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Purpose To assess the feasibility of using Clinical Practice Research Datalink (CPRD) data for identifying populations of patients with chronic obstructive pulmonary disease (COPD) eligible for a hypothetical pragmatic trial. Methods A retrospective multidatabase cohort study using CPRD primary care and linked secondary care data to describe the characteristics of populations of patients with COPD. Patients' demographic and lifestyle factors, comorbidity profile, spirometry measurements and treatment changes were evaluated, as was the distribution of follow‐up time and types of losses during follow‐up. Characteristics were evaluated using descriptive statistics. Results A total of 322 991 patients from 1148 primary care practices in the United Kingdom across two CPRD primary care databases, CPRD GOLD and CPRD Aurum, were potentially eligible to participate in a hypothetical trial using CPRD, starting on 31 December 2017. Patients with COPD in CPRD GOLD and CPRD Aurum were comparable in terms of age (median age 70 vs. 68 years), gender (50% vs. 52% male), disease severity (e.g., 25% vs. 24% Medical Research Council [MRC] dyspnoea score grades 3–5) and history of respiratory conditions (e.g., 43% vs. 38% asthma). High proportions of patients with COPD in CPRD GOLD and CPRD Aurum were available on 31 December 2012 for follow‐up at 1, 2, and 5 years (92%, 85% and 67%, respectively). Conclusions Patients and data from CPRD GOLD and CPRD Aurum were comparable across key aspects relevant to COPD trials. A pragmatic trial using CPRD to recruit patients with COPD is scientifically feasible.

This study measured the exposure to different categories of medicinal products discussed by the European Union (EU) Pharmacovigilance Risk Assessment Committee from September to November 2018 in four electronic primary care health databases: IQVIA Medical Research Data-UK, IQVIA Medical Research Data-France, IQVIA Medical Research Data-Germany, and Clinical Practice Research Datalink Aurum, in the entire lifespan of each database until August 31, 2018. The assessment of 83 centrally authorized products and 45 nationally authorized products showed that coverage was better for products marketed for longer duration and worse for orphan drugs. The ability to detect associations against hypothetical comparators was better for more common events and for larger effect sizes. Coverage of advanced therapies was worse for those typically administered in a specialized rather than primary care setting. This study shows that to enable better informed regulatory decisions there is a need to access complementary data sources, particularly capturing secondary care prescribing.

The use of primary care databases has been integral in pharmacoepidemiological studies and pharmacovigilance. Primary care databases derive from electronic health records and offer a comprehensive description of aggregate patient data, from demography to medication history, and good sample sizes. Studies using these databases improve our understanding of prescribing characteristics and associated risk factors to facilitate better patient care, but there are limitations. We describe eight key scenarios where study data outcomes can be affected by absent prescriptions in UK primary care databases: (1) out-of-hours, urgent care and acute care prescriptions; (2) specialist-only prescriptions; (3) alternative community prescribing, such as pharmacy, family planning clinic or sexual health clinic medication prescriptions; (4) newly licensed medication prescriptions; (5) medications that do not require prescriptions; (6) hospital inpatient and outpatient prescriptions; (7) handwritten prescriptions; and (8) private pharmacy and private doctor prescriptions. The significance of each scenario is dependent on the type of medication under investigation, nature of the study and expected outcome measures. We recommend that all researchers using primary care databases be aware of the potential for missing prescribing data and be sensitive to how this can vary substantially between items, drug classes, patient groups and over time. Close liaison with practising primary care clinicians in the UK is often essential to ensure awareness of nuances in clinical practice.

