End of 2022/23 Season Influenza Vaccine Effectiveness in Primary Care in Great Britain.

BACKGROUND: The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2-13 (and 14-15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom. METHODS: End-of-season adjusted vaccine effectiveness (VE) estimates against sentinel primary-care attendance for influenza-like illness, where influenza infection was laboratory confirmed, were calculated using the test negative design, adjusting for potential confounders. METHODS: Results In the mainland United Kingdom, end-of-season VE against all laboratory-confirmed influenza for all those > 65 years of age, most of whom received adjuvanted quadrivalent vaccines, was 30% (95% CI: -6% to 54%). VE for those aged 18-64, who largely received cell-based vaccines, was 47% (95% CI: 37%-56%). Overall VE for 2-17 year olds, predominantly receiving live attenuated vaccines, was 66% (95% CI: 53%-76%). CONCLUSION: The paper provides evidence of moderate influenza VE in 2022/23.

Postpandemic Sentinel Surveillance of Respiratory Diseases in the Context of the World Health Organization Mosaic Framework: Protocol for a Development and Evaluation Study Involving the English Primary Care Network 2023-2024.

BACKGROUND: Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO's mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza. The Oxford-Royal College of General Practitioner Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA) has provided sentinel surveillance since 1967, including virology since 1993. OBJECTIVE: We aim to describe the RSC's plans for sentinel surveillance in the 2023-2024 season and evaluate these plans against the WHO mosaic framework. METHODS: Our approach, which includes patient and public involvement, contributes to surveillance objectives across all 3 domains of the mosaic framework. We will generate an ARI phenotype to enable reporting of this indicator in addition to ILI. These data will support UKHSA's sentinel surveillance, including vaccine effectiveness and burden of disease studies. The panel of virology tests analyzed in UKHSA's reference laboratory will remain unchanged, with additional plans for point-of-care testing, pneumococcus testing, and asymptomatic screening. Our sampling framework for serological surveillance will provide greater representativeness and more samples from younger people. We will create a biomedical resource that enables linkage between clinical data held in the RSC and virology data, including sequencing data, held by the UKHSA. We describe the governance framework for the RSC. RESULTS: We are co-designing our communication about data sharing and sampling, contextualized by the mosaic framework, with national and general practice patient and public involvement groups. We present our ARI digital phenotype and the key data RSC network members are requested to include in computerized medical records. We will share data with the UKHSA to report vaccine effectiveness for COVID-19 and influenza, assess the disease burden of respiratory syncytial virus, and perform syndromic surveillance. Virological surveillance will include COVID-19, influenza, respiratory syncytial virus, and other common respiratory viruses. We plan to pilot point-of-care testing for group A streptococcus, urine tests for pneumococcus, and asymptomatic testing. We will integrate test requests and results with the laboratory-computerized medical record system. A biomedical resource will enable research linking clinical data to virology data. The legal basis for the RSC's pseudonymized data extract is The Health Service (Control of Patient Information) Regulations 2002, and all nonsurveillance uses require research ethics approval. CONCLUSIONS: The RSC extended its surveillance activities to meet more but not all of the mosaic framework's objectives. We have introduced an ARI indicator. We seek to expand our surveillance scope and could do more around transmissibility and the benefits and risks of nonvaccine therapies.

Uptake of COVID-19 vaccinations amongst 3,433,483 children and young people: meta-analysis of UK prospective cohorts.

SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5-17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake. We found that uptake of the first COVID-19 vaccine among CYP was low across all four nations compared to other age groups and diminished with subsequent doses. Age and vaccination status of adults living in the same household were identified as important risk factors associated with vaccine uptake in CYP. For example, 5-11 year-olds were less likely to receive their first vaccine compared to 16-17 year-olds (adjusted Hazard Ratio [aHR]: 0.10 (95%CI: 0.06-0.19)), and CYP in unvaccinated households were less likely to receive their first vaccine compared to CYP in partially vaccinated households (aHR: 0.19, 95%CI 0.13-0.29).

Risk of severe COVID-19 outcomes after autumn 2022 COVID-19 booster vaccinations: a pooled analysis of national prospective cohort studies involving 7.4 million adults in England, Northern Ireland, Scotland and Wales.

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.

Thrombocytopenic, thromboembolic and haemorrhagic events following second dose with BNT162b2 and ChAdOx1: self-controlled case series analysis of the English national sentinel cohort.

