An intercountry comparison of the impact of the paediatric live attenuated influenza vaccine (LAIV) programme across the UK and the Republic of Ireland (ROI), 2010 to 2017.

Background: The universal paediatric live attenuated influenza vaccine (LAIV) programme commenced in the United Kingdom (UK) in 2013/2014. Since 2014/2015, all pre-school and primary school children in Scotland and Northern Ireland have been offered the vaccine. England and Wales incrementally introduced the programme with additional school age cohorts being vaccinated each season. The Republic of Ireland (ROI) had no universal paediatric programme before 2017. We evaluated the potential population impact of vaccinating primary school-aged children across the five countries up to the 2016/2017 influenza season. Methods: We compared rates of primary care influenza-like illness (ILI) consultations, confirmed influenza intensive care unit (ICU) admissions, and all-cause excess mortality using standardised methods. To further quantify the impact, a scoring system was developed where each weekly rate/z-score was scored and summed across each influenza season according to the weekly respective threshold experienced in each country. Results: Results highlight ILI consultation rates in the four seasons' post-programme, breached baseline thresholds once or not at all in Scotland and Northern Ireland; in three out of the four seasons in England and Wales; and in all four seasons in ROI. No differences were observed in the seasons' post-programme introduction between countries in rates of ICU and excess mortality, although reductions in influenza-related mortality were seen. The scoring system also reflected similar results overall. Conclusions: Findings of this study suggest that LAIV vaccination of primary school age children is associated with population-level benefits, particularly in reducing infection incidence in primary care.

Impact of General Practitioner Education on Acceptance of an Adjuvanted Seasonal Influenza Vaccine among Older Adults in England.

Seasonal vaccination against influenza and in-pandemic COVID-19 vaccination are top public health priorities; vaccines are the primary means of reducing infections and also controlling pressures on health systems. During the 2018-2019 influenza season, we conducted a study of the knowledge, attitudes, and behaviours of 159 general practitioners (GPs) and 189 patients aged ≥65 years in England using a combination of qualitative and quantitative approaches to document beliefs about seasonal influenza and seasonal influenza vaccine. GPs were surveyed before and after a continuing medical education (CME) module on influenza disease and vaccination with an adjuvanted trivalent influenza vaccine (aTIV) designed for patients aged ≥65 years, and patients were surveyed before and after a routine visit with a GP who participated in the CME portion of the study. The CME course was associated with significantly increased GP confidence in their ability to address patients' questions and concerns about influenza disease and vaccination (p < 0.001). Patients reported significantly increased confidence in the effectiveness and safety of aTIV after meeting their GP. Overall, 82.2% of the study population were vaccinated against influenza (including 137 patients vaccinated during the GP visit and 15 patients who had been previously vaccinated), a rate higher than the English national average vaccine uptake of 72.0% that season. These findings support the value of GP-patient interactions to foster vaccine acceptance.

The Effect of the COVID-19 Pandemic on Glycemic Monitoring and Other Processes of Care for Type 2 Diabetes: Protocol for a Retrospective Cohort Study.

