Early and ongoing stable glycaemic control is associated with a reduction in major adverse cardiovascular events in people with type 2 diabetes: A primary care cohort study.

AIM: To determine whether achieving early glycaemic control, and any subsequent glycaemic variability, was associated with any change in the risk of major adverse cardiovascular events (MACE). MATERIALS AND METHODS: A retrospective cohort analysis from the Oxford-Royal College of General Practitioners Research and Surveillance Centre database-a large, English primary care network-was conducted. We followed newly diagnosed patients with type 2 diabetes, on or after 1 January 2005, aged 25 years or older at diagnosis, with HbA1c measurements at both diagnosis and after 1 year, plus five or more measurements of HbA1c thereafter. Three glycaemic bands were created: groups A (HbA1c < 58 mmol/mol [<7.5%]), B (HbA1c ≥ 58 to 75 mmol/mol [7.5%-9.0%]) and C (HbA1c ≥ 75 mmol/mol [≥9.0%]). Movement between bands was determined from diagnosis to 1 year. Additionally, for data after the first 12 months, a glycaemic variability score was calculated from the number of successive HbA1c readings differing by 0.5% or higher (≥5.5 mmol/mol). Risk of MACE from 1 year postdiagnosis was assessed using time-varying Cox proportional hazards models, which included the first-year transition and the glycaemic variability score. RESULTS: From 26 180 patients, there were 2300 MACE. Compared with group A->A transition over 1 year, those with C->A transition had a reduced risk of MACE (HR 0.75; 95% CI 0.60-0.94; P = .014), whereas group C->C had HR 1.21 (0.81-1.81; P = .34). Compared with the lowest glycaemic variability score, the greatest variability increased the risk of MACE (HR 1.51; 1.11-2.06; P = .0096). CONCLUSION: Early control of HbA1c improved cardiovascular outcomes in type 2 diabetes, although subsequent glycaemic variability had a negative effect on an individual's risk.

National record-linkage study of hospital admissions for schizophrenia in childhood and adolescence in England.

BACKGROUND: There is a lack of information on changes in hospital admission rates for childhood-onset schizophrenia (COS), or on patient characteristics, to inform clinical research and health service provision. AIMS: To report age- and sex-specific incidence rates of hospital admissions and day patient care for schizophrenia (ICD-10 F20) and non-affective psychosis (ICD-10 F20-29), by year of occurrence and age, in childhood and adolescence. METHODS: Population-based study using person-linked data for England (available 2001-2016); time-periods in single years and 4-year groups. RESULTS: Hospitalised incidence for schizophrenia increased with increasing age, from 0.03 (95% confidence interval (CI) 0.02-0.05) and 0.01 (0-0.01) per 100,000 in, respectively, males and females aged 5-12 years, to 3.67 (3.44-3.91) in males and 1.58 (1.43-1.75) in females aged 13-17 years. There was no gender difference in hospitalised incidence rates in children aged 5-12, but in 13-17 years old, there was a male excess. Rates for schizophrenia were stable over time in 5-12 years old. In ages 13-17, rates for schizophrenia decreased between 2001-2004 and 2013-2016 in males, from 6.65 (6.04-7.31) down to 1.40 (1.13-1.73), and in females from 2.42 (2.05-2.83) to 1.18 (0.92-1.48). The hospitalisation rates for schizophrenia and non-affective psychosis, combined, in 13-17 years old decreased in males from 14.20 (13.30-15.14) in 2001-2004 to 10.77 (9.97-11.60) in 2013-2016, but increased in females from 7.49 (6.83-8.20) to 10.16 (9.38-11.00). CONCLUSIONS: The study confirms that childhood-onset schizophrenia is extremely rare, with only 32 cases identified over a 15-year period in the whole of England. The incidence of schizophrenia and non-affective psychosis increased substantially in adolescence; however, the marked reduction in the proportion of those diagnosed with schizophrenia in this age group suggests a possible change in diagnostic practice.

Low levels of respiratory syncytial virus activity in Europe during the 2020/21 season: what can we expect in the coming summer and autumn/winter?

Since the introduction of non-pharmacological interventions to control COVID-19, respiratory syncytial virus (RSV) activity in Europe has been limited. Surveillance data for 17 countries showed delayed RSV epidemics in France (≥ 12 w) and Iceland (≥ 4 w) during the 2020/21 season. RSV cases (predominantly small children) in France and Iceland were older compared with previous seasons. We hypothesise that future RSV epidemic(s) could start outside the usual autumn/winter season and be larger than expected. Year-round surveillance of RSV is of critical importance.

