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OBJECTIVES: Discontinuation of low-dose acetylsalicylic acid (ASA) therapy may increase the risk of ischemic events. This study evaluated the risk of ischemic stroke (IS) and TIA after low-dose ASA discontinuation in patients with cardiovascular disease or cerebrovascular disease. METHODS: The Health Improvement Network UK primary care database was used to identify a cohort of individuals aged 50-84 years with a first prescription for low-dose ASA (75-300 mg/day) for the secondary prevention of cardiovascular or cerebrovascular events in 2000-2007 (n = 39,512). Individuals were followed up for a mean of 3.4 years to identify cases of IS/TIA. Nested case-control analyses were used to assess risk factors for IS/TIA, including low-dose ASA discontinuation. RESULTS: The overall incidence of IS/TIA was 5.0 per 1,000 person-years (95% confidence interval [CI] 4.6-5.4). IS/TIA was significantly more common in patients with a previous diagnosis of cerebrovascular disease (relative risk [RR] 2.79; 95% CI 2.05-3.80) or atrial fibrillation (RR 1.71; 95% CI 1.28-2.29) than in those without these conditions. Compared with current users of low-dose ASA, those who discontinued treatment 31-180 days before the index date had a significantly increased overall risk of IS/TIA (RR 1.40; 95% CI 1.03-1.92). The most common reason for discontinuation was patient nonadherence. CONCLUSION: In patients prescribed low-dose ASA for the secondary prevention of cardiovascular or cerebrovascular events, discontinuation of low-dose ASA was associated with a 40% increase in the risk of IS/TIA compared with continuation of therapy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that discontinuation of low-dose ASA is associated with a 40% increased risk of stroke within 31-180 days of discontinuation.

CONTEXT: Serum total bilirubin levels in healthy patients reflect genetic and environmental factors that could influence the risk of developing respiratory disease. OBJECTIVE: To examine the relationship between bilirubin levels and respiratory disease. DESIGN, SETTING, AND PARTICIPANTS: Cohort study among 504,206 adults from a UK primary care research database (the Health Improvement Network) with serum bilirubin levels recorded but no evidence of hepatobiliary or hemolytic disease. Data were recorded between January 1988 and December 2008. MAIN OUTCOME MEASURES: Incidence of chronic obstructive pulmonary disease (COPD), lung cancer, and all-cause mortality. RESULTS: Median bilirubin levels were 0.64 mg/dL (interquartile range, 0.47-0.88 mg/dL) in men and 0.53 mg/dL (interquartile range, 0.41-0.70 mg/dL) in women. There were 1341 cases of lung cancer, 5863 cases of COPD, and 23,103 deaths, with incidence rates of 2.5, 11.9, and 42.5 per 10,000 person-years, respectively. The incidence of lung cancer per 10,000 person-years in men was 5.0 (95% confidence interval [CI], 4.2-6.0) in the first decile category of bilirubin compared with 3.0 (95% CI, 2.3-3.8) in the fifth decile. The corresponding incidences for COPD in men were 19.5 (95% CI,17.7-21.4) and 14.4 (95% CI, 12.7-16.2). The mortality rates per 10,000 person-years in men were 51.3 (95% CI, 48.5-54.2) in the first decile category compared with 38.1 (95% CI, 35.5-40.8) in the fifth decile. The associations were similar for women. After adjusting for other important health indicators, regression estimates for incidence rate of lung cancer per 0.1-mg/dL increase in bilirubin level were an 8% decrease (95% CI, 5%-11%) for men and an 11% decrease (95% CI, 7%-14%) for women. The regression estimate for COPD in men per 0.1-mg/dL increase in bilirubin level was a 6% decrease (95% CI, 5%-7%) and for mortality in men was a 3% decrease (95% CI, 2%-3%) after accounting for other health indicators. The results for COPD and mortality in women were very similar. CONCLUSION: Among patients with normal-range bilirubin levels in primary care practices, relatively higher levels of bilirubin were associated with a lower risk of respiratory disease and all-cause mortality.

