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Background: UK COVID-19 vaccination policy has evolved to offering COVID-19 booster doses to individuals at increased risk of severe Illness from COVID-19. Building on our analyses of vaccine effectiveness of first, second and initial booster doses, we aimed to identify individuals at increased risk of severe outcomes (i.e., COVID-19 related hospitalisation or death) post the autumn 2022 booster dose. Methods: We undertook a national population-based cohort analysis across all four UK nations through linked primary care, vaccination, hospitalisation and mortality data. We included individuals who received autumn 2022 booster doses of BNT162b2 (Comirnaty) or mRNA-1273 (Spikevax) during the period September 1, 2022 to December 31, 2022 to investigate the risk of severe COVID-19 outcomes. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for the association between demographic and clinical factors and severe COVID-19 outcomes after the autumn booster dose. Analyses were adjusted for age, sex, body mass index (BMI), deprivation, urban/rural areas and comorbidities. Stratified analyses were conducted by vaccine type. We then conducted a fixed-effect meta-analysis to combine results across the four UK nations. Findings: Between September 1, 2022 and December 31, 2022, 7,451,890 individuals ≥18 years received an autumn booster dose. 3500 had severe COVID-19 outcomes (2.9 events per 1000 person-years). Being male (male vs female, aHR 1.41 (1.32-1.51)), older adults (≥80 years vs 18-49 years; 10.43 (8.06-13.50)), underweight (BMI <18.5 vs BMI 25.0-29.9; 2.94 (2.51-3.44)), those with comorbidities (≥5 comorbidities vs none; 9.45 (8.15-10.96)) had a higher risk of COVID-19 hospitalisation or death after the autumn booster dose. Those with a larger household size (≥11 people within household vs 2 people; 1.56 (1.23-1.98)) and from more deprived areas (most deprived vs least deprived quintile; 1.35 (1.21-1.51)) had modestly higher risks. We also observed at least a two-fold increase in risk for those with various chronic neurological conditions, including Down's syndrome, immunodeficiency, chronic kidney disease, cancer, chronic respiratory disease, or cardiovascular disease. Interpretation: Males, older individuals, underweight individuals, those with an increasing number of comorbidities, from a larger household or more deprived areas, and those with specific underlying health conditions remained at increased risk of COVID-19 hospitalisation and death after the autumn 2022 vaccine booster dose. There is now a need to focus on these risk groups for investigating immunogenicity and efficacy of further booster doses or therapeutics. Funding: National Core Studies-Immunity, UK Research and Innovation (Medical Research Council and Economic and Social Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.
RESUMO
PURPOSE: To evaluate the effect of aprotinin withdrawal in 2008 on patient outcomes, to assess the likely risks and benefits of its re-introduction, and to consider the relevance of existing evidence from clinical trials to 'real-world' practice. METHODS: We performed a nested case-control study of two cohorts undergoing adult cardiac surgery in a single tertiary centre. The first group underwent surgery between 1 January 2005 and 30 July 2007 (n = 3,578), prior to aprotinin withdrawal; the second group underwent surgery between 1 January 2009 and 31 December 2010 (n = 3,030), after aprotinin withdrawal. Propensity matching was used to select patients matched for 24 covariates in both groups (n = 3,508). We also estimated the effect of aprotinin withdrawal on a subgroup of high-risk patients (n = 1,002). Results were expressed as adjusted odds ratios (OR) and 95% confidence intervals (CI) for categorical data and hazard ratios (HR) for time-to-event data. RESULTS: In propensity-matched cohorts, the withdrawal of aprotinin from clinical use was associated with more bleeding, higher rates of emergency re-sternotomy, OR 2.10 (1.04-4.25), and acute kidney injury (AKI), OR 1.86 (1.53-2.25). In high-risk patients, the increases in bleeding and AKI following aprotinin withdrawal were of a greater magnitude. Aprotinin withdrawal was also associated with a significant increase in 30-day mortality, HR 2.51 (1.00-6.29), in the high-risk group. The results were not altered by sensitivity analyses that adjusted for potential selection bias, time series bias and unmeasured confounders. CONCLUSIONS: Aprotinin withdrawal was associated with increased complication rates and patient deaths following cardiac surgery. These real-world findings are at odds with those of randomised trials and cohort studies that have considered the clinical role of aprotinin.