A Randomized Clinical Trial Testing Hydroxychloroquine for Reduction of SARS-CoV-2 Viral Shedding and Hospitalization in Early Outpatient COVID-19 Infection.

Early in the COVID-19 pandemic, no effective treatment existed to prevent clinical worsening of COVID-19 among recently diagnosed outpatients. At the University of Utah, Salt Lake City, Utah, we conducted a phase 2 prospective parallel group randomized placebo-controlled trial (NCT04342169) to determine whether hydroxychloroquine given early in disease reduces the duration of SARS-CoV-2 shedding. We enrolled nonhospitalized adults (≥18 years of age) with a recent positive diagnostic test for SARS-CoV-2 (within 72 h of enrollment) and adult household contacts. Participants received either 400 mg hydroxychloroquine by mouth twice daily on day 1 followed by 200 mg by mouth twice daily on days 2 to 5 or oral placebo with the same schedule. We performed SARS-CoV-2 nucleic acid amplification testing (NAAT) on oropharyngeal swabs on days 1 to 14 and 28 and monitored clinical symptomatology, rates of hospitalization, and viral acquisition by adult household contacts. We identified no overall differences in the duration of oropharyngeal carriage of SARS-CoV-2 (hazard ratio of viral shedding time comparing hydroxychloroquine to placebo, 1.21; 95% confidence interval [CI], 0.91, 1.62). Overall, 28-day hospitalization incidence was similar between treatments (4.6% hydroxychloroquine versus 2.7% placebo). No differences were seen in symptom duration, severity, or viral acquisition in household contacts between treatment groups. The study did not reach the prespecified enrollment target, which was likely influenced by a steep decline in COVID-19 incidence corresponding to the initial vaccine rollout in the spring of 2021. Oropharyngeal swabs were self-collected, which may introduce variability in these results. Placebo treatments were not identical to hydroxychloroquine treatments (capsules versus tablets) which may have led to inadvertent participant unblinding. In this group of community adults early in the COVID-19 pandemic, hydroxychloroquine did not significantly alter the natural history of early COVID-19 disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT04342169). IMPORTANCE Early in the COVID-19 pandemic, no effective treatment existed to prevent clinical worsening of COVID-19 among recently diagnosed outpatients. Hydroxychloroquine received attention as a possible early treatment; however, quality prospective studies were lacking. We conducted a clinical trial to test the ability of hydroxychloroquine to prevent clinical worsening of COVID-19.

Using gamification to enhance clinical trial start-up activities.

Background: The Trial Innovation Network (TIN) is a collaborative initiative within the National Center for Advancing Translational Science (NCATS) Clinical and Translational Science Awards (CTSA) Program. To improve and innovate the conduct of clinical trials, it is exploring the uses of gamification to better engage the trial workforce and improve the efficiencies of trial activities. The gamification structures described in this article are part of a TIN website gamification toolkit, available online to the clinical trial scientific community. Methods: The game designers used existing electronic trial platforms to gamify the tasks required to meet trial start-up timelines to create friendly competitions. Key indicators and familiar metrics were mapped to scoreboards. Webinars were organized to share and applaud trial and game performance. Results: Game scores were significantly associated with an increase in achieving start-up milestones in activation, institutional review board (IRB) submission, and IRB approval times, indicating the probability of completing site activation faster by using games. Overall game enjoyment and feelings that the game did not apply too much pressure appeared to be an important moderator of performance in one trial but had little effect on performance in a second. Conclusion: This retrospective examination of available data from gaming experiences may be a first-of-kind use in clinical trials. There are signals that gaming may accelerate performance and increase enjoyment during the start-up phase of a trial. Isolating the effect of gamification on trial outcomes will depend on a larger sampling from future trials, using well-defined, hypothesis-driven statistical analysis plans.

Will-powered: Synchronic regulation is the difference maker for self-control.

Philosophers, psychologists, and economists have reached the consensus that one can use two different kinds of regulation to achieve self-control. Synchronic regulation uses willpower to resist current temptation. Diachronic regulation implements a plan to avoid future temptation. Yet this consensus may rest on contaminated intuitions. Specifically, agents typically use willpower (synchronic regulation) to achieve their plans to avoid temptation (diachronic regulation). So even if cases of diachronic regulation seem to involve self-control, this may be because they are contaminated by synchronic regulation. We therefore developed a novel multifactorial method to disentangle synchronic and diachronic regulation. Using this method, we find that ordinary usage assumes that only synchronic--not diachronic--regulation counts as self-control. We find this pattern across four experiments involving different kinds of temptation, as well as a paradigmatic case of diachronic regulation based on the classic story of Odysseus and the Sirens. Our final experiment finds that self-control in a diachronic case depends on whether the agent uses synchronic regulation at two moments: when she (1) initiates and (2) follows-through on a plan to resist temptation. Taken together, our results strongly suggest that synchronic regulation is the sole difference maker in the folk concept of self-control.