R01CA176828), the American Association for Cancer Research (Research Acceleration grant to M.G. and M.I.C.), Goldman grants (J.R.E. and M.G.), the Lustgarten Foundation for Pancreatic Cancer Research, the Jimmy V Foundation, the Michael Rolfe Foundation, Michael Hooven and Susan Spies, Hugh and Rachel Victor, and the Karp Family H.H. & M. Metals, Inc, Fund. NR 38 TC 14 Z9 14 U1 0 U2 2 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 MAY PY 2015 VL 13 IS 5 BP 963 EP U469 DI 10.1016/j.cgh.2014.11.028 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CG1XN UT WOS:000353069000027 PM 25481712 ER PT J AU Gerber, DE Oxnard, GR Govindan, R AF Gerber, D. E. Oxnard, G. R. Govindan, R. TI ALCHEMIST: Bringing Genomic Discovery and Targeted Therapies to Early-Stage Lung Cancer SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB The identification of druggable molecular alterations represents one of the greatest advances in cancer treatment. Such progress is particularly evident for lung cancer, which now has numerous molecularly defined subsets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. However, understanding of the significance of these genomic alterations is largely limited to incurable, metastatic lung cancer. ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) is a National Cancer Institute-sponsored initiative to address these questions in earlier-stage disease. C1 [Gerber, D. E.] UT SW Med Ctr, Harold C Simmons Canc Ctr, Div Hematol & Oncol, Dallas, TX 75235 USA. [Oxnard, G. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Govindan, R.] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. RP Gerber, DE (reprint author), UT SW Med Ctr, Harold C Simmons Canc Ctr, Div Hematol & Oncol, Dallas, TX 75235 USA. EM david.gerber@utsouthwestern.edu FU NCI NIH HHS [U10 CA180833, R21 CA170063, U10 CA180870] NR 5 TC 16 Z9 16 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2015 VL 97 IS 5 BP 447 EP 450 DI 10.1002/cpt.91 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG4DT UT WOS:000353233900004 PM 25677079 ER PT J AU Capp, R Horton, CL Takhar, SS Ginde, AA Peak, DA Zane, R Marill, KA AF Capp, Roberta Horton, Cheryl Lynn Takhar, Sukhjit S. Ginde, Adit A. Peak, David A. Zane, Richard Marill, Keith A. TI Predictors of Patients Who Present to the Emergency Department With Sepsis and Progress to Septic Shock Between 4 and 48 Hours of Emergency Department Arrival SO CRITICAL CARE MEDICINE LA English DT Article DE admission; emergency department; predictors; progression; sepsis; septic shock ID HEALTH-CARE-SYSTEM; INTENSIVE-CARE; UNITED-STATES; GUIDELINES; MANAGEMENT; OUTCOMES; SUPPORT; RISK AB Objectives: Approximately one in every four patients who present to the emergency department with sepsis progresses to septic shock within 72 hours of arrival. In this study, we describe key patient characteristics present within 4 hours of emergency department arrival that are associated with developing septic shock between 4 and 48 hours of emergency department arrival. Design and Setting: This study was a retrospective chart review study of all patients hospitalized from the emergency department with two or more systemic inflammatory response syndrome criteria present within 4 hours of emergency department arrival from September 2010 to February 2011 at two large academic institutions. Patients were excluded if they presented with a ST-elevation myocardial infarction, acute stroke, or trauma; had a cardiac arrest prior to arrival; were pregnant; or admitted from the emergency department psychiatric unit or transferred from an outside hospital. We identified patients with within 4 hours of emergency department arrival and identified those with septic shock at 48 hours after emergency department arrival, using a standard set of guidelines. The primary objective was identifying the number of patients who present with sepsis and progress to septic shock between 4 and 48 hours of emergency department arrival. As to the second objective, we used multivariate logistic regression analysis to identify patient factors associated with the progression of sepsis to septic shock for the aforementioned population. Measurements and Main Results: A total of 18,100 patients were admitted from the emergency department, of which 3,960 patients had two or more systemic inflammatory response syndrome criteria, and 1,316 patients had sepsis within 4 hours of emergency department arrival. Although 50 patients presented to the emergency department with septic shock within 4 hours of arrival, 111 patients with sepsis (8.4%) progressed to septic shock between 4 and 48 hours of emergency department arrival. Characteristics associated with the progression of septic shock between 4 and 48 hours of emergency department arrival included female gender (odds ratio, 1.59; 95% CI, 1.02-2.47), nonpersistent hypotension (odds ratio, 6.24; 95% CI, 3.58-10.86), bandemia at least 10% (odds ratio, 2.60; 95% CI, 1.50-4.51), lactate at least 4.0 mmol/L (odds ratio, 5.30; 95% CI, 2.59-10.84), and past medical of coronary artery disease (odds ratio, 2.01; 95% 1.26-3.44). Conclusion: Approximately 12% of septic emergency department patients develop shock within 48 hours of presentation, and more than half of these patients develop shock after the first 4 hours of emergency department arrival. Over a third of patients who have sepsis within 4 hours of emergency department arrival and develop septic shock between 4 and 48 hours of emergency department arrival are not admitted to an ICU. C1 [Capp, Roberta; Ginde, Adit A.; Zane, Richard] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO 80045 USA. [Horton, Cheryl Lynn; Takhar, Sukhjit S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Peak, David A.; Marill, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Capp, R (reprint author), Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO 80045 USA. EM roberta.capp@ucdenver.edu RI bebarta, vikhyat/K-3476-2015; Siry, Bonnie/D-7189-2017 FU Partners HealthCare System Quality Improvement grant; National Institutes of Health (NIH); NIH Translational Research/Partners Quality Improvement Research [TR001080] FX Supported, in part, by the Partners HealthCare System Quality Improvement grant.; Dr. Capp received support for article research from the National Institutes of Health (NIH) and hospital-based grants. She and her institution received grant support from the NIH Translational Research/Partners Quality Improvement Research (TR001080/hospital-based grant to improve quality of care). Dr. Marill is employed by Massachusetts General Physicians Organization. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 19 TC 7 Z9 9 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2015 VL 43 IS 5 BP 983 EP 988 DI 10.1097/CCM.0000000000000861 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA CG1UT UT WOS:000353061000023 PM 25668750 ER PT J AU Beitler, JR Thompson, BT Matthay, MA Talmor, D Liu, KD Zhuo, HJ Hayden, D Spragg, RG Malhotra, A AF Beitler, Jeremy R. Thompson, B. Taylor Matthay, Michael A. Talmor, Daniel Liu, Kathleen D. Zhuo, Hanjing Hayden, Douglas Spragg, Roger G. Malhotra, Atul TI Estimating Dead-Space Fraction for Secondary Analyses of Acute Respiratory Distress Syndrome Clinical Trials SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; acute respiratory distress syndrome; capnography; clinical trials as topic; respiratory dead space ID ACUTE LUNG INJURY; CRITICALLY-ILL PATIENTS; RESTING METABOLIC-RATE; ENERGY-EXPENDITURE; TIDAL VOLUME; MECHANICAL VENTILATION; BERLIN DEFINITION; PULMONARY-ARTERY; PROGNOSTIC VALUE; PRESSURE AB Objectives: Pulmonary dead-space fraction is one of few lung-specific independent predictors of mortality from acute respiratory distress syndrome. However, it is not measured routinely in clinical trials and thus altogether ignored in secondary analyses that shape future research directions and clinical practice. This study sought to validate an estimate of dead-space fraction for use in secondary analyses of clinical trials. Design: Analysis of patient-level data pooled from acute respiratory distress syndrome clinical trials. Four approaches to estimate dead-space fraction were evaluated: three required estimating metabolic rate; one estimated dead-space fraction directly. Setting: U. S. academic teaching hospitals. Patients: Data from 210 patients across three clinical trials were used to compare performance of estimating equations with measured dead-space fraction. A second cohort of 3,135 patients from six clinical trials without measured dead-space fraction was used to confirm whether estimates independently predicted mortality. Interventions: None. Measurements and Main Results: Dead-space fraction estimated using the unadjusted Harris-Benedict equation for energy expenditure was unbiased (mean +/- sd Harris-Benedict, 0.59 +/- 0.13; measured, 0.60 +/- 0.12). This estimate predicted measured dead-space fraction to within +/- 0.10 in 70% of patients and +/- 0.20 in 95% of patients. Measured dead-space fraction independently predicted mortality (odds ratio, 1.36 per 0.05 increase in dead-space fraction; 95% CI, 1.10-1.68; p < 0.01). The Harris-Benedict estimate closely approximated this association with mortality in the same cohort (odds ratio, 1.55; 95% CI, 1.21-1.98; p < 0.01) and remained independently predictive of death in the larger Acute Respiratory Distress Syndrome Network cohort. Other estimates predicted measured dead-space fraction or its association with mortality less well. Conclusions: Dead-space fraction should be measured in future acute respiratory distress syndrome clinical trials to facilitate incorporation into secondary analyses. For analyses where dead-space fraction was not measured, the Harris-Benedict estimate can be used to estimate dead-space fraction and adjust for its association with mortality. C1 [Beitler, Jeremy R.; Spragg, Roger G.; Malhotra, Atul] Univ Calif San Diego, Div Pulm & Crit Care Med, San Diego, CA 92103 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Matthay, Michael A.