Using an Ontology to Facilitate More Accurate Coding of Social Prescriptions Addressing Social Determinants of Health: Feasibility Study.

BACKGROUND: National Health Service (NHS) England supports social prescribing in order to address social determinants of health, which account for approximately 80% of all health outcomes. Nevertheless, data on ongoing social prescribing activities are lacking. Although NHS England has attempted to overcome this problem by recommending 3 standardized primary care codes, these codes do not capture the social prescribing activity to a level of granularity that would allow for fair attribution of outcomes to social prescribing. OBJECTIVE: In this study, we explored whether an alternative approach to coding social prescribing activity, specifically through a social prescribing ontology, can be used to capture the social prescriptions used in primary care in greater detail. METHODS: The social prescribing ontology, implemented according to the Web Ontology Language, was designed to cover several key concepts encompassing social determinants of health. Readv2 and Clinical Terms Version 3 codes were identified using the NHS Terms Browser. The Royal College of General Practitioners Research Surveillance Centre, a sentinel network of over 1000 primary care practices across England covering a population of more than 4,000,000 registered patients, was used for data analyses for a defined period (ie, January 2011 to December 2019). RESULTS: In all, 668 codes capturing social prescriptions addressing different social determinants of health were identified for the social prescribing ontology. For the study period, social prescribing ontology codes were used 5,504,037 times by primary care practices of the Royal College of General Practitioners Research Surveillance Centre as compared to 29,606 instances of use of social prescribing codes, including NHS England's recommended codes. CONCLUSIONS: A social prescribing ontology provides a powerful alternative to the codes currently recommended by NHS England to capture detailed social prescribing activity in England. The more detailed information thus obtained will allow for explorations about whether outputs or outcomes of care delivery can be attributed to social prescriptions, which is essential for demonstrating the overall value that social prescribing can deliver to the NHS and health care systems.

Effect of Exhaust- and Nonexhaust-Related Components of Particulate Matter on Long-Term Survival After Stroke.

BACKGROUND AND PURPOSE: Outdoor air pollution represents a potentially modifiable risk factor for stroke. We examined the link between ambient pollution and mortality up to 5 years poststroke, especially for pollutants associated with vehicle exhaust. METHODS: Data from the South London Stroke Register, a population-based register covering an urban, multiethnic population, were used. Hazard ratios (HR) for a 1 interquartile range increase in particulate matter <2.5 µm diameter (PM2.5) and PM <10 µm (PM10) were estimated poststroke using Cox regression, overall and broken down into exhaust and nonexhaust components. Analysis was stratified for ischemic and hemorrhagic strokes and was further broken down by Oxford Community Stroke Project classification. RESULTS: The hazard of death associated with PM2.5 up to 5 years after stroke was significantly elevated (P=0.006) for all strokes (HR=1.28; 95% confidence interval [CI], 1.08-1.53) and ischemic strokes (HR, 1.32; 95% CI, 1.08-1.62). Within ischemic subtypes, PM2.5 pollution increased mortality risk for total anterior circulation infarcts by 2-fold (HR, 2.01; 95% CI, 1.17-3.48; P=0.012) and by 78% for lacunar infarcts (HR, 1.78; 95% CI, 1.18-2.66; P=0.006). PM10 pollution was associated with 45% increased mortality risk for lacunar infarct strokes (HR, 1.45; 95% CI, 1.06-2.00; P=0.022). Separating PM2.5 and PM10 into exhaust and nonexhaust components did not show increased mortality. CONCLUSIONS: Exposure to certain outdoor PM pollution, particularly PM2.5, increased mortality risk poststroke up to 5 years after the initial stroke.

Mortality following hospital discharge with a diagnosis of eating disorder: national record linkage study, England, 2001-2009.

OBJECTIVE: To calculate mortality of people with eating disorders (ED) in England, relative to that of people of the same age and sex, between 2001 and 2009. We were specifically interested in mortality amongst adolescents and young adults (15-24 years), and older adults (25-44 years). METHOD: We analyzed a NHS Hospital Episode Statistics (HES) dataset for all England, linked to death registrations, to calculate age- and sex-specific discharge rates for people with a diagnosis of ED and their subsequent mortality by one year after discharge. RESULTS: The standardized mortality ratio (SMR) for adolescents and young adults with a diagnosis of ED was 7.8 (95% confidence interval: 4.4-11.2). This compares with an SMR for people of the same age with schizophrenia of 10.2 (8.3-12.2), with bipolar disorder of 3.6 (1.1-6.1, and with depression of 4.5 (3.6-5.3). Of the ED, the SMR for anorexia nervosa (AN) in people aged 15-24 was 11.5 (6.0-17.0), for bulimia nervosa (BN) was 4.1 (0-8.7), and eating disorders not otherwise specified (ED NOS) was 1.4 (0-4.0). For older adults aged 25-44 years, the SMR for ED was 10.7 (7.7-13.6). Specifically, for AN was 14.0 (9.2-18.8), for BN was 7.7 (3.5-11.9), and ED NOS was 4.7 (1.4-8.0), for schizophrenia was 7.3 (6.6-7.9), for bipolar disorder was 4.3 (3.5-5.1) and for depression was 4.9 (4.6-5.3). No deaths were recorded below 15 years of age. DISCUSSION: This study confirms the high SMR associated with ED, notably with anorexia and bulimia.

