Clinical Practice Research Datalink GOLD Research Articles

P145 Safety of colchicine or NSAID prophylaxis when initiating allopurinol for gout: propensity score-matched cohort studies

Abstract Background/Aims Initiating urate-lowering therapy for gout commonly triggers a gout flare and hence co-prescription of colchicine or non-steroidal anti-inflammatory drug (NSAID) prophylaxis is recommended. However, little is known about the incidence of adverse events associated with prophylaxis. We aimed to determine the risk of adverse events severe enough to warrant seeking healthcare associated with colchicine or NSAID prophylaxis when initiating allopurinol for gout. Methods We conducted two matched retrospective cohort studies, using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) datasets. Adults aged ≥18 years with a Read code for gout and a new allopurinol prescription between 1997 and 2016 were identified. We compared those prescribed (1) colchicine or (2) NSAID prophylaxis with those prescribed no prophylaxis, individually matched by age, sex and propensity to receive prophylaxis, to reduce the impact of confounding by indication. Adverse events were identified in CPRD and HES using Read and ICD10 codes respectively. Associations between colchicine or NSAID prophylaxis and the first occurrence of each outcome were investigated using weighted Cox proportional hazards models. CPRD Gold and Aurum datasets were analysed separately and then combined using 2-stage individual patient data meta-analysis. Results 13,945 individuals who initiated allopurinol with colchicine prophylaxis were matched to 13,945 who initiated without prophylaxis (mean age 63.62 years [95%CI 63.54, 63.70]; 78% male). Diarrhoea was the most common adverse event in the colchicine group, followed by nausea/vomiting, myocardial infarction (MI), neuropathy, myalgia, and bone marrow suppression (Table). Diarrhoea, MI, neuropathy, myalgia, and bone marrow suppression were significantly more common with colchicine prophylaxis compared with no prophylaxis. 22,880 individuals who initiated allopurinol with NSAID prophylaxis were matched to 22,880 who initiated without prophylaxis (mean age 63.34 years [95%CI 63.26, 63.42]; 78% male). Angina, acute kidney injury, MI, and peptic ulcer disease were significantly more common with NSAID prophylaxis than without (Table). Conclusion Gastrointestinal, cardiorenal, myoneuropathic, and haematological adverse events were associated with prophylaxis, although absolute event rates were low. This information can inform treatment decisions and choice of colchicine or NSAID for prophylaxis when initiating allopurinol. Disclosure E. Roddy: None. R. Bajpai: None. H. Forrester: None. R. Partington: None. C.D. Mallen: Grants/research support; Keele University School Of Medicine has received funding from BMS to support a non-pharmacological atrial fibrillation screening study. L. Clarson: None. N. Padmanabhan: None. R. Whittle: None. S. Muller: None.

OA21 Continuing specialist care beyond age 16 in young people with juvenile idiopathic arthritis: a descriptive study using electronic health records in England

Abstract Background/Aims It is estimated that juvenile idiopathic arthritis (JIA) persists into adulthood in at least one-third of patients, but it is unclear how frequently hospital services are used beyond age 16. This study aimed to describe characteristics related to continued specialist care in young people (YP) with JIA using electronic health records (EHR) in England. Methods YP with JIA were identified from primary care EHR (Clinical Practice Research Datalink GOLD and Aurum databases combined) between 2003 and 2018. JIA was identified if they had a Read code for JIA and either > =3 Hospital Episode Statistics (HES) outpatient specialist care (rheumatology/ophthalmology) appointments or a HES inpatient admission coded with JIA, prior to age 16. Further, cases needed to have linkage to HES data, registration at the same GP for >1 year beyond age 16. Cases were followed from the earliest of first Read code or first HES outpatient appointment until leaving their GP or end of 2018. YP with > =1 specialist care outpatient appointment beyond age 16 were identified. YP were considered discharged from specialist care (a proxy for disease remission) if they had > =1 year between the last appointment and end of study follow-up. Patient characteristics and characteristics of discharged are presented, stratified by continued specialist care. Results Of 1095 YP eligible for the study, followed for a median of 12 years beyond 16, 774 (70.7%) continued specialist care beyond age 16. These patients were older at first JIA code and more likely to be female (Table 1). Overall, 543 (51.9%) continued in specialist care beyond age 18. The median age of the last visit was 14 for those not continuing specialist care and 18 for those discharged after the age of 16. Disease duration was longer in those discharged after age 16. Conclusion Over two-third of patients with JIA continue to have hospital visits beyond age 16. Of those, however, approximately one-third were discharged from specialist care by the age of 18. These data provide important information for YP with JIA and their families, as well as clinicians running, developing and planning young adult services in paediatric and adult rheumatology. Disclosure R.E. Costello: None. L. Kearsley-Fleet: None. J.E. McDonagh: None. K. Hyrich: None. J.H. Humphreys: None.