BACKGROUND: Social distancing and other nonpharmaceutical interventions to reduce the spread of COVID-19 infection in the United Kingdom have led to substantial changes in delivering ongoing care for patients with chronic conditions, including type 2 diabetes mellitus (T2DM). Clinical guidelines for the management and prevention of complications for people with T2DM delivered in primary care services advise routine annual reviews and were developed when face-to-face consultations were the norm. The shift in consultations from face-to-face to remote consultations caused a reduction in direct clinical contact and may impact the process of care for people with T2DM. OBJECTIVE: The aim of this study is to explore the impact of the COVID-19 pandemic's first year on the monitoring of people with T2DM using routine annual reviews from a national primary care perspective in England. METHODS: A retrospective cohort study of adults with T2DM will be performed using routinely collected primary care data from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We will describe the change in the rate of monitoring of hemoglobin A1c (HbA1c) between the first year of the COVID-19 pandemic (2020) and the preceding year (2019). We will also report any change in the eight checks that make up the components of these reviews. The change in HbA1c monitoring rates will be determined using a multilevel logistic regression model, adjusting for patient and practice characteristics, and similarly, the change in a composite measure of the completeness of all eight checks will be modeled using ordinal regression. The models will be adjusted for the following patient-level variables: age, gender, socioeconomic status, ethnicity, COVID-19 shielding status, duration of diabetes, and comorbidities. The model will also be adjusted for the following practice-level variables: urban versus rural, practice size, Quality and Outcomes Framework achievement, the National Health Service region, and the proportion of face-to-face consultations. Ethical approval was provided by the University of Oxford Medical Sciences Interdivisional Research Ethics Committee (September 2, 2021, reference R77306/RE001). RESULTS: The analysis of the data extract will include 3.96 million patients with T2DM across 700 practices, which is 6% of the available Oxford-RCGP RSC adult population. The preliminary results will be submitted to a conference under the domain of primary care. The resulting publication will be submitted to a peer-reviewed journal on diabetes and endocrinology. CONCLUSIONS: The COVID-19 pandemic has impacted the delivery of care, but little is known about the process of caring for people with T2DM. This study will report the impact of the COVID-19 pandemic on these processes of care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35971.

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.

Household presentation of influenza and acute respiratory illnesses to a primary care sentinel network: retrospective database studies (2013-2018).

BACKGROUND: Direct observation of the household spread of influenza and respiratory infections is limited; much of our understanding comes from mathematical models. The study aims to determine household incidence of influenza-like illness (ILI), lower (LRTI) and upper (URTI) respiratory infections within a primary care routine data and identify factors associated with the diseases' incidence. METHODS: We conducted two five-year retrospective analyses of influenza-like illness (ILI), lower (LRTI) and upper (URTI) respiratory infections using the England Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care sentinel network database; a cross-sectional study reporting incident rate ratio (IRR) from a negative binomial model and a retrospective cohort study, using a shared gamma frailty survival model, reporting hazard ratios (HR). We reported the following household characteristics: children < 5 years old, each extra household member, gender, ethnicity (reference white), chronic disease, pregnancy, and rurality. RESULTS: The IRR where there was a child < 5 years were 1·62 (1·38-1·89, p < 0·0001), 2·40 (2.04-2.83, p < 0·0001) and 4·46 (3.79-5.255, p < 0·0001) for ILI, LRTI and URTI respectively. IRR also increased with household size, rurality and presentations and by female gender, compared to male. Household incidence of URTI and LRTI changed little between years whereas influenza did and were greater in years with lower vaccine effectiveness. The HR where there was a child < 5 years were 2·34 (95%CI 1·88-2·90, p < 0·0001), 2·97 (95%CI 2·76-3·2, p < 0·0001) and 10·32 (95%CI 10.04-10.62, p < 0·0001) for ILI, LRTI and URTI respectively. HR were increased with female gender, rurality, and increasing household size. CONCLUSIONS: Patterns of household incidence can be measured from routine data and may provide insights for the modelling of disease transmission and public health policy.

Optimising age coverage of seasonal influenza vaccination in England: A mathematical and health economic evaluation.

