Vasa Curcin

Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database

Objective To investigate the risk of incident myocardial infarction, congestive heart failure, and all cause mortality associated with prescription of oral antidiabetes drugs. Design Retrospective cohort study. Setting UK general practice research database, 1990-2005. Participants 91 521 people with diabetes. Main outcome measures Incident myocardial infarction, congestive heart failure, and all cause mortality. Person time intervals for drug treatment were categorised by drug class, excluding non-drug intervals and intervals for insulin. Results 3588 incident cases of myocardial infarction, 6900 of congestive heart failure, and 18 548 deaths occurred. Compared with metformin, monotherapy with first or second generation sulphonylureas was associated with a significant 24% to 61% excess risk for all cause mortality (P<0.001) and second generation sulphonylureas with an 18% to 30% excess risk for congestive heart failure (P=0.01 and P<0.001). The thiazolidinediones were not associated with risk of myocardial infarction; pioglitazone was associated with a significant 31% to 39% lower risk of all cause mortality (P=0.02 to P<0.001) compared with metformin. Among the thiazolidinediones, rosiglitazone was associated with a 34% to 41% higher risk of all cause mortality (P=0.14 to P=0.01) compared with pioglitazone. A large number of potential confounders were accounted for in the study; however, the possibility of residual confounding or confounding by indication (differences in prognostic factors between drug groups) cannot be excluded. Conclusions Our findings suggest a relatively unfavourable risk profile of sulphonylureas compared with metformin for all outcomes examined. Pioglitazone was associated with reduced all cause mortality compared with metformin. Pioglitazone also had a favourable risk profile compared with rosiglitazone; although this requires replication in other studies, it may have implications for prescribing within this class of drugs.

Scientific workflow systems - can one size fit all?

The past decade has witnessed a growing trend in designing and using workflow systems with a focus on supporting the scientific research process in bioinformatics and other areas of life sciences. The aim of these systems is mainly to simplify access, control and orchestration of remote distributed scientific data sets using remote computational resources, such as EBI web services. In this paper we present the state of the art in the field by reviewing six such systems: Discovery Net, Taverna, Triana, Kepler, Yawl and BPEL. We provide a high-level framework for comparing the systems based on their control flow and data flow properties with a view of both informing future research in the area by academic researchers and facilitating the selection of the most appropriate system for a specific application task by practitioners.

Discovery net: towards a grid of knowledge discovery

This paper provides a blueprint for constructing collaborative and distributed knowledge discovery systems within Grid-based computing environments. The need for such systems is driven by the quest for sharing knowledge, information and computing resources within the boundaries of single large distributed organisations or within complex Virtual Organisations (VO) created to tackle specific projects. The proposed architecture is built on top of a resource federation management layer and is composed of a set of different resources. We show how this architecture will behave during a typical KDD process design and deployment, how it enables the execution of complex and distributed data mining tasks with high performance and how it provides a community of e-scientists with means to collaborate, retrieve and reuse both KDD algorithms, discovery processes and knowledge in a visual analytical environment.

Statin Induced Myopathy and Myalgia: Time Trend Analysis and Comparison of Risk Associated with Statin Class from 1991–2006

Background Statins are widely used as a cholesterol lowering medication, reduce cardiovascular mortality and morbidity in high risk patients; and only rarely cause serious adverse drug reactions (ADRs). UK primary care databases of morbidity and prescription data, which now cover several million people, have potential for more powerful analytical approaches to study ADRs including adjusting for confounders and examining temporal effects. Methods Case-crossover design in detecting statin associated myopathy ADR in 93, 831 patients, using two independent primary care databases (1991–2006). We analysed risk by drug class, by disease code and cumulative year, exploring different cut-off exposure times and confounding by temporality. Results Using a 12 and 26 week exposure period, large risk ratios (RR) are associated with all classes of statins and fibrates for myopathy: RR 10.6 (9.8–11.4) and 19.9 (17.6–22.6) respectively. At 26 weeks, the largest risks are with fluvastatin RR 33.3 (95% CI 16.8–66.0) and ciprofibrate (with previous statin use) RR 40.5 (95% CI 13.4–122.0). AT 12 weeks the differences between cerivastatin and atorvastatin RR for myopathy were found to be significant, RR 2.05 (95% CI 1.2–3.5), and for rosuvastatin and fluvastatin RR 3.0 (95% CI 1.6–5.7). After 12 months of statin initiation, the relative risk for myopathy for all statins and fibrates increased to 25.7 (95% CI 21.8–30.3). Furthermore, this signal was detected within 2 years of first events being recorded. Our data suggests an annual incidence of statin induced myopathy or myalgia of around 11.4 for 16, 591 patients or 689 per million per year. Conclusion There may be differential risks associated with some classes of statin and fibrate. Myopathy related to statin or fibrate use may persist after a long exposure time (12 months or more). These methods could be applied for early detection of harmful drug side effects, using similar primary care diagnostic and prescribing data.