Diagnoses after newly recorded abdominal pain in primary care: observational cohort study.

BackgroundNon-acute abdominal pain in primary care is diagnostically challenging.AimTo quantify the 1-year cumulative incidence of 35 non-malignant diagnoses and nine cancers in adults after newly recorded abdominal pain in primary care.Design and settingObservational cohort study of 125 793 Clinical Practice Research Datalink GOLD records.MethodParticipants, aged ≥40 years, had newly recorded abdominal pain between 1 January 2009 and 31 December 2013. Age- and sex-stratified 1-year cumulative incidence by diagnosis is reported.ResultsMost (>70%) participants had no pre-specified diagnoses after newly recorded abdominal pain. Non-malignant diagnoses were most common: upper gastrointestinal problems (gastro-oesophageal reflux disease, hiatus hernia, gastritis, oesophagitis, and gastric/duodenal ulcer) in males and urinary tract infection in females. The incidence of upper gastrointestinal problems plateaued at age ≥60 years (aged 40–59 years: males 4.9%, 95% confidence interval [CI] = 4.6 to 5.1, females 4.0%, 95% CI = 3.8 to 4.2; aged 60–69 years: males 5.8%, 95% CI = 5.4 to 6.2, females 5.4%, 95% CI = 5.1 to 5.8). Urinary tract infection incidence increased with age (aged 40–59 years: females 5.1%, 95% CI = 4.8 to 5.3, males 1.1%, 95% CI = 1.0 to 1.2; aged ≥70 years: females 8.0%, 95% CI = 7.6 to 8.4, males 3.3%, 95% CI = 3.0 to 3.6%). Diverticular disease incidence rose with age, plateauing at 4.2% (95% CI = 3.9 to 4.6) in males aged ≥60 years, increasing to 6.1% (95% CI = 5.8 to 6.4) in females aged ≥70 years. Irritable bowel syndrome incidence was higher in females (aged 40–59 years: 2.9%, 95% CI = 2.7 to 3.1) than males (aged 40–59 years: 2.1%, 95% CI = 1.9 to 2.3), decreasing with age to 1.3% (95% CI = 1.2 to 1.5) in females and 0.6% (95% CI = 0.5 to 0.8) in males aged ≥70 years.ConclusionAlthough abdominal pain commonly remains unexplained, non-malignant diagnosis are more likely than cancer.

Characteristics of patients with lung cancer in clinical practice and their potential eligibility for clinical trials evaluating tyrosine kinase inhibitors or immune checkpoint inhibitors

IntroductionIn- and exclusion criteria of randomized clinical trials (RCTs) aim to include a homogeneous study-population. This study compared characteristics of lung cancer patients from phase III RCTs evaluating tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) with characteristics of lung cancer patients in a real world setting in the United Kingdom. MethodsA retrospective study was conducted using the Clinical Practice Research Datalink GOLD. Patients (N = 9239) with a first ever lung cancer registration between 2014 and 2018 were identified. Eligibility for inclusion was assessed for twelve RCTs (evaluating TKIs or ICIs). Reasons for potential exclusion and the number of unmet criteria were assessed for each RCT independently. OS was assessed using Kaplan-Meier and Cox proportional hazards analyses. ResultsThe proportion of potentially eligible patients was 74.3% and 51.9% for TKI and ICI RCTs, respectively. History of another malignancy, renal insufficiency or concomitant drug-use were main reasons for exclusion. OS was considerably longer for potentially eligible patients. Hazards ratios varied from 1.17 (95% confidence interval, 1.11–1.24) to 1.35 (1.20–1.42) across the RCTs. ConclusionThis study showed that a considerable proportion of lung cancer patients in a real-world setting would have been ineligible for participation in phase III RCTs and that potentially ineligible patients experienced a shorter OS.

Development and external validation of a clinical prediction model to aid coeliac disease diagnosis in primary care: An observational study

SummaryBackgroundCoeliac disease (CD) affects approximately 1% of the population, although only a fraction of patients are diagnosed. Our objective was to develop diagnostic prediction models to help decide who should be offered testing for CD in primary care.MethodsLogistic regression models were developed in Clinical Practice Research Datalink (CPRD) GOLD (between Sep 9, 1987 and Apr 4, 2021, n=107,075) and externally validated in CPRD Aurum (between Jan 1, 1995 and Jan 15, 2021, n=227,915), two UK primary care databases, using (and controlling for) 1:4 nested case-control designs. Candidate predictors included symptoms and chronic conditions identified in current guidelines and using a systematic review of the literature. We used elastic-net regression to further refine the models.FindingsThe prediction model included 24, 24, and 21 predictors for children, women, and men, respectively. For children, the strongest predictors were type 1 diabetes, Turner syndrome, IgA deficiency, or first-degree relatives with CD. For women and men, these were anaemia and first-degree relatives. In the development dataset, the models showed good discrimination with a c-statistic of 0·84 (95% CI 0·83–0·84) in children, 0·77 (0·77–0·78) in women, and 0·81 (0·81–0·82) in men. External validation discrimination was lower, potentially because ‘first-degree relative’ was not recorded in the dataset used for validation. Model calibration was poor, tending to overestimate CD risk in all three groups in both datasets.InterpretationThese prediction models could help identify individuals with an increased risk of CD in relatively low prevalence populations such as primary care. Offering a serological test to these patients could increase case finding for CD. However, this involves offering tests to more people than is currently done. Further work is needed in prospective cohorts to refine and confirm the models and assess clinical and cost effectiveness.FundingNational Institute for Health Research Health Technology Assessment Programme (grant number NIHR129020)