In a national primary care database sample of older people (≥65 years), 81% (83 588/103 821) of community and 58% (1702/2940) of care home residents with diabetes or heart disease had depression case finding recently recorded; 66% (1418/2145) of community and 22% (26/118) of care home residents with a new depression episode had a depression-severity assessment recorded. Age, sex, and higher care home dementia prevalence did not explain these differences. Case finding and assessment of depression need to be improved in older people, particularly care home residents.

OBJECTIVE: To determine the incremental cost of healthcare and clinical outcomes in the 12 months following incident hip fractures among postmenopausal women in the UK. METHODS: Retrospective cohort study of women aged 50 years or older hospitalized for an incident hip fracture within 1 week of the fracture date who were age- and comorbidity-matched to women without fracture. Cohorts were identified in the Health Improvement Network database, and followed up for 1 year. RESULTS: Among 2,427 women who had a hip fracture and a recorded hospitalization, the mean [SD] age was 81 [9.3] years. About 18% of women without fractures were hospitalized during follow-up and 18% of women with hip fractures and 4% of women without fractures had at least one emergency admission (RR, 4.7; 95% CI, 3.8-5.8). There were no major differences in use of general practitioner visit, referral visits, or in prescription of medications. Mortality was 18% in the hip fracture cohort and 7% in the non-fracture cohort (RR, 2.5; 95% CI, 2.1-3.0). The overall 1-year mean incremental cost of hip fractures was £4,222 (95% CI, £4,105-4,339); most of this cost (97%) was for hospitalizations, with an increment of £4,095. About 98% of the incremental cost occurred in the first 6 months following hip fracture. CONCLUSIONS: The results of this study indicate that the cost and clinical burden associated with hip fractures in postmenopausal women in the UK are considerable. The incremental cost is mostly related to the cost of hospitalization and treatment of the hip fracture. Key limitations were the inclusion of only those women with a recorded hospitalization, and that costs associated with rehabilitation services, social services, and long-term care were not recorded in this study, although these are important contributors to the total cost of fractures.

BACKGROUND: hip fractures result in a significant burden to the patient, their caregivers and the health care system. Patients with Alzheimer's disease (AD) have a higher incidence of hip fracture compared with other older people without AD, although it is not clear if AD is an independent risk factor for hip fracture. METHODS: a retrospective cohort study was conducted using anonymised electronic medical records from primary care practices in the United Kingdom. Proportional hazards regression modelling with adjustment for potential confounders was used to evaluate AD as an independent risk factor for predicting hip fractures. RESULTS: the incidence of hip fracture among patients with and without AD was 17.4 (95% CI, 15.7-19.2) and 6.6 (95% CI, 5.8-7.6) per 1,000 person years, respectively. Patients with AD had a hazard that was 3.2 (95% CI, 2.4-4.2) times that of non-AD patients after controlling for potential confounders. AD patients who experienced a hip fracture also had an increased mortality rate compared with non-AD patients who experienced a hip fracture (hazard ratio = 1.5; 95% CI, 1.1-1.9). CONCLUSION: patients with AD and their caregivers should be advised on how to prevent hip fractures and more attention should be given to AD patients who are undergoing rehabilitation following a hip fracture.

