Scientific
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BACKGROUND: A small number of risk scores for the risk of developing diabetes have been produced but none has yet been widely used in clinical practice in the UK. The aim of this study is to independently evaluate the performance of QDSCORE(®) for predicting the 10-year risk of developing diagnosed Type 2 diabetes in a large independent UK cohort of patients from general practice. METHODS: A prospective cohort study of 2.4 million patients (13.6 million person years) aged between 25 and 79 years from 364 practices from the UK contributing to The Health Improvement Network (THIN) database between 1 January 1993 and 20 June 2008. RESULTS: QDSCORE(®) showed good performance data when evaluated on a large external data set. The score is well calibrated with reasonable agreement between observed and predicted outcomes. There is a slight underestimation of risk in both men and women aged 60 years and above, although the magnitude of underestimation is small. The ability of the score to differentiate between those who develop diabetes and those who do not is good, with values for the area under the receiver operating characteristic curve exceeding 0.8 for both men and women. Performance data in this external validation are consistent with those reported in the development and internal validation of the risk score. CONCLUSIONS: QDSCORE(®) has shown to be a useful tool to predict the 10-year risk of developing Type 2 diabetes in the UK.

OBJECTIVE: So far, few data are available to characterize the flare history of patients with gout. The objective of this study was to describe the frequency and risk factors of gout flares with special consideration of the comorbidity. METHODS: A cohort study was conducted in a U.K. general practice database (The Health Improvement Network) including all patients aged 20-89 years diagnosed with incident gout between the years 2000 and 2007. RESULTS: In this study, 23 857 incident gout patients (mean age 61.9 years) were included, overall incidence rate was 2.68 (95% CI 2.65, 2.72) per 1000 person-years. The proportion of patients with at least one flare during the follow-up period (mean 3.8 years) was 36.9% (n=8806). A history of ischaemic heart disease [hazard ratio (HR) 1.12 (95% CI 1.06, 1.19)], hypertension [HR 1.15 (95% CI 1.10, 1.20)] and renal failure [HR 1.33 (95% CI 1.20, 1.48)] were independently associated with a higher risk of a first gout flare. Use of allopurinol at initial gout diagnosis was associated with a lower risk [HR 0.80 (95% CI 0.75, 0.85)]. CONCLUSIONS: Gout flares are relatively common among patients with gout. Some of the underlying cardiometabolic comorbid conditions are themselves independent risk factors for flares, which further contribute to the complexity of treatment of gout flares.

BACKGROUND: Brief cessation advice delivered to smokers during routine primary care consultations increases smoking cessation rates. However, in previous studies investigating recall of smoking cessation advice, smokers have reported more advice being received than is actually documented in their medical records. Recording of smoking cessation advice in UK primary care medical records has increased since the introduction of the Quality and Outcomes Framework (QOF) in 2004, and so we compare recall and recording of cessation advice since this time to assess whether or not agreement between these two data sources has improved. METHODS: For each year from 2000 to 2009, the proportion of patients in The Health Improvement Network Database (THIN) with a recording of cessation advice in their notes in the last 12 months was calculated. In 2004, 2005 and 2008, these figures were compared to rates of patients recalling having received cessation advice in the last 12 months in the Primary Care Trust (PCT) Patient Surveys, with adjustment for age, sex and regional differences between the populations. RESULTS: In 2004 there was good agreement between the proportion of THIN patients who had cessation advice recorded in their medical records and the proportion recalling advice in the Patient Survey. However, in both 2005 and 2008, more patients had cessation advice recorded in their medical records than recalled receiving advice. CONCLUSIONS: Since the introduction of the QOF, the rate of recording of cessation advice in primary care medical records has exceeded that of patient recall. Whilst both data sources have limitations, our study suggests that, in recent years, the proportion of smokers being advised to quit by primary care health professionals may not have improved as much as the improved recording rates imply.

