The reporting and diagnosis of uterine fibroids in the UK: an observational study.

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.

Migraine and risk of hemorrhagic stroke: a study based on data from general practice.

BACKGROUND: We investigated the association between hemorrhagic stroke and migraine using data from The Health Improvement Network database. FINDINGS: We ascertained 1,797 incident cases of intracerebral hemorrhage (ICH) and 1,340 of subarachnoid hemorrhage (SAH). Density-based sampling was used to select 10,000 controls free from hemorrhagic stroke. Using unconditional logistic regression models, we calculated the risk of hemorrhagic stroke associated with migraine, adjusting for age, sex, calendar year, alcohol, body mass index, hypertension, previous cerebrovascular disease, oral contraceptive use, and health services utilization.The risk (odds ratio [OR]) of ICH among migraineurs was 1.2 (95% confidence interval [CI] 0.9-1.5), and of SAH was (1.2, 95% CI 0.9-1.5). The association with ICH was stronger for migraine diagnosed ≥20 years prior to ICH (OR 1.6, 95% CI 1.0-2.4), but not with SAH (OR 1.1, 95% CI 0.6-2.1). In analyses stratified by migraine type and gender, the OR of ICH in women with migraine with aura was 1.7 (95% CI 0.9-3.4) and the corresponding OR of SAH in women was 1.2 (95% CI 0.6-2.3). CONCLUSION: No clear increased risk of ICH or SAH was observed in migraineurs.

Anaphylaxis epidemiology in patients with and patients without asthma: a United Kingdom database review.

BACKGROUND: There are currently limited data regarding the epidemiology of anaphylaxis. OBJECTIVE: To estimate the incidence of anaphylaxis from all causes, to explore the variety of diagnoses that may predispose to an anaphylactic episode, and to estimate the rate of recurrence of anaphylaxis in patients with no asthma, nonsevere asthma, and severe asthma. METHODS: The Health Improvement Network database provided data on individuals 10 to 79 years old who had been enrolled for at least 1 year with a general practitioner in the United Kingdom and had at least 1 health contact in the year before entering the study. RESULTS: Anaphylaxis incidence rates (per 100,000 person-years) were 21.28 (95% CI, 17.64-25.44) and 50.45 (95% CI, 44.67-56.76) in the no asthma and overall asthma cohorts, respectively. Risk of anaphylaxis was greater in the nonsevere asthma (relative risk, 2.07; 95% CI, 1.65-2.60) and severe asthma (relative risk, 3.29; 95% CI, 2.47-3.47) subgroups compared with the no asthma cohort. The incidence rate of anaphylaxis was higher in women than men (22.65 vs 19.56 per 100,000 person-years). Within the overall asthma population, patients at significantly increased risk of anaphylaxis included those with allergic rhinitis or atopic dermatitis, and current users of antihistamines, oral steroids, or antibiotics (compared with nonusers). Drug and food allergies were the most common known causes of anaphylaxis. CONCLUSION: Patients with asthma have a greater risk of anaphylaxis than those without asthma, and the risk is greater in severe than nonsevere asthma. Women are at higher risk of anaphylaxis than men, especially those with severe asthma.

Public health impact of low-dose aspirin on colorectal cancer, cardiovascular disease and safety in the UK - Results from micro-simulation model.

BACKGROUND: Low-dose aspirin therapy reduces the risk of cardiovascular disease and may have a positive effect on the prevention of colorectal cancer. We evaluated the population-level expected effect of regular low-dose aspirin use on cardiovascular disease (CVD), colorectal cancer (CRC), gastrointestinal bleeding, symptomatic peptic ulcers, and intracranial hemorrhage, using a microsimulation study design. METHODS: We used individual-level state transition modeling to assess the impact of aspirin in populations aged 50-59 or 60-69 years old indicated for low-dose aspirin usage for primary or secondary CVD prevention. Model parameters were based on data from governmental agencies from the UK or recent publications. RESULTS: In the 50-59 years cohort, a decrease in incidence rates (IRs per 100 000 person years) of non-fatal CVD (-203 and -794) and fatal CVD (-97 and-381) was reported in the primary and secondary CVD prevention setting, respectively. The IR reduction of CRC (-96 and -93) was similar for primary and secondary CVD prevention. The IR increase of non-fatal (116 and 119) and fatal safety events (6 and 6) was similar for primary and secondary CVD prevention. Similar results were obtained for the 60-69 years cohort. CONCLUSIONS: The decrease in fatal CVD and CRC events was larger than the increase in fatal safety events and this difference was more pronounced when low-dose aspirin was used for secondary compared to primary CVD prevention. These results provide a comprehensive image of the expected effect of regular low-dose aspirin therapy in a UK population indicated to use aspirin for CVD prevention.

Validation of ischemic cerebrovascular diagnoses in the health improvement network (THIN).

