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

Platform drowning leading to cool-water carbonate deposition: Evolution of a late ordovician (Turinian-Chatfieldian) mixed-sediment platform within the taconic orogen (Long Point Group, Newfoundland Appalachians)

Late Ordovician (Turinian–Chatfieldian) drowning of a mixed carbonate–siliciclastic platform within the Taconic Orogen (Newfoundland Appalachians) is recorded by net deepening of an initial warm, shallow-water platform succession (Lourdes Formation) culminating in a metre-scale thick condensed interval that characterizes a drowning succession punctuated by storm deposits. Composition of transported material suggests that seaward drowning was coupled with back-stepping of a high-energy carbonate factory related to hinterland uplift and erosion that would eventually lead to drowning of the outer platform beneath marine-transported siliciclastic sediments (Winterhouse Formation). In the new offshore shelf setting, a sparse reciprocal stratigraphy of fine- to very coarse-grained phosphatic carbonate and mixed sediment is interpreted to document gravity-flow deposition downgradient from either a sustained or episodically developed high-energy cool-water carbonate source along the inner shelf. Transported carbonate was cemented rapidly at temperatures no warmer than 16 °C– 23 °C, possibly within a seasonal oceanic thermocline. An upsection decrease in abundance of carbonate by the early Edenian is associated with a dramatic increase in siliciclastic supply. The Turinian–Edenian succession of platform drowning, oceanographic transition to cool-water carbonate production, and, later, its termination by increased siliciclastic supply reflects a first-order tectonic control proximal to uplift within the Taconic Orogen. Similar structural and oceanographic changes along the contemporary distal Laurentian margin provides the basis, with improved biostratigraphic control, for future analysis of the significance of proximal–distal stratigraphies in response to regional foreland tectonism

Radiological survey of the inactive uranium-mill tailings at Lakeview, Oregon

The results of the radiological survey of the inactive uranium-mill site at Lakeview, Oregon, show that the average gamma-ray exposure rate 1 m above the tailings pile and the evaporation pond area (now dry) is close to the average background level for the area (11 ..mu..R/hr). The /sup 226/Ra concentration in most of the surface soil and sediment samples is also at or below the average background value for surface soil samples in the area (0.8 pCi/g). Calculated /sup 226/Ra concentrations, based on gamma radiation measurements in shallow (1-m-deep) holes, are in agreement with the results of surface soil and sediment analyses and with gamma-ray exposure rate measurements. The tailings at this site have been stabilized by the addition of 46 to 60 cm (18 to 24 in.) of soil that supports vigorous growth of vegetation. This treatment, coupled with a low-level inventory of /sup 226/Ra in the tailings (50 Ci), has resulted in limited spread of tailings by wind and water

Radiological survey of the radioactive sands and residues at Lowman, Idaho

No uranium ore milling was performed at the Lowman site, which is located approximately 0.8 km northeast of the town of Lowman, Idaho. Nevertheless, approximately 80,000 metric tons of radioactive sands and residues from upgrading of heavy minerals by physical processing methods remain on the site grounds. Measurements of external gamma radiation 1 m above the surface showed exposure rates up to 2.4 mR/hr on site, but the exposure rate off site quickly dropped to the background level in all directions. Analysis of surface soil and sediment samples for /sup 226/Ra and /sup 232/Th indicated a limited spread of radioactive material