OBJECTIVE: To assess the impact of a pay for performance incentive on quality of care and outcomes among UK patients with hypertension in primary care. DESIGN: Interrupted time series. SETTING: The Health Improvement Network (THIN) database, United Kingdom. PARTICIPANTS: 470 725 patients with hypertension diagnosed between January 2000 and August 2007. INTERVENTION: The UK pay for performance incentive (the Quality and Outcomes Framework), which was implemented in April 2004 and included specific targets for general practitioners to show high quality care for patients with hypertension (and other diseases). MAIN OUTCOME MEASURES: Centiles of systolic and diastolic blood pressures over time, rates of blood pressure monitoring, blood pressure control, and treatment intensity at monthly intervals for baseline (48 months) and 36 months after the implementation of pay for performance. Cumulative incidence of major hypertension related outcomes and all cause mortality for subgroups of newly treated (treatment started six months before pay for performance) and treatment experienced (started treatment in year before January 2001) patients to examine different stages of illness. RESULTS: After accounting for secular trends, no changes in blood pressure monitoring (level change 0.85, 95% confidence interval -3.04 to 4.74, P=0.669 and trend change -0.01, -0.24 to 0.21, P=0.615), control (-1.19, -2.06 to 1.09, P=0.109 and -0.01, -0.06 to 0.03, P=0.569), or treatment intensity (0.67, -1.27 to 2.81, P=0.412 and 0.02, -0.23 to 0.19, P=0.706) were attributable to pay for performance. Pay for performance had no effect on the cumulative incidence of stroke, myocardial infarction, renal failure, heart failure, or all cause mortality in both treatment experienced and newly treated subgroups. CONCLUSIONS: Good quality of care for hypertension was stable or improving before pay for performance was introduced. Pay for performance had no discernible effects on processes of care or on hypertension related clinical outcomes. Generous financial incentives, as designed in the UK pay for performance policy, may not be sufficient to improve quality of care and outcomes for hypertension and other common chronic conditions.

OBJECTIVES: Previous studies have shown an association between isotretinoin and inflammatory bowel disease (IBD). The majority of patients prescribed isotretinoin for their acne are previously on an extended course of antibiotics. Therefore, it is important to consider antibiotic use as a confounding variable for the development of IBD. METHODS: We performed a retrospective cohort study using The Health Improvement Network database of the United Kingdom. We identified 94,487 individuals with acne who were followed up by a general practitioner for 406,294 person-years. RESULTS: >A prescription for minocycline was received by 24,085 individuals, for tetracycline/oxytetracycline by 38,603 individuals, and doxycycline by 15,032 individuals. IBD was noted in 41 individuals exposed to minocycline, 79 individuals exposed to tetracycline/oxytetracycline, 32 individuals exposed to doxycycline, and 55 (0.11%) individuals not exposed to any of these antibiotics. The hazard ratio (HR) for developing IBD for any exposure to a tetracycline antibiotic was 1.39 (1.02, 1.90). HRs for individual antibiotics were 1.19 (0.79, 1.79) for minocycline, 1.43 (1.02, 2.02) for tetracycline/oxytetracycline, and 1.63 (1.05, 2.52) for doxycycline. For ulcerative colitis, the associations (HR) were 1.10 (0.76, 1.82) for minocycline, 1.27 (0.78, 2.07) for tetracycline/oxytetracycline, and 1.06 (0.53, 2.13) for doxycycline. For Crohn's disease (CD), the associations (HR) were 1.28 (0.72, 2.30) for minocycline, 1.61 (0.995, 2.63) for tetracycline/oxytetracycline, and 2.25 (1.27 4.00) for doxycycline. CONCLUSIONS: Tetracycline class antibiotics, and particularly doxycycline use may be associated with the development of IBD, particularly CD. Potential confounding by previous doxycycline exposure should be considered when assessing whether treatment with other acne medications increases the risk of IBD.

BACKGROUND: the process of registering new patients in primary care provides an ideal opportunity to assess their smoking status systematically and record this in electronic medical records; this identification then allows smokers to be targeted with effective cessation interventions. OBJECTIVE: to use a dataset of electronic primary care medical records to assess the extent to which primary care patients' smoking status is recorded in their electronic records at the time of their registering with a new GP. METHODS: patients who registered with a general practice contributing data to The Health Improvement Network (THIN) database each year between 1990 and 2006 were identified, and their electronic medical records examined to identify the date on which their smoking status was first recorded. RESULTS: in total, 74.2% of adults registering with a new GP in 1990 failed to have their smoking status recorded in their electronic medical records within 90 days of registration, improving to 26.7% of adults registering in 2006. CONCLUSIONS: that over one-quarter of adults registering with a THIN practice in 2006 did not have their smoking status recorded at registration represents substantial missed opportunities for identifying smokers and also, potentially, for offering them support to quit.

