Scientific
publications

INTRODUCTION: Transient ischaemic attack (TIA) is defined by short-lasting, stroke-like symptoms, and is recognised as a medical emergency. Symptoms are assumed to completely resolve, and treatment is focused on secondary stroke/TIA prevention. However, evidence suggests that patients with TIA may experience ongoing residual impairments, which they do not receive therapy for as standard practice. TIA-induced sequelae could impact on patients' quality of life and ability to return to work or social activities. We aim to investigate whether TIA is associated with subsequent consultation for fatigue, psychological or cognitive impairment in primary care. METHODS AND ANALYSIS: A retrospective open cohort study of patients with first-ever TIA and matched controls. Relevant data will be extracted from The Health Improvement Network (THIN) database, an anonymised primary care database which includes data for over 12 million patients and covers approximately 6% of the UK population. Outcomes will be the first consultation for fatigue, anxiety, depression, post-traumatic stress disorder or cognitive impairment. Principal analysis will use Kaplan-Meier survivor functions to estimate time to first consultation, with log-rank tests to compare TIA and control patients. Cox proportional hazard models will predict the effect of demographic and patient characteristics on time to first consultation. ETHICS AND DISSEMINATION: Approval was granted by a THIN Scientific Review Committee (ref: 14-008). The study's findings will be published in a peer-reviewed journal and disseminated at national and international conferences and through social media.

BACKGROUND: Illicit drug use is a multifaceted public-health problem with potentially serious impacts. The United Kingdom has one of the highest prevalence of illegal drug use in Europe. Reduction of overall illegal drug use in England and Wales has decreased from 11% to 8.2% (2012/13) over the past 10 years. People who use drugs often seek help from their family doctors. AIMS: To investigate General Practitioners (family doctors) first recording of drug use and opioid substitute treatment in primary care settings. DESIGN: A descriptive study design. Males and females (16-64 years old) were extracted from The Health Improvement Network (THIN) database. SETTING: England and Wales primary care. METHOD: The first recording of drug use and opioid substitution treatment in primary care was estimated for the period (1994-2012). Poisson regressions were conducted to estimate incidence risk ratios (IRR). RESULTS: We identified 33,508 first recordings of drug use and 10,869 individuals with prescriptions for opioid substitute treatment. Overall, males (IRR 2.02, 95% CI:1.97-2.07), people in the age-group; 16-24 (IRR 6.7, 95% CI:6.4-6.9) compared to those over 25 years and the most deprived (IRR 4.2, 95% CI:3.9-4.4) were more likely to have a recording of drug use. Males (IRR 1.2 95% CI:1.2-1.3), in the age-group; 25-34 (IRR 1.8 95% CI:1.7-1.9) and the most deprived (IRR 3.9 95% CI:3.6-4.3) were the groups more likely to have a opioid substitute treatment prescription. CONCLUSION: It is evident from this study that there is little recording of drug use and opioid substitute treatment in primary care. Most drug users do not receive treatment in primary care.

BACKGROUND: Current screening guidelines for colorectal cancer (CRC) do not consider thyroid dysfunction as a risk factor for disease development. We sought to determine the risk of developing CRC in patients with thyroid dysfunction, with and without thyroid hormone replacement (THR). METHODS: We conducted a nested case-control study using a large population-based medical records database from the United Kingdom. Study case patients were defined as those with any medical code of CRC. Subjects with familial colorectal cancer syndromes or inflammatory bowel disease (IBD) were excluded. For every case patient, four eligible control patients matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence density sampling. Exposure was THR therapy before index date. We further divided the THR unexposed group into patients with hypothyroidism (TSH > 4 mg/dl), patients with hyperthyroidism (TSH < 0.4 mg/dl), and subjects without documented thyroid abnormality. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CRC were estimated using conditional logistic regression. All statistical tests were two-sided. RESULTS: We identified 20990 CRC patients and 82054 control patients. The adjusted odds ratio for CRC associated with THR was 0.88 (95% CI = 0.79 to 0.99, P = .03) and 0.68 (95% CI = 0.55 to 0.83, P < .001) for treatment initiated five to 10 years and more than 10 years before index date, respectively. This protective association increased with cumulative duration of therapy. In contrast, hyperthyroidism (adjusted OR = 1.21, 95% CI = 1.08 to 1.36, P = .001) or untreated hypothyroidism (adjusted OR = 1.16, 95% CI = 1.08 to 1.24, P < .001) were associated with increased risk of CRC. CONCLUSION: Long-term THR is associated with a decreased risk of CRC. Hyperthyroidism and untreated hypothyroidism are associated with modestly elevated risk of CRC.

