General Surveillance Research Articles

Integrating electronic health records with other data sources for postmarket drug safety signal identification: a review

Electronic health records (EHRs) have emerged as resources for both the identification of adverse drug events (ADEs) and general population health surveillance, however questions remain around how best to utilize EHR data for drug safety signal identification. While the majority of signal identification research has utilized spontaneous reports and health insurance claims, these data also have limitations. Pharmacovigilance approaches combining EHR data with other data sources have the potential to address many of the shortcomings of individual sources. This mini-review seeks to provide an overview of some of the recent research leveraging EHR data in combination with spontaneous reports, claims data, and other pharmacovigilance data sources for drug safety signal identification. Studies have shown that combining EHR data with these and other sources is often beneficial compared to the use of a single source alone, however the synergism or friction introduced is insufficiently explored in current literature. Our review explores how EHR data benefits signal identification when used in combination with other sources, what methods have been applied, and what considerations have previously been noted. Finally, we identify gaps in current research and highlight important considerations for future work using multiple real world data sources for drug safety surveillance.

Impact of frailty in older people on health care demand: simulation modelling of population dynamics to inform service planning.

As populations age, frailty and the associated demand for health care increase. Evidence needed to inform planning and commissioning of services for older people living with frailty is scarce. Accurate information on incidence and prevalence of different levels of frailty and the consequences for health outcomes, service use and costs at population level is needed. To explore the incidence, prevalence, progression and impact of frailty within an ageing general practice population and model the dynamics of frailty-related healthcare demand, outcomes and costs, to inform the development of guidelines and tools to facilitate commissioning and service development. A retrospective observational study with statistical modelling to inform simulation (system dynamics) modelling using routine data from primary and secondary health care in England and Wales. Modelling was informed by stakeholder engagement events conducted in Hampshire, England. Data sources included the Royal College of General Practitioners Research and Surveillance Centre databank, and the Secure Anonymised Information Linkage Databank. Population prevalence, incidence and progression of frailty within an ageing cohort were estimated using the electronic Frailty Index tool, and associated service use and costs were calculated. Association of frailty with outcomes, service use and costs was explored with multistate and generalised linear models. Results informed development of a prototype system dynamics simulation model, exploring population impact of frailty and future scenarios over a 10-year time frame. Simulation model population projections were externally validated against retrospective data from Secure Anonymised Information Linkage. The Royal College of General Practitioners Research and Surveillance Centre sample comprised an open cohort of the primary care population aged 50 + between 2006 and 2017 (approx. 2.1 million people). Data were linked to Hospital Episode Statistics data and Office for National Statistics death data. A comparable validation data set from Secure Anonymised Information Linkage was generated. Electronic Frailty Index score calculated annually and stratified into Fit, Mild, Moderate and Severe frailty categories. Other variables included age, sex, Index of Multiple Deprivation score, ethnicity and Urban/rural. Frailty transitions, mortality, hospitalisations, emergency department attendances, general practitioner visits and costs. Frailty is already present in people aged 50-64. Frailty incidence was 47 cases per 1000 person-years. Frailty prevalence increased from 26.5% (2006) to 38.9% (2017). Older age, higher deprivation, female sex, Asian ethnicity and urban location independently predict frailty onset and progression; 4.8% of 'fit' people aged 50-64 years experienced a transition to a higher frailty state in a year, compared to 21.4% aged 75-84. Individual healthcare use rises with frailty severity, but Mild and Moderate frailty groups have higher overall costs due to larger population numbers. Simulation projections indicate frailty will increase by 7.1%, from 41.5% to 48.7% between 2017 and 2027, and associated costs will rise by £5.8 billion (in England) over an 11-year period. Simulation modelling indicates that frailty prevalence and associated service use and costs will continue to rise in the future. Scenario analysis indicates reduction of incidence and slowing of progression, particularly before the age of 65, has potential to substantially reduce future service use and costs, but reducing unplanned admissions in frail older people has a more modest impact. Study outputs will be collated into a commissioning toolkit, comprising guidance on drivers of frailty-related demand and simulation model outputs. This study is registered as NCT04139278 www.clinicaltrials.gov. This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 16/116/43) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 44. See the NIHR Funding and Awards website for further award information.

Validation of an acute respiratory infection phenotyping algorithm to support robust computerised medical record-based respiratory sentinel surveillance, England, 2023.

