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.
Intensive broiler (meat) chicken production now exceeds 800 million birds each year in the United Kingdom and 2 x 10(10) birds worldwide, but it attracts accusations of poor welfare. The European Union is currently adopting standards for broilers aimed at a chief welfare concern--namely, overcrowding--by limiting maximum 'stocking density' (bird weight per unit area). It is not clear, however, whether this will genuinely improve bird welfare because evidence is contradictory. Here we report on broiler welfare in relation to the European Union proposals through a large-scale study (2.7 million birds) with the unprecedented cooperation of ten major broiler producers in an experimental manipulation of stocking density under a range of commercial conditions. Producer companies stocked birds to five different final densities, but otherwise followed company practice, which we recorded in addition to temperature, humidity, litter and air quality. We assessed welfare through mortality, physiology, behaviour and health, with an emphasis on leg health and walking ability. Our results show that differences among producers in the environment that they provide for chickens have more impact on welfare than has stocking density itself.
Data from a large commercial-scale experiment in which 10 major broiler producer companies stocked whole houses of birds at 30, 34, 38, 42, and 46 kg/m2 were analyzed to identify 1) temperature and humidity profiles achieved throughout the growth cycle, 2) management practices and equipment that contributed to observed variation in environmental conditions, and 3) the extent to which environmental variables affected bird welfare. The study involved a total of 2.7 million birds in 114 houses on commercial farms with measurement of a wide range of environmental and bird variables. Much of the variation in broiler health and welfare was associated with the percentage of time a company could maintain house temperature and RH within limits recommended by the breeder company. RH in the first week of life was particularly important to later health, suggesting that better control of humidity might lead to improved welfare. Key management factors affecting bird welfare were those relating to good ventilation and air control such as the type of ventilation, type of drinker, numbers of stockmen, and litter type. Controlling the environment, particularly temperature, humidity, and air and litter quality, is crucial to broiler chicken welfare. This does not mean that stocking density is unimportant, but lowering stocking density on its own, without regard to the environment the birds experience, is not sufficient. Genuine improvements in bird welfare will come from setting standards that combine stocking density, safeguards on the environment, and the genetic makeup of the birds.
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