Purpose\ud UK primary care provides a rich data source for research. The impact of proposed data collection restrictions is unknown. This study aimed to assess the impact of restricting the scope of electronic health record (EHR) data collection on the ability to conduct research. The study estimated the consequences of restricted data collection on published Clinical Practice Research Datalink studies from high impact journals or referenced in clinical guidelines.\ud \ud Methods\ud A structured form was used to systematically analyse the extent to which individual studies would have been possible using a database with data collection restrictions in place: (1) retrospective collection of specified diseases only; (2) retrospective collection restricted to a 6‐ or 12‐year period; (3) prospective and retrospective collection restricted to non‐sensitive data. Outcomes were categorised as unfeasible (not reproducible without major bias); compromised (feasible with design modification); or unaffected.\ud \ud Results\ud Overall, 91% studies were compromised with all restrictions in place; 56% studies were unfeasible even with design modification. With restrictions on diseases alone, 74% studies were compromised; 51% were unfeasible. Restricting collection to 6/12 years had a major impact, with 67 and 22% of studies compromised, respectively. Restricting collection of sensitive data had a lesser but marked impact with 10% studies compromised.\ud \ud Conclusion\ud EHR data collection restrictions can profoundly reduce the capacity for public health research that underpins evidence‐based medicine and clinical guidance. National initiatives seeking to collect EHRs should consider the implications of restricting data collection on the ability to address vital public health questions.

ObjectivesWe aimed to evaluate recording of antibiotic prescribing from two primary care electronic health record systems.DesignCohort study.SettingUK general practices contributing to the Clinical Practice Research Datalink (CPRD) databases: CPRD GOLD (Vision data) and CPRD Aurum (EMIS data). English CPRD GOLD general practices were analysed as a subgroup, as all CPRD Aurum practices were located in England.Participants158 305 patients were randomly sampled from CPRD Aurum and 160 394 from CPRD GOLD.Outcome measuresAntibiotic prescriptions in 2017 were identified. Age-standardised and sex-standardised antibiotic prescribing rates per 1000 person years were calculated. Prescribing of individual antibiotic products and associated medical diagnoses was evaluated.ResultsThere were 101 360 antibiotic prescriptions at 883 CPRD Aurum practices and 112 931 prescriptions at 290 CPRD GOLD practices, including 112 general practices in England. The age-standardised and sex-standardised antibiotic prescribing rate in 2017 was 512.6 (95% CI 510.4 to 514.9) per 1000 person years in CPRD Aurum and 584.3 (582.1 to 586.5) per 1000 person years in CPRD GOLD (505.2 (501.6 to 508.9) per 1000 person years if restricted to practices in England). The 25 most frequently prescribed antibiotic products were similar in both databases. One or more medical codes were recorded on the same date as an antibiotic prescription for 72 989 (74%) prescriptions in CPRD Aurum, 84 756 (78%) in CPRD GOLD and 28 471 (78%) for CPRD GOLD in England. Skin, respiratory and genitourinary tract infections were recorded for 39 035 (40%) prescriptions in CPRD Aurum, 41 326 (38%) in CPRD GOLD, with 15 481 (42%) in English CPRD GOLD practices only.ConclusionEstimates for antibiotic prescribing and infection recording were broadly similar in both databases suggesting similar recording across EMIS and Vision systems. Future research on antimicrobial stewardship can also be conducted using primary care data in CPRD Aurum.

Summary Background Clostridioides difficile infection (CDI) increases the risk of complications and mortality. We assessed the magnitude of these outcomes in a large cohort of English patients with initial and recurrent CDI. Aim To compare the risk of complications and all-cause mortality, within 12 months, among hospitalized patients ≥18 years old with hospital-associated- (HA-) CDI and recurrent CDI. Methods Patients with HA-CDI during 2002–2013 were identified using inpatient hospital data linked to primary care and death data. Each HA-CDI case was frequency matched to two hospitalized patients without CDI on age group, sex, calendar year of admission, admission method and number of hospital care episodes. A second CDI episode starting on days 13–56 was defined as recurrence. Risks of mortality and complications at 12 months were analysed using Cox proportional hazard models. Findings We included 6862 patients with HA-CDI and 13,724 without CDI. Median age was 81.0 years (IQR 71.0–87.0). Patients with HA-CDI had more comorbidities than those without CDI, and significantly higher risks of mortality (adjusted hazard ratio (95% confidence interval) 1.77 (1.67–1.87)) and complications (1.66 (1.46–1.88)) within 12 months from hospital admission. Of those with HA-CDI, 1140 (16.6%) experienced CDI recurrence. Patients with recurrent versus non-recurrent CDI also had significantly increased risk of mortality (1.32 (1.20–1.45)) and complications (1.37 (1.01–1.84)) in the 12 months from the initial CDI. Conclusions HA-CDI (versus no CDI) and recurrent CDI are both associated with significantly higher risks of complications or death within 12 months of the initial CDI episode.