For infectious disease prevention, policy-makers are typically required to base policy decisions in light of operational and monetary restrictions, prohibiting implementation of all candidate interventions. To inform the evidence-base underpinning policy decision making, mathematical and health economic modelling can be a valuable constituent. Applied to England, this study aims to identify the optimal target age groups when extending a seasonal influenza vaccination programme of at-risk individuals to those individuals at low risk of developing complications following infection. To perform this analysis, we utilise an age- and strain-structured transmission model that includes immunity propagation mechanisms which link prior season epidemiological outcomes to immunity at the beginning of the following season. Making use of surveillance data from the past decade in conjunction with our dynamic model, we simulate transmission dynamics of seasonal influenza in England from 2012 to 2018. We infer that modified susceptibility due to natural infection in the previous influenza season is the only immunity propagation mechanism to deliver a non-negligible impact on the transmission dynamics. Further, we discerned case ascertainment to be higher for young infants compared to adults under 65 years old, and uncovered a decrease in case ascertainment as age increased from 65 to 85 years of age. Our health economic appraisal sweeps vaccination age space to determine threshold vaccine dose prices achieving cost-effectiveness under differing paired strategies. In particular, we model offering vaccination to all those low-risk individuals younger than a given age (but no younger than two years old) and all low-risk individuals older than a given age, while maintaining vaccination of at-risk individuals of any age. All posited strategies were deemed cost-effective. In general, the addition of low-risk vaccination programmes whose coverage encompassed children and young adults (aged 20 and below) were highly cost-effective. The inclusion of elder age-groups to the low-risk programme typically lessened the cost-effectiveness. Notably, elderly-centric programmes vaccinating from 65-75 years and above had the least permitted expense per vaccine.

Use and impact of social prescribing: a mixed-methods feasibility study protocol.

INTRODUCTION: Social prescribing aims to address social determinants of health, which account for 80%-90% of health outcomes, but the evidence base behind it is limited due to a lack of data linkingsocial prescribing activity and outcomes. METHODS AND ANALYSIS: The objective of the quantitative component of this feasibility studyisto identify the characteristics of individuals who receive social prescriptions and describe the use and estimate the impact of social prescribing; the latter will be done on a homeless subgroup. We will use the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care sentinel network, whose general practicescover a population of over 4 000 000 patients. Social prescribing data will be extracted onall recorded patients for 5 years up to 31 January 2020. The objective for the qualitative component of the study isto explore approaches to understand the contextual factors that will have influenced our quantitative findings to identify mechanisms to encourage adoption of social prescribing in primary care while improving data quality. Itwill comprise up to three 90-120 minute advisory group meetings for six to eight participants. Participants will be recruited based on their experience of delivering primary care within Oxfordshire and Surrey. The advisory group outputs will be analysed using framework analysis and will be used to create a survey instrument consisting of statements that surveyees, who will consist of primary care practitioners within the RCGP RSC, can agree or disagree with. ETHICS AND DISSEMINATION: All RCGP RSC data are pseudonymised at the point of data extraction. No personally identifiable data are required for this investigation. This protocol follows the Good Reporting of a Mixed Methods Study checklist. The study results will be published in a peer-reviewed journal and the dataset will be available to other researchers.

CASNET2: evaluation of an electronic safety netting cancer toolkit for the primary care electronic health record: protocol for a pragmatic stepped-wedge RCT.

INTRODUCTION: Safety-netting in primary care is the best practice in cancer diagnosis, ensuring that patients are followed up until symptoms are explained or have resolved. Currently, clinicians use haphazard manual solutions. The ubiquitous use of electronic health records provides an opportunity to standardise safety-netting practices.A new electronic safety-netting toolkit has been introduced to provide systematic ways to track and follow up patients. We will evaluate the effectiveness of this toolkit, which is embedded in a major primary care clinical system in England:Egerton Medical Information System(EMIS)-Web. METHODS AND ANALYSIS: We will conduct a stepped-wedge cluster RCT in 60 general practices within the RCGP Research and Surveillance Centre (RSC) network. Groups of 10 practices will be randomised into the active phase at 2-monthly intervals over 12 months. All practices will be activated for at least 2 months. The primary outcome is the primary care interval measured as days between the first recorded symptom of cancer (within the year prior to diagnosis) and the subsequent referral to secondary care. Other outcomes include referrals rates and rates of direct access cancer investigation.Analysis of the clustered stepped-wedge design will model associations using a fixed effect for intervention condition of the cluster at each time step, a fixed effect for time and other covariates, and then include a random effect for practice and for patient to account for correlation between observations from the same centre and from the same participant. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the North West-Greater Manchester West National Health Service Research Ethics Committee (REC Reference 19/NW/0692). Results will be disseminated in peer-reviewed journals and conferences, and sent to participating practices. They will be published on the University of Oxford Nuffield Department of Primary Care and RCGP RSC websites. TRIAL REGISTRATION NUMBER: ISRCTN15913081; Pre-results.