PURPOSE: To evaluate the validity of recorded diagnoses of ischemic cerebrovascular events requiring hospitalization within The Health Improvement Network (THIN) UK primary care database. METHODS: We identified 15 397 individuals aged 40-84 years with a first recorded ischemic event in 2000-2004. Of these, 4239 had a code suggestive of a hospitalization within 2 weeks of the event. A three-step strategy was used to validate the records of these patients: manual review of computerized medical records excluding free-text comments; manual review including free-text comments (which include information gained from specialists, hospital discharge letters and results of diagnostic tests) of a random sample of possible cases (n = 300) and non-cases (n = 100); and review of full medical records of this random sample and a questionnaire completed by their primary care physician. The positive predictive value (PPV) of each step was calculated. The confirmation rate was used to estimate incidence in the general population. RESULTS: After step 1, 3447 individuals were classified as possible cases and 792 were excluded as non-cases. After step 2, 82% of possible cases were still classified as such. Step 3 showed that inclusion of free-text comments increased the PPV of a diagnosis from 76 to 86%. The weighted incidence of hospitalized ischemic cerebrovascular events was 1.73 per 1000 person-years (95% CI:1.68-1.77). CONCLUSIONS: THIN demonstrates a high validity for the study of ischemic cerebrovascular events when reviewing computer records with additional free-text comments. Accuracy of hospitalization status was not as well recorded.

Acid-suppressive drugs and community-acquired pneumonia.

BACKGROUND: Acid suppression may increase the risk of community-acquired pneumonia. We investigated this association in the United Kingdom primary care system taking account of the potential for confounding by indication. METHODS: We identified patients aged 20-79 years in The Health Improvement Network database with a new diagnosis of pneumonia between 2000 and 2005 (n = 7297). Cases were validated by manual review and compared with age- and sex-matched controls (n = 9993). Using unconditional logistic regression, we estimated the relative risk (RR) of pneumonia associated with current use of acid-suppressive drugs compared to nonuse. RESULTS: Newly diagnosed community-acquired pneumonia was increased with current use of proton pump inhibitors (RR = 1.16 [95% confidence interval 1.03-1.31]) but not H2-receptor antagonists (0.98 [0.80-1.20]). An increased risk of pneumonia was evident only in the first 12 months of treatment with proton pump inhibitors. There was some evidence of a dose response. Among patients taking proton pump inhibitors for less than 1 year, the risk of community-acquired pneumonia was stronger when current use was for dyspepsia or peptic ulcer (1.73 [1.29-2.34]) than for gastroesophageal reflux disease or prevention of upper gastrointestinal injury associated with aspirin or nonsteroidal anti-inflammatory drugs (1.22 [0.97-1.52]). CONCLUSIONS: We observed a small increase in the risk of community-acquired pneumonia associated with current proton pump inhibitor use, particularly during the first 12 months of treatment and at higher doses. This may be due in part to the underlying indication.

The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada.

BACKGROUND: Meta-analyses of observational studies show variability in the risk of acute myocardial infarction (AMI) among non-steroidal anti-inflammatory drugs (NSAIDs), with an increase in risk for rofecoxib and diclofenac, and no increase in risk for celecoxib, naproxen, or ibuprofen. METHODS AND RESULTS: We identified a cohort of 364 658 individuals aged 40-84 years who were enrolled in Saskatchewan Health, Canada, from 15 November 1999 to 31 December 2001. A nested case-control analysis compared 3252 incident cases of hospitalized AMI and out-of-hospital CHD deaths with 20 002 controls randomly sampled from the cohort. The incidence of AMI/CHD was 5.1 per 1000 person-years (95%CI: 5.0-5.3). The adjusted ORs (95%CI) of AMI/CHD in current users of individual NSAIDs compared with non-use were: celecoxib (1.11; 0.84-1.47), rofecoxib (1.32; 0.91-1.91), diclofenac (1.02; 0.75-1.38), naproxen (1.57; 0.98-2.52), ibuprofen (1.59; 0.88-2.89), and indomethacin (1.34; 0.81-2.19). Long-term use of rofecoxib was compatible with an increased risk (OR = 1.46; 0.97-2.22) while estimates of other individual NSAIDs were close to unity. Overall NSAID use was associated with a 30% increased risk of nonfatal AMI but was absent for fatal AMI/CHD. CONCLUSIONS: This study showed a modest increased risk of AMI/CHD with various traditional NSAIDs and COX-2 inhibitors. Confidence intervals of estimated ORs included the null value for most comparisons. The study confirmed that the differentiation between traditional NSAIDs and COX-2 inhibitors is not a reliable tool for predicting cardiovascular risk associated with NSAIDs.

Irritable bowel syndrome and gastroesophageal reflux disease in primary care: is there a link?

