Ana Ruigómez

Validity of the General Practice Research Database

The United Kingdom General Practice Research Database (GPRD) is an office‐based, computer‐generated, medical resource designed from its inception to be used for epidemiologic research. A distinct version of the GPRD is maintained by the Boston Collaborative Drug Surveillance Program and has been the source of more than 130 scientific articles primarily addressing drug safety issues. We reviewed evidence related to the validity of the GPRD. Specifically, with our extensive experience with this automated database, we evaluated the quality and completeness of the data that it contains.

Natural history of gastro‐oesophageal reflux disease diagnosed in general practice

Background : Cross‐sectional studies indicate that gastro‐oesophageal reflux disease symptoms have a prevalence of 10–20% in Western countries and are associated with obesity, smoking, oesophagitis, chest pain and respiratory disease.

Incidence of chronic atrial fibrillation in general practice and its treatment pattern

The object of this article was to estimate the incidence rate of chronic atrial fibrillation (AF) in a general practice setting, to identify factors predisposing to its occurrence, and to describe treatment patterns in the year following the diagnosis. The method used was a population-based cohort study using the General Practice Research Database (GPRD) in the UK. We identified patients aged 40-89 years with a first ever recorded diagnosis of AF. The diagnosis was validated through a questionnaire sent to the general practitioners. A nested case-control analysis was performed to assess risk factors for AF using 1,035 confirmed incident cases of chronic AF and a random sample of 5,000 controls from the original source population. The incidence rate of chronic AF was 1.7 per 1,000 person-years, and increased markedly with age. The age adjusted rate ratio among males was 1.4 (95% CI 1.2-1.6). The major risk factors were age, high BMI, excessive alcohol consumption, and prior cardiovascular comorbidity, in particular, valvular heart disease and heart failure. Digoxin was used in close to 70% of the patients, and close to 15% did not receive any antiarrhythmic treatment. Close to 40% did not receive either warfarin or aspirin in the 3 months period after the diagnosis. Among the potential candidates for anticoagulation only 22% of those aged 70 years or older were prescribed warfarin in comparison to 49% among patients aged 40-69 years. Chronic AF is a disease of the elderly, with women presenting a lower incidence rate than men specially in young age. Age, weight, excessive alcohol consumption, and cardiovascular morbidity were the main independent risk factors for AF. Less than half of patients with chronic AF and no contraindications for anticoagulation received warfarin within the first trimester after the diagnosis.

Geriatric Drug Therapy and Healthcare Utilization in the United Kingdom

OBJECTIVE: To describe the use of prescription drug therapy, especially polypharmacy, in an elderly general population; to relate that use to age, gender, and different types of healthcare utilization; and to investigate the influence of selection of different time windows on the result of the quantity as well as the categories of drugs used. METHODS: Data on a sample of 5000 patients aged 65–90 years in 1996 were derived from the General Practice Research Database (GPRD). The population covered by GPRD is broadly representative of the UK population treated in general practice. Drug use was assessed using 2 time windows — Current use of individual drugs on a random day (index date) and 1 month following the index date. Healthcare utilization was analyzed by use of information on visits to general practitioners (GPs), hospitalizations, and referrals to specialists. RESULTS: Women used more drugs than men; however, the prevalence of polypharmacy, defined as concomitant use of ≥5 drugs, was similar in both genders. The most frequently used therapeutic groups were cardiovascular, central nervous, and gastrointestinal system drugs. Almost 80% of both women and men visited a GP at least once a year. Overall, women used more ambulatory care services and men were hospitalized more often. Use of random date compared with 1-month period resulted in a significant underestimation of the amount of drugs used for acute conditions and, consequently, the risk of polypharmacy. CONCLUSIONS: The overall results confirm the findings in earlier studies suggesting that the GPRD might be a useful tool in further studies on prescription drug use among elderly persons. More information on the appropriateness of drug use is needed to prevent overuse as well as underuse of medications among the elderly.