OBJECTIVE: Excessive use of antipsychotic medication by older people is an international concern, but there is limited comparative information on their use in different residential settings. This paper describes and compares antipsychotic prescribing to older people in care homes and the community in England and Wales. METHOD: Analysis of a primary care database (THIN) with 403 259 community and 10 387 care home residents aged 65-104 years in 2008-9. RESULTS: 3677 (0.9%) patients in the community and 2173 (20.9%) in care homes (20.5% in residential homes, 21.7% in nursing homes) received an antipsychotic medication prescription in the last 90 days. Most patients had received prescriptions for more than three months and 60% of prescriptions were for atypical antipsychotics. In patients without severe mental illness, 2367 (0.6%) patients in the community and 1765 (18.2%) in care homes received antipsychotic medication; such prescribing was common for patients with recorded dementia (30.2% in care home, 10.1% in the community). In care homes, younger age and living in the North of England predicted prescribing, but care home type did not. In the community, female gender, increasing age, living in a deprived area and the North predicted prescribing. CONCLUSIONS: Despite safety concerns, antipsychotic prescribing is markedly higher in care homes than in the community, and strongly associated with dementia in both settings. In England and Wales, we estimate that 54 000 older care home patients and 50 000 community patients receive antipsychotic medication without a diagnosis of severe mental illness with important implications for health and social services.

AIM: The extent to which different referral pathways following a primary care diagnosis of iron deficiency anaemia (IDA) are associated with delay in diagnosis of colorectal cancer (CRC) was determined. METHOD: Eligible patients aged 40 or more years, with IDA diagnosed in primary care, and a subsequent diagnosis of CRC, were studied retrospectively. Referral pathways were identified using the specialty of first recorded GP referral following IDA diagnosis. Differences in time to diagnosis of CRC were assessed by referral specialty. Differences in the proportion of cases referred before and after the re-issue of the NICE urgent referral guidelines for suspected lower gastrointestinal (GI) cancer were also assessed. RESULTS: Of 628,882 eligible patients, 3.1% (n = 19,349) were diagnosed with IDA during the study period; 3.0% (n = 578) were subsequently diagnosed with CRC. Two hundred and fifty-nine (44.8%) patients had no recorded referral or a referral unrelated to anaemia or the GI tract. Only 35% (n = 201) of patients were referred to a relevant specialty. Median time to CRC diagnosis ranged from 2.5 months (referral to a relevant surgical specialty) to 31.9 months (haematology). Time to diagnosis was longer in patients referred to a medical compared with a relevant surgical specialty (P = 0.024). There was no significant difference in time to CRC diagnosis before and after the NICE guidelines were re-issued in 2005. CONCLUSION: Significant differences exist between referral specialties in time to CRC diagnosis following a primary care diagnosis of IDA. Despite NICE referral recommendations, a significant proportion of patients are still not managed within recommended care pathways to CRC diagnosis.

OBJECTIVE: To determine whether statins protect against all cause mortality after a diagnosis of pneumonia. DESIGN: Cohort study using propensity score based method to control for differences between people prescribed and not prescribed statins. SETTING: United Kingdom Health Improvement Network database, which contains electronic primary care medical records of more than six million patients. PARTICIPANTS: Every patient starting a statin between 1995 and 2006 (129,288) matched with up to five non-statin users (n = 600,241); 9073 patients had a recorded diagnosis of pneumonia, of whom 1398 were using a statin. MAIN OUTCOME MEASURE: All cause mortality within six months of diagnosis of pneumonia. RESULTS: Among users and non-users of statins with comparable propensity scores, 95/942 users and 686/3615 non-users died on the day that pneumonia was diagnosed. In the following six month period, 109/847 statin users died compared with 578/2927 non-users, giving an adjusted hazard ratio of 0.67 (0.49 to 0.91). If these observed benefits translated into clinical practice, 15 patients would need to be treated with a statin for six months after pneumonia to prevent one death. CONCLUSIONS: Compared with people who were not taking statins, the risk of dying in the six month period after pneumonia was substantially lower among people who were already established on long term statin treatment when the pneumonia occurred. Whether some or all of this protective effect would be obtained if statin treatment begins when a patient first develops pneumonia is not known. However, given that statins are cheap, safe, and well tolerated, a clinical trial in which people with pneumonia are randomised to a short period of statin treatment is warranted.

