BackgroundChronic kidney disease (CKD) is a common health problem associated with increased risk of cardiovascular disease (CVD), end-stage kidney disease (ESKD), and premature death. It is estimated that one-third of people aged ≥70 years have CKD globally, many of whom are undiagnosed, but little is known about the value of screening.AimTo compare the risk of adverse health outcomes between people with an existing diagnosis of CKD and those identified through screening, and identify factors associated with mortality in CKD.Design & settingProspective cohort study of 892 primary care patients aged ≥60 years with CKD (existing and screening detected) in Oxfordshire, with data linkage to civil death registry and secondary care.MethodHazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models to compare the risk of all-cause mortality, hospitalisation, CVD, ESKD separately, and as a composite between CKD groups, as well as to identify factors associated with mortality.ResultsAfter a median follow-up of 3–5 years, 49 people died, 512 were hospitalised, 78 had an incident CVD event, and none had an ESKD event. There was no difference in the composite outcome between those with existing CKD and those identified through screening (HR 0.94, 95% CI = 0.67 to 1.33). Older age (HR 1.10, 95% CI = 1.06 to 1.15), male sex (HR 2.31, 95% CI = 1.26 to 4.24), and heart failure (HR 5.18, 95% CI = 2.45 to 10.97) were associated with increased risk of death.ConclusionScreening older people for CKD may be of value, as their risk of short-term mortality, hospitalisation, and CVD is comparable with people routinely diagnosed. Larger studies with longer follow-up in more diverse and representative populations of older adults are needed to corroborate these findings.

BACKGROUND:International guidelines recommend the administration of two doses of pre-exposure hepatitis A vaccination for people with chronic liver disease to prevent severe complications. We aimed to describe hepatitis A vaccination coverage and mortality in adults with chronic liver disease in England. METHODS:We did a retrospective cohort study using routinely collected medical record data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre (RSC) primary care sentinel network. We included people aged 18 years or older who were diagnosed with chronic liver disease between Jan 1, 2012, and Dec 31, 2022. The primary outcome of interest was hepatitis A vaccination. Hepatitis A vaccination coverage was calculated using the number of vaccinated people with chronic liver disease as the numerator and the chronic liver disease population in the RSC dataset as the denominator. We compared individual characteristics by vaccination status using descriptive statistics. We used a multistate survival model to estimate the transition probabilities between four states: (1) diagnosis of chronic liver disease; (2) first hepatitis A vaccination; (3) second hepatitis A vaccination; and (4) death. FINDINGS:664 571 individuals aged 18 years or older with chronic liver disease were identified from the RSC sentinel network population, of whom 625 079 individuals were included in our analysis. Of 625 079 individuals with chronic liver disease, 13 875 (2·2%) had received a first hepatitis A vaccination, 3007 (0·4%) had received a second dose, 732 (5·3%) of 13 875 vaccinated individuals died, and 101 065 (16·5%) of 611 204 individuals without vaccination died during the study period. Adjusting for death as a competing risk, vaccination was more likely among younger age quintiles (hazard ratio 5·46 [95% CI 5·13-5·81]), non-smokers (1·59 [1·54-1·65]), residents of urban areas (1·28 [1·21-1·35]), individuals with higher socioeconomic status (1·06 [1·03-1·10]), and individuals with a diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD; 1·71 [1·64-1·78]). Individuals with a history of harmful alcohol use (0·36 [0·32-0·39]), type 1 diabetes (0·46 [0·36-0·57]), chronic kidney disease (0·63 [0·57-0·70]), or mental disorders (0·66 [0·64-0·69]) were less likely to be vaccinated. The lowest risk of mortality was in people with chronic liver disease of infectious or autoimmune aetiology and in people with MASLD. INTERPRETATION:Hepatitis A vaccine uptake among people with chronic liver disease in England is low, with disparities by age, location (urban vs rural), and socioeconomic status. Steps should be taken to reduce the inequalities in vaccine administration. FUNDING:GlaxoSmithKline's Investigator Sponsored Studies Program.

