Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Assessing Endothelial Responsiveness After Cardiopulmonary Bypass: Insights on Different Perfusion Modalities

Objective Cardiopulmonary bypass (CPB) exerts several deleterious effects on inflammatory pathways. Most of these can be related to an endothelial insult leading to endothelial dysfunction. To date, the degree of endothelial damage only has been evaluated on a cellular and molecular level, but no studies exist looking at the functional effects of CPB on the endothelium. Design Previous studies hypothesized a negative effect of continuous flow as opposed to the physiologic pulsatile flow. The aim of the present retrospective study was to investigate how different perfusion modalities during CPB (ie, continuous v pulsatile flow) or its avoidance differently impact endothelial function. Setting Cardiovascular operating room and intensive care unit of a large tertiary University Hospital in Monza, Italy. Participants Flow-mediated dilatation (FMD) of the brachial artery was assessed in 29 patients undergoing elective myocardial revascularization. Ten patients receiving continuous-flow CPB, 10 receiving pulsatile-flow CPB, and 9 scheduled for beating-heart revascularization were studied. Interventions Patients were studied at baseline (after induction of general anesthesia), after CPB upon intensive care unit (ICU) admission after surgery, and on the first postoperative day before discharge from the ICU (on average, 24 hours after CPB discontinuation). Measurements and Main Results The continuous-flow CPB group demonstrated a significant reduction in FMD after CPB, (12.8%±9.7% v 1.6%±1.5%, p<0.01), which lasted up to the first postoperative day (5.9%±4.1%). On the other hand, FMD did not change in the pulsatile-flow group (12.5%±10.5%, 11.0%±7.2%, and 16.6%±11.7%, respectively). FMD also was unaffected in the beating-heart group, thus suggesting a direct effect of CPB itself on endothelial function. Conclusions In conclusion, in this study population of adult patients undergoing elective coronary revascularization, continuous-flow CPB markedly impaired endothelial function, although this was not the case with pulsatile-flow CPB. This study posed the rationale for further investigations on the potential value of FMD to predict cardiovascular events in these patients

Regiões-províncias na Guerra da Tríplice Aliança

O texto destaca as principais incidências políticas dos países envolvidos na Guerra do Paraguai e os principais efeitos pela mesma. Serão tratados os problemas apresentados pelos componentes da Tríplice Aliança: da Confederação Argentina, tanto no litoral quanto no noroeste; do Uruguai, muito dependente das questões argentinas; do Brasil serão examinadas as questões relativas ao Rio Grande do Sul, aquela província mais diretamente envolvida pela guerra. A hipótese de que a Guerra do Paraguai não foi um fator de consolidação daquelas nações que compuseram a Tríplice Aliança obriga a formulação de outra questão: quais seriam as entidades políticas de fato na América platina, e em que medida a guerra a um inimigo externo mantinha ou mesmo reforçava as identidades regionais em contrapartida a uma unidade política nacional. O presente texto apresenta a hipótese de que eram as "regiões-províncias" as reais unidades políticas do espaço platino