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.

Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

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The role of sulfur cycling in arsenic behavior under reducing conditions is not well-understood in previous investigations. This study provides observations of sulfur and oxygen isotope fractionation in sulfate and evaluation of sulfur cycling-related biogeochemical processes controlling dissolved arsenic groundwater concentrations using multiple isotope approaches. As a typical basin hosting high arsenic groundwater, the western Hetao basin was selected as the study area. Results showed that, along the groundwater flow paths, groundwater δS, δO, and δC increased with increases in arsenic, dissolved iron, hydrogen sulfide and ammonium concentrations, while δC decreased with decreasing Eh and sulfate/chloride. Bacterial sulfate reduction (BSR) was responsible for many of these observed changes. The δS indicated that dissolved sulfate was mainly sourced from oxidative weathering of sulfides in upgradient alluvial fans. The high oxygen-sulfur isotope fractionation ratio (0.60) may result from both slow sulfate reduction rates and bacterial disproportionation of sulfur intermediates (BDSI). Data indicate that both the sulfide produced by BSR and the overall BDSI reduce arsenic-bearing iron(III) oxyhydroxides, leading to the release of arsenic into groundwater. These results suggest that sulfur-related biogeochemical processes are important in mobilizing arsenic in aquifer systems.

BackgroundThis study explored the prevalence and severity of post-traumatic stress disorder (PTSD) in college students who lived in earthquake center one year after the Wenchuan earthquake on May 12, 2008, the factors affecting the prevalence of PTSD was also investigated.Methods2987 students studying at the senior normal school in Tibetan autonomous region which was one of the most devastated regions were selected for this study. The PTSD Checklist-Civilian Version (PCL-C) was used as a screening instrument.ResultsA total of 420 cases (14.1%) were diagnosed with PTSD, among which mild, moderate, severe and extreme symptoms were reported in 122, 185, 106 and 7 cases, respectively. The PTSD prevalence in college students lived in the severely affected area was significantly higher than that in the less severe area (P < 0.001). According to the multivariate logistic regression analysis, the students who were injured in the earthquake, those lost their first degree relative, and those confronted with dead bodies were more likely to express PTSD. Male students were more prone than female students to develop PTSD. However, the students who received psychological tutorship were less prone to express PTSD.ConclusionsAt one year after the earthquake, the PTSD rate in college students in the severely affected area was high. The social support, psychological help and rehabilitation project should be strengthened to improve their ability to cope with the trauma.