BACKGROUND: There are well-established socio-economic differences in the prevalence of smoking in the UK, but conventional socio-economic measures may not capture the range and degree of these associations. We have used a commercial geodemographic profiling system, Mosaic, to explore associations with smoking prevalence in a large primary care dataset and to establish whether this tool provides new insights into socio-economic determinants of smoking. METHODS: We analysed anonymised data on over 2 million patients from The Health Improvement Network (THIN) database, linked via patients' postcodes to Mosaic classifications (11 groups and 61 types) and quintiles of Townsend Index of Multiple Deprivation. Patients' current smoking status was identified using Read Codes, and logistic regression was used to explore the associations between the available measures of socioeconomic status and smoking prevalence. RESULTS: As anticipated, smoking prevalence increased with increasing deprivation according to the Townsend Index (age and sex adjusted OR for highest vs lowest quintile 2.96, 95% CI 2.92-2.99). There were more marked differences in prevalence across Mosaic groups (OR for group G vs group A 4.41, 95% CI 4.33-4.49). Across the 61 Mosaic types, smoking prevalence varied from 8.6% to 42.7%. Mosaic types with high smoking prevalence were characterised by relative deprivation, but also more specifically by single-parent households living in public rented accommodation in areas with little community support, having no access to a car, few qualifications and high TV viewing behaviour. CONCLUSION: Conventional socio-economic measures may underplay social disparities in smoking prevalence. Newer classification systems, such as Mosaic, encompass a wider range of demographic, lifestyle and behaviour data, and are valuable in identifying characteristics of groups of heavy smokers which might be used to tailor cessation interventions.

OBJECTIVE: Although hyperuricaemia and gout are associated with an increased future risk of diabetes, diabetes may reduce the future risk of gout through the uricosuric effect of glycosuria or the impaired inflammatory response. The present work evaluates the impact of diabetes on the future risk of developing gout. METHODS: A case-control study nested in a UK general practice database (the health improvement network) was conducted by identifying all incident cases of gout (N=24 768) and randomly sampling 50,000 controls who were 20-89 years between 2000 and 2007. The independent effect of type 1 and type 2 diabetes on the development of incident gout was examined. RESULTS: After adjusting for age, sex, body mass index, general practitioner visits, smoking, alcohol intake, ischaemic heart disease and presence of cardiovascular risk factors, the RR for incident gout among patients with diabetes, as compared with individuals with no diabetes was 0.67 (95% CI 0.63 to 0.71). The multivariate RRs with the duration of diabetes of 0-3, 4-9 and ≥ 10 years were 0.81 (95% CI 0.74 to 0.90), 0.67 (95% CI 0.61 to 0.73) and 0.52 (95% CI 0.46 to 0.58), respectively. The inverse association was stronger with type 1 diabetes than with type 2 diabetes (multivariate RR, 0.33 vs 0.69) and stronger among men than women (p value for interaction < 0.001). CONCLUSIONS: Individuals with diabetes are at a lower future risk of gout independent of other risk factors. These data provide support for a substantial role of the pathophysiology associated with diabetes against the risk of developing gout.

