Publications
scientifiques

OBJECTIVE: Caring for a partner with dementia and partner bereavement are independently associated with poor health. An understanding of the health effects of living with a partner dying with dementia can help optimise support. We describe health in the year before and after loss of a partner with dementia compared with other bereavements. METHODS: In a UK primary care database, 2624 older individuals whose partner died with dementia during 2005-2012 were matched with 7512 individuals experiencing bereavement where the deceased partner had no dementia recorded. RESULTS: Prior to bereavement, partners of the deceased with dementia were more likely to be diagnosed with depression (OR 2.31, 1.69-3.14) and receive psychotropic medication (OR 1.34, 1.21-1.49) than partners from bereavements without dementia. In contrast, psychotropic medication initiation two months after dementia bereavement was lower (HR 0.69, 0.56-0.85). Compared with other bereaved individuals, mortality after bereavement was lower in men experiencing a dementia bereavement (HR 0.68, 0.49-0.94) but similar in women (HR 1.02, 0.75-1.38). Prior to bereavement, those who died with dementia were less likely to receive palliative care (OR 0.47, 0.41-0.54). CONCLUSION: In the year before bereavement, partners of individuals dying with dementia experience poorer mental health than those facing bereavement from other causes, and their partner is less likely to receive palliative care. In the year after, individuals whose partner died with dementia experience some attenuation of the adverse health effects of bereavement. Services need to address the needs of carers for individuals dying with dementia and improve access to palliative care. Copyright © 2016 John Wiley & Sons, Ltd.

BACKGROUND: Bleeding events have been associated with the use of antiplatelet agents. This study estimated the incidence of bleeding events in patients previously hospitalized for a serious coronary event and determined the risks of bleeding associated with the use of acetylsalicylic acid (ASA) and/or clopidogrel. METHODS: A UK primary care database was used to identify 27,707 patients aged 50 to 84 years, hospitalized for a serious coronary event during 2000 to 2007 and who were alive 30 days later (start date). Patients were followed up until they reached an endpoint (hemorrhagic stroke, upper or lower gastrointestinal bleeding [UGIB/LGIB]), death or end of study [June 30, 2011]) or met an exclusion criterion. Risk factors for bleeding were determined in a nested case-control analysis. RESULTS: Incidences of hemorrhagic stroke, UGIB, and LGIB were 5.0, 11.9, and 25.5 events per 10,000 person-years, respectively, and increased with age. UGIB and LGIB led to hospitalization in 73 and 23 % of patients, respectively. Non-users of ASA, who were mostly discontinuers, and current users of ASA had similar risks of hemorrhagic stroke, UGIB, and LGIB. Users of combined antithrombotic therapy (warfarin and antiplatelets) experienced an increased risk of hemorrhagic stroke (odds ratio [OR], 6.36; 95 % confidence interval [CI], 1.34-30.16), whereas users of combined antiplatelet therapy (clopidogrel and ASA) experienced an increased risk of UGIB (OR, 2.42; 95 % CI, 1.09-5.36). An increased risk of LGIB (OR, 1.86; 95 % CI, 1.34-2.57) was also observed in users of clopidogrel. CONCLUSIONS: In patients previously hospitalized for a serious coronary event, combined antithrombotic therapy was associated with an increased risk of hemorrhagic stroke, whereas combined antiplatelet therapy was associated with an increased risk of UGIB.Non-use of ASA was rare in this population and use of ASA was not associated with a significantly increased risk of hemorrhagic stroke, UGIB, or LGIB.

