Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Background: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (COVID-19) on the basis of in vitro activity, uncontrolled data, and small randomized studies. Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of hydroxychloroquine vs. usual care alone. The primary outcome was 28-day mortality. Results: 1561 patients randomly allocated to receive hydroxychloroquine were compared with 3155 patients concurrently allocated to usual care. Overall, 418 (26.8%) patients allocated hydroxychloroquine and 788 (25.0%) patients allocated usual care died within 28 days (rate ratio 1.09; 95% confidence interval [CI] 0.96 to 1.23; P=0.18). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to hydroxychloroquine were less likely to be discharged from hospital alive within 28 days (60.3% vs. 62.8%; rate ratio 0.92; 95% CI 0.85-0.99) and those not on invasive mechanical ventilation at baseline were more likely to reach the composite endpoint of invasive mechanical ventilation or death (29.8% vs. 26.5%; risk ratio 1.12; 95% CI 1.01-1.25). There was no excess of new major cardiac arrhythmia. Conclusions: In patients hospitalized with COVID-19, hydroxychloroquine was not associated with reductions in 28-day mortality but was associated with an increased length of hospital stay and increased risk of progressing to invasive mechanical ventilation or death.
To measure the impact of maternal syphilis on pregnancy outcome in the Mwanza Region of Tanzania, 380 previously unscreened pregnant women were recruited into a retrospective cohort at delivery and tested for syphilis. Stillbirth was observed in 18 (25%) of 73 women with high-titer active syphilis (i.e., women with a rapid plasma reagin titer > or = 1 :8 and a positive Treponema pallidum hemagglutination assay or indirect fluorescent treponemal antibody test result), compared with 3 (1%) of 233 uninfected women (risk ratio [RR], 18.1; P<.001). Women with high-titer active syphilis were also at the greatest risk of having low-birth-weight or preterm live births (RR, 3.0 and 6.1, respectively), compared with women with other serological stages of syphilis. Among unscreened women, 51% of stillbirths, 24% of preterm live births, and 17% of all adverse pregnancy outcomes were attributable to maternal syphilis. Syphilis continues to be a major cause of pregnancy loss and adverse pregnancy outcome among women who do not receive antenatal syphilis screening and treatment.
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