Scientific
publications

OBJECTIVES: To examine patterns of prescribing of oral antibiotics during pregnancy and to determine whether women were more or less likely to receive specific types of antibiotics in pregnancy than in the years before and after pregnancy. Finally, to identify socio-demographic factors associated with antibiotic prescribing in pregnancy. PATIENTS AND METHODS: We identified 114 999 women who gave live birth between 1992 and 2007 in The Health Improvement Network (THIN) UK primary care database. Antibiotic prescribing during pregnancy was estimated for each calendar year between 1992 and 2007. Self-controlled case series (SCCS) methodology was used to compare antibiotic prescribing during pregnancy with the years before and after pregnancy, and Poisson regression to examine association between demographic factors and antibiotic prescribing. RESULTS: A third of pregnant women received at least one antibiotic prescription during pregnancy. In each trimester, 14% of women received at least one antibiotic. Prescribing of antibiotics was lower in pregnancy than during a comparable period 1 year earlier [incidence rate ratio (IRR) 0.91 (95% CI 0.90-0.93)], but some antibiotics were prescribed more frequently in pregnancy: broad-spectrum penicillins [IRR 1.46 (1.42-1.49)]; cephalosporins [IRR 2.22 (2.13-2.31)]; and antibiotics for urinary tract infections [IRR 2.29 (2.01-2.61)]. Respiratory, urinary, skin and ear infections were the commonest indications. Urinary indications increased and respiratory, skin and ear infection indications declined during pregnancy, although a large proportion were prescribed without indication. Young age and social deprivation were associated with increased antibiotic prescribing during pregnancy. CONCLUSIONS: Antibiotic prescribing is widespread in pregnancy although marginally reduced compared with the year before pregnancy. There were substantial changes in types of antibiotics as well as in their indications during pregnancy. This may be explained by changes in threshold for treatment, diseases, detection and recording. Younger women and women from deprived areas were most likely to receive antibiotics in pregnancy.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) has not been shown to respond to corticosteroid therapy; however, many patients receive these drugs at the time of diagnosis. The factors that are associated with the decision to prescribe corticosteroids have not been examined. METHODS: We conducted a retrospective cohort study of 1126 patients with a new diagnosis of IPF using The Health Improvement Network (THIN) database from the United Kingdom. We used generalized estimating equation (GEE) regression models to test the association of patient characteristics, co-morbid diseases, and disease characteristics with the use of corticosteroids within 30 days of IPF diagnosis. RESULTS: Bivariable analyses demonstrated an association between female sex, the presence of dyspnea, the need for oxygen, past steroid use, and the use of corticosteroids immediately prior to diagnosis with the use of corticosteroids at the time of diagnosis. After adjustment with multivariable GEE regression, only the use of oxygen at the time of diagnosis (OR 1.69, CI 1.14-2.49), the past use of corticosteroids (OR 1.50, CI 1.04-2.15), and use of corticosteroids immediately prior to diagnosis (OR 5.72, CI 3.80-8.60) remained significantly associated with the use of corticosteroids immediately following diagnosis. No association was found between prior diabetes, osteoporosis, glaucoma, hypertension, congestive heart failure, obesity, or peptic ulcer disease and use of corticosteroids at diagnosis. CONCLUSIONS: The decision to prescribe corticosteroids is associated with oxygen use and past corticosteroid use but is not influenced by factors such as age, gender, or common co-morbid conditions that may pre-dispose patients to adverse events of therapy.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease with no known aetiology and no proven treatment. Despite the absence of efficacy data, many physicians treat IPF with corticosteroids either as monotherapy or in combination with a cytotoxic agent. Specialty society guidelines published in 1999 and 2000 recognize that treatment may not be appropriate for all patients with IPF, but recommend that if treatment is to be initiated, a combination of corticosteroids with a cytotoxic agent is preferred over corticosteroids alone. It is not known how the use of corticosteroids and cytotoxic agents in the treatment of IPF has changed over time and whether published guidelines have altered prescribing practices. WHAT THIS STUDY ADDS: The results of this study demonstrate a modest but statistically significant reduction in the overall use of corticosteroids since the publication of treatment guidelines. At the same time, there was a more pronounced increase in the combined use of corticosteroids and cytotoxic agents consistent with recommendations. Even with the increase in the use of combination therapy, corticosteroid monotherapy remained the most commonly prescribed regimen among treated patients. Given the lack of established benefit and the risks associated with corticosteroid therapy, the reasons for the continued use of corticosteroid monotherapy in the majority of treated patients warrant further investigation. AIMS: To assess the impact of specialty society guidelines on the use of corticosteroids and cytotoxic agents in the initial management of patients with idiopathic pulmonary fibrosis. METHODS: A retrospective cohort study of 941 patients with an incident diagnosis of IPF was conducted using a large medical records database. The primary outcome was a new prescription for corticosteroids with or without a cytotoxic agent within 30 days of diagnosis. The primary exposure was whether diagnosis occurred before or after the publication of treatment guidelines. Logistic regression was used to control for changes in population demographics and disease characteristics across time. RESULTS: In total, 187 patients (19.9%) received a new corticosteroid prescription within 30 days of diagnosis. Fewer patients received corticosteroids after the publication of guidelines (22.2% vs. 17.7%; adjusted OR for steroid use after the publication of guidelines 0.65, 95% confidence interval 0.46, 0.92, P = 0.014). Among the 187 patients treated with corticosteroids, 22 (11.8%) also received a cytotoxic agent. The use of cytotoxic agents among users of corticosteroids increased significantly after the publication of guidelines (5.1% vs. 19.3%) with a fully adjusted OR = 4.71 (95% CI 1.56, 14.21, P = 0.006). CONCLUSIONS: Since the publication of treatment guidelines, there has been a small reduction in the overall use of corticosteroids. Consistent with these guidelines, the use of cytotoxic agents among those prescribed corticosteroids has increased significantly; however, the use of these agents remains uncommon.

