Steroid dependency and trends in prescribing for inflammatory bowel disease - a 20-year national population-based study.

BACKGROUND: It is unclear whether adherence to prescribing standards has been achieved in inflammatory bowel disease (IBD). AIM: To determine how prescribing of 5-aminosalicylates (5-ASAs), steroids and thiopurines has changed in response to emerging evidence. METHODS: We examined trends in oral and topical therapies in 23 509 incident IBD cases (6997 with Crohn's disease and 16 512 with ulcerative colitis) using a nationally representative sample between 1990 and 2010. We created five eras according to the year of diagnosis: era 1 (1990-1993), era 2 (1994-1997), era 3 (1998-2001), era 4 (2002-2005) and era 5 (2006-2010). We calculated the proportion of patients treated with prolonged 5-ASAs (>12 months) and steroid dependency, defined as prolonged steroids (>3 months) or recurrent (restarting within 3 months) steroid exposure. We calculated the cumulative probability of receiving each medication using survival analysis. RESULTS: Half of the Crohn's disease patients were prescribed prolonged oral 5-ASAs during the study, although this decreased between era 3 and 5 from 61.8% to 56.4% (P = 0.002). Thiopurine use increased from 14.0% to 47.1% (P < 0.001) between era 1 and 5. This coincided with a decrease in steroid dependency from 36.5% to 26.8% (P < 0.001) between era 1 and 2 and era 4 and 5 respectively. In ulcerative colitis, 49% of patients were maintained on prolonged oral 5-ASAs. Despite increasing thiopurine use, repeated steroid exposure increased from 15.3% to 17.8% (P = 0.02) between era 1 and 2 and era 4 and 5 respectively. CONCLUSIONS: Prescribing in clinical practice insufficiently mirrors the evidence base. Physicians should direct management towards reducing steroid dependency and optimising 5-ASA use in patients with IBD.

Impact of early thiopurines on surgery in 2770 children and young people diagnosed with inflammatory bowel disease: a national population-based study.

BACKGROUND: The role of early thiopurine treatment in inflammatory bowel disease (IBD) is unproven. AIM: To quantify the impact of timing and duration of thiopurines on the risk of first surgery in children and young people with IBD using a population-based cohort. METHODS: We constructed an incident cohort of children and young people aged <25 years, diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) from 1990 to 2009. We used Cox proportional hazards modelling to determine the impact of early thiopurine use, commenced within a year of diagnosis on risk of first surgery. RESULTS: We identified 1595 and 1175 incident cases of CD and UC respectively with a mean length of follow-up of 4.3 years/person. There were 216 (13.5%) and 73 (6.2%) surgeries for CD and UC patients between 1990 and 2009 respectively. In CD among thiopurine users, the absolute risk of surgery at 5 years for early thiopurine use vs. late was 15.3% (95% CI: 10.5-22.1) vs. 22.1% (95% CI: 18.1-26.9) respectively. After adjustment, the early use of thiopurines was associated with a reduction in risk of first surgery of 39% (HR 0.61, 95% CI: 0.41-0.91) over the 20-year study period. In UC, early thiopurine use offered no additional benefit. CONCLUSIONS: In Crohn's disease, early treatment with thiopurines in children and young people is associated with an appreciable reduction in the risk of surgery, but early treatment does not reduce surgical risk in UC.

The impact of timing and duration of thiopurine treatment on colectomy in ulcerative colitis: a national population-based study of incident cases between 1989-2009.

BACKGROUND: The role of thiopurines in altering the risk of colectomy in ulcerative colitis (UC) remains unclear. AIMS: To examine predictors of colectomy in UC and determine the impact of thiopurines on the risk of colectomy. METHODS: We constructed a population-based cohort of incident cases of UC in the United Kingdom between 1989 and 2009. We determined trends in thiopurine usage and colectomy for three defined cohorts: era 1 (1989-1995), era 2 (1996-2002), era 3 (2003-2009). We used Cox regression to determine predictors of colectomy and quantified the impact of duration and timing of thiopurine use on the risk of colectomy. RESULTS: We identified 8673 incident cases of UC. 5-year colectomy rates increased from 4.2%, 5.1% to 6.9% (P = 0.001) for era 1, era 2 and era 3, respectively, despite increasing thiopurine use. This was not significant after adjustment for predictors of colectomy (P = 0.06). There was a higher risk of colectomy in men (HR 1.44, 95% CI: 1.19-1.73), those diagnosed at an early age (HR 1.35, 95% CI: 1.04-1.75; 16-24 vs. 25-64) and early steroid users (HR 1.94, 95% CI: 1.59-2.37). 5-ASA users were less likely to require a colectomy (HR 0.35, 95% CI: 0.28-0.44). Amongst thiopurine users, those treated for greater than 12 months had a 71% reduction in risk of colectomy (HR 0.29, 95% CI: 0.21-0.40). Early thiopurines offered no additional benefit. CONCLUSIONS: Thiopurine exposure for greater than 12 months reduces the likelihood of colectomy by 71%. Young men and those requiring steroids within 3 months of diagnosis are at greatest risk of colectomy, and most likely to benefit from sustained thiopurine use.