OBJECTIVE: Few data exist on the treatment of gastroesophageal reflux disease (GERD) in paediatrics. The objective of this study was to examine treatment patterns of GERD in paediatrics in the primary care. METHODS: Incident GERD cases among paediatric patients were identified using The Health Improvement Network UK primary care database. We assessed prescription treatments in 30 days before and any time after the date of diagnosis. Initial treatment was defined as that received in 30 days either side of diagnosis. Odds ratios and 95% confidence intervals of receiving the treatment were calculated by multiple logistic regressions. RESULTS: The incident GERD cohort comprised 1700 paediatric patients aged 1-17 years. Antacids were initially prescribed in 49.2% of patients. Similar proportions of patients (23.3 and 22.9%) received histamine-2 receptor antagonists (H(2)RAs) and proton pump inhibitors (PPIs); 7.5% were prescribed prokinetics and 19.3% received no prescribed treatment. Overall, 24.7% of initial H(2)RA users switched to PPIs, and 9.8% of those using PPIs switched to H(2)RAs. The likelihood of the use of PPI increased with age and was lower in girls than in boys (odds ratio: 0.7; 95% confidence interval: 0.5-0.9). CONCLUSIONS: Antacids are the drugs most frequently prescribed by primary care physicians to paediatric patients with GERD, and approximately half receive an initial course of antisecretory treatment with H(2)RAs or PPIs. This study suggests that treatment patterns in paediatrics differ from those in adults.

BACKGROUND: Psoriasis is a common disease frequently studied in large databases. To date the validity of psoriasis information has not been established in The Health Improvement Network (THIN). OBJECTIVES: To investigate the validity of THIN for identifying patients with psoriasis and to determine if the database can be used to determine the natural history of the disease. METHODS: First, we conducted a cross-sectional study to determine if psoriasis prevalence in THIN is similar to expected. Second, we created a cohort of 4900 patients, aged 45-64 years, with a psoriasis diagnostic Read Code and surveyed their general practitioners (GPs) to confirm the diagnosis clinically. Third, we created models to determine if psoriasis descriptors (extent, severity, duration and dermatologist confirmation) could be accurately captured from database records. RESULTS: Psoriasis prevalence was 1·9%, and showed the characteristic age distribution expected. GP questionnaires were received for 4634 of 4900 cohort patients (95% response rate), and psoriasis diagnoses were confirmed in 90% of patients. Duration of disease in the database showed substantial agreement with physician query (κ = 0·69). GPs confirmed that the psoriasis diagnosis was corroborated by a dermatologist in 91% of patients whose database records contained a dermatology referral code associated with a psoriasis code. We achieved good discrimination between patients with and without extensive disease based on the number of psoriasis codes received per year (area under curve = 0·8). CONCLUSIONS: THIN is a valid data resource for studying psoriasis and can be used to identify characteristics of the disease such as duration and confirmation by a dermatologist.

Previous small studies and case reports have suggested that neurological disorders may be associated with bullous pemphigoid (BP). The objective of this study was to assess BP risk in patients with neurological diseases. Computerized medical records from the Health Improvement Network, a large population-based UK general practice database, were used to conduct a matched case-control analysis. Conditional logistic regression was used to calculate odds ratios for specified neurological disorders. Comparing cases (n=868) to controls (n=3,453), stroke was seen in 8 vs. 5%, odds ratio (OR) 1.8 (1.3-2.5); dementia in 7 vs. 2%, OR 3.4 (2.4-4.8); Parkinson's disease in 3 vs. 1%, OR 3.0 (1.8-5.0); epilepsy in 2 vs. 1%, OR 1.7 (1.0-3.0); and multiple sclerosis in 1 vs 0.1% (OR 10.7 (2.8-40.2). Estimates were not altered greatly when diagnoses up to 3 years before BP were excluded, except the association with epilepsy was no longer significant. Significant associations were only observed where neurological disease was diagnosed before the onset of pemphigoid. Study findings, except the association with epilepsy, were robust to sensitivity analysis. Strong associations were observed between specific neurological diseases and the later development of BP, supporting possible causal associations. Mechanisms for disease occurrence based on these findings include immobility or age-related autoimmunity.