Qualitative evaluation of a molecular point-of-care testing study for influenza in UK primary care.

BACKGROUND: Influenza contributes to the surge in winter infections and the consequent winter pressures on the health service. Molecular point-of-care testing(POCT) for influenza might improve patient management by providing rapid and accurate clinical diagnosis to inform the timely initiation of antiviral therapy and reduce unnecessary admissions and antibiotics use. AIM: To explore factors that influence the adoption or non-adoption of POCT in English general practices and provide insights to enable its integration into routine practice workflows. DESIGN & SETTING: A qualitative implementation evaluation was conducted in ten general practices within the English national sentinel network (Oxford-RCGP Research and Surveillance Centre), from April to July 2023. METHOD: Using the nonadoption, abandonment, scale-up, spread, and sustainability framework, data collection and analysis were conducted across ten practices. We made ethnographic observations of the POCT workflow and surveyed the practice staff for their perspectives on POCT implementation. Data were analysed using a mix of descriptive statistics, graphical modelling techniques and framework approach. RESULTS: Ethnographic observations identified two modes of POCT integration into practice workflow: 1) clinician POCT workflow - typically involving batch testing due to time constraints, 2) research nurse/healthcare assistant POCT workflow - characterised by immediate testing of individual patients. Survey indicated that most primary care staff considered the POCT training offered was sufficient, and these practices were ready for change and had the capacity and resources to integrate POCT in workflows. CONCLUSION: General practices should demonstrate flexibility in the workflow and workforce they deploy to integrate POCT into routine clinical workflow.

A Profile of Influenza Vaccine Coverage for 2019-2020: Database Study of the English Primary Care Sentinel Cohort.

BACKGROUND: Innovation in seasonal influenza vaccine development has resulted in a wider range of formulations becoming available. Understanding vaccine coverage across populations including the timing of administration is important when evaluating vaccine benefits and risks. OBJECTIVE: This study aims to report the representativeness, uptake of influenza vaccines, different formulations of influenza vaccines, and timing of administration within the English Primary Care Sentinel Cohort (PCSC). METHODS: We used the PCSC of the Oxford-Royal College of General Practitioners Research and Surveillance Centre. We included patients of all ages registered with PCSC member general practices, reporting influenza vaccine coverage between September 1, 2019, and January 29, 2020. We identified influenza vaccination recipients and characterized them by age, clinical risk groups, and vaccine type. We reported the date of influenza vaccination within the PCSC by International Standard Organization (ISO) week. The representativeness of the PCSC population was compared with population data provided by the Office for National Statistics. PCSC influenza vaccine coverage was compared with published UK Health Security Agency's national data. We used paired t tests to compare populations, reported with 95% CI. RESULTS: The PCSC comprised 7,010,627 people from 693 general practices. The study population included a greater proportion of people aged 18-49 years (2,982,390/7,010,627, 42.5%; 95% CI 42.5%-42.6%) compared with the Office for National Statistics 2019 midyear population estimates (23,219,730/56,286,961, 41.3%; 95% CI 4.12%-41.3%; P<.001). People who are more deprived were underrepresented and those in the least deprived quintile were overrepresented. Within the study population, 24.7% (1,731,062/7,010,627; 95% CI 24.7%-24.7%) of people of all ages received an influenza vaccine compared with 24.2% (14,468,665/59,764,928; 95% CI 24.2%-24.2%; P<.001) in national data. The highest coverage was in people aged ≥65 years (913,695/1,264,700, 72.3%; 95% CI 72.2%-72.3%). The proportion of people in risk groups who received an influenza vaccine was also higher; for example, 69.8% (284,280/407,228; 95% CI 69.7%-70%) of people with diabetes in the PCSC received an influenza vaccine compared with 61.2% (983,727/1,607,996; 95% CI 61.1%-61.3%; P<.001) in national data. In the PCSC, vaccine type and brand information were available for 71.8% (358,365/498,923; 95% CI 71.7%-72%) of people aged 16-64 years and 81.9% (748,312/913,695; 95% CI 81.8%-82%) of people aged ≥65 years, compared with 23.6% (696,880/2,900,000) and 17.8% (1,385,888/7,700,000), respectively, of the same age groups in national data. Vaccination commenced during ISO week 35, continued until ISO week 3, and peaked during ISO week 41. The in-week peak in vaccination administration was on Saturdays. CONCLUSIONS: The PCSC's sociodemographic profile was similar to the national population and captured more data about risk groups, vaccine brands, and batches. This may reflect higher data quality. Its capabilities included reporting precise dates of administration. The PCSC is suitable for undertaking studies of influenza vaccine coverage.

