Comparative risk of major cardiovascular events associated with second-line antidiabetic treatments: a retrospective cohort study using UK primary care data linked to hospitalization and mortality records.

AIMS: To examine the risk of major cardiovascular events associated with second-line diabetes therapies, in patients with type 2 diabetes, after adjusting for known cardiovascular risk factors. METHODS: This was a retrospective cohort study of patients prescribed second-line regimens between 1998 and 2011 after first-line metformin. The UK Clinical Practice Research Datalink, with linked national hospitalization and mortality data, for the period up to December 2013, was used. Inverse probability of treatment-weighted time-varying Cox regression models was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing a major cardiovascular event (cardiovascular death, myocardial infarction, stroke, acute coronary syndrome, unstable angina, or coronary revascularization) associated with second-line therapies. Analyses adjusted for patient demographic characteristics, comorbidities, glycated haemoglobin, socio-economic status, ethnicity, smoking status and concurrent medications. RESULTS: A total of 10 118 initiators of a second-line add-on to metformin of either a sulphonylurea (n = 6740), dipeptidyl peptidase-4 (DPP-4) inhibitor (n = 1030) or thiazolidinedione (n = 2348) were identified. After a mean (standard deviation) of 2.4 (1.9) years of follow-up, 386, 36 and 95 major cardiovascular events occurred in sulphonylurea-, DPP-4 inhibitor- and thiazolidinedione-initiators, respectively. In comparison with the metformin-sulphonylurea regimen, adjusted HRs were 0.78 (95% CI 0.55; 1.11) for the metformin-DPP-4 inhibitor regimen and 0.68 (95% CI 0.54; 0.85) for the metformin-thiazolidinedione regimen. CONCLUSIONS: Thiazolidinedione add-on treatments to metformin were associated with lower risks of major cardiovascular disease or cardiovascular death compared with sulphonylurea add-on treatment to metformin. Lower, but non-statistically significant, risks were also found with DPP-4 inhibitor add-on therapies.

A comparison of medication adherence/persistence for asthma and chronic obstructive pulmonary disease in the United Kingdom.

AIM: To describe and compare adherence and persistence with maintenance therapies in patients with asthma or chronic obstructive pulmonary disease (COPD) in the United Kingdom (UK). METHODS: A retrospective prescribing database cohort was obtained from 44 general practitioner surgeries in National Health Service Forth Valley Scotland. Patients with physician-diagnosed asthma or COPD who received maintenance therapy between January 2008 and December 2009 were included. Five classes of therapy were assessed: inhaled corticosteroids, long-acting beta-agonists, combination therapy inhalers, theophyllines and long-acting muscarinic antagonists. Adherence was calculated using the medication possession ratio (MPR) and persistence was determined using Kaplan-Meier survival analysis for the time to discontinuation (TTD) over 1 year. Two step-wise logistic regressions were performed to assess the contribution of diagnosis to adherence/persistence. RESULTS: A total of 13,322 patients were included in the analysis: 10,521 patients with asthma and 2801 patients with COPD. 25.2% of medication episodes for asthma and 45.6% of medication episodes for COPD were classified as having an adequate medication supply (MPR of 80-120%). The overall median TTD was 92 days (IQR, interquartile range: 50-186 days) for patients with asthma and 116 days (IQR: 58-259 days, comparison p < 0.001) for patients with COPD. Patients with COPD were found to be more likely to achieve an MPR of at least 80% (OR: 1.27, 95% CI: 1.15-1.40), but had a similar likelihood of persistence at 1 year to patients with asthma. CONCLUSION: Adherence and persistence with respiratory therapies in the UK is relatively low. There is suggestion that patients with COPD may display more adherent behaviours than patients with asthma.

Presence of bacteriuria caused by trimethoprim resistant bacteria in patients prescribed antibiotics: multilevel model with practice and individual patient data.

OBJECTIVE: To look for evidence of a relation between antibiotic resistance and prescribing by general practitioners by analysis of prescribing at both practice and individual patient level. DESIGN: Repeated cross-sectional study in 1995 and 1996. SETTING: 28 general practices in the Ninewells Hospital laboratory catchment area, Tayside, Scotland. SUBJECTS REVIEWED: 8833 patients registered with the 28 practices who submitted urine samples for analysis. MAIN OUTCOME MEASURES: Resistance to trimethoprim in bacteria isolated from urine samples at practice and individual level simultaneously in a multilevel model. RESULTS: Practices showed considerable variation in both the prevalence of trimethoprim resistance (26-50% of bacteria isolated) and trimethoprim prescribing (67-357 prescriptions per 100 practice patients). Although variation in prescribing showed no association with resistance at the practice level after adjustment for other factors (P = 0.101), in the multilevel model resistance to trimethoprim was significantly associated with age, sex, and individual-level exposure to trimethoprim (P < 0.001) or to other antibiotics (P = 0.002). The association with trimethoprim resistance was strongest for people recently exposed to trimethoprim, and there was no association for people with trimethoprim exposure more than six months before the date of the urine sample. DISCUSSION: Analysis of practice level data obscured important associations between antibiotic prescribing and resistance. The results support efforts to reduce unnecessary prescribing of antibiotics in the community and show the added value of individual patient data for research on the outcomes of prescribing.