Impact of the herpes zoster vaccination programme on hospitalised and general practice consulted herpes zoster in the 5 years after its introduction in England: a population-based study.

OBJECTIVES: To assess the impact of herpes zoster vaccination in the 5 years after introduction for 70- to 79-year-olds in England in September 2013. DESIGN: Population based ecological impact assessment. SETTING: Hospitals covering the whole English population for the period 2008 to 2018 and 293 general practices (GP) for the period 2005 to 2018, in England. PARTICIPANTS: Over the period the population contributed 117·5 million person-years for hospitalisation events and 6.96 million person-years for GP events in individuals aged 60 to 89. INTERVENTIONS: Live attenuated herpes zoster vaccination (Zostavax), first used on 1st September 2013, in 70- and 79-year-olds with continued use in new 70 year-olds and with a staged catch-up of those aged 71 to 78 years in 2013. OUTCOME MEASURES: Herpes zoster and postherpetic neuralgia (PHN) consultation and hospitalisation rates in age-cohorts according to vaccine eligibility. Incidence rate ratios in age-cohorts eligible for vaccination compared with those non-eligible were calculated by Poisson regression. This was used to estimate prevented cases and, along with vaccine coverage, to estimate vaccine effectiveness. RESULTS: Large and prolonged reductions in herpes zoster and PHN consultations and hospitalisations were observed in the 5 years post-implementation. For example, in 79 year-olds first eligible in 2013, the incidence rate ratio for consultations 5 years later was 0·65 (95% CI: 0·52 to 0·81). Over the whole period an estimated 40 500 fewer zoster consultations and 1840 fewer zoster hospitalisations occurred because of the vaccination programme. These reductions were consistent with effectiveness in the routine cohorts (vaccinated aged 70) of between 37% (for hospitalised zoster) and 75% (for PHN consultations) and, in catch up cohorts (vaccinated aged 78 to 79) of between 49% (for hospitalised PHN) and 66% (for PHN consultations). CONCLUSION: Given the clear and sustained impact of herpes zoster vaccination over the 5-year period since introduction, optimising vaccination coverage is important to attain maximum benefit.

Integrating molecular point-of-care testing for influenza into primary care: a mixed-methods feasibility study.

BACKGROUND: Molecular point-of-care testing (POCT) for influenza in primary care could influence clinical care and patient outcomes. AIM: To assess the feasibility of incorporating influenza POCT into general practice in England. DESIGN AND SETTING: A mixed-methods study conducted in six general practices that had not previously participated in respiratory virology sampling, which are part of the Royal College of General Practitioners Research and Surveillance Centre English sentinel surveillance network, from February 2019 to May 2019. METHOD: A sociotechnical perspective was adopted using the Public Health England POCT implementation toolkit and business process modelling notation to inform qualitative analysis. Quantitative data were collected about the number of samples taken, their representativeness, and the virology results obtained, comparing them with the rest of the sentinel system over the same weeks. RESULTS: A total of 312 POCTs were performed; 276 were used for quantitative analysis, of which 60 were positive for influenza and 216 were negative. The average swabbing rate was 0.4 per 1000 population and swab positivity was between 16.7% (n = 14/84) and 41.4% (n = 12/29). Given a positive influenza POCT result, the odds ratio of receiving an antiviral was 14.1 (95% confidence intervals [CI] = 2.9 to 70.0, P<0.001) and of receiving an antibiotic was 0.4 (95% CI = 0.2 to 0.8, P = 0.01), compared with patients with a negative result. Qualitative analysis showed that it was feasible for practices to implement POCT, but there is considerable variation in the processes used. CONCLUSION: Testing for influenza using POCT is feasible in primary care and may improve antimicrobial use. However, further evidence from randomised trials of influenza POCT in general practice is needed.

