Effect of Bile Acid Sequestrants on Glycaemic Control: Protocol for a Systematic Review With Meta-Analysis of Randomised Controlled Trials.

Effect of bile acid sequestrants on glycaemic control: protocol for a systematic review with meta-analysis of randomised controlled trials.

Filed under: Drug and Alcohol Rehabilitation

BMJ Open. 2012; 2(6):
Hansen M, Sonne DP, Mikkelsen KH, Gluud LL, Vilsbøll T, Knop FK

INTRODUCTION: In addition to the lipid-lowering effect of bile acid sequestrants (BASs), they also lower blood glucose and, therefore, could be beneficial in the treatment of patients with type 2 diabetes mellitus (T2DM). Three oral BASs are approved by the US Food and Drug Administration (FDA) for the treatment of hypercholesterolaemia: colestipol, cholestyramine and colesevelam. The BAS colestimide/colestilan is used in Japan. Colesevelam was recently approved by the FDA for the treatment of T2DM. We plan to provide a systematic review with meta-analysis of the glucose-lowering effect of BASs with the aim to evaluate their potential as glucose-lowering agents in patients with T2DM. METHODS AND ANALYSIS: In accordance with the preferred reporting items for systematic reviews and meta-analyses statement, a systematic review with meta-analysis of randomised clinical trials of BASs (vs placebo, oral antidiabetes drugs or insulin), reporting measures of glycaemic control in adult patients with T2DM, will be performed. Change in glycated haemoglobin constitutes the primary endpoint, and secondary endpoints include changes in fasting plasma glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglycerides, body weight and body mass index and adverse events. Electronic searches will be performed in The Cochrane Library, MEDLINE and EMBASE, along with manual searches in the reference lists of relevant papers. The analyses will be performed based on individual patient data and summarised data. The primary meta-analysis will be performed using random effects models owing to expected intertrial heterogeneity. Dichotomous data will be analysed using risk difference and continuous data using weighted mean differences, both with 95% CIs. ETHICS AND DISSEMINATION: The study will evaluate the potential of BASs as glucose-lowering agents and possibly contribute to the clinical management of patients with T2DM. RESULTS: The study will be disseminated by peer-review publication and conference presentation. PROTOCOL REGISTRATION: PROSPERO CRD42012002552.
HubMed – drug

A randomised efficacy and discontinuation study of etanercept versus adalimumab (RED SEA) for rheumatoid arthritis: a pragmatic, unblinded, non-inferiority study of first TNF inhibitor use: outcomes over 2 years.

Filed under: Drug and Alcohol Rehabilitation

BMJ Open. 2012; 2(6):
Jobanputra P, Maggs F, Deeming A, Carruthers D, Rankin E, Jordan AC, Faizal A, Goddard C, Pugh M, Bowman SJ, Brailsford S, Nightingale P

To compare adalimumab versus etanercept in patients with active rheumatoid arthritis (RA) to test the hypothesis that adalimumab was not inferior to etanercept in terms of drug continuation by a margin of 15% after 52 weeks of treatment.Pragmatic, randomised, parallel group, multicentre, unblinded and non-inferiority trial. Randomisation stratified by baseline use of methotrexate.125 adults with active RA despite treatment with two disease-modifying drugs (DMARDs), including methotrexate randomised (1?:?1) to adalimumab 40 mg alternate weeks or etanercept 50 mg weekly, added to existing medication.The primary outcome was proportion of patients continuing treatment after 52 weeks. Secondary outcomes included: disease activity score using 28 joints (DAS28), treatment satisfaction (TSQM V.2), health status (Euroqol-5D), drug toxicity and persistence with therapy after 2 years.Persistence with therapy was 65% for adalimumab versus 56.7% for etanercept (one-sided 95% CI for proportion still taking adalimumab minus proportion on etanercept ?-7.9%); demonstrating non-inferiority at the 15% margin. After 2 years these figures were: adalimumab 58.3% and etanecept 43.3% (CI ?-1.7%). The proportion of good, moderate and non-responders based on DAS28-C reactive protein, after 52 weeks, were 26.3%, 33.3% and 40.4%, respectively, for adalimumab versus 16.7%, 31.7% and 51.7%, respectively, for etanercept (p=0.158). Baseline median EQ-5D scores improved from 0.52 to 0.69 for adalimumab and from 0.52 to 0.64 for etanercept (p=0.046) after 52 weeks. Global satisfaction, effectiveness, side effects and convenience scores based on the TSQM were similar for both drugs. Fourteen serious adverse events occurred including two deaths from myocardial infarction, one patient with ovarian cancer and one with acute myeloid leukaemia.Clinicians choosing a first tumour necrosis factor inhibitor for active RA, despite trying two DMARDs including methotrexate, may choose either adalimumab or etanercept in the knowledge that these drugs are similarly effective.EU Clinical Trials Register 2006-006275-21/GB.
HubMed – drug

State-of-the-art technology in modern computer-aided drug design.

Filed under: Drug and Alcohol Rehabilitation

Brief Bioinform. 2012 Nov 12;
Dalkas GA, Vlachakis D, Tsagkrasoulis D, Kastania A, Kossida S

The quest for small drug-like compounds that selectively inhibit the function of biological targets has always been a major focus in the pharmaceutical industry and in academia as well. High-throughput screening of compound libraries requires time, cost and resources. Therefore, the use of alternative methods is necessary for facilitating lead discovery. Computational techniques that dock small molecules into macromolecular targets and predict the affinity and activity of the small molecule are widely used in drug design and discovery, and have become an integral part of the industrial and academic research. In this review, we present an overview of some state-of-the-art technologies in modern drug design that have been developed for expediting the search for novel drug candidates.
HubMed – drug

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