Characterization of the deterioration of diabetes control in patients with a subsequent diagnosis of pancreatic cancer: A descriptive study

BackgroundDeterioration of diabetes control can be the first harbinger of pancreatic cancer. However, little is known about how to distinguish patients with pancreatic cancer-related diabetes deterioration from those with type 2 diabetes progression. We aimed to characterize the glycated hemoglobin (HbA1c) and body weight profile of pancreatic cancer patients with deteriorating diabetes before the cancer diagnosis. MethodsUsing data from the UK-based Clinical Practice Research Datalink (CPRD) GOLD, we established a study population including pancreatic cancer patients with diabetes deterioration in the >0.5–3 years before the cancer diagnosis and non-cancer patients with deterioration of type 2 diabetes (comparison group). Patients were considered to have diabetes deterioration if their glucose-lowering treatment was intensified. We characterized the longitudinal trajectories of HbA1c and body weight in pancreatic cancer patients compared with non-cancer patients before and after treatment intensification. ResultsThe mean absolute increase in HbA1c from the pre-deterioration period, i.e. the time >1–2 years before treatment intensification, to the time of treatment intensification, was 1.5% ± 1.6% in pancreatic cancer patients vs. 0.9% ± 1.4% in non-cancer patients. After treatment intensification, mean HbA1c remained elevated in pancreatic cancer patients, while it returned to the pre-deterioration level in non-cancer patients. Body weight decreased by 1.9% ± 6.4% in cancer patients and increased by 0.3% ± 5.2% in non-cancer patients between the pre-deterioration period and treatment intensification, on average. ConclusionsPancreatic cancer-related diabetes deterioration may frequently be characterized by pronounced increases in HbA1c, persistent elevation of HbA1c after treatment intensification, and concomitant weight loss.

Clustering of comorbidities and associated outcomes in people with osteoarthritis - A UK Clinical Practice Research Datalink study

To examine the clusters of chronic conditions present in people with osteoarthritis and the associated risk factors and health outcomes. Clinical Practice Research Datalink (CPRD) GOLD was used to identify people diagnosed with incident osteoarthritis (n=221,807) between 1997 and 2017 and age (±2 years), gender, and practice matched controls (no osteoarthritis, n=221,807) from UK primary care. Clustering of people was examined for 49 conditions using latent class analysis. The associations between cluster membership and covariates were quantified by odds ratios (OR) using multinomial logistic regression. General practice (GP) consultations, hospitalisations, and all-cause mortality rates were compared across the clusters identified at the time of first diagnosis of osteoarthritis (index date). In both groups, conditions largely grouped around five clusters: relatively healthy; cardiovascular (CV), musculoskeletal-mental health (MSK-MH), CV-musculoskeletal (CV-MSK) and metabolic (MB). In the osteoarthritis group, compared to the relatively healthy cluster, strong associations were seen for 1) age with all clusters; 2) women with the MB cluster (OR 5.55: 5.14-5.99); 3) obesity with the CV-MSK (OR 2.11: 2.03-2.20) and CV clusters (OR 2.03: 1.97-2.09). The CV-MSK cluster in the osteoarthritis group had the highest number of GP consultations and hospitalisations, and the mortality risk was 2.45 (2.33-2.58) times higher compared to the relatively healthy cluster. Of the five identified clusters, CV-MSK, CV, and MSK-MH are more common in OA and CV-MSK cluster had higher health utilisation. Further research is warranted to better understand the mechanistic pathways and clinical implications.

Trends in the Annual Consultation Incidence and Prevalence of Low Back Pain and Osteoarthritis in England from 2000 to 2019: Comparative Estimates from Two Clinical Practice Databases.

