ABSTRACT
AIMS: To summarize evidence from and assess the quality of published systematic reviews evaluating the safety, efficacy and effectiveness of incretin-based medications used in the treatment of type 2 diabetes. METHODS: We identified systematic reviews of randomized controlled trials or observational studies published in any language that evaluated the safety and/or effectiveness of glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl-peptidase-4 (DPP-4) inhibitors. Data sources used include the Cochrane Library, PubMed, EMBASE, Web of Science, International Pharmaceutical Abstracts, table of contents of diabetes journals, and hand-searching of reference lists and clinical practice guidelines. The methodological quality of systematic reviews was independently assessed by two reviewers using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist. Our study protocol was registered with PROSPERO (2013:CRD42013005149). The primary outcomes were pooled treatment effect estimates for glycaemic control, macrovascular and microvascular complications, and hypoglycaemic events. RESULTS: We identified 467 unique citations of which 84 systematic reviews met our inclusion criteria. There were 51 reviews that evaluated GLP-1 receptor agonists and 64 reviews that evaluated DPP-4 inhibitors. The median (interquartile range) AMSTAR score was 6 (3) out of 11 for quantitative and 1 (1) for non-quantitative reviews. Among the 66 quantitative systematic reviews, there were a total of 718 pooled treatment effect estimates reported for our primary outcomes and 1012 reported pooled treatment effect estimates for secondary outcomes. CONCLUSIONS: Clinicians and policy makers, when using the results of systematic reviews to inform decision-making with regard to round clinical care or healthcare policies for incretin-based medications, should consider the variability in quality of reviews.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Glucagon-Like Peptide-1 Receptor/agonists , Incretins/therapeutic use , Review Literature as Topic , Humans , Observational Studies as Topic , Randomized Controlled Trials as TopicABSTRACT
The isolation and characterization of a novel bacteriophage active against the obligately alkaliphilic bacterium Bacillus clarkii is described. The bacteriophage, designated BCJA1. is a member of the Siphoviridae family with a B1 morphology. It possesses an isometric head, which measures 65 nm between opposite apices, and a noncontractile tail of 195 nm length. It had a buoyant density of 1.518 g/ml and an estimated particle mass of 37 x 10(7) daltons. BCJA1 was stable over the pH range of 6-11. A one-step growth experiment conducted at pH 10 demonstrated a latent period of about 40 min and a burst size of approximately 40. The purified bacteriophage appeared to consist of 10 proteins with the major head and tail proteins likely to be of molecular weight 36500 and 28000, respectively. The genome size was estimated to be between 32.1 and 34.8 kb. The percent G + C content of purified bacteriophage DNA was 45.6. The wildtype bacteriophage is temperate but a clear plaque mutant was isolated.