BACKGROUND: This study evaluated the risk of upper gastrointestinal bleeding (UGIB) associated with use of low-dose acetylsalicylic acid (ASA) alone and in combination with other gastrotoxic medications. METHODS AND RESULTS: The Health Improvement Network UK primary care database was used to identify individuals 40 to 84 years of age with a UGIB diagnosis in 2000 to 2007 (n = 2049). An age-, sex-, and calendar year-matched control group (n = 20,000) was identified from the same source population. The relative risk (RR) of UGIB associated with use of low-dose ASA (75 to 300 mg/d), clopidogrel, and other commonly coadministered medications was estimated by multivariate logistic regression. The risk of UGIB was increased in current users of low-dose ASA (RR, 1.80; 95% confidence interval [CI], 1.59 to 2.03) or clopidogrel (RR, 1.67; 95% CI, 1.24 to 2.24) compared with nonusers. Compared with low-dose ASA monotherapy, the risk of UGIB was significantly increased when low-dose ASA was coadministered with clopidogrel (RR, 2.08; 95% CI, 1.34 to 3.21), oral anticoagulants (RR, 2.00; 95% CI, 1.15 to 3.45), low-/medium-dose nonsteroidal antiinflammatory drugs (RR, 2.63; 95% CI, 1.93 to 3.60), high-dose nonsteroidal antiinflammatory drugs (RR, 2.66; 95% CI, 1.88 to 3.76), or high-dose oral corticosteroids (RR, 4.43; 95% CI, 2.10 to 9.34); this was not apparent with coadministration of statins (RR, 0.99; 95% CI, 0.81 to 1.21) or low-dose oral corticosteroids (RR, 1.01; 95% CI, 0.58 to 1.77). CONCLUSIONS: Use of low-dose ASA is associated with an almost 2-fold increase in the risk of UGIB compared with nonuse. This risk is increased further in individuals taking low-dose ASA along with clopidogrel, oral anticoagulants, nonsteroidal antiinflammatory drugs, or high-dose oral corticosteroids.

OBJECTIVE: To describe the quality of care for chronic diseases among older people in care homes (nursing and residential) compared with the community in a pay for performance system. DESIGN: Retrospective analysis of The Health Improvement Network (THIN), a large primary care database. SETTING: 326 English and Welsh general practices, 2008-9. PARTICIPANTS: 10,387 residents of care homes and 403,259 residents in the community aged 65 to 104 and registered for 90 or more days with their general practitioner. MAIN OUTCOME MEASURE: 16 process quality indicators for chronic disease management appropriate for vulnerable older people for conditions included in the UK Quality and Outcomes Framework. RESULTS: After adjustment for age, sex, dementia, and length of registration, attainment of quality indicators was significantly lower for residents of care homes than for those in the community for 14 of 16 indicators. The largest differences were for prescribing in heart disease (β blockers in coronary heart disease, relative risk 0.70, 95% confidence interval 0.65 to 0.75) and monitoring of diabetes (retinal screening, 0.75, 0.71 to 0.80). Monitoring hypothyroidism (0.93, 0.90 to 0.95), blood pressure in people with stroke (0.92, 0.90 to 0.95), and electrolytes for those receiving loop diuretics (0.89, 0.87 to 0.92) showed smaller differences. Attainment was lower in nursing homes than in residential homes. Residents of care homes were more likely to be identified by their doctor as unsuitable or non-consenting for all Quality and Outcomes Framework indicators for a condition allowing their exclusion from targets; 33.7% for stroke and 34.5% for diabetes. CONCLUSION: There is scope for improving the management of chronic diseases in care homes, but high attainment of some indicators shows that pay for performance systems do not invariably disadvantage residents of care homes compared with those living in the community. High use of exception reporting may compromise care for vulnerable patient groups. The Quality and Outcomes Framework, and other pay for performance systems, should monitor attainment and exception reporting in vulnerable populations such as residents of care homes and consider measures that deal with the specific needs of older people.