ObjectiveWe evaluated whether recording of antibiotic prescribing across two primary care electronic health record (EHR) systems is similar. Data were analysed from the Clinical Practice Research Datalink (CPRD) databases: CPRD GOLD (Vision data) and CPRD Aurum (EMIS data).MethodsCohorts of patients were randomly sampled from both databases, stratifying by general practice, age-group and gender. All antibiotic prescriptions in 2017 were identified. Age- and sex-standardised antibiotic prescribing rates per 1,000 person years were calculated. Prescribing of individual antibiotic products and associated medical diagnosis recorded on the same date was also evaluated. English CPRD GOLD general practices were analysed as a subgroup, because all CPRD Aurum practices sampled were in England.ResultsThere were 101,360 antibiotic prescriptions among 158,305 sampled patients at 883 CPRD Aurum practices, and 112,931 prescriptions among 160,394 sampled patients at 290 CPRD GOLD practices. The age- and sex-standardised antibiotic prescribing rate in 2017 was 512.6 (95% confidence interval 510.4 to 514.9) per 1,000 person years in CPRD Aurum and 584.3 (582.1 to 586.5) per 1,000 person years in CPRD GOLD [505.2 (501.6 to 508.9) per 1,000 person years if restricted to practices in England]. The 25 most frequently prescribed antibiotic products were similar in both databases. One or more medical codes were recorded on the same date as an antibiotic prescription for 72,989 (74%) prescriptions in CPRD Aurum, 84,756 (78%) in CPRD GOLD, and 28,471 (78%) for CPRD GOLD in England. Skin, respiratory and genito-urinary tract infections were recorded for 39,035 (40%) prescriptions in CPRD Aurum, 41,326 (38%) in CPRD GOLD, with 15,481 (42%) in English CPRD GOLD practices only.ConclusionSimilar estimates for antibiotic prescribing and infection recording were found for both databases suggesting similar recording across EMIS and Vision systems. Future research on antimicrobial stewardship can be conducted in CPRD Aurum informed by previous results from CPRD GOLD. It may also be possible to combine CPRD GOLD and CPRD Aurum data in research on antibiotic prescribing.

Jens Dollerup,1 Jørgen Vestbo,2 Tarita Murray-Thomas,3 Alan Kaplan,4 Richard J Martin,5 Emilio Pizzichini,6 Marcia M M Pizzichini,6 Anne Burden,7 Jessica Martin,7 David B Price7,8 1Dollerup Medical Consultancy, Kongens Lyngby, Denmark; 2Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, UK; 3Clinical Practice Research Datalink, Medicines and Healthcare products Regulatory Agency, London, UK; 4Family Physician Airways Group of Canada, Richmond Hill, ON, Canada; 5National Jewish Health, Denver, CO, USA; 6Federal University of Santa Catarina, Santa Catarina, Brazil; 7Observational and Pragmatic Research Institute Pte Ltd, Singapore; 8Centre for Academic Primary Care, University of Aberdeen, Aberdeen, UK Background: Previous research suggests exposure to nicotine replacement therapy (NRT) may be associated with an increased risk of cardiovascular disease (CVD).Methods: Using data from the United Kingdom’s Clinical Practice Research Datalink, this study aimed to evaluate CVD events and survival among individuals who attempted smoking cessation with the support of NRT compared with those aided by smoking cessation advice only. We studied CVD outcomes over 4 and 52 weeks in 50,214 smokers attempting to quit – 33,476 supported by smoking cessation advice and 16,738 with the support of NRT prescribed by their primary care physician. Patients were matched (2 smoking cessation advice patients:1 NRT patient) on demographic and clinical characteristics during a baseline year preceding their quit attempt. Cox proportional hazard regression, conditional negative binomial regression model, and conditional logistic regression were used to analyze data.Results: Mean (standard deviation) population age was 47 (11.2) years; 51% were females. Time to first diagnosis of ischemic heart disease (IHD) among NRT and smoking cessation advice patients was similar within the first 4 weeks, but shorter for NRT patients over 52 weeks (hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.03–1.77). A similar trend was observed for cerebrovascular disease (HR: 1.54, 95% CI: 1.08–2.19). NRT patients with a prior diagnosis of IHD or cerebrovascular disease had a higher rate of primary or secondary care consultations for IHD or cerebrovascular disease by 52 weeks (rate ratio: 1.50, 95% CI: 1.14–1.99). Patients prescribed NRT had a shorter survival time over 52 weeks, compared with those receiving advice only (HR: 1.39, 95% CI: 1.09–1.76).Conclusion: Our findings suggest that treatment with NRT over 4 weeks does not appear to have an impact on cardiovascular risks. However, a longer follow-up period of 52 weeks resulted in an increase in cardiovascular events for patients prescribed NRT, compared with those receiving smoking cessation advice only.ENCePP registration ENCePP/SDPP/4238 Keywords: smokers, cardiovascular, risk, nicotine replacement therapy, smoking cessation advice