BACKGROUND: Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy. The ICS-to-total-asthma-medication ratios, calculated from claims data, indicate potentially risky disease management in asthma. Our aim was to assess the utility of ICS-to-total-asthma-medication ratios from primary care electronic medical records (EMRs) in detecting patients at risk of asthma exacerbation, as approached by prescription of oral corticosteroids and/or antibiotics. METHODS: Retrospective cohort studies were identified, using the Health Improvement Network general practice database (THIN, United Kingdom) and the Cegedim Longitudinal Patient Data (France). We selected asthma patients aged 16-40 years, with ≥ 4 prescriptions for asthma medications in 2007 and ≥ 1 prescription in 2008. For each country, three groups were defined according to ratio value in 2008: 0% (non-ICS users), <50% (low-ICS-ratio group) and ≥ 50% (high-ICS-ratio group). Outcomes were marker of asthma exacerbations: systemic corticosteroids and antibiotics. They were compared between groups in each country. RESULTS: Among 38,637 British and 4,587 French patients, higher numbers of prescriptions per patient of systemic corticosteroids, antibiotics and total asthma medications were observed in the low-ICS-ratio groups compared to other groups (p < 0.0001 for each outcome in both countries). Likewise, low-ICS-ratio patients had more medical contacts (p < 0.0001 in both countries), suggesting poorly controlled asthma. ICS-treated patients had lower risks of receiving systemic corticosteroids in 2008 in the high-ICS-ratio group, compared to the low-ICS-ratio group: RR = 0.54, 95%CI = [0.50-0.57] and RR = 0.78, 95%CI = [0.67-0.91] in the UK and France, respectively. CONCLUSIONS: Patients with high ICS-to-total-asthma-medication ratios presented fewer asthma-related outcomes. The low ICS-to-total-asthma-medication ratio calculated with EMRs data reflects insufficient prescribing of ICS relative to all asthma medications, which may lead to deteriorated asthma control.

About 1% of the general population receives long-term systemic glucocorticoids. The monitoring provided to these patients is unknown. We conducted a population-based cohort study using The Health Improvement Network database. A total of 100,944 adult patients prescribed systemic glucocorticoids for >3 months between January 2000 and December 2012 were studied. The monitoring done before prescribing glucocorticoid therapy and during exposure to the drug was examined. This included measurement of body weight, blood pressure, lipids, glucose and potassium levels, referrals for dual-energy X-ray absorptiometry (DEXA-scan) or to an ophthalmologist/optician, and vaccinations. We assessed factors associated with the odds of being monitored before and during exposure. Before glucocorticoid initiation, weight and blood pressure were monitored in < 20% and < 50% of patients, respectively. Glucose and lipid levels were monitored in less than one-third of the patients, while DEXA-scan and eye monitoring were offered to <15% of them. Vaccination against flu and pneumococcus was given to 57% and 46% of the patients, respectively. During exposure to the drug, <60% of patients who were prescribed the drug for more than a year had their weight, glucose, or lipid levels recorded at least once and <25% of patients were referred at least once for DEXA-scan or screening for eye diseases. Overall, the odds of being monitored were higher in older patients and in those with comorbidities. There were variations in the level of monitoring provided across the UK, but the monitoring has improved over the last 12 years. Although the extent of monitoring of people on long-term glucocorticoids has improved over time, the overall monitoring provided is not satisfactory, particularly in young patients and those without comorbidities.