INTRODUCTION: Antipsychotic drugs (APDs) are used to treat several mental illnesses. Some APDs have long been known to be associated with QT prolongation, potentially leading to torsades de pointes (TdP) and sudden cardiac death (SCD). In 2005, thioridazine was withdrawn because of the risk of SCD, bringing further attention to the arrhythmogenic potential of APDs. AIM: The aim of the current study was to evaluate the use of APDs in five European countries during the years 1996-2010. METHODS: A cohort study was conducted using prescription/dispensing data from seven healthcare databases [the AARHUS University Hospital Database (Denmark), the German Pharmacoepidemiological Research Database (GePaRD) (Germany), Health Search Database/Thales (HSD) and Emilia Romagna Regional Database (ERD) (Italy), PHARMO Database Network and Integrated Primary Care Information (IPCI) (the Netherlands) and The Health Improvement Network (THIN) (the UK), covering a population of 27 million individuals. The annual prescription rate of APDs was measured overall and for individual medications. APDs were classified as torsadogenic according to the Arizona-CERT list. All analyses were stratified by age, gender and calendar year. RESULTS: A total of 559 276 person-years (PYs) of exposure to APDs was captured. The crude annual prescription rate of APD use ranged from 3.0/1000 PYs in ERD to 7.7/1000 PYs in AARHUS. Among APDs with established torsadogenic potential, thioridazine was the most frequently used medication in the UK. Haloperidol was commonly prescribed in Italy and the Netherlands. The use of APDs with torsadogenic potential was much higher in elderly patients. CONCLUSIONS: Substantial use of APDs with torsadogenic potential has been reported in Europe in recent years, in spite of increasing concerns about their arrhythmogenic potential. This use was even greater in elderly patients, who are at higher risk of SCD.

BACKGROUND: A pro-inflammatory gut microbiota was described in both Parkinson's disease and colorectal cancer (CRC) and recently α-synuclein was demonstrated in the enteric nervous system. We sought to evaluate the association between Parkinson's disease and CRC. METHODS: We conducted a nested case-control study using a large primary-care database. Cases were defined as all individuals with CRC. Up to 4 controls were matched with each case based on age, sex, practice-site and duration of follow-up. The primary exposure of interest was diagnosis of Parkinson's disease prior to CRC as well as disease duration, and Parkinson's specific therapies. The primary analysis was a conditional logistic-regression to estimate odds ratios (ORs) and 95% confidence interval (95%CI). RESULTS: The study included 22,093 CRC cases and 85,833 matched controls. Past medical history of Parkinson's disease >1 year before index-date was associated with lower CRC risk (OR 0.74, 95%CI 0.59-0.94). The inverse association was more prominent among females compared to males (0.64, 95%CI 0.42-0.96 and 0.8, 95%CI 0.60-1.07, respectively). While patients who received no therapy or therapy with dopamine agonists had a non-significant decrease in cancer risk, patients who were treated with dopamine had a non-significant elevated cancer risk. CONCLUSION: Parkinson's disease is inversely associated with CRC risk.

BACKGROUND: Clustered randomised controlled trials (CRCTs) are increasingly common in primary care. Outcomes within the same cluster tend to be correlated with one another. In sample size calculations, estimates of the intra-cluster correlation coefficient (ICC) are needed to allow for this nonindependence. In studies with observations over more than one time period, estimates of the inter-period correlation (IPC) and the within-period correlation (WPC) are also needed. METHODS: This is a retrospective cross-sectional study of all patients aged 18 or over with a diagnosis of type-2 diabetes, from The Health Improvement Network (THIN) database, between 1 October 2007 and 31 March 2010. We report estimates of the ICC, IPC, and WPC for typical outcomes using unadjusted and adjusted generalised linear mixed models with cluster and cluster by period random effects. For binary outcomes we report on the proportions scale, which is the appropriate scale for trial design. Estimated ICCs were compared to those reported from a systematic search of CRCTs undertaken in primary care in the UK in type-2 diabetes. RESULTS: Data from 430 general practices, with a median [IQR] number of diabetics per practice of 241 [150-351], were analysed. The ICC for HbA1c was 0.032 (95 % CI 0.026-0.038). For a two-period (each of 12 months) design, the WPC for HbA1c was 0.035 (95 % CI 0.030-0.040) and the IPC was 0.019 (95 % CI 0.014-0.026). The difference between the WPC and the IPC indicates a decay of correlation over time. Following dichotomisation at 7.5 %, the ICC for HbA1c was 0.026 (95 % CI 0.022-0.030). ICCs for other clinical measurements and clinical outcomes are presented. A systematic search of ICCs used in the design of CRCTs involving type-2 diabetes with HbA1c (undichotomised) as the outcome found that published trials tended to use more conservative ICC values (median 0.047, IQR 0.047-0.050) than those reported here. CONCLUSIONS: These estimates of ICCs, IPCs, and WPCs for a variety of outcomes commonly used in diabetes trials can be useful for the design of CRCTs. In studies with observations taken at different time-points, the correlation of observations may decay over time, as reflected in lower values for the IPC than for the ICC. The IPC and WPC estimates are the first reported for UK primary care data.