ObjectivesTo estimate the incidence of migraine and describe treatment patterns for an indicative year.MethodsPatients ≥18 years old in the Clinical Practice Research Datalink with an incident diagnosis of migraine between 01/04/2007–31/07/2017. The incidence of migraine was estimated. Treatment groups were categorised as none, acute only, prophylactic only, acute and prophylactic. 12-month treatment patterns amongst patients initiating prophylactic treatment with amitriptyline, propranolol or topiramate were classified as continuous use, augmentation, switching or discontinuation. Treatment adherence was defined as medication possession ratio (MPR); patients were ‘adherent’ if their MPR was ≥0.80.Results89,442 patients with incident migraine were included. Mean age at diagnosis was 40 years [SD 15]; 76.6% were females. The cumulative incidence of migraine rate was 25.8/10,000 person-years [95%CI: 25.6–26.0]. 86.7% of patients received prophylactic and/or acute treatment; 37.6% and 20.1% had received ≥2 and ≥3 prophylactic treatments, respectively.1,636 patients initiated prophylactic treatment in 2015. Propranolol (47.8%) and amitriptyline (47.4%) were most commonly prescribed. Although 80–85% of patients were adherent while on treatment, only 20–30% continued treatment up to 12 months.ConclusionsMigraine treatment remains a challenge. Most patients receive one or more pharmacotherapies but the majority discontinue prophylactic treatment within 12 months of initiation.

Aims: To assess adherence to the United Kingdom’s (UK) National Institute for Health and Care Excellence (NICE) guidelines for initiating and continuing glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes (T2DM).Research Design & Methods: A retrospective cohort study of 7,133 primary care patients ≥40 years with a first prescription for GLP-1 receptor agonist following publication of NICE guideline/guidance. Patient characteristics and levels of clinical monitoring were assessed using descriptive analyses.Main outcome measures: Main outcomes were the proportion of patients initiating GLP-1 receptor agonist as part of NICE recommended dual- or triple-therapy regimens; the proportions meeting NICE triple therapy initiation criteria (glycosylated haemoglobin [HbA1c] ≥7.5% and body mass index [BMI] ≥35kg/m2) and the proportions continuing GLP-1 receptor agonist at 6 months according to NICE recommendations.Results: Mean age at initiating GLP-1 receptor agonist was 58.2 years (SD 9.4), BMI 38.4 kg/m2 (SD 6.8) and HbA1c 9.2% (SD 3.2%). Overall, only 25% of patients initiated GLP-1 receptor agonist as part of a NICE-recommended regimen. Of patients initiated on a recommended triple-therapy regimen, 50% (646/1284) fulfilled both NICE HbA1c and BMI initiation criteria. Approximately 18% (32/174) of patients continuing NICE-recommended dual-therapy at 6 months achieved a 1% reduction in HbA1c and 6.4% (33/515) continuing with NICE recommended triple-therapy achieved both NICE’s target reductions for HbA1c and body weight. About 8% of patients continuing exenatide as triple therapy (N=243) achieved both targets.Conclusions: Adherence to NICE guidance for initiating and continuing GLP-1 receptor agonists is low. However, lack of data on ethnicity (for assessing NICE’s BMI criteria) and on contraindications and/or hypersensitivity to other diabetes medication in the treatment pathway have limited our ability to fully assess adherence to GLP-1 prescribing.Further research is warranted to better understand general practitioners prescribing decisions given the cost of prescribing GLP-receptor agonists.

