Mark McGilchrist

Primary non-compliance with prescribed medication in primary care.

OBJECTIVE--To determine the rate of patients not redeeming their prescriptions (primary noncompliance) and assess the factors influencing this. DESIGN--Observational study comparing copies of prescriptions written by general practitioners with those dispensed by pharmacists and subsequent case record review. SETTING--A large rural general practice in Tayside. SUBJECTS--All 4854 patients who received prescriptions (20,921) written between January 1989 and March 1989. MAIN OUTCOME MEASURES--The rate of non-redemption of prescriptions. RESULTS--Seven hundred and two patients (14.5%) did not redeem 1072 (5.2%) prescriptions during the study period, amounting to 11.5% of men and 16.3% of women. Non-redemption was highest in women aged 16-29 (27.6% of women) and men aged 40-49 (18.3% of men). Of prescriptions issued to women for oral contraceptives 24.8% were not redeemed during the study period. In those who redeemed prescriptions 17% were not exempt from prescription charges compared with 33% of patients who failed to redeem them. The non-redemption rate was highest for prescriptions issued at the weekends, although this was a small proportion of all prescribing. Prescriptions issued by trainee general practitioners were also less likely to be redeemed. CONCLUSIONS--Non-redemption varies with age, sex, general practitioner, exemption status, and with day of the week the prescription was written. Observational studies of drug exposure can be more accurately estimated from dispensing rather than prescribing data.

Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study.

Abstract Objectives: To determine the profile of risk of upper gastrointestinal toxicity during continuous treatment with, and after cessation of, non-steroidal anti-inflammatory drugs. Design: Cohort study with a prospectively constructed, population based, record linkage database containing details of exposure to all community dispensed non-steroidal anti-inflammatory drugs and also all admissions to hospital for upper gastrointestinal diagnoses. Setting: The population of Tayside, Scotland. Subjects: 52 293 subjects aged 50 and over who received one or more non-steroidal anti-inflammatory between 1 January 1989 and 31 December 1991 and 73 792 subjects who did not receive one during the same period (controls). Main outcome measures: Admission to hospital for upper gastrointestinal bleeding and perforation, and admission for other upper gastrointestinal diagnoses. Results: About 2% of the non-steroidal anti-inflammatory cohort were admitted with an upper gastrointestinal event during the study period compared with 1.4% of controls. The risk of admission for upper gastrointestinal haemorrhage and perforation was constant during continuous non-steroidal anti-inflammatory exposure and carried over after the end of exposure. The results were similar for admissions for all upper gastrointestinal events. Conclusion: This study provides evidence that non-steroidal anti-inflammatory toxicity persists with continuous exposure. There seems to be carryover toxicity after the end of prescribing. These findings have implications for the management of patients requiring non-steroidal anti-inflammatory drugs. Key messages The risk of upper gastrointestinal toxicity associated with non-steroidal anti-inflammatory drugs is constant with continuous exposure Gastrointestinal toxicity continues for some time after treatment stops Such toxicity is common in older patients and patients with a history of upper gastrointestinal disease Non-steroidal anti-inflammatory drugs should be avoided when possible; when they are used the lowest effective dose of the least toxic drug should be used for the shortest period possible

Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study

Abstract Objective: To evaluate the relation between topically applied non-steroidal anti-inflammatory drugs and upper gastrointestinal bleeding and perforation. Design: A case-control study with 1103 patients admitted to hospital for upper gastrointestinal bleeding or perforation between January 1990 and December 1992 (cases). Two different control groups were used, with six community controls and with two hospital controls for each case. Previous exposure to topical and oral non-steroidal anti-inflammatory drugs and ulcer healing drugs was assessed. Study population--The population of 319465 people who were resident in Tayside and were registered with a Tayside general practitioner between January 1989 and October 1994. A record linkage database containing all data on hospital events and dispensed drugs between 1989 and 1992 was used for this population. Main outcome measures: Unadjusted and adjusted odds ratios of exposure in those admitted to hospital compared with controls. Results: Significant unadjusted associations were detected between all three classes of drug and upper gastrointestinal complications. The significant association detected for topical non-steroidal anti-inflammatory drugs was no longer evident in analyses which adjusted for the confounding effect of concomitant exposure to oral anti-inflammatories and ulcer healing drugs (odds ratio=1.45; 95% confidence interval 0.84 to 2.50 with community controls; 1.06; 0.60 to 1.88 with hospital controls). Conclusion: In this study topical non-steroidal anti-inflammatory drugs were not significantly associated with upper gastrointestinal bleeding and perforation after adjustment for the confounding effects of concomitant use of oral anti-inflammatories and ulcer healing drugs.

Drug exposure risk windows and unexposed comparator groups for cohort studies in pharmacoepidemiology

Aim—To determine the appropriate size of risk windows in both exposed and unexposed sub‐cohorts.

A cohort study (with re-sampled comparator groups) to measure the association between new NSAID prescribing and upper gastrointestinal hemorrhage and perforation☆

This cohort study examined the relationship between newly prescribed NSAIDs (none in the previous six months) and upper gastrointestinal hemorrhage and perforation in Tayside, Scotland. Exposure was classified by prescription duration. The study population consisted of the population of Tayside. A Comparator Group was chosen at random (within age and sex strata). Two hundred re-sampled comparator groups were created. Statistical analyses were carried out by Poisson regression (repeated for each of the re-samples). The analyses controlled for age, sex, prior hospitalization for upper gastrointestinal events, prior endoscopy, and the use of ulcer healing drugs. There were 78,191 subjects in the NSAID group, and 78,207 in each of the comparator groups. The increased risk with NSAIDs was only apparent for subjects without a history of upper gastrointestinal events; univariate rate ratio = 2.76 (1.90, 4.01). The final, re-sampled estimate of NSAID risk was rate ratio = 2.48 (1.87, 3.29).