OBJECTIVE:COVID-19 vaccine surveillance detected thrombotic thrombocytopenia syndrome (TTS), a rare combination of thrombosis and thrombocytopenia, after COVID-19 vaccination. We evaluated TTS risk within 28 days of AZD1222 and BNT162b2 exposure. METHODS:Matched case-control (MCCS) and self-controlled case series (SCCS) studies used Oxford-Royal College of General Practitioners Research and Surveillance Centre data linked to immunization, hospitalization and death data. English patient records extracted from December 2, 2020 to October 31, 2022 were used to identify TTS cases and age, sex, and practice matched controls. Conditional logistic regression and conditional Poisson regression were used for MCCS and SCCS analyses, respectively. RESULTS:Of 666 TTS events identified, >90% happened without AZD1222/BNT162b2 exposure in the preceding 28 days. MCCS analyses showed no association between TTS and a composite of both first and second AZD1222 dose (adjusted odds ratio [aOR]: 1.45 [95% CI: 0.90-2.34]). Both studies showed increased TTS risk after AZD1222 first dose (MCCS, aOR: 2.12 [1.14-3.92]; SCCS, incidence rate ratio: 3.49 [2.22-5.49]). No association between TTS and BNT162b2 was observed. CONCLUSION:Consistent with previous studies, we found an association between TTS and receiving a first dose of AZD1222. There were no associations of TTS with AZD1222 second dose and BNT162b2 first or second doses.

BACKGROUND:Primary care computerised medical records (CMR) are used to report the incidence of acute respiratory infections (ARI) for public health surveillance. These systems could increase their utility by also reporting population-level severity of ARI; however, this is rarely done. OBJECTIVES:To identify candidate markers of ARI severity suitable for use in primary care CMR-based surveillance. METHODS:We undertook a systematic review of bibliographic databases and grey literature. Eligible studies reported characteristics for > 500 patients with ARI, severe ARI, influenza-like illness or suspected COVID-19. Studies had to report at least one potential marker of severity. A panel of clinical primary care informaticians reviewed candidate severity markers and assessed each for severity, specificity, relevance to primary care and whether it was likely to be recorded in a CMR. RESULTS:We included 126 studies from 84 countries. Seventy-seven candidate severity markers were identified across 11 groups. These included four outcome groups (complications, hospital events, intensive care events and death) and seven predictor groups (symptoms, signs, scores, investigations, treatments, absenteeism and treatment-seeking behaviour). Thirty markers were considered most suitable for primary care CMR-based ARI surveillance: 7 outcomes (such as hospital admission, attendance and death) and 23 predictors (such as shortness of breath, oxygen levels, work absence and antibiotics). Predictors were generally considered more timely, as they are likely recorded during the consultation. CONCLUSIONS:This review provides a list of severity markers that could support the development of population-level severity indicators for ARI surveillance in primary care. This could improve real-time situational awareness during respiratory outbreaks.

BACKGROUND:Hypertension is a key risk factor for death and disability, and blood pressure reduction is associated with significant reductions in cardiovascular risk. Large trials have shown that interventions including self-monitoring of blood pressure can reduce blood pressure but real-world data from wider implementation are lacking. AIM:The self-monitoring and management service evaluation in primary care (SHIP) study will evaluate a novel digital intervention for hypertension management and medication titration platform ("Hypertension-Plus") that is currently undergoing initial implementation into primary care in several parts of the UK. METHODS AND ANALYSES:The study will use a mixed methods approach including both quantitative analysis of anonymised electronic health record data and qualitative analyses of interview and customer support log data. Pseudonymised data will be extracted from electronic health records and outcomes compared between those using the digital intervention and their own historical data, as well as to those not registered to the system. The primary outcome will be difference in systolic blood pressure in the 12 months before and after implementation. A further analysis will utilise self-monitored blood pressure data from the Hypertension-Plus system itself. Semi-structured qualitative interviews will be completed with implementation and clinical leads, staff and patients in six general practices located in two different geographical areas in England. Informed by the non-adoption, abandonment, scale-up, spread, and sustainability (NASSS) framework, our analysis will identify the challenges to successful implementation and sustainability of the digital intervention in routine clinical practice and in patients' homes. ETHICS AND DISSEMINATION:The analyses of pseudonymised data were assessed by the sponsor (The University of Oxford) as service evaluation not requiring individual consent and hence did not require ethical approval. Ethics approval for the qualitative analyses was provided by Wales REC 4 (21/WA/0280) and individual written informed consent will be gained for all participants. Results will be published in peer-reviewed journals, presented at national and international conferences and disseminated via patient and health service organisations. DISCUSSION:This study will provide an in-depth analysis of the impact and acceptance of initial implementation of a novel digital intervention, enhancing our understanding and supporting more effective implementation of telemonitoring based hypertension management systems for blood pressure control in England.

Introduction Respiratory 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. Aim This study describes and validates the RSC’s new ARI phenotyping algorithm. Methods We 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. Results The 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. Conclusion We 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.