IntroductionRespiratory sentinel surveillance systems leveraging computerised medical records (CMR) use phenotyping algorithms to identify cases of interest, such as acute respiratory infection (ARI). The Oxford-Royal College of General Practitioners Research and Surveillance Centre (RSC) is the English primary care-based sentinel surveillance network.AimThis study describes and validates the RSC's new ARI phenotyping algorithm.MethodsWe developed the phenotyping algorithm using a framework aligned with international interoperability standards. We validated our algorithm by comparing ARI events identified during the 2022/23 influenza season in England through use of both old and new algorithms. We compared clinical codes commonly used for recording ARI.ResultsThe new algorithm identified an additional 860,039 cases and excluded 52,258, resulting in a net increase of 807,781 cases (33.84%) of ARI compared to the old algorithm, with totals of 3,194,224 cases versus 2,386,443 cases. Of the 860,039 newly identified cases, the majority (63.7%) were due to identification of symptom codes suggestive of an ARI diagnosis not detected by the old algorithm. The 52,258 cases incorrectly identified by the old algorithm were due to inadvertent identification of chronic, recurrent, non-infectious and other non-ARI disease.ConclusionWe developed a new ARI phenotyping algorithm that more accurately identifies cases of ARI from the CMR. This will benefit public health by providing more accurate surveillance reports to public health authorities. This new algorithm can serve as a blueprint for other CMR-based surveillance systems wishing to develop similar phenotyping algorithms.

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.

Lifetime incidence and healthcare disparities in alopecia areata: A UK population-based cohort study.

Alopecia areata (AA) is an immune-mediated form of hair loss that can occur at any age, often with a significant mental health burden. We aimed to provide estimates of the lifetime incidence of AA, and the impacts on mental health, healthcare utilisation and work-related outcomes, assessing variation across major sociodemographic subgroups. AA cases were identified in primary care from the UK population-based Oxford-Royal College of General Practitioners Research and Surveillance Centre database (2009-2018). Lifetime incidence of AA was estimated at age 80 using modified time-to-event models with age as the timescale, overall and stratified by sex, ethnicity, deprivation, and geography. Mental health, healthcare utilisation and work-related outcomes were assessed in the two years after AA diagnosis compared to matched unaffected controls, and stratified by the same sociodemographic subgroups . 6,961 people developed AA during the study period. Overall lifetime incidence of AA was 2.11% (95% Confidence Interval [CI] 2.06, 2.16%). Females had a higher lifetime incidence 2.35% (95%CI 2.28, 2.43%) than males 1.88% (95%CI 1.81, 1.94%). Lifetime incidence was higher in those of Asian ethnicity 5.87% (95%CI 5.51, 6.24), other 4.47% (95%CI 3.63, 5.31), mixed 4.44% (95%CI 3.50, 5.37) and black 3.03% (95%CI 2.63, 3.42) ethnicity, compared to white ethnicity 1.74% (95%CI 1.68, 1.80). Lifetime incidence was highest in those with the greatest deprivation; most-deprived quintile 2.92% (95%CI 2.77, 3.07%) compared to least-deprived 1.68% (95%CI 1.59, 1.78%). Across sociodemographic subgroups, people with AA of black ethnicity were most likely to have anxiety (adjusted Odds Ratio versus matched controls 2.92, 95%CI 1.71, 4.91), and had the greatest risk of time off work (adjusted Hazard Ratio versus matched controls 2.54, 95%CI 1.80, 3.56). AA affects around 1 in 50 people over their lifetime. Incidence and the impact of AA on mental health and work outcomes, is highest in ethnic groups other than white. Clinicians should be aware of the marked heterogeneity in the incidence and impact of AA, and support targeted healthcare to groups at the highest risk of alopecia and its consequences.The study protocol for this retrospective observational study was registered with ClinicalTrials.gov (Identifier: NCT05727306).

The Relationship between Serum Sodium Concentration and Albuminuria: A Retrospective Cohort Study.

Lowering dietary salt intake reduces albuminuria, an early marker of renal damage and a sensitive predictor of adverse cardiovascular outcomes. The mechanisms underlying this effect are uncertain but small changes in serum sodium concentration may be important: this retrospective cohort study investigated the hypothesis that higher serum sodium concentration is a risk factor for albuminuria (defined as a urine albumin:creatinine ratio [UACR], ≥3 mg/mmol). Primary care data from the Royal College of General Practitioners Research and Surveillance Centre were used to identify 47,294 individuals with a UACR result available between April 2010 and March 2015, and no known albuminuria prior to this. Exclusion criteria were missing or abnormal serum sodium concentration at baseline (<135 or >146 mmol/L); age <18 years; diabetes mellitus; decompensated liver disease; heart failure; and stage 5 chronic kidney disease. After adjustment for known risk factors, there was a significant "U-shaped" relationship between serum sodium concentration and albuminuria. The lowest risk was associated with a serum sodium of 138-140 mmol/L. In comparison, the risk of albuminuria was 18% higher with a serum sodium of 135-137 mmol/L and 19% higher with a serum sodium of 144-146 mmol/L. There was no association between serum sodium concentration and blood pressure. The finding of a positive association between higher serum sodium concentration and albuminuria is in support of the hypothesis, but the inverse relationship between serum sodium concentration and albuminuria at lower concentrations warrants further explanation.