OBJECTIVES: To determine the prevalence and incidence of a diagnosis of gastroesophageal reflux disease (GERD) in children and adolescents in UK primary care, and to assess comorbidities that are associated with a diagnosis of GERD. MATERIAL AND METHODS: Incident GERD cases during 2000-05 were identified from The Health Improvement Network (THIN) UK primary care database via a computer search for diagnostic codes for GERD, followed by manual review of the patient records. RESULTS: We identified 1700 children with a first diagnosis of GERD during 2000-05. The incidence of GERD was 0.84 per 1000 person-years. The incidence decreased with age from 1.48 per 1000 person-years among 1-year-old children until the age of 12 years, whereupon it increased to a maximum at 16-17 years of 2.26 per 1000 person-years for girls and 1.75 per 1000 person-years for boys. Pregnant adolescents were not included in the study. In addition to typical GERD symptoms (epigastric pain, heartburn, reflux, regurgitation), 21.2% of children reported nausea or vomiting. Children with neurological disorders were at increased risk of a GERD diagnosis. Hiatus hernia and congenital esophageal disorders were also associated with a diagnosis of GERD. Children and adolescents using antiepileptics, oral/inhaled steroids, beta-agonists and paracetamol had an increased risk of a GERD diagnosis. CONCLUSIONS: The incidence of a GERD diagnosis was age-dependent and was highest among very young children and older female adolescents. Children with neurological impairments and other comorbidities were at increased risk of a GERD diagnosis.

BACKGROUND: Previous studies have suggested that children of mothers who experience depression during the perinatal period may have more infections, but such studies are few in number and none have been carried out in the United Kingdom (UK) population. The aim of this study was to investigate the association between perinatal depression in mothers and the risk of childhood infections in offspring in the UK general population. METHODS: We used data from The Health Improvement Network (THIN), a large database of electronic primary care medical records to conduct a cohort study among all first-born singleton children born and enrolled in THIN between 1988 and 2004. We used Poisson regression to compare the incidence of gastrointestinal infections and lower respiratory tract infections reported between birth and age 4 years among children of mothers with a record of perinatal depression with those born to mothers with no such history. RESULTS: Children of mothers with perinatal depression had a 40% increased risk of gastrointestinal infections and a 27% increased risk of lower respiratory tract infections compared with children of mothers without perinatal depression (incidence rate ratios = 1.40 and 1.27; 95% confidence intervals 1.37-1.42 and 1.22-1.32, respectively). On restricting to antibiotic-treated infections there was a slight increase in the magnitude of association with gastrointestinal infections but a decrease in that with lower respiratory tract infections (incidence rate ratios = 1.47 and 1.19; 95% confidence intervals 1.34-1.61 and 1.11-1.27, respectively). CONCLUSIONS: Maternal perinatal depression is associated with increased rates of childhood gastrointestinal infections, particularly more severe infections, and lower respiratory tract infections in the UK. Preventing maternal perinatal depression may avoid substantial morbidity among offspring, although further work is also needed to investigate the detailed reasons for these findings.

OBJECTIVE: Previous observational studies have found an increased risk of acute pancreatitis among type 2 diabetic patients. However, limited information is available on this association and specifically on the role of antidiabetic treatment. Our aim, therefore, was to further assess the risk of acute pancreatitis in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed a population-based case-control analysis nested in a cohort of 85,525 type 2 diabetic patients and 200,000 diabetes-free individuals from the general population using data from The Health Improvement Network database. Subjects were followed up to ascertain incident cases of acute pancreatitis. RESULTS: We identified 419 cases of acute pancreatitis, 243 in the general population and 176 in the diabetes cohort. Incidence rates were 30.1 and 54.0 per 100,000 person-years in the general population and the diabetes cohort, respectively. In the cohort analysis, the adjusted incidence rate ratio of acute pancreatitis in diabetic patients versus that in the general population was 1.77 (95% CI 1.46-2.15). The magnitude of this association decreased with adjustment for multiple factors in the nested case-control analysis (adjusted odds ratio 1.37 [95% CI 0.99-1.89]). Furthermore, we found that the risk of acute pancreatitis was decreased among insulin-treated diabetic patients (0.35 [0.20-0.61]). CONCLUSIONS: Type 2 diabetes may be associated with a slight increase in the risk of acute pancreatitis. We also found that insulin use in type 2 diabetes might decrease this risk. Further research is warranted to confirm these associations.