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 similar to 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. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association.

BackgroundAdults classified as immunosuppressed have been disproportionately affected by the COVID-19 pandemic. Compared to the immunocompetent, certain patients are at increased risk of suboptimal vaccine response and adverse health outcomes if infected. However, there has been insufficient work to pinpoint where these risks concentrate within the immunosuppressed spectrum; surveillance efforts typically treat the immunosuppressed as a single entity, leading to wide confidence intervals. A clinically meaningful and computerised medical record (CMR) compatible method to subdivide immunosuppressed COVID-19 data is urgently needed.MethodsWe conducted a rapid scoping review into COVID-19 mortality across UK immunosuppressed categories to assess if differential mortality risk was a viable means of subdivision. We converted the risk hierarchy that surfaced into a pilot digital phenotype—a valueset and series of ontological rules ready to extract immunosuppressed patients from CMR data and stratify outcomes of interest in COVID-19 surveillance dataflows.ResultsThe rapid scoping review returned COVID-19 mortality data for all immunosuppressed subgroups assessed and revealed significant heterogeneity across the spectrum. There was a clear distinction between heightened COVID-19 mortality in haematological malignancy and transplant patients and mortality that approached the immunocompetent baseline amongst cancer therapy recipients, autoimmune patients, and those with HIV. This process, complemented by expert clinical input, informed the curation of the five-part digital phenotype now ready for testing in real-world data; its ontological rules will enable mutually exclusive, hierarchical extraction with nuanced time and treatment conditions. Unique categorisations have been introduced, including ‘Bone Marrow Compromised’ and those dedicated to differentiating prescriptions related and unrelated to cancer. Codification was supported by existing reference sets of medical codes; absent or redundant codes had to be resolved manually.DiscussionAlthough this work is in its earliest phases, the development process we report has been highly informative. Systematic review, clinical consensus building, and implementation studies will test the validity of our results and address criticisms of the rapid scoping exercise they are predicated on.ConclusionComprehensive testing for COVID-19 has differentiated mortality risks across the immunosuppressed spectrum. This risk hierarchy has been codified into a digital phenotype for differentiated COVID-19 surveillance; this marks a step towards the needs-based management of these patients that is urgently required.

Background. Observational studies suggest sodium-glucose co-transporter 2 (SGLT2) inhibitor kidney outcome trials are not representative of the broader population of people with chronic kidney disease (CKD). However, there are limited data on the generalizability to those without co-existing type 2 diabetes (T2D), and the representativeness of the Study of Heart and Kidney Protection with Empagliflozin (EMPA-KIDNEY) trial has not been adequately explored. We hypothesized that SGLT2 inhibitor kidney outcome trials are more representative of people with co-existing T2D than those without, and that EMPA-KIDNEY is more representative than previous trials. Methods. A cross-sectional analysis of adults with CKD in English primary care was conducted using the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. The proportions that met the eligibility criteria of SGLT2 inhibitor kidney outcome trials were determined, and their characteristics described. Logistic regression analyses were performed to identify factors associated with trial eligibility. Results. Of 6 670 829 adults, 516 491 (7.7%) with CKD were identified. In the real-world CKD population, 0.9%, 2.2% and 8.0% met the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), Dapagliflozin and Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (DAPA-CKD) and EMPA-KIDNEY eligibility criteria, respectively. All trials were more representative of people with co-existing T2D than those without T2D. Trial participants were 9-14 years younger than the real-world CKD population, and had more advanced CKD, including higher levels of albuminuria. A higher proportion of the CREDENCE (100%), DAPA-CKD (67.6%) and EMPA-KIDNEY (44.5%) trial participants had T2D compared with the real-world CKD population (32.8%). Renin-angiotensin system inhibitors were prescribed in almost all trial participants, compared with less than half of the real-world CKD population. Females were under-represented and less likely to be eligible for the trials. Conclusion. SGLT2 inhibitor kidney outcome trials represent a subgroup of people with CKD at high risk of adverse kidney events. Our study highlights the importance of complementing trials with real-world studies, exploring the effectiveness of SGLT2 inhibitors in the broader population of people with CKD.

