Clinical Practice Research Datalink Research Articles

Risk of Venous Thromboembolism in Statin Users Compared to Fibrate Users in the United Kingdom Clinical Practice Research Datalink (UK CPRD) GOLD.

A substantial proportion of adults receive statins for treatment of hypercholesterolemia and cardiovascular risk, and statins have been found to improve outcomes in this patient population. However, studies have not consistently demonstrated the potential benefits of statins in preventing venous thromboembolism (VTE). Therefore, we conducted this study to investigate this association. We conducted a cohort analysis in a study sample comprised of 40-79-year-old patients with hyperlipidemia who received at least one fibrate or statin prescription between January 1995 and December 2018 in the United Kingdom Clinical Practice Research Datalink (CPRD) GOLD. We evaluated the association between statin use and incident unprovoked VTE, compared to fibrate use, an active comparator, using Kaplan-Meier (KM) analysis, Poisson regression (with and without propensity score matching), and inverse probability of treatment weights (IPTW) marginal structural models (MSM). In this cohort of 166,292 patients with hyperlipidemia, 0.81% (N=1,353) developed incident unprovoked VTE. In analyses using the KM method, patients who received statins had a slightly lower risk of VTE compared to those who received fibrates (Log rank test: p=0.0524). The adjusted incident rate ratio (95% CI) for VTE, calculated using Poisson regression, controlling for serum cholesterol and other baseline covariates, in patients prescribed statins compared to fibrates was 0.77 (0.45-1.33) in the full cohort, 0.74 (0.38-1.45) in the propensity score matched analysis, and 0.51 (95% conservative CI: 0.34-0.76) in the IPTW MSM analysis. While the magnitude of effect varied across the different analytic methods, there is consistent evidence for a protective effect of statin use on the occurrence of unprovoked VTE.

Pharmacologic Treatments for Dementia and the Risk of Developing Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness among people aged 50 years or older worldwide. There is a need for new strategies for the prevention and treatment of AMD. There is some limited evidence to suggest the possibility of a protective association of dementia medications with the development of some types of AMD, but the evidence is weak. To investigate whether the dementia medications memantine and donepezil are associated with the risk of developing AMD. Three population-based cohort studies were performed using data from the Clinical Practice Research Datalink GOLD and Aurum databases from May 15, 2002, to June 21, 2022. Participants included individuals with dementia (vascular dementia, nonvascular dementia, or Alzheimer disease) aged 40 years or older. Statistical analysis was carried out between February and November 2023. Exposures were dementia medications. Cohort 1 compared patients prescribed donepezil with those prescribed rivastigmine or galantamine using the new-user design. Cohort 2 compared memantine with donepezil, rivastigmine, or galantamine using the prevalent new-user design. In a sensitivity analysis, cohort 3 compared memantine with rivastigmine or galantamine only. New diagnosis of AMD. There were 132 846 individuals (mean [SD] age, 80.4 [7.6] years; 61.8% women; mean [SD] body mass index [BMI], 25.5 [4.6]) with a diagnosis of dementia included in cohort 1, 159 419 individuals (mean [SD] age, 81.2 [7.6] years; 59.7% women; mean [SD] body mass index [BMI], 25.6 [4.7]) with a diagnosis of dementia included in cohort 2, and 92 328 individuals with a diagnosis of dementia included in cohort 3 (mean [SD] age, 80.9 [7.7] years; 58.5% women; mean [SD] body mass index [BMI], 25.5 [4.7]). The adjusted hazard ratio (HR) for donepezil compared with rivastigmine or galantamine (cohort 1) was 0.95 (95% CI, 0.67-1.35). The adjusted HR for memantine compared with donepezil, rivastigmine, or galantamine (cohort 2) was 1.03 (95% CI, 0.83-1.27). The adjusted HR for memantine vs rivastigmine or galantamine only (cohort 3) was 1.24 (95% CI, 0.83-1.86). This cohort study of patients with dementia found no significant associations between memantine or donepezil compared with other dementia medications and the risk of development of AMD. Further research is recommended to examine any possible pathophysiological protective action of memantine and other dementia medications against the development of AMD.

Investigating the Potential Short-term Adverse Effects of the Quadrivalent Human Papillomavirus Vaccine: A Novel Regression Discontinuity Analysis.

