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Background: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19).Objective: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.Design: Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668).Setting: Internet-based trial across the United States and Canada (40 states and 3 provinces).Participants: Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset.Intervention: Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo.Measurements: Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days.Results: Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, -0.27 point [95% CI, -0.61 to 0.07 point]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19-related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).Limitation: Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.Conclusion: Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.Primary Funding Source: Private donors. [ABSTRACT FROM AUTHOR]

Objective: To investigate neonatal morbidity and maternal complication rates with delivery body mass index (BMI) 60 or greater.Methods: This retrospective, multicenter cohort study included singleton pregnancies between 23 and 42 weeks of gestation from January 2005 to April 2016. Women with BMI 60 or greater were compared with a random sample of women with BMI 30-59. The primary outcome, composite neonatal morbidity, was defined as 5-minute Apgar score less than 7, hypoglycemia, respiratory distress syndrome, sepsis, hospital stay greater than 5 days, neonatal intensive care unit admission, or neonatal death. Secondary outcomes included maternal labor and delivery characteristics and complication rates. Kruskal-Wallis tests and χ or Fisher exact tests were used to compare BMI categories. Multivariable logistic regression was used for adjusted analysis.Results: The study included 338 women, with 39 in the BMI 60 or greater group. An association between obesity and neonatal morbidity was found. Increasing BMI correlated with increasing neonatal morbidity, with the highest rates among those with BMI 60 or greater (BMI 30-39 [17%], 40-49 [19%], 50-59 [22%], 60 or greater [56%]; P<.001). After adjustment for confounders, obese women with BMI less than 60 had at least a 75% reduction in odds of neonatal morbidity compared with women with BMI 60 or greater (BMI 30-39 adjusted odds ratio [OR] 0.22 [0.1-0.5], 40-49 adjusted OR 0.23 [0.1-0.6], 50-59 adjusted OR 0.25 [0.1-0.6]). Maternal complication rates including labor induction, cesarean delivery, wound complication, postpartum hemorrhage, and hospital stay greater than 5 days were also significantly increased with BMI 60 or greater.Conclusion: A BMI 60 or greater at the time of delivery is significantly associated with increased neonatal morbidity and increased maternal complication rates. In addition, neonatal morbidity and maternal complication rates with BMI 60 or greater were significantly higher when compared with women in any lesser obese BMI cohort between 30 and 59. [ABSTRACT FROM AUTHOR]

Purpose: To update the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for a markedly heterogeneous patient population, patients with melanoma and brain metastases, using a larger, more current cohort, including molecular markers.Methods: The original Melanoma-GPA is based on data from 483 patients whose conditions were diagnosed between 1985 and 2005. This is a multi-institutional retrospective database analysis of 823 melanoma patients with newly diagnosed brain metastases from January 1, 2006, to December 31, 2015. Multivariable analyses identified significant prognostic factors, which were weighted and included in the updated index (Melanoma-molGPA). Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios to design the updated Melanoma-molGPA in which scores of 4.0 and 0.0 are associated with the best and worst prognoses, as with all of the diagnosis-specific GPA indices. Log-rank tests were used to compare adjacent classes.Results: There were 5 significant prognostic factors for survival (age, Karnofsky performance status [KPS], extracranial metastases [ECM], number of brain metastases, and BRAF status), whereas only KPS and the number of brain metastases were significant in the original Melanoma-GPA. Median survival improved from 6.7 to 9.8 months between the 2 treatment eras, and the median survival times for patients with Melanoma-molGPA of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 4.9, 8.3, 15.8, and 34.1 months (P<.0001 between each adjacent group).Conclusions: Survival and our ability to estimate survival in melanoma patients with brain metastases has improved significantly. The updated Melanoma-molGPA, a user-friendly tool to estimate survival, will facilitate clinical decision making regarding whether and which treatment is appropriate and will also be useful for stratification of future clinical trials. To further simplify use, a free online/smart phone app is available at brainmetgpa.com. [ABSTRACT FROM AUTHOR]