A qualitative, multi-centre approach to the current state of digitalisation and automation of surveillance in infection prevention and control in German hospitals

BackgroundHealthcare associated infections (HAI) pose a major threat to healthcare systems resulting in an increased burden of disease. Surveillance plays a key role in rapidly identifying these infections and preventing further transmissions. Alas, in German hospitals, the majority of surveillance efforts have been heavily relying on labour intensive processes like manual chart review. In order to be able to identify further starting points for future digital tools and interventions to aid the surveillance of HAI we aimed to gain an understanding of the current state of digitalisation in the context of the general surveillance organisation in German clinics across all care-levels. The end user perspective of infection prevention and control (IPC) professionals was chosen to identify digital interventions that have the biggest impact on the daily surveillance work routines of IPC professionals. Perceived impediments in the advancement of surveillance digitalisation should be explored.MethodsFollowing the development of an interview guideline, eight IPC professionals from seven German hospitals of different care levels were questioned in semi- structured interviews between December 2022 and January 2023. These included questions about general surveillance organisation, access to digital data sources, software to aid the surveillance process as well as current issues in the surveillance process and implementation of software systems. Subsequently, after full transcription, the interview sections were categorized in code categories (first deductive then inductive coding) and analysed qualitatively.ResultsResults were characterised by high heterogeneity in terms of general surveillance organisation and access to digital data sources. Software configuration of hospital and laboratory information systems (HIS/LIS) as well as patient data management systems (PDMS) varied not only between hospitals of different care levels but also between hospitals of the same care level. Outside research projects, neither fully automatic software nor solutions utilising artificial intelligence have currently been implemented in clinical routine in any of the hospitals.ConclusionsAccess to digital data sources and software is increasingly available to aid surveillance of HAI. Nevertheless, surveillance processes in hospitals analysed in this study still heavily rely on manual processes. In the analysed hospitals, there is an implementation and funding gap of (semi-) automatic surveillance solutions in clinical practice, especially in healthcare facilities of lower care levels.

Occurrence and trends of Clostridioides difficile infections in hospitalized patients: a prospective multi-centre cohort study in six German university hospitals, 2016–2020

For Clostridioides difficile infections (CDIs) in Germany no longitudinal multi-centre studies with standardized protocols for diagnosing CDI are available. Recent evaluations of general surveillance databases in Germany indicate a downward trend in CDI rates. We aimed to describe the actual burden and trends of CDI in German university hospitals from 2016 to 2020. Our study was a prospective multi-centre study covering six German university hospitals. We report the data in total, stratified by year, by medical specialty as well as by CDI severity. Multi-variable regression analyses were performed to assess risk factors for severe CDI. We registered 3780 CDI cases among 1,436,352 patients. The median length of stay (LOS) of CDI cases was 20 days (interquartile range 11-37) compared with a general LOS of 4.2 days. In-hospital all-cause mortality in CDI patients was 11.7% (N= 444/3780), while mortality attributed to CDI was 0.4% (N= 16/3761). CDI recurrence rate was comparatively low at 7.2%. The incidence density of severe healthcare-associated healthcare onset (HAHO)-CDI showed a significant decrease from 2.25/10,000 patient days (pd) in 2016 to 1.49/10,000 pd in 2020 (trend calculation P=0.032). Compared with a European point-prevalence study in 2013/2014, where overall CDI incidence density was 11.2 cases/10,000 pd in Germany (EUCLID), we see in our study halved overall CDI rates of 5.6 cases/10,000 pd in 2020. Our study shows current data on the distribution of CDI cases in German university hospitals and thus provides international comparative data on the key indicators of CDI.

Characteristics of surveillance systems for suicide and self-harm: A scoping review.