Clinical data integration model. Core interoperability ontology for research using primary care data.

INTRODUCTION: This article is part of the Focus Theme of METHODS of Information in Medicine on "Managing Interoperability and Complexity in Health Systems". BACKGROUND: Primary care data is the single richest source of routine health care data. However its use, both in research and clinical work, often requires data from multiple clinical sites, clinical trials databases and registries. Data integration and interoperability are therefore of utmost importance. OBJECTIVES: TRANSFoRm's general approach relies on a unified interoperability framework, described in a previous paper. We developed a core ontology for an interoperability framework based on data mediation. This article presents how such an ontology, the Clinical Data Integration Model (CDIM), can be designed to support, in conjunction with appropriate terminologies, biomedical data federation within TRANSFoRm, an EU FP7 project that aims to develop the digital infrastructure for a learning healthcare system in European Primary Care. METHODS: TRANSFoRm utilizes a unified structural / terminological interoperability framework, based on the local-as-view mediation paradigm. Such an approach mandates the global information model to describe the domain of interest independently of the data sources to be explored. Following a requirement analysis process, no ontology focusing on primary care research was identified and, thus we designed a realist ontology based on Basic Formal Ontology to support our framework in collaboration with various terminologies used in primary care. RESULTS: The resulting ontology has 549 classes and 82 object properties and is used to support data integration for TRANSFoRm's use cases. Concepts identified by researchers were successfully expressed in queries using CDIM and pertinent terminologies. As an example, we illustrate how, in TRANSFoRm, the Query Formulation Workbench can capture eligibility criteria in a computable representation, which is based on CDIM. CONCLUSION: A unified mediation approach to semantic interoperability provides a flexible and extensible framework for all types of interaction between health record systems and research systems. CDIM, as core ontology of such an approach, enables simplicity and consistency of design across the heterogeneous software landscape and can support the specific needs of EHR-driven phenotyping research using primary care data.

Obesity paradox in people newly diagnosed with type 2 diabetes with and without prior cardiovascular disease.

AIM: To address the debate on 'obesity paradox' in patients with type 2 diabetes mellitus (T2DM) by evaluating the cardiovascular and mortality risks associated with normal and overweight patients compared to obese at diagnosis of diabetes, separately for patients with and without cardiovascular disease (CVD) before diagnosis. METHODS: A retrospective study with two study cohorts with/without prior CVD (n = 10237/37272) with complete measures of body mass index (BMI) at diagnosis of T2DM from UK General Practice Research Database. Primary outcomes were long-term risks of cardiovascular events (CVEs) and all-cause mortality in patients with normal weight, overweight and obesity at diagnosis. RESULTS: The mortality rates per 1000 person-years in normal weight, overweight and obese patients among patients without prior CVD were 13.1, 8.6 and 6.0, respectively, during 5 years of median follow-up. For patients with prior CVD, these estimates were 30.1, 21.1 and 15.5, respectively. Among patients without and with prior CVD, normal weight patients had 47% (hazard ratio, HR CI: 1.29, 1.69) and 30% (HR CI: 1.11, 1.53) increased mortality risk respectively compared to obese patients. In the cohort without prior CVD, compared to obese patients, those with normal body weight did not have increased CVE risk. Interactions between age, HbA1c and BMI at diagnosis were observed in both cohorts. CONCLUSIONS: Adults with normal weight at the diagnosis of T2DM have significantly higher mortality risk compared to those who are obese, with significant interactions between age, BMI and HbA1c. Elevated cardiovascular risk was not observed in normal weight patients without prior CVD.

Key concepts to assess the readiness of data for international research: data quality, lineage and provenance, extraction and processing errors, traceability, and curation. Contribution of the IMIA Primary Health Care Informatics Working Group.

OBJECTIVE: To define the key concepts which inform whether a system for collecting, aggregating and processing routine clinical data for research is fit for purpose. METHODS: Literature review and shared experiential learning from research using routinely collected data. We excluded socio-cultural issues, and privacy and security issues as our focus was to explore linking clinical data. RESULTS: Six key concepts describe data: (1) DATA QUALITY: the core Overarching concept - Are these data fit for purpose? (2) Data provenance: defined as how data came to be; incorporating the concepts of lineage and pedigree. Mapping this process requires metadata. New variables derived during data analysis have their own provenance. (3) Data extraction errors and (4) Data processing errors, which are the responsibility of the investigator extracting the data but need quantifying. (5) Traceability: the capability to identify the origins of any data cell within the final analysis table essential for good governance, and almost impossible without a formal system of metadata; and (6) Curation: storing data and look-up tables in a way that allows future researchers to carry out further research or review earlier findings. CONCLUSION: There are common distinct steps in processing data; the quality of any metadata may be predictive of the quality of the process. Outputs based on routine data should include a review of the process from data origin to curation and publish information about their data provenance and processing method.