COVID-19 and influenza vaccine uptake among pregnant women in national cohorts of England and Wales.

Vaccines against COVID-19 and influenza can reduce the adverse outcomes caused by infections during pregnancy, but vaccine uptake among pregnant women has been suboptimal. We examined the COVID-19 and influenza vaccine uptake and disparities in pregnant women during the COVID-19 pandemic to inform vaccination interventions. We used data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre database in England and the Secure Anonymised Information Linkage Databank in Wales. The uptake of at least one dose of vaccine was 40.2% for COVID-19 and 41.8% for influenza among eligible pregnant women. We observed disparities in COVID-19 and influenza vaccine uptake, with socioeconomically deprived and ethnic minority groups showing lower vaccination rates. The suboptimal uptake of COVID-19 and influenza vaccines, especially in those from socioeconomically deprived backgrounds and Black, mixed or other ethnic groups, underscores the necessity for interventions to reduce vaccine hesitancy and enhance acceptance in pregnant women.

Phenotype execution and modeling architecture to support disease surveillance and real-world evidence studies: English sentinel network evaluation.

Objective: To evaluate Phenotype Execution and Modelling Architecture (PhEMA), to express sharable phenotypes using Clinical Quality Language (CQL) and intensional Systematised Nomenclature of Medicine (SNOMED) Clinical Terms (CT) Fast Healthcare Interoperability Resources (FHIR) valuesets, for exemplar chronic disease, sociodemographic risk factor, and surveillance phenotypes. Method: We curated 3 phenotypes: Type 2 diabetes mellitus (T2DM), excessive alcohol use, and incident influenza-like illness (ILI) using CQL to define clinical and administrative logic. We defined our phenotypes with valuesets, using SNOMED's hierarchy and expression constraint language, and CQL, combining valuesets and adding temporal elements where needed. We compared the count of cases found using PhEMA with our existing approach using convenience datasets. We assessed our new approach against published desiderata for phenotypes. Results: The T2DM phenotype could be defined as 2 intensionally defined SNOMED valuesets and a CQL script. It increased the prevalence from 7.2% to 7.3%. Excess alcohol phenotype was defined by valuesets that added qualitative clinical terms to the quantitative conceptual definitions we currently use; this change increased prevalence by 58%, from 1.2% to 1.9%. We created an ILI valueset with SNOMED concepts, adding a temporal element using CQL to differentiate new episodes. This increased the weekly incidence in our convenience sample (weeks 26-38) from 0.95 cases to 1.11 cases per 100 000 people. Conclusions: Phenotypes for surveillance and research can be described fully and comprehensibly using CQL and intensional FHIR valuesets. Our use case phenotypes identified a greater number of cases, whilst anticipated from excessive alcohol this was not for our other variable. This may have been due to our use of SNOMED CT hierarchy. Our new process fulfilled a greater number of phenotype desiderata than the one that we had used previously, mostly in the modeling domain. More work is needed to implement that sharing and warehousing domains.

AZD1222 effectiveness against severe COVID-19 in individuals with comorbidity or frailty: The RAVEN cohort study.

