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 .)
SummaryBackground and objectives The effect of increased fluid intake on kidney function is unclear. This study evaluates the relationship between urine volume and renal decline over 6 years in a large community-based cohort.Design, setting, participants, & measurements This prospective cohort study was undertaken in Canada from 2002 to 2008. We obtained 24-hour urine samples from adult participants with an estimated GFR (eGFR) Ն60ml/min per 1.73 m 2 at study entry. Percentage annual change in eGFR from baseline was categorized as average decline Ͻ1% per year, between 1% and 4.9% (mild-to-moderate decline) or Ն5% (rapid decline).Results 2148 participants provided valid 24-hour urine samples, grouped as Ͻ1 L/d (14.5%); 1 to 1.9 L/d (51.5%); 2 to 2.9 L/d (26.3%); and Ն3 L/d (7.7%). Baseline eGFR for each category of urine volume was 90, 88, 84, and 87 ml/min per 1.73 m 2 , respectively. Overall, eGFR declined by 1% per year, with 10% demonstrating rapid decline and 40% demonstrating mild-to-moderate decline. An inverse, graded relationship was evident between urine volume and eGFR decline: For each increasing category of 24-hour urine volume, percentage annual eGFR decline was progressively slower, from 1.3%, 1.0%, 0.8%, to 0.5%, respectively; P ϭ 0.02. Compared with those with urine volume 1 to 1.9 L/d, those with urine volume Ն3 L/d were significantly less likely to demonstrate mild-to-moderate decline (adjusted odds ratio 0.66; 95% confidence interval 0.46 to 0.94) or rapid decline (adjusted odds ratio 0.46; 95% confidence interval 0.23 to 0.92); adjusted for age, gender, baseline eGFR, medication use for hypertension (including diuretics), proteinuria, diabetes, and cardiovascular disease. ConclusionsIn this community-based cohort, decline in kidney function was significantly slower in those with higher versus lower urine volume.
Basiliximab in combination with cyclosporine, steroids, and azathioprine triple therapy was highly effective in reducing the incidence of acute renal allograft rejection without increasing the incidence of infections and other side effects.
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