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. [Matthay, Michael A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Matthay, Michael A.; Zhuo, Hanjing] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Talmor, Daniel] Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. [Liu, Kathleen D.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Liu, Kathleen D.] Univ Calif San Francisco, Div Crit Care Med, San Francisco, CA 94143 USA. [Hayden, Douglas] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Beitler, JR (reprint author), Univ Calif San Diego, Div Pulm & Crit Care Med, San Diego, CA 92103 USA. EM jbeitler@ucsd.edu FU National Institutes of Health (NIH); National Heart, Lung, and Blood Institute (NHLBI) [T32-HL007633]; NIH; NIH/NHLBI [N01-HR56179]; NIH [R37-HL51856, SCCOR HL-74005, UM1-HL108724, K24-HL093218]; NHLBI; National Institute of Allergy and Infectious Diseases (NIAID); ATS; NIAID; NIH-NHLBI Acute Respiratory Distress Syndrome Network (ARDSNet) [HHSN268200536179C, 219579]; NIH-NHLBI as the ARDSNet Clinical Coordinating Center [HHSN268200536179C, 219579] FX Dr. Beitler received support for article research from the National Institutes of Health (NIH). His institution received grant support from the National Heart, Lung, and Blood Institute (NHLBI) (T32-HL007633). Dr. Thompson received support for article research from the NIH. His institution received grant support from the NIH/NHLBI (N01-HR56179). Dr. Matthay received support for article research from the NIH (R37-HL51856 and SCCOR HL-74005), served as a board member for Roche DSMB, and consulted for Cerus and GSK. His institution received grant support from the NHLBI and National Institute of Allergy and Infectious Diseases (NIAID). Dr. Talmor received grant support from the NHLBI and received support for article research from the NIH (UM1-HL108724). Dr. Liu served as a board member for Astute Biomedical (Clinical Events Adjudication Committee), Complexa (Scientific Advisory Board), Cytopheryx (Data Safety Monitoring Board), and Roche DSMB. She received support for travel from the American Thoracic Society (ATS) (Member of publications committee; trip to planning meeting paid for by ATS), American Society of Nephrology (Reimbursement for travel to national meeting for presentation), and Continuous Renal Replacement Therapies Meeting (Reimbursement for travel to national meeting for presentation). She consulted for Chemocentryx, Cerus, and GSK; lectured for the NIH; has stock in Amgen; disclosed other support from Abbott (gift of reagents for biomarker assays) and CMIC (gift of reagents for biomarker assays); and received support for article research from the NIH. Her institution received grant support from the NIH, NHLBI, and NIAID. Dr. Hayden is employed by a contract with the NIH-NHLBI Acute Respiratory Distress Syndrome Network (ARDSNet) (HHSN268200536179C, Fund Number: 219579) and received support for article research from the NIH. His institution received grant support from the NIH-NHLBI as the ARDSNet Clinical Coordinating Center (HHSN268200536179C, Fund Number: 219579). Dr. Malhotra received support for article research from the NIH (K24-HL093218). His institution consulted for Pfizer, SHC, SGS, Apnex, and Apnicure (relinquished all outside personal income in 2012). The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 48 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2015 VL 43 IS 5 BP 1026 EP 1035 DI 10.1097/CCM.0000000000000921 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA CG1UT UT WOS:000353061000029 PM 25738857 ER PT J AU Sullivan, BA Hollister-Lock, J Bonner-Weir, S Weir, GC AF Sullivan, Brooke A. Hollister-Lock, Jennifer Bonner-Weir, Susan Weir, Gordon C. TI Reduced Ki67 Staining in the Postmortem State Calls Into Question Past Conclusions About the Lack of Turnover of Adult Human beta-Cells SO DIABETES LA English DT Article ID HUMAN ISLETS; IN-VIVO; REGENERATION; REPLICATION; PREGNANCY; EXPANSION; APOPTOSIS; ESTROGEN; GROWTH; LIFE AB Some report that adult human beta-cells do not replicate, but we postulate this assumption is erroneous due a postmortem decline in replication markers such as Ki67. Our earlier report showed that Ki67-marked beta-cells were rarely found in human cadaveric pancreases but were in the range of 0.2-0.5% in human islets transplanted into mice. This study subjected 4-week-old mice to autopsy conditions that typically occur with humans. Mice were killed, left at room temperature for 3 h, and then placed at 4 degrees C for 3, 9, or 21 h. There was a rapid marked fall in Ki67 staining of beta-cells compared with those fixed immediately. Values at death were 6.9 +/- 0.9% (n = 6) after a 24-h fast, 4.1 +/- 0.9% (n = 6) at 3 h room temperature, 2.7 +/- 0.7% (n = 5) at 6 h, 1.6 +/- 0.6% (n = 5) at 12 h, and 2.9 +/- 0.8% (n = 5) at 24 h. Similar postmortem conditions in newborn pigs resulted in very similar declines in Ki67 staining of their beta-cells. These data support the hypothesis that conclusions on the lack of replication of adult human beta-cells are incorrect and suggest that adult human beta-cells replicate at a low but quantitatively meaningful rate. C1 [Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol,Res Div, Boston, MA 02115 USA. Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol,Res Div, Boston, MA 02115 USA. EM gordon.weir@joslin.harvard.edu FU JDRF; National Institutes of Health [R01-DK-066056, DK-093909, P30-DK-036836]; Diabetes Research & Wellness Foundation FX This study was supported by grants from JDRF (G.C.W.), National Institutes of Health grants R01-DK-066056 and DK-093909 (S.B.-W.) and P30-DK-036836 (Joslin Diabetes Research Center and its Advanced Microscopy Core), and the Diabetes Research & Wellness Foundation. NR 25 TC 11 Z9 11 U1 0 U2 1 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 MAY PY 2015 VL 64 IS 5 BP 1698 EP 1702 DI 10.2337/db14-1675 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG6RX UT WOS:000353431200025 PM 25488899 ER PT J AU Weinstock, RS Trief, PM El Ghormli, L Goland, R McKay, S Milaszewski, K Preske, J Willi, S Yasuda, PM AF Weinstock, Ruth S. Trief, Paula M. El Ghormli, Laure Goland, Robin McKay, Siripoom Milaszewski, Kerry Preske, Jeff Willi, Steven Yasuda, Patrice M. TI Parental Characteristics Associated With Outcomes in Youth With Type 2 Diabetes: Results From the TODAY Clinical Trial SO DIABETES CARE LA English DT Article ID EATING-DISORDER EXAMINATION; QUALITY-OF-LIFE; MATERNAL DEPRESSION; GLYCEMIC CONTROL; ADOLESCENTS; CHILD; RETINOPATHY; PREVALENCE; MELLITUS; MICROALBUMINURIA AB OBJECTIVEThis study examined parental factors associated with outcomes of youth in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial.RESEARCH DESIGN AND METHODSOf 699 youth with type 2 diabetes in the TODAY cohort, 623 (89.1%) had a parent participate and provide data at baseline, including weight, HbA(1c), blood pressure, symptoms of depression, binge eating (BE), and medical history. Youth were followed 2-6.5 years. Data were analyzed using regression models and survival curve methods.RESULTSParental diabetes (43.6% of parents) was associated with higher baseline HbA(1c) (P < 0.0001) and failure of youths to maintain glycemic control on study treatment (53.6% vs. 38.2% failure rate among those without a diabetic parent, P = 0.0002). Parental hypertension (40.6% of parents) was associated with hypertension in youth during TODAY (40.4% vs. 27.4% of youth with and without parental hypertension had hypertension, P = 0.0008) and with higher youth baseline BMI z scores (P = 0.0038). Parents had a mean baseline BMI of 33.6 kg/m(2). Parental obesity (BMI >30 kg/m(2)) was associated with higher baseline BMI z scores in the youth (P < 0.0001). Depressive symptoms in parents (20.6% of parents) were related to youth depressive symptoms at baseline only (P = 0.0430); subclinical BE in parents was related to the presence of subclinical BE (P = 0.0354) and depressive symptoms (P = 0.0326) in youth throughout the study period.CONCLUSIONSParental diabetes and hypertension were associated with lack of glycemic control, hypertension, and higher BMI z scores in youth. Further research is needed to better understand and address parental biological and behavioral factors to improve youth health outcomes. C1 [Weinstock, Ruth S.; Trief, Paula M.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [El Ghormli, Laure] George Washington Univ, Ctr Biostat, Rockville, MD 20052 USA. [Goland, Robin] Columbia Univ, New York, NY USA. [McKay, Siripoom] Baylor Coll Med, Houston, TX 77030 USA. [Milaszewski, Kerry] Joslin Diabet Ctr, Boston, MA 02215 USA. [Preske, Jeff] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Willi, Steven] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Willi, Steven] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Yasuda, Patrice M.] Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA. [Yasuda, Patrice M.