Association of systolic and diastolic blood pressure and all cause mortality in people with newly diagnosed type 2 diabetes: retrospective cohort study

Objective To examine the effect of systolic and diastolic blood pressure achieved in the first year of treatment on all cause mortality in patients newly diagnosed with type 2 diabetes, with and without established cardiovascular disease. Design Retrospective cohort study. Setting United Kingdom General Practice Research Database, between 1990 and 2005. Participants 126 092 adult patients (age ≥18 years) with a new diagnosis of type 2 diabetes who had been registered with participating practices for at least 12 months. Main outcome measure All cause mortality. Results Before diagnosis, 12 379 (9.8%) patients had established cardiovascular disease (myocardial infarction or stroke). During a median follow-up of 3.5 years, we recorded 25 495 (20.2%) deaths. In people with cardiovascular disease, tight control of systolic (<130 mm Hg) and diastolic (<80 mm Hg) blood pressure was not associated with improved survival, after adjustment for baseline characteristics (age at diagnosis, sex, practice level clustering, deprivation score, body mass index, smoking, HbA1c and cholesterol levels, and blood pressure). Low blood pressure was also associated with an increased risk of all cause mortality. Compared with patients who received usual control of systolic blood pressure (130-139 mm Hg), the hazard ratio of all cause mortality was 2.79 (95% confidence interval 1.74 to 4.48, P<0.001) for systolic blood pressure at 110 mm Hg. Compared with patients who received usual control of diastolic blood pressure (80-84 mm Hg), the hazard ratios were 1.32 (1.02 to 1.78, P=0.04) and 1.89 (1.40 to 2.56, P<0.001) for diastolic blood pressures at 70-74 mm Hg and lower than 70 mm Hg, respectively. Similar associations were found in people without cardiovascular disease. Subgroup analyses of people diagnosed with hypertension and who received treatment for hypertension confirmed initial findings. Conclusion Blood pressure below 130/80 mm Hg was not associated with reduced risk of all cause mortality in patients with newly diagnosed diabetes, with or without known cardiovascular disease. Low blood pressure, particularly below 110/75 mm Hg, was associated with an increased risk for poor outcomes.

The impact of timing and duration of thiopurine treatment on first intestinal resection in Crohn's disease: national UK population-based study 1989-2010.

OBJECTIVES:The efficacy of thiopurines (TPs) in altering the risk of surgery in Crohns disease (CD) remains controversial. We evaluated the impact of TP therapy, optimal timing, and duration of TP therapy on first intestinal resection rates using a population-based cohort.METHODS:We constructed a population-based cohort of incident cases of CD between 1989 and 2005. We used the Kaplan–Meier analysis to calculate time trends in TP use and first intestinal resection in three groups defined by time period of diagnosis: 1989–1993, 1994–1999, and 2000–2005 groups A, B, and C, respectively. We quantified impact of duration and timing of TP treatment on likelihood of surgery using Cox regression and propensity score matching.RESULTS:We identified 5,640 eligible patients with CD. The 5-year cumulative probability of TP use increased from 12, 18, to 25% ( P<0.0001) while probability of first intestinal resection decreased from 15, 12 to 9% (P<0.001) in groups A, B, and C, respectively. Patients treated with at least 6 months of TP therapy had a 44% reduction in the risk of surgery (hazards ratio (HR): 0.56; 95% confidence interval (CI): 0.37–0.85) and those receiving at least 12 months of TP therapy had a 69% reduction in the risk of surgery (HR: 0.31; 95% CI: 0.22–0.44). Early treatment (<12 months from diagnosis) vs. late treatment with TP showed no additional benefit in reducing risk of surgery (HR: 0.41; 95% CI: 0.27–0.61 vs. 0.21; 95% CI: 0.13–0.34).CONCLUSIONS:Over the past 20 years, TP use has doubled, whereas intestinal surgery has fallen by one-third among the UK population of Crohns patients. Prolonged exposure is associated with a reduced likelihood of surgery whereby more than 12 months TP therapy reduces the risk of first intestinal surgery two-fold; however, early initiation of TP treatment offered no apparent additional benefit.