Due to the heterogeneity of existing European sources of observational healthcare data, data source-tailored choices are needed to execute multi-data source, multi-national epidemiological studies. This makes transparent documentation paramount. In this proof-of-concept study, a novel standard data derivation procedure was tested in a set of heterogeneous data sources. Identification of subjects with type 2 diabetes (T2DM) was the test case. We included three primary care data sources (PCDs), three record linkage of administrative and/or registry data sources (RLDs), one hospital and one biobank. Overall, data from 12 million subjects from six European countries were extracted. Based on a shared event definition, sixteeen standard algorithms (components) useful to identify T2DM cases were generated through a top-down/bottom-up iterative approach. Each component was based on one single data domain among diagnoses, drugs, diagnostic test utilization and laboratory results. Diagnoses-based components were subclassified considering the healthcare setting (primary, secondary, inpatient care). The Unified Medical Language System was used for semantic harmonization within data domains. Individual components were extracted and proportion of population identified was compared across data sources. Drug-based components performed similarly in RLDs and PCDs, unlike diagnoses-based components. Using components as building blocks, logical combinations with AND, OR, AND NOT were tested and local experts recommended their preferred data source-tailored combination. The population identified per data sources by resulting algorithms varied from 3.5% to 15.7%, however, age-specific results were fairly comparable. The impact of individual components was assessed: diagnoses-based components identified the majority of cases in PCDs (93-100%), while drug-based components were the main contributors in RLDs (81-100%). The proposed data derivation procedure allowed the generation of data source-tailored case-finding algorithms in a standardized fashion, facilitated transparent documentation of the process and benchmarking of data sources, and provided bases for interpretation of possible inter-data source inconsistency of findings in future studies.

PURPOSE: Activation of Hedgehog (Hh) signaling has been implicated in early stages of bladder cancer development while loss of Hh signaling has been described during progression to more invasive disease. Itraconazole, an antifungal, is the only azole known to be a potent Hh pathway antagonist. We evaluated whether itraconazole use is associated with bladder cancer risk or progression. MATERIALS AND METHODS: We performed a case-control study nested in a United Kingdom database in 13,440 bladder cancer cases and 52,421 matched controls between 1995 and 2013. The use of itraconazole and other azoles was measured as the number of prescriptions. Conditional logistic regression was used for estimated AORs and the 95% CI of the association of bladder cancer with ever use and an increasing number of itraconazole prescriptions. Logistic regression was done to determine whether itraconazole use in patients diagnosed with bladder cancer was associated with invasive bladder cancer requiring cystectomy relative to the use of other azoles. RESULTS: Itraconazole was not associated with the risk of bladder cancer relative to never use (ever use AOR 0.89, 95% CI 0.70-1.14 and 4 or more prescriptions AOR 0.87, 95% CI 0.42-1.81). However, among patients diagnosed with bladder cancer there was a significantly increased risk of bladder cancer requiring cystectomy with itraconazole use (ever use AOR 2.05, 95% CI 1.12-3.38 and 2 or more prescriptions AOR 2.30, 95% CI 1.12-4.72). CONCLUSIONS: Inhibition of the Hh pathway with itraconazole was not associated with a risk of bladder cancer overall but it was associated with a higher risk of invasive bladder cancer requiring cystectomy. These data provide clinical evidence supporting the role of Hh signaling in regulating bladder cancer progression.

BACKGROUND: There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine. METHODS AND FINDINGS: We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64-3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45-0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45-0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47-0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40-0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29-0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09-0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13-0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10-0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14-0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07-0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31-2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47-2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24-2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06-1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects. CONCLUSIONS: Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options.