To determine the prevalence and risk factors for worsening renal function (WRF) among patients hospitalized for decompensated heart failure (HF) and the association with subsequent re-hospitalization and mortality.We prospectively enrolled 299 patients across eight European countries (mean age 68, 74% men). HF was defined using the European Society of Cardiology criteria, but only patients with a history of ejection fractionor =40% on echocardiography were recruited. WRF was defined as an increase in serum creatinine26 micromol/L ( approximately 0.3 mg/dL) from admission. Follow-up was 95% complete to 6 months. Nearly one-third of patients [72 of 248 patients, 29% (95% CI 26-32%)] developed WRF during hospitalization, excluding patients who had a major in-hospital complication likely to compromise renal function. The risk of WRF in this group was independently associated with serum creatinine levels on admission [odds ratio (OR) 3.02 (95% CI 1.58-5.76)], pulmonary oedema [OR 3.35 (1.79-6.27)], and a history of atrial fibrillation [OR 0.35 (0.18-0.67)]. Although the mortality of WRF patients was not increased significantly, the length of stay was 2 days longer [median 11 days (90% range (4-41) vs. 9 days (4-34), P=0.006]. The re-hospitalization rate was similar in both groups.WRF is common in patients admitted to European hospitals with decompensated HF. Such patients have longer duration admissions, but a similar mortality and re-hospitalization rate to those without WRF (if patients experiencing a major in-hospital complication are excluded).

OBJECTIVES: Atrial fibrillation (AF) is the most common cardiac rhythm disorder with a significant health burden. The aim of this study was to characterise patients with recently diagnosed AF and to estimate the rates of comorbidities and outcome events requiring hospitalisation in routine clinical practice. DESIGN: Pharmacoepidemiological cohort study using observational data. METHODS/SETTING: This study included 16 513 patients with a first diagnosis of AF between 1 January 2005 and 28 February 2010 (newly diagnosed patients) using data from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and the Office for National Statistics mortality data. Exposure was stratified by vitamin K antagonist (VKA) exposure (non-use, current, recent and past exposure) based on prescriptions and/or international normalised ratio measurements, and followed for outcome events of interest based on diagnosis codes in the databases, that is, vascular outcomes, bleeding events and others. The main focus of the study was on outcome events requiring hospitalisation using the HES data. RESULTS: The incidence of vascular outcome hospitalisations (myocardial infarction (MI), stroke or systemic arterial peripheral embolism) was 3.8 (95% CI 3.5 to 4.0)/100 patient-years. The incidence of stroke was 0.9 (0.8 to 1.1) during current VKA exposure, 2.2 (1.6 to 2.9) for recent, 2.4 (1.9 to 2.9) for past and 3.4 (3.1 to 3.7) during non-use. MI incidence was 0.7 (0.6 to 0.9) for current VKA exposure, 0.7 (0.4 to 1.2) for recent, 1.1 (0.8 to 1.5) for past and 1.9 (1.7 to 2.1) during non-use. The incidence of bleeding event hospitalisations was 3.8 (3.4 to 4.2) for current VKA exposure, 4.5 (3.7 to 5.5) for recent, 2.7 (2.2 to 3.3) for past and 2.9 (2.6 to 3.2) during non-use; 38% of intracranial bleeds and 6% of gastrointestinal bleeds were fatal. CONCLUSIONS: This population-based study from recent years provides a comprehensive characterisation of newly diagnosed patients with AF and incidence estimates of common outcomes with a focus on hospitalised events stratified by VKA exposure. This study will help to place future data on new oral anticoagulants into perspective.

Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers.Methods. The General Practice Research Database (GPRD) was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease.Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical), 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR) of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64–1.87); cardiac mortality 1.72 (95% CI: 1.42–2.07); SCD primary definition 5.76 (95% CI: 2.90–11.45); SCD secondary definition 2.15 (95% CI: 1.64–2.81); CHD 1.16 (95% CI: 0.94–1.44); and VA 1.16 (95% CI: 1.02–1.31). aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80–0.85); cardiac mortality 0.89 (95% CI: 0.82–0.97); and SCD secondary definition 0.76 (95% CI: 0.55–1.04).Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort.

