Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses.

BACKGROUND World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)

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

Assembling places and persons: a tenth-century Viking boat burial from Swordle Bay on the Ardnamurchan peninsula, western Scotland

A rare, intact Viking boat burial in western Scotland contained a rich assemblage of grave goods, providing clues to the identity and origins of both the interred individual and the people who gathered to create the site. The burial evokes the mundane and the exotic, past and present, as well as local, national and international identities. Isotopic analysis of the teeth hints at a possible Scandinavian origin for the deceased, while Scottish, Irish and Scandinavian connections are attested by the grave goods. Weapons indicate a warrior of high status; other objects imply connections to daily life, cooking and work, farming and food production. The burial site is itself rich in symbolic associations, being close to a Neolithic burial cairn, the stones of which may have been incorporated into the grave

Assembling places and persons: a tenth-century Viking boat burial from Swordle Bay on the Ardnamurchan peninsula, western Scotland

A rare, intact Viking boat burial in western Scotland contained a rich assemblage of grave goods, providing clues to the identity and origins of both the interred individual and the people who gathered to create the site. The burial evokes the mundane and the exotic, past and present, as well as local, national and international identities. Isotopic analysis of the teeth hints at a possible Scandinavian origin for the deceased, while Scottish, Irish and Scandinavian connections are attested by the grave goods. Weapons indicate a warrior of high status; other objects imply connections to daily life, cooking and work, farming and food production. The burial site is itself rich in symbolic associations, being close to a Neolithic burial cairn, the stones of which may have been incorporated into the grave

Modelo de regressão para a previsão de produdividade de cafeeiros no Estado de Minas Gerais A regression model to predict coffee productivity in Southern Minas Gerais, Brazil

Com este trabalho, objetivou-se parametrizar e testar um modelo de regressão linear múltipla aplicado sobre os componentes principais mais significativos obtidos de séries de produtividades da cultura do café, representativas de três municípios da região Sul do Estado de Minas Gerais, tomando-se por base o modelo de Stewart et al. (1976), porém se acrescentando novas variáveis representadas por elementos agrometeorológicos, além das penalizações hídricas para os quatro trimestres do ciclo agrícola (julho a junho) da cultura. Tendo em vista ser o número de observações inferior à quantidade de variáveis, recorreu-se à análise multivariada de componentes principais para reduzir a dimensão do conjunto dessas variáveis. A análise de regressão linear múltipla foi aplicada nos três primeiros componentes principais. Os resultados dos testes apresentaram erros relativos percentuais das estimativas bastante discrepantes, ocorrendo tendência de superestimarem as produtividades; contudo, verificou-se que as estimativas pelo modelo tenderam a apresentar comportamento similar ao dos dados observados.<br>The objective of this work was to set up and test a multiple linear regression model applied to principal components for representative coffee crop yield series for three places in Southern Minas Gerais, based on the model proposed by Stewart et al. (1976), with new variables, represented by agrometeorological elements, besides the soil water depletion for the four quarterly periods in agricultural cycle (July to June). Since the number of observations was lower than the amount number of variables, we resorted to principal component analysis to reduce the dimension of this set of variables. The multiple linear regression analysis was applied to the first three principal components. In agreement with the tests, the model presented relative errors of estimates with high discrepancies and a tendency to overestimate productivity for the three places. However, it was verified that the estimates for the model tended to present behavior similar to observed data