Suicide is a complex public health issue. Surveillance systems play a vital role in identifying trends and epidemiologic needs, informing public health strategies, and tailoring effective context-based suicide prevention interventions. To identify and summarise the characteristics of specific surveillance systems and general health behaviour that include data onsuicide and self-harm. A scoping review following the JBI recommendations and PRISMA-ScR guidelines identified 29 relevant studies on suicide and self-harm surveillance systems. A systematic search was performed on Cinahl, Embase, Lilacs-Latin American and Caribbean Health Sciences Literature, PubMed-US National Library of Medicine, Scopus, and Google Scholar. The eligibility criteria include papers that use qualitative, quantitative or mixed methods with no restrictions on time or language. The following papers were excluded regarding euthanasia and assisted suicide, as well as papers that did not explicitly describe suicide, self-harm, and surveillance systems. Two researchers independently screened the materials for eligibility and extracted data from the included studies. Data analysis was conducted using content analysis. Twenty-nine references were included, and 30 surveillance systems were identified and classified into general health behaviour surveillance (n = 15) and specific systems for suicide and self-harm (n = 15). General health behaviour systems often operate at national data collection level, collecting non-fatal data in healthcare settings, mainly emergency departments. The specific systems exhibited greater variability in terms of context, involved actors, data collection level, data collection procedures, and case classification. Limitations found by the studies pointed mostly to case definitions and data quality. Co-production, intersectoral collaboration, clear case definition criteria and data standardisation are essential to improve surveillance systems for suicide and self-harm. This review identified the characteristics of surveillance systems for suicide and self-harm. Monitoring and evaluation are crucial for ongoing relevance and impact on prevention efforts.

Pathogen prioritisation for wastewater surveillance ahead of the Paris 2024 Olympic and Paralympic Games, France.

BackgroundWastewater surveillance is an effective approach to monitor population health, as exemplified by its role throughout the COVID-19 pandemic.AimThis study explores the possibility of extending wastewater surveillance to the Paris 2024 Olympic and Paralympic Games, focusing on identifying priority pathogen targets that are relevant and feasible to monitor in wastewater for these events.MethodsA list of 60 pathogens of interest for general public health surveillance for the Games was compiled. Each pathogen was evaluated against three inclusion criteria: (A) analytical feasibility; (B) relevance, i.e. with regards to the specificities of the event and the characteristics of the pathogen; and (C) added value to inform public health decision-making. Analytical feasibility was assessed through evidence from peer-reviewed publications demonstrating the detectability of pathogens in sewage, refining the initial list to 25 pathogens. Criteria B and C were evaluated via expert opinion using the Delphi method. The panel consisting of some 30 experts proposed five additional pathogens meeting criterion A, totalling 30 pathogens assessed throughout the three-round iterative questionnaire. Pathogens failing to reach 70% group consensus threshold underwent further deliberation by a subgroup of experts.ResultsSix priority targets suitable for wastewater surveillance during the Games were successfully identified: poliovirus, influenza A virus, influenza B virus, mpox virus, SARS-CoV-2 and measles virus.ConclusionThis study introduced a model framework for identifying context-specific wastewater surveillance targets for a mass gathering. Successful implementation of a wastewater surveillance plan for Paris 2024 could incentivise similar monitoring efforts for other mass gatherings globally.

Deploying an asthma dashboard to support quality improvement across a nationally representative sentinel network of 7.6 million people in England

Every year, there are ~100,000 hospital admissions for asthma in the UK, many of which are potentially preventable. Evidence suggests that carefully conceptualised and implemented audit and feedback (A&F) cycles have the potential to improve clinical outcomes for those with chronic conditions. We wanted to investigate the technical feasibility of developing a near-real time asthma dashboard to support A&F interventions for asthma management in primary care. We extracted cross-sectional data on asthma from 756 participating GP practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) database in England comprising 7.6 million registered people. Summary indicators for a GP practice were compared to all participating RCGP RSC practices using practice-level data, for the week 6–12th-Mar-2023. A weekly, automated asthma dashboard with features that can support electronic-A&F cycles that compared key asthma indicators for a GP practice to RCGP RSC could be created (https://tinyurl.com/3ydtrt85): 12-weeks-incidence 0.4% vs 0.4%, annual prevalence 6.1% vs 6.7%, inhaled relievers to preventer 1.2 vs 1.1, self-management plan given 83.4% vs 60.8%, annual reviews 36.8% vs 57.3%, prednisolone prescriptions 2.0% vs 3.2%, influenza vaccination 56.6% vs 55.5%, pneumococcal vaccination ever (aged ≥65 years) 90.2% vs 84.1% and current smokers 14.9% vs 14.8%. Across the RCGP RSC, the rate of hospitalisations was 0.024%; comparative data had to be suppressed for the study practice because of small numbers. We have successfully created an automated near real-time asthma dashboard that can be used to support A&F initiatives to improve asthma care and outcomes in primary care.

Mycobacterium tuberculosis Infection in School Contacts of Tuberculosis Cases: A Systematic Review and Meta-Analysis.