OBJECTIVES: The choice of an adequate sample size for a Cox regression analysis is generally based on the rule of thumb derived from simulation studies of a minimum of 10 events per variable (EPV). One simulation study suggested scenarios in which the 10 EPV rule can be relaxed. The effect of a range of binary predictors with varying prevalence, reflecting clinical practice, has not yet been fully investigated. STUDY DESIGN AND SETTING: We conducted an extended resampling study using a large general-practice data set, comprising over 2 million anonymized patient records, to examine the EPV requirements for prediction models with low-prevalence binary predictors developed using Cox regression. The performance of the models was then evaluated using an independent external validation data set. We investigated both fully specified models and models derived using variable selection. RESULTS: Our results indicated that an EPV rule of thumb should be data driven and that EPV ≥ 20 ​ generally eliminates bias in regression coefficients when many low-prevalence predictors are included in a Cox model. CONCLUSION: Higher EPV is needed when low-prevalence predictors are present in a model to eliminate bias in regression coefficients and improve predictive accuracy.

AIM: To identify risk factors of diabetic retinopathy (DR) among people with Type 2 diabetes mellitus in UK primary care. METHODS: A case-control study nested in a cohort of incident Type 2 diabetes identified in The Health Improvement Network database from 2000 to 2007. Cases were people with DR (N=7735) and controls were a DR-free sample (N=9395). No age restrictions were applied. Adjusted odds ratios and 95% CIs were estimated. RESULTS: 21% of DR cases were identified during the first semester after Type 2 diabetes diagnosis. After controlling for delay on the Type 2 diabetes diagnosis, the DR risk increased with the duration of diabetes. DR increased with a mean systolic BP ≥150mmHg (1.18; 1.10-1.27), high alcohol consumption (1.34; 1.11-1.61), glycated haemoglobin (≥75 to <86: 1.14; 1.00-1.31; ≥86 to <97mmol/mol: 1.25; 1.07-1.45; ≥97mmol/mol: 1.21; 1.07-1.37), microalbuminuria (1.16; 1.06-1.27), and retinal vein occlusion (2.47; 1.67-3.66). Glaucoma and retinal arterial occlusion showed an OR of 0.71 (0.60-0.84) and 0.63 (0.40-1.01), respectively. HDL ≥1.55mmol/l (0.88; 0.80-0.98), high triglycerides (2.3-5.6mmol/l: 0.90; 0.82-0.99; >5.6mmol/l: 0.85; 0.64-1.13) or smoking (0.89; 0.81-0.97) had a slightly reduced DR risk. Users of hypoglycaemic agents had an increased DR risk. CONCLUSION: Some DR cases were identified near the diabetes diagnosis date suggesting that a delayed diabetes diagnosis is still common. Glaucoma, retinal arterial occlusion and high HDL levels were inversely associated with DR, while retinal vein occlusion, alcohol and other well-known risk factors were positively associated.

BACKGROUND: Uterine fibroids (UFs) are the most common benign tumour in women, and many undergo hysterectomy or uterus-preserving procedures (UPPs) to manage their symptoms. We aimed to validate the recording of UFs in a primary care database, The Health Improvement Network (THIN), and to determine the incidence of UFs in the UK. METHODS: In this observational study, women in THIN aged 15-54 years between January 2000 and December 2009 with no previous record of UFs, hysterectomy or UPPs were identified. Individuals were followed up until there was a Read code indicating UFs, they reached 55 years of age or died, or the study ended. Among those without a UF code, women were identified with a code for hysterectomy, UPPs or heavy menstrual bleeding (HMB). Anonymized patient profiles from each category were randomly selected and reviewed. Subsequently, primary care physicians were asked to complete questionnaires to verify the diagnosis for a randomly selected subgroup. RESULTS: In total, 737,638 women were identified who met the initial inclusion criteria. The numbers of women with a code for UFs, hysterectomy, UPPs and HMB were 9380, 11,002, 3220 and 60,915, respectively; the proportions of confirmed cases of UFs were 88.8, 29.7, 57.7 and 15.9 %. The estimated number of women with UFs was 23,140 (64.0 % without a recorded UF diagnosis). The overall incidence of UFs was 5.8 per 1000 woman-years. CONCLUSIONS: UFs were confirmed in a high proportion of women with UF Read codes. However, almost two-thirds of cases were identified among women with a code for hysterectomy, UPPs or HMB. These results show that UFs are under-recorded in UK primary care, and suggest that primary care physicians tend to code the symptoms of UFs more often than the diagnosis.