Brand-specific enhanced safety surveillance of GSK's Fluarix Tetra seasonal influenza vaccine in England: 2017/2018 season.

In compliance with the European Medicine Agency guidance to detect any potential safety concerns associated with influenza vaccination, an enhanced safety surveillance study was conducted in England during the 2017/18 influenza season. The primary objective was to estimate the incidence rates of adverse events occurring within seven days of vaccination with Fluarix Tetra. In nine General Practices, seasonal influenza vaccine was administered to patients according to local guidelines. Events following immunization were collected using customized cards (enhanced component) combined with electronic health records [EHRs] (EHR component) to estimate incidence rates of adverse events experienced post vaccination. The study ran from 01-Sep-2017 to 30-Nov-2017. A total of 23,939 subjects were vaccinated of whom 16,433 received Fluarix Tetra. The cumulative incidence rates of adverse events of interest for Fluarix Tetra were 7.25% [95% CI, 5.95-8.73] for events reported by card alone, and 9.21% [95% CI, 7.37-11.34] when combined with EHR data. The type and frequency of events reported were consistent with the Fluarix Tetra Summary of Product Characteristics. The study supports and confirms the safety profile of Fluarix Tetra. ClinicalTrials.gov number: NCT03278067.

Clinical Ontologies Improve Case Finding of Primary Biliary Cholangitis in UK Primary and Secondary Care.

INTRODUCTION: PBC registries in the UK focus on data from secondary care without clear coordinated contribution from primary care. The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) receives data from > 500 primary care practices (PCPs). Notably, the Lancet commissioning group is extracting data from the RCGP RSC database to shape UK policy on liver disease. AIMS: To create a novel ontology to facilitate PBC case finding from primary care provider (PCP) records. METHODS: RCGP RSC data were collected from participating PCPs in the county of Surrey, UK. PBC diagnostic criteria of the AASLD and EASL guidelines were used to develop 725 data codes to facilitate patient record searches. A scoring system built into the ontology allowed categorization of cases as PBC definite, PBC probable, and PBC unlikely. RESULTS: A total of 218,099 records were searched from participating PCPs. Of these, there were 58 PBC definite, 2317 PBC probable, and 215,724 PBC unlikely patients. There were 32 PBC definite patients who did not match to our regional PBC database and were henceforth included as new-found cases. Two of these cases were not labeled as PBC by the PCP. From the PBC unlikely group, 7/215,724 (0.003%) patients were labeled as PBC in secondary care records; however, none of them were coded as having PBC by their PCPs. CONCLUSIONS: Utilization of the UK National RCGP RSC database supported by novel ontology score has successfully helped us identify (i) new cases of PBC not known to local/regional secondary care providers and (ii) de novo PBC cases. There are many PBC probable cases whose data merit further careful evaluation.

End of season influenza vaccine effectiveness in primary care in adults and children in the United Kingdom in 2018/19.

2018/19 was the first season of introduction of a newly licensed adjuvanted influenza vaccine (aTIV) for adults aged 65 years and over and the sixth season in the roll-out of a childhood influenza vaccination programme with a quadrivalent live attenuated influenza vaccine (LAIV). The season saw mainly A(H1N1)pdm09 and latterly A(H3N2) circulation. End-of-season adjusted vaccine effectiveness (aVE) estimates against laboratory confirmed influenza infection in primary care were calculated using the test negative case control method adjusting for key confounders. End-of-season aVE was 44.3% (95% CI: 26.8, 57.7) against all laboratory-confirmed influenza; 45.7% (95% CI: 26.0, 60.1) against influenza A(H1N1)pdm09 and 35.1% (95% CI: -3.7,59.3) against A(H3N2). Overall aVE was 49.9% (95%CI: -13.7, 77.9) for all those ≥ 65 years of age and 62.0% (95% CI: 3.4, 85.0) for those who received aTIV. Overall aVE for 2-17 year olds receiving LAIV was 48.6% (95% CI: -4.4, 74.7). The paper provides evidence of overall significant influenza VE in 2018/19, most notably against influenza A(H1N1)pdm09, however, as seen in 2017/18, there was reduced, non-significant VE against A(H3N2). aTIV provided significant protection for those 65 years of age and over.