Background: Thrombosis associated with thrombocytopenia was a matter of concern post first and second doses of BNT162b2 and ChAdOx1 COVID-19 vaccines. Therefore, it is important to investigate the risk of thrombocytopenic, thromboembolic and haemorrhagic events following a second dose of BNT162b2 and ChAdOx1 COVID-19 vaccines. Methods: We conducted a large-scale self-controlled case series analysis, using routine primary care data linked to hospital data, among 12.3 million individuals (16 years old and above) in England. We used the nationally representative Oxford-Royal College of General Practitioners (RCGP) sentinel network database with baseline and risk periods between 8th December 2020 and 11th June 2022. We included individuals who received two vaccine (primary) doses of the BNT162b2 mRNA (Pfizer-BioNTech) and two vaccine doses of ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in our analyses. We carried out a self-controlled case series (SCCS) analysis for each outcome using a conditional Poisson regression model with an offset for the length of risk period. We reported the incidence rate ratios (IRRs) and 95% confidence intervals (CI) of thrombocytopenic, thromboembolic (including arterial and venous events) and haemorrhagic events, in the period of 0-27 days after receiving a second dose of BNT162b2 or ChAdOx1 vaccines compared to the baseline period (14 or more days prior to first dose, 28 or more days after the second dose and the time between 28 or more days after the first and 14 or more days prior to the second dose). We adjusted for a range of potential confounders, including age, sex, comorbidities and deprivation. Findings: Between December 8, 2020 and February 11, 2022, 6,306,306 individuals were vaccinated with two doses of BNT162b2 and 6,046,785 individuals were vaccinated with two doses of ChAdOx1. Compared to the baseline, our analysis show no increased risk of venous thromboembolic events (VTE) for both BNT162b2 (IRR 0.71, 95% CI: 0.65-0.770) and ChAdOx1 (IRR 0.91, 95% CI: 0.84-0.98); and similarly there was no increased risk for cerebral venous sinus thrombosis (CVST) for both BNT162b2 (IRR 0.87, 95% CI: 0.41-1.85) and ChAdOx1 (IRR 1.73, 95% CI: 0.82-3.68). We additionally report no difference in IRR for pulmonary embolus, and deep vein thrombosis, thrombocytopenia, including idiopathic thrombocytopenic purpura (ITP), and haemorrhagic events post second dose for both BNT162b2. Interpretation: Reassuringly, we found no associations between increased risk of thrombocytopenic, thromboembolic and haemorrhagic events post vaccination with second dose for either of these vaccines. Funding: Data and Connectivity: COVID-19 Vaccines Pharmacovigilance study.

Antibiotic management of urinary tract infection in elderly patients in primary care and its association with bloodstream infections and all cause mortality: population based cohort study.

OBJECTIVE: To evaluate the association between antibiotic treatment for urinary tract infection (UTI) and severe adverse outcomes in elderly patients in primary care. DESIGN: Retrospective population based cohort study. SETTING: Clinical Practice Research Datalink (2007-15) primary care records linked to hospital episode statistics and death records in England. PARTICIPANTS: 157 264 adults aged 65 years or older presenting to a general practitioner with at least one diagnosis of suspected or confirmed lower UTI from November 2007 to May 2015. MAIN OUTCOME MEASURES: Bloodstream infection, hospital admission, and all cause mortality within 60 days after the index UTI diagnosis. RESULTS: Among 312 896 UTI episodes (157 264 unique patients), 7.2% (n=22 534) did not have a record of antibiotics being prescribed and 6.2% (n=19 292) showed a delay in antibiotic prescribing. 1539 episodes of bloodstream infection (0.5%) were recorded within 60 days after the initial UTI. The rate of bloodstream infection was significantly higher among those patients not prescribed an antibiotic (2.9%; n=647) and those recorded as revisiting the general practitioner within seven days of the initial consultation for an antibiotic prescription compared with those given a prescription for an antibiotic at the initial consultation (2.2% v 0.2%; P=0.001). After adjustment for covariates, patients were significantly more likely to experience a bloodstream infection in the deferred antibiotics group (adjusted odds ratio 7.12, 95% confidence interval 6.22 to 8.14) and no antibiotics group (8.08, 7.12 to 9.16) compared with the immediate antibiotics group. The number needed to harm (NNH) for occurrence of bloodstream infection was lower (greater risk) for the no antibiotics group (NNH=37) than for the deferred antibiotics group (NNH=51) compared with the immediate antibiotics group. The rate of hospital admissions was about double among cases with no antibiotics (27.0%) and deferred antibiotics (26.8%) compared with those prescribed immediate antibiotics (14.8%; P=0.001). The risk of all cause mortality was significantly higher with deferred antibiotics and no antibiotics than with immediate antibiotics at any time during the 60 days follow-up (adjusted hazard ratio 1.16, 95% confidence interval 1.06 to 1.27 and 2.18, 2.04 to 2.33, respectively). Men older than 85 years were particularly at risk for both bloodstream infection and 60 day all cause mortality. CONCLUSIONS: In elderly patients with a diagnosis of UTI in primary care, no antibiotics and deferred antibiotics were associated with a significant increase in bloodstream infection and all cause mortality compared with immediate antibiotics. In the context of an increase of Escherichia coli bloodstream infections in England, early initiation of recommended first line antibiotics for UTI in the older population is advocated.

Use of hospital services by age and comorbidity after an index heart failure admission in England: an observational study.