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP El Ghormli, L (reprint author), George Washington Univ, Ctr Biostat, Rockville, MD 20052 USA. EM elghorml@bsc.gwu.edu FU National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health [U01-DK-061212, U01-DK-061230, U01-DK-061239, U01-DK-061242, U01-DK-061254]; National Center for Research Resources General Clinical Research Centers Program [M01-RR-000036, M01-RR-000043-45, M01-RR-000069, M01-RR-000084, M01-RR-001066, M01-RR-000125, M01-RR-014467]; National Center for Research Resources Clinical and Translational Science Awards [UL1-RR-024134, UL1-RR-024139, UL1-RR-024153, UL1-RR-024989, UL1-RR-024992, UL1-RR-025758, UL1-RR-025780] FX This work was completed with funding from National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health grant numbers U01-DK-061212, U01-DK-061230, U01-DK-061239, U01-DK-061242, and U01-DK-061254, from the National Center for Research Resources General Clinical Research Centers Program grant numbers M01-RR-000036 (Washington University School of Medicine), M01-RR-000043-45 (Children's Hospital Los Angeles), M01-RR-000069 (University of Colorado Denver), M01-RR-000084 (Children's Hospital of Pittsburgh), M01-RR-001066 (Massachusetts General Hospital), M01-RR-000125 (Yale University), and M01-RR-014467 (University of Oklahoma Health Sciences Center), and from National Center for Research Resources Clinical and Translational Science Awards grant numbers UL1-RR-024134 (Children's Hospital of Philadelphia), UL1-RR-024139 (Yale University), UL1-RR-024153 (Children's Hospital of Pittsburgh), UL1-RR-024989 (Case Western Reserve University), UL1-RR-024992 (Washington University in St. Louis), UL1-RR-025758 (Massachusetts General Hospital), and UL1-RR-025780 (University of Colorado Denver). NR 39 TC 1 Z9 1 U1 2 U2 18 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 MAY PY 2015 VL 38 IS 5 BP 784 EP 792 DI 10.2337/dc14-2393 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG7SP UT WOS:000353505600017 PM 25784663 ER PT J AU Araneta, MRG Kanaya, AM Hsu, WC Chang, HK Grandinetti, A Boyko, EJ Hayashi, T Kahn, SE Leonetti, DL McNeely, MJ Onishi, Y Sato, KK Fujimoto, WY AF Araneta, Maria Rosario G. Kanaya, Alka M. Hsu, William C. Chang, Healani K. Grandinetti, Andrew Boyko, Edward J. Hayashi, Tomoshige Kahn, Steven E. Leonetti, Donna L. McNeely, Marguerite J. Onishi, Yukiko Sato, Kyoko K. Fujimoto, Wilfred Y. TI Optimum BMI Cut Points to Screen Asian Americans for Type 2 Diabetes SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; JAPANESE-AMERICANS; PACIFIC ISLANDERS; NATIVE HAWAIIANS; RISK; PREVALENCE; WOMEN; COMPLICATIONS; INTOLERANCE; FILIPINO AB OBJECTIVEAsian Americans manifest type 2 diabetes at low BMI levels but may not undergo diagnostic testing for diabetes if the currently recommended BMI screening cut point of 25 kg/m(2) is followed. We aimed to ascertain an appropriate lower BMI cut point among Asian-American adults without a prior diabetes diagnosis.RESEARCH DESIGN AND METHODSWe consolidated data from 1,663 participants, ages 45 years, without a prior diabetes diagnosis, from population- and community-based studies, including the Mediators of Atherosclerosis in South Asians Living in America study, the North Kohala Study, the Seattle Japanese American Community Diabetes Study, and the University of California San Diego Filipino Health Study. Clinical measures included a 2-h 75-g oral glucose tolerance test, BMI, and glycosylated hemoglobin (HbA(1c)).RESULTSMean age was 59.7 years, mean BMI was 25.4 kg/m(2), 58% were women, and type 2 diabetes prevalence (American Diabetes Association 2010 criteria) was 16.9%. At BMI 25 kg/m(2), sensitivity (63.7%), specificity (52.8%), and Youden index (0.16) values were low; limiting screening to BMI 25 kg/m(2) would miss 36% of Asian Americans with type 2 diabetes. For screening purposes, higher sensitivity is desirable to minimize missing cases, especially if the diagnostic test is relatively simple and inexpensive. At BMI 23 kg/m(2), sensitivity (84.7%) was high in the total sample and by sex and Asian-American subgroup and would miss only approximate to 15% of Asian Americans with diabetes.CONCLUSIONSThe BMI cut point for identifying Asian Americans who should be screened for undiagnosed type 2 diabetes should be <25 kg/m(2), and 23 kg/m(2) may be the most practical. C1 [Araneta, Maria Rosario G.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Kanaya, Alka M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Hsu, William C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Chang, Healani K.; Grandinetti, Andrew] Univ Hawaii Manoa, Honolulu, HI 96822 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Boyko, Edward J.; Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Boyko, Edward J.; Kahn, Steven E.; McNeely, Marguerite J.; Fujimoto, Wilfred Y.] Univ Washington, Dept Med, Seattle, WA USA. [Hayashi, Tomoshige; Sato, Kyoko K.] Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Osaka 558, Japan. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. [Onishi, Yukiko] Asahi Life Fdn, Inst Adult Dis, Tokyo, Japan. RP Araneta, MRG (reprint author), Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. EM haraneta@ucsd.edu RI Hayashi, Tomoshige/N-8508-2015; OI Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health [DK-31801, R03-DK-60575, HL-093009, K24-HL-112827, DK-31170, DK-02654, DK-02860, DK-48152, DK-50703, DK-55460, DK-17047, DK-35876, HL-07028, HL-49293, RR-00037, HL-29393, U01-HL-079163, G12-RR-03061]; Department of Veterans Affairs FX This work was supported by the National Institutes of Health (DK-31801, R03-DK-60575, HL-093009, K24-HL-112827, DK-31170, DK-02654, DK-02860, DK-48152, DK-50703, DK-55460, DK-17047, DK-55460, DK-35876, HL-07028, HL-49293, RR-00037, HL-29393, U01-HL-079163, and G12-RR-03061) and the Department of Veterans Affairs. NR 22 TC 19 Z9 19 U1 0 U2 10 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 MAY PY 2015 VL 38 IS 5 BP 814 EP 820 DI 10.2337/dc14-2071 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG7SP UT WOS:000353505600021 PM 25665815 ER PT J AU Sosenko, JM Skyler, JS Beam, CA Boulware, D Mahon, JL Krischer, JP Greenbaum, CJ Rafkin, LE Matheson, D Herold, KC Palmer, JP AF Sosenko, Jay M. Skyler, Jay S. Beam, Craig A. Boulware, David Mahon, Jeffrey L. Krischer, Jeffrey P. Greenbaum, Carla J. Rafkin, Lisa E. Matheson, Della Herold, Kevan C. Palmer, Jerry P. CA Type 1 Diabet TrialNet Study Grp Diabet Prevention Trial-Type 1 TI The Development and Utility of a Novel Scale That Quantifies the Glycemic Progression Toward Type 1 Diabetes Over 6 Months SO DIABETES CARE LA English DT Article ID TRIAL-TYPE 1; C-PEPTIDE; NATURAL-HISTORY; GLUCOSE; DESIGN AB OBJECTIVEWe developed a scale to serve as a potential end point for 6-month glycemic progression (PS6M) toward type 1 diabetes (T1D) in autoantibody-positive relatives of individuals with T1D.RESEARCH DESIGN AND METHODSThe PS6M was developed from Diabetes Prevention Trial-Type 1 (DPT-1) data and tested in the TrialNet Pathway to Prevention Study (PTP). It is the difference between 6-month glucose sum values (30-120 min oral glucose tolerance test values) and values predicted for nonprogressors.RESULTSThe PS6M predicted T1D in the PTP (P < 0.001). The area under the receiver operating chacteristic curve was greater (P < 0.001) for the PS6M than for the baseline-to-6-month difference. PS6M values were higher in those with two or more autoantibodies, 30-0 min C-peptide values <2.00 ng/mL, or DPT-1 Risk Scores >7.00 (P < 0.001 for all).CONCLUSIONSThe PS6M is an indicator of short-term glycemic progression to T1D that could be a useful tool for assessing preventive treatments and biomarkers. C1 [Sosenko, Jay M.; Skyler, Jay S.; Rafkin, Lisa E.; Matheson, Della] Univ Miami, Div Endocrinol, Miami, FL 33124 USA. [Beam, Craig A.] Western Michigan Univ, Sch Med, Div Epidemiol & Biostat, Kalamazoo, MI 49008 USA. [Boulware, David; Krischer, Jeffrey P.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA. [Mahon, Jeffrey L.] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Greenbaum, Carla J.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. [Herold, Kevan C.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Palmer, Jerry P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Palmer, Jerry P.] Univ Washington, Div Endocrinol Metab & Nutr, Seattle, WA 98195 USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL 33124 USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016; OI Tack, Jan/0000-0002-3206-6704 FU National Institutes of Health through the National Center for Research Resources; JDRF; American Diabetes Association FX This work was funded by the 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, National Center for Research Resources, the JDRF, and the American Diabetes Association. NR 10 TC 4 Z9 4 U1 0 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 MAY PY 2015 VL 38 IS 5 BP 940 EP 942 DI 10.2337/dc14-2787 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG7SP UT WOS:000353505600040 PM 25758770 ER PT J AU He, ZHH D'Eon, SA Tinsley, LJ Fitzgerald, S Hastings, SM Khamaisi, M Sun, JK Turek, SJ Schaefer, EJ King, GL Keenan, HA AF He, Zhiheng H. D'Eon, Stephanie A. Tinsley, Liane J. Fitzgerald, Shane Hastings, Stephanie M. Khamaisi, Mogher Sun, Jennifer K. Turek, Sara J. Schaefer, Ernst J. King, George L. Keenan, Hillary A. TI Cardiovascular Disease Protection in Long-Duration Type 1 Diabetes and Sex Differences SO DIABETES CARE LA English DT Letter ID AMERICAN-HEART-ASSOCIATION; SCIENTIFIC STATEMENT; MELLITUS C1 [He, Zhiheng H.] