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Waning effectiveness of BNT162b2 and ChAdOx1 covid-19 vaccines over six months since second dose: OpenSAFELY cohort study using linked electronic health records.
ObjectiveTo estimate waning of covid-19 vaccine effectiveness over six months after second dose.DesignCohort study, approved by NHS England.SettingLinked primary care, hospital, and covid-19 records within the OpenSAFELY-TPP database.ParticipantsAdults without previous SARS-CoV-2 infection were eligible, excluding care home residents and healthcare professionals.ExposuresPeople who had received two doses of BNT162b2 or ChAdOx1 (administered during the national vaccine rollout) were compared with unvaccinated people during six consecutive comparison periods, each of four weeks.Main outcome measuresAdjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, positive SARS-CoV-2 test, and non-covid-19 related death comparing vaccinated with unvaccinated people. Waning vaccine effectiveness was quantified as ratios of adjusted hazard ratios per four week period, separately for subgroups aged ≥65 years, 18-64 years and clinically vulnerable, 40-64 years, and 18-39 years.Results1 951 866 and 3 219 349 eligible adults received two doses of BNT162b2 and ChAdOx1, respectively, and 2 422 980 remained unvaccinated. Waning of vaccine effectiveness was estimated to be similar across outcomes and vaccine brands. In the ≥65 years subgroup, ratios of adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test ranged from 1.19 (95% confidence interval 1.14 to 1.24)to 1.34 (1.09 to 1.64) per four weeks. Despite waning vaccine effectiveness, rates of covid-19 related hospital admission and death were substantially lower among vaccinated than unvaccinated adults up to 26 weeks after the second dose, with estimated vaccine effectiveness ≥80% for BNT162b2, and ≥75% for ChAdOx1. By weeks 23-26, rates of positive SARS-CoV-2 test in vaccinated people were similar to or higher than in unvaccinated people (adjusted hazard ratios up to 1.72 (1.11 to 2.68) for BNT162b2 and 1.86 (1.79 to 1.93) for ChAdOx1).ConclusionsThe rate at which estimated vaccine effectiveness waned was consistent for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test and was similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination.
A qualitative comparison of data infrastructures for COVID-19 health-related data: lessons for the European Health Data Space
The COVID-19 pandemic has represented the first global health emergency to be tackled through widespread data collection via a broad array of digital health technologies. Throughout Europe, data infrastructures for the acquisition, processing, and management of COVID-19 data were either implemented ex novo or “repurposed” towards this end. Analysing and comparing these data practices may hold great value to the upcoming European Health Data Space (EHDS) implementation. This study investigates the implementation of COVID-19 data infrastructures in four European countries–Italy, Sweden, Denmark, and England–to highlight challenges related to technical, ethical, and legal aspects of secondary uses of health-related data, particularly given the implementation of the EHDS. The data infrastructures included in the study reveal profound differences in design and data access practices, partly owing to the social contexts in which they were established. Challenges for data-sharing and integration include fragmentation of standards and requirements, ethical concerns about access by corporate actors to publicly collected datasets, and lack of robust legal bases. Investigating such infrastructures is crucial to probe challenges in data sharing practices within the European context and represents a revealing test case to anticipate opportunities and challenges in aligning current technical and legal standards with EHDS’ requirements.
No evidence of difference in mortality with amoxicillin versus co-amoxiclav for hospital treatment of community-acquired pneumonia.
ObjectivesCurrent guidelines recommend broad-spectrum antibiotics for high-severity community-acquired pneumonia (CAP), potentially contributing to antimicrobial resistance (AMR). We aim to compare outcomes in CAP patients treated with amoxicillin (narrow-spectrum) versus co-amoxiclav (broad-spectrum), to understand if narrow-spectrum antibiotics could be used more widely.MethodsWe analysed electronic health records from adults (≥16 y) admitted to hospital with a primary diagnosis of pneumonia between 01-January-2016 and 30-September-2023 in Oxfordshire, United Kingdom. Patients receiving baseline ([-12 h,+24 h] from admission) amoxicillin or co-amoxiclav were included. The association between 30-day all-cause mortality and baseline antibiotic was examined using propensity score (PS) matching and inverse probability treatment weighting (IPTW) to address confounding by baseline characteristics and disease severity. Subgroup analyses by disease severity and sensitivity analyses with missing covariates imputed were also conducted.ResultsAmong 16,072 admissions with a primary diagnosis of pneumonia, 9685 received either baseline amoxicillin or co-amoxiclav. There was no evidence of a difference in 30-day mortality between patients receiving initial co-amoxiclav vs. amoxicillin (PS matching: marginal odds ratio 0.97 [0.76-1.27], p = 0.61; IPTW: 1.02 [0.78-1.33], p = 0.87). Results remained similar across stratified analyses of mild, moderate, and severe pneumonia. Results were also similar with missing data imputed. There was also no evidence of an association between 30-day mortality and use of additional macrolides or additional doxycycline.ConclusionsThere was no evidence of co-amoxiclav being advantageous over amoxicillin for treatment of CAP in 30-day mortality at a population-level, regardless of disease severity. Wider use of narrow-spectrum empirical treatment of moderate/severe CAP should be considered to curb potential for AMR.
Prospective evaluation of 92 protein biomarkers for early detection of endometrial cancer.