OBJECTIVES: Despite being prioritized during initial COVID-19 vaccine rollout, vulnerable individuals at high risk of severe COVID-19 (hospitalization, intensive care unit admission, or death) remain underrepresented in vaccine effectiveness (VE) studies. The RAVEN cohort study (NCT05047822) assessed AZD1222 (ChAdOx1 nCov-19) two-dose primary series VE in vulnerable populations. METHODS: Using the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub, linked to secondary care, death registration, and COVID-19 datasets in England, COVID-19 outcomes in 2021 were compared in vaccinated and unvaccinated individuals matched on age, sex, region, and multimorbidity. RESULTS: Over 4.5 million AZD1222 recipients were matched (mean follow-up ∼5 months); 68% were ≥50 years, 57% had high multimorbidity. Overall, high VE against severe COVID-19 was demonstrated, with lower VE observed in vulnerable populations. VE against hospitalization was higher in the lowest multimorbidity quartile (91.1%; 95% CI: 90.1, 92.0) than the highest quartile (80.4%; 79.7, 81.1), and among individuals ≥65 years, higher in the 'fit' (86.2%; 84.5, 87.6) than the frailest (71.8%; 69.3, 74.2). VE against hospitalization was lowest in immunosuppressed individuals (64.6%; 60.7, 68.1). CONCLUSIONS: Based on integrated and comprehensive UK health data, overall population-level VE with AZD1222 was high. VEs were notably lower in vulnerable groups, particularly the immunosuppressed.

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.

Integrated Management Systems (IMS) to Support and Sustain Quality One Health Services: International Lessons from the COVID-19 Pandemic by the IMIA Primary Care Working Group.

OBJECTIVES: One Health considers human, animal and environment health as a continuum. The COVID-19 pandemic started with the leap of a virus from animals to humans. Integrated management systems (IMS) should provide a coherent management framework, to meet reporting requirements and support care delivery. We report IMS deployment during, and retention post the COVID-19 pandemic, and exemplar One Health use cases. METHODS: Six volunteer members of the International Medical Association's (IMIA) Primary Care Working Group provided data about any IMS and One Health use to support the COVID-19 pandemic initiatives. We explored how IMS were: (1) Integrated with organisational strategy; (2) Utilised standardised processes, and (3) Met reporting requirements, including public health. Selected contributors provided Unified Modelling Language (UML) use case diagram for a One Health exemplar. RESULTS: There was weak evidence of synergy between IMS and health system strategy to the COVID-19 pandemic. However, there were rapid pragmatic responses to COVID-19, not citing IMS. All health systems implemented IMS to link COVID test results, vaccine uptake and outcomes, particularly mortality and to provide patients access to test results and vaccination certification. Neither proportion of gross domestic product alone, nor vaccine uptake determined outcome. One Health exemplars demonstrated that animal, human and environmental specialists could collaborate. CONCLUSIONS: IMS use improved the pandemic response. However, IMS use was pragmatic rather than utilising an international standard, with some of their benefits lost post-pandemic. Health systems should incorporate IMS that enables One Health approaches as part of their post COVID-19 pandemic preparedness.

Brand-specific estimates of influenza vaccine effectiveness for the 2021-2022 season in Europe: results from the DRIVE multi-stakeholder study platform.

Introduction: Development of Robust and Innovative Vaccine Effectiveness (DRIVE) was a European public-private partnership (PPP) that aimed to provide annual, brand-specific estimates of influenza vaccine effectiveness (IVE) for regulatory and public health purposes. DRIVE was launched in 2017 under the umbrella of the Innovative Medicines Initiative (IMI) and conducted IVE studies from its pilot season in 2017-2018 to its final season in 2021-2022. Methods: In 2021-2022, DRIVE conducted four primary care-based test-negative design (TND) studies (Austria, Italy, Iceland, and England; involving >1,000 general practitioners), nine hospital-based TND studies (France, Iceland, Italy, Romania, and Spain, for a total of 21 hospitals), and one population-based cohort study in Finland. In the TND studies, patients with influenza-like illness (primary care) or severe acute respiratory infection (hospital) were enrolled, and laboratory tested for influenza using RT-PCR. Study contributor-specific IVE was calculated using logistic regression, adjusting for age, sex, and calendar time, and pooled by meta-analysis. Results: In 2021-2022, pooled confounder-adjusted influenza vaccine effectiveness (IVE) estimates against laboratory-confirmed influenza (LCI) overall and per type and subtype/lineage was produced, albeit with wide confidence intervals (CI). The limited circulation of influenza in Europe did not allow the network to reach the optimal sample size to produce precise IVE estimates for all the brands included. The most significant IVE estimates were 76% (95% CI 23%-93%) for any vaccine and 81% (22%-95%) for Vaxigrip Tetra in adults ≥65 years old and 64% (25%-83%) for Fluenz Tetra in children (TND primary care setting), 85% (12%-97%) for any vaccine in adults 18-64 years (TND hospital setting), and 38% (1%-62%) in children 6 months-6 years (population-based cohort, mixed setting). Discussion: Over five seasons, DRIVE collected data on >35,000 patients, more than 60 variables, and 13 influenza vaccines. DRIVE demonstrated that estimating brand-specific IVE across Europe is possible, but achieving sufficient sample size to obtain precise estimates for all relevant stratifications remains a challenge. Finally, DRIVE's network of study contributors and lessons learned have greatly contributed to the development of the COVID-19 vaccine effectiveness platform COVIDRIVE.