PurposeTo compare estimates of annual person-consulting incidence and prevalence of low back pain (LBP) and osteoarthritis for two national English electronic health record databases (Clinical Practice Research Datalink (CPRD) Aurum and CPRD GOLD).Patients and MethodsRetrospective, population-based, longitudinal cohort study. LBP and osteoarthritis cases were defined using established codelists in people aged ≥15 and ≥45 years, respectively. Incident cases were new recorded cases in a given calendar year with no relevant consultation in the previous 3 years (denominator = exact person-time in the same calendar year for the at-risk population). Prevalent cases were individuals with ≥1 consultation for the condition of interest recorded in a given calendar year, irrespective of prior consultations for the same condition (denominator = all patients with complete registration history in the previous 3 years). We estimated age-sex standardised incidence and annual (12-month period) prevalence for both conditions in 2000–2019, overall, and by sex, age group, and region.ResultsStandardised incidence and prevalence of LBP from Aurum were lower than those from GOLD until 2014, after which estimates were similar. Both databases showed recent declines in incidence and prevalence of LBP: declines began earlier in GOLD (after 2012–2014) than Aurum (after 2014–2015). Standardised incidence (after 2011) and prevalence of osteoarthritis (after 2003) were higher in Aurum than GOLD and showed different trends: incidence and prevalence were stable or increasing in Aurum, decreasing in GOLD. Stratified estimates in CPRD Aurum suggested consistently higher occurrence among women, older age groups, and those living in the north of England.ConclusionComparative analyses of two English databases produced conflicting estimates and trends for two common musculoskeletal conditions. Aurum estimates appeared more consistent with external sources and may be useful for monitoring population musculoskeletal health and healthcare demand, but they remain sensitive to analytic decisions and data quality.

Investigating the optimal handling of uncertain pregnancy episodes in the CPRD GOLD Pregnancy Register: a methodological study using UK primary care data.

ObjectivesTo investigate why episodes of pregnancy identified from electronic health records may be incomplete or conflicting (overlapping), and provide guidance on how to handle them.SettingPregnancy Register generated from the Clinical Practice Research Datalink (CPRD) GOLD UK primary care database.ParticipantsFemale patients with at least one pregnancy episode in the Register (01 January 1937−31 December 2017) which had no recorded outcome or conflicted with another episode.DesignWe identified multiple scenarios potentially explaining why uncertain episodes occur. Criteria were established and systematically applied to determine whether episodes had evidence of each scenario. Linked Hospital Episode Statistics were used to identify pregnancy events not captured in primary care.ResultsOf 5.8 million pregnancy episodes in the Register, 932 604 (16%) had no recorded outcome, and 478 341 (8.5%) conflicted with another episode (251 026 distinct conflicting pairs of episodes among 210 593 women). 826 146 (89%) of the episodes without outcome recorded in primary care and 215 577 (86%) of the conflicting pairs were consistent with one or more of our proposed scenarios. For 689 737 (74%) episodes with recorded outcome missing and 215 544 (86%) of the conflicting pairs (at least one episode), supportive evidence (eg, antenatal records, linked hospital records) suggested they were true and current pregnancies. Furthermore, 516 818 (55 %) and 160 936 (64%), respectively, were during research quality follow-up time. For a sizeable proportion of uncertain episode, there is evidence to suggest that historical outcomes being recorded by the general practitioner during an ongoing pregnancy may offer explanation (73 208 (29.2%) and 349 874 (37.5%)).ConclusionsThis work provides insight to users of the CPRD Pregnancy Register on why uncertain pregnancy episodes exist and indicates that most of these episodes are likely to be real pregnancies. Guidance is given to help researchers consider whether to include/exclude uncertain pregnancies from their studies, and how to tailor approaches to minimise underestimation and bias.

POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USING PRE-PANDEMIC RISK OF MORTALITY IN INDIVIDUALS WITH CHRONIC KIDNEY DISEASE

Chronic Kidney Disease (CKD) is a global burden on public health, both as a risk factor for mortality, and as the end syndrome of underlying diseases. CKD is a common comorbidity associated with increased risk of severe coronavirus infection and poor clinical outcomes. The pandemic has had both direct (through infection) and indirect impact. The direct impact on individuals with CKD and other underlying conditions is related to baseline risk, influenced by age, multimorbidity and other socio-demographic factors. However, previous studies of COVID-19 in CKD have been small scale (12-1099 cases), mostly focused on end-stage CKD, and ignored major comorbidities. Thus, using large-scale, population-based electronic health records, in people with incident CKD we aimed to (a) identify the most common comorbidities; (b) estimate 1-year (pre-pandemic) risk of mortality and (c) predict excess deaths related to COVID-19 over 1-year of pandemic based on pre-pandemic risk of mortality at different population infection rates and relative risks. We used linked primary and secondary care records (Clinical Practice Research Datalink GOLD data) from England; of 3,862,012 individuals aged ≥ 30 registered with a GP practice between 1997 and 2017. Incident CKD was identified based on diagnosis codes and eGFR levels; classified mutually exclusively into five CKD Stages. The underlying conditions were obtained using validated phenotyping algorithms in CALIBER and the most prevalent ones were identified. The 1-year mortality were estimated using Kaplan–Meier survival analysis; stratified by key demographic factors and number of comorbidities. Using these pre-pandemic risk estimates and our recently published Lancet model, we calculated excess COVID-19 related deaths at different population infection rates and relative risks. For validation, we identified the number of people who died with both CKD and positive COVID-19 test result during 1-year of pandemic using the contemporary NHSD TRE data of England (NHS Digital Trusted Research Environment, n=54 million). We identified 294,381 individuals with incident CKD (mean age 72.5 years; female: 59%). Multimorbidity was common among CKD patients especially the presence of hypertension (61.4%) and CVD complications (35.6%) (Fig 1 ). The proportion of CKD patients having at least one underlying condition increases significantly either by age or CKD stage whilst age was the main confounder within each CKD stage. Age, Stage of CKD and underlying conditions combined to influence pre-pandemic risk (Fig 2 ). At an IR of 10%, we predicted 31003 and 46505 excess deaths at RR of 2 and 3 respectively (Table 1 ) which is close to actual observed mortality (47214) from the NHSD TREin England. View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Individuals with CKD have high risk of pre-pandemic mortality particularly those with comorbidities. The data on multimorbidity, CKD stage and age together could help prioritise patients for vaccination, post-COVID policy, and designing stratified pathways for CKD patients. We illustrate that the direct burden of pandemic could be predicted using pre-pandemic large scale EHR data.