OBJECTIVE: To evaluate the performance of ASSIGN against the Framingham equations for predicting 10 year risk of cardiovascular disease in a UK cohort of patients from general practice and to make the evaluation comparable to an independent evaluation of QRISK on the same cohort. DESIGN: Prospective open cohort study. Setting 288 practices from England and Wales contributing to The Health Improvement Network (THIN) database. PARTICIPANTS: Patients registered with 288 UK practices for some period between January 1995 and March 2006. The number of records available was 1,787,169. MAIN OUTCOME MEASURES: First diagnosis of myocardial infarction, coronary heart disease, stroke and transient ischaemic attacks recorded. Methods We implemented the Anderson Framingham Coronary Heart Disease and Stroke models, ASSIGN, and a more recent Framingham Cox proportional-hazards model and analysed their calibration and discrimination. RESULTS: Calibration showed that all models tested over-estimated risk particularly for men. ASSIGN showed better discrimination with higher AUROC (0.756/0.792 for men/women), D statistic (1.35/1.58 for men/women), and R²(30.47%/37.39% for men/women). The performance of ASSIGN was comparable to that of QRISK on the same cohort. Models agreed on 93-97% of categorical (high/lower) risk assessments and when they disagreed, ASSIGN was often closer to the estimated Kaplan-Meier incidence. ASSIGN also provided a steeper gradient of deprivation and discriminated between those with and without recorded family history of CVD. The estimated incidence was twice/three times as high for women/men with a recorded family history of CVD. CONCLUSIONS: For systematic CVD risk assessment all models could usefully be applied, but ASSIGN improved on the gradient of deprivation and accounted for recorded family history whereas the Framingham equations did not. However, all models display relatively low specificity and sensitivity. An additional conclusion is that the recording of family history of CVD in primary care databases needs to improve given its importance in risk assessment.

BACKGROUND: A number of historical studies have suggested that early life deprivation increases the risk of developing chronic obstructive pulmonary disease (COPD) in adult life, but whether this is still true now that living conditions have improved is not known. The aim of this study is to quantify the current association between adult height (a marker of socioeconomic status in early life) and COPD and to determine how this varies by age. METHODS: We obtained data on 1,204,110 people (aged over 35 years old) from The Health Improvement Network--a general practice database. We used a cross-sectional analysis to quantify the odds of having doctor-diagnosed COPD in relation to height using logistic regression. RESULTS: In our dataset, we had information on adult height for 1,025,662 (85%) people, and of these 2.7% had a diagnosis of COPD. The risk of having COPD decreased with each increase in quintile of height--OR 0.90 (95% CI 0.89 to 0.91). There was evidence of effect modification by age group such that this association was strongest in people aged 35 to 49 years (OR 0.86, 95% CI 0.82 to 0.89) and decreased progressively with age. CONCLUSIONS: The risk of developing COPD is still strongly associated with adult height. This association is strongest in the youngest age category, suggesting that early life experience will remain an important risk factor for COPD for some time to come and possibly that COPD related to early life deprivation is more severe and tends to present at a younger age.

