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.
BackgroundIn a single general practice (GP) surgery in England, there was an eightfold increase in the prevalence of type 2 diabetes (T2D) in three decades with 57 cases and 472 cases recorded in 1987 and 2018, respectively. This mirrors the growing burden of T2D on the health of populations round the world along with healthcare funding and provision more broadly. Emerging evidence suggests beneficial effects of carbohydrate-restricted diets on glycaemic control in T2D, but its impact in a ‘real-world’ primary care setting has not been fully evaluated.MethodsAdvice on a lower carbohydrate diet was offered routinely to patients with newly diagnosed and pre-existing T2D or prediabetes between 2013 and 2019, in the Norwood GP practice with 9800 patients. Conventional ‘one-to-one’ GP consultations were used, supplemented by group consultations, to help patients better understand the glycaemic consequences of their dietary choices with a particular focus on sugar, carbohydrates and foods with a higher Glycaemic Index. Those interested were computer coded for ongoing audit to compare ‘baseline’ with ‘latest follow-up’ for relevant parameters.ResultsBy 2019, 128 (27%) of the practice population with T2D and 71 people with prediabetes had opted to follow a lower carbohydrate diet for a mean duration of 23 months. For patients with T2D, the median (IQR) weight dropped from of 99.7 (86.2, 109.3) kg to 91.4 (79, 101.1) kg, p<0.001, while the median (IQR) HbA1c dropped from 65.5 (55, 82) mmol/mol to 48 (43, 55) mmol/mol, p<0.001. For patients with prediabetes, the median (IQR) HbA1c dropped from 44 (43, 45) mmol/mol to 39 (38, 41) mmol/mol, p<0.001. Drug-free T2D remission occurred in 46% of participants. In patients with prediabetes, 93% attained a normal HbA1c. Since 2015, there has been a relative reduction in practice prescribing of drugs for diabetes leading to a T2D prescribing budget £50 885 per year less than average for the area.ConclusionsThis approach to lower carbohydrate dietary advice for patients with T2D and prediabetes was incorporated successfully into routine primary care over 6 years. There were statistically significant improvements in both groups for weight, HbA1c, lipid profiles and blood pressure as well as significant drug budget savings. These results suggest a need for more empirical research on the effects of lower carbohydrate diet and long-term glycaemic control while recording collateral impacts to other metabolic health outcomes.
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