Scientific
publications

AIMS: To use association rule mining methods to investigate prescribing of smoking cessation medication in the UK primary care and to identify the characteristics of numerically important groups of patients who typically do, or do not, receive cessation therapy. DESIGN: An association rule mining study using The Health Improvement Network Database. SETTINGS AND PARTICIPANTS: 282 433 patients aged 16 years and over from 419 UK general practices, who were registered with the practice throughout 2008 and recorded as a current smoker during that year. OUTCOME: Prescription for any type of smoking cessation medications in 2008 (nicotine replacement therapy, bupropion or varenicline). VARIABLES: Age, gender, lifestyle indicators and co-morbidity. RESULTS: Of the current smokers, 37 731 (13.4%) were given prescriptions for smoking cessation treatment during 2008. Prescriptions were particularly likely to be given to women, those aged 31-60 years, and people with diagnoses of chronic obstructive pulmonary disease and depression. On the contrary, of patients with dementia, with alcohol intake over recommended levels, atrial fibrillation or chronic kidney disease was extremely unlikely to be prescribed a smoking cessation medication. However, the largest group of patients who did not receive therapy was young and otherwise healthy individuals. CONCLUSIONS: This novel approach identified sizeable and easily definable groups of patients who are systematically failing to receive support for smoking cessation in primary care. Association rule mining can be used to identify key numerically important groups at high or low risk of receiving treatment and hence potentially to improve healthcare delivery.

BACKGROUND: Recent hospital-based studies have suggested a sixfold increased risk of pulmonary embolism (PE) in rheumatoid arthritis (RA) in the year following admission. We evaluated the risk of PE and deep vein thrombosis (DVT) and associated time trend among RA patients (84.5% without a history of hospitalisation during the past year) derived from the general population. METHODS: We conducted a cohort study using an electronic medical records database representative of the UK general population, collected from 1986 to 2010. Primary definitions of the RA cohort (exposure) and PE/DVT outcomes required physician diagnoses followed by corresponding treatments. We estimated relative risks (RRs) of PE and DVT compared with a matched non-RA comparison cohort, adjusting for age, sex, smoking, body mass index, comorbidities and hospitalisations. RESULTS: Among 9589 individuals with RA (69% female, mean age of 58 years), 82 developed PE and 110 developed DVT (incidence rates, 1.5 and 2.1 per 1000 person-years). Compared with non-RA individuals (N=95 776), the age-, sex- and entry-time-matched RRs were 2.23 (95% CI 1.75 to 2.86) for PE and 2.20 (CI 1.78 to 2.71) for DVT. Adjusting for other covariates, the corresponding RRs were 2.16 (CI 1.68 to 2.79) and 2.16 (CI 1.74 to 2.69). The time-specific RRs for PE were 3.27, 1.88 and 2.35 for follow-up times of <1 year, 1-4.9 years, and ≥5 years, and corresponding RRs for DVT were 3.16, 1.82 and 2.32. CONCLUSIONS: This population-based study indicates an increased risk of PE and DVT in RA, supporting increased monitoring of venous-thromboembolic complications and risk factors in RA, regardless of hospitalisation.

OBJECTIVES: To evaluate the risk of incident myocardial infarction (MI), stroke and peripheral vascular disease (PVD) in individuals with systemic sclerosis (SSc) in a general population context. METHODS: We conducted a cohort study using a UK primary care database containing records from 1986 to 2011. SSc diagnoses, outcomes and cardiovascular risk factors were identified from electronic medical records. We conducted two cohort analyses: (1) MI and stroke, and (2) PVD, excluding individuals with prevalent disease at baseline for each analysis. We estimated HRs comparing SSc with age-, sex- and entry time-matched comparison cohorts, adjusting for potential cardiovascular risk factors. RESULTS: Among 865 individuals with SSc (85.8% women, mean age 58.7 years), the incidence rates (IRs) of MI and stroke were 4.4 and 4.8 per 1000 person-years (PY), versus 2.5 and 2.5 per 1000 PY in the comparison cohort. The corresponding adjusted HRs were 1.80 (95% CI 1.07 to 3.05) for MI and 2.61 (95% CI 1.54 to 4.44) for stroke. Among 858 individuals with SSc (85.3% female, mean age 58.9 years), the IR of PVD was 7.6 per 1000 PY versus 1.9 per 1000 PY in the comparison cohort, with an adjusted HR of 4.35 (95% CI 2.74 to 6.93). CONCLUSIONS: These findings provide the first general population-based evidence that SSc is associated with an increased risk of developing MI, stroke and PVD. Further insight into disease mechanisms, as well as how disease subtype, organ involvement and medication use may alter these increased risks, is needed.