Abstract Background and Aims Observational studies suggest that sodium-glucose co-transporter-2 (SGLT2) inhibitor kidney outcome trials are not representative of people with chronic kidney disease (CKD). However, there are limited data on the generalisability to those without co-existing type 2 diabetes (T2D) and representativeness of the EMPA-KIDNEY trial. Method A cross-sectional analysis of adults with CKD in English primary care was conducted using the Oxford-Royal College of General Practitioners Clinical Information Digital Hub database. The proportions of people with CKD that met the eligibility criteria of SGLT2 inhibitor kidney outcome trials were determined, and their characteristics described. Logistic regression analyses were performed to identify factors associated with trial eligibility. Results Of 6 670 829 adults, 516 491 (7.7%) with CKD were identified, including 32.8% (n = 169 443) with co-existing T2D. In the total CKD cohort, 0.9%, 2.2%, and 8.0% met the CREDENCE, DAPA-CKD, and EMPA-KIDNEY eligibility criteria, respectively. All trials were more representative of people with co-existing T2D than those without T2D. Trial participants were 9-14 years younger than the trial eligible populations, and had more advanced CKD, including higher levels of albuminuria. A higher proportion of the CREDENCE (100%), DAPA-CKD (67.6%) and EMPA-KIDNEY (44.5%) trial participants had T2D compared to the total CKD population (32.8%). Renin-angiotensin-aldosterone system inhibitors were prescribed in almost all trial participants compared to less than half of the total CKD population. Females were underrepresented and less likely to be eligible for the trials. Conclusion SGLT2 inhibitor kidney outcome trials are not representative of most people with CKD in English Primary Care. These findings highlight the importance of complementing trials with real-world studies, exploring the effectiveness of SGLT2 inhibitors in the broader population of people with CKD treated in routine clinical practice.

Objective To evaluate Phenotype Execution and Modelling Architecture (PhEMA), to express sharable phenotypes using Clinical Query Language (CQL) and intensional SNOMED CT Fast Healthcare Interoperability Resources (FHIR) valuesets, for exemplar chronic disease, sociodemographic risk factor and surveillance phenotypes. Method We curated three phenotypes: Type 2 diabetes (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 (ECL), 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. Results The T2DM phenotype could be defined as two 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 to 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.

Summary: Background: 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. Methods: A cross-sectional study of adults with CKD registered with UK primary care practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network on the 31st December 2022 was undertaken. Pseudonymised data from electronic health records held securely within the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) were extracted. An update to a previously described ontological approach was used to identify the study population, using a combination of Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) indicating a diagnosis of CKD and laboratory confirmed CKD based on Kidney Disease: Improving Global Outcomes (KDIGO) diagnostic criteria. We examined the extent to which SGLT2 inhibitor guidelines apply to and are then implemented in adults with CKD. A logistic regression model was used to identify factors associated with SGLT2 inhibitor prescribing, reported as odds ratios (ORs) with 95% confidence intervals (CI). The four guidelines under investigation were the United Kingdom Kidney Association (UKKA) Clinical Practice Guideline SGLT2 Inhibition in Adults with Kidney Disease (October 2021), American Diabetes Association (ADA) and KDIGO Consensus Report on Diabetes Management in CKD (October 2022), National Institute for Health and Care Excellence (NICE) Guideline Type 2 Diabetes in Adults: Management (June 2022), and NICE Technology Appraisal Dapagliflozin for Treating CKD (March 2022). Findings: 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 people with CKD and 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 <0.1% (n = 2) in those without T2D. In adjusted multivariable analysis of people with CKD and T2D, females (OR 0.69, 95% CI 0.67–0.72, p <0.0001), individuals of Black ethnicity (OR 0.84, 95% CI 0.77–0.91, p <0.0001) and those of lower socio-economic status (OR 0.72, 95% CI 0.68–0.76, p <0.0001) were less likely to be prescribed an SGLT2 inhibitor. Those with an estimated glomerular filtration rate (eGFR) <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 <0.0001, eGFR 30–45 mL/min/1.73 m2 OR 0.73, 95% CI 0.69–0.78, p <0.0001, eGFR 15–30 mL/min/1.73 m2 OR 0.52, 95% CI 0.46–0.60, p <0.0001, eGFR <15 mL/min/1.73 m2 OR 0.03, 95% CI 0.00–0.23, p = 0.0037, 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 <0.0001). Interpretation: SGLT2 inhibitor guidelines in CKD have not yet been successfully implemented into clinical practice, most notably in those without co-existing T2D. Individuals at higher risk of adverse outcomes are paradoxically less likely to receive SGLT2 inhibitor treatment. The timeframe between the publication of guidelines and data extraction may have been too short to observe changes in clinical practice. 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. Funding: None.