The Impact of Point-of-Care Testing for Influenza on Antimicrobial Stewardship (PIAMS) in UK Primary Care: Protocol for a Mixed Methods Study.

BACKGROUND: Molecular point-of-care testing (POCT) used in primary care can inform whether a patient presenting with an acute respiratory infection has influenza. A confirmed clinical diagnosis, particularly early in the disease, could inform better antimicrobial stewardship. Social distancing and lockdowns during the COVID-19 pandemic have disturbed previous patterns of influenza infections in 2021. However, data from samples taken in the last quarter of 2022 suggest that influenza represents 36% of sentinel network positive virology, compared with 24% for respiratory syncytial virus. Problems with integration into the clinical workflow is a known barrier to incorporating technology into routine care. OBJECTIVE: This study aims to report the impact of POCT for influenza on antimicrobial prescribing in primary care. We will additionally describe severe outcomes of infection (hospitalization and mortality) and how POCT is integrated into primary care workflows. METHODS: The impact of POCT for influenza on antimicrobial stewardship (PIAMS) in UK primary care is an observational study being conducted between December 2022 and May 2023 and involving 10 practices that contribute data to the English sentinel network. Up to 1000 people who present to participating practices with respiratory symptoms will be swabbed and tested with a rapid molecular POCT analyzer in the practice. Antimicrobial prescribing and other study outcomes will be collected by linking information from the POCT analyzer with data from the patient's computerized medical record. We will collect data on how POCT is incorporated into practice using data flow diagrams, unified modeling language use case diagrams, and Business Process Modeling Notation. RESULTS: We will present the crude and adjusted odds of antimicrobial prescribing (all antibiotics and antivirals) given a POCT diagnosis of influenza, stratifying by whether individuals have a respiratory or other relevant diagnosis (eg, bronchiectasis). We will also present the rates of hospital referrals and deaths related to influenza infection in PIAMS study practices compared with a set of matched practices in the sentinel network and the rest of the network. We will describe any difference in implementation models in terms of staff involved and workflow. CONCLUSIONS: This study will generate data on the impact of POCT testing for influenza in primary care as well as help to inform about the feasibility of incorporating POCT into primary care workflows. It will inform the design of future larger studies about the effectiveness and cost-effectiveness of POCT to improve antimicrobial stewardship and any impact on severe outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46938.

Assessing the Clinical and Socioeconomic Burden of Respiratory Syncytial Virus in Children Aged Under 5 Years in Primary Care: Protocol for a Prospective Cohort Study in England and Report on the Adaptations of the Study to the COVID-19 Pandemic.

BACKGROUND: Respiratory syncytial virus (RSV) commonly causes lower respiratory tract infections and hospitalization in children. In 2019-2020, the Europe-wide RSV ComNet standardized study protocol was developed to measure the clinical and socioeconomic disease burden of RSV infections among children aged <5 years in primary care. RSV has a recognized seasonality in England. OBJECTIVE: We aimed to describe (1) the adaptations of the RSV ComNet standardized study protocol for England and (2) the challenges of conducting the study during the COVID-19 pandemic. METHODS: This study was conducted by the Oxford-Royal College of General Practitioners Research and Surveillance Centre-the English national primary care sentinel network. We invited all (N=248) general practices within the network that undertook virology sampling to participate in the study by recruiting eligible patients (registered population: n=3,056,583). Children aged <5 years with the following case definition of RSV infection were included in the study: those consulting a health care practitioner in primary care with symptoms meeting the World Health Organization's definition of acute respiratory illness or influenza-like illness who have laboratory-confirmed RSV infection. The parents/guardians of these cases were asked to complete 2 previously validated questionnaires (14 and 30 days postsampling). A sample size of at least 100 RSV-positive cases is required to estimate the percentage of children that consult in primary care who need hospitalization. Assuming a swab positivity rate of 20% in children aged <5 years, we estimated that 500 swabs are required. We adapted our method for the pandemic by extending sampling planned for winter 2020-2021 to a rolling data collection, allowing verbal consent and introducing home swabbing because of increased web-based consultations during the COVID-19 pandemic. RESULTS: The preliminary results of the data collection between International Organization for Standardization (ISO) weeks 1-41 in 2021 are described. There was no RSV detected in the winter of 2020-2021 through the study. The first positive RSV swab collected through the sentinel network in England was collected in ISO week 17 and then every week since ISO week 25. In total, 16 (N=248, 6.5%) of the virology-sampling practices volunteered to participate; these were high-sampling practices collecting the majority of eligible swabs across the sentinel network-200 (43.8%) out of 457 swabs, of which 54 (N=200, 27%) were positive for RSV. CONCLUSIONS: Measures to control the COVID-19 pandemic meant there was no circulating RSV last winter; however, RSV has circulated out of season, as detected by the sentinel network. The sentinel network practices have collected 40% (200/500) of the required samples, and 27% (54/200) were RSV positive. We have demonstrated the feasibility of implementing a European-standardized RSV disease burden study protocol in England during a pandemic, and we now need to recruit to this adapted protocol. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38026.