Population-based studies have shown that gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) coexist more commonly than expected by chance. We aimed to investigate the relationship between GERD and IBS in primary care. The General Practice Research Database was used to identify patients with a first diagnosis of GERD (n=6,421) or IBS (n=2,932). Patients were followed up for 12 months after diagnosis to investigate the incidence of IBS among GERD patients and GERD among IBS patients. The relative risk (RR) of developing IBS was 3.5 (95% CI: 2.3-5.4) in the GERD cohort compared with the comparison cohort. The RR of developing GERD was 2.8 (95% CI: 1.7-4.9) in the IBS cohort compared with the comparison cohort. A first diagnosis of either IBS or GERD significantly increases the risk of a subsequent diagnosis of the other condition.

Use of oral corticosteroids and the risk of acute myocardial infarction.

INTRODUCTION: A few epidemiological studies suggested an increased coronary heart disease (CHD) risk with high doses of oral corticosteroids. METHODS: We performed a cohort study with nested case-control analysis to estimate the risk of acute myocardial infarction (AMI) associated with the use of oral corticosteroids by dose and duration. We followed-up 404,183 persons, 50-84 years old, without cancer from the general UK population. After validation of a random sample (confirmation rate of 96%), we included 4795 hospitalised cases of AMI or CHD deaths. We randomly sampled 20,000 controls, frequency matched by sex, age and calendar year. Relative risks were estimated using unconditional logistic regression. RESULTS: The adjusted OR for AMI in current users of oral corticosteroids compared to non-users was 1.42 (95% CI: 1.17-1.72). The risk during the first 30 days of use (OR=2.24; 95% CI: 1.56-3.20) was greater than with longer duration (OR=1.22; 95% CI 0.98-1.52). The risk was more pronounced (OR=2.15; 95% CI 1.45-3.14) among users of prednisolone equivalent doses >10mg/day. The dose effect was observed both among patients with and without CHD or COPD/asthma. CONCLUSION: These results suggest a small increased risk of AMI with oral corticosteroid use with a greater risk observed among users of high corticosteroid dose.

Gastroesophageal reflux disease and asthma: a longitudinal study in UK general practice.

STUDY OBJECTIVES: Gastroesophageal reflux disease (GERD) and asthma are common causes for consultation in primary care, but the relationship between the two remains unclear. The aim of our study was to investigate the temporal relationship between first diagnoses of GERD and asthma in general practice. METHODS: We used the UK General Practice Research Database to identify a cohort of patients with a first diagnosis of GERD (n = 5,653) and another cohort of patients with a first diagnosis of asthma (n = 9,712) during 1996, which we compared with age-matched and sex-matched control cohorts drawn from the general population without either diagnosis. We investigated the incidence of a GERD diagnosis among the asthma patients and control subjects, and the incidence of an asthma diagnosis among the GERD patients and control subjects during a mean follow-up period of 3 years. We calculated the relative risk (RR) of these diagnoses using Cox regression analysis and examined the risk associated with medication use using nested case-control analysis. RESULTS: The incidence rates of GERD and asthma among the control cohorts were 4.4 and 3.8 per 1,000 person-years, respectively. During the follow-up period, the RR of an incident asthma diagnosis in patients with a new diagnosis of GERD was 1.2 (95% confidence interval [CI], 0.9 to 1.6), while the RR of an incident GERD diagnosis among patients with a new diagnosis of asthma was 1.5 (95% CI, 1.2 to 1.8) after adjustment for age, sex, smoking, prior comorbidity, and number of health-care contacts. This increased risk was mainly seen during the first year of follow-up. The prior use of prescription medications for asthma and GERD had no significant effects on the risk of GERD and asthma diagnosis, respectively. CONCLUSIONS: Patients with asthma are at a significantly increased risk of developing GERD, mainly during the first year following diagnosis. A nonsignificant increase in the risk of developing asthma was evident among GERD patients. The relationship between GERD and asthma warrants further investigation.

Incidence of serious upper gastrointestinal bleeding/perforation in the general population: review of epidemiologic studies.

The object of this study was to quantify the incidence of serious upper gastrointestinal complications among nonusers of nonsteroidal anti-inflammatory drugs (NSAIDs). Systematic review of epidemiologic studies published between 1980 and 2000 that provided data on the incidence of upper gastrointestinal bleeding, perforation, or other upper gastrointestinal tract event resulting in death, hospitalization, or visit to a specialist among nonusers of nonsteroidal anti-inflammatory drugs. The authors calculated summary incidence rates and analyzed heterogeneity among results according to outcome definition, population characteristics, and methodology of primary studies. Forty-one population-based studies were reviewed, and 12 were included in the final analysis. Differences in outcome definitions accounted for much of the variability in incidence rate estimates reported in original studies. The pooled incidence rate estimate among nonusers of prescription NSAIDs per 1,000 person-years was 0.1 (95% confidence interval: 0.04-0.23) for perforations alone, 0.8 (0.58-0.68) for bleeding lesions alone, 0.9 (0.66-1.27) for bleeding or perforated lesions, and 1.0 (0.83-1.15) for serious gastrointestinal ulcer (complicated or without bleeding). Rates increased with age, and were approximately twice as high in men than in women. Epidemiologic studies based on automated data may slightly under- or overestimate the true incidence rate among nonusers of NSAIDs. Overall, the incidence rate of serious upper gastrointestinal complications was in the order of 1 per 1,000 person-years among nonusers of prescription NSAIDs.