Changes in treatment after the start of oral hypoglycaemic therapy in Type 2 diabetes: a population-based study.

AIMS: To determine the changes in oral hypoglycaemic therapy and the time to incidence of insulin therapy in people with Type 2 diabetes. METHODS: A retrospective incidence cohort was constructed of 1305 subjects with Type 2 diabetes, who obtained a first prescription for oral hypoglycaemic medication between 1 July 1993 and 31 December 1994 in Tayside, Scotland. The primary endpoint of changes in oral hypoglycaemic therapy and time to insulin was determined up to the end of the follow-up, on 31 December 1995. RESULTS: Overall, 9.4% of subjects switched to insulin, while 11% of those initially on sulphonylurea, and 6% of those initially on metformin switched to insulin therapy. Approximately three-quarters (72%) remained on the same class of drug throughout the study period (median follow-up 588 days). Only 9% died during the follow-up and this did not differ appreciably by drug group. Males were more likely to switch to insulin compared with females (10.3% vs. 8.5%), and those who switched were slightly younger with a mean age of 58 years compared with a mean age of 60 years of those who did not switch. The median time of switching to insulin was 186 days or approximately 6 months for this cohort, giving a rate of switching to insulin of 5.84% per year. Poorer glycaemic control (HBA1c) and low body mass index (BMI) were associated with switching to insulin. CONCLUSIONS: Following initial therapy with oral hypoglycaemic medication in the population, switching to insulin occurred at a rate of 5.84% per year. Switching to insulin was associated with being younger, male, having low BMI and higher HbA1c.

Epidemiology and economic burden of viral hepatitis: an observational population based study.

OBJECTIVE: To describe the epidemiology and estimate the health resource use of patients with viral hepatitis in Tayside, Scotland, using record linkage techniques. DESIGN: A retrospective observational study. SETTING: Liver disease database, Tayside, Scotland. PATIENTS: All subjects resident in Tayside in the study period 1989-1999 and registered on the Epidemiology of Liver Disease in Tayside (ELDIT) database. MAIN OUTCOME MEASURES: Incidence and prevalence of known viral hepatitis in Tayside, survival of subjects diagnosed with viral hepatitis, and the health resource use with respect to hospital admissions compared with the general population. RESULTS: There were 4992 patients identified with viral hepatitis in the study period 1989-1999; 86 were IgM positive anti-hepatitis A, 187 patients were hepatitis B surface antigen (HBsAg) positive, and 469 were anti-hepatitis C (HCV) positive. HCV and HBsAg seropositive patients were more likely to be hospitalised and stay in hospital longer, less likely to survive after six years, and used more drugs of potential abuse than the general population. There was an increase in cost per admission and per patient as a consequence of liver disease. CONCLUSIONS: A record linkage population based study of viral hepatitis allows outcomes to be identified and costed. Those at risk of viral hepatitis infection in the Tayside population should be informed about the future implication to their health and costs to society. The health service should investigate the cost effectiveness of vaccination and opportunity costs to the health service of viral hepatitis taking into consideration the increasing incidence and prevalence of disease.

Prior trimethoprim use and trimethoprim-resistant urinary tract infection: a nested case-control study with multivariate analysis for other risk factors.

Trimethoprim resistance is increasingly prevalent in community-acquired urinary infections. The objective of this study was to evaluate the association between exposure to community-prescribed trimethoprim and other risk factors in subjects and subsequent trimethoprim-resistant urinary tract infection. The design was a nested case-control study using a record-linkage database. Study subjects submitted a urine sample to the Ninewells Hospital Laboratory between July 1993 and December 1995. Antibiotic exposure in subjects with trimethoprim-resistant isolates (cases) was compared with antibiotic exposure in subjects with trimethoprim-susceptible isolates (controls). Study subjects were drawn from the catchment area of a large teaching hospital in Tayside, Scotland. There were 13765 males and females aged 1-106 years who submitted their first urine sample for culture during the study period. After adjustment for significant risk factors and confounding variables, logistic regression analysis showed exposure to trimethoprim [odds ratio (OR) 4.35] or any antibiotic other than trimethoprim (OR 1.32) to be predictive of resistance. The growth of Proteus spp. (OR 115.14) and bacterial growth other than Escherichia coli and Proteus spp. (OR 2.83) were also predictor variables. Hospitalization in the previous 6 months was not independently associated with trimethoprim resistance. In conclusion, trimethoprim resistance was independently associated with exposure to trimethoprim and to antibiotics other than trimethoprim. Reduction in trimethoprim prescribing alone may not reduce the prevalence of trimethoprim resistance.

Practice factors that influence antibiotic prescribing in general practice in Tayside.

A cohort design was used to evaluate antibiotic prescribing in relation to patient and general practice characteristics. The study included prescribing to all subjects resident in Tayside, from January to December 1994 and found 215217 antibiotic prescriptions dispensed to 118596 people. Training status of general practitioners (GPs) was found to be the characteristic most associated with prescribing. Adjusting for other GP characteristics had little effect on these results. Training practice status was the dominant factor associated with significant differences in rates of antibiotic prescribing, in class of antibiotic prescribed and in performance indicators of antibiotic prescribing.