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Div Endocrinol Diabet & Metab, Cambridge, MA 02138 USA. [D'Eon, Stephanie A.; Tinsley, Liane J.; Fitzgerald, Shane; Hastings, Stephanie M.; Khamaisi, Mogher; Sun, Jennifer K.; Turek, Sara J.; King, George L.; Keenan, Hillary A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Schaefer, Ernst J.] Boston Heart Diagnost, Framingham, MA USA. RP Keenan, HA (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. EM hillary.keenan@joslin.harvard.edu FU NCRR NIH HHS [UL1 RR025758-03, UL1 RR025758]; NIDDK NIH HHS [R24 DK083957-01, P30 DK036836, DP3DK094333-01, T32DK007260, P30DK036836, R24 DK083957, DP3 DK094333, T32 DK007260] NR 5 TC 0 Z9 0 U1 0 U2 3 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 MAY PY 2015 VL 38 IS 5 BP E73 EP E74 DI 10.2337/dc15-0017 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG7SP UT WOS:000353505600003 PM 25908159 ER PT J AU Brima, W Eden, DJ Mehdi, SF Bravo, M Wiese, MM Stein, J Almonte, V Zhao, DZ Kurland, I Pessin, JE Zima, T Tanowitz, HB Weiss, LM Roth, J Nagajyothi, F AF Brima, Wunnie Eden, Daniel J. Mehdi, Syed Faizan Bravo, Michelle Wiese, Mohammad M. Stein, Joanna Almonte, Vanessa Zhao, Dazhi Kurland, Irwin Pessin, Jeffrey E. Zima, Tomas Tanowitz, Herbert B. Weiss, Louis M. Roth, Jesse Nagajyothi, Fnu TI The brighter (and evolutionarily older) face of the metabolic syndrome: evidence from Trypanosoma cruzi infection in CD-1 mice SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE metabolic syndrome; high-fat diet; Trypanosoma cruzi; metformin; infectious disease; mortality ID DENSITY-LIPOPROTEIN RECEPTOR; NECROSIS-FACTOR-ALPHA; CHAGAS-DISEASE; BRAZIL STRAIN; OBESITY; METFORMIN; CELLS; CARDIOMYOPATHY; TUBERCULOSIS; ASSOCIATION AB BackgroundInfection with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, results in chronic infection that leads to cardiomyopathy with increased mortality and morbidity in endemic regions. In a companion study, our group found that a high-fat diet (HFD) protected mice from T.cruzi-induced myocardial damage and significantly reduced post-infection mortality during acute T.cruzi infection. MethodsIn the present study metabolic syndrome was induced prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated with anti-diabetic drug metformin. ResultsIn the present study, the lethality of T.cruzi (Brazil strain) infection in CD-1 mice was reduced from 55% to 20% by an 8-week pre-feeding of an HFD to induce obesity and metabolic syndrome. The addition of metformin reduced mortality to 3%. ConclusionsIt is an interesting observation that both the high fat diet and the metformin, which are known to differentially attenuate host metabolism, effectively modified mortality in T.cruzi-infected mice. In humans, the metabolic syndrome, as presently construed, produces immune activation and metabolic alterations that promote complications of obesity and diseases of later life, such as myocardial infarction, stroke, diabetes, Alzheimer's disease and cancer. Using an evolutionary approach, we hypothesized that for millions of years, the channeling of host resources into immune defences starting early in life ameliorated the effects of infectious diseases, especially chronic infections, such as tuberculosis and Chagas disease. In economically developed countries in recent times, with control of the common devastating infections, epidemic obesity and lengthening of lifespan, the dwindling benefits of the immune activation in the first half of life have been overshadowed by the explosion of the syndrome's negative effects in later life. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Brima, Wunnie; Eden, Daniel J.; Mehdi, Syed Faizan; Bravo, Michelle; Wiese, Mohammad M.; Roth, Jesse] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Lab Diabet & Diabet Related Res, Manhasset, NY USA. [Brima, Wunnie; Almonte, Vanessa; Zhao, Dazhi; Tanowitz, Herbert B.; Weiss, Louis M.; Roth, Jesse; Nagajyothi, Fnu] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. [Brima, Wunnie] Mt Sinai Med Ctr Hlth Syst, James J Peters VA Med Ctr, Bronx, NY USA. [Brima, Wunnie; Zima, Tomas] Charles Univ Prague, Prague, Czech Republic. [Stein, Joanna] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Biostat Unit, Manhasset, NY USA. [Kurland, Irwin; Pessin, Jeffrey E.; Tanowitz, Herbert B.; Weiss, Louis M.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Roth, Jesse] North Shore Long Isl Jewish Hlth Syst, Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. RP Roth, J (reprint author), 149-37 Powells Cove Blvd, Whitestone, NY 11357 USA. EM jesserothmd@hotmail.com; fnu.nagajyothi@einstein.yu.edu FU Feinstein Institute for Medical Research of the North Shore-Long Island Jewish Health System; Alan and Tatyana Forman Family; Russell Berrie Foundation; National Heart, Lung and Blood Institute (National Institutes of Health) [HL-112099] FX This study was supported by funds from the Feinstein Institute for Medical Research of the North Shore-Long Island Jewish Health System, the Alan and Tatyana Forman Family and the Russell Berrie Foundation. This work was also supported by grants from the National Heart, Lung and Blood Institute (National Institutes of Health HL-112099) to Fnu Nagajyothi. NR 40 TC 5 Z9 5 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1520-7560 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAY PY 2015 VL 31 IS 4 BP 346 EP 359 DI 10.1002/dmrr.2636 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG6GR UT WOS:000353396700004 PM 25613819 ER PT J AU Rasbach, LE Volkening, LK Markowitz, JT Butler, DA Katz, ML Laffel, LMB AF Rasbach, Lisa E. Volkening, Lisa K. Markowitz, Jessica T. Butler, Deborah A. Katz, Michelle L. Laffel, Lori M. B. TI Youth and Parent Measures of Self-Efficacy for Continuous Glucose Monitoring: Survey Psychometric Properties SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID EXCHANGE CLINIC REGISTRY; PROBLEM AREAS; YOUNG-PEOPLE; PUMP THERAPY; TYPE-1; CHILDREN; ADOLESCENTS; MANAGEMENT; BURDEN; SYSTEM AB Background: This study aimed to describe the development and psychometric evaluation of novel youth and parent measures of self-efficacy related to continuous glucose monitoring (CGM) in pediatric patients with type 1 diabetes. This evaluation also assessed the predictive validity of the CGM Self-Efficacy (CGM-SE) surveys on CGM use and hemoglobin A1c (HbA1c) levels. Subjects and Methods: Study participants included 120 youth with type 1 diabetes for >= 1 year enrolled in a 2-year randomized clinical trial comparing CGM use with and without the addition of a family-focused CGM behavioral intervention. Youth and parents completed the CGM-SE surveys at randomization after a 1-week run-in to assess CGM tolerability. Analyses of predictive validity excluded the intervention group and included 61 youth in the control group in order to assess CGM use and HbA1c outcomes 3 and 6 months after randomization. Results: At study entry, youth were 12.7 +/- 2.7 years old with a diabetes duration of 6.1 +/- 3.6 years and an HbA1c level of 8.0 +/- 0.8% (64 +/- 9 mmol/mol); blood glucose monitoring frequency was 6.8 +/- 2.4 times/day, and 84% received pump therapy. CGM-SE surveys had acceptable internal consistency (Cronbach's alpha=0.80 for youth and 0.82 for parents). Youth reporting higher baseline CGM self-efficacy (CGM-SE score of >80) had significantly greater CGM use and lower HbA1c level after 3 and 6 months compared with youth reporting lower baseline CGM self-efficacy (CGM-SE score of <= 80). Conclusions: The CGM-SE surveys appear to have strong psychometric properties. CGM self-efficacy may offer an opportunity to assess the likelihood of CGM adherence and glycemic improvement in youth with type 1 diabetes in clinical and research settings. C1 [Rasbach, Lisa E.; Volkening, Lisa K.; Markowitz, Jessica T.; Butler, Deborah A.; Katz, Michelle L.; Laffel, Lori M. B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Sect, Boston, MA 02115 USA. [Rasbach, Lisa E.; Volkening, Lisa K.; Markowitz, Jessica T.; Butler, Deborah A.; Katz, Michelle L.; Laffel, Lori M. B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Adolescent & Young Adult Sect, Boston, MA 02115 USA. [Rasbach, Lisa E.; Volkening, Lisa K.; Markowitz, Jessica T.; Butler, Deborah A.; Katz, Michelle L.; Laffel, Lori M. B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02115 USA. [Rasbach, Lisa E.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [R01DK089349, P30DK036836]; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund; Eleanor Chesterman Beatson Fund FX We thank the families who participated in this investigation and the research staff for their efforts. We would also like to thank Carolyn Jenkins, DrPH, MSN, RD, LD, FAAN, Mathew Gregoski, PhD, and Martina Mueller, PhD, of the Medical University of South Carolina College of Nursing for their helpful comments and suggestions. This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers R01DK089349 and P30DK036836, the Katherine Adler Astrove Youth Education Fund, the Maria Griffin Drury Pediatric Fund, and the Eleanor Chesterman Beatson Fund. NR 33 TC 1 Z9 1 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD MAY 1 PY 2015 VL 17 IS 5 BP 327 EP 334 DI 10.1089/dia.2014.0366 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG7LS UT WOS:000353485700007 PM 25695341 ER PT J AU Coletta, DK Fernandez, M Cersosimo, E Gastaldelli, A Musi, N DeFronzo, RA AF Coletta, D. K. Fernandez, M. Cersosimo, E. Gastaldelli, A. Musi, N. DeFronzo, R. A. TI The effect of muraglitazar on adiponectin signalling, mitochondrial function and fat oxidation genes in human skeletal muscle in vivo SO DIABETIC MEDICINE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; ACTIVATED PROTEIN-KINASE; PLACEBO-CONTROLLED TRIAL; INSULIN SENSITIVITY; GLYCEMIC CONTROL; PPAR-GAMMA; PIOGLITAZONE; METABOLISM; RESISTANCE; RECEPTOR AB AimsThe molecular mechanisms by which muraglitazar (peroxisome proliferator-activated receptor / agonist) improves insulin sensitivity in Type2 diabetes mellitus are not fully understood. We hypothesized that muraglitazar would increase expression of 5-monophosphate-activated protein kinase and genes involved in adiponectin signalling, free fatty acid oxidation and mitochondrial function in skeletal muscle. MethodsSixteen participants with Type2 diabetes received muraglitazar, 5mg/day (n=12) or placebo (n=4). Before and after 16weeks, participants had vastus lateralis muscle biopsy followed by 180min euglycaemic hyperinsulinaemic clamp. ResultsMuraglitazar increased plasma adiponectin (9.01.1 to 