Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. 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. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Exploration de raies spectrales stellaires en inclinant un interféromètre Fabry-Perot

Tests are described of an arrangement for the direct photoelectric recording of stellar spectra, using a Fabry-Perot etalon in combination with a prism monochromator. The addition of the etalon allows the monochromator to be used with a wider entrance slit for given wavelength resolution : this results not only in a gain of light, but also in a reduction of the fluctuations caused by the motion of the stellar image under the influence of atmospheric turbulence.Description de tests effectués sur un dispositif d'enregistrement photoélectrique direct de spectres stellaires, utilisant la combinaison d'un étalon Fabry-Perot et d'un monochromateur à prisme. L'addition de l'étalon permet, pour une résolution donnée, d'élargir la fente d'entrée du monochromateur, ce qui se traduit, non seulement par un gain de lumière, mais encore par une réduction des fluctuations produites par le mouvement de l'image stellaire sous l'influence de la turbulence atmosphérique

Alluvial Sedimentation and Erosion in an Urbanizing Watershed,Gwynn Falls, Maryland

Earlier measurements of stream channel geometry on 19 reaches were repeated to provide a longitudinal study of stream channel adjustment over 13 years (1987-2000) in the urbanizing Gwynns Falls, Maryland watershed. We observed both enlargement and reduction in channel size, depending on the extent of upstream development, the timing and location of urbanization and upstream channel adjustment, and the presence of hydrologic constrictions and grade controls. Based on a relatively simple visual assessment of the composition, size, and extent of instream sediment storage, we categorized stream reaches into three phases: aggraded (7 sites), early erosion (7 sites), and late erosion (5 sites). Aggraded sites had point and lateral bars mantled with fine-grained sediment and experienced some reduction in cross-sectional area, primarily through the deposition of fine-grained material on bars in the channel margins. Early erosion sites had smaller bars and increases in channel cross-sectional area as a consequence of the evacuation of in-channel fine-grained sediment. Fine-grained sediments were either entirely absent or found only at a few high bar elevations at late erosion sites. Sediment evacuation from late erosion sites has both enlarged and simplified channels, as demonstrated by an increase in cross-sectional area and a strong decrease in channel width variation. Channel cross-sectional area enlargement, reduced channel width variation, and channel incision were ubiquitous at erosion sites. As a result, overbank flows were less common in the erosion sites as determined by high water marks left by a 2-year flood that occurred during the study period. Principal causes for channel changes appear to be increased high flow durations and reduced sediment supply. Spatial variation in channel conditions could not be tied simply to sub-basin impervious cover or watershed area. In-channel sediment storage is a useful indicator of channel form and adjustment. When combined with information on development and sedimentation conditions in the contributing drainage, instream sediment storage can be used to effectively assess future channel adjustments