PURPOSE: Evaluation of tobacco policy requires high quality and timely data on smoking cessation behaviour in the general population and in relevant target groups. Electronic primary care databases have the potential to provide a valuable source of data due to their size and continuity, and the availability of demographic and socioeconomic data. We therefore sought to investigate whether The Health Improvement Network (THIN) prescribing data are complete and can therefore be used to monitor trends in the prescribing of smoking cessation medications. METHODS: The THIN smoking cessation medication prescriptions data for England were compared with smoking cessation medication dispensing data from NHS Prescription Services for January 2004 to December 2005. RESULTS: Throughout the period the rates of prescribing and dispensing were very similar, both for nicotine replacement therapy (NRT) and bupropion combined, and for each type of medication alone. For NRT, dispensing exceeded recorded GP prescribing by 5.5% during the study period. For bupropion, prescribing exceeded dispensing by 5%. CONCLUSIONS: THIN prescribing and national dispensing data are highly comparable. THIN prescribing data could potentially be used to monitor longitudinal trends in prescribing for smoking cessation medications.

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.

BACKGROUND: Chronic Kidney Disease is a major cause of morbidity and interventions now exist which can reduce risk. We sought to develop and validate two new risk algorithms (the QKidney Scores) for estimating (a) the individual 5 year risk of moderate-severe CKD and (b) the individual 5 year risk of developing End Stage Kidney Failure in a primary care population. METHODS: We conducted a prospective open cohort study using data from 368 QResearch general practices to develop the scores. We validated the scores using two separate sets of practices--188 separate QResearch practices and 364 practices contributing to the THIN database.We studied 775,091 women and 799,658 men aged 35-74 years in the QResearch derivation cohort, who contributed 4,068,643 and 4,121,926 person-years of observation respectively.We had two main outcomes (a) moderate-severe CKD (defined as the first evidence of CKD based on the earliest of any of the following: kidney transplant; kidney dialysis; diagnosis of nephropathy; persistent proteinuria; or glomerular filtration rate of < 45 mL/min) and (b) End Stage Kidney Failure.We derived separate risk equations for men and women. We calculated measures of calibration and discrimination using the two separate validation cohorts. RESULTS: Our final model for moderate-severe CKD included: age, ethnicity, deprivation, smoking, BMI, systolic blood pressure, diabetes, rheumatoid arthritis, cardiovascular disease, treated hypertension, congestive cardiac failure; peripheral vascular disease, NSAID use and family history of kidney disease. In addition, it included SLE and kidney stones in women. The final model for End Stage Kidney Failure was similar except it did not include NSAID use.Each risk prediction algorithms performed well across all measures in both validation cohorts. For the THIN cohort, the model to predict moderate-severe CKD explained 56.38% of the total variation in women and 57.49% for men. The D statistic values were high with values of 2.33 for women and 2.38 for men. The ROC statistic was 0.875 for women and 0.876 for men. CONCLUSIONS: These new algorithms have the potential to identify high risk patients who might benefit from more detailed assessment, closer monitoring or interventions to reduce their risk.

OBJECTIVE: To derive and validate risk algorithms so that the risks of four clinical outcomes associated with statin use can be estimated for individual patients. DESIGN: Prospective open cohort study using routinely collected data from 368 QResearch general practices in England and Wales to develop the scores. The scores were validated using two separate sets of practices-188 separate QResearch practices and 364 practices contributing to the THIN database. SUBJECTS: In the QResearch derivation cohort 225 922 new users of statins and 1 778 770 non-users of statins were studied. In the QResearch validation cohort 118 372 statin users and 877 812 non-users of statins were studied. In the THIN validation cohort, we studied 282 056 statin users and 1 923 840 non-users of statins were studied. METHODS: Cox proportional hazards models in the derivation cohort to derive risk equations. Measures of calibration and discrimination in both validation cohorts. OUTCOMES: 5-Year risk of moderate/serious myopathic events; moderate/serious liver dysfunction; acute renal failure and cataract. RESULTS: The performance of three of the risk prediction algorithms in the THIN cohort was very good. For example, in women, the algorithm for moderate/serious myopathy explained 42.15% of the variation. The corresponding D statistics was 1.75. The acute renal failure algorithm explained 59.62% of the variation (D statistic=2.49). The cataract algorithm explained 59.14% of the variation (D statistic=2.46). The algorithms to predict moderate/severe liver dysfunction only explained 15.55% of the variation (D statistics=0.89). The performance of each algorithm was similar for both sexes when tested on the QResearch validation cohort. CONCLUSIONS: The algorithms to predict acute renal failure, moderate/serious myopathy and cataract could be used to identify patients at increased risk of these adverse effects enabling patients to be monitored more closely. Further research is needed to develop a better algorithm to predict liver dysfunction.