Human papillomavirus (HPV) vaccination has been offered in over a hundred countries worldwide (including the United Kingdom, since September 2008). Controversy around adverse effects persists, with inconsistent evidence from follow-up of randomized controlled trials and confounding by indication limiting the conclusions drawn from larger-scale observational studies. This study aims to estimate the association between receiving a quadrivalent HPV vaccine and the reporting of short-term adverse effects and to demonstrate the utility of regression discontinuity design for examining side effects in routine data. We applied a novel regression discontinuity approach to a retrospective population-based cohort using primary care data from the UK Clinical Practice Research Datalink linked to hospital and social deprivation data. We examined the new onset of gastrointestinal, neuromuscular, pain, and headache/migraine symptoms using READ and International Classification of Diseases, tenth revision diagnostic codes. For each year between 2012 and 2017, we compared girls in school year 8 (born July/August) who were eligible to receive the vaccine with girls in year 7 (born September/October) who were not eligible. Of the 21,853 adolescent girls in the cohort, 10,881 (50%) were eligible for HPV vaccination. There was no evidence of increased new gastrointestinal symptoms (adjusted odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.85, 1.15), headache/migraine symptoms (OR: 0.84; 95% CI: 0.70, 1.01), or pain symptoms (OR: 1.05; 95% CI: 0.95, 1.16) when comparing those eligible and ineligible for HPV vaccination. This study found no evidence that HPV vaccination eligibility is associated with reporting short-term adverse effects among adolescent girls.

Incidence, prevalence, and survival of lung cancer in the United Kingdom from 2000-2021: a population-based cohort study.

Lung cancer is the leading cause of cancer-associated mortality worldwide. In the United Kingdom (UK), there has been a major reduction in smoking, the leading risk factor for lung cancer. Therefore, an up-to-date assessment of the trends of lung cancer is required in the UK. This study aims to describe lung cancer burden and trends in terms of incidence, prevalence, and survival from 2000-2021, using two UK primary care databases. We performed a population-based cohort study using the UK primary care Clinical Practice Research Datalink (CPRD) GOLD database, compared with CPRD Aurum. Participants aged 18+ years, with 1-year of prior data availability, were included. We estimated lung cancer incidence rates (IRs), period prevalence (PP), and survival at 1, 5 and 10 years after diagnosis using the Kaplan-Meier (KM) method. Overall, 11,388,117 participants, with 45,563 lung cancer cases were studied. The IR of lung cancer was 52.0 [95% confidence interval (CI): 51.5 to 52.5] per 100,000 person-years, with incidence increasing from 2000 to 2021. Females aged over 50 years of age showed increases in incidence over the study period, ranging from increases of 8 to 123 per 100,000 person-years, with the greatest increase in females aged 80-89 years. Alternatively, for males, only cohorts aged over 80 years showed increases in incidence over the study period. The highest IR was observed in people aged 80-89 years. PP in 2021 was 0.18%, with the largest rise seen in participants aged over 60 years. Median survival post-diagnosis increased from 6.6 months in those diagnosed between 2000-2004 to 10.0 months between 2015-2019. Both short and long-term survival was higher in younger cohorts, with 82.7% 1-year survival in those aged 18-29 years, versus 24.2% in the age 90+ years cohort. Throughout the study period, survival was longer in females, with a larger increase in survival over time than in males. The incidence and prevalence of lung cancer diagnoses in the UK have increased, especially in female and older populations, with a small increase in median survival. This study will enable future comparisons of overall disease burden, so the overall impact may be seen.

Identifying markers of health-seeking behaviour and healthcare access in UK electronic health records

ObjectiveTo assess the feasibility of identifying markers of health-seeking behaviour and healthcare access in UK electronic health records (EHR), for identifying populations at risk of poor health outcomes and adjusting...

Excess health care use is significantly and persistently reduced following diagnosis of late‐onset epilepsy