Enhanced Safety Surveillance of Influenza Vaccines in General Practice, 2015-16: Feasibility Study.

BACKGROUND: The European Medicines Agency (EMA) requires vaccine manufacturers to conduct enhanced real-time surveillance of seasonal influenza vaccination. The EMA has specified a list of adverse events of interest to be monitored. The EMA sets out 3 different ways to conduct such surveillance: (1) active surveillance, (2) enhanced passive surveillance, or (3) electronic health record data mining (EHR-DM). English general practice (GP) is a suitable setting to implement enhanced passive surveillance and EHR-DM. OBJECTIVE: This study aimed to test the feasibility of conducting enhanced passive surveillance in GP using the yellow card scheme (adverse events of interest reporting cards) to determine if it has any advantages over EHR-DM alone. METHODS: A total of 9 GPs in England participated, of which 3 tested the feasibility of enhanced passive surveillance and the other 6 EHR-DM alone. The 3 that tested EPS provided patients with yellow (adverse events) cards for patients to report any adverse events. Data were extracted from all 9 GPs' EHRs between weeks 35 and 49 (08/24/2015 to 12/06/2015), the main period of influenza vaccination. We conducted weekly analysis and end-of-study analyses. RESULTS: Our GPs were largely distributed across England with a registered population of 81,040. In the week 49 report, 15,863/81,040 people (19.57% of the registered practice population) were vaccinated. In the EPS practices, staff managed to hand out the cards to 61.25% (4150/6776) of the vaccinees, and of these cards, 1.98% (82/4150) were returned to the GP offices. Adverse events of interests were reported by 113 /7223 people (1.56%) in the enhanced passive surveillance practices, compared with 322/8640 people (3.73%) in the EHR-DM practices. CONCLUSIONS: Overall, we demonstrated that GPs EHR-DM was an appropriate method of enhanced surveillance. However, the use of yellow cards, in enhanced passive surveillance practices, did not enhance the collection of adverse events of interests as demonstrated in this study. Their return rate was poor, data entry from them was not straightforward, and there were issues with data reconciliation. We concluded that customized cards prespecifying the EMA's adverse events of interests, combined with EHR-DM, were needed to maximize data collection. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2016-015469.

Feasibility of Point-of-Care Testing for Influenza Within a National Primary Care Sentinel Surveillance Network in England: Protocol for a Mixed Methods Study.

BACKGROUND: Point-of-care testing (POCT) for influenza promises to provide real-time information to influence clinical decision making and improve patient outcomes. Public Health England has published a toolkit to assist implementation of these tests in the UK National Health Service. OBJECTIVE: A feasibility study will be undertaken to assess the implementation of influenza POCT in primary care as part of a sentinel surveillance network. METHODS: We will conduct a mixed methods study to compare the sampling rates in practices using POCT and current virology swabbing practices not using POCT, and to understand the issues and barriers to implementation of influenza POCT in primary care workflows. The study will take place between March and May 2019. It will be nested in general practices that are part of the English national sentinel surveillance network run by the Royal College of General Practitioners Research and Surveillance Centre. The primary outcome is the number of valid influenza swabs taken and tested by the practices involved in the study using the new POCT. RESULTS: A total of 6 practices were recruited, and data collection commenced on March 11, 2019. Moreover, 312 swab samples had been collected at the time of submission of the protocol, which was 32.5% (312/960) of the expected sample size. In addition, 68 samples were positive for influenza, which was 20.1% (68/338) of the expected sample size. CONCLUSIONS: To the best of our knowledge, this is the first time an evaluation study has been undertaken on POCT for influenza in general practice in the United Kingdom. This proposed study promises to shed light on the feasibility of implementation of POCT in primary care and on the views of practitioners about the use of influenza POCT in primary care, including its impact on primary care workflows. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14186.

