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

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

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Metallurgical, Mechanical and Electrochemical Behavior Study of the Lamellar Gray Cast Iron Treated with Vanadium

This study is concerned with the research and development in the field of materials science, leading to the industrial applications especially for the development of materials by moulding process. The purpose of this study was to determine the influence of vanadium on microstructural, mechanical and electrochemical properties of gray cast iron with lamellar graphite EN-FGL250. We investigated the effect of adding element (vanadium), during the casting of the metal in the mould, in a powder form having a particle size of 0.5 mm with the amounts of 1%, 3% and 5% in weight percent on microstructural and mechanical properties of gray cast iron with lamellar graphite. The originality of this work is the addition of the vanadium powder during the last stage of cooling of the melted gray cast iron EN-FGL250. These additions have a significant impact on the solidification phenomenon since the deposited vanadium powder into the sand moulds creates the new sites of nucleation and absorbs a lot of heat leading to the fast cooling. From the experimental results, we can confirm that the cooling rate directly affects the microstructural, mechanical and electrochemical behavior of the cast gray iron treated with vanadium. As result, it was observed that there is a slight decrease of the elasticity modulus of the work pieces, and a reduction of the maximum tensile resistance R_{m}. Finally, the addition of vanadium considerably reduces the corrosion current of gray cast iron treated with vanadium

Metallurgical, Mechanical and Electrochemical Behavior Study of the Lamellar Gray Cast Iron Treated with Vanadium

This study is concerned with the research and development in the field of materials science, leading to the industrial applications especially for the development of materials by moulding process. The purpose of this study was to determine the influence of vanadium on microstructural, mechanical and electrochemical properties of gray cast iron with lamellar graphite EN-FGL250. We investigated the effect of adding element (vanadium), during the casting of the metal in the mould, in a powder form having a particle size of 0.5 mm with the amounts of 1%, 3% and 5% in weight percent on microstructural and mechanical properties of gray cast iron with lamellar graphite. The originality of this work is the addition of the vanadium powder during the last stage of cooling of the melted gray cast iron EN-FGL250. These additions have a significant impact on the solidification phenomenon since the deposited vanadium powder into the sand moulds creates the new sites of nucleation and absorbs a lot of heat leading to the fast cooling. From the experimental results, we can confirm that the cooling rate directly affects the microstructural, mechanical and electrochemical behavior of the cast gray iron treated with vanadium. As result, it was observed that there is a slight decrease of the elasticity modulus of the work pieces, and a reduction of the maximum tensile resistance R_{m}. Finally, the addition of vanadium considerably reduces the corrosion current of gray cast iron treated with vanadium

Metallurgical, Mechanical and Electrochemical Behavior Study of the Lamellar Gray Cast Iron Treated with Vanadium

This study is concerned with the research and development in the field of materials science, leading to the industrial applications especially for the development of materials by moulding process. The purpose of this study was to determine the influence of vanadium on microstructural, mechanical and electrochemical properties of gray cast iron with lamellar graphite EN-FGL250. We investigated the effect of adding element (vanadium), during the casting of the metal in the mould, in a powder form having a particle size of 0.5 mm with the amounts of 1%, 3% and 5% in weight percent on microstructural and mechanical properties of gray cast iron with lamellar graphite. The originality of this work is the addition of the vanadium powder during the last stage of cooling of the melted gray cast iron EN-FGL250. These additions have a significant impact on the solidification phenomenon since the deposited vanadium powder into the sand moulds creates the new sites of nucleation and absorbs a lot of heat leading to the fast cooling. From the experimental results, we can confirm that the cooling rate directly affects the microstructural, mechanical and electrochemical behavior of the cast gray iron treated with vanadium. As result, it was observed that there is a slight decrease of the elasticity modulus of the work pieces, and a reduction of the maximum tensile resistance Rm. Finally, the addition of vanadium considerably reduces the corrosion current of gray cast iron treated with vanadium

Niobium addition effect in molds at last cooling step on EN-GJL250 gray cast iron: Microstructural changes and electrochemical behavior

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PAGES Zaragoza 2017 : global challenges for our common future : a paleoscience perspective : abstract book

As climate model uncertainties remain very large for future rainfall in the Sahel, a multi-centennial perspective is required to assess the relationship between global warming and the Sahel hydroclimate. We present here a new record of hydrologic conditions over the past 1600 years in Senegal, obtained from stable oxygen isotope analyses (δ18O) in archaeological shell middens in the Saloum Delta. During the preindustrial period, the Sahel was relatively humid, particularly from AD 1500 to AD 1800, during the coolest period of the last two millennia, referred to as the Little Ice Age. A strong negative link is observed at the centennial scale between global temperature and humidity in the Sahel, in direct contrast with the relationship observed elsewhere in the northern tropics, which shows that the processes linking the Intertropical Convergence Zone (ITCZ) and the West African Monsoon (WAM) are more complex than previously thought. The relationships between changes in the annual mean state and seasonal to interannual variability are explored using monthly resolved shell isotope records. In the context of the past 1600 years, the Western Sahel appears to be experiencing unprecedented drought conditions, resulting from a rapid aridification since AD 1800 that points to local and global anthropogenic forcings. This new long-term perspective suggests that under future global warming the potential for severe Sahel droughts may increase significantly

Positive precipitation-evaporation budget from AD 460 to 1090 in the Saloum Delta (Senegal) indicated by mollusk oxygen isotopes

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