BACKGROUND: We conducted three differently designed nested case-control studies to evaluate whether the protective effect of low-dose aspirin against colorectal cancer (CRC) is explained by selection bias. METHODS: Using a large validated UK primary care database, we followed different cohorts of patients, who varied in their demographic and clinical characteristics, to identify first ever cases of CRC. In Studies 1 and 2, two cohorts were followed, i) new users of low-dose aspirin at start of follow-up (N = 170,336 in Study 1, N = 171,527 in Study 2) and either ii) non-users of low-dose aspirin (Study 1, N = 170,336) or new users of paracetamol (Study 2, N = 149,597) at start of follow-up. In Study 3 a single cohort of individuals näive to low-dose aspirin at the start of observation was followed. Controls were selected using incidence sampling and logistic regression used to obtain an unbiased estimate of the incidence rate ratio (RR) with 95% confidence intervals (CIs). Low-dose aspirin exposure was analyzed 'as-treated' before the index date (CRC date for cases, random date for controls). RESULTS: In the three studies, median (maximum) follow-up was 5.1 (12), 5.8 (12) and 7.5 (13) years, respectively. 3033 incident CRC cases were identified in Study 1, 3174 in Study 2, and 12,333 in Study 3. Current use of low-dose aspirin was associated with a significantly reduced risk of 34%, 29% and 31% in the three studies, respectively; corresponding RRs (95% CIs) were 0.66 (0.60-0.73), 0.71 (0.63-0.80) and 0.69 (0.64-0.74). In each study, significantly reduced risks of CRC were seen when low-dose aspirin was used for primary or secondary cardiovascular disease prevention, in both sexes, and across all age groups evaluated. CONCLUSION: Low-dose aspirin is associated with a significantly reduced risk of CRC. The consistency of our findings across different studies makes selection bias an unlikely explanation.

BACKGROUND: Dual lipid-lowering and anti-inflammatory properties of statins may lead to survival benefits in patients with rheumatoid arthritis (RA). However, data on this topic are limited, and the role of statins in RA remains unclear. OBJECTIVES: To examine the association of statin use with overall mortality among patients with RA in a general population context. METHODS: We conducted an incident user cohort study with time-stratified propensity score matching using a UK general population database. The study population included individuals aged ≥20 years who had a diagnosis of RA and had used at least one disease-modifying antirheumatic drug (DMARD) between January 2000 and December 2012. To closely account for potential confounders, we compared propensity score matched cohorts of statin initiators and comparators (non-initiators) within 1-year cohort accrual blocks. RESULTS: 432 deaths occurred during follow-up (mean 4.51 years) of the 2943 statin initiators for an incidence rate of 32.6/1000 person-years (PY), while the 513 deaths among 2943 matched comparators resulted in an incidence rate of 40.6/1000 PY. Baseline characteristics were well-balanced across the two groups. Statin initiation was associated with a 21% lower risk of all-cause mortality (HR=0.79, 95% CI 0.68 to 0.91). When we defined RA by its diagnosis code alone (not requiring DMARD use), the corresponding HR was 0.81 (95% CI 0.74 to 0.90). CONCLUSIONS: Statin initiation is associated with a lower risk of mortality among patients with RA. The magnitude of association is similar to that seen in previous randomised trials among the general population.

BACKGROUND: Screening for alcohol use disorders is an important priority in the healthcare of people with bipolar disorder, incentivised in UK primary care since 2011, through the Quality and Outcomes Framework (QOF). The extent of alcohol monitoring in primary care, and impact of QOF, is unknown. The aim was to examine recording of alcohol consumption in primary care. METHODS: Poisson regression of biennial alcohol recording rates between 2000 and 2013 among 14,051 adults with bipolar disorder and 90,023 adults without severe mental illness (SMI), from 484 general practices contributing to The Health Improvement Network UK-wide primary care database. RESULTS: Alcohol recording rates among people with bipolar disorder increased from 88.6 records per 1000 person-years (95% confidence interval 81.2-96.6) in 2000/2002 to 837.4 records per 1000 person-years (817.4-858.0) in 2011/2013; a more than nine-fold increase, mainly occurring after the introduction of the QOF incentive in 2011. In 2000/2002 alcohol recording levels among people with bipolar disorder were not statistically significantly different from those without SMI (adjusted rate ratio 0.96, 0.88-1.05). By 2011/2013, people with bipolar disorder were over four times as likely to have an alcohol record: adjusted rate ratio 4.45 (4.15-4.77). LIMITATIONS: The routinely collected data may be incomplete. Alcohol data entered as free-text was not captured. CONCLUSIONS: The marked rise in alcohol consumption recording highlights what can be achieved. It is most likely attributable to QOF, suggesting that QOF, or similar schemes, can be powerful tools in promoting aspects of healthcare.