Pay for perfomance and the quality of diabetes management in individuals with and without co-morbid medical conditions

Summary Objective To examine the impact of the Quality and Outcomes Framework, a major pay-for-performance incentive introduced in the UK during 2004, on diabetes management in patients with and without co-morbidity. Design Cohort study comparing actual achievement of treatment targets in 2004 and 2005 with that predicted by the underlying (pre-intervention) trend in diabetes patients with and without co-morbid conditions. Setting A total of 422 general practices participating in the General Practice Research Database. Main outcomes measures Achievement of diabetes treatment targets for blood pressure (< 140/80 mm Hg), HbA1c (≤ 7.0%) and cholesterol (≤ 5 mmol/L). Results The percentage of diabetes patients with co-morbidity reaching blood pressure and cholesterol targets exceeded that predicted by the underlying trend during the first two years of pay for perfomance (by 3.1% [95% CI 1.1–5.1] for BP and 4.1% [95% CI 2.2–6.0] for cholesterol among patients with ≥ 5 co-morbidities in 2005). Similar improvements were evident in patients without co-morbidity, except for cholesterol control in 2004 (−0.2% [95% CI −1.7–1.4]). The percentage of patients meeting the HbA1c target in the first two years of this program was significantly lower than predicted by the underlying trend in all patients, with the greatest shortfall in patients without co-morbidity (3.8% [95% CI 2.6–5.0] lower in 2005). Patients with co-morbidity remained significantly more likely to meet treatment targets for cholesterol and HbA1c than those without after the introduction of pay for perfomance. Conclusions Diabetes patients with co-morbid conditions appear to have benefited more from this pay-for-performance program than those without co-morbidity.

Web services in the life sciences

Web services provide a standard way of publishing applications and data sources over the internet, enabling mass dissemination of knowledge. In the life sciences, the web-service approach is seen as being a road to standardizing the multitude of tools available from different providers. In this article, we present an overview of the technology (focusing on life-science applications), we list the currently available service providers and we discuss advanced issues raised by the concept.

A unified structural/terminological interoperability framework based on LexEVS: application to TRANSFoRm

Objective Biomedical research increasingly relies on the integration of information from multiple heterogeneous data sources. Despite the fact that structural and terminological aspects of interoperability are interdependent and rely on a common set of requirements, current efforts typically address them in isolation. We propose a unified ontology-based knowledge framework to facilitate interoperability between heterogeneous sources, and investigate if using the LexEVS terminology server is a viable implementation method. Materials and methods We developed a framework based on an ontology, the general information model (GIM), to unify structural models and terminologies, together with relevant mapping sets. This allowed a uniform access to these resources within LexEVS to facilitate interoperability by various components and data sources from implementing architectures. Results Our unified framework has been tested in the context of the EU Framework Program 7 TRANSFoRm project, where it was used to achieve data integration in a retrospective diabetes cohort study. The GIM was successfully instantiated in TRANSFoRm as the clinical data integration model, and necessary mappings were created to support effective information retrieval for software tools in the project. Conclusions We present a novel, unifying approach to address interoperability challenges in heterogeneous data sources, by representing structural and semantic models in one framework. Systems using this architecture can rely solely on the GIM that abstracts over both the structure and coding. Information models, terminologies and mappings are all stored in LexEVS and can be accessed in a uniform manner (implementing the HL7 CTS2 service functional model). The system is flexible and should reduce the effort needed from data sources personnel for implementing and managing the integration.

Association of practice size and pay-for-performance incentives with the quality of diabetes management in primary care.

Background: Not enough is known about the association between practice size and clinical outcomes in primary care. We examined this association between 1997 and 2005, in addition to the impact of the Quality and Outcomes Framework, a pay-for-performance incentive scheme introduced in the United Kingdom in 2004, on diabetes management. Methods: We conducted a retrospective open-cohort study using data from the General Practice Research Database. We enrolled 422 general practices providing care for 154 945 patients with diabetes. Our primary outcome measures were the achievement of national treatment targets for blood pressure, glycated hemoglobin (HbA1c) levels and total cholesterol. Results: We saw improvements in the recording of process of care measures, prescribing and achieving intermediate outcomes in all practice sizes during the study period. We saw improvement in reaching national targets after the introduction of the Quality and Outcomes Framework. These improvements significantly exceeded the underlying trends in all practice sizes for achieving targets for cholesterol level and blood pressure, but not for HbA1c level. In 1997 and 2005, there were no significant differences between the smallest and largest practices in achieving targets for blood pressure (1997 odds ratio [OR] 0.98, 95% confidence interval [CI] 0.82 to 1.16; 2005 OR 0.92, 95% CI 0.80 to 1.06 in 2005), cholesterol level (1997 OR 0.94, 95% CI 0.76 to 1.16; 2005 OR 1.1, 95% CI 0.97 to 1.40) and glycated hemoglobin level (1997 OR 0.79, 95% CI 0.55 to 1.14; 2005 OR 1.05, 95% CI 0.93 to 1.19). Interpretation: We found no evidence that size of practice is associated with the quality of diabetes management in primary care. Pay-for-performance programs appear to benefit both large and small practices to a similar extent.