Substantial tuberculosis transmission occurs outside of households, and tuberculosis surveillance in schools has recently been proposed. However, the yield of tuberculosis outcomes from school contacts is not well characterized. We assessed the prevalence of Mycobacterium tuberculosis infection among close school contacts by performing a systematic review. We searched PubMed, Elsevier, China National Knowledge Infrastructure, and Wanfang databases. Studies reporting the number of children who were tested overall and who tested positive were included. Subgroup analyses were performed by study location, index case bacteriological status, type of school, and other relevant factors. In total, 28 studies including 54,707 school contacts screened for M. tuberculosis infection were eligible and included in the analysis. Overall, the prevalence of M. tuberculosis infection determined by the QuantiFERON Gold in-tube test was 33.2% (95% CI, 0.0-73.0%). The prevalences of M. tuberculosis infection based on the tuberculin skin test (TST) using 5 mm, 10 mm, and 15 mm as cutoffs were 27.2% (95% CI, 15.1-39.3%), 24.3% (95% CI, 15.3-33.4%), and 12.7% (95% CI, 6.3-19.0%), respectively. The pooled prevalence of M. tuberculosis infection (using a TST ≥5-mm cutoff) was lower in studies from China (22.8%; 95% CI, 16.8-28.8%) than other regions (36.7%; 95% CI, 18.1-55.2%). The pooled prevalence of M. tuberculosis infection was higher when the index was bacteriologically positive (43.6% [95% CI, 16.5-70.8%] versus 23.8% [95% CI, 16.2-31.4%]). These results suggest that contact investigation and general surveillance in schools from high-burden settings merit consideration as means to improve early case detection in children.

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

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. 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). 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. 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. 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.

#60 Implementation of chronic kidney disease guidelines for sodium-glucose co-transporter-2 inhibitor use in primary care: a cross-sectional study

Abstract Background and Aims The cardiovascular and kidney benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in people with chronic kidney disease (CKD) are well established. The implementation of updated SGLT2 inhibitor guidelines and prescribing in the real-world CKD population remains largely unknown. Method We performed a cross-sectional study of adults with CKD registered with primary care practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network on the 31st December 2022. We examined the extent to which SGLT2 inhibitor guidelines apply to and are then implemented in adults with CKD. We used a logistic regression model to identify independent factors associated with SGLT2 inhibitor prescribing. Results Of 6,670,829 adults we identified 516,491 (7·7%) with CKD, including 32·8% (n = 169,443) who had co-existing type 2 diabetes (T2D). 26·8% (n = 138,183) of the overall CKD population had a guideline directed indication for SGLT2 inhibitor treatment. A higher proportion of CKD patients with co-existing T2D were indicated for treatment, compared to those without T2D (62·8% [n = 106,468] vs. 9·1% [n = 31,715]). SGLT2 inhibitors were prescribed to 17·0% (n = 23,466) of those with an indication for treatment, and prescriptions were predominantly in those with co-existing T2D; 22·0% (n = 23,464) in those with T2D, and &amp;lt;0·1% (n = 2) in those without T2D. In adjusted multivariable analysis of people with CKD and T2D, females (OR 0·70, 95% CI 0·67-0·72, p &amp;lt; 0·001), individuals of Black ethnicity (OR 0·87, 95% CI 0·79-0·95, p &amp;lt; 0·001) and those of lower socio-economic status (OR 0·71, 95% CI 0·68-0·75, p &amp;lt; 0.001) were less likely to be prescribed an SGLT2 inhibitor. Those with an estimated glomerular filtration rate (eGFR) &amp;lt;60 mL/min/1.73 m2 had a lower likelihood of receiving an SGLT2 inhibitor compared to those with an eGFR ≥60 mL/min/1.73 m2 (eGFR 45-60 mL/min/1·73 m2 OR 0·65, 95% CI 0·62-0·68, p &amp;lt; 0·001, eGFR 30-45 mL/min/1·73 m2 OR 0·73, 95% CI 0·69-0·78, p &amp;lt; 0·001, eGFR 15-30 mL/min/1·73 m2 OR 0·52, 95% CI 0·46-0·60, p &amp;lt; 0·001, eGFR &amp;lt;15 mL/min/1·73 m2 OR 0·03, 95% CI 0·00-0·23, p = 0·004, respectively). Those with albuminuria (urine albumin-to-creatinine ratio 3-30 mg/mmol) were less likely to be prescribed an SGLT2 inhibitor, compared to those without albuminuria (OR 0·78, 95% CI 0·75-0·82, p &amp;lt; 0·001). Conclusion SGLT2 inhibitor guidelines in CKD have not yet been successfully implemented into clinical practice, most notably in those without co-existing T2D. Enhanced efforts to embed SGLT2 inhibitors equitably into routine care for people with CKD are urgently needed, particularly in those at highest risk of adverse outcomes and in the absence of T2D.