17.81.5g/ml, P<0.05), while no significant change was observed with placebo. After 16weeks with muraglitazar, fasting plasma glucose declined by 31%, fasting plasma insulin decreased by 44%, insulin-stimulated glucose disposal increased by 81%, HbA(1c) decreased by 21% and plasma triglyceride decreased by 39% (all P<0.05). Muraglitazar increased mRNA levels of 5-monophosphate-activated protein kinase, adiponectin receptor1, adiponectin receptor2, peroxisome proliferator-activated receptor gamma coactivator-1 alpha and multiple genes involved in mitochondrial function and fat oxidation. In the placebo group, there were no significant changes in expression of these genes. ConclusionsMuraglitazar increases plasma adiponectin, stimulates muscle 5-monophosphate-activated protein kinase expression and increases expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation. These changes represent important cellular mechanisms by which dual peroxisome proliferator-activated receptor agonists improve skeletal muscle insulin sensitivity. What's new? Skeletal muscle insulin resistance is a characteristic feature of Type2 diabetes mellitus. Muraglitazar, a peroxisome proliferator-activated receptor / agonist augments insulin sensitivity, improves -cell function, mobilizes fat out of the liver and muscle, and improves dyslipidaemia. However, the molecular mechanisms by which muraglitazar exert its insulin-sensitizing effect remain unclear. This study demonstrates that muraglitazar increases plasma adiponectin levels and mRNA muscle expression of adiponectin receptors, 5-monophosphate-activated protein kinase and genes involved in mitochondrial function and fat oxidation. To our knowledge, no other study has investigated the molecular actions of muraglitazar in human skeletal muscle. C1 [Coletta, D. K.] Mayo Clin Arizona, Scottsdale, AZ USA. [Coletta, D. K.] Arizona State Univ, Sch Life Sci, Tempe, AZ USA. [Coletta, D. K.] Univ Arizona, Coll Med, Dept Basic Med Sci, Phoenix, AZ USA. [Fernandez, M.; Cersosimo, E.; Gastaldelli, A.; Musi, N.; DeFronzo, R. A.] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78229 USA. [Fernandez, M.; Cersosimo, E.; Musi, N.; DeFronzo, R. A.] Texas Diabet Inst, San Antonio, TX USA. [Gastaldelli, A.] CNR, Inst Clin Physiol, Pisa, Italy. [DeFronzo, R. A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Coletta, DK (reprint author), Mayo Clin Arizona, Scottsdale, AZ USA. EM dawn.coletta@asu.edu RI Coletta, Dawn/G-6382-2016; Gastaldelli, Amalia/H-3319-2014; OI Gastaldelli, Amalia/0000-0003-2594-1651; Coletta, Dawn/0000-0001-5819-5152 FU Bristol Myers Squibb; Veterans Administration Service FX This work was supported by a research grant from Bristol Myers Squibb. Ralph A. DeFronzo's salary is supported by the Veterans Administration Service. NR 30 TC 1 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 EI 1464-5491 J9 DIABETIC MED JI Diabetic Med. PD MAY PY 2015 VL 32 IS 5 BP 657 EP 664 DI 10.1111/dme.12664 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG4BE UT WOS:000353224800013 PM 25484175 ER PT J AU Raghavan, S Porneala, B McKeown, N Fox, CS Dupuis, J Meigs, JB AF Raghavan, Sridharan Porneala, Bianca McKeown, Nicola Fox, Caroline S. Dupuis, Josee Meigs, James B. TI Metabolic factors and genetic risk mediate familial type 2 diabetes risk in the Framingham Heart Study SO DIABETOLOGIA LA English DT Article DE Diet; Family history; Genetic risk; Metabolic syndrome; Physical activity; Type 2 diabetes ID INSULIN-SECRETION; LIFE-STYLE; GLUCOSE-TOLERANCE; PHYSICAL-ACTIVITY; YOUNG ADULTHOOD; GLYCEMIC TRAITS; MELLITUS; ASSOCIATION; PARENTS; HERITABILITY AB Aims/hypothesis Type 2 diabetes mellitus in parents is a strong determinant of diabetes risk in their offspring. We hypothesise that offspring diabetes risk associated with parental diabetes is mediated by metabolic risk factors. Methods We studied initially non-diabetic participants of the Framingham Offspring Study. Metabolic risk was estimated using beta cell corrected insulin response (CIR), HOMA-IR or a count of metabolic syndrome components (metabolic syndrome score [MSS]). Dietary risk and physical activity were estimated using questionnaire responses. Genetic risk score (GRS) was estimated as the count of 62 type 2 diabetes risk alleles. The outcome of incident diabetes in offspring was examined across levels of parental diabetes exposure, accounting for sibling correlation and adjusting for age, sex and putative mediators. The proportion mediated was estimated by comparing regression coefficients for parental diabetes with (beta (adj)) and without (beta (unadj)) adjustments for CIR, HOMA-IR, MSS and GRS (percentage mediated = 1 - beta(adj)/beta(unadj)). Results Metabolic factors mediated 11% of offspring diabetes risk associated with parental diabetes, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.96. GRS mediated 9% of risk, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.99. Conclusions/interpretation Metabolic risk factors partially mediated offspring type 2 diabetes risk conferred by parental diabetes to a similar magnitude as genetic risk. However, a substantial proportion of offspring diabetes risk associated with parental diabetes remains unexplained by metabolic factors, genetic risk, diet and physical activity, suggesting that important familial influences on diabetes risk remain undiscovered. C1 [Raghavan, Sridharan; Porneala, Bianca; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Raghavan, Sridharan; Porneala, Bianca; Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McKeown, Nicola] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA. [Fox, Caroline S.] NHLBI, Lab Metab & Populat Hlth, Framingham, MA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Meigs, JB (reprint author), Harvard Univ, Sch Med, Dept Med, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org FU National Institutes of Health National Research Service [T32HP10251]; Ryoichi Sasakawa Fellowship Fund; NIH [RO1DK78616]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix for genotyping services [N02-HL-6-4278]; USDA [1950-51530-011-00D]; [K24 DK080140] FX SR is supported by National Institutes of Health National Research Service Award T32HP10251 and the Ryoichi Sasakawa Fellowship Fund. JBM and JD are supported by NIH RO1DK78616, and JBM is also supported by K24 DK080140. We gratefully acknowledge the FHS study participants and staff for their contributions. This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix for genotyping services (Contract No. N02-HL-6-4278). NM is supported by USDA agreement number 1950-51530-011-00D. NR 32 TC 1 Z9 1 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2015 VL 58 IS 5 BP 988 EP 996 DI 10.1007/s00125-015-3498-7 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CF6CL UT WOS:000352644200015 PM 25619168 ER PT J AU Renstrom, F Koivula, RW Varga, TV Hallmans, G Mulder, H Florez, JC Hu, FB Franks, PW AF Renstrom, Frida Koivula, Robert W. Varga, Tibor V. Hallmans, Goran Mulder, Hindrik Florez, Jose C. Hu, Frank B. Franks, Paul W. TI Season-dependent associations of circadian rhythm-regulating loci (CRY1, CRY2 and MTNR1B) and glucose homeostasis: the GLACIER Study SO DIABETOLOGIA LA English DT Article DE Circadian rhythm; CRY1; CRY2; GLACIER Study; Glucose homeostasis; MTNR1B; Season ID TYPE-2 DIABETES RISK; INSULIN-SECRETION; VARIANTS; METABOLISM; GENES AB Aims/hypothesis The association of single nucleotide polymorphisms (SNPs) proximal to CRY2 and MTNR1B with fasting glucose is well established. CRY1/2 and MTNR1B encode proteins that regulate circadian rhythmicity and influence energy metabolism. Here we tested whether season modified the relationship of these loci with blood glucose concentration. Methods SNPs rs8192440 (CRY1), rs11605924 (CRY2) and rs10830963 (MTNR1B) were genotyped in a prospective cohort study from northern Sweden (n = 16,499). The number of hours of daylight exposure during the year ranged from 4.5 to 22 h daily. Owing to the non-linear distribution of daylight throughout the year, season was dichotomised based on the vernal and autumnal equinoxes. Effect modification was assessed using linear regression models fitted with a SNP x season interaction term, marginal effect terms and putative confounding variables, with fasting or 2 h glucose concentrations as outcomes. Results The rs8192440 (CRY1) variant was only associated with fasting glucose among participants (n = 2,318) examined during the light season (beta = -0.04 mmol/l per A allele, 95% CI -0.08, -0.01, p = 0.02, p (interaction) = 0.01). In addition to the established association with fasting glucose, the rs11605924 (CRY2) and rs10830963 (MTNR1B) loci were associated with 2 h glucose concentrations (beta = 0.07 mmol/l per A allele, 95% CI 0.03, 0.12, p = 0.0008, n = 9,605, and beta = -0.11 mmol/l per G allele, 95% CI -0.15, -0.06, p < 0.0001, n = 9,517, respectively), but only in participants examined during the dark season (p (interaction) = 0.006 and 0.04, respectively). Repeated measures analyses including data collected 10 years after baseline (n = 3,500) confirmed the results for the CRY1 locus (p (interaction) = 0.01). Conclusions/interpretation In summary, these observations suggest a biologically plausible season-dependent association between SNPs at CRY1, CRY2 and MTNR1B and glucose homeostasis. C1 [Renstrom, Frida; Koivula, Robert W.; Varga, Tibor V.; Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden. [Renstrom, Frida; Hu, Frank B.; Franks, Paul W.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Renstrom, Frida] Umea Univ, Dept Biobank Res, Umea, Sweden. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Sect Nutr Res, Umea, Sweden. [Mulder, Hindrik] Lund Univ, Dept Clin Sci, Unit Mol Metab, Malmo, Sweden. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Med Sect, Umea, Sweden. RP Renstrom, F (reprint author), Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Clin Res Ctr Bldg 91,Level 10, SE-20502 Malmo, Sweden. EM frida.renstrom@med.lu.se OI Koivula, Robert/0000-0002-1646-4163 FU Swedish Heart-Lung Foundation; Swedish Diabetes Association; Pahlsson's Foundation; Swedish Research Council; Umea Medical Research Foundation; Novo Nordisk; Heart Foundation of Northern Sweden; Innovative Medicines Initiative Joint Undertaking [115317 (DIRECT)]; European Union; STAR Novo Nordisk - PhD fellowship FX The GLACIER Study was funded by project grants from the Swedish Heart-Lung Foundation, the Swedish Diabetes Association, the Pahlsson's Foundation, the Swedish Research Council, the Umea Medical Research Foundation, Novo Nordisk and The Heart Foundation of Northern Sweden (all to PWF). RWK was funded by a grant from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115317 (DIRECT) as part of the European Union's Seventh Framework Program (FP7/2007-2013) (to PWF) and a STAR Novo Nordisk co-financed PhD fellowship. FR was supported by a postdoctoral stipend from the Swedish Heart-Lung Foundation. NR 29 TC 4 Z9 4 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2015 VL 58 IS 5 BP 997 EP 1005 DI 10.1007/s00125-015-3533-8 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CF6CL UT WOS:000352644200016 PM 25707907 ER PT J AU Wildfeuer, J Schnell, MW Schulz, C AF Wildfeuer, Janina Schnell, Martin W. Schulz, Christian TI Talking about dying and death: On new discursive constructions of a formerly postulated taboo SO DISCOURSE & SOCIETY LA English DT Article DE Critical discourse analysis; discursive constructions of dying and death; multimodality; taboo ID PALLIATIVE CARE AB In this article, we pursue a critical and multimodal discourse analysis of texts in the context of the innovative German discourse project 30 young people talk to dying people and their relatives' - an initiative by two German universities encouraging young people to develop an explicit attitude towards death. We take a detailed look at the various text forms (short films about discussions between the young people and dying patients, online postings about their experiences, etc.) by asking how the concepts of dying' and death' are new and differently constructed in these various textual artefacts. A formal as well as critical analysis of the semantic content produced by the participants will examine how this content is produced and how new types of sociocultural practices become visible in these texts. C1 [Wildfeuer, Janina] Univ Bremen, Fac Linguist & Literary Sci, D-28359 Bremen, Germany. [Schnell, Martin W.] Univ Witten Herdecke, Philosophy, Witten, Germany. [Schnell, Martin W.] Univ Witten Herdecke, Inst Eth & Commun, D-58448 Witten, Germany. [Schulz, Christian] Harvard Univ, Sch Med, Dept Psychosocial Oncol & Palliat Care, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Schulz, Christian] Univ Dusseldorf, Dusseldorf, Germany. RP Schnell, MW (reprint author), Univ Witten Herdecke, Alfred Herrhausen Str 50, D-58448 Witten, Germany. EM martin.schnell@uni-wh.de FU German Federal Ministry of Education and Research [01GP1177B] FX This research project is based on and refers to a public discourse project funded by the German Federal Ministry of Education and Research (01GP1177B). NR 38 TC 0 Z9 0 U1 3 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0957-9265 EI 1460-3624 J9 DISCOURSE SOC JI niscl. Soc. PD MAY PY 2015 VL 26 IS 3 BP 366 EP 390 DI 10.1177/0957926514564739 PG 25 WC Communication; Psychology, Multidisciplinary; Sociology SC Communication; Psychology; Sociology GA CG7HN UT WOS:000353473700005 ER PT J AU Lynes, MD Schulz, TJ Pan, AJ Tseng, YH AF Lynes, Matthew D. Schulz, Tim J. Pan, Andrew J. Tseng, Yu-Hua TI Disruption of Insulin Signaling in Myf5-Expressing Progenitors Leads to Marked Paucity of Brown Fat but Normal Muscle Development SO ENDOCRINOLOGY LA English DT Article ID ADIPOSE-TISSUE; GENE-EXPRESSION; WHITE ADIPOCYTES; BODY-WEIGHT; RECEPTOR; MICE; DIFFERENTIATION; KNOCKOUT; THERMOGENESIS; ADIPOGENESIS AB Insulin exerts pleiotropic effects on cell growth, survival, and metabolism, and its role in multiple tissues has been dissected using conditional knockout mice; however, its role in development has not been studied. Lineage tracing experiments have demonstrated that interscapular brown adipose tissue (BAT) arises from a Myf5-positive lineage shared with skeletal muscle and distinct from the majority of white adipose tissue (WAT) precursors. In this study, we sought to investigate the effects of impaired insulin signaling in the Myf5-expressing precursor cells by deleting the insulin receptor gene. Mice lacking insulin receptor in the Myf5 lineage (Myf5IRKO) have a decrease of interscapular BAT mass; however, muscle development appeared normal. Histologically, the residual BAT had decreased cell size but appeared mature and potentially functional. Expression of adipogenic inhibitors preadipocyte factor-1, Necdin, and wingless-type MMTV integration site member 10a in the residual BAT tissue was nonetheless increased compared with controls, and there was an enrichment of progenitor cells with impaired adipogenic differentiation capacity, suggesting a suppression of adipogenesis in BAT. Surprisingly, when cold challenged, Myf5IRKO mice did not show impaired thermogenesis. This resistance to cold could be attributed to an increased presence of uncoupling protein 1-positive brown adipocytes in sc WAT as well as increased expression of lipolytic activity in BAT. These data suggest a critical role of insulin signaling in the development of interscapular BAT from Myf5-positive progenitor cells, but it appears to be dispensable for muscle development. They also underscore the importance of compensatory browning of sc WAT in the absence of BAT for thermoregulation. C1 [Lynes, Matthew D.; Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Schulz, Tim J.] German Inst Human Nutr, Dept Adipocyte Dev, D-14558 Potsdam, Germany. [Pan, Andrew J.] Harvard Univ, Stem Cell & Regenerat Biol Dept, Cambridge, MA 02138 USA. [Tseng, Yu-Hua] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Tseng, YH (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM yu-hua.tseng@joslin.harvard.edu RI Schulz, Tim/F-4842-2013 OI Schulz, Tim/0000-0002-8413-3972 FU National Institute of Health (NIH) [R01DK077097, T32DK007260, F32DK102320]; Joslin Diabetes Center's Diabetes Research Center [P30DK036836]; American Diabetes Foundation [ADA 7-12-BS-191]; Harvard Stem Cell Institute; Mary K. Iacocca Foundation; German Research Foundation [DFG SCHU2445/1-1]; Harvard College Research Program FX This work was supported in part by the National Institute of Health (NIH) Grant R01DK077097 (to Y.-H.T.), the Joslin Diabetes Center's Diabetes Research Center Grant P30DK036836, a research grant from the American Diabetes Foundation (ADA 7-12-BS-191), and by funding from the Harvard Stem Cell Institute (to Y.-H.T.). M.D.L. was supported by NIH Fellowships T32DK007260 and F32DK102320. T.J.S. was supported by the Mary K. Iacocca Foundation and the German Research Foundation Grant DFG SCHU2445/1-1. A.J.P. was supported by the Harvard College Research Program. NR 42 TC 1 Z9 1 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 MAY PY 2015 VL 156 IS 5 BP 1637 EP 1647 DI 10.1210/en.2014-1773 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG4RO UT WOS:000353274500007 PM 25625589 ER PT J AU Henry, KE Elfers, CT Burke, RM Chepurny, OG Holz, GG Blevins, JE Roth, CL Doyle, RP AF Henry, Kelly E. Elfers, Clinton T. Burke, Rachael M. Chepurny, Oleg G. Holz, George G. Blevins, James E. Roth, Christian L. Doyle, Robert P. TI Vitamin B-12 Conjugation of Peptide-YY3-36 Decreases Food Intake Compared to Native Peptide-YY3-36 Upon Subcutaneous Administration in Male Rats SO ENDOCRINOLOGY LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; C-FOS EXPRESSION; ORAL DELIVERY; BODY-WEIGHT; BRAIN-STEM; OBESE CHILDREN; RODENT MODELS; VAGUS NERVE; GUT HORMONE; YY3-36 AB Challenges to peptide-based therapies include rapid clearance, ready degradation by hydrolysis/proteolysis, and poor intestinal uptake and/or a need for blood brain barrier transport. This work evaluates the efficacy of conjugation of vitamin B-12 (B-12) on sc administered peptide tyrosine tyrosine (PYY)(3-36) function. In the current experiments, a B-12-PYY3-36 conjugate was tested against native PYY3-36, and an inactive conjugate B-12-PYYC36 (null control) in vitro and in vivo. In vitro experiments demonstrated similar agonism for the neuropeptide Y2 receptor by the B-12-PYY3-36 conjugate (EC50 26.5nM) comparedwith native PYY3-36(EC50 16.0 nM), with the null control having an EC50 of 1.8 mu M. In vivo experiments were performed in young adult male Sprague Dawley rats (9 wk). Daily treatments were delivered sc in five 1-hour pulses, each pulse delivering 5-10 nmol/kg, by implanted microinfusion pumps. Increases in hindbrain Fos expression were comparable 90 minutes after B-12-PYY3-36 or PYY3-36 injection relative to saline or B-12-PYYC36. Food intake was reduced during a 5-day treatment for both B-12-PYY3-36- (24%, P = .001) and PYY3-36-(13%, P = .008) treated groups relative to baseline. In addition, reduction of food intake after the three dark cycle treatment pulses was more consistent with B-12-PYY3-36 treatment (-26%, -29%, -27%) compared with the PYY3-36 treatment (-3%, -21%, -16%), and B-12-PYY3-36 generated a significantly longer inhibition of food intake vs PYY3-36 treatment after the first two pulses (P = .041 and P = .036, respectively). These findings demonstrate a stronger, more consistent, and longer inhibition of food intake after the pulses of B-12-PYY3-36 conjugate compared with the native PYY3-36. C1 [Henry, Kelly E.; Burke, Rachael M.; Doyle, Robert P.] Syracuse Univ, Ctr Sci & Technol, Dept Chem, Syracuse, NY 13244 USA. [Elfers, Clinton T.; Roth, Christian L.] Seattle Childrens Res Inst, Div Endocrinol, Ctr Integrat Brain Res, Seattle, WA 98101 USA. [Chepurny, Oleg G.; Holz, George G.; Doyle, Robert P.] SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. [Holz, George G.] SUNY Upstate Med Univ, Dept Pharmacol, Syracuse, NY 13210 USA. [Blevins, James E.