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Portland, OR, United States

Turner E.H.,Oregon Health And Science University | Turner E.H.,Portland Veterans Affairs Medical Center | Knoepflmacher D.,Oregon Health And Science University | Shapley L.,Oregon Health And Science University
PLoS Medicine | Year: 2012

Background: Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e.g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine whether publication bias is present and quantify the extent to which it inflates apparent drug efficacy. Methods and Findings: FDA Drug Approval Packages for eight second-generation antipsychotics-aripiprazole, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting injection (risperidone LAI), and ziprasidone-were used to identify a cohort of 24 FDA-registered premarketing trials. The results of these trials according to the FDA were compared with the results conveyed in corresponding journal articles. The relationship between study outcome and publication status was examined, and effect sizes derived from the two data sources were compared. Among the 24 FDA-registered trials, four (17%) were unpublished. Of these, three failed to show that the study drug had a statistical advantage over placebo, and one showed the study drug was statistically inferior to the active comparator. Among the 20 published trials, the five that were not positive, according to the FDA, showed some evidence of outcome reporting bias. However, the association between trial outcome and publication status did not reach statistical significance. Further, the apparent increase in the effect size point estimate due to publication bias was modest (8%) and not statistically significant. On the other hand, the effect size for unpublished trials (0.23, 95% confidence interval 0.07 to 0.39) was less than half that for the published trials (0.47, 95% confidence interval 0.40 to 0.54), a difference that was significant. Conclusions: The magnitude of publication bias found for antipsychotics was less than that found previously for antidepressants, possibly because antipsychotics demonstrate superiority to placebo more consistently. Without increased access to regulatory agency data, publication bias will continue to blur distinctions between effective and ineffective drugs. Please see later in the article for the Editors' Summary. Source

Qaseem A.,The American College | Barry M.J.,Massachusetts General Hospital | Kansagara D.,Portland Veterans Affairs Medical Center
Annals of Internal Medicine | Year: 2016

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness of treatment with second-generation antidepressants versus nonpharmacologic treatments for major depressive disorder in adults. Methods: This guideline is based on a systematic review of published, English-language, randomized, controlled trials from 1990 through September 2015 identified using several databases and through hand searches of references of relevant studies. Interventions evaluated include psychotherapies, complementary and alternative medicines (including acupuncture,-3 fatty acids, S-adenosyl-L-methionine, St. John's wort [Hypericum perforatum]), exercise, and second-generation antidepressants. Evaluated outcomes included response, remission, functional capacity, quality of life, reduction of suicidality or hospitalizations, and harms. The target audience for this guideline includes all clinicians, and the target patient population includes adults with major depressive disorder. This guideline grades the evidence and recommendations using ACP's clinical practice guidelines grading system. Recommendation: ACP recommends that clinicians select between either cognitive behavioral therapy or second-generation antidepressants to treat patients with major depressive disorder after discussing treatment effects, adverse effect profiles, cost, accessibility, and preferences with the patient (Grade: strong recommendation, moderate-quality evidence). © 2016 American College of Physicians. Source

Subramanya A.R.,University of Pittsburgh | Ellison D.H.,Oregon Health And Science University | Ellison D.H.,Portland Veterans Affairs Medical Center
Clinical Journal of the American Society of Nephrology | Year: 2014

The distal convoluted tubule is the nephron segment that lies immediately downstream of the macula densa. Although short in length, the distal convoluted tubule plays a critical role in sodium, potassium, and divalent cation homeostasis. Recent genetic and physiologic studies have greatly expanded our understanding of how the distal convoluted tubule regulates these processes at the molecular level. This article provides an update on the distal convoluted tubule, highlighting concepts and pathophysiology relevant to clinical practice. Copyright © 2014 by the American Society of Nephrology. Source

Shen K.-Z.,Oregon Health And Science University | Johnson S.W.,Oregon Health And Science University | Johnson S.W.,Portland Veterans Affairs Medical Center
Journal of Neuroscience | Year: 2010

Excessive burst firing of action potentials in subthalamic nucleus (STN) neurons has been correlated with the bradykinesia and rigidity seen in Parkinson's disease. Consequently, there is much interest in characterizing mechanisms that promote burst firing, such as the regulation of NMDA receptor function. Using whole-cell recording techniques in rat brain slices, we report that inward currents evoked by NMDA are greatly potentiated by ATP-sensitive K+ (K-ATP) channel blocking agents in STN neurons but not in dopamine neurons in the substantia nigra. Moreover, we found that the ability of NMDA to evoke K-ATP current was blocked by inhibitors of nitric oxide synthase, guanylyl cyclase, and calcium/calmodulin. By altering firing patterns of STN neurons, this NMDA/K-ATP interaction may exert an important influence on basal ganglia output and thereby affect the clinical expression of Parkinson's disease. Copyright © 2010 the authors. Source

Qaseem A.,The American College | Humphrey L.L.,Portland Veterans Affairs Medical Center | Chou R.,Oregon Health And Science University | Snow V.,Pfizer | Shekelle P.,West Los Angeles Veterans Affairs Medical Center
Annals of Internal Medicine | Year: 2011

Description: The American College of Physicians (ACP) developed this guideline to present the evidence for the link between the use of intensive insulin therapy to achieve different glycemic targets and health outcomes in hospitalized patients with or without diabetes mellitus. Methods: Published literature on this topic was identified by using MEDLINE and the Cochrane Library. Additional articles were obtained from systematic reviews and the reference lists of pertinent studies, reviews, and editorials, as well as by consulting experts; unpublished studies on ClinicalTrials.gov were also identified. The literature search included studies published from 1950 through March 2009. Searches were limited to English-language publications. The primary outcomes of interest were short-term mortality and hypoglycemia. This guideline grades the evidence and recommendations by using the ACP clinical practice guidelines grading system. Recommendation 1: ACP recommends not using intensive insulin therapy to strictly control blood glucose in non-surgical intensive care unit (SICU)/medical intensive care unit (MICU) patients with or without diabetes mellitus (Grade: strong recommendation, moderate-quality evidence). Recommendation 2: ACP recommends not using intensive insulin therapy to normalize blood glucose in SICU/MICU patients with or without diabetes mellitus (Grade: strong recommendation, highquality evidence). Recommendation 3: ACP recommends a target blood glucose level of 7.8 to 11.1 mmol/L (140 to 200 mg/dL) if insulin therapy is used in SICU/MICU patients (Grade: weak recommendation, moderate-quality evidence). © 2011 American College of Physicians. Source

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