Seasonal influenza: Modelling approaches to capture immunity propagation.

Seasonal influenza poses serious problems for global public health, being a significant contributor to morbidity and mortality. In England, there has been a long-standing national vaccination programme, with vaccination of at-risk groups and children offering partial protection against infection. Transmission models have been a fundamental component of analysis, informing the efficient use of limited resources. However, these models generally treat each season and each strain circulating within that season in isolation. Here, we amalgamate multiple data sources to calibrate a susceptible-latent-infected-recovered type transmission model for seasonal influenza, incorporating the four main strains and mechanisms linking prior season epidemiological outcomes to immunity at the beginning of the following season. Data pertaining to nine influenza seasons, starting with the 2009/10 season, informed our estimates for epidemiological processes, virological sample positivity, vaccine uptake and efficacy attributes, and general practitioner influenza-like-illness consultations as reported by the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We performed parameter inference via approximate Bayesian computation to assess strain transmissibility, dependence of present season influenza immunity on prior protection, and variability in the influenza case ascertainment across seasons. This produced reasonable agreement between model and data on the annual strain composition. Parameter fits indicated that the propagation of immunity from one season to the next is weaker if vaccine derived, compared to natural immunity from infection. Projecting the dynamics forward in time suggests that while historic immunity plays an important role in determining annual strain composition, the variability in vaccine efficacy hampers our ability to make long-term predictions.

End of season influenza vaccine effectiveness in adults and children in the United Kingdom in 2017/18.

BackgroundIn the United Kingdom (UK), in recent influenza seasons, children are offered a quadrivalent live attenuated influenza vaccine (LAIV4), and eligible adults mainly trivalent inactivated vaccine (TIV).AimTo estimate the UK end-of-season 2017/18 adjusted vaccine effectiveness (aVE) and the seroprevalence in England of antibodies against influenza viruses cultured in eggs or tissue.MethodsThis observational study employed the test-negative case-control approach to estimate aVE in primary care. The population-based seroprevalence survey used residual age-stratified samples.ResultsInfluenza viruses A(H3N2) (particularly subgroup 3C.2a2) and B (mainly B/Yamagata/16/88-lineage, similar to the quadrivalent vaccine B-virus component but mismatched to TIV) dominated. All-age aVE was 15% (95% confidence interval (CI): -6.3 to 32) against all influenza; -16.4% (95% CI: -59.3 to 14.9) against A(H3N2); 24.7% (95% CI: 1.1 to 42.7) against B and 66.3% (95% CI: 33.4 to 82.9) against A(H1N1)pdm09. For 2-17 year olds, LAIV4 aVE was 26.9% (95% CI: -32.6 to 59.7) against all influenza; -75.5% (95% CI: -289.6 to 21) against A(H3N2); 60.8% (95% CI: 8.2 to 83.3) against B and 90.3% (95% CI: 16.4 to 98.9) against A(H1N1)pdm09. For ≥ 18 year olds, TIV aVE against influenza B was 1.9% (95% CI: -63.6 to 41.2). The 2017 seroprevalence of antibody recognising tissue-grown A(H3N2) virus was significantly lower than that recognising egg-grown virus in all groups except 15-24 year olds.ConclusionsOverall aVE was low driven by no effectiveness against A(H3N2) possibly related to vaccine virus egg-adaption and a new A(H3N2) subgroup emergence. The TIV was not effective against influenza B. LAIV4 against influenza B and A(H1N1)pdm09 was effective.

Analysis of Primary Care Computerised Medical Records with Deep Learning.