Objective. Assess risk of cardiac events and mortality among users of olanzapine and other antipsychotics relative to nonusers. Methods. The General Practice Research Database was used to identify cohorts of antipsychotic users and nonusers with psychiatric illness. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Results. 183,392 antipsychotic users (including 20,954 olanzapine users) and 193,920 psychiatric nonusers were identified. There was a significantly higher rate of cardiac mortality (adjusted RR [aRR]: 1.53, CI, 1.12–2.09) in olanzapine users relative to psychiatric nonusers, consistent with findings for both atypical and typical antipsychotics. Relative to psychiatric nonusers, no increased risk of all-cause mortality was observed among olanzapine users (aRR: 1.04, CI, 0.93–1.17), but elevated all-cause mortality risk was observed when compared to all antipsychotic users (aRR: 1.75, CI, 1.64–1.87). There was no increased risk of CHD or VA among olanzapine users relative to psychiatric nonusers, consistent with findings for atypical but not typical antipsychotics. SCD cases were uncommon. Conclusions. Use of antipsychotic agents was associated with increased risk of all-cause and cardiac mortality. Patients treated with olanzapine were found to be at increased risk of cardiac mortality versus psychiatric nonusers.

Background Electronic health records from primary care are increasingly utilised as a resource for epidemiological research in cancer. The present study aimed to evaluate the validity of cancer diagnoses recorded in a primary care database compared with cancer registry data in England. Methods Eligible cancer codes were reviewed and agreed by two epidemiologists with experience in cancer and primary care. The eligible cohort comprised 42,556 participants, registered with English general practices in the General Practice Research Database (GPRD) that consented to cancer registry linkage, who presented with haematuria, haemoptysis, dysphagia or rectal bleeding or were diagnosed with cancer of the lung, urinary tract, oesophagus/stomach, or colon/rectum between 2002 and 2006. Cancer registry (CR) records were linked through a unique identifier by a third party. Cancer registry and primary care records were compared for cancer diagnosis, date of cancer diagnosis and death. Results There were 5,429 cancer diagnoses in GPRD and 5,710 in the CR, with 5,216 (91% of CR total) diagnosed in both sources. There were 494 (9%) diagnosed in CR but not in GPRD and 213 (4%) that were diagnosed in GPRD but not CR. The predictive value of a GPRD cancer diagnosis was 96% for lung cancer, 92% for urinary tract cancer, 96% for gastro-oesophageal cancer and 98% for colorectal cancer. ‘False negative’ primary care records were sometimes accounted for by registration end dates being shortly before cancer diagnosis dates. The median (interquartile range) difference in date of cancer diagnosis (CR minus GPRD) was -11 (-30 to 6) days. Death records were consistent for the two sources for 3,337/3,397 (99%) of cases. Conclusion Recording of cancer diagnosis and mortality in primary care electronic records is generally consistent with cancer registrations in England. Linkage studies must pay careful attention to selection of codes to define eligibility and timing of diagnoses in relation to beginning and end of record.

Background Epididymo-orchitis is a common urological presentation in men but recent incidence data are lacking. Guidelines for management recommend detailed investigation and treatment for sexually transmitted pathogens, such as Chlamydia trachomatis. Data from secondary care indicate that these guidelines are poorly followed. It is not known how epididymo-orchitis is managed in UK general practice. Aim To estimate the incidence of cases of epididymo-orchitis seen in UK general practice, and to describe their management. Design of study Cohort study. Setting UK general practices contributing to the General Practice Research Database (GPRD). Method Men, aged 15-60 years, consulting with a first episode of epididymo-orchitis between 30 June 2003 and 30 June 2008 were identified. All records within 28 days either side of the diagnosis date were analysed to describe the management of these cases (including location) and to compare this management with guidelines. Results A total of 12 615 patients with a first episode of epididymo-orchitis were identified. The incidence was highest in 2004-2005 (25/10 000) and declined in the later years of the study. Fifty-seven per cent (6943) of patients were managed entirely within general practice. Of these, over 92% received an antibiotic, with ciprofloxacin being the most common one prescribed. Only 18% received a prescription for doxycycline. Most men, including those under 35 years, had no investigation recorded and fewer than 3% had a test for chlamydia. Conclusion These results indicate low rates of specific testing and treatment for sexually transmitted infections in males who attend general practice with symptoms of epididymo-orchitis. There is a need for further research to understand the pattern of care delivered in general practice.