Detection of Colorectal Tumor and Inflammatory Bowel Disease during Follow-up of Patients with Initial Diagnosis of Irritable Bowel Syndrome

BACKGROUND We wanted to estimate the incidence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) in the general population, and the detection of colorectal tumor (CRT) and inflammatory bowel disease (IBD) after the diagnosis of IBS and FD. METHODS Patients aged 20-79 years newly diagnosed with IBS (N = 2956) or FD (N = 9900), together with a comparison cohort randomly sampled from the general source population, were followed-up during a mean time of 3 years. RESULTS We found an overall incidence of 10.3 per 1000 person-years for FD and 2.6 per 1000 person-years for IBS. There was a greater prevalence of depression, stress, fatigue, and pain disorders among IBS and FD patients than in the general population. During the 1st year after a diagnosis of IBS the cumulative risk of detecting CRT was close to 1% in IBS patients. After the 1st year the risk of CRT in IBS patients was close to that in the general population. We found a significantly increased risk of detecting IBD among patients initially diagnosed as having IBS (relative risk (RR), 16.3; 95% confidence interval (CI), 6.6-40.7), which was constant during all the follow-up period. No association was found between dyspepsia and CRT, or IBD. CONCLUSION IBS and FD shared some comorbidity features, yet demographics and incidence rates were different. Unlike the detection of colorectal tumor, the excess risk of IBD after an initial diagnosis of IBS was cumulatively increased during all the follow-up period. The continuously increased risk of IBD detection in IBS patients favors a true association between IBS and IBD.Background: We wanted to estimate the incidence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) in the general population, and the detection of colorectal tumor (CRT) and inflammatory bowel disease (IBD) after the diagnosis of IBS and FD. Methods: Patients aged 20-79 years newly diagnosed with IBS (N = 2956) or FD (N = 9900), together with a comparison cohort randomly sampled from the general source population, were followed-up during a mean time of 3 years. Results: We found an overall incidence of 10.3 per 1000 person-years for FD and 2.6 per 1000 person-years for IBS. There was a greater prevalence of depression, stress, fatigue, and pain disorders among IBS and FD patients than in the general population. During the 1st year after a diagnosis of IBS the cumulative risk of detecting CRT was close to 1% in IBS patients. After the 1st year the risk of CRT in IBS patients was close to that in the general population. We found a significantly increased risk of detecting IBD among patients initially diagnosed as having IBS (relative risk (RR), 16.3; 95% confidence interval (CI), 6.6-40.7), which was constant during all the follow-up period. No association was found between dyspepsia and CRT, or IBD. Conclusion: IBS and FD shared some comorbidity features, yet demographics and incidence rates were different. Unlike the detection of colorectal tumor, the excess risk of IBD after an initial diagnosis of IBS was cumulatively increased during all the follow-up period. The continuously increased risk of IBD detection in IBS patients favors a true association between IBS and IBD.

Incidence of newly diagnosed heart failure in UK general practice.

To estimate the incidence rate of heart failure in the general population and to assess risk factors associated with the occurrence of newly diagnosed heart failure.

Predictors and prognosis of paroxysmal atrial fibrillation in general practice in the UK

BackgroundNatural history of paroxysmal atrial fibrillation (AF) is not very well documented. Clinical experience suggests that paroxysmal AF could progress to chronic AF with estimates ranging between 15 and 30% over a period of 1–3 years. We performed an epidemiologic study to elucidate the natural history of paroxysmal AF, this study estimated its incidence in a general practice setting, identified associated factors and analyzed the progression into chronic AF as well as the mortality rate.MethodsUsing the UK General Practice Research Database (GPRD), we identified patients aged 40–89 years with a first-recorded episode of paroxysmal AF during 1996. Risk factors were assessed using 525 incident paroxysmal AF cases confirmed by the general practitioner (GP) and a random sample of controls. We follow-up paroxysmal AF patients and estimated their mortality rate and progression to chronic AF.ResultsThe incidence of paroxysmal AF was 1.0 per 1,000 person-years. Major risk factors for paroxysmal AF were age and prior valvular heart disease, ischaemic heart disease, heart failure and hyperthyroidism. During a mean follow-up of 2.7 years, 70 of 418 paroxysmal AF patients with complete information progressed to chronic AF. Risk factors associated with progression were valvular heart disease (OR 2.7, 95% CI 1.2–6.0) and moderate to high alcohol consumption (OR 3.0, 95% CI 1.1–8.0). Paroxysmal AF patients did not carry an increased risk of mortality, compared to an age and sex matched sample of the general population. There was a suggestion of a small increased risk among patients progressing to chronic AF (RR 1.5, 96% CI 0.8–2.9).ConclusionParoxysmal AF is a common arrhythmia in the general practice setting, increasing with age and commonly associated with other heart diseases. It sometimes is the initial presentation and then progress to chronic AF. A history of valvular heart disease and alcohol consumption are associated with this progression.

