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BACKGROUND Trials of statin therapy have had conflicting findings on the risk of development of diabetes mellitus in patients given statins. We aimed to establish by a meta-analysis of published and unpublished data whether any relation exists between statin use and development of diabetes. METHODS We searched Medline, Embase, and the Cochrane Central(More)
A study was made of the relation between tinnitus masker composition (frequency, bandwidth, intensity duration) and the time course and magnitude of residual inhibition (RI). RI was determined by methods of (a) loudness estimation - where the subject varied the pointer position on a loudness scale (b) loudness balance - where the tinnitus loudness was(More)
The increasing availability of personal genomic tests has led to discussions about the validity and utility of such tests and the balance of benefits and harms. A multidisciplinary workshop was convened by the National Institutes of Health and the Centers for Disease Control and Prevention to review the scientific foundation for using personal genomics in(More)
BACKGROUND For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard(More)
Interim analyses have become an essential part of the monitoring process of clinical trials. Stochastic curtailment has been used in such analyses. This procedure allows for calculation of the probability of rejecting the null hypothesis at the end of a trial given the current data and assuming the null or an alternative hypothesis for the remainder of the(More)
BACKGROUND Randomized clinical trials, particularly for comparative effectiveness research (CER), are frequently criticized for being overly restrictive or untimely for health-care decision making. PURPOSE Our prospectively designed REsearch in ADAptive methods for Pragmatic Trials (RE-ADAPT) study is a 'proof of concept' to stimulate investment in(More)
OBJECTIVES MMP-9 and -12 function in tissue remodeling and may play roles in cardiovascular disease (CVD). We assessed associations of four MMP polymorphisms and three antihypertensive drugs with cardiovascular outcomes. METHODS Hypertensives (n = 42,418) from a double-blind, randomized, clinical trial were randomized to chlorthalidone, amlodipine,(More)
The findings of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) have generated worldwide reaction from clinicians and researchers, including a recent commentary in this journal. Such response was expected for a trial of ALLHAT's size and scope, especially since its results challenged some widely held beliefs. This(More)
Background: The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, double-blind, active-controlled trial designed to compare the rate of coronary heart disease events in high-risk hypertensive participants initially randomized to a diuretic (chlorthalidone) versus each of three alternative antihypertensive(More)
Nitric oxide synthase 3 (NOS3) catalyzes production of NO in the endothelium and may play a role in cardiovascular disease (CVD). We assessed the pharmacogenetic associations of three NOS3 polymorphisms and three antihypertensive drugs with CVD outcomes. Hypertensive subjects (n = 30,280) from a multi-center, double-blind clinical trial were randomized to(More)