Scientific
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BACKGROUND: The April 2004 contract for UK general practitioners (GPs) is an ambitious attempt to produce substantial changes in clinical practice. We investigated the impact of this on delivery of primary care smoking cessation interventions. METHODS: We analysed data from patients' medical records that were held within a large database called The Health Improvement Network (THIN). We calculated for each year between 1990 and 2005 and for each quarter-year from 2003 the incidence of recording of smoking status in medical records and, in smokers, the receipt of GPs' smoking cessation advice and prescriptions for nicotine addiction treatments. FINDINGS: Recording of smoking status increased temporarily around 1993-4 and then rose gradually from the year 2000. This rise was more marked from 2003, with an 88% increase between the first quarters of 2003 and 2004. The latter quarter was just prior to the introduction of the GP contract and higher rates of recording smoking status were sustained for the subsequent year. In smokers, there was a broadly similar pattern for the proportion recorded as having received brief cessation advice. However, while there was a sharp increase in prescriptions for nicotine addiction treatments from 2000, no comparable acceleration in this trend from 2003 was apparent. INTERPRETATION: The 2004 GP contract increased primary care rates of smoking status ascertainment and recording of advice against smoking. The public health impact of this contract could be maximized if it also improved GPs' prescribing of nicotine addiction treatments.

The protective association between having older siblings and the risk of subsequent allergic disease may be due to decreased fertility among women with allergic disease. In this study, the authors compared fertility rates among women with asthma, eczema, or hay fever with those in the general female population. Computerized primary-care data from the United Kingdom were used to conduct a cohort analysis of 491,516 women. General fertility rates and age-specific fertility rates for 1994-2004 were estimated. Using Poisson regression, the authors compared fertility rates among women with asthma, eczema, or hay fever with rates in women without these diagnoses. Fertility rates were 53.0 and 52.3 livebirths per 1,000 person-years in women with and without asthma, respectively. The fertility rate ratio for women with asthma compared with women without asthma was 1.02 (95% confidence interval (CI): 1.00, 1.04) after adjustment for age, smoking, body mass index, and socioeconomic status. Equivalent fertility rate ratios for eczema and hay fever were 1.15 (95% CI: 1.13, 1.17) and 1.08 (95% CI: 1.06, 1.10), respectively. The authors found no evidence that the fertility rates of women with asthma, eczema, or hay fever are lower than those of women in the general population.

RATIONALE: Previous studies have raised concern that women with asthma have increased risks of adverse obstetric and pediatric complications, but these have generally been underpowered. OBJECTIVES: To quantify risks of major adverse pregnancy outcomes and obstetric complications in women with and without asthma. METHODS: We extracted information on 281,019 pregnancies from the Health Improvement Network database between 1988 and 2004. We analyzed the data using logistic regression. MEASUREMENTS AND MAIN RESULTS: In 37,585 pregnancies of women with asthma compared with 243,434 pregnancies of women without asthma, risks of stillbirth and therapeutic abortion were similar; however, the risk of miscarriage was slightly higher (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.06-1.13). Risks of most obstetric complications (placental abruption, placental insufficiency, placenta previa, preeclampsia, hypertension, gestational diabetes, thyroid disorders in pregnancy, and assisted delivery) were not higher in pregnancies of women with asthma compared with those without asthma, with the exception of increases in antepartum (OR, 1.20; 95% CI, 1.08-1.34) or postpartum (OR, 1.38; 95% CI, 1.21-1.57) hemorrhage, anemia (OR, 1.06; 95% CI, 1.01-1.12), depression (OR, 1.52; 95% CI, 1.36-1.69), and caesarean section (OR, 1.11; 95% CI, 1.07-1.16). Risks of miscarriage, depression, and caesarean section increased moderately in women with more severe asthma and previous asthma exacerbations. CONCLUSIONS: We found some increased risks in women with asthma that need to be considered in the future; however, our results indicate that women with asthma have similar reproductive risks compared with women without asthma in the general population for most of the range of outcomes studied.