National rates and disparities in childhood vaccination and vaccine-preventable disease during the COVID-19 pandemic: English sentinel network retrospective database study.

OBJECTIVES: To describe rates and variation in uptake of pneumococcal and measles, mumps and rubella (MMR) vaccines in children and associated change in vaccine-preventable diseases (VPDs) across the first and second waves of the COVID-19 pandemic. METHODS: Retrospective database study of all children aged <19 registered with a general practice in the Oxford Royal College of General Practitioners Research and Surveillance Centre English national sentinel surveillance network between 2 November 2015 and 18 July 2021. RESULTS: Coverage of booster dose of pneumococcal vaccine decreased from 94.5% (95% CI 94.3% to 94.7%) at its height on International Organization for Standardization (ISO) week 47 (2020) to 93.6% (95% CI 93.4% to 93.8%) by the end of the study. Coverage of second dose of MMR decreased from 85.0% (95% CI 84.7% to 85.3%) at its height on ISO week 37 (2020) to 84.1% (95% CI 83.8% to 84.4%) by the end of the study. The break point in trends for MMR was at ISO week 34 (2020) (95% CI weeks 32-37 (2020)), while for pneumococcal vaccine the break point was later at ISO week 3 (2021) (95% CI week 53 (2020) to week 8 (2021)). Vaccination coverage for children of white ethnicity was less likely to decrease than other ethnicities. Rates of consultation for VPDs fell and remained low since August 2020. CONCLUSION: Childhood vaccination rates started to fall ahead of the onset of the second wave; this fall is accentuating ethnic, socioeconomic and geographical disparities in vaccine uptake and risks widening health disparities. Social distancing and school closures may have contributed to lower rates of associated VPDs, but there may be increased risk as these measures are removed.

Mental Health Presentations Across Health Care Settings During the First 9 Months of the COVID-19 Pandemic in England: Retrospective Observational Study.

BACKGROUND: The COVID-19 pandemic has resulted in an unprecedented impact on the day-to-day lives of people, with several features potentially adversely affecting mental health. There is growing evidence of the size of the impact of COVID-19 on mental health, but much of this is from ongoing population surveys using validated mental health scores. OBJECTIVE: This study investigated the impact of the pandemic and control measures on mental health conditions presenting to a spectrum of national health care services monitored using real-time syndromic surveillance in England. METHODS: We conducted a retrospective observational descriptive study of mental health presentations (those calling the national medical helpline, National Health Service [NHS] 111; consulting general practitioners [GPs] in and out-of-hours; calling ambulance services; and attending emergency departments) from January 1, 2019, to September 30, 2020. Estimates for the impact of lockdown measures were provided using an interrupted time series analysis. RESULTS: Mental health presentations showed a marked decrease during the early stages of the pandemic. Postlockdown, attendances for mental health conditions reached higher than prepandemic levels across most systems-a rise of 10% compared to that expected for NHS 111 and 21% for GP out-of-hours service-while the number of consultations to GP in-hours service was 13% lower compared to the same time previous year. Increases were observed in calls to NHS 111 for sleep problems. CONCLUSIONS: These analyses showed marked changes in the health care attendances and prescribing for common mental health conditions across a spectrum of health care provision, with some of these changes persisting. The reasons for such changes are likely to be complex and multifactorial. The impact of the pandemic on mental health may not be fully understood for some time, and therefore, these syndromic indicators should continue to be monitored.

Changes in primary care visits arising from the COVID-19 pandemic: an international comparative study by the International Consortium of Primary Care Big Data Researchers (INTRePID).