BACKGROUND: The patterns and determinants of saxagliptin use among patients with type 2 diabetes mellitus (T2DM) are unknown in real-world settings. We compared the characteristics of T2DM patients who were new initiators of saxagliptin to those who were new initiators of non-dipeptidyl peptidase-4 (DPP-4) inhibitor oral anti-diabetic drugs (OADs) and identified factors associated with saxagliptin use. METHODS: We conducted a cross-sectional study within the Clinical Practice Research Datalink (CPRD), The Health Improvement Network (THIN), US Medicare, and the HealthCore Integrated Research Database (HIRD(SM)) across the first 36 months of saxagliptin availability (29 months for US Medicare). Patients were included if they were: 1) ≥18 years old, 2) newly prescribed saxagliptin or a non-DPP-4 inhibitor OAD, and 3) enrolled in their respective database for 180 days. For each saxagliptin initiator, we randomly selected up to ten non-DPP-4 inhibitor OAD initiators matched on age, sex, and geographic region. Conditional logistic regression was used to identify determinants of saxagliptin use. RESULTS: We identified 64,079 saxagliptin initiators (CPRD: 1,962; THIN: 2,084; US Medicare: 51,976; HIRD(SM): 8,057) and 610,660 non-DPP-4 inhibitor OAD initiators (CPRD: 19,484; THIN: 19,936; US Medicare: 493,432; HIRD(SM): 77,808). Across all four data sources, prior OAD use, hypertension, and hyperlipidemia were associated with saxagliptin use. Saxagliptin initiation was also associated with hemoglobin A1c results >8% within the UK data sources, and a greater number of hemoglobin A1c measurements in the US data sources. CONCLUSIONS: In these UK and US data sources, initiation of saxagliptin was associated with prior poor glycemic control, prior OAD use, and diagnoses of hypertension and hyperlipidemia. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT01086280 , NCT01086293 , NCT01086319 , NCT01086306 , and NCT01377935.

BACKGROUND: Diabetes and chronic kidney disease (CKD) are independent predictors of death and cardiovascular events and their concomitant prevalence has increased in recent years. The aim of this study was to characterize the effect of the estimated glomerular filtration rate (eGFR) and other factors on the risk of death and cardiovascular events in patients with type 2 diabetes. METHODS: A cohort of 57,946 patients with type 2 diabetes who were aged 20-89 years in 2000-2005 was identified from The Health Improvement Network, a UK primary care database. Incidence rates of death, myocardial infarction (MI), and ischemic stroke or transient ischemic attack (IS/TIA) were calculated overall and by eGFR category at baseline. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) study equation. Death, MI and IS/TIA cases were detected using an automatic computer search and IS/TIA cases were further ascertained by manual review of medical records. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) for death, MI, and IS/TIA associated with eGFR category and other factors were estimated using Cox regression models adjusted for potential confounders. RESULTS: Overall incidence rates of death (mean follow-up time of 6.76 years), MI (6.64 years) and IS/TIA (6.56 years) were 43.65, 9.26 and 10.39 cases per 1000 person-years, respectively. A low eGFR (15-29 mL/min) was associated with an increased risk of death (HR: 2.79; 95% CI: 2.57-3.03), MI (HR: 2.33; 95% CI: 1.89-2.87) and IS/TIA (HR: 1.77; 95% CI: 1.43-2.18) relative to eGFR ≥ 60 mL/min. Other predictors of death, MI and IS/TIA included age, longer duration of diabetes, poor control of diabetes, hyperlipidemia, smoking and a history of cardiovascular events. CONCLUSIONS: In patients with type 2 diabetes, management of cardiovascular risk factors and careful monitoring of eGFR may represent opportunities to reduce the risks of death, MI and IS/TIA.

AIM: The aim of this analysis was to investigate total healthcare costs, HbA1c, and weight changes over a 36-month period in patients with type 2 diabetes initiated on NPH or long-acting insulin analogs. METHODS: Electronic patient data from 479 general practices in the UK (THIN database) were examined for new users of glargine (n = 794), detemir (n = 252), or NPH insulin (n = 430). Annualized healthcare costs and clinical outcomes in years 1, 2, and 3 following insulin initiation were quantified and compared with baseline, using ANOVA and linear regression models. RESULTS: A significant difference (p < 0.05) in total healthcare costs increases at year 1 vs baseline was observed between glargine and detemir, detemir and NPH, but not between glargine and NPH (increase: +£486, +£635, and +£420 for glargine, detemir, and NPH users, respectively). However, increases by year 3 were not significantly different between the insulins. A propensity score analysis comparing analog and NPH insulin showed that, following insulin initiation, increases in costs were higher with insulin analogs at year one (+£220), but this difference decreased over time in each year following insulin initiation (+£168 and +£146, respectively, for years 2 and 3). HbA1c reductions were not significantly different between the groups at all time points. Differences in weight gain between glargine and NPH were statistically significant at year 1 (0.87 kg vs 1.11 kg) and year 3 (1.15 kg vs 1.57 kg), but other estimates of between-group differences in weight gain were non-significant. CONCLUSIONS: Following insulin initiation, the difference in healthcare costs of long-acting analogs compared to NPH insulin was transient. By year 3, the cost differences were not significantly different between the two cohorts, driven by an observed reduction in the cost of self-monitoring of blood glucose (SMBG) in the analog group and an increase in the cost of bolus insulin in the NPH group.