AbstractObjectiveThe incidence of late‐onset epilepsy (LOE) is rising, and these patients may use an excess of health care resources. This study aimed to measure pre‐/post‐diagnostic health care use (HCU) for patients with LOE compared to controls.MethodsThis was an observational open cohort study covering years 1998–2019 using UK population‐based linked primary care (Clinical Practice Research Datalink [CPRD]) and hospital (HES) electronic health records. The participants included patients with incident LOE enrolled in CPRD and 1:10 age‐, sex‐, and general practice–matched controls. The exposure was incident LOE (diagnosed at age ≥65) using a 5‐year washout. The main outcome was all HCU (primary care [PC], accident and emergency [A&E], admitted patient and outpatient care) using inverse proportional weighting to PC use and HCU by setting. An interrupted time‐series analysis was used to examine pre‐/post‐diagnostic HCU between patients with LOE and controls over 4 years either side of diagnosis/matching date. An adjusted mixed‐effects negative binomial regression was used for post‐diagnosis HCU interactions.ResultsOf 2 569 874 people ≥65 years of age, 1048 (4%) developed incident LOE. Mean weighted total HCU increased by 32 visits per patient‐year (95% confidence interval [95% CI]: 13–50, p = .003) until LOE diagnosis, and then dropped by a mean of 60 visits per patient‐year (95% CI: −81 to −40). There was an acute rise and fall over the 1–2 years immediately pre‐/post‐diagnosis. Incident HCU remained higher for LOE compared to controls post‐diagnosis (adjusted incidence rate ratio: 1.72; 95% CI: 1.65–1.70; p < .001), including A&E, outpatient, and admitted care.SignificanceHealth care use demonstrates an acute on chronic rise over the 4 years before diagnosis of LOE. To what extent the partial reversal of the acute pre‐diagnosis rise, and the mediators of the accelerated increase compared to controls are attributed to epilepsy, comorbid and bidirectional disease states, or a combination of both warrants further exploration.

Incidence, Prevalence, and Survival of Prostate Cancer in the UK

ImportanceIncidence, prevalence, and survival are pertinent measures to inform the management and provision of prostate cancer care.ObjectiveTo calculate the incidence, prevalence, and survival rates for prostate cancer in the UK from 2000 to 2021.Design, Setting, and ParticipantsThis population-based cohort study uses routinely collected primary care data from the UK. Male patients aged 18 years or older with at least 1 year of history registered in Clinical Practice Research Datalink (CPRD) GOLD or Aurum were included. Data were analyzed from January 2023 to March 2024.Main Outcomes and MeasuresProstate cancer incidence rates (IR), period prevalence (PP), and 1-, 5-, and 10-year survival after diagnosis between 2000 and 2021, stratified by age and calendar years.ResultsThis study included 64 925 and 133 200 patients with prostate cancer in CPRD GOLD and Aurum, respectively, with a median age of 72 (65-78) years. The overall IR of prostate cancer was 151.7 (95% CI, 150.6 to 152.9) per 100 000 person-years in GOLD to 153.1 (95% CI, 152.3 to 153.9) per 100 000 person-years for Aurum and increased with age. The incidence of prostate cancer increased from 109 per 100 000 person-years in 2000 to 159 per 100 000 person-years in 2021. Peaks of incidence occurred in 2004 and 2018, before a decline in 2020. PP increased 3.5 times over the study period for both databases, from 0.4% in 2000 to 1.4% in 2021. IR and PP were highest in those aged 80 to 89 years. Median (95% CI) survival was similar in both databases (GOLD: 10.9 [95% CI, 10.7-11.1] years and Aurum: 11.1 [95% CI, 11.0-11.2] years). Survival at 1, 5, and 10 years after diagnosis were 93.4% (95% CI, 93.2%-93.6%), 71.8% (95% CI, 71.4%-72.2%), 53.2% (95% CI, 52.6%-53.7%) in GOLD and 93.9% (95% CI, 93.7%-94.0%), 72.7% (95% CI, 72.5%-73.0%), 53.7% (95% CI, 53.3%-54.1%) in AURUM, respectively. Survival increased over time: 1-year survival was 94.8% (95% CI, 94.5%-95.2%) in those diagnosed between 2015 to 2019 compared with 90.8% (95% CI, 90.2%-91.3%) from 2000 to 2004; 5-year survival improved from 65.3% (95% CI, 64.4%-66.3%) from 2000 to 2004 to 75.3% (95% CI, 74.4%-76.3%) in 2015 to 2019.Conclusions and RelevanceIn this population-based cohort study, incidence and prevalence increased with older age, with high survival rates reflecting a high burden of disease, particularly in the management of cancer survivorship in an aging population. Health care systems should consider this when managing the increasing numbers of people with prevalent prostate cancer.