Analysis of a European general wildlife health surveillance program: Chances, challenges and recommendations.

In a One Health perspective general wildlife health surveillance (GWHS) gains importance worldwide, as pathogen transmission among wildlife, domestic animals and humans raises health, conservation and economic concerns. However, GWHS programs operate in the face of legal, geographical, financial, or administrative challenges. The present study uses a multi-tiered approach to understand the current characteristics, strengths and gaps of a European GWHS that operates in a fragmented legislative and multi-stakeholder environment. The aim is to support the implementation or improvement of other GWHS systems by managers, surveillance experts, and administrations. To assess the current state of wildlife health investigations and trends within the GWHS, we retrospectively analyzed 20 years of wildlife diagnostic data to explore alterations in annual case numbers, diagnosed diseases, and submitter types, conducted an online survey and phone interviews with official field partners (hunting administrators, game wardens and hunters) to assess their case submission criteria as well as their needs for post-mortem investigations, and performed in-house time estimations of post-mortem investigations to conduct a time-per-task analysis. Firstly, we found that infectious disease dynamics, the level of public awareness for specific diseases, research activities and increasing population sizes of in depth-monitored protected species, together with biogeographical and political boundaries all impacted case numbers and can present unexpected challenges to a GWHS. Secondly, we found that even a seemingly comprehensive GWHS can feature pronounced information gaps, with underrepresentation of common or easily recognizable diseases, blind spots in non-hunted species and only a fraction of discovered carcasses being submitted. Thirdly, we found that substantial amounts of wildlife health data may be available at local hunting administrations or disease specialist centers, but outside the reach of the GWHS and its processes. In conclusion, we recommend that fragmented and federalist GWHS programs like the one addressed require a central, consistent and accessible collection of wildlife health data. Also, considering the growing role of citizen observers in environmental research, we recommend using online reporting systems to harness decentrally available information and fill wildlife health information gaps.

Prodromal Status of Rapid Eye Movement Sleep Behavior Disorder: Clinical Significance and Future Perspectives

Rapid eye movement (REM) sleep behavior disorder (RBD) is a prodromal stage for major neurodegenerative diseases, particularly α-synucleinopathies. Recently, the spectrum of RBD is expanding and its prodromal state has been recognized and categorized into isolated REM sleep without atonia and isolated dream-enacting behavior. Although unclear, prodromal RBD frequently occurs in the aged population, with a significantly high phenoconversion rate to RBD and an increased risk of developing neurodegenerative disorders. More active and structured general surveillance of this condition may contribute to the effective modulation of major neurodegenerative diseases. However, the clinical and polysomnographic profiles of prodromal RBD, methods for effective screening and diagnosis of prodromal RBD, and biomarkers for disease progression and phenoconversion must be investigated.

P126 Use of oral contraceptives in females with rheumatoid arthritis is not associated with an increased risk of venous thromboembolism: United Kingdom-population based study