OBJECTIVE: To estimate the incidence and prevalence of polycystic ovary syndrome (PCOS) in UK primary care and investigate prescribing patterns before and after a PCOS diagnosis. DESIGN: Retrospective cohort study. SETTING: UK primary care (2004-2014). PARTICIPANTS: Women aged 15-45 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence and prevalence of diagnosed PCOS and probable PCOS (ie, those without a confirmed diagnosis but with at least 2 PCOS features recorded within 3 years). Among women with diagnosed or probable PCOS, the prevalence of prescribing of drugs typically used to treat PCOS was calculated prior to and in the 24 months after the diagnosis of PCOS. RESULTS: We identified 7233 women with PCOS diagnoses and 7057 women with records suggestive of probable PCOS, corresponding to incidence rates of 0.93 and 0.91 per 1000 person-years at risk (PYAR) and an overall rate of 1.84 per 1000 PYAR. Women aged 20-24 years and women living in deprived areas had the highest incidence of PCOS. The prevalence of PCOS in 2014 was ∼2%. The proportion of women with a prescription in the 24 months after their PCOS index date varied by drug type: 10.2% metformin, 15.2% combined oral contraceptives, 18.8% acne-related treatments, 1.93% clomiphene, 1.0% spironolactone, 0.28% cyproterone and 3.11% eflornithine. Acne-related treatments were more commonly used to treat probable (28.3%) than diagnosed (12.3%) cases, while metformin was prescribed much more commonly in diagnosed cases. CONCLUSIONS: In conclusion, compared to rates estimated in community samples, the incidence and prevalence of women presenting in primary care with PCOS diagnoses and features are low, indicating that PCOS is an under-recognised condition. Although considerable variation is observed in treatments prescribed to women with PCOS, the treatments initiated following a confirmed diagnosis generally reflect the long-term prognostic concerns raised in PCOS consensuses.

BACKGROUND: In secondary cardiovascular prevention, discontinuation of acetylsalicylic acid (ASA) is associated with an increased risk of cardiovascular events. This study assessed the impact of ASA reinitiation on the risk of myocardial infarction and coronary heart disease death. METHODS: Patients prescribed ASA for secondary cardiovascular prevention and who had had a period of ASA discontinuation of ≥90 days in 2000-2007 were identified from The Health Improvement Network (N = 10,453). Incidence of myocardial infarction/coronary heart disease death was calculated. Survival analyses using adjusted Cox proportional hazard models were performed to calculate hazard ratios and 95% confidence intervals for the risk of myocardial infarction/coronary heart disease death associated with ASA use patterns after the initial period of discontinuation. Individuals who were prescribed ASA during follow-up were considered reinitiators. RESULTS: The incidence of myocardial infarction/coronary heart disease death was 8.90 cases per 1000 person-years. Risk of myocardial infarction/coronary heart disease death was similar for current ASA users, who had been continuously exposed since reinitiation, and patients who had not reinitiated ASA (hazard ratio 1.27, 95% confidence interval 0.93-1.73). Among reinitiators, an additional period of ASA discontinuation was associated with increased risk of myocardial infarction/coronary heart disease death compared with no reinitiation (current users: hazard ratio 1.46, 95% confidence interval 1.13-1.90; noncurrent users: hazard ratio 1.70, 95% confidence interval 1.31-2.21). CONCLUSIONS: ASA reinitiation was not associated with a decreased risk of myocardial infarction/coronary heart disease death. This may be explained by confounding by indication/comorbidity, whereby higher-risk patients are more likely to reinitiate therapy. An additional period of ASA discontinuation among reinitiators was associated with an increased risk of myocardial infarction/coronary heart disease death.