Optimal risk-assessment scheduling for primary prevention of cardiovascular disease

Abstract In this work, we introduce a personalized and age-specific net benefit function, composed of benefits and costs, to recommend optimal timing of risk assessments for cardiovascular disease (CVD) prevention. We extend the 2-stage landmarking model to estimate patient-specific CVD risk profiles, adjusting for time-varying covariates. We apply our model to data from the Clinical Practice Research Datalink, comprising primary care electronic health records from the UK. We find that people at lower risk could be recommended an optimal risk-assessment interval of 5 years or more. Time-varying risk factors are required to discriminate between more frequent schedules for high-risk people.

Trends in the prevalence and pharmacological management of migraine during pregnancy in the UK, 2000–2018

BackgroundMigraine is common in women of reproductive age. This study aimed to (1) describe the prevalence of migraine in pregnant women in the UK, (2) identify drugs commonly prescribed for...

Foundational model aided automatic high-throughput drug screening using self-controlled cohort study.

Developing medicine from scratch to governmental authorization and detecting adverse drug reactions (ADR) have barely been economical, expeditious, and risk-averse investments. The availability of large-scale observational healthcare databases and the popularity of large language models offer an unparalleled opportunity to enable automatic high-throughput drug screening for both repurposing and pharmacovigilance. To demonstrate a general workflow for automatic high-throughput drug screening with the following advantages: (i) the association of various exposure on diseases can be estimated; (ii) both repurposing and pharmacovigilance are integrated; (iii) accurate exposure length for each prescription is parsed from clinical texts; (iv) intrinsic relationship between drugs and diseases are removed jointly by bioinformatic mapping and large language model - ChatGPT; (v) causal-wise interpretations for incidence rate contrasts are provided. Using a self-controlled cohort study design where subjects serve as their own control group, we tested the intention-to-treat association between medications on the incidence of diseases. Exposure length for each prescription is determined by parsing common dosages in English free text into a structured format. Exposure period starts from initial prescription to treatment discontinuation. A same exposure length preceding initial treatment is the control period. Clinical outcomes and categories are identified using existing phenotyping algorithms. Incident rate ratios (IRR) are tested using uniformly most powerful (UMP) unbiased tests. We assessed 3,444 medications on 276 diseases on 6,613,198 patients from the Clinical Practice Research Datalink (CPRD), an UK primary care electronic health records (EHR) spanning from 1987 to 2018. Due to the built-in selection bias of self-controlled cohort studies, ingredients-disease pairs confounded by deterministic medical relationships are removed by existing map from RxNorm and nonexistent maps by calling ChatGPT. A total of 16,901 drug-disease pairs reveals significant risk reduction, which can be considered as candidates for repurposing, while a total of 11,089 pairs showed significant risk increase, where drug safety might be of a concern instead. This work developed a data-driven, nonparametric, hypothesis generating, and automatic high-throughput workflow, which reveals the potential of natural language processing in pharmacoepidemiology. We demonstrate the paradigm to a large observational health dataset to help discover potential novel therapies and adverse drug effects. The framework of this study can be extended to other observational medical databases.

Effectiveness and risk of ARB and ACEi among different ethnic groups in England: A reference trial (ONTARGET) emulation analysis using UK Clinical Practice Research Datalink Aurum-linked data.