Background Studies of cancer incidence and early management will increasingly draw on routine electronic patient records. However, data may be incomplete or inaccurate. We developed a generalisable strategy for investigating presenting symptoms and delays in diagnosis using ovarian cancer as an example. Methods The General Practice Research Database was used to investigate the time between first report of symptom and diagnosis of 344 women diagnosed with ovarian cancer between 01/06/2002 and 31/05/2008. Effects of possible inaccuracies in dating of diagnosis on the frequencies and timing of the most commonly reported symptoms were investigated using four increasingly inclusive definitions of first diagnosis/suspicion: 1. "Definite diagnosis" 2. "Ambiguous diagnosis" 3. "First treatment or complication suggesting pre-existing diagnosis", 4 "First relevant test or referral". Results The most commonly coded symptoms before a definite diagnosis of ovarian cancer, were abdominal pain (41%), urogenital problems(25%), abdominal distension (24%), constipation/change in bowel habits (23%) with 70% of cases reporting at least one of these. The median time between first reporting each of these symptoms and diagnosis was 13, 21, 9.5 and 8.5 weeks respectively. 19% had a code for definitions 2 or 3 prior to definite diagnosis and 73% a code for 4. However, the proportion with symptoms and the delays were similar for all four definitions except 4, where the median delay was 8, 8, 3, 10 and 0 weeks respectively. Conclusion Symptoms recorded in the General Practice Research Database are similar to those reported in the literature, although their frequency is lower than in studies based on self-report. Generalisable strategies for exploring the impact of recording practice on date of diagnosis in electronic patient records are recommended, and studies which date diagnoses in GP records need to present sensitivity analyses based on investigation, referral and diagnosis data. Free text information may be essential in obtaining accurate estimates of incidence, and for accurate dating of diagnoses.

Objectives To determine the diagnostic accuracy of the measurement of plasma B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) in patients referred by their general practitioners (GPs) with symptoms suggestive of heart failure. Additionally, to compare the diagnostic accuracy of the resting 12-lead electrocardiogram (ECG) with that of the peptides. Design A diagnostic accuracy study. Setting Rapid-access heart failure clinics in five hospitals. Participants 306 patients referred by their GPs with suspected heart failure. Main outcome measures Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios for BNP, NTproBNP and the ECG for the diagnosis of heart failure. Area under the receiver operating characteristics (ROC) curves for the two natriuretic peptides. Results The diagnosis of heart failure was confirmed in 104 (34%) patients. The area under the ROC curve was 0.84 [95% CI 0.79−0.89] for BNP and 0.85 [0.81−0.90] for NTproBNP. At the manufacturers' recommended decision cut-points, NTproBNP provided a higher NPV (0.97) than BNP (0.87), but at lower PPV (0.44 versus 0.59). An abnormal ECG did not add any further predictive value to that of NTproBNP. Conclusions We have confirmed the value of the measurement of plasma BNP or NTproBNP as a ‘rule-out’ test for heart failure in patients currently referred by GPs to rapid access diagnostic clinics. A simple classification of the 12-lead ECG into ‘normal’ or ‘abnormal’ adds little value to ruling out heart failure in these circumstances. Further work is necessary to establish the best decision cut-points for use in clinical practice.