β-Blockers and the Risk of Depression: A Matched Case-Control Study.

IntroductionDepression is a commonly cited adverse effect of β-blockers but the evidence for a causal relationship is limited.ObjectiveWe aimed to explore whether β-blockers are associated with an increased risk of new-onset depression.MethodsWe conducted a case–control study using the UK population-based Clinical Practice Research Datalink (CPRD) GOLD. We identified patients aged 18−80 years with an incident depression diagnosis between 2000 and 2016, and matched controls, and estimated the risk (odds ratio [OR]) of depression in association with use of β-blockers. We also conducted analyses of exposure, categorised by number and timing of prescriptions and by indication for β-blocker use.ResultsThe study encompassed 118,705 patients with incident depression and the same number of matched controls. The odds of developing depression were increased for current short-term use of any β-blocker (adjusted OR [aOR] 1.91, 95% confidence interval [CI] 1.72−2.12), whereas current long-term use was not associated with the risk of depression compared with never use. The elevated risk of depression among short-term users was mostly confined to propranolol users with a neuropsychiatric disorder (aOR 6.33, 95% CI 5.16–7.76), while propranolol users with a cardiovascular indication were only at marginally increased risk of depression (aOR 1.44, 95% CI 1.14–1.82).ConclusionsThis study suggests that the association between use of β-blockers and depression may not be causal but rather a result of protopathic bias. Propranolol is often prescribed to treat neuropsychiatric symptoms, suggesting that the onset of depression may be related to the underlying indication rather than to an effect of a β-blocker therapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01140-5.

Glucocorticoids and Risk of Venous Thromboembolism in Asthma Patients Aged 20-59 Years in the United Kingdom's CPRD 1995-2015.

BackgroundGlucocorticoids, the class of steroids used in management of asthma, have been observed to be associated with adverse events such as increased coagulation and inhibition of fibrinolysis. This study evaluated the risk of VTE in relation to the use of glucocorticoids in patients with asthma.MethodsWe conducted a nested case–control study among patients aged 20–59 years with asthma who received at least one glucocorticoid prescription during 1995–2015 in the UK-based Clinical Practice Research Datalink GOLD. We used descriptive analyses and conditional logistic regression to evaluate the risk of VTE associated with glucocorticoid use.ResultsThe adjusted ORs (aORs) (95% CI) for VTE in patients exposed to glucocorticoids were 1.9 (1.6–2.3), 1.4 (1.1–1.8), and 1.2 (0.9–1.5) for current, recent, and past glucocorticoid users, respectively, compared to the unexposed. The aORs (95% CI) for VTE in patients exposed to systemic glucocorticoid and inhaled glucocorticoids, compared to the unexposed, were 3.5 (2.7–4.5) and 1.5 (1.3–1.8), respectively.ConclusionCurrent and systemic glucocorticoid use was associated with a dose-response increased risk of incident idiopathic VTE.

The importance of blood pressure thresholds versus predicted cardiovascular risk on subsequent rates of cardiovascular disease: a cohort study in English primary care