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.

Translational Medicine and Patient Safety in Europe: TRANSFoRm—Architecture for the Learning Health System in Europe

The Learning Health System (LHS) describes linking routine healthcare systems directly with both research translation and knowledge translation as an extension of the evidence-based medicine paradigm, taking advantage of the ubiquitous use of electronic health record (EHR) systems. TRANSFoRm is an EU FP7 project that seeks to develop an infrastructure for the LHS in European primary care. Methods. The project is based on three clinical use cases, a genotype-phenotype study in diabetes, a randomised controlled trial with gastroesophageal reflux disease, and a diagnostic decision support system for chest pain, abdominal pain, and shortness of breath. Results. Four models were developed (clinical research, clinical data, provenance, and diagnosis) that form the basis of the projects approach to interoperability. These models are maintained as ontologies with binding of terms to define precise data elements. CDISC ODM and SDM standards are extended using an archetype approach to enable a two-level model of individual data elements, representing both research content and clinical content. Separate configurations of the TRANSFoRm tools serve each use case. Conclusions. The project has been successful in using ontologies and archetypes to develop a highly flexible solution to the problem of heterogeneity of data sources presented by the LHS.

Cardiovascular risk factors associated with the metabolic syndrome are more prevalent in people reporting chronic pain: Results from a cross-sectional general population study

Summary The prevalence of cardiovascular risk factors and metabolic syndrome are increased in chronic pain. This may contribute to the reduced life expectancy in these patients. ABSTRACT To explore whether chronic pain is associated with cardiovascular risk factors and identify whether increased distribution or intensity of pain is associated with cardiovascular risk, participants in Generation Scotland: The Scottish Family Health study completed pain questionnaires recording the following: presence of chronic pain, distribution of pain, and intensity of chronic pain. Blood pressure, lipids, blood glucose, smoking history, waist–hip ratio, and body mass index were recorded; Framingham 10‐year coronary heart disease (CHD) risk scores were calculated and a diagnosis of metabolic syndrome derived. Associations between chronic pain and cardiovascular risk were explored. Of 13,328 participants, 1100 (8.3%) had high CHD risk. Chronic pain was reported by 5209 (39%), 1294 (9.7%) reported widespread chronic pain, and 707 (5.3%) reported high‐intensity chronic pain. In age‐ and gender‐adjusted analyses, chronic pain was associated with elevated CHD risk scores (odds ratio 1.11, 95% confidence interval 1.01–1.23) and the metabolic syndrome (odds ratio 1.42, 95% confidence interval 1.24–1.62). Multivariate analyses identified dyslipidaemia, age, gender, smoking, obesity, and high waist–hip ratio as independently associated with chronic pain. Within the chronic pain subgroup, widespread pain did not confer any additional cardiovascular disease risk. However, cardiovascular disease risk factors contributing to metabolic syndrome were more prevalent in those reporting high‐intensity chronic pain. This large population‐based study has demonstrated that chronic pain, and in particular high‐intensity chronic pain, is associated with an increased prevalence of cardiovascular risk factors and metabolic syndrome. The 10‐year CHD risk score and metabolic syndrome correlate well with increased pain intensity, but not with widespread pain.

Assuring the confidentiality of shared electronic health records

Sharing data between multiple institutions offers better regulation and public protection

Sero-Prevalence and Incidence of A/H1N1 2009 Influenza Infection in Scotland in Winter 2009–2010

Background Sero-prevalence is a valuable indicator of prevalence and incidence of A/H1N1 2009 infection. However, raw sero-prevalence data must be corrected for background levels of cross-reactivity (i.e. imperfect test specificity) and the effects of immunisation programmes. Methods and Findings We obtained serum samples from a representative sample of 1563 adults resident in Scotland between late October 2009 and April 2010. Based on a microneutralisation assay, we estimate that 44% (95% confidence intervals (CIs): 40–47%) of the adult population of Scotland were sero-positive for A/H1N1 2009 influenza by 1 March 2010. Correcting for background cross-reactivity and for recorded vaccination rates by time and age group, we estimated that 34% (27–42%) were naturally infected with A/H1N1 2009 by 1 March 2010. The central estimate increases to >40% if we allow for imperfect test sensitivity. Over half of these infections are estimated to have occurred during the study period and the incidence of infection in late October 2009 was estimated at 4.3 new infections per 1000 people per day (1.2 to 7.2), falling close to zero by April 2010. The central estimate increases to over 5.0 per 1000 if we allow for imperfect test specificity. The rate of infection was higher for younger adults than older adults. Raw sero-prevalences were significantly higher in more deprived areas (likelihood ratio trend statistic = 4.92,1 df, P = 0.03) but there was no evidence of any difference in vaccination rates. Conclusions We estimate that almost half the adult population of Scotland were sero-positive for A/H1N1 2009 influenza by early 2010 and that the majority of these individuals (except in the oldest age classes) sero-converted as a result of natural infection with A/H1N1 2009. Public health planning should consider the possibility of higher rates of infection with A/H1N1 2009 influenza in more deprived areas.