Esophageal Stricture: Incidence, Treatment Patterns, and Recurrence Rate

OBJECTIVES:We aimed to determine the incidence, natural history, and recurrence rate of esophageal stricture diagnosed in primary care.METHODS:From the U.K. General Practice Research Database, we identified patients with a stricture diagnosis recorded between 1994 and 2000. Diagnoses were confirmed by general practitioner-completed questionnaires. Patients with stricture were compared to an age- and sex-matched sample of controls from the original source population. We estimated the incidence of stricture, potential risk factors, and comorbidities, and relative risk (RR) for subsequent stricture recurrence and mortality.RESULTS:The incidence of esophageal stricture was 1.1 per 10,000 person-years and increased markedly with age. Incidence of stricture decreased from 1994 to 2000, concomitant with a substantial increase in proton pump inhibitor (PPI) use. The majority of stricture cases (68%) were peptic. Prior dysphagia, gastroesophageal reflux disease (GERD), hiatus hernia, peptic ulcer disease, and heavy alcohol use were associated with an increased risk of stricture. The rate of stricture recurrence was 11.1 per 100 person-years. Risk of recurrence associated with long-term PPI use adjusting for other factors was 0.6 (95% CI 0.3–1.1). Mortality in patients with peptic stricture was similar to that in the control population.CONCLUSIONS:Esophageal stricture is a rare event, and most cases in primary care are peptic strictures. Prior GERD, hiatus hernia, and peptic ulcer are associated with an increased risk of peptic stricture. Incidence of stricture decreased from 1994 to 2000.

Rheumatoid arthritis in UK primary care: incidence and prior morbidity

Objectives: To estimate the incidence of rheumatoid arthritis (RA) in primary care and to investigate associations with consultation behaviour, risk factors, and comorbidities, using the UK General Practice Research Database (GPRD). Methods: Subjects with a first‐ever diagnosis of RA between 1 January 1996 and 31 December 1997 (n = 579) were identified from a cohort of 1 206 918 subjects aged 20−79 years without cancer. Controls from the same cohort were frequency‐matched to the RA group by age, sex, and calendar year (n = 4234). Odds ratios (ORs) and 95% confidence intervals (CIs) of being diagnosed with RA in association with a range of factors were estimated using logistic regression analysis. Results: RA incidence was 0.15 per 1000 person‐years, was higher in women than in men, and increased with age in both sexes. Consultations and use of non‐steroidal anti‐inflammatory drugs (NSAIDs) prior to diagnosis were increased in subjects with RA. An increased risk of RA was observed in association with anaemia in the previous year (OR 2.63, 95% CI 1.54–4.48) and with smoking (1.33, 1.07–1.67). A decreased risk of RA was observed in association with infectious diseases (0.68, 0.50–0.94) and pregnancy in the previous year (0.22, 0.06–0.77), diabetes (0.45, 0.26–0.78), and hypertension (0.74, 0.57–0.94). We found no association with alcohol intake, obesity, or use of low‐dose aspirin, oral contraceptives, or hormone replacement therapy (HRT). Conclusions: Smoking was identified as the only significant lifestyle‐related risk factor for RA. Infection in the previous year was associated with a reduced likelihood of RA.

A Review of Epidemiologic Research on Drug‐Induced Acute Liver Injury Using the General Practice Research Data Base in the United Kingdom

Drug hepatotoxicities have been evaluated in case histories, surveys based on retrospective record reviews, and spontaneous adverse drug reactions reported to national pharmacovigilance systems, but in relatively few epidemiologic studies. To identify and quantify the risk of acute liver injury associated with individual drugs, we reviewed and integrated all the published epidemiologic research on the subject. The source population for the eight studies was general population registered on a single large general practice‐based computerized data base. All were retrospective cohort studies, but some had a case‐control design nested within the source cohort. Participants were selected according to their use of selected agents (nonsteroidal antiinflammatory drugs [NSAIDs], antibiotics, acid‐suppressing drugs, other drugs suspected of being hepatotoxic) during the study period. Among the agents, we found a group of important hepatotoxic drugs with an associated incidence rate of acute liver injury greater than 100/100,000 users, including chlorpromazine and isoniazid. Agents with less risk but greater than 10/100,000 users were amoxicillin‐clavulanic acid and cimetidine. A third group of drugs had an associated incidence rate of acute liver injury of less than 10/100,000 users. Our results provide evidence of relative safety for commonly administered agents such as NSAIDs, amoxicillin, omeprazole, and ranitidine. We also quantified important suspected liver toxicity, providing a reasonable precise risk estimate of clinical liver injury associated with chlorpromazine, isoniazid, and amoxicillin‐clavulanic acid.