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

Torpor in Australian birds

Energy-conserving torpor is characterized by pronounced reductions in body temperature and metabolic rate and, in Australian birds, is known to occur in the Caprimulgiformes (spotted nightjar, Australian owlet-nightjar, tawny frogmouth), Apodiformes (white-throated needletail) and the Passeriformes (dusky woodswallow). Anecdotal evidence suggests that it also may occur in the white-fronted honeyeater, crimson chat, banded whiteface, red-capped robin, white-backed swallow, mistletoebird, and perhaps welcome swallow. Daily torpor (bouts lasting for several hours) appears to be the most common pattern, although anecdotal evidence indicates that white-backed swallows can undergo prolonged torpor. Diurnal birds enter torpor only during the night but nocturnal birds may use it by the day and/or night, and often in more than one bout/day. Body temperatures fall from ~38–41°C during activity to ~29°C during torpor in spotted nightjars, tawny frogmouths, dusky woodswallows and white-throated needletails, and to ~22°C in Australian owlet-nightjars. In the spotted nightjar, a reduction in Tb by ~10°C resulted in a 75% reduction in metabolic rate, emphasizing energy conservation potential. Since torpor is likely to be more crucial for the survival of small birds, a detailed understanding of its use is important, not only for physiologists but also ecologists and wildlife managers. It is thus disappointing that so much information on torpidity in Australian birds is anecdotal, and that so little effort has been made to characterize its patterns and quantify the resulting energy savings and survival benefits for birds in the wild

Dosing of praziquantel by height in sub-Saharan African adults

The cornerstone of schistosomiasis control is mass praziquantel treatment in high prevalence areas. Adults are an important target population, given increasing recognition of the burden of male and female genital schistosomiasis. However, use of weighing scales to calculate praziquantel dosing in rural areas can be challenging. For school-age children, the World Health Organization (WHO) has approved a dose pole to simplify praziquantel dosing based on height. We modified the pediatric dose pole by adding two height categories and incorporating a simple overweight/obesity adjustment, for simplified mass treatment of adults in sub-Saharan Africa. Using the rural Zimbabwean Demographic and Health Survey data, we show that the modified dose pole with body mass index adjustment would result in > 98% of adults receiving an acceptable dose (30–60 mg/kg), with only 1.4% and 0.3% receiving an inadequate dose (< 30 mg/kg) or high dose (> 60 mg/kg), respectively. An adult dose pole may provide a more feasible alternative to weighing scales in community-based praziquantel treatment programs