BACKGROUND: The Health Improvement Network (THIN) is a new medical records database that contains records from general practices some of which have or continue to participate in the General Practice Research Database (GPRD) and others that never participated in GPRD. We sought to replicate in THIN well-established associations from the medical literature and to compare results from the GPRD practices to the non-GPRD practices within THIN. METHODS: Using THIN data from 1986-2003, we conducted case-control studies of associations between diseases (e.g., hypertension and stroke) and between diseases and drugs (e.g., aspirin and colon cancer). Conditional logistic regression was used to calculate odds ratios adjusted for potential confounders. Differences between GPRD and non-GPRD practices were assessed by testing for a statistical interaction by practice type in each outcome-exposure association. RESULTS: We observed the expected positive associations (p < 0.05) of stroke with hypertension and diabetes mellitus; of myocardial infarction with hypertension, hypercholesterolemia, obesity, and smoking; and of peptic ulcer disease with aspirin, NSAIDs, and potassium. We observed the expected negative associations (p < 0.05) of colorectal cancer with aspirin, NSAIDs, and cox-2 inhibitors. The expected protective effect of aspirin use for myocardial infarction was not observed. In all cases, the results obtained from the GPRD practices were similar to the results obtained from the non-GPRD practices, only being statistically different for the associations of myocardial infarction with diabetes and aspirin use. CONCLUSIONS: THIN data that are collected outside of the GPRD appear as valid as the data collected as part of the GPRD.

Regular aspirin and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use is associated with a reduced risk of colorectal cancer. The effect of NSAIDs on the risk of other cancers remains unclear. To evaluate whether use of aspirin or other specific NSAIDs protects against lung cancer, we conducted a case-control study nested in a cohort of subjects 40-84 years old in 1995-2004, without a diagnosis of cancer before the study start date, and with at least 2 years of enrollment with a general practitioner providing data to the The Health Improvement Network (THIN) database in the UK. Patients who had a first diagnosis of primary lung cancer during the study period were considered cases. A random sample of 10,000 controls was frequency-matched to the cases for age, sex and calendar year. The index date for exposure definition was 1 year before the date of diagnosis for cases and 1 year before a random date within the study period for controls. Relative risks and 95% confidence intervals were estimated using conditional logistic regression stratified for matching factors. Factors such as smoking, chronic obstructive pulmonary disease, cardiovascular diseases and body mass index were introduced in the model. We identified 4,336 cases with primary incident lung cancer (incidence rate 7.6 per 10,000 person-years). Compared with subjects with no prescription of non-aspirin NSAID prior to the index date, the risk of lung cancer was 0.76 (0.61-0.94) among those who received a prescription the previous year and had a treatment duration of at least 1 year. The corresponding relative risk was 1.15 (0.99-1.34) for aspirin. In conclusion, prescription of non-aspirin NSAIDs for at least 1 year might be associated with a slightly reduced risk of lung cancer. Aspirin was not associated with a risk reduction, perhaps due to residual confounding.

OBJECTIVE: To evaluate predictors of changing the type of phosphodiesterase type 5 (PDE5) inhibitor (switching) among men with erectile dysfunction (ED) in the UK, the largest consumer of PDE5 inhibitors in Europe, as switching medication is often associated with higher resource use, and there are three oral PDE5 inhibitor medications currently available. PATIENTS AND METHODS: Patients were identified from The Health Improvement Network database in the UK; men initiating therapy with sildenafil, tadalafil or vardenafil from May 2003 to August 2004 with >/= 6 months of prescription history before and after their initial PDE5 inhibitor prescription were included. Switching was evaluated as the proportion of second PDE5 inhibitor prescriptions that were for a drug differing from the first. Logistic regression was used to adjust for factors that might be associated with switching (dose, age and the presence of hypertension, dyslipidaemia, diabetes or depression). RESULTS: Of the 2703 eligible men who initiated PDE5 inhibitor treatment during the study period, 91 (3.4%) switched to a different PDE5 inhibitor at their second prescription. The choice of initial PDE5 inhibitor therapy was a highly significant predictor of switching; men initiated on sildenafil were less likely to switch than those initiated on tadalafil (P < 0.001) or vardenafil (P < 0.003). Age and the presence of comorbidities were not significantly associated with switching (P > 0.05). CONCLUSION: Initiating ED therapy with sildenafil was associated with the lowest rate of PDE5 inhibitor switching, which might reflect treatment satisfaction and patient preference.

