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

Profound and reproducible patterns of reduced regional gray matter characterize major depressive disorder

10.1038/s41398-019-0512-8Translational Psychiatry9117

Antiviral drugs for the treatment of influenza: a systematic review and economic evaluation

Objectives: To evaluate the clinical effectiveness (including adverse events) and cost-effectiveness of antivirals for the treatment of naturally acquired influenza for 'at-risk' and otherwise healthy populations. Data sources: Eleven electronic databases (MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Pascal, Science Citation Index, BIOSIS, Latin American and Caribbean Health Sciences, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database) were searched from October 2001 to November 2007. A supplementary search was undertaken in June 2008 for information relating to drug resistance during the 2007–8 influenza season. Review methods: Systematic reviews of the evidence on the clinical effectiveness and cost-effectiveness of antivirals for the treatment of influenza were undertaken. Twenty-nine randomised controlled trials comparing antivirals with each other, placebo, or best symptomatic care were included in the evaluation of clinical effectiveness in patients presenting with an influenza-like illness (ILI). Primary outcomes were measures of symptom duration (median time to alleviation of symptoms and median time to return to normal activity). Incidence of complications, mortality, hospitalisations, antibiotic use (as a surrogate for complications) and adverse events was also assessed. In addition, an independent decision model was developed to evaluate the cost-effectiveness of antiviral treatment from the perspective of the UK NHS. Results: Amantadine was excluded at an early stage, owing to a lack of any new trials that met the inclusion criteria and the limitations of the existing evidence. The review therefore focused on the neuraminidase inhibitors (NIs) oseltamivir and zanamivir, both of which were found to be effective in reducing symptom duration (zanamavir by 0.5–1.0 days and oseltamivir by 0.5–1.5 days). However, the effect sizes were often small and unlikely to be clinically significant in many cases, particularly in healthy adults. For the at-risk subgroups, effect sizes for differences in symptom duration were generally larger, and potentially more clinically significant, than those seen in healthy adults (median duration of symptoms reduced by 1–2 days with zanamivir and 0.50–0.75 days with oseltamivir). However, there was greater uncertainty around these results, with estimates often failing to reach statistical significance. The most consistent data and strongest evidence related to antibiotic use, with both zanamivir and oseltamivir resulting in statistically significant reductions in antibiotic use. In general, the estimates from the cost-effectiveness model were more favourable in at-risk populations (including adults and children with comorbid conditions and the elderly) compared with otherwise healthy populations. Zanamivir was the optimal NI treatment in each of the at-risk populations considered, and oseltamivir was optimal for healthy populations (both adults and children). Conclusions: The clinical effectiveness data for population subgroups used to inform the multiparameter evidence synthesis and cost-effectiveness modelling were, in places, limited and this should be borne in mind when interpreting the findings of this review. Trials were often not designed to determine clinical effectiveness in population subgroups and hence, although the direction of effect was clear, estimates of differences in symptom duration tended to be subject to greater uncertainty in subgroups. Despite some concerns, the use of NIs in at-risk populations appeared to be a cost-effective approach for the treatment of influenza. Well-designed observational studies might also be considered to evaluate the clinical course of influenza in terms of complications, hospitalisation, mortality and quality of life, as well as the impact of NIs

Morphogenetic traits and biomass accumulation of Brachiaria brizantha cv. Xaraés subjected to nitrogen doses

The objective of this experiment was to evaluate the morphogenetic traits and biomass accumulation of Brachiaria brizantha cv. Xaraés subjected to doses of N (0, 125, 250, 375 and 500 kg.ha-1 N). The treatments were arranged in a completely randomized design with four replications. Morphogenetic traits and biomass accumulation of dry matter (DM).ha-1 were evaluated. The results were subjected to statistical analysis by grouping the data in two periods, rainy season and throughout the year. Nitrogen doses influenced leaf appearance in the rainy season and throughout the year, with significant increase in leaf elongation during the rainy season, an increase of 56% compared with control. During this period, maximum dose of N (248.1 kg.ha-1) produced 214.49 kg.ha-1.day-1 DM of leaf blade, which was 133% higher than the control. However, the higher N dose in the rainy season resulted in an increase of 137% in the stalk accumulation compared with non-fertilized grass; estimating maximum accumulation of salk of 84.97 kg.ha-1.day-1 of DM for the application of 326.2 kg.ha-1 N. Doses of N also intensified leaf senescence during the rainy season and throughout the year. The control treatment presented 32% less senescence compared with maximum N dose (270.1 kg.ha-1 N) in the rainy season. Forage loss was estimated at 26.08 kg ha-1.day-1 DM at the maximum dose of 295.0 kg.ha-1 N for this period. All variables studied responded positively to N supply in the rainy season. The accumulation of biomass of the plant reached the maximum point with fertilization close to 250 kg.ha-1 N in the rainy season and 375 kg.ha-1 N throughout the year