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA 98108 USA. [Blevins, James E.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Roth, Christian L.] Univ Washington, Dept Pediat, Div Endocrinol, Seattle, WA 98105 USA. RP Doyle, RP (reprint author), Syracuse Univ, Ctr Sci & Technol, Dept Chem, 111 Coll Pl, Syracuse, NY 13244 USA. EM christian.roth@seattlechildrens.org; rpdoyle@syr.edu FU National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health/Department of Health and Human Services [NIH-R15DK097675-01A1]; Arnold and Mabel Beckman Foundation; Department of Veterans Affairs Merit Review Research Program; 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 and National Institutes of Health [P30DK017047] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health/Department of Health and Human Services Grant NIH-R15DK097675-01A1 (to R.P.D. and C.L.R.), the Arnold and Mabel Beckman Foundation (to R.P.D.), and by the Department of Veterans Affairs Merit Review Research Program (to J.E.B.). Additional support included 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 National Institutes of Health Grant P30DK017047. NR 46 TC 5 Z9 5 U1 2 U2 9 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 MAY PY 2015 VL 156 IS 5 BP 1739 EP 1749 DI 10.1210/en.2014-1825 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG4RO UT WOS:000353274500016 PM 25658456 ER PT J AU Schadendorf, D Amonkar, MM Stroyakovskiy, D Levchenko, E Gogas, H de Braud, F Grob, JJ Bondarenko, I Garbe, C Lebbe, C Larkin, J Chiarion-Sileni, V Millward, M Arance, A Mandala, M Flaherty, KT Nathan, P Ribas, A Robert, C Casey, M DeMarini, DJ Irani, JG Aktan, G Long, GV AF Schadendorf, Dirk Amonkar, Mayur M. Stroyakovskiy, Daniil Levchenko, Evgeny Gogas, Helen de Braud, Filippo Grob, Jean-Jacques Bondarenko, Igor Garbe, Claus Lebbe, Celeste Larkin, James Chiarion-Sileni, Vanna Millward, Michael Arance, Ana Mandala, Mario Flaherty, Keith T. Nathan, Paul Ribas, Antoni Robert, Caroline Casey, Michelle DeMarini, Douglas J. Irani, Jhangir G. Aktan, Gursel Long, Georgina V. TI Health-related quality of life impact in a randomised phase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Melanoma; Protein kinase inhibitors; Molecular targeted therapy; Proto-oncogene proteins; B-raf; Dabrafenib; Trametinib ID HIGH-RISK MELANOMA; EUROPEAN-ORGANIZATION; DOSE INTERFERON-ALPHA-2B; QUESTIONNAIRE QLQ-C30; IMPROVED SURVIVAL; MUTATED MELANOMA; CONTROLLED-TRIAL; MEK INHIBITION; CANCER; VEMURAFENIB AB Aim: To present the impact of treatments on health-related quality of life (HRQoL) from the double-blind, randomised phase III COMBI-d study that investigated the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600E/K-mutant metastatic melanoma. COMBI-d showed significantly prolonged progression-free survival for the combination. Methods: HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, a generic cancer questionnaire (completed at baseline, during study treatment, at progression and post progression) assessing various dimensions (global health/QoL, functional status, and symptom impact). A mixed-model, repeated-measures analyses of covariance evaluated differences between arms. Results: Questionnaire completion rates were >95% at baseline, >85% to week 40 and >70% at disease progression. Baseline scores across both arms were comparable for all dimensions. Global health dimension scores were significantly better at weeks 8, 16 and 24 for patients receiving the combination during treatment and at progression. The majority of functional dimension scores (physical, social, role, emotional and cognitive functioning) trended in favour of the combination. Pain scores were significantly improved and clinically meaningful (6-13 point difference) for patients receiving the combination for all follow-up assessments versus those receiving dabrafenib monotherapy. For other symptom dimensions (nausea and vomiting, diarrhoea, dyspnoea, and constipation), scores trended in favour of dabrafenib monotherapy. Conclusion: This analysis demonstrates that the combination of dabrafenib and trametinib provides better preservation of HRQoL and pain improvements versus dabrafenib monotherapy while also delaying progression. (Clinicaltrials.gov registration number: NCT01584648). (C) 2015 Elsevier Ltd. All rights reserved. C1 [Schadendorf, Dirk] Univ Klinikum Essen, D-45147 Essen, Germany. [Amonkar, Mayur M.; Casey, Michelle; DeMarini, Douglas J.; Irani, Jhangir G.; Aktan, Gursel] GlaxoSmithKline, Collegeville, PA 19426 USA. [Stroyakovskiy, Daniil] Moscow City Oncol Hosp 62, Moscow 143423, Russia. [Levchenko, Evgeny] Petrov Res Inst Oncol, St Petersburg 197758, Russia. [Gogas, Helen] Univ Athens, Athens 11527, Greece. [de Braud, Filippo] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Grob, Jean-Jacques] Ctr Hosp Univ St Marguerite, Serv Dermatol, F-13009 Marseille, France. [Bondarenko, Igor] Dnepropetrovsk State Med Acad, UA-49044 Dnepropetrovsk, Ukraine. [Garbe, Claus] Univ Tubingen Hosp, Dept Dermatol, D-72076 Tubingen, Germany. [Lebbe, Celeste] Univ Paris Diderot, INSERM, U976, Hop St Louis,APHP,Dermatol CIC, F-75010 Paris, France. [Larkin, James] Royal Marsden Hosp, London SW3 6JJ, England. [Chiarion-Sileni, Vanna] Veneto Oncol Inst IRCCS, Melanoma & Esophageal Oncol Unit, I-35128 Padua, Italy. [Millward, Michael] Sir Charles Gairdner Hosp, Perth, WA 6009, Australia. [Arance, Ana] Hosp Clin Barcelona, E-08036 Barcelona, Spain. [Mandala, Mario] Papa Giovanni XIII Hosp, I-24127 Bergamo, Italy. [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Nathan, Paul] Mt Vernon Canc Ctr, Northwood HA6 2RN, Middx, England. [Ribas, Antoni] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Robert, Caroline] Gustave Roussy, F-94805 Villejuif, France. [Robert, Caroline] Univ Paris 11, F-94805 Villejuif, France. [Long, Georgina V.] Melanoma Inst Australia, Sydney, NSW 2060, Australia. [Long, Georgina V.] Univ Sydney, Sydney, NSW 2060, Australia. RP Schadendorf, D (reprint author), Univ Klinikum Essen, Dept Dermatol, Hufelandstr 55, D-45147 Essen, Germany. EM Dirk.Schadendorf@uk-essen.de; mayur.m.amonkar@gsk.com; sdaniel@mail.ru; levchenko@newmail.ru; hgogas@hol.gr; filippo.debraud@istitutotumori.mi.it; jean-jacques.grob@ap-hm.fr; oncology@dsma.dp.ua; claus.garbe@med.uni-tuebingen.de; celeste.lebbe@sls.aphp.fr; james.larkin@rmh.nhs.uk; mgaliz@tiscali.it; michael.millward@uwa.edu.au; amarance@clinic.ub.es; mmandala@hpg23.it; kflaherty@partners.org; p.nathan@nhs.net; aribas@mednet.ucla.edu; Caroline.Robert@igr.fr; meshellcasey@yahoo.com; douglas.j.demarini@gsk.com; jhangir.g.irani@gsk.com; gursel.aktan@gmail.com; georgina.long@sydney.edu.au RI de Braud, Filippo/B-9997-2017; OI de Braud, Filippo/0000-0003-0103-730X; Bondarenko, Igor/0000-0002-7071-2471 FU GlaxoSmithKline [NCT01584648] FX Funding for this study was provided by GlaxoSmithKline (NCT01584648). All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. The authors wish to acknowledge all the patients, families, investigators and staff at the sites involved in the COMBI-d (MEK115306) clinical trial. Editorial support in the form of collating author comments and copyediting was provided by SciMentum and was funded by GlaxoSmithKline. NR 26 TC 17 Z9 18 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD MAY PY 2015 VL 51 IS 7 BP 833 EP 840 DI 10.1016/j.ejca.2015.03.004 PG 8 WC Oncology SC Oncology GA CG1LT UT WOS:000353034800006 PM 25794603 ER PT J AU Jaeger, M van der Lee, R Cheng, SC Johnson, MD Kumar, V Ng, A Plantinga, TS Smeekens, SP Oosting, M Wang, X Barchet, W Fitzgerald, K Joosten, LAB Perfect, JR Wijmenga, C van de Veerdonk, FL Huynen, MA Xavier, RJ Kullberg, BJ Netea, MG AF Jaeger, M. van der Lee, R. Cheng, S-C. Johnson, M. D. Kumar, V. Ng, A. Plantinga, T. S. Smeekens, S. P. Oosting, M. Wang, X. Barchet, W. Fitzgerald, K. Joosten, L. A. B. Perfect, J. R. Wijmenga, C. van de Veerdonk, F. L. Huynen, M. A. Xavier, R. J. Kullberg, B. J. Netea, M. G. TI The RIG-I-like helicase receptor MDA5 (IFIH1) is involved in the host defense against Candida infections SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article DE Candida albicans; Host defense; Candidemia; Genetic susceptibility; MDA5; IFIH1 ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; NOSOCOMIAL CANDIDEMIA; STAT1 MUTATIONS; UNITED-STATES; HUMAN GENOME; POLYMORPHISMS; ALBICANS; SUSCEPTIBILITY; RECOGNITION; ASSOCIATION AB The induction of host defense against Candida species is initiated by recognition of the fungi by pattern recognition receptors and activation of downstream pathways that produce inflammatory mediators essential for infection clearance. In this study, we present complementary evidence based on transcriptome analysis, genetics, and immunological studies in knockout mice and humans that the cytosolic RIG-I-like receptor MDA5 (IFIH1) has an important role in the host defense against C. albicans. Firstly, IFIH1 expression in macrophages is specifically induced by invasive C. albicans hyphae, and patients suffering from chronic mucocutaneous candidiasis (CMC) express lower levels of MDA5 than healthy controls. Secondly, there is a strong association between missense variants in the IFIH1 gene (rs1990760 and rs3747517) and susceptibility to systemic Candida infections. Thirdly, cells from Mda5 knockout mice and human peripheral blood mononuclear cells (PBMCs) with different IFIH1 genotypes display an altered cytokine response to C. albicans. These data strongly suggest that MDA5 is involved in immune responses to Candida infection. As a receptor for viral RNA, MDA5 until now has been linked to antiviral host defense, but these novel studies show unexpected effects in antifungal immunity as well. Future studies are warranted to explore the potential of MDA5 as a novel target for immunotherapeutic strategies. C1 [Jaeger, M.; Cheng, S-C.; Plantinga, T. S.; Smeekens, S. P.; Oosting, M.; Wang, X.; Joosten, L. A. B.; van de Veerdonk, F. L.; Kullberg, B. J.; Netea, M. G.