Brief Report: Dipyridamole Decreases Gut Mucosal Regulatory T-Cell Frequencies Among People With HIV on Antiretroviral Therapy.

BACKGROUND: We had previously conducted a double-blind, randomized placebo-controlled, partial cross-over trial showing that 12 weeks of dipyridamole decreased CD8 T-cell activation among treated HIV(+) individuals by increasing extracellular adenosine levels. METHODS: In this substudy, rectosigmoid biopsies were obtained from 18 participants (9 per arm), to determine whether 12 weeks of dipyridamole affects mucosal immune cells. Participants randomized to placebo were then switched to dipyridamole for 12 weeks while the treatment arm continued dipyridamole for another 12 weeks. We evaluated T-cell frequencies and plasma markers of microbial translocation and intestinal epithelial integrity. Linear regression models on log-transformed outcomes were used for the primary 12-week analysis. RESULTS: Participants receiving dipyridamole had a median 70.2% decrease from baseline in regulatory T cells (P = 0.007) and an 11.3% increase in CD8 T cells (P = 0.05). There was a nonsignificant 10.80% decrease in plasma intestinal fatty acid binding protein levels in the dipyridamole arm compared with a 9.51% increase in the placebo arm. There were no significant differences in plasma levels of ß-D-glucan. In pooled analyses, there continued to be a significant decrease in regulatory T cells (-44%; P = 0.004). There was also a trend for decreased CD4 and CD8 T-cell activation. CONCLUSION: Increasing extracellular adenosine levels using dipyridamole in virally suppressed HIV (+) individuals on antiretroviral therapy can affect regulation of gut mucosal immunity.

Creating an academic research organization to efficiently design, conduct, coordinate, and analyze clinical trials: The Center for Clinical Trials & Data Coordination.

When properly executed, the randomized controlled trial is one of the best vehicles for assessing the effectiveness of one or more interventions. However, numerous challenges may emerge in the areas of study startup, recruitment, data quality, cost, and reporting of results. The use of well-run coordinating centers could help prevent these issues, but very little exists in the literature describing their creation or the guiding principles behind their inception. The Center for Clinical Trials & Data Coordination (CCDC) was established in 2015 through institutional funds with the intent of 1) providing relevant expertise in clinical trial design, conduct, coordination, and analysis; 2) advancing the careers of clinical investigators and CCDC-affiliated faculty; and 3) obtaining large data coordinating center (DCC) grants. We describe the organizational structure of the CCDC as well as the homegrown clinical trial management system integrating nine crucial elements: electronic data capture, eligibility and randomization, drug and external data tracking, safety reporting, outcome adjudication, data and safety monitoring, statistical analysis and reporting, data sharing, and regulatory compliance. Lastly, we share numerous lessons that can be taken from our experience. Specifically, we focus on 1) funding for DCCs, 2) the importance of DCCs to clinical researchers, 3) the expertise of DCC personnel, and 4) continually striving to improve. In conclusion, the CCDC strives to provide high-quality support for the design, conduct, coordination, and analyses of clinical trials, and we hope this paper will serve as a blueprint for future clinical trialists involved in DCCs.

A checklist is associated with increased quality of reporting preclinical biomedical research: A systematic review.

Irreproducibility of preclinical biomedical research has gained recent attention. It is suggested that requiring authors to complete a checklist at the time of manuscript submission would improve the quality and transparency of scientific reporting, and ultimately enhance reproducibility. Whether a checklist enhances quality and transparency in reporting preclinical animal studies, however, has not been empirically studied. Here we searched two highly cited life science journals, one that requires a checklist at submission (Nature) and one that does not (Cell), to identify in vivo animal studies. After screening 943 articles, a total of 80 articles were identified in 2013 (pre-checklist) and 2015 (post-checklist), and included for the detailed evaluation of reporting methodological and analytical information. We compared the quality of reporting preclinical animal studies between the two journals, accounting for differences between journals and changes over time in reporting. We find that reporting of randomization, blinding, and sample-size estimation significantly improved when comparing Nature to Cell from 2013 to 2015, likely due to implementation of a checklist. Specifically, improvement in reporting of the three methodological information was at least three times greater when a mandatory checklist was implemented than when it was not. Reporting the sex of animals and the number of independent experiments performed also improved from 2013 to 2015, likely from factors not related to a checklist. Our study demonstrates that completing a checklist at manuscript submission is associated with improved reporting of key methodological information in preclinical animal studies.