IMPORTANCE Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit. OBJECTIVE To determine whether ivermectin is an efficacious treatment for mild COVID-19. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state's health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020. INTERVENTION Patients were randomized to receive ivermectin, 300 μg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200). MAIN OUTCOMES AND MEASURES Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected. RESULTS Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group). CONCLUSION AND RELEVANCE Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes.

IMPORTANCEOpioid prescriptions for treatment of pain in emergency departments (EDs) are associated with long-term opioid use. The temporal pattern of opioid prescribing in the context of the opioid epidemic remains unknown. OBJECTIVE To examine the temporal pattern of opioid prescribing within an ED for varying pain conditions between 2009 and 2018. DESIGN, SETTING, AND PARTICIPANTS A population-based, cross-sectional study was conducted at the ED of an urban academic medical center. All patients treated within that ED between January 1, 2009, and December 31, 2018, were included. MAIN OUTCOMES AND MEASURESThe proportion of patients prescribed an opioid for treatment of pain in the ED temporally by condition, condition type, patient demographics, and physician prescriber.

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Background: Despite increasing information in the literature regarding congenital Zika infection, gaps remain in our knowledge of its clinical manifestations. Methods: We did a prospective observational study of exposed fetuses and infants whose mothers developed symptomatic and confirmed Zika infection during pregnancy in Valle del Cauca, Colombia. We performed neurological, ophthalmologic and audiologic evaluations, and classified outcomes as possibly or uncertainly related to Zika. Frequencies of outcomes were compared according to the trimester of pregnancy when infection occurred. Results: We evaluated 171 products of gestation including 17 pregnancy losses and 154 patients evaluated postnatally. Ninety (52.6%) pregnancies presented an adverse outcome, 36% possibly related with Zika and the remaining 64% of uncertain relation. Infection in the first trimester had the highest frequencies of adverse outcomes possibly related with Zika compared with the second and third trimesters (39% vs. 12.5% vs. 12%) with risk ratios of adverse outcomes possibly related to Zika in pregnancies infected in the first versus second or third trimester of 3.1 (95% CI: 2.4–4.1) and 3.3 (95% CI: 2.5–4.2), respectively. The frequencies of pregnancy loss and microcephaly were 9.4% and 4.5%, respectively. Auditory and ophthalmic abnormalities possibly related with Zika were present in 3% and 6% of the patients evaluated, respectively. Conclusions: We observed a high frequency of gestational and neonatal complications in pregnant women who acquired Zika infection, especially in early pregnancy, resulting in a broad spectrum of clinical manifestations. Preventive measures are urgently needed to reduce the clinical burden during future Zika outbreaks.