SummaryBackgroundFor five decades, blood pressure lowering treatment has been recommended for patients with hypertension (currently defined as blood pressure of ≥140/90 mm Hg). In the past 20 years, guidelines for treatment began incorporating predicted absolute cardiovascular disease risk (predicted risk) and reducing blood pressure thresholds. The blood pressure threshold at which to start treatment has become a secondary consideration in some countries. We aimed to provide descriptive data to assess the relative importance of blood pressure thresholds versus predicted risk on the subsequent rate of cardiovascular disease to inform treatment decisions.MethodsIn this English population-based cohort study, we used linked data from the Clinical Practice Research Datalink (CPRD) GOLD, Hospital Episode Statistics Admitted Patient Care, and the Office for National Statistics mortality data, and area-based deprivation indices (Townsend scores). Eligible patients were aged 30–79 years on Jan 1, 2011 (cohort entry date) and could be linked to hospital, mortality, and deprivation data. Patients were followed up until death, end of CPRD follow-up, or Nov 31, 2018. We examined three outcomes: cardiovascular disease, markers of potential target organ damage, and incident dementia without a known cause. The rate of each outcome was estimated and stratified by systolic blood pressure and predicted 10-year risk of cardiovascular disease (QRISK2 algorithm).FindingsBetween Jan 1, 2011, and Nov 31, 2018, 1 098 991 patients were included in the cohort and followed up for a median of 4·3 years (IQR 2·6–6·0; total follow-up of 4·6 million person-years). Median age at entry was 52 years (IQR 42–62) and 629 711 (57·3%) patients were female. There were 51 996 cardiovascular disease events and the overall rate of cardiovascular disease was 11·2 per 1000 person-years (95% CI 11·1–11·3). Median QRISK2 10-year predicted risk was 4·6% (IQR 1·4–12·0) and mean systolic blood pressure before cohort entry was 129·1 mm Hg (SD 15·7). Within strata of predicted risk, the effect of increasing systolic blood pressure on outcomes was small. For example, in the group with 10·0–19·9% predicted risk, rates of all cardiovascular disease rose from 20·1 to 23·6 per 1000 person-years between systolic blood pressures less than 110 mm Hg and 180 and higher mm Hg. But among patients with systolic blood pressure 140·0–149·9 mm Hg, rates rose from 6·9 to 52·3 per 1000 person-years between those with less than 10·0% risk and those with 30·0% or higher predicted risk.InterpretationFor a wide range of blood pressures, the rate of cardiovascular disease and effectiveness of blood pressure drug treatment was mainly determined by predicted risk, with blood pressure thresholds 140/90 mm Hg or 160/100 mm Hg—ubiquitous in most countries—adding little useful information. When medium-term predicted risk is low, there is no urgency to initiate drug treatment, allowing time to attempt non-pharmacological blood pressure reduction.FundingNational Institute for Health Research.

Suicide and death by other causes among patients with a severe mental illness: cohort study comparing risks among patients discharged from inpatient care v. those treated in the community.

People diagnosed with a severe mental illness (SMI) are at elevated risk of dying prematurely compared to the general population. We aimed to understand the additional risk among people with SMI after discharge from inpatient psychiatric care, when many patients experience an acute phase of their illness. In the Clinical Practice Research Datalink (CPRD) GOLD and Aurum datasets, adults aged 18 years and older who were discharged from psychiatric inpatient care in England between 2001 and 2018 with primary diagnoses of SMI (schizophrenia, bipolar disorder, other psychoses) were matched by age and gender with up to five individuals with SMI and without recent hospital stays. Using survival analysis approaches, cumulative incidence and adjusted hazard ratios were estimated for all-cause mortality, external and natural causes of death, and suicide. All analyses were stratified by younger, middle and older ages and also by gender. In the year after their discharge, the risk of dying by all causes examined was higher than among individuals with SMI who had not received inpatient psychiatric care recently. Suicide risk was 11.6 times (95% CI 6.4-20.9) higher in the first 3 months and remained greater at 2-5 years after discharge (HR 2.3, 1.7-3.2). This risk elevation remained after adjustment for self-harm in the 6 months prior to the discharge date. The relative risk of dying by natural causes was raised in the first 3 months (HR 1.6, 1.3-1.9), with no evidence of elevation during the second year following discharge. There is an additional risk of death by suicide and natural causes for people with SMI who have been recently discharged from inpatient care over and above the general risk among people with the same diagnosis who have not recently been treated as an inpatient. This mortality gap shows the importance of continued focus, following discharge, on individuals who require inpatient care.

Body mass index and cancer mortality in patients with incident type 2 diabetes: A population-based study of adults in England.

We evaluated the relationship between body mass index (BMI) and cancer mortality in incident type 2 diabetes. We used the Clinical Practice Research Datalink GOLD (1998-2015), linked with the Office of National Statistics mortalities, and derived an incident type 2 diabetes cohort (N=176 886; aged 30-85 years). We determined BMI ±12 months diabetes diagnosis. The primary outcome was cancer mortality, categorized into deaths from obesity-related cancers (ORCs) and non-ORCs. Secondary outcomes were site-specific cancer mortality and main causes of deaths [cancer, cardiovascular disease (CVD), non-cancer non-CVD]. We developed gender-specific Cox models and expressed risk as hazard ratios and 95% confidence intervals, stratified by smoking status. With 886 850 person-years follow-up, 7593 cancer deaths occurred. Among women who never smoked, there were positive associations between BMI and deaths from endometrial (hazard ratios per 5 kg/m2 : 1.43; 95% confidence interval 1.26-1.61). Among men, associations between BMI and ORC mortality were inverse but attenuated towards null among never smokers and excluding deaths in the first 2 years. In men, the proportion of CVD deaths increased from 36.8% in BMI category 22.5 to 24.9 kg/m2 to 43.6% in BMI category ≥40 kg/m2 (p < .001). We found some relationships between BMI and cancer mortality in patients with type 2 diabetes, but interpretations need to account for smoking status, reverse causality and deaths from CVD.