Guidelines by the National Institute for Health and Care Excellence recommend an angiotensin receptor blocker (ARB) rather than an angiotensin-converting enzyme inhibitor (ACEi) for the treatment of hypertension for people of African and Caribbean descent, due to an increased risk of angioedema associated with ACEi use observed in US trials. However, the effectiveness and risk of these drugs in Black populations in UK routine care is unknown. We applied a reference trial emulation approach to UK Clinical Practice Research Datalink Aurum data (linked with data from Hospital Episode Statistics and Office for National Statistics) to study the comparative effectiveness of ARB and ACEi in ethnic minority groups in England, after benchmarking results against the ONTARGET trial. Approximately 17,593 Black, 30,805 South Asian, and 524,623 White patients receiving a prescription for ARB/ACEi between 1 January 2001 and 31 July 2019 were included with a median follow-up of 5.2 years. The primary composite outcome was cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure with individual components studied as secondary outcomes. Angioedema was a safety endpoint. We assessed outcomes using an inverse-probability-weighted Cox proportional hazards model for ARB versus ACEi with heterogeneity by ethnicity assessed on the relative and absolute scale. For the primary outcome, 27,327 (18.0%) events were recorded in the ARB group (event rate: 25% per 5.5 person-years) and 80,624 (19.1%) events (event rate: 26% per 5.5 person-years) in the ACEi group. We benchmarked results against ONTARGET and observed hazard ratio (HR) 0.96 (95% CI: 0.95, 0.98) for the primary outcome, with an absolute incidence rate difference (IRD)% of -1.01 (95% CI: -1.42, -0.60) per 5.5 person-years. We found no evidence of treatment effect heterogeneity by ethnicity for the primary outcome on the multiplicative (Pint = 0.422) or additive scale (Pint = 0.287). Results were consistent for most secondary outcomes. However, for cardiovascular-related death, which occurred in 37,554 (6.6%) people, there was strong evidence of heterogeneity on the multiplicative (Pint = 0.002) and additive scale (Pint < 0.001). Compared to ACEi, ARB were associated with more events in Black individuals (HR 1.20 (95% CI: 1.02, 1.40); IRD% 1.07 (95% CI: 0.10, 2.04); number-needed-to-harm (NNH): 93) and associated with fewer events in White individuals (HR 0.91 (95% CI: 0.88, 0.93); IRD% -0.87 (95% CI: -1.10, -0.63); number-needed-to-treat (NNT): 115), and no differences in South Asian individuals (HR 0.97 (95% CI: 0.86, 1.09); IRD% -0.17 (95% CI: -0.87, 0.53)). For angioedema, HR 0.56 (95% CI: 0.46, 0.67) with no heterogeneity for ARB versus ACEi on the multiplicative scale (Pint = 0.306). However, there was heterogeneity on the additive scale (Pint = 0.023). Absolute risks were higher in Black individuals (IRD% -0.49 (95% CI: -0.79, -0.18); NNT: 204) compared with White individuals (IRD% -0.06 (95% CI: -0.09, -0.03); NNT: 1667) and no difference among South Asian individuals (IRD% -0.05 (95% CI: -0.15, 0.05) for ARB versus ACEi. These results demonstrate variation in drug effects of ACEi and ARB for some outcomes by ethnicity and suggest the potential for adverse consequences from current UK guideline recommendations for ARB in preference to ACEi for Black individuals.

Enhancing the usability of health data for inequalities research: a UK quality improvement project and code list curation.

Objective and ApproachPrimary care datasets provide a rich source of information for inequalities research; however, the value derived from these depends largely on the comprehensiveness of the code lists used by researchers. To date, no standardised code list for inequalities research has been developed. The aim of this project was to develop a comprehensive code list for groups of interest to inequalities research, namely: people with learning disabilities (LDs), people with severe mental illness (SMI), people from ethnic minority groups, and people who are transgender. Existing code lists were extracted from the Clinical Practice Research Datalink (CPRD) Bibliography (the largest research dataset in the UK), and four UK code list repositories: OpenCodelists, Health Data Research UK, University of Cambridge, and London School of Hygiene and Tropical Medicine. Comprehensive code lists were then curated through collation and removal of duplicates. Results16 code lists were identified for LDs, 18 for SMI, 16 for ethnicity, and 2 for transgender. From these, 661, 733, 346 and 68 unique codes were identified, respectively. Preliminary testing of the curated code lists, in a CPRD dataset, indicated that the number of individuals belonging to these groups was increased by 90% (compared to the original code list). Conclusions and ImplicationsOur findings suggest that the curated code lists improved data capture. These lists now need to be validated by healthcare specialists, before being made publicly available. The inclusion of code-specific definitions will enable international researchers to adapt the code lists to their medical systems.

Socio-demographic variations in prostate cancer diagnosis recording: Primary care compared to the Cancer Registry in England

