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.

Aim:To analyse how age-related losses in crystalline lens transmittance and pupillary area affect circadian photoreception and compare the circadian performance of phakic and pseudophakic individuals of the same age.Methods:The spectral sensitivity of circadian photoreception peaks in the blue part of the spectrum at approximately 460 nm. Photosensitive retinal ganglion cells send unconscious information about environmental illumination to non-visual brain centres including the human body’s master biological clock in the suprachiasmatic nuclei. This information permits human physiology to be optimised and aligned with geophysical day–night cycles using neural and hormonal messengers including melatonin. Age-related transmittance spectra of crystalline lenses and photopic pupil diameter are used with the spectral sensitivity of melatonin suppression and the transmittance spectra of intraocular lenses (IOLs) to analyse how ageing and IOL chromophores affect circadian photoreception.Results:Ageing increases crystalline lens light absorption and decreases pupil area resulting in progressive loss of circadian photoreception. A 10-year-old child has circadian photoreception 10-fold greater than a 95-year-old phakic adult. A 45-year-old adult retains only half the circadian photoreception of early youth. Pseudophakia improves circadian photoreception at all ages, particularly with UV-only blocking IOLs which transmit blue wavelengths optimal for non-visual photoreception.Conclusions:Non-visual retinal ganglion photoreceptor responses to bright, properly timed light exposures help assure effective circadian photoentrainment and optimal diurnal physiological processes. Circadian photoreception can persist in visually blind individuals if retinal ganglion cell photoreceptors and their suprachiasmatic connections are intact. Retinal illumination decreases with ageing due to pupillary miosis and reduced crystalline lens light transmission especially of short wavelengths. Inadequate environmental light and/or ganglion photoreception can cause circadian disruption, increasing the risk of insomnia, depression, numerous systemic disorders and possibly early mortality. Artificial lighting is dimmer and less blue-weighted than natural daylight, contributing to age-related losses in unconscious circadian photoreception. Optimal intraocular lens design should consider the spectral requirements of both conscious and unconscious retinal photoreception.

Our analysis indicates that smoking is associated with a higher likelihood of 30-day mortality and serious postoperative complications. Quantification of increased likelihood of 30-day mortality and a broad range of serious smoking-related complications may enhance the clinician's ability to motivate smoking cessation in surgical patients.

No abstract

No abstract