INTRODUCTION: Through the INTernational ConsoRtium of Primary Care BIg Data Researchers (INTRePID), we compared the pandemic impact on the volume of primary care visits and uptake of virtual care in Australia, Canada, China, Norway, Singapore, South Korea, Sweden, the UK and the USA. METHODS: Visit definitions were agreed on centrally, implemented locally across the various settings in INTRePID countries, and weekly visit counts were shared centrally for analysis. We evaluated the weekly rate of primary care physician visits during 2019 and 2020. Rate ratios (RRs) of total weekly visit volume and the proportion of weekly visits that were virtual in the pandemic period in 2020 compared with the same prepandemic period in 2019 were calculated. RESULTS: In 2019 and 2020, there were 80 889 386 primary care physician visits across INTRePID. During the pandemic, average weekly visit volume dropped in China, Singapore, South Korea, and the USA but was stable overall in Australia (RR 0.98 (95% CI 0.92 to 1.05, p=0.59)), Canada (RR 0.96 (95% CI 0.89 to 1.03, p=0.24)), Norway (RR 1.01 (95% CI 0.88 to 1.17, p=0.85)), Sweden (RR 0.91 (95% CI 0.79 to 1.06, p=0.22)) and the UK (RR 0.86 (95% CI 0.72 to 1.03, p=0.11)). In countries that had negligible virtual care prepandemic, the proportion of visits that were virtual were highest in Canada (77.0%) and Australia (41.8%). In Norway (RR 8.23 (95% CI 5.30 to 12.78, p<0.001), the UK (RR 2.36 (95% CI 2.24 to 2.50, p<0.001)) and Sweden (RR 1.33 (95% CI 1.17 to 1.50, p<0.001)) where virtual visits existed prepandemic, it increased significantly during the pandemic. CONCLUSIONS: The drop in primary care in-person visits during the pandemic was a global phenomenon across INTRePID countries. In several countries, primary care shifted to virtual visits mitigating the drop in in-person visits.

Representativeness, Vaccination Uptake, and COVID-19 Clinical Outcomes 2020-2021 in the UK Oxford-Royal College of General Practitioners Research and Surveillance Network: Cohort Profile Summary.

BACKGROUND: The Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) is one of Europe's oldest sentinel systems, working with the UK Health Security Agency (UKHSA) and its predecessor bodies for 55 years. Its surveillance report now runs twice weekly, supplemented by online observatories. In addition to conducting sentinel surveillance from a nationally representative group of practices, the RSC is now also providing data for syndromic surveillance. OBJECTIVE: The aim of this study was to describe the cohort profile at the start of the 2021-2022 surveillance season and recent changes to our surveillance practice. METHODS: The RSC's pseudonymized primary care data, linked to hospital and other data, are held in the Oxford-RCGP Clinical Informatics Digital Hub, a Trusted Research Environment. We describe the RSC's cohort profile as of September 2021, divided into a Primary Care Sentinel Cohort (PCSC)-collecting virological and serological specimens-and a larger group of syndromic surveillance general practices (SSGPs). We report changes to our sampling strategy that brings the RSC into alignment with European Centre for Disease Control guidance and then compare our cohort's sociodemographic characteristics with Office for National Statistics data. We further describe influenza and COVID-19 vaccine coverage for the 2020-2021 season (week 40 of 2020 to week 39 of 2021), with the latter differentiated by vaccine brand. Finally, we report COVID-19-related outcomes in terms of hospitalization, intensive care unit (ICU) admission, and death. RESULTS: As a response to COVID-19, the RSC grew from just over 500 PCSC practices in 2019 to 1879 practices in 2021 (PCSC, n=938; SSGP, n=1203). This represents 28.6% of English general practices and 30.59% (17,299,780/56,550,136) of the population. In the reporting period, the PCSC collected >8000 virology and >23,000 serology samples. The RSC population was broadly representative of the national population in terms of age, gender, ethnicity, National Health Service Region, socioeconomic status, obesity, and smoking habit. The RSC captured vaccine coverage data for influenza (n=5.4 million) and COVID-19, reporting dose one (n=11.9 million), two (n=11 million), and three (n=0.4 million) for the latter as well as brand-specific uptake data (AstraZeneca vaccine, n=11.6 million; Pfizer, n=10.8 million; and Moderna, n=0.7 million). The median (IQR) number of COVID-19 hospitalizations and ICU admissions was 1181 (559-1559) and 115 (50-174) per week, respectively. CONCLUSIONS: The RSC is broadly representative of the national population; its PCSC is geographically representative and its SSGPs are newly supporting UKHSA syndromic surveillance efforts. The network captures vaccine coverage and has expanded from reporting primary care attendances to providing data on onward hospital outcomes and deaths. The challenge remains to increase virological and serological sampling to monitor the effectiveness and waning of all vaccines available in a timely manner.