The human epididymis protein 4 (HE4) remains the best available endometrial cancer (EC) biomarker; however, its discrimination between cases and cancer-free individuals is limited and might be improved when combined with other protein markers. We evaluated the discrimination capacity of 92 proteins as potential early detection biomarkers for EC in nested case-control studies in the European Prospective Investigation into Cancer and Nutrition (EPIC) (63 cases, 123 controls) and Janus (75 cases, 146 controls) cohorts, evaluating blood samples taken ≤2 years prior to diagnosis. Proteins were measured with the Olink Target 96 Oncology II panel assays. Areas under the receiver operating characteristic curves (AUCs) were calculated using logistic regression. The discrimination between cases and controls of top-performing proteins was modest (EPIC: HE4, CA125, CAIX, and S100A4; Janus: HE4, CA125, FURIN, CXCL13, and IL6; AUC range: 0.65 [S100A4], 0.76 [HE4, EPIC] within 0 to <12 months of blood collection) and decreased as the time between blood draw and cancer diagnosis increased (12-24 months AUC range: 0.49 [S100A4], 0.69 [CA125, Janus]). The combination of these other markers with HE4 did not improve discrimination. HE4 and other candidate proteins had limited discrimination between EC cases and controls and hence do not appear to be useful for early detection of this disease in women at average population risk.
Amount and intensity of daily total physical activity, step count and risk of incident cancer in the UK Biobank.
ObjectivesTo investigate associations between daily physical activity, activity intensity and step counts with incident cancer risk.MethodsProspective analysis of UK Biobank participants who wore wrist-based accelerometers for 7 days, followed for cancer incidence (mean follow-up 5.8 years, SD 1.3). Time-series machine-learning models derived total physical activity, sedentary behaviour (SB), light-intensity physical activity (LIPA), moderate-vigorous-intensity physical activity (MVPA) and step counts. The outcome was a composite of 13 cancers previously associated with low physical activity in questionnaire-based studies. Cox proportional hazard models estimated HRs and 95% CIs, adjusted for demographic, health and lifestyle factors. We also explored associations of LIPA, MVPA and SB with cancer risk.ResultsAmong 85 394 participants (median age 63 (IQR 56-68)), 2633 were diagnosed with cancer during follow-up. Compared with individuals in the lowest quintile of total physical activity (<21.6 milligravity units), those in the highest (34.3+) had a 26% lower cancer risk (HR=0.74 (95% CI 0.65 to 0.84)). After mutual adjustment, LIPA (HR=0.94 (95% CI 0.90 to 0.98)) and MVPA (HR=0.87 (95% CI 0.79 to 0.94)) were associated with lower risk, but SB was not. Similar associations were observed for substituting 1 hour/day of SB with LIPA or MVPA. Daily step counts were inversely associated with cancer, with the dose-response beginning to plateau at around 9 000 steps/day (HR=0.89 (95% CI 0.83 to 0.96) 7000 vs 5000 steps; HR=0.84 (95% CI 0.76 to 0.93) 9000 vs 5000 steps). There was no significant association between stepping intensity (peak 30-minute cadence) and cancer after adjusting for step count.ConclusionTotal physical activity, LIPA, MVPA and step counts were inversely associated with incident cancer.
The role of the enrolling clinician in emergency research conducted under an exception from informed consent.
The Exception from Informed Consent (EFIC) permits patient enrolment into therapeutic emergency research where obtaining informed consent is challenging. Yet this fails to resolve a core ethical conflict in the research and has generated controversy. This is because existing justification and practice has relied on applying EFIC per study-a wholesale permission to enroll irrespective of circumstance-instead of per patient. Our novel justification for enrolment centers on applying EFIC per patient, which empowers the enrolling clinician to judge whether to enroll patients with an Exception. This contrasts with the idea that clinician judgment is surplus to the judgements already made by institutions in deciding the research may proceed. Instead, we show that enrolling clinician's judgment is ethically significant and should not be overlooked: attending to this strengthens the research ethically and reduces controversy. There should be a bigger role for the clinician in the research enrolment space.
Improving Outcomes in Mental Health (IOMH)-an Australian longitudinal clinical study of families with children with neurodevelopmental problems: cohort profile.
PurposeChildren with neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) face a range of challenges which impact their daily functioning and that of their family. NDDs are often associated with significant mental health problems which can influence the course. The Improving Outcomes in Mental Health cohort described in this article aims to investigate the risk factors for the persistence and severity of mental health problems in children with NDDs.ParticipantsA total of 1084 families (primary caregivers and children) were recruited from the Child Development Program at the Children's Health Queensland Hospital and Health Service in Brisbane, Australia. 1471 caregivers (female n=1036) participated in the study, which included 382 families with 2 or more caregivers participating. The children were predominantly male (71%), with the average age of all children 5.6 years.Findings to dateThe most prevalent child clinical diagnoses were ASD and ADHD, with half of children receiving more than one diagnosis. Caregiver reports indicated that children were experiencing clinical levels of depression (30.8%) and anxiety (27.6%). Approximately 39% of caregivers scored in the subclinical or clinical range for at least one Diagnostic and Statistical Manual of Mental Disorders measure, the majority reporting depressive problems.Future plansFuture plans for this data set include analysis of environmental variables such as family structure, income, school achievements and leisure activities as risk factors for the persistence of mental health problems in children with NDDs. Genetic data will be used to provide insights into the heritability of mental illness and improve prediction.
Call for a fairer approach to authorship in publishing biomedical research.
In this Perspective article, we call for a fairer approach to authorship practice in collaborative biomedical research to promote equity and inclusiveness. Current practice does not adequately recognise all contributors involved in different stages of the work and may exacerbate preexisting inequalities. Here, we discuss some key features of contemporary collaborative research practice that complicate authorship decisions. These include the project size, complexity of multidisciplinary team involvement and researchers having varying degrees of expertise and experience. We conclude by making some suggestions to address these concerns.