BACKGROUND: Some recent reports suggest an increased risk of fractures with use of proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs), although results are inconsistent and a causal relationship has yet to be proven. As these acid-suppressive drugs may have uncommon adverse effects on the central nervous system (CNS), such as dizziness, we investigated whether their use is associated with falls as a possible mechanism for increasing fracture risk. METHODS: A cohort study with nested case-control analysis and two validation strategies was performed using data from UK patients (aged 40-89 years) included in The Health Improvement Network database (2000-2008). Due to the large number of falls, a random sample of 20,000 cases was used for the analysis. RESULTS: The overall incidence of falls per 1000 person-years was 13.0 (95% confidence interval [CI] = 12.9-13.1). After adjustment for potential confounders, there was no relationship between falls and current use of single PPIs (odds ratio [OR] = 0.95; 95% CI = 0.89-1.02) or H2RAs (OR = 1.01; 95% CI = 0.90-1.14); there was no relationship with dose or duration of treatment. Falls were associated with CNS disorders and treatment with various pharmacological agents including antiparkinson drugs (OR = 2.7; 95% CI = 2.2-3.3) and antiepileptics (OR = 2.1; 95% CI = 1.8-2.3). CONCLUSIONS: There was no association between falls and use of PPIs or H2RAs. Any potential increase in the risk of fractures proposed to be associated with the use of acid-suppressive drugs is not via an increased risk of falls.

BACKGROUND: Guidelines indicate eligibility for lipid lowering drugs, but it is not known to what extent GPs' follow guidelines in routine clinical practice or whether additional clinical factors systematically influence their prescribing decisions. METHODS: A retrospective cohort analysis was undertaken using electronic primary care records from 421 UK general practices. At baseline (May 2008) patients were aged 30 to 74 years, free from cardiovascular disease and not taking lipid lowering drugs. The outcome was prescription of a lipid lowering drug within the next two years. The proportions of eligible and ineligible patients prescribed lipid lowering drugs were reported and multivariable logistic regression models were used to investigate associations between age, sex, cardiovascular risk factors and prescribing. RESULTS: Of 365,718 patients with complete data, 13.8% (50,558) were prescribed lipid lowering drugs: 28.5% (21,101/74,137) of those eligible and 10.1% (29,457/291,581) of those ineligible. Only 41.7% (21,101/50,558) of those prescribed lipid lowering drugs were eligible. In multivariable analysis prescribing was most strongly associated with increasing age (OR for age ≥ 65 years 4.21; 95% CI 4.05-4.39); diabetes (OR 4.49; 95% CI 4.35-4.64); total cholesterol level ≥ 7 mmol/L (OR 2.20; 95% CI 2.12-2.29); and ≥ 4 blood pressure measurements in the past year (OR 4.24; 95% CI 4.06-4.42). The predictors were similar in eligible and ineligible patients. CONCLUSIONS: Most lipid lowering drugs for primary prevention are prescribed to ineligible patients. There is underuse of lipid lowering drugs in eligible patients.

OBJECTIVE: The aim of the present work was to assess the short-term effects of stimulant medication use on risk of injury among children diagnosed as having attention deficit hyperactivity disorder (ADHD). METHODS: The study group for this self-controlled case series study was children aged 1-18 years old diagnosed as having ADHD who experienced an incident medically-attended injury event and received at least one prescription for stimulant medication between 1993 and 2008 (n=328), identified from The Health Improvement Network primary care database from the UK. Conditional Poisson regression was used to estimate incident rate ratios (IRR) and 95% CIs for injury comparing periods of time exposed to stimulant medication to unexposed periods. RESULTS: Among children with ADHD prescribed stimulant medication, the rate of medically-attended injury was decreased during periods of stimulant medication use as compared to unexposed periods (IRR 0.68, 95% CI 0.50 to 0.91). There was evidence of a protective association among males and among children aged 10-14 years. This effect did not change over time on treatment. CONCLUSIONS: Stimulant medication use may decrease the risk of injury among children treated for ADHD, although unmeasured time varying confounding may be an alternative explanation. Injury risk may be considered during the decision-making process with regard to medication continuation among children with ADHD.

