Risk of Mortality (including Sudden Cardiac Death) and Major Cardiovascular Events in Users of Olanzapine and Other Antipsychotics: A Study with the General Practice Research Database.

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

Risk of mortality (including sudden cardiac death) and major cardiovascular events in atypical and typical antipsychotic users: a study with the general practice research database.

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

Use of Primary Care Data in Research and Pharmacovigilance: Eight Scenarios Where Prescription Data are Absent

Abstract: 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

Cardiovascular risks in smokers treated with nicotine replacement therapy : a historical cohort study

The authors would like to thank Julie von Ziegenweidt, Daina Lim, and Muzammil Ali, who assisted with the analysis. Many thanks to Alison Chisholm for contribution to the study design and critical review of the manuscript, Derek Skinner for preparation of data for analysis, Rosalind Bonomally, and Martina Stagno d’Alcontres for medical writing. The study data were provided by the CPRD without charge (via a Medical Research Council study grant). The analysis was conducted by the Observational and Pragmatic Research Institute Pte Ltd, in collaboration with the Respiratory Effectiveness Group (REG), and funded by the Observational and Pragmatic Research Institute Pte Ltd. Manuscript costs were covered by the REG.Peer reviewedPublisher PD

Determining the date of diagnosis – is it a simple matter? The impact of different approaches to dating diagnosis on estimates of delayed care for ovarian cancer in UK primary care

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

Adherence to NICE guidance on glucagon-like peptide-1 receptor agonists among patients with type 2 diabetes mellitus: an evaluation using the Clinical Practice Research Datalink

<div><p></p><p><b>Aims:</b></p><p>To assess adherence to the UK’s 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).</p><p><b>Research design and methods:</b></p><p>A retrospective cohort study of 7133 primary care patients ≥40 years with a first prescription for a GLP-1 receptor agonist following publication of NICE guideline/guidance. Patient characteristics and levels of clinical monitoring were assessed using descriptive analyses.</p><p><b>Main outcome measures:</b></p><p>Main outcomes were the proportion of patients initiating GLP-1 receptor agonists as part of NICE-recommended dual- or triple-therapy regimens; the proportions meeting NICE triple therapy initiation criteria (glycosylated hemoglobin [HbA1c] ≥7.5% and body mass index [BMI] ≥35 kg/m²) and the proportions continuing GLP-1 receptor agonist at 6 months according to NICE recommendations.</p><p><b>Results:</b></p><p>Mean age at initiating GLP-1 receptor agonists 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 agonists 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 NICE’s target reductions for both HbA1c and body weight. About 8% of patients continuing exenatide as triple therapy (<i>N</i> = 243) achieved both targets.</p><p><b>Conclusions:</b></p><p>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-1 receptor agonists.</p></div

Risk of complications and mortality following recurrent and non-recurrent Clostridioides (Clostridium) difficile infection: a retrospective, observational, database study in England

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 6,862 patients with HA-CDI and 13,724 without CDI. Median age was 81.0 (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, 1,140 (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

Management of first-episode pelvic inflammatory disease in primary care: results from a large UK primary care database

Background Prompt and effective treatment of pelvic inflammatory disease (PID) may help prevent long-term complications. Many PID cases are seen in primary care but it is not known how well management follows recommended guidelines. Aim To estimate the incidence of first-episode PID cases seen in UK general practice, describe their management, and assess its adequacy in relation to existing guidelines. Design of study Cohort study. Setting UK general practices contributing to the General Practice Research Database (GPRD). Method Women aged 15 to 40 years, consulting with a first episode of PID occurring between 30 June 2003 and 30 June 2008 were identified, based on the presence of a diagnostic code. The records within 28 days either side of the diagnosis date were analysed to describe management. Results A total of 3797 women with a first-ever coded diagnosis of PID were identified. Incidence fell during the study period from 19.3 to 8.9/10 000 person-years. Thirty-four per cent of cases had evidence of care elsewhere, while 2064 (56%) appeared to have been managed wholly within the practice. Of these 2064 women, 34% received recommended treatment including metronidazole, and 54% had had a Chlamydia trachomatis test, but only 16% received both. Management was more likely to follow guidelines in women in their 20s, and later in the study period. Conclusion These analyses suggest that the management of PID in UK primary care, although improving, does not follow recommended guidelines for the majority of women. Further research is needed to understand the delivery of care in general practice and the coding of such complex syndromic conditions