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

Technical data summary supporting the spent nuclear fuel environment impact statement, March 1994

This report has been compiled by the WSRC Nuclear Materials Processing Division`s Planning Section at the request of the Office of Spent Fuel Management and Special Projects (EM-37) to support issuance of the Spent Nuclear Fuel Environmental Impact Statement. Savannah River Site input data evaluates five programmatic options (including {open_quotes}No Action{close_quotes}) ranging up to transfer of all DOE responsibility spent fuel to the SRS. For each option, a range of management/disposition scenarios has been examined. Each case summary provides information relative to the technical proposal, technical issues, environmental impacts, and projected costs for a forty year period (FY-35) when it is assumed that the material will be dispositioned from the SRS. The original issue of the report which was prepared under severe time constraints contained many simplifications and assumptions. Although the revisions have corrected some of the shortcomings of the original report, it is still highly recommended that significant additional study be performed before basing key decisions upon the data contained in this report. The data represents the best effort by a significant group of technical personnel familiar with nuclear materials processing, handling, and storage; but it is likely that careful scrutiny will reveal numerous discrepancies, inconsistencies and omissions. Nor does this report attempt to analyze every potential disposal pathway, but probably establishes the bounds for the most of the viable pathways. The bulk of the effort went into defining the engineering approaches necessary to execute the various mission scenarios which were changed since the last revision. The decision to limit reprocessing to only SRS aluminum clad required a major alteration of the TDS. Collection and/or calculation of much of the various waste, emission, and utility consumption data, so important to an EIS, has been updated since the last revision, but not thoroughly completed

Ambulatory Care and orthopaedic capacity planning

Ambulatory Care facilities (often referred to as diagnosis and treatment centres) separate the routine elective activity from the uncertainty of complex inpatient and emergency treatment. Only routine patients with predictable outcomes should be treated in Ambulatory Care. Hence the centre should be able to plan its activities effectively. This paper considers the consequences for the remaining elective inpatient bed and theatre requirements. Computer models are used to simulate many years of activity in an orthopaedic department at a typical District General hospital. The adoption of Ambulatory Care will increase the proportion of day case treatment but the reduction in the overall bed requirement will be relatively small (at most 10%). Separating the elective theatre activity into day case and inpatient sessions will tend to produce inpatient theatre sessions with a disproportionate number of longer procedures. This can reduce overall theatre utilisation by up to 15%, which implies the need for an increase of up to 18% in the number of theatre sessions if waiting times are to be maintained

A pipelined first level trigger for the H1 forward muon spectrometer

SIGLEAvailable from British Library Document Supply Centre- DSC:8053.4153(RAL--94-126) / BLDSC - British Library Document Supply CentreGBUnited Kingdo