Abstract 4223 Objective: To describe the characteristics of patients with recently diagnosed atrial fibrillation (AF) and to estimate the incidence of vascular outcomes in patients with AF. Methods: A cohort study in newly diagnosed AF patients (2005–2010) without heart valve replacement/problems was performed in the General Practice Research Database (GPRD), UK. Linked data to the Hospital Episode Statistics (HES) and death certificates from the Office of National Surveillance (ONS) were included. Current vitamin K antagonists (VKA) treatment was defined as a valid prescription/INR measurement during the last 28 days, recent as a treatment period from 28 to 90 days after the last prescription/INR measurement, and past treatment as more than 90 days after last treatment/INR measurement. No treatment was the time between diagnosis of AF and first prescription/INR measurement, or the whole follow-up for patients that have never been treated. Vascular outcomes – first ever recorded – were assessed as primary hospital admission diagnosis recorded in HES, i.e. myocardial infarction (MI), stroke, and systemic peripheral arterial embolism (SPAE). Results: Data from 16,513 AF patients could be linked; 48% were female, the mean age (std) was 74 (12) years, the median duration of follow-up was 1.7 years (range 0–5). According to CHADS2 score 21% were at low risk, 65% at moderate and 14% at high risk for stroke. Overall 55.8% of the patients had at least one period of VKA use. Overall, 1,151 vascular events were recorded (403 MIs, 716 strokes, 68 SPAE). The incidence (per 100 patient years (95% CIs)) of vascular events was 3.8 (3.5 – 4.0), 1.3 (1.2 – 1.4) for MI, 2.3 (2.1 – 2.5) for stroke and 0.2 (0.2 – 0.3) for SPAE. Stratification by period of VKA use resulted in incidences for current, recent, past and non users for MI of 0.7 (0.6 – 0.9), 0.7 (0.4 – 1.2), 1.1 (0.8 – 1.5), 1.9 (1.7 – 2.1), for stroke of 0.9 (0.8 – 1.1), 2.2 (1.6 – 2.9), 2.4 (1.9 – 2.9), 3.4 (3.1 – 3.7), and for SPAE of 0.2 (0.2 – 0.3), 0.2 (0.1 – 0.3), 0.3 (0.1 – 0.6), 0.2 (0.1 – 0.3), 0.2 (0.2 – 0.3). Conclusion: In this cohort study, a trend towards lower incidences of vascular events, specifically stroke and MI, was detected during VKA use compared to past/no use. No causal conclusions can be drawn from these crude incidence estimates, but the trends are in line with the clinical expectations of anticoagulation in AF patients. Disclosures: Clemens: Boehringer Ingelheim Pharma GmbH & Co. KG: Employment. Diana:Boehringer Ingelheim GmbH: Employment. Bartels:Boehringer Ingelheim GmbH: Employment.

Background Asthma management guidelines recommend a stepwise approach to instituting and adjusting anti-inflammatory controller therapy for children with asthma. The objective of this retrospective observational study was to describe prescribing patterns of asthma controller therapies for children in a primary care setting. Methods Data from the UK General Practice Research Database were examined for children with recorded asthma or recurrent wheezing who, from September 2006 through February 2007, were ≤ 14 years old at the time of a first asthma controller prescription after ≥ 6 months without a controller prescription. We evaluated demographic characteristics, asthma duration, comorbidities, asthma-related health care resource use, and prescribed daily dose of controller medication. In addition, physicians for 635 randomly selected patients completed a survey retrospectively classifying asthma severity at the prescription date and describing therapy and health care utilization for 6 prior months. Results We identified 10,004 children, 5942 (59.4%) of them boys, of mean (SD) age of 8.0 (3.8) years. Asthma controller prescriptions were for inhaled corticosteroid (ICS) monotherapy for 9059 (90.6%) children; ICS plus long-acting β2-agonist (LABA) for 698 (7.0%); leukotriene antagonist monotherapy for 91 (0.9%); ICS plus leukotriene antagonist for 55 (0.6%); and other therapy for 101 (1.0%), including 45 (0.45%) children who were prescribed LABA as monotherapy. High doses of ICS (> 400 μg) were prescribed for 44/2140 (2.1%) children < 5 years old and for 420/7452 (5.6%) children ≥ 5 years. Physicians reported asthma severity as intermittent for 346/635 (55%) patients and as mild, moderate, and severe persistent for 159 (25%), 71 (11%), and 11 (2%), respectively (severity data missing for 48 [8%]). The baseline characteristics and controller therapy prescriptions of the survey cohort were similar to those of the full cohort. Conclusions Physician classifications of asthma severity did not always correspond to guideline recommendations, as leukotriene receptor antagonists were rarely used and high-dose ICS or add-on LABA was prescribed even in intermittent and mild disease. In UK primary care, monotherapy with ICS is the most common controller therapy at all levels of asthma severity.