OBJECTIVES: We sought to determine whether unexpected bereavement has a greater impact on mortality in the surviving partner than death of a partner with preexisting chronic disease or disability. METHODS: In a UK primary care database (The Health Improvement Network), we identified 171,720 couples aged 60 years and older. We compared the rise in mortality in the first year after bereavement in those whose partner died without recorded chronic disease (unexpected bereavement) to those whose deceased partner had a diagnosis of chronic disease (known morbidity). RESULTS: For unexpected bereavement (13.4% of all bereavements), the adjusted hazard ratio for death in the first year after bereavement was 1.61 (95% confidence interval [CI] = 1.39, 1.86) compared with 1.21 (95% CI = 1.14, 1.30) where the partner had known morbidity. Differences between bereaved groups were significant (P = .001) and present for both men and women. CONCLUSIONS: Unexpected bereavement has a greater relative mortality impact than bereavement preceded by chronic disease. Our findings highlight the potential value of preparing individuals for the death of a spouse with known morbidity and providing extra support after bereavement for those experiencing sudden unexpected bereavement.

BACKGROUND: Smoking prevalence is particularly high amongst more deprived social groups. This cross-sectional study uses the Mosaic classification to explore socioeconomic variations in the delivery and/or uptake of cessation interventions in UK primary care. METHODS: Data from 460,938 smokers registered in The Health Improvement Network between 2008 and 2010 were analysed. Logistic regression was used to calculate odds ratios for smokers having a record of receiving cessation advice or a prescription for a cessation medication during the study period by Townsend quintile and for each of the 11 Mosaic groups and 61 Mosaic types. Both of these measures are area-level indicators of deprivation. Profiles of Mosaic categories were used to suggest ways to target specific groups to increase the provision of cessation support. RESULTS: Odds ratios for smokers having a record of advice or a prescription increased with increasing Townsend deprivation quintile. Similarly, smokers in more deprived Mosaic groups and types were more likely to have a documented cessation intervention. The odds of smokers receiving cessation advice if they have uncertain employment and live in social housing in deprived areas were 35% higher than the odds for successful professionals living in desirable areas (odds ratio (OR) 1.35, 95% confidence interval (CI) 1.20-1.52; absolute risks 57.2% and 50.1% respectively), and those in low-income families living in estate-based social housing were 50% more likely to receive a prescription than these successful professionals (OR 1.50, 95% CI 1.31-1.73; absolute risks 19.5% and 13% respectively). Smokers who did not receive interventions were generally well educated, financially successful, married with no children, read broadsheet newspapers and had broadband internet access. CONCLUSIONS: Wide socioeconomic variations exist in the delivery and/or uptake of smoking cessation interventions in UK primary care, though encouragingly the direction of this variation may help to reduce smoking prevalence-related socioeconomic inequalities in health. Groups with particularly low intervention rates may be best targeted through broadsheet media, the internet and perhaps workplace-based interventions in order to increase the delivery and uptake of effective quit support.

BACKGROUND: Few studies have evaluated the prevention of upper gastrointestinal complications (UGIC; bleeding or perforation) in patients with uncomplicated peptic ulcer (PU). We assessed the effect of proton pump inhibitors (PPI) in a non-randomized setting. To maximize exchangeability of exposed and unexposed groups we restricted the study to patients with a new diagnosis of PU, i.e., a clear indication. To minimize selection bias we mimicked an intention to treat approach by assessing the effect of PPI prescription after PU diagnosis. METHODS: Within a population of subjects aged 40-84 years from The Health Improvement Network database, 1997-2006, we identified 3,850 patients with incident PU. Among them, we confirmed 74 first UGIC episodes during a mean follow-up of 4 years. Exposure was prescription coverage during the month following PU diagnosis. We performed a nested case-control analysis and compared UGIC cases with 400 controls matched for age, sex, year and duration of follow-up. Relative risks (RR) and 95 % confidence intervals (CI) were estimated. RESULTS: The overall incidence of UGIC was 4.6 cases/1,000 person-years; it was highest during the months after PU diagnosis, increased with age, and it was higher in men and subjects with Helicobacter pylori infection, anemia, and alcohol use at PU diagnosis. The RR for UGIC associated with PPI prescriptions during the month after PU diagnosis was 0.56 (95 % CI 0.31-1.0). The RR for NSAIDs with and without a PPI was 1.72 (0.68-4.45) and 3.27 (0.85-12.67), respectively. CONCLUSIONS: Findings suggest that prescription of PPIs after a PU diagnosis is associated with a reduced risk of UGIC.