Abstract Background/Aims While the use of oral contraceptives in females with immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) is acknowledged as a risk factor for venous thromboembolism (VTE), the interaction between oral contraceptive use and RA is poorly understood. In a large population-based study, we aimed to estimate RA-attributable VTE risk in females using oestrogen contraceptives and/or on hormone replacement therapy (HRT). Methods Females registered with a general practice from January 1999 to December 2018 were identified from the Royal College of General Practitioners Research (RCGP) and Surveillance Centre (RSC) database. Female RA patients and VTE outcome (composite of pulmonary embolism and deep vein thrombosis) were determined using previously-validated algorithms. Female unaffected controls (UCs) were matched 4:1 with RA patients by current age (per year), calendar time, and years since practice registration using nearest neighbour matching, with replacement. Absolute VTE rates over 20 years were compared in RA patients versus matched UCs, overall and in two different subgroups defined by the use of oestrogen contraceptives or HRT. Relative VTE risk over the same period was estimated using Cox proportional hazards models adjusted for sociodemographic and clinical features and established VTE risk factors (BMI [body-mass index], smoking status, alcohol use, evidence of reduced mobility, thrombophilia, fracture of the lower limb and family history of VTE). Results A total of 82,082 female adults were included in this study, of whom 16,634 were RA patients and 65,448 were UCs. Average study follow-up was 8.3 years (standard deviation [SD]=6.2 years). Female RA patients (mean age 58.3, SD 16.5; mean BMI 27.0, SD 5.9) were similar to matched UCs in their clinical characteristics. Compared to UCs, females with RA were less likely to receive oral contraceptives (RA n = 545 [3.3%], UCs n = 2,542 [3.9], p &amp;lt; 0.001) but more likely to receive HRT (RA n = 752 [4.5%], UCs n = 2,460 [3.8], p &amp;lt; 0.001). Unadjusted VTE events rates were consistently higher in females with RA compared to UCs (430.2 per 100,000 person-years [py], 95% confidence interval [CI]: 396.1, 466.3; UC: 260.5 per 100,000 py, 95%CI: 247.1, 274.4) and in those receiving and not receiving oral contraceptives and HRT. Overall, relative risk of VTE was 52% higher in females with RA compared UCs (adjusted hazard ratio [aHR]= 1.52, 95%CI: 1.36, 1.71, p &amp;lt; 0.001). Compared to UCs, relative risk increases were not statistically significant for females with RA receiving oral contraceptives (aHR 1.43; 95%CI 0.60, 3.63, p = 0.46) and HRT (aHR 2.32; 95%CI 0.92, 5.85, p = 0.08). Conclusion UK data suggest that all women with RA are at a similarly increased risk of VTE irrespective of the use of oestrogen contraceptives or HRT, although larger studies are needed to confirm this finding. It is therefore advisable to conduct routine VTE risk factor assessments for all females with RA. Disclosure J. Galloway: Honoraria; JG has received honoraria from Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UC. V. Basey: Corporate appointments; Pfizer employee. A. Barkaway: Corporate appointments; Pfizer employee. S. de Lusignan: Grants/research support; SdeL has received funding through his universities from Eli Lilly, GSK, Astra Zeneca, MSD, Sanofi, Seqirus, Takeda and Moderna. Other; Director of the RCGP RSC. M.H. Buch: Consultancies; M.H.B. has provided expert advice and received/paid to employer consultant fees from AbbVie, Eli Lilly, EMD serono, Gilead, Pfizer and Sanofi. Grants/research support; .H.B. has received research grants paid to her employer from Gilead Ltd, Pfizer Ltd, Roche and UCB.

P052 Rheumatoid arthritis associated risk of venous thromboembolism is not dependent on disease duration: United Kingdom-based population study

Abstract Background/Aims Risk of venous thromboembolism (VTE) is higher in patients with rheumatoid arthritis (RA) compared to the general population; however, whether this risk changes with RA disease duration remains poorly understood. Acknowledging potential heterogeneity in risk by RA duration could support more tailored screening and effective preventive approaches. In a large population-based study, we aimed to characterise the RA-attributable VTE risk in patients with varying disease durations. Methods Adults registered with a general practice from January 1999 to December 2018 were identified from the Royal College of General Practitioners Research (RCGP) and Surveillance Centre (RSC) primary care database. RA patients (diagnosed prior to and during the study period), VTE outcome (as a composite of pulmonary embolism [PE] or deep vein thrombosis [DVT]) and individual PE and DVT outcomes were determined using previously validated algorithms. RA-unaffected controls (UCs) were matched 4:1 with RA patients by current age, sex, calendar time, and years since practice registration using nearest neighbour matching with replacement. Absolute VTE, PE and DVT rates over 20 years were compared in RA patients versus matched UC across four subgroups defined by disease duration (0-2, 2-5, 5-10 and ≥10 years since diagnosis). Across the same subgroups, relative risks over the same period were estimated using Cox proportional hazards models adjusted for sociodemographic and clinical features and established VTE risk factors (body-mass index [BMI], smoking status, alcohol use, evidence of reduced mobility, thrombophilia, fracture of the lower limb and family history of VTE). Results 117,050 individuals were included, of whom 93,640 were UCs and 23,410 were RA patients. Among those with RA, 63.9% were included at or within two years of diagnosis, 7.8% within two to five years of diagnosis, 9.8% within five to ten years of diagnosis, and 18.5% more than 10 years after diagnosis. Average study follow-up for the primary outcome (VTE) was 8.2 years (standard deviation [SD]=6.6 years). RA patients (mean age 59.0, SD 15.5; 28.9% male [n = 6776]; mean BMI 27.1, SD 5.6) were similar to matched UCs in clinical characteristics. Unadjusted VTE events rates were consistently higher in RA patients compared to UCs across all subgroups. Relative risk of VTE was similarly increased in RA patients compared to the general population regardless of the time elapsed since RA diagnosis (adjusted hazard ratios [aHR] range: 1.49-1.63, all p &amp;lt; 0.001). The results obtained when PE (aHR range 1.46-2.02, all p &amp;lt; 0.001) and DVT (aHR range 1.43-1.89, all p &amp;lt; 0.001) were analysed separately were similar to those observed in the composite outcome. Conclusion Healthcare professionals should recognize that individuals with RA face a consistently elevated VTE risk compared to the general population, irrespective of disease duration. This highlights the need for vigilant monitoring and assessment of VTE risk factors even in early-stage cases. Disclosure J. Galloway: Honoraria; JG has received honoraria from Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UC. V. Basey: Corporate appointments; Pfizer employee. S. Rana: Corporate appointments; Pfizer employee. S. de Lusignan: Grants/research support; SdeL has received funding through his universities from Eli Lilly, GSK, Astra Zeneca, MSD, Sanofi, Seqirus, Takeda and Moderna. Other; Director of the RCGP RSC. M.H. Buch: Consultancies; M.H.B. has provided expert advice and received/paid to employer consultant fees from AbbVie, Eli Lilly, EMD serono, Gilead, Pfizer and Sanofi. Grants/research support; M.H.B. has received research grants paid to her employer from Gilead Ltd, Pfizer Ltd, Roche and UCB.