IntroductionIn the UK, primary care data are often used for cancer-related research, but the accuracy of cancer information is uncertain. ObjectiveWe investigated socio-demographic variation based on the recording date of prostate cancer diagnosis between primary care and the National Cancer Registry (CR). ApproachWe utilised a data extract of 1,600,000 patients over 65 years from Clinical Practice Research Datalink (CPRD). We extracted prostate cancer diagnoses using Read and SNOMED-CT codes from primary care, and ICD-10 from CR. Initial code entry determined diagnosis dates. We categorised recording timing differences as earlier, same-day or later in primary care than CR and used the chi-squared test and logistic regression (adjusted for recording year) to compare these discrepancies across age, deprivation, and ethnicity. ResultsWe included 26,875 men with prostate cancer diagnoses commonly recorded in both sources during 2000-2016 (1,030 excluded with missing ethnicity). Compared to CR, 1,747 (7%) had diagnoses recorded on the same day in primary care, while 20,615 (77%) had later recordings with a median delay of 21 days (IQR: 13-38). Age at diagnosis was associated with recording discrepancies (p&lt;0.001); older men were more likely to have earlier/same-day recordings. Adjusted ORs for age groups were 1.4 (95%CI: 1.3-1.5) for 60-69, 1.3 (1.2-1.5) for 70-79, and 0.9 (0.8-1.0) for ≥80 compared to &lt;60. No associations were found between deprivation (p=0.096) or ethnicity (p=0.067) and recording differences. Conclusion/ ImplicationsThe discrepancy in prostate cancer information between primary care and CR underscores potential biases in studies relying solely on one data source.

Mental health of children with epilepsy compared to their peers: population-based cohort from linked primary and secondary healthcare record in England

BackgroundChildren with epilepsy have higher rates of internalising mental health (MH) conditions compared to their peers, although available evidence is limited by small and selective samples. We used linked primary care and hospital admission records covering approximately 4.42% of English population to describe incidence of mental health problems in children with epilepsy compared to their peers. MethodsWe developed a cohort of young people aged 7-17 years old between 2010-2019, with minimum 1 year of follow-up until death, 18th birthday or 2020 using linked data from the Clinical Practice Research Datalink and Hospital Episodes Statistics. Epilepsy (exposure), depression and anxiety (outcomes) were identified using a combination of diagnostic codes, and primary care prescribing records. We estimated incident rate ratios (IRR) for anxiety/depression/any MH condition for children with epilepsy compared to their peers using negative binomial regression adjusted for sex, age, and area-level deprivation. ResultsStudy cohort included 510,177 children and young people, of whom 3,011 (0.59%) had epilepsy. Children with epilepsy had higher incidence of any MH condition (IRR: 1.39, 95% CI: 1.11–1.73) and anxiety (IRR: 1.38, 95% CI: 1.06–1.77), with differences in depression being non-significant (IRR: 1.25, 95% CI: 0.92–1.66). DiscussionChildren with epilepsy have higher rates of MH problems than their peers. Further work will examine if this can be partially explained by increased opportunity for MH diagnosis due to more healthcare contacts. Our findings emphasise the importance of integrated care models that address both neurological and psychological aspects of epilepsy management.

Primary Liver Cancer Risk and Mortality in Patients With Alcohol-Related Cirrhosis in England and Denmark: Observational Cohort Studies.

Patients with alcohol-related cirrhosis (ALD cirrhosis) have an increased risk of primary liver cancer (hepatocellular carcinoma [HCC] or intrahepatic cholangiocarcinoma [iCCA]). England recommends surveillance for HCC in these patients, while Denmark does not. We performed an observational cohort study using the English Clinical Practice Research Datalink and the nationwide Danish healthcare registries to identify 17,110 English (2000-2016) and 22,122 Danish (1994-2022) patients with diagnosis codes of ALD cirrhosis. We computed and compared incidence rates and cumulative incidence of primary liver cancer, annual ultrasound scan rates, and mortality following diagnosis of primary liver cancer. The overall risk of primary liver cancer was similar in England and Denmark: 5-year risk was 2.24% (95% confidence interval 2.00-2.49) in England (iCCA 0.07%, HCC 2.16%) and 2.36% (2.15-2.57) in Denmark (iCCA 0.05%, HCC 2.30%). The annual rate of ultrasound scans per person was 0.65 (0.63-0.67) in England and 0.44 (0.42-0.46) in Denmark. The 1-year mortality after a diagnosis of primary liver cancer was 59.2% (54.4-64.0) in England and 60.9% (57.4-64.4) in Denmark. The 3-year risks of HCC in those on vs off surveillance in England were 2.3% (1.0-4.6) vs 1.5% (1.0-2.2). The risk of primary liver cancer was the same in English and Danish patients with ALD cirrhosis, and HCCs constituted 97% of primary liver cancers. Mortality with primary liver cancer was equally high in both countries. Notably, in England, where guidance recommends biannual HCC surveillance with ultrasound, patients with ALD cirrhosis were undergoing fewer than 1 ultrasound scan per year.