The analysis of primary care data plays an important role in understanding health at an individual and population level. Currently the utilization of computerized medical records is low due to the complexities, heterogeneities and veracity associated with these data. We present a deep learning methodology that clusters 11,000 records in an unsupervised manner identifying non-linear patterns in the data. This provides a useful tool for visualization as well as identify features driving the formation of clusters. Further analysis reveal the features that differentiate sub-groups that can aid clinical decision making. Our results uncover subsets that contain the highest proportion of missing data, specifically Episode type, as well as the sources that provide the most complete data.

Serological surveillance of influenza in an English sentinel network: pilot study protocol.

BACKGROUND: Rapidly undertaken age-stratified serology studies can produce valuable data about a new emerging infection including background population immunity and seroincidence during an influenza pandemic. Traditionally seroepidemiology studies have used surplus laboratory sera with little or no clinical information or have been expensive detailed population based studies. We propose collecting population based sera from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), a sentinel network with extensive clinical data. AIM: To pilot a mechanism to undertake population based surveys that collect serological specimens and associated patient data to measure seropositivity and seroincidence due to seasonal influenza, and create a population based serology bank. METHODS AND ANALYSIS: Setting and Participants: We will recruit 6 RCGP RSC practices already taking nasopharyngeal virology swabs. Patients who attend a scheduled blood test will be consented to donate additional blood samples. Approximately 100-150 blood samples will be collected from each of the following age bands - 18- 29, 30- 39, 40- 49, 50- 59, 60- 69 and 70+ years. METHODS: We will send the samples to the Public Health England (PHE) Seroepidemiology Unit for processing and storage. These samples will be tested for influenza antibodies, using haemagglutination inhibition assays. Serology results will be pseudonymised, sent to the RCGP RSC and combined using existing processes at the RCGP RSC secure hub. The influenza seroprevalence results from the RCGP cohort will be compared against those from the annual PHE influenza residual serosurvey. ETHICS AND DISSEMINATION: Ethical approval was granted by the Proportionate Review Sub- Committee of the London - Camden & Kings Cross on 6 February 2018. This study received approval from Health Research Authority on 7 February 2018. On completion the results will be made available via peer-reviewed journals.

Enhanced passive surveillance of influenza vaccination in England, 2016-2017- an observational study using an adverse events reporting card.

Influenza is a major public health burden, mainly prevented by vaccination. Recommendations on influenza vaccine composition are updated annually and constant benefit-risk monitoring is therefore needed. We conducted near-real-time enhanced passive surveillance (EPS) for the influenza vaccine, Fluarix Tetra, according to European Medicines Agency guidance, in 10 volunteer general practices in England using Fluarix Tetra as their principal influenza vaccine brand, from 1-Sep to 30-Nov-2016. The EPS method used a combination of routinely collected data from electronic health records (EHR) and a customized adverse events reporting card (AERC) distributed to participants vaccinated with Fluarix Tetra. For participants vaccinated with a different influenza vaccine, data were derived exclusively from the EHR. We reported weekly and cumulative incidence of pre-defined adverse events of interest (AEI) occurring within 7 days post-vaccination, adjusted for clustering effect. Of the 97,754 eligible participants, 19,334 (19.8%) received influenza vaccination, of whom 13,861 (71.7%) received Fluarix Tetra. A total of 1,049 participants receiving Fluarix Tetra reported AEIs; 703 (67%) used the AERC (adjusted cumulative incidence rate 4.96% [95% CI: 3.92-6.25]). Analysis by individual pre-specified AEI categories identified no safety signal for Fluarix Tetra. A total of 62 individuals reported an AEI with a known brand of non-GSK influenza vaccine and 54 with an unknown brand (adjusted cumulative incidence rate 2.59% [1.93-3.47] and 1.77% [1.42-2.20], respectively). In conclusion, the study identified no safety signal for Fluarix Tetra and showed that the AERC was a useful tool that complemented routine pharmacovigilance by allowing more comprehensive capture of AEIs.