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.

Long-term use of anti-inflammatory drugs and risk of atrial fibrillation.

BACKGROUND: Previous reports have described an association between the use of corticosteroids (steroidal anti-inflammatory drugs [SAIDs]) and the risk of atrial fibrillation (AF). We sought to determine the existence of a similar association for non-SAIDs (NSAIDs). METHODS: We identified patients aged 40 to 89 years with a first-ever diagnosis of AF in 1996 in a United Kingdom primary care database and classified them as having paroxysmal or chronic AF. After validation with their primary care physicians, 1035 patients were confirmed as having incident chronic AF and 525 as having paroxysmal AF. Two separate nested case-control analyses estimated the risk of first-time chronic and paroxysmal AF among users of SAIDs and NSAIDs. RESULTS: We confirmed the previously reported association between current use of SAIDs and chronic AF (rate ratio [RR], 2.49; 95% confidence interval [CI], 1.56-3.97). However, we also found that the current use of NSAIDs was associated with an increased risk of chronic AF (RR, 1.44; 95% CI, 1.08-1.91). Such risk was further increased among long-term users with a treatment duration of longer than 1 year (RR, 1.80; 95% CI, 1.20-2.72). The increased risk of chronic AF was not explained by the occurrence of heart failure. The use of NSAIDs was not associated with paroxysmal AF. CONCLUSIONS: The use of NSAIDs, as for SAIDs, is associated with an increased risk of chronic AF. Because the use of anti-inflammatory drugs in general is a marker for underlying inflammatory disorders, inflammation may be the common cause for the use of anti-inflammatory drugs and chronic AF.

Chest pain in general practice: incidence, comorbidity and mortality.

BACKGROUND: Chest pain is a common symptom that presents the primary care physician with a complex diagnostic and therapeutic challenge. AIMS: To evaluate the natural history and management of patients diagnosed with chest pain of unspecified type or origin in primary care. DESIGN: Population-based case-control study. METHODS: The study included 13,740 patients with a first diagnosis of unspecified chest pain and 20,000 age- and sex-matched controls identified from the UK General Practice Research Database. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. Risk estimates were adjusted for age, sex and number of physician visits. RESULTS: The incidence of a new diagnosis of chest pain was 15.5 per 1000 person-years and increased with age, particularly in men. The risk of a chest pain diagnosis was greatest in patients with prior diagnoses of coronary heart disease (OR: 7.1; 95% CI: 6.1-8.2) and gastroesophageal reflux disease (OR: 2.0; 95% CI: 1.7-2.3). In the year after diagnosis, chest pain patients were more likely than controls to be newly diagnosed with coronary heart disease (OR: 14.9; 95% CI: 12.7-17.4) and heart failure (OR: 4.7; 95% CI: 3.6-6.1). A new diagnosis of chest pain was associated with an increased risk of death in the following year (RR: 2.3; 95% CI: 1.9-2.8). CONCLUSIONS: Some causes of chest pain are underdiagnosed in primary care. This is of particular consequence for the minority of chest pain patients with cardiac disease.

Association between captopril, other antihypertensive drugs and risk of prostate cancer.

BACKGROUND: There has been some debate on the existence of an association between hypertension, antihypertensive medications and cancer risk. METHODS: We performed a nested case-control study to assess the association between the risk of prostate cancer and the use of the angiotensin converting enzyme (ACE)-inhibitor captopril, and other antihypertensive drugs. We used data from the General Practice Research Database in UK. RESULTS: We found an incidence rate of prostate cancer of 1.61 per 1,000 person-years among male patients aged 50-79 years old. Patients with a history of benign prostatic hyperplasia and/or prostatism carried a two-fold greater risk of prostate cancer than those without such antecedents. None of the other studied co-morbidities were associated with prostate cancer. We found that users of captopril had a relative risk of 0.7 (95% CI: 0.4-1.2) to develope prostate cancer. None of the other studied individual ACE-inhibitors shared a similar effect with the one observed for captopril. CONCLUSIONS: No clear association was apparent between the use of antihypertensive drugs and prostate cancer. However, specific focus on users of captopril showed a lower risk of subsequent prostate cancer. Further research is needed to explore this association.