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 <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 < 0·001), individuals of Black ethnicity (OR 0·87, 95% CI 0·79-0·95, p < 0·001) and those of lower socio-economic status (OR 0·71, 95% CI 0·68-0·75, p < 0.001) were less likely to be prescribed an SGLT2 inhibitor. Those with an estimated glomerular filtration rate (eGFR) <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 < 0·001, eGFR 30-45 mL/min/1·73 m2 OR 0·73, 95% CI 0·69-0·78, p < 0·001, eGFR 15-30 mL/min/1·73 m2 OR 0·52, 95% CI 0·46-0·60, p < 0·001, eGFR <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 < 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.

Aim: To conduct a systematic review of observational studies to explore the real-world kidney benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors in a large and diverse population of adults with type 2 diabetes (T2D). Materials and Methods: We searched MEDLINE, EMBASE and Web of Science for observational studies that investigated kidney disease progression in adults with T2D treated with SGLT2 inhibitors compared to other glucose-lowering therapies. Studies published from database inception to July 2022 were independently reviewed by two authors and evaluated using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. A random-effects meta-analysis was performed on studies with comparable outcome data, reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: We identified 34 studies performed across 15 countries with a total population of 1 494 373 for inclusion. In the meta-analysis of 20 studies, SGLT2 inhibitors were associated with a 46% lower risk of kidney failure events compared with other glucose-lowering drugs (HR 0.54, 95% CI 0.47-0.63). This finding was consistent across multiple sensitivity analyses and was independent of baseline estimated glomerular filtration rate (eGFR) or albuminuria status. SGLT2 inhibitors were associated with a lower risk of kidney failure when compared with dipeptidyl peptidase-4 inhibitors and a combination of other glucose-lowering drug classes (HR 0.50, 95% CI 0.38-0.67 and HR 0.51, 95% CI 0.44-0.59, respectively). However, when compared to glucagon-like peptide 1 receptor agonists there was no statistically significant difference in the risk of kidney failure (HR 0.93, 95% CI 0.80-1.09). Conclusions: The reno-protective benefits of SGLT2 inhibitors apply to a broad population of adults with T2D treated in routine clinical practice, including those at lower risk of kidney events with normal eGFR and without albuminuria. These findings support the early use of SGLT2 inhibitors in T2D for preservation of kidney health.

BACKGROUND:Hepatitis A outbreaks in the United Kingdom are uncommon. Most people develop mild to moderate symptoms that resolve, without sequelae, within months. However, in high-risk groups, including those with underlying chronic liver disease (CLD), hepatitis A infection can be severe, with a higher risk of mortality and morbidity. The Health Security Agency and the National Institute of Health and Care Excellence recommend preexposure hepatitis A vaccination given in 2 doses to people with CLD, regardless of its cause. There are currently no published reports of vaccination coverage for people with CLD in England or internationally. OBJECTIVE:This study aims to describe hepatitis A vaccination coverage in adults with CLD in a UK primary care setting and compare liver disease etiology, sociodemographic characteristics, and comorbidities in people who are and are not exposed to the hepatitis A vaccine. METHODS:We will conduct a retrospective cohort study with data from the Primary Care Sentinel Cohort of the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub database, which is nationally representative of the English population. We will include people aged 18 years and older who have been registered in general practices in the Research and Surveillance Centre network and have a record of CLD between January 1, 2012, and December 31, 2022, including those with alcohol-related liver disease, chronic hepatitis B, chronic hepatitis C, nonalcohol fatty liver disease, Wilson disease, hemochromatosis, and autoimmune hepatitis. We will carefully curate variables using the Systematized Nomenclature of Medicine Clinical Terms. We will report the sociodemographic characteristics of those who are vaccinated. These include age, gender, ethnicity, population density, region, socioeconomic status (measured using the index of multiple deprivation), obesity, alcohol consumption, and smoking. Hepatitis A vaccination coverage for 1 and 2 doses will be calculated using an estimate of the CLD population as the denominator. We will analyze the baseline characteristics using descriptive statistics, including measures of dispersion. Pairwise comparisons of case-mix characteristics, comorbidities, and complications will be reported according to vaccination status. A multistate survival model will be fitted to estimate the transition probabilities among four states: (1) diagnosed with CLD, (2) first dose of hepatitis A vaccination, (3) second dose of hepatitis A vaccination, and (4) death. This will identify any potential disparities in how people with CLD get vaccinated. RESULTS:The Research and Surveillance Centre population comprises over 8 million people. The reported incidence of CLD is 20.7 cases per 100,000. International estimates of hepatitis A vaccine coverage vary between 10% and 50% in this group. CONCLUSIONS:This study will describe the uptake of the hepatitis A vaccine in people with CLD and report any disparities or differences in the characteristics of the vaccinated population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):PRR1-10.2196/51861.