BACKGROUND: Extrinsic allergic alveolitis (EAA) is an important clinical entity, but its incidence and significance in the general population are uncertain. AIM: To estimate the incidence of EAA, and resulting mortality, in the UK. DESIGN: General-population-based cohort study in a UK primary care database (THIN). METHODS: THIN patients with an incident diagnosis of EAA were compared with a general population cohort whose members were 4:1 matched with EAA patients by age, sex and GP practice. Follow-up started at the first diagnosis of EAA (and at the same date in the matched controls) and ended at death or end of follow-up, whichever came first. Poisson, logistic, and Cox proportional hazard regression models were used; mortality rate, odd ratios, and hazard ratios were calculated. RESULTS: We identified 271 incident cases of EAA (mean age at diagnosis 57 years, 51% male). Between 1991 and 2003, the incident rate for EAA was stable at approximately 0.9 cases per 100000 person-years. In comparison to the 1084 general population controls, patients with EAA were less likely to smoke (odds ratio 0.56, 95%CI 0.39-0.81), but had a marked increase in the risk of death (hazard ratio 2.98, 95%CI 2.05-4.33). DISCUSSION: The incidence of EAA in the UK population appears to be stable overtime, and suggests about 600 new cases of EAA each year. People with EAA are less likely to smoke than the general population, but have a markedly increased mortality rate.

BACKGROUND & AIMS: Traditional nonaspirin, nonsteroidal anti-inflammatory drugs (tNSAIDs) have been associated with a 3- to 5-fold increased risk in upper gastrointestinal complications (UGIC). Whether use of selective inhibitors of cyclooxygenase-2 (COXIBs) will translate into a clinically relevant reduced toxicity has not been widely investigated in the general population. METHODS: We conducted a nested case control study using The Health Improvement Network Database identifying 1561 cases of UGIC between January 2000 and 2005. A random sample of 10,000 controls was frequency matched to the cases by age, sex, and calendar year. RESULTS: The adjusted relative risk (RR) of UGIC associated with current use was 3.7 (95% CI: 3.1-4.3) for tNSAIDs and 2.6 (95% CI: 1.9-3.6) for COXIBs. Daily dose was a predictor of increased risk for both tNSAIDs and COXIBs. Users of tNSAIDs with a prolonged plasma half-life or slow release formulations had an augmented risk of UGIC. Overall, the estimate of RR associated with COXIBs was 0.8 (95% CI: 0.6-1.1) compared with current use of tNSAIDs, and, among nonusers of aspirin, the corresponding estimate of RR associated with COXIBs was 0.6 (95% CI: 0.4-0.9). CONCLUSIONS: COXIBs present a better upper gastrointestinal safety than tNSAIDs, although the risk of UGIC for an individual drug is determined by its daily dose and plasma drug exposure in addition to its selectivity for cyclooxygenase-2. Also, concomitant use of aspirin is a strong effect modifier of COXIBs that negates the superior gastrointestinal safety over tNSAIDs in the absence of aspirin use.

BACKGROUND: COX-2 and NSAIDS differ in their gastrointestinal (GI) and cardiovascular (CV) toxicity from pharmacological, clinical and epidemiologic point of views. OBJECTIVE: Describe the patterns of use of NSAIDS and COX-2 in The Health Improvement Network (THIN) database in UK and the PharMetrics database in USA. METHODS: We examined the experience of 10 distinct cohorts of new users of diclofenac, naproxen, ibuprofen, piroxicam, other NSAIDS, meloxicam, celecoxib, etoricoxib, rofecoxib and valdecoxib. The study period was 1 January 1995 through 2004 (31 March in UK and 28 February in USA). We collected information on covariates including history of upper GI disease, CV disease, hepatic disease, dosage, concomitant medication, and visits to a rheumatologist. RESULTS: We identified 486 076 unique patient-drug pairs in UK and 1 533 239 in USA. In UK population 78 201 (16%) were COX-2 users and in PharMetrics 324 206 (21%) were COX-2 users. Diclofenac and ibuprofen (NSAIDS), and celecoxib and rofecoxib (COX-2) were the agents prescribed most frequently. The duration of therapy was longer among celecoxib and rofecoxib users than among other users. More COX-2 users than NSAIDS users received concomitant gastroprotective agents (GPA), corticosteroids and anti-platelet therapy, and had a history of thromboembolic events and hypertension. PharMetrics patients were prescribed higher doses of NSAIDS and COX-2. The use of any single agent for more than 90 days was uncommon, but more frequent in PharMetrics. Switching was uncommon and was generally to a NSAID. DISCUSSION: Our results confirm some previous findings from other authors such as the presence of both GI and CV channelling to COX-2 agents but refute others, such as the frequency of drug switching between these agents. The typical use of COX-2 agents in practice is for shorter duration, and at lower doses, than was employed in randomized clinical trials. This difference may help clarify the apparent discrepancy with respect to CV toxicity between the results from clinical trials, which showed a higher CV risk with these drugs, and non-experimental epidemiologic studies, which showed lower or no increase in risk.