OBJECTIVES: To describe hospital inpatient, emergency department (ED) and outpatient department (OPD) activity for patients in the year following their first emergency admission for heart failure (HF). To assess the proportion receiving specialist assessment within 2 weeks of hospital discharge, as now recommended by guidelines. DESIGN: Observational study of national administrative data. SETTING: All acute NHS hospitals in England. PARTICIPANTS: 82 241 patients with an index emergency admission between April 2009 and March 2011 with a primary diagnosis of HF. MAIN OUTCOME MEASURES: Cardiology OPD appointment within 2 weeks and within a year of discharge from the index admission; emergency department (ED) and inpatient use within a year. RESULTS: 15.1% died during the admission. Of the 69 848 survivors, 19.7% were readmitted within 30 days and half within a year, the majority for non-HF diagnoses. 6.7% returned to the ED within a week of discharge, of whom the majority (77.6%) were admitted. The two most common OPD specialties during the year were cardiology (24.7% of the total appointments) and anticoagulant services (12.5%). Although half of all patients had a cardiology appointment within a year, the proportion within the recommended 2 weeks of discharge was just 6.8% overall and varied by age, from 2.4% in those aged 90+ to 19.6% in those aged 18-45 (p<0.0001); appointments in other specialties made up only some of the shortfall. More comorbidity at any age was associated with higher rates of cardiology OPD follow-up. CONCLUSIONS: Patients with HF are high users of hospital services. Postdischarge cardiology OPD follow-up rates fell well below current National Institute for Health and Care Excellence guidelines, particularly for the elderly and those with less comorbidity.

Relation between process measures and diagnosis-specific readmission rates in patients with heart failure.

OBJECTIVES: To explore the relations between cause-specific readmission rates and National Heart Failure Audit process of care measures in patients admitted for heart failure (HF). METHODS: Using admissions data for all acute hospitals in England for April 2009-March 2012, we defined an index admission as the first emergency admission with a primary diagnosis of HF for at least three years. We compared risk-adjusted readmission rates for HF and for all non-HF diagnoses combined, risk-adjusted in-hospital mortality rates and performance on six Audit process measures. RESULTS: 14.7% of 123,644 patients died during the index admission. Of 105,441 index live discharges, 6853 (6.5%) were readmitted as emergencies within 7 days and 20,144 (19.1%) within 30 days. Index admission mortality rates correlated positively but weakly with non-HF readmission rates but not at all with HF rates. There was modest positive correlation at 7 days between HF and non-HF readmission rates (r=+0.24) but no significant relation at 30 or 365 days. All six process measures (prescribing of ACE inhibitors and beta-blockers, echocardiogram, cardiology inpatient and follow-up by cardiologist and HF liaison) correlated modestly but significantly with lower HF readmission rates at 7 days (r at most -0.26), only three did at 30 days and only cardiology follow-up did for non-HF at either 7 or 30 days; all associations were diminished at 365 days. CONCLUSIONS: Hospitals scoring higher on evidence-based HF process measures had lower readmission rates, though the association seems limited to HF readmissions and is modest in strength and duration.

Increased perioperative mortality following aprotinin withdrawal: a real-world analysis of blood management strategies in adult cardiac surgery.

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.

Family doctor responses to changes in incentives for influenza immunization under the U.K. Quality and Outcomes Framework pay-for-performance scheme.

OBJECTIVE: To analyze the effect of setting higher targets, in a primary care pay-for-performance scheme, on rates of influenza immunization and exception reporting. STUDY SETTING: The U.K. Quality and Outcomes Framework links financial rewards for family practices to four separate influenza immunization rates for patients with coronary heart disease (CHD), chronic obstructive pulmonary disease, diabetes, and stroke. There is no additional payment for immunization rates above an upper threshold. Patients for whom immunization would be inappropriate can be excepted from the practice for the calculation of the practice immunization rate. DATA: Practice-level information on immunizations and exceptions extracted from electronic records of all practices in England 2004/05 to 2009/10 (n=8,212-8,403). STUDY DESIGN: Longitudinal random effect multilevel linear regressions comparing changes in practice immunization and exception rates for the four chronic conditions before and after the increase in the upper threshold immunization rate for CHD patients in 2006/07. PRINCIPAL FINDINGS: The 5 percent increase in the upper payment threshold for CHD was associated with increases in the proportion of immunized CHD patients (0.41 percent, CI: 0.25-0.56 percent), and exception was reported (0.26 percent, CI: 0.12-0.40 percent). CONCLUSIONS: Making quality targets more demanding can not only lead to improvement in quality of care but can also have other consequences.

Determinants of general practitioners' wages in England.

We analyse the determinants of annual net income and wages (net income/hours) of general practitioners (GPs) using data for 2271 GPs in England recorded during Autumn 2008. The average GP had an annual net income of £97,500 and worked 43 h per week. The mean wage was £51 per h. Net income and wages depended on gender, experience, list size, partnership size, whether or not the GP worked in a dispensing practice, whether they were salaried of self-employed, whether they worked in a practice with a nationally or locally negotiated contract, and the characteristics of the local population (proportion from ethnic minorities, rurality, and income deprivation). The findings have implications for pay discrimination by GP gender and ethnicity, GP preferences for partnership size, incentives for competition for patients, and compensating differentials for local population characteristics. They also shed light on the attractiveness to GPs in England of locally negotiated (personal medical services) versus nationally negotiated (general medical services) contracts.