Community antibiotic therapy, hospitalization and subsequent respiratory tract isolation of Haemophilus influenzae resistant to amoxycillin: a nested case-control study.

The study objective was to determine whether recent community antibiotic prescribing and hospitalization are associated with beta-lactam resistance in respiratory isolates of Haemophilus influenzae. Data obtained for hospitalization and community prescribing (in the previous 3 months) from 412 adults (>15 years) in whom an episode of respiratory tract infection had been described, during which H. influenzae was isolated, were analysed. Seventy-three (17.7%) isolates of H. influenzae were resistant to amoxycillin. Resistance was associated with recent hospitalization [odds ratio (OR) 3.2, 1.8-5.6] and antibiotic exposure in the community (2.1, 1.2-3.6). These variables were independently associated with amoxycillin resistance [hospitalization (OR 4.5, 1. 7-12.5) and community beta-lactam antibiotic exposure (3.9, 1.6-9. 8)]. Hospitalized patients probably received antibiotics during their admission although aquisition of the organism or the beta-lactamase via plasmids from other Gram-negative organisms in the hospital could also be a factor. Control measures to reduce the inappropriate use of antimicrobials in the community and in hospital need to be reinforced.

Selegiline and mortality in subjects with Parkinson's disease: a longitudinal community study.

OBJECTIVE: To estimate mortality by drug use in a cohort of patients with PD relative to age- and sex-matched comparators. METHODS: two longitudinal cohorts of patients with 7 and 11 years' duration of PD were constructed with matched comparators in Tayside, Scotland. Subjects were eligible for inclusion if they received a first prescription for an anti-Parkinson's drug from July 1989 to December 1995, with no PD drug prescription in the previous 6 months. Those who had previously taken a neuroleptic drug or were younger than 40 years of age were excluded. RESULTS: Overall, subjects with PD in relation to comparators had higher mortality with a rate ratio (RR) of 1.76 (95% CI 1.11, 2.81) in the 7-year cohort. There was significantly greater mortality in patients with PD who received levodopa monotherapy (RR = 2.45, 95% CI 1.42, 4.23) relative to the comparators, adjusting for previous cardiovascular drug use and diabetes. However, there was no significant difference in mortality in those with PD receiving combination therapy of selegiline with levodopa and other drugs in relation to the comparators (RR = 0.92, 95% CI 0.37, 2.31). CONCLUSIONS: Subjects with PD had twice the rate of mortality relative to age- and sex-matched comparators. However, those subjects who received selegiline at any time in combination with co-careldopa or co-beneldopa showed no significant difference in mortality compared with the comparators. Monotherapy with levodopa was associated with the highest mortality.

Factors associated with trimethoprim-resistant bacteria isolated from urine samples.

Urine samples with trimethoprim-resistant or trimethoprim-sensitive Gram-negative bacteria and samples with no bacterial growth (NG) were identified. Age-sex matched community controls were generated with each trimethoprim-resistant case. These four groups were evaluated for exposure. Prior trimethoprim use was significantly more common in the trimethoprim-resistant group when compared with the trimethoprim-sensitive or the NG group. Prior hospitalization was significantly less common in the trimethoprim-resistant than the trimethoprim-sensitive group, but not with the NG group. Prior oestrogen exposure was associated with trimethoprim resistance. There were no associations found for diabetes or prior corticosteroid exposure. Community controls were found to be inappropriate controls for the study of trimethoprim-resistant bacteria in urine samples.

The doctor-patient relationship and prescribing patterns. A view from primary care.

The doctor-patient relationship has been described in economic terms as an 'agency relationship' where informed agents make decisions for uninformed clients. However, the decision to prescribe and the decision to accept the prescription by the patient are more complex in nature and involve many variables. Other factors, such as the 'need' for the prescription and the disease state (acute or chronic) also influence prescribing practice. Communication between the physician and patient was found to be important for rational and effective prescribing. The client can make better decisions with the relevant information, thus breaking down the agency relationship that once existed.

Do H2-receptor antagonists cause acute pancreatitis?

The aim of this study was to investigate the association between H(2)-receptor antagonists and acute pancreatitis. The automated database of the Medicines Monitoring Unit (MEMO) was used to carry out a case-control study, supplemented with information on possible confounding factors from hospital and GP medical records. Cases were patients hospitalized with a computerized diagnosis of acute pancreatitis, and two sets of controls were drawn from (1) the study population and from (2) the same GP practice as the case. Current or 60-day exposure to cimetidine and ranitidine was analysed. In adjusted analyses, cimetidine exposure and ranitidine exposure were associated with an increased risk of hospitalization for acute pancreatitis, as were alcohol abuse and cholelithiasis. The risks were lower in unadjusted analyses, suggesting that the association is confounded, although they did not disappear completely. A possible explanation is that data on confounding were incomplete. This study cannot discount the existence of an association between H(2)-antagonists and acute pancreatitis, and highlights the difficulties involved in obtaining complete and accurate data on confounding factors that are not collected routinely.