Introduction: Anemia is common in chronic kidney disease (CKD) and is associated with increased cardiovascular risk and reduced quality of life, but is often sub-optimally managed. Most patients are managed in primary care alongside other comorbidities. Interventions to improve the management of anemia in CKD in this setting are needed. Methods: We conducted a qualitative study to evaluate how an audit-based education (ABE) intervention might improve the management of anemia in CKD. We explored outcomes that would be relevant to practitioners and patients, that exposed variation of practice from National Institute for Health and Care Excellence (NICE) guidelines, and whether the intervention was feasible and acceptable. Results: Practitioners (n = 5 groups) and patients (n = 7) from 4 London general practices participated in discussions. Practitioners welcomed the evidence-based step-wise intervention. However, prescribing erythropoiesis-stimulating agents (ESAs) was felt to be outside of their scope of practice. There was a gap between NICE guidance and clinical practice in primary care. Iron studies were not well understood and anemia management was often conservative or delayed. Patients were often unaware of having CKD, and were more concerned about their other comorbidities, but largely trusted their GPs to manage them appropriately. Conclusions: The first steps of the intervention were welcomed by practitioners, but they expressed concerns about independently prescribing ESAs. Renal physicians and GPs could develop shared care protocols for ESA use in primary care. There is scope to improve awareness of renal anemia, and enhance knowledge of guideline recommendations; and our intervention should be modified accordingly.

BACKGROUND:The Data and Connectivity COVID-19 Vaccines Pharmacovigilance (DaC-VaP) UK-wide collaboration was created to monitor vaccine uptake and effectiveness and provide pharmacovigilance using routine clinical and administrative data. To monitor these, pooled analyses may be needed. However, variation in terminologies present a barrier as England uses the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), while the rest of the United Kingdom uses the Read v2 terminology in primary care. The availability of data sources is not uniform across the United Kingdom. OBJECTIVE:This study aims to use the concept mappings in the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) to identify common concepts recorded and to report these in a repeated cross-sectional study. We planned to do this for vaccine coverage and 2 adverse events of interest (AEIs), cerebral venous sinus thrombosis (CVST) and anaphylaxis. We identified concept mappings to SNOMED CT, Read v2, the World Health Organization's International Classification of Disease Tenth Revision (ICD-10) terminology, and the UK Dictionary of Medicines and Devices (dm+d). METHODS:Exposures and outcomes of interest to DaC-VaP for pharmacovigilance studies were selected. Mappings of these variables to different terminologies used across the United Kingdom's devolved nations' health services were identified from the Observational Health Data Sciences and Informatics (OHDSI) Automated Terminology Harmonization, Extraction, and Normalization for Analytics (ATHENA) online browser. Lead analysts from each nation then confirmed or added to the mappings identified. These mappings were then used to report AEIs in a common format. We reported rates for windows of 0-2 and 3-28 days postvaccine every 28 days. RESULTS:We listed the mappings between Read v2, SNOMED CT, ICD-10, and dm+d. For vaccine exposure, we found clear mapping from OMOP to our clinical terminologies, though dm+d had codes not listed by OMOP at the time of searching. We found a list of CVST and anaphylaxis codes. For CVST, we had to use a broader cerebral venous thrombosis conceptual approach to include Read v2. We identified 56 SNOMED CT codes, of which we selected 47 (84%), and 15 Read v2 codes. For anaphylaxis, our refined search identified 60 SNOMED CT codes and 9 Read v2 codes, of which we selected 10 (17%) and 4 (44%), respectively, to include in our repeated cross-sectional studies. CONCLUSIONS:This approach enables the use of mappings to different terminologies within the OMOP CDM without the need to catalogue an entire database. However, Read v2 has less granular concepts than some terminologies, such as SNOMED CT. Additionally, the OMOP CDM cannot compensate for limitations in the clinical coding system. Neither Read v2 nor ICD-10 is sufficiently granular to enable CVST to be specifically flagged. Hence, any pooled analysis will have to be at the less specific level of cerebrovascular venous thrombosis. Overall, the mappings within this CDM are useful, and our method could be used for rapid collaborations where there are only a limited number of concepts to pool.