Recurrent cardiovascular and limb events in 294,428 patients with coronary or peripheral artery disease or ischemic stroke on antiplatelet monotherapy: The RESRISK cohort study

Background and aimsUtilising real-world data, we quantified the burden of cardiovascular risk factors and long-term residual risk of atherothrombotic events among routine care cohorts with coronary (CAD) or peripheral (PAD) artery disease or ischemic stroke (IS) on guideline-recommended antiplatelet monotherapy (APMT). MethodsRetrospective cohort study using data (2010–2020) from the United Kingdom Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics, including adults with CAD, PAD or IS who were first prescribed APMT (CAD/IS: aspirin; PAD: clopidogrel). Primary outcomes (recurrent events): major adverse cardiovascular events (MACE) for CAD/PAD/IS cohorts, major adverse limb events (MALE) for PAD. Results266,478 CAD, 13,162 PAD, and 14,788 IS patients were included (mean age: 71 years; women 37.7%–47.5 %). Risk factor burden was high and attainment of recommended goals was low. There were 73,691, 3,121 and 7,137 MACE among CAD, PAD and IS patients, respectively (median follow-up: 89.9, 42.4 and 75.9 months, respectively), and 4,767 MALE among PAD patients. MACE incidence rate per 1000 person-years was higher in IS (268.7; 95%CI 265.3–272.0) than CAD (92.9; 95%CI 92.5–93.4) or PAD cohorts (97.2; 95%CI 94.6–99.8). MALE incidence rate was 195.9 (95%CI 192.2–199.6) per 1000 person-years. IS patients presented a lower rate of hospitalisations and longer time-to-first hospitalisation, but once hospitalised, they had a longer length-of-stay. PAD patients had the highest hospitalisation rate. ConclusionsAmong a contemporary cohort with cardiovascular disease on APMT, long-term residual atherothrombotic risk remains high despite being on APMT. Greater attention to risk factor control and use of appropriate evidence-based therapy is required to reduce residual risk among this very high-risk population.

The association of type 2 diabetes-related characteristics with fracture risk at different sites.

To determine the association of diabetes-related characteristics with fractures at different sites in individuals with type 2 diabetes (T2D). We conducted a cohort study using the Clinical Practice Research Datalink (CPRD) GOLD. Patients aged over 30 years with T2D were identified within the CPRD. Patients were followed from the start of diabetes treatment until the end of data collection, death, or the occurrence of a fracture. Cox proportional hazards models were used to estimate the hazard ratios for the association of the individual characteristics (diabetes duration, glycated haemoglobin [HbA1c] level, and microvascular complications) with fracture risk, adjusted for demographics, comorbidities and comedication. A diabetes duration of >10 years was associated with an increased risk of any fracture and major osteoporotic fractures (MOFs), while a diabetes duration of >8 years was associated with an increased hip fracture risk, compared to a duration <2 years. An HbA1c level <6% was associated with an increased fracture risk compared to HbA1c values of 6% to <7%. The presence of one or two microvascular complications was associated with an increased risk of any fracture and MOFs and the presence of two microvascular complications was associated with an increased hip fracture risk, compared to no microvascular complications. In conclusion, our study shows that a diabetes duration of 10 years or more, strict glycaemic control resulting in HbA1c levels below 6%, and/or the presence of at least one microvascular complication increased the risk of any fracture, hip fractures, MOFs, and humerus fractures, but not ankle, scapula or skull fractures.

The use of locum doctors in the NHS: understanding and improving the quality and safety of care.

