Background World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19). Methods We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. Results At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. Conclusions These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151 ; ClinicalTrials.gov number, NCT04315948 .)
Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Heritability and polygenic predictionIn the EUR sample, the SNP-based heritability (h 2 SNP ) (that is, the proportion of variance in liability attributable to all measured SNPs)
Background Depression and anxiety are two of the leading causes of disease burden in low-to-middle income coutnries. The World Health Organisation has engaged in a programme of scaling-up mental health services, but significant challenges remain. Improving mental health literacy in children and young people, a core part of recent, global health strategies has the potential to address some of these challenges. The study aims to co-develop and feasibility test, a culturally-appropriate toolkit to promote depression and anxiety focused mental health literacy and self-management skills in Indonesia, for children aged 11–15 years. Methods A mixed methods study comprising four phases. Through a systematic review of existing evidence, phase 1 will review approaches to improve mental health literacy and self-management in South East Asia and critically review current evidence regarding intervention effect. Phase 2 will explore stakeholders’ views on depression, anxiety and mental health more broadly and identify priorities for the intervention through the use of semi-structured interviews and/or focus groups with policy makers, clinicians, teachers, adolescent service users, carers and young people aged 11–15. Phase 3 will comprise iterative workshops with local stakeholders to present our findings and co-produce a testable, culturally appropriate toolkit to promote mental health literacy and depression/anxiety focused self-management in 11–15 year olds in Java, Indonesia. Phase 4 comprises feasibility evaluation of our developed intervention via nine in-depth case studies (Jakarta, Bogor and Magelang). We will examine the impact, acceptability and feasibility of our prototype intervention and produce evidence-based guidelines for wider implementation. Discussion Tools to support mental health literacy and self-management are a low cost way in which mental health services in LMICs can attempt to address the burden of anxiety and depression amongst children and young people. However, this is an underexplored area in Indonesia. Working closely with local stakeholders, this study will design and undertake feasibility evaluation of co-produced mental health literacy and anxiety and depression focussed interactive self-management tools. This abstract has also been published on the funders website (UK Research and Innovation. Improving Mental Health Literacy Among Young People aged 12-15 years in Indonesia 2019). Electronic supplementary material The online version of this article (10.1186/s12913-019-4328-2) contains supplementary material, which is available to authorized users.
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