Development and Validation of a Primary Care Electronic Health Record Phenotype to Study Migration and Health in the UK.

International migrants comprised 14% of the UK’s population in 2020; however, their health is rarely studied at a population level using primary care electronic health records due to difficulties in their identification. We developed a migration phenotype using country of birth, visa status, non-English main/first language and non-UK-origin codes and applied it to the Clinical Practice Research Datalink (CPRD) GOLD database of 16,071,111 primary care patients between 1997 and 2018. We compared the completeness and representativeness of the identified migrant population to Office for National Statistics (ONS) country-of-birth and 2011 census data by year, age, sex, geographic region of birth and ethnicity. Between 1997 to 2018, 403,768 migrants (2.51% of the CPRD GOLD population) were identified: 178,749 (1.11%) had foreign-country-of-birth or visa -status codes, 216,731 (1.35%) non-English-main/first-language codes, and 8288 (0.05%) non-UK-origin codes. The cohort was similarly distributed versus ONS data by sex and region of birth. Migration recording improved over time and younger migrants were better represented than those aged ≥50. The validated phenotype identified a large migrant cohort for use in migration health research in CPRD GOLD to inform healthcare policy and practice. The under-recording of migration status in earlier years and older ages necessitates cautious interpretation of future studies in these groups.

The Long-Term Impact of Vaginal Surgical Mesh Devices in UK Primary Care: A Cohort Study in the Clinical Practice Research Datalink.

PurposeStress urinary incontinence (SUI) and pelvic organ prolapse (POP) may be treated with surgical mesh devices; evidence of their long-term complications is lacking.Patients and MethodsRates of diagnoses of depression, anxiety or self-harm (composite measure) and sexual dysfunction, and rates of prescriptions for antibiotics and opioids were estimated in women with and without mesh surgery, with a diagnostic SUI/POP code, registered in the Clinical Practice Research Datalink (CPRD) gold database.ResultsThere were 220,544 women eligible for inclusion; 74% (n = 162,687) had SUI, 37% (n = 82,123) had POP, and 11% (n = 24,266) had both. Women undergoing mesh surgery for SUI or POP had about 1.1 times higher rates of antibiotic use. Women with no previous history of the outcome, who underwent mesh surgery had 2.43 (95% CI 2.19–2.70) and 1.47 (95% CI 1.19–1.81) times higher rates of depression, anxiety, or self-harm, 1.88 (95% CI 1.50–2.36) and 1.64 (95% CI 1.02–2.63) times higher rates of sexual dysfunction and 1.40 (95% CI 1.26–1.56) and 1.23 (95% CI 1.01–1.49) times higher opioid use for SUI and POP, respectively. Women with a history of depression, anxiety and self-harm had 0.3 times lower rates of these outcomes with SUI or POP mesh surgery (HR for SUI 0.70 (95% CI 0.67-0.73), HR for POP 0.72 (95% CI 0.65-0.79)). Women with a history of opioid use who had POP mesh surgery had about 0.09 times lower rates (HR 0.91 (95% CI 0.86–0.96)) of prescriptions. Negative control outcome analyses showed no evidence of an association between asthma consultations and mesh surgery in women with POP, but the rate was 0.09 times lower (HR 0.91 (95% CI 0.87–0.94)) in women with SUI mesh surgery, suggesting that study results are subject to some residual confounding.ConclusionMesh surgery was associated with poor mental and sexual health outcomes, alongside increased opioid and antibiotic use, in women with no history of these outcomes and improved mental health, and lower opioid use, in women with a previous history of these outcomes. Although our results suggest an influence of residual confounding, careful consideration of the benefits and risk of mesh surgery for women with SUI or POP on an individual basis is required.

Consultation patterns and frequent attenders in UK primary care from 2000 to 2019: a retrospective cohort analysis of consultation events across 845 general practices

ObjectiveTo describe the distribution of consultations at the practice level and examine whether increases are uniform or driven by people who consult more frequently.DesignRetrospective cohort study.SettingUK general practice data from...

Cardiovascular risk profiles: A cross-sectional study evaluating the generalizability of the glucagon-like peptide-1 receptor agonist cardiovascular outcome trials REWIND, LEADER and SUSTAIN-6 to the real-world type 2 diabetes population in the United Kingdom.