OA38 Venous thromboembolism risk is consistently increased in people with rheumatoid arthritis across different ages, sexes and obesity status: United Kingdom population-based study

Abstract Background/Aims Risk of venous thromboembolism (VTE) is increased in people with rheumatoid arthritis (RA) when compared to the general population, but the variation of this risk among patients is not well understood. Acknowledging the heterogeneity in RA-attributable VTE risk could support tailoring of treatment plans and screening protocols based on an individual’s specific risk profile. In a large population-based study, we aimed to evaluate for variation in RA-attributable VTE risk by age, sex and body-mass index (BMI). Methods Adults registered with a general practice from January 1999 to December 2018 were identified from the Royal College of General Practitioners Research (RCGP) and Surveillance Centre (RSC) primary care database. RA patients and VTE outcome (composite of pulmonary embolism and deep vein thrombosis) were determined using previously validated algorithms. RA-unaffected controls (UCs) were matched 4:1 with RA patients by current age, sex, calendar time, and years since practice registration using nearest neighbour matching with replacement. Absolute VTE rates over 20 years were compared in RA patients versus matched UCs, overall and by age category (18-49, 50-69, ≥70), sex, and BMI category (BMI &amp;lt;25, 25-29.9, ≥30). Across the same subgroups, relative VTE risk over the same period was estimated using Cox proportional hazards models adjusted for sociodemographic and clinical features and established VTE risk factors (BMI, smoking status, alcohol use, evidence of reduced mobility, thrombophilia, fracture of the lower limb and family history of VTE). Results 117,050 individuals were included, of whom 23,410 were RA patients and 93,640 were UCs. Average follow-up was 8.2 years (standard deviation [SD]=6.6 years). RA patients (mean age 59.0, SD 15.5; 28.9% male [n = 6776]; mean BMI 27.1, SD 5.6) were similar to matched UCs in clinical characteristics. Unadjusted VTE events rates were consistently higher in RA patients compared to UCs overall and across all subgroups (overall rates RA: 442.4 per 100,000 person-years [py], 95% confidence interval [CI]: 413.0, 473.2; UC: 262.2 per 100,000 py, 95%CI: 251.9, 273.9); subgroup rates). Similarly, overall relative VTE risk was 46% higher in people with RA compared to UCs (adjusted hazard ratio [aHR]= 1.46, 95%CI: 1.36, 1.56; p &amp;lt; 0.001), and was consistently higher across age-, sex- and BMI-defined subgroups (aHR range: 1.34-2.13, all p &amp;lt; 0.001). Although relative risk was highest in RA patients under 50 years (aHR= 2.13, 95%CI: 1.62-2.79; p &amp;lt; 0.001), this patient subgroup had the lowest absolute risk of VTE (approximately 2.2- and 3.4-fold lower than that observed in those aged 50-69 and ≥70, respectively). Conclusion Clinicians should be aware that risk of VTE is consistently higher in people with RA compared to the general population, regardless of age, sex and BMI. Findings suggest close monitoring and assessment of VTE risk factors is required even in younger individuals with RA. Disclosure J. Galloway: Honoraria; JG has received honoraria from Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UC. V. Basey: Corporate appointments; Pfizer employee. M. Mclean: Corporate appointments; Pfizer employee. S. de Lusignan: Grants/research support; SdeL has received funding through his universities from Eli Lilly, GSK, Astra Zeneca, MSD, Sanofi, Seqirus, Takeda and Moderna. Other; Director of the RCGP RSC. M.H. Buch: Consultancies; M.H.B. has provided expert advice and received/paid to employer consultant fees from AbbVie, Eli Lilly, EMD serono, Gilead, Pfizer and Sanofi. Grants/research support; M.H.B. has received research grants paid to her employer from Gilead Ltd, Pfizer Ltd, Roche and UCB.

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.

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. 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. 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. 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. 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.