INTRODUCTION: The objective of this study was to investigate the contemporary incidence of gout, examine potential risk factors, and evaluate specific gout treatment patterns in the general population. METHODS: Using the health improvement network (THIN) UK primary care database, we estimated the incidence of gout based on 24,768 newly diagnosed gout patients among a cohort of 1,775,505 individuals aged 20 to 89 years between 2000 and 2007. We evaluated potential risk factors for incident gout in a nested case-control study with 50,000 controls frequency-matched by age, sex and calendar time. We calculated odds ratios (OR) by means of unconditional logistic regression adjusting for demographic variables, lifestyle variables, relevant medical conditions and drug exposures. RESULTS: The incidence of gout per 1,000 person-years was 2.68 (4.42 in men and 1.32 in women) and increased with age. Conventional risk factors were significantly and strongly associated with the risk of gout, with multivariate ORs of 3.00 (95% confidence interval (CI)) for excessive alcohol intake (that is, more than 42 units per week), 2.34 (95% CI 2.22 to 2.47) for obesity (body mass index > = 30 kg/m2), 2.48 (95% CI 2.19 to 2.81) for chronic renal impairment, and 3.00 (95% CI 2.85 to 3.15) for current diuretic use. For other medical conditions the multivariate OR were 1.84 (95% CI 1.70 to 2.00) for heart failure, 1.45 (95% CI 1.18 to 1.79) for hypertriglyceridemia and 1.12 (95% CI 1.04 to 1.22) for psoriasis. Use of cyclosporine was associated with an OR of 3.72 (95% CI, 2.17 to 6.40). Among gout-specific therapies, allopurinol was the most frequently used with a one-year cumulative incidence of 28% in a cohort of incident gout diagnosed from 2000 to 2001. Use of gout-specific treatment has not changed over recent years except for an increase of colchicine. CONCLUSIONS: The contemporary incidence of gout in UK remains substantial. In this general population cohort, associations with previously purported risk factors were evident including psoriasis, heart failure, hypertriglyceridemia, and cyclosporine therapy. Use of gout-specific treatment has remained relatively constant in recent years except for an increase of colchicine.

BACKGROUND: Understanding myocardial infarction (MI) incidence and case fatality trends across the four UK constituent countries is of importance following devolution of the government of health-care services. METHODS: Retrospective cohort study using a primary care database (5.19 million patients) examining trends in incidence of first MI and 30-day case fatality. RESULTS: From 1996 to 2005, the incidence of MI decreased in all countries, but reductions were greater in England (men, -3.1%; women, -2.8%) and Wales (men, -3.3%; women, -4.6%) than in Scotland (men, -1.9%; women, -0.6%) and Northern Ireland (men no change, women, -0.8%) (average annual percentage change). Greater reductions in England and Wales than Scotland and Northern Ireland meant a widening of north-south difference in MI incidence over the study period. Downward trends in 30-day case fatality were found in each country but less regional variation was evident (England men, -12.0%, women, -11.0%; Wales men, -18.4%, women, -12.6%; Scotland men, -9.5%, women, -9.0%; Northern Ireland men, -8.6%, women, -13.0%). CONCLUSION: From 1996 to 2005, downward trends in the incidence of first MI and 30-day case fatality were evident in each constituent country. Greater improvements in case fatality, compared with incidence, were found within each country.

BACKGROUND: Epidemiological studies investigating a possible association between bisphosphonates and atrial fibrillation (AF) have reported conflicting findings. The objective of our study was to determine whether exposure to oral nitrogen-containing bisphosphonates alendronate and risedronate are associated with increased incidence of atrial fibrillation. METHODS: In a retrospective cohort study we analyzed data from three large independent databases, two from the United States (MarketScan(®) and Ingenix(®)) and one from the United Kingdom (THIN). 144,548 women, age 50-89, bisphosphonate users during 2002-2005 were compared to 668,891 sex- and age-matched controls (1:4). Our primary outcome measure was new incident atrial fibrillation for up to three years; Cox models adjusted for disease and drug history were used to estimated relative risks. RESULTS: We identified a total of 8,001, 1,984, and 817 AF cases in oral bisphosphonate users and nonusers during 744,340 (MarketScan), 243,898 (Ingenix), and 148,779 (THIN) person-years of follow-up, respectively. Compared to nonusers, overall adjusted relative risk (adjRR) (95% confidence interval [CI]) for AF in oral bisphosphonates users was 0.92 (0.85-0.99; MarketScan), 1.00 (0.87-1.16; Ingenix), and 0.97 (0.79-1.20; THIN); overall adjRR (95% CI) for any cardiac dysrrhythmia for MarketScan was 1.01 (0.98-1.05), Ingenix 1.06 (0.99-1.13), and THIN 0.97 (0.79-1.20). CONCLUSIONS: In all three databases from the two countries, the risk of AF or cardiac dysrrhythmia was not increased in postmenopausal women treated for up to three years with oral alendronate or risedronate.