AimsTo determine the proportion of UK patients with type 2 diabetes (T2D) who meet the cardiovascular (CV) or combined CV/core eligibility criteria used for the CV outcome trials (CVOTs) of UK‐marketed glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) showing CV benefit (dulaglutide in REWIND, liraglutide in LEADER and injectable semaglutide in SUSTAIN‐6).Materials and MethodsAdults with T2D on/before June 2018 were identified from the UK Clinical Practice Research Datalink GOLD primary care database and linked to Hospital Episode Statistics data (Protocol 19_262). Patient CV and clinical data were evaluated against the CVOT eligibility criteria. Data were analysed descriptively.ResultsThe study cohort (N = 33 118 patients with T2D) had a mean (standard deviation) age of 66.0 (13.3) years and 56.6% were male. Almost two‐thirds (64.5%) of the study cohort met the CV criteria for REWIND, versus 43.0% for both LEADER and SUSTAIN‐6. The proportions of the study cohort who met the CVOT criteria of “established CV disease” and “CV risk factors only” for REWIND were 22.4% and 42.1%, respectively, versus 38.7% and 4.3%, respectively, for both LEADER and SUSTAIN‐6. The proportions of patients satisfying both CV and core criteria were 44.4% for REWIND, 13.3% for LEADER and 13.5% for SUSTAIN‐6. Study findings remained consistent when restricted to GLP‐1RA users.ConclusionsREWIND captured a trial population more representative of the real‐world T2D population in the United Kingdom than LEADER or SUSTAIN‐6 with regard to both CV and combined CV/core eligibility criteria.

Risk of acute respiratory infection and acute cardiovascular events following acute respiratory infection among adults with increased cardiovascular risk in England between 2008 and 2018: a retrospective, population-based cohort study

SummaryBackgroundAlthough acute respiratory infections can lead to cardiovascular complications, the effect of underlying cardiovascular risk on the incidence of acute respiratory infections and cardiovascular complications following acute respiratory infection in individuals without established cardiovascular disease is unknown. We aimed to investigate whether cardiovascular risk is associated with increased risk of acute respiratory infection and acute cardiovascular events after acute respiratory infection using 10 years of linked electronic health record (EHR) data in England.MethodsIn this retrospective, population-based cohort study we used EHRs from primary care providers registered on the Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases in England. Eligible individuals were aged 40–64 years, did not have established cardiovascular disease or a chronic health condition that would make them eligible for influenza vaccination, were registered at a general practice contributing to the CPRD, and had linked Hospital Episode Statistics Admitted Patient Care data in England from Sept 1, 2008, to Aug 31, 2018. We classified cardiovascular risk on the basis of diagnosed hypertension and overall predicted cardiovascular risk, estimated by use of the QRISK2 risk-prediction tool (comparing a score of ≥10% [increased risk] with a score of <10% [low risk]). Using multivariable Poisson regression models, we calculated incidence rate ratios (IRRs) for systemic acute respiratory infection. Among individuals who had an acute respiratory infection, we used multivariable Cox regression to calculate hazard ratios (HRs) for the risk of acute cardiovascular events within 1 year of infection.FindingsWe identified 6 075 321 individuals aged 40–64 years with data in the CPRD and linked data in the Hospital Episode Statistics Admitted Patient Care database between Sept 1, 2008, and Aug 31, 2018. Of these individuals, 4 212 930 (including 526 480 [12·5%] with hypertension and 607 087 [14·4%] with a QRISK2 score of ≥10%) were included in the assessment of the incidence of acute respiratory infection. After adjusting for confounders (age, sex, ethnicity, socioeconomic status, body-mass index, alcohol consumption, smoking status, and consultation frequency in the hypertension analysis; and alcohol consumption and consultation frequency in the QRISK2 analysis), the incidence of acute respiratory infection was higher in individuals with hypertension than those without (IRR 1·04 [95% CI 1·03–1·05]) and higher in those with a QRISK2 score of 10% or higher than in those with a QRISK2 score of less than 10% (1·39 [1·37–1·40]). Of the 442 408 individuals who had an acute respiratory infection, 4196 (0·9%) had an acute cardiovascular event within 1 year of infection. After adjustment (for age, sex, ethnicity, socioeconomic status, body-mass index, alcohol consumption, and smoking status in the hypertension analysis; and for alcohol consumption in the QRISK2 analysis), hypertension (HR 1·98 [95% CI 1·83–2·15]) and a QRISK2 score of 10% or higher (3·65 [3·42–3·89]) were associated with a substantially increased risk of acute cardiovascular events after acute respiratory infection.InterpretationPeople with increased cardiovascular risk but without diagnosed cardiovascular disease, measured by diagnosed hypertension or overall predicted cardiovascular risk, could benefit from influenza and pneumococcal vaccine prioritisation to reduce their risk of both acute respiratory infection and cardiovascular complications following an acute respiratory infection.FundingBritish Heart Foundation and the Wellcome Trust.