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Objective: High-attrition rates have been observed in long-term clinical trials of weight loss agents. We evaluated the impact of an innovative retention programme on 1-year retention., Methods: Three Phase 3 global multicentre clinical trials evaluated the efficacy and safety of a CB1 receptor antagonist in subjects with BMI ≥ or = 27 kg/m 2 . The impact of a multifaceted retention programme including a dietitian screening interview, a comprehensive culturally adapted lifestyle modification programme, and a dietitian support system to maximize lifestyle adherence, was evaluated in 4,410 subjects from four subpopulations (non-US English-speaking, non-English-speaking, US-without dietitian screening and US-with dietitian screening) comprising 208 centres from 15 countries., Results: The median proportion retained over the first year among subjects in three protocols was 82%. Non-English-speaking countries showed higher retention rates (89%) compared with the USA (73%) and non-US English-speaking (81%) countries. Within the USA, behavioural screening was associated with 29% reduction in dropout rate; for every five monthly teleconferences attended above 11, there was a 32% decrease in dropout rate., Conclusions: This novel retention programme greatly improved upon reported retention rates of studies conducted with other weight loss agents in long-term clinical trials. Its effectiveness should be confirmed in future trials.

Three double-blind, placebo-controlled, three-parallel-group, multicenter phase 3 trials were conducted to assess the efficacy and safety of CP-945,598 for weight loss and weight-loss maintenance. Two trials were designed to be 2 years in duration (in obese and overweight patients) and one as a 1-year study (in obese and overweight patients with type 2 diabetes). However, the 2-year trials and the CP-945,598 development program were terminated before completion due to changing regulatory perspectives of CB1 receptor-related drugs. In total, 1,253 and 2,536 participants in the two 2-year multinational and North American studies were randomized to 10-mg CP-945,598 (n = 360; 718); 20-mg CP-945,598 (n = 534, 1,084) and placebo (n = 359, 734), respectively; and 975 participants were randomized to 10-mg CP-945,598 (n = 318); 20-mg CP-945,598 (n = 320); and placebo (n = 337) in the 1-year multinational diabetes trial. Baseline demographics were similar between treatment groups within each trial. One year of treatment with CP-945,598 resulted in a dose-related mean percentage reduction from baseline body-weight in all trials. A significant proportion of all participants also achieved 5% and 10% weight loss after 1 year. In participants with mainly well-controlled type 2 diabetes, the combination of lifestyle and CP-945,598 induced substantial improvements in glycemic control. The most frequent adverse events (AEs) for CP-945,598 were: diarrhea, nausea, nasopharyngitis, and headache. Self-reported experiences of anxiety and suicidal thoughts were higher with CP-945,598 than placebo, as were the incidence of depression and depressed mood. However, the reported increases in psychiatric symptoms were not consistently dose dependent.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.