Translating Violence Prevention Programs from Research to Practice: SafERteens Implementation in an Urban Emergency Department.

BACKGROUND: Youth violence is a leading cause of adolescent mortality, underscoring the need to integrate evidence-based violence prevention programs into routine emergency department (ED) care. OBJECTIVES: To examine the translation of the SafERteens program into clinical care. METHODS: Hospital staff provided input on implementation facilitators/barriers to inform toolkit development. Implementation was piloted in a four-arm effectiveness-implementation trial, with youth (ages 14-18 years) screening positive for past 3-month aggression randomized to either SafERteens (delivered remotely or in-person) or enhanced usual care (EUC; remote or in-person), with follow-up at post-test and 3 months. During maintenance, ED staff continued in-person SafERteens delivery and external facilitation was provided. Outcomes were measured using the RE-AIM implementation framework. RESULTS: SafERteens completion rates were 77.6% (52/67) for remote and 49.1% (27/55) for in-person delivery. In addition to high acceptability ratings (e.g., helpfulness), post-test data demonstrated increased self-efficacy to avoid fighting among patients receiving remote (incidence rate ratio [IRR] 1.22, 95% confidence interval [CI] 1.09-1.36) and in-person (IRR 1.23, 95% CI 1.12-1.36) SafERteens, as well as decreased pro-violence attitudes among patients receiving remote (IRR 0.83, 95% CI 0.75-0.91) and in-person (IRR 0.87, 95% CI 0.77-0.99) SafERteens when compared with their respective EUC groups. At 3 months, youth receiving remote SafERteens reported less non-partner aggression (IRR 0.52, 95% CI 0.31-0.87, Cohen's d -0.39) and violence consequences (IRR 0.47, 95% CI 0.22-1.00, Cohen's d -0.49) compared with remote EUC; no differences were noted for in-person SafERteens delivery. Barriers to implementation maintenance included limited staff availability and a lack of reimbursement codes. CONCLUSIONS: Implementing behavioral interventions such as SafERteens into routine ED care is feasible using remote delivery. Policymakers should consider reimbursement for violence prevention services to sustain long-term implementation.

Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice.

The COVID-19 pandemic remains uncontrolled despite the rapid rollout of safe and effective SARS-CoV-2 vaccines, underscoring the need to develop highly effective antivirals. In the setting of waning immunity from infection and vaccination, breakthrough infections are becoming increasingly common and treatment options remain limited. Additionally, the emergence of SARS-CoV-2 variants of concern with their potential to escape therapeutic monoclonal antibodies emphasizes the need to develop second-generation oral antivirals targeting highly conserved viral proteins that can be rapidly deployed to outpatients. Here, we demonstrate the in vitro antiviral activity and in vivo therapeutic efficacy of GS-621763, an orally bioavailable prodrug of GS-441524, the parental nucleoside of remdesivir, which targets the highly conserved RNA-dependent RNA polymerase. GS-621763 exhibited significant antiviral activity in lung cell lines and two different human primary lung cell culture systems. The dose-proportional pharmacokinetic profile observed after oral administration of GS-621763 translated to dose-dependent antiviral activity in mice infected with SARS-CoV-2. Therapeutic GS-621763 significantly reduced viral load, lung pathology, and improved pulmonary function in COVID-19 mouse model. A direct comparison of GS-621763 with molnupiravir, an oral nucleoside analog antiviral currently in human clinical trial, proved both drugs to be similarly efficacious. These data demonstrate that therapy with oral prodrugs of remdesivir can significantly improve outcomes in SARS-CoV-2 infected mice. Thus, GS-621763 supports the exploration of GS-441524 oral prodrugs for the treatment of COVID-19 in humans.