AIMS: We investigated use and efficacy of glucagon-like peptide-1 (GLP-1) receptor agonists in UK practice. METHODS: People starting a GLP-1 receptor agonist (exenatide, liraglutide) or insulin (glargine, detemir, NPH) after a regimen of two or three oral glucose-lowering agents were identified from The Health Information Network observational primary care database (2007-2011). Mean change in HbA1c and body weight were compared at 1 year between cohorts, adjusting for baseline characteristics. RESULTS: Baseline characteristics of GLP-1 receptor agonist (n = 1123) vs. insulin (n = 1842) users were HbA1c 78 vs. 84 mmol/mol (9.3 vs. 9.8%) and BMI 38.2 vs. 30.9 kg/m². The GLP-1 receptor agonist cohort was younger, had shorter diabetes duration and follow-up, less microvascular disease and heart failure, higher estimated glomerular filtration rate and more use of oral glucose-lowering agents. Lower HbA1c reduction on GLP-1 receptor agonist [7 vs. 13 mmol/mol (0.6 vs. 1.2%) (n = 366 vs. 892)] was not statistically significant [adjusted mean difference -1.4 (95% CI -4.1, 1.2) mmol/mol], except in the highest HbA1c quintile [>96 mmol/mol (>10.9%); adjusted mean difference -17.8 (-28.6, -7.0) mmol/mol]. GLP-1 receptor agonist users lost weight [-4.5 vs. +1.5 kg; adjusted mean difference 4.7 (3.7, 5.8) kg; n = 335 vs. 634]. A UK 6-month target reduction for GLP-1 receptor agonists of 11 mmol/mol (1.0%) HbA1c and 3% weight was reached by 24.9% of those continuing treatment. CONCLUSIONS: Those starting GLP-1 receptor agonists are heavier with better glycaemic control than those starting basal insulin. Subsequently, they have improved weight change, with similar HbA1c reduction unless baseline HbA1c is very high. The UK 6-month GLP-1 receptor agonist target is usually not reached.

BACKGROUND: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. METHOD: A computer-based model was constructed depicting the management of PKU patients over the first 36 years of their life, derived from patients suffering from this metabolic disorder in The Health Improvement Network database (a nationally representative database of patients registered with general practitioners in the UK). The model was used to estimate the incidence of co-morbidities and the levels of healthcare resource use and corresponding costs over the 36 years. RESULTS: Patients who remained on a phenylalanine-restricted diet accounted for 38% of the cohort. Forty-seven per cent of patients discontinued their phenylalanine-restricted diet between 15 and 25 years of age. Of these, 73% remained off diet and 27% restarted a restricted diet at a mean 30 years of age. Fifteen per cent of the cohort had untreated PKU. Eleven per cent of patients who remained on a phenylalanine-restricted diet for 36 years received the optimum amount of prescribed amino acid supplements. Patients had a mean 12 general practitioner visits per year and one hospital outpatient visit annually, but phenylalanine levels were only measured once every 18 to 24 months. The mean NHS cost (at 2007/08 prices) of managing a PKU sufferer over the first 36 years of their life was estimated to range between £21 000 and £149 000, depending on the amount of prescribed nutrition they received. CONCLUSION: The findings suggest that the majority of patients with PKU were under-treated. The NHS cost of patient management should not be an obstacle to encouraging patients to remain on a restricted diet until further information becomes available about the long-term clinical impact of stopping such a diet. Nevertheless, patients require counselling and managed follow up regardless of the choices they make about their diet.

BACKGROUND: UK HIV guidelines identify 37 clinical indicator conditions for adult HIV infection that should prompt an HIV test. However, few data currently exist to show their predictive value in identifying undiagnosed HIV. AIM: To identify symptoms and clinical diagnoses associated with HIV infection and assess their relative importance in identifying HIV cases, using data from The Health Improvement Network (THIN) general practice database. DESIGN AND SETTING: A case-control study in primary care. METHOD: Cases (HIV-positive patients) were matched to controls (not known to have HIV). Data from 939 cases and 2576 controls were included (n = 3515). Statistical analysis assessed the incidence of the 37 clinical conditions in cases and controls, and their predictive value in indicating HIV infection, and derived odds ratios (ORs) for each indicator condition. RESULTS: Twelve indicator conditions were significantly associated with HIV infection; 74.2% of HIV cases (n = 697) presented with none of the HIV indicator conditions prior to diagnosis. The conditions most strongly associated with HIV infection were bacterial pneumonia (OR = 47.7; 95% confidence interval [CI] = 5.6 to 404.2) and oral candidiasis (OR = 29.4; 95% CI = 6.9 to 125.5). The signs and symptoms most associated with HIV were weight loss (OR = 13.4; 95% CI = 5.0 to 36.0), pyrexia of unknown origin (OR = 7.2; 95% CI = 2.8 to 18.7), and diarrhoea (one or two consultations). CONCLUSION: This is the first study to quantify the predictive value of clinical diagnoses related to HIV infection in primary care. In identifying the conditions most strongly associated with HIV, this study could aid GPs in offering targeted HIV testing to those at highest risk.