The use of locum doctors in the National Health Service is widely believed to have increased, and there have been widespread and sustained concerns among policy-makers, healthcare providers, professional associations and professional regulators about the quality/safety, cost and effective use of locum doctors. To provide evidence on the extent, quality and safety of medical locum practice and the implications of medical locum working for health service organisation and delivery in primary and secondary care in the English National Health Service, to support policy and practice. Four interlinked work packages involving surveys of National Health Service trusts and of general practices in England; semistructured interviews and focus groups across 11 healthcare organisations in England; analysis of existing routine data sets on the medical workforce in primary care and in National Health Service trusts in England from National Health Service Digital and National Health Service Improvement; and analysis of data from the Clinical Practice Research Datalink in primary care and of electronic patient record data from two National Health Service hospitals in secondary care. In primary care, about 6% of general practice medical consultations were undertaken by locums in 2010 and this had risen slightly to about 7.1% in 2021. In National Health Service trusts (mostly secondary care and mental health), about 4.4% of medical staff full-time equivalent was provided by locum doctors. But those overall national rates of locum use hide a great deal of variation. In primary care, we found the National Health Service Digital workforce returns showed the rate of locum use by Clinical Commissioning Group varied from 1% to almost 31%. Among National Health Service trusts, the reported rate of locum use varied from < 1% to almost 16%. We found that there was poor awareness of and adherence to national guidance on locum working arrangements produced by National Health Service England. Our research showed that locum working can have adverse consequences for the quality and safety of care, but that such consequences were probably more likely to result from the organisational setting and the working arrangements than they were from the locum doctors themselves and their competence, clinical practice or behaviours. Our research was hampered in some respects by the COVID pandemic which both resulted in some delays and other challenges. Our efforts to use electronic patient record data in secondary care to explore locum doctor working were stymied by the problems of data access and quality. Locum doctors are a key component of the medical workforce in the National Health Service, and provide necessary flexibility and additional capacity for healthcare organisations and services. We found that the extent of reliance on locum doctors varied considerably, but that an over-reliance on locums for service provision was undesirable. Some differences in practice and performance between locum and permanent doctors were found, but these seemed often to arise from organisational characteristics. We found that patients were more concerned with the clinical expertise and skills of the doctor they saw than whether they were a locum or not. Organisational arrangements for locum working could be improved in many respects. This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR128349) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 37. See the NIHR Funding and Awards website for further award information.

Time trends in the epidemiology of food allergy in England: an observational analysis of Clinical Practice Research Datalink data

Estimates for the prevalence of food allergy vary widely, with a paucity of data for adults. The aim of this analysis was to report trends in the incidence and prevalence of food allergy in England, using a national primary care dataset. We analysed data from Clinical Practice Research Datalink between 1998 and 2018, with linked data to relevant hospital encounters in England. The main outcomes were incidence and prevalence of food allergy, according to three definitions of food allergy: possible food allergy, probable food allergy, and probable food allergy with adrenaline autoinjectors prescription. We also evaluated the difference in proportion of patients prescribed adrenaline autoinjectors by English Index of Multiple Deprivation (IMD), age, and by previous food anaphylaxis, and explored differences in patient encounters (general practice vs emergency department setting). 7 627 607 individuals in the dataset were eligible for inclusion, of whom 150 018 (median age 19 years [IQR 4-34]; 82 614 [55·1%] female and 67 404 [44·9%] male) had a possible food allergy. 121 706 met diagnostic criteria for probable food allergy, of whom 38 288 were prescribed adrenaline autoinjectors. Estimated incidence of probable food allergy doubled between 2008 and 2018, from 75·8 individuals per 100 000 person-years (95% CI 73·7-77·9) in 2008 to 159·5 (156·6-162·3) individuals per 100 000 person-years in 2018. Prevalence increased from 0·4% (23 399 of 6 432 383) to 1·1% (82 262 of 7 627 607) over the same period and was highest in children under 5 years (11 951 [4·0%] of 296 406 in 2018) with lower prevalence in school-aged children (from 11 353 [2·4%] of 473 597 in 2018 for children aged 5-9 years to 6896 [1·7%] of 404 525 for those aged 15-19 years) and adults (42 848 [0·7%] of 5 992 454 in 2018). In those with previous food anaphylaxis, only 2321 (58·3%) of 3980 (975 [64·0%] of 1524 children and young people and 1346 [54·8%] of 2456 adults) had a prescription for adrenaline autoinjector. Adrenaline autoinjectors prescription was less common in those resident in more deprived areas (according to IMD). In the analysis of health-care encounters, 488 604 (97·1%) of 503 198 visits recorded for food allergy occurred in primary care, with 115 655 (88·4%) of 130 832 patients managed exclusively in primary care. These estimates indicate an important and increasing burden of food allergy in England. Our findings that most patients with food allergy are managed outside the hospital system, with low rates of adrenaline autoinjector prescription in those with previous anaphylaxis, highlight a need to better support those working in primary care to ensure optimal management of patients with food allergy. UK Food Standards Agency and UK Medical Research Council.

Patient pathways for four major chronic respiratory diseases in England between 2008 and 2021

BackgroundNot all chronic diseases have clear pathways and time targets for diagnosis. We explored pathways and timings for four major chronic respiratory diseases in England.MethodsUsing deidentified electronic healthcare records from...