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med 463, NL-6500 HB Nijmegen, Netherlands. [van der Lee, R.; Huynen, M. A.] Radboud Univ Nijmegen, Med Ctr, Ctr Mol & Biomol Informat, Radboud Inst Mol Life Sci, NL-6500 HB Nijmegen, Netherlands. [Johnson, M. D.; Perfect, J. R.] Duke Univ, Med Ctr, Div Infect Dis, Durham, NC USA. [Johnson, M. D.] Campbell Univ, Dept Clin Res, Coll Pharm & Hlth Sci, Buies Creek, NC 27506 USA. [Kumar, V.; Wijmenga, C.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Ng, A.; Xavier, R. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Ng, A.; Xavier, R. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ng, A.; Xavier, R. J.] Broad Inst MIT & Harvard Univ, Cambridge, MA 02142 USA. [Barchet, W.] Univ Bonn, Inst Clin Chem & Clin Pharmacol, Univ Hosp Bonn, Bonn, Germany. [Fitzgerald, K.] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. RP Netea, MG (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Internal Med 463, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM mihai.netea@radboudumc.nl RI Plantinga, Theo/A-6895-2015; Joosten, Leo/H-3138-2015; Cheng, Shih-Chin/H-4567-2015; Smeekens, Sanne/G-8307-2011; Kullberg, Bart Jan/C-8520-2013; Netea, Mihai/N-5155-2014; Huynen, Martijn/A-1530-2014; van der Lee, Robin/P-6920-2015; van de Veerdonk, Frank/C-7256-2008; Jaeger, Martin/H-3359-2015; Oosting, Marije/H-7437-2015 OI Johnson, Melissa/0000-0002-6606-9460; Cheng, Shih-Chin/0000-0003-1251-8774; Smeekens, Sanne/0000-0002-7835-914X; van der Lee, Robin/0000-0001-7391-9438; van de Veerdonk, Frank/0000-0002-1121-4894; FU ERC Consolidator Grant [310372]; Virgo Consortium - Dutch government [FES0908]; Netherlands Genomics Initiative [050-060-452]; ERC Advanced Grant [ERC-671274]; NSFC [11101321, 61263039] FX We thank Martin Oti for the helpful discussions. MJ and MGN were supported by an ERC Consolidator Grant (nr. 310372 to MGN). RvdL and MAH were supported by the Virgo Consortium, funded by the Dutch government (FES0908), and by the Netherlands Genomics Initiative (050-060-452). CW was supported by the ERC Advanced Grant, ERC-671274. XW was supported by NSFC 11101321 and NSFC 61263039 grants. NR 50 TC 9 Z9 9 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0934-9723 EI 1435-4373 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD MAY PY 2015 VL 34 IS 5 BP 963 EP 974 DI 10.1007/s10096-014-2309-2 PG 12 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA CG7GK UT WOS:000353470600014 PM 25579795 ER PT J AU Saggese, G Vierucci, F Boot, AM Czech-Kowalska, J Weber, G Camargo, CA Mallet, E Fanos, M Shaw, NJ Holick, MF AF Saggese, Giuseppe Vierucci, Francesco Boot, Annemieke M. Czech-Kowalska, Justyna Weber, Giovanna Camargo, Carlos A., Jr. Mallet, Eric Fanos, Margherita Shaw, Nick J. Holick, Michael F. TI Vitamin D in childhood and adolescence: an expert position statement SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Review DE Vitamin D; 25-Hydroxyvitamin D; Children; Adolescents; Supplementation ID RANDOMIZED-CONTROLLED-TRIAL; SERUM 25-HYDROXYVITAMIN D; BREAST-FED INFANTS; BONE-MINERAL DENSITY; FORMULA-FED INFANTS; D SUPPLEMENTATION; D DEFICIENCY; NUTRITIONAL RICKETS; PRETERM INFANTS; PARATHYROID-HORMONE AB Vitamin D is a key hormone in the regulation of calcium and phosphorus metabolism and plays a pivotal role in bone health, particularly during pediatric age when nutritional rickets and impaired bone mass acquisition may occur. Great interest has been placed in recent years on vitamin D's extraskeletal actions. However, while recent data suggest a possible role of vitamin D in the pathogenesis of several pathological conditions, including infectious and autoimmune diseases, the actual impact of vitamin D status on the global health of children and adolescents, other than bone, remains a subject of debate. In the meantime, pediatricians still need to evaluate the determinants of vitamin D status and consider vitamin D supplementation in children and adolescents at risk of deficiency. This review is the result of an expert meeting that was held during the congress "Update on vitamin D and bone disease in childhood" convened in Pisa, Italy, in May 2013. Conclusion: The collaboration of the international group of experts produced this "state of the art" review on vitamin D in childhood and adolescence. After dealing with vitamin D status and its determinants, the review outlines the current debate on vitamin D's health benefits, concluding with a practical approach to vitamin D supplementation during childhood and adolescence. C1 [Saggese, Giuseppe; Fanos, Margherita] Univ Hosp, Pediat Endocrine Unit, Dept Pediat, I-56126 Pisa, Italy. [Vierucci, Francesco] San Luca Hosp, Pediat Unit, Lucca, Italy. [Boot, Annemieke M.] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat,Div Endocrinol, NL-9700 AB Groningen, Netherlands. [Czech-Kowalska, Justyna] Childrens Mem Hlth Inst, Dept Neonatol & Neonatal Intens Care, Warsaw, Poland. [Weber, Giovanna] Univ Vita Salute San Raffaele, San Raffaele Sci Ist, Dept Pediat, Milan, Italy. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Mallet, Eric] Univ Hosp Charles Nicolle, Dept Pediat, Rouen, France. [Shaw, Nick J.] Birmingham Childrens Hosp, Dept Endocrinol & Diabet, Birmingham, W Midlands, England. [Holick, Michael F.] Boston Univ, Med Ctr, Dept Med, Sect Endocrinol Nutr & Diabet & Vitamin D Skin, Boston, MA USA. [Holick, Michael F.] Boston Univ, Med Ctr, Bone Res Lab, Boston, MA USA. RP Saggese, G (reprint author), Univ Hosp, Pediat Endocrine Unit, Dept Pediat, Via Roma 67, I-56126 Pisa, Italy. EM giuseppe.saggese@med.unipi.it; vieruf@hotmail.it; a.m.boot@umcg.nl; j.kowalska@czd.pl; giovanna.weber@hsr.it; ccamargo@partners.org; eric.mallet@chu-rouen.fr; margherita.fanos@gmail.com; nick.shaw@bch.nhs.uk; mfholick@bu.edu OI WEBER, Giovanna/0000-0002-2172-381X NR 97 TC 16 Z9 17 U1 3 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6199 EI 1432-1076 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD MAY PY 2015 VL 174 IS 5 BP 565 EP 576 DI 10.1007/s00431-015-2524-6 PG 12 WC Pediatrics SC Pediatrics GA CG4XU UT WOS:000353293600001 PM 25833762 ER PT J AU Ananthakrishnan, AN Kane, SV AF Ananthakrishnan, Ashwin N. Kane, Sunanda V. TI The Toronto Consensus Guidelines for Nonhospitalized Ulcerative Colitis: A Welcome Update but Not the End of the Story SO GASTROENTEROLOGY LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; COMBINATION THERAPY; RANDOMIZED-TRIAL; INFLIXIMAB; AZATHIOPRINE; MAINTENANCE; IMMUNOSUPPRESSION; GASTROENTEROLOGY; METHOTREXATE C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. [Kane, Sunanda V.] Mayo Clin, Rochester, MN USA. RP Ananthakrishnan, AN (reprint author), MGH Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU NIDDK NIH HHS [K23DK097142] NR 25 TC 0 Z9 0 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 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2015 VL 148 IS 5 BP 877 EP 880 DI 10.1053/j.gastro.2015.03.025 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CG5MJ UT WOS:000353335700010 PM 25805424 ER PT J AU O'Keeffe, MS Song, JH Liao, GX De Calisto, J Halibozek, PJ Mora, JR Bhan, AK Wang, N Reinecker, HC Terhorst, C AF O'Keeffe, Michael S. Song, Joo-Hye Liao, Gongxian De Calisto, Jaime Halibozek, Peter J. Mora, J. Rodrigo Bhan, Atul K. Wang, Ninghai Reinecker, Hans-Christian Terhorst, Cox TI SLAMF4 Is a Negative Regulator of Expansion of Cytotoxic Intraepithelial CD8(+) T Cells That Maintains Homeostasis in the Small Intestine SO GASTROENTEROLOGY LA English DT Article DE Immune Regulation; Intestinal Epithelium; T-Cell Development; Immunity ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INFLAMMATORY-BOWEL-DISEASE; NATURAL-KILLER-CELLS; CUTTING EDGE; FAMILY RECEPTORS; DENDRITIC CELLS; 2B4 CD244; ACTIVATION; COLITIS; MACROPHAGES AB BACKGROUND & AIMS: Intraepithelial T lymphocyte cells (IEL) are the first immune cells to respond to pathogens; they help maintain the integrity of the epithelial barrier. We studied the function of the mouse glycoprotein Signaling Lymphocyte Activation Molecule Family receptor (SLAMF) 4 (encoded by Slamf4) on the surface of CD8 alpha beta alpha beta T-cell receptor (TCR)(+) IELs, and the roles of these cells in homeostasis of the small intestine in mice. METHODS: SLAMF4 CD8(+) alpha beta TCR+ cells isolated from spleens of OT-I Rag1(-/-) mice were induced to express gut- homing receptors and transferred to C57BL/6J mice; levels of SLAMF4(+) cells were measured in small intestine tissues. After administration of anti- CD3 or antigen, with or without anti- SLAM4, to C57BL/6J and Slamf4(-/-) mice, CD8 alpha beta alpha beta TCR+ IELs were collected; cytokine production and cytotoxicity were measured. Depletion of CX3CR1(+) phagocytes was assessed in mice by live- cell confocal imaging or by cytofluorometry; small intestine tissues were analyzed by histology and inflammation was quantified. RESULTS: Splenic CD8(+) alpha beta TCR+ cells began to express SLAMF4 only after migrating to the small intestine. Injection of C57BL/6J mice with anti- SLAMF4 and anti- CD3 increased levels of interleukin 10 and interferon gamma secretion by IEL