Risk of Suicidal Behavior With Use of Efavirenz: Results from the Strategic Timing of Antiretroviral Treatment Trial.

Background: Randomized trials have shown increased risk of suicidality associated with efavirenz (EFV). The START (Strategic Timing of Antiretroviral Treatment) trial randomized treatment-naive human immunodeficiency virus (HIV)-positive adults with high CD4 cell counts to immediate vs deferred antiretroviral therapy (ART). Methods: The initial ART regimen was selected prior to randomization (prespecified). We compared the incidence of suicidal and self-injurious behaviours (suicidal behavior) between the immediate vs deferred ART groups using proportional hazards models, separately for those with EFV and other prespecified regimens, by intention to treat, and after censoring participants in the deferred arm at ART initiation. Results: Of 4684 participants, 271 (5.8%) had a prior psychiatric diagnosis. EFV was prespecified for 3515 participants (75%), less often in those with psychiatric diagnoses (40%) than without (77%). While the overall intention-to-treat comparison showed no difference in suicidal behavior between arms (hazard ratio [HR], 1.07, P = .81), subgroup analyses suggest that initiation of EFV, but not other ART, is associated with increased risk of suicidal behavior. When censoring follow-up at ART initiation in the deferred group, the immediate vs deferred HR among those who were prespecified EFV was 3.31 (P = .03) and 1.04 (P = .93) among those with other prespecified ART; (P = .07 for interaction). In the immediate group, the risk was higher among those with prior psychiatric diagnoses, regardless of prespecified treatment group. Conclusions: Participants who used EFV in the immediate ART group had increased risk of suicidal behavior compared with ART-naive controls. Those with prior psychiatric diagnoses were at higher risk.

Statewide Antibiotic Stewardship: : An eBrightHealth Choosing Wisely Initiative.

OBJECTIVE: To implement a collaborative statewide antibiotic stewardship initiative in both the ambulatory and inpatient settings. METHODS: Five participating Delaware health systems each convened internal team(s) to translate the vision set forth by the eBrightHealth LLC Choosing Wisely Work Group into clinical action through process improvement efforts at their institutions. The teams focused on implementing antibiotic time-outs, and on improving antibiotic prescribing for upper respiratory infections in ambulatory settings. The learning network utilized an "all teach, all learn" methodology via monthly conference calls and quarterly face-to-face meetings. RESULTS: All inpatient teams implemented antibiotic time-outs for at least 1 unit. Other interventions included commitment posters; submitting antibiotic utilization data nationally; provider/patient surveys; local stewardship champions; and provider prescribing data feedback. Barriers to implementation included competing priorities, lack of reliable utilization data, and suboptimal provider engagement. Overall antibiotic utilization decreased by 9%, compared to the pre-intervention period. CONCLUSIONS: This initiative has demonstrated the value of multidisciplinary teams, from varying healthcare systems, coming together to work on a single project. While each team's interventions and specific goals differed slightly, all teams implemented new initiatives to promote appropriate use of antibiotics. POLICY IMPLICATIONS: Antibiotic stewardship is a national priority. Acute care hospitals are required to have antibiotic stewardship programs; similar programs are proposed for ambulatory settings.