Scientific
publications

BACKGROUND: Early identification of colorectal cancer is an unresolved challenge and the predictive value of single symptoms is limited. We evaluated the performance of QCancer (Colorectal) prediction model for predicting the absolute risk of colorectal cancer in an independent UK cohort of patients from general practice records. METHODS: A total of 2.1 million patients registered with a general practice surgery between 01 January 2000 and 30 June 2008, aged 30-84 years (3.7 million person-years) with 3712 colorectal cancer cases were included in the analysis. Colorectal cancer was defined as incident diagnosis of colorectal cancer during the 2 years after study entry. RESULTS: The results from this independent and external validation of QCancer (Colorectal) prediction model demonstrated good performance data on a large cohort of general practice patients. QCancer (Colorectal) had very good discrimination with an area under the ROC curve of 0.92 (women) and 0.91 (men), and explained 68% (women) and 66% (men) of the variation. QCancer (Colorectal) was well calibrated across all tenths of risk and over all age ranges with predicted risks closely matching observed risks. CONCLUSION: QCancer (Colorectal) appears to be a useful tool for identifying undetected cases of undiagnosed colorectal cancer in primary care in the United Kingdom.

BACKGROUND: Data on the epidemiology and aetiology of meningioma are limited. METHODS: The Health Improvement Network UK primary care database was used to ascertain incident cases of meningioma between January 1996 and June 2008. Ten thousand controls analysis were frequency-matched by age, sex and year. A nested case control analysis was performed to determine risk factors for meningioma. RESULTS: The incidence of meningioma was 5.30 per 100,000 person-years over the study period. The incidence was higher in women than in men (7.19 vs. 3.05 per 100,000 person-years). Cerebrovascular disease (OR 1.86; 95% CI 1.46-2.36) and a history of cancer, thyroid disease, epilepsy, migraine and headache and exposure to antiepileptics were significantly associated with an increased risk of meningioma. Ischemic heart disease and exposure to antiepileptics were associated with a decreased risk of meningioma. CONCLUSIONS: The incidence of meningioma in the UK remained stable over the 12-year study period and was twofold higher in women than men. Although the prevalence and incidence of meningioma remained stable during the study, further research into risk factors and predisposing conditions for the onset of meningioma and early symptoms of tumor development is warranted to improve prevention and early diagnosis of this disease.

BACKGROUND: Findings of prior studies have been inconclusive about the ocular effects of thiazolidinediones on diabetic macular edema (DME). We evaluated, in patients with type 2 diabetes (T2D), the short-term and long-term risks of developing DME among users vs nonusers of thiazolidinediones. METHODS: A retrospective cohort study of 103,368 patients with T2D and no DME at baseline using The Health Improvement Network (THIN) database. Clinical, biochemical, and demographic information was obtained for the period January 1, 2000, through November 30, 2009. RESULTS: At 1 year, the incidence of DME was 1.3% (n = 41) and 0.2% (n = 227) among thiazolidinedione users (n = 3227) and nonusers (n = 100,141), respectively (odds ratio [OR], 5.7 [95% CI, 4.1-7.9]). After Cox multiple regression analysis (adjusted for age; systolic blood pressure; levels of lipids and hemoglobin A(1c); and use of aspirin, fibrates, insulin, oral antidiabetic drugs, or renin-angiotensin system blockers), multiple imputation analysis to adjust for missing values, and propensity score analysis to exclude for any selection bias, thiazolidinedione use was associated with an increased risk of DME at 1-year follow-up (OR, 2.3 [95% CI, 1.5-3.6]) and 10-year follow-up (hazard ratio [HR], 2.3; [95% CI, 1.7-3.0]). The effect was similar for pioglitazone and rosiglitazone. Combination therapy with insulin plus a thiazolidinedione was associated with a higher risk of DME after propensity score adjustment (HR, 3.0 [95% CI, 1.5-5.9]), while aspirin use (HR, 0.6 [95% CI, 0.4-0.9]) and angiotensin-converting enzyme inhibitor use (HR, 0.4 [95% CI, 0.2-0.7]) were associated with a reduced risk of DME. CONCLUSION: Among patients with T2D, treatment with a thiazolidinedione was associated with an increased risk of DME at 1-year and 10-year follow-up evaluations.

BACKGROUND: Information is lacking on how concerns about child maltreatment are recorded in primary care records. AIM: To determine how the recording of child maltreatment concerns can be improved. DESIGN AND SETTING: Development of a quality improvement intervention involving: clinical audit, a descriptive survey, telephone interviews, a workshop, database analyses, and consensus development in UK general practice. METHOD: Descriptive analyses and incidence estimates were carried out based on 11 study practices and 442 practices in The Health Improvement Network (THIN). Telephone interviews, a workshop, and a consensus development meeting were conducted with lead GPs from 11 study practices. RESULTS: The rate of children with at least one maltreatment-related code was 8.4/1000 child years (11 study practices, 2009-2010), and 8.0/1000 child years (THIN, 2009-2010). Of 25 patients with known maltreatment, six had no maltreatment-related codes recorded, but all had relevant free text, scanned documents, or codes. When stating their reasons for undercoding maltreatment concerns, GPs cited damage to the patient relationship, uncertainty about which codes to use, and having concerns about recording information on other family members in the child's records. Consensus recommendations are to record the code 'child is cause for concern' as a red flag whenever maltreatment is considered, and to use a list of codes arranged around four clinical concepts, with an option for a templated short data entry form. CONCLUSION: GPs under-record maltreatment-related concerns in children's electronic medical records. As failure to use codes makes it impossible to search or audit these cases, an approach designed to be simple and feasible to implement in UK general practice was recommended.

OBJECTIVE: Up to one-third of patients with gastroesophageal reflux disease (GERD) in primary care have residual symptoms despite proton pump inhibitor (PPI) therapy. We aimed to characterize partial response to PPIs among adult patients in UK primary care. MATERIAL AND METHODS: Newly diagnosed GERD patients aged 20-79 years who were prescribed PPI for treatment of GERD were identified in The Health Improvement Network. Those with a treatment change suggesting partial response to PPIs (new treatment added to PPI, increased PPI dose, or switching PPI) during the subsequent 6 months were identified as potential cases and confirmed after manual review of each patient's complete computer medical record including free-text comments. Patients without these treatment changes were study controls. A nested case-control analysis was conducted using logistic regression. RESULTS: The proportion of newly diagnosed GERD patients with partial response to PPI therapy was 18.6% (1201/6453). Partial response was associated with female gender (odds ratio [OR]: 1.20; 95% confidence interval [CI]: 1.05-1.37), anxiety or depression (OR: 1.15; 95% CI: 1.00-1.31), and prescription of ≥ 6 drugs in the month before GERD diagnosis (OR: 1.42; 95% CI: 1.14-1.78). Among new PPI users (n = 2907), partial response was associated with esophageal ulcer or Barrett's esophagus at initial diagnosis (OR: 3.14; 95% CI: 1.60-6.17). CONCLUSIONS: Approximately one in five newly diagnosed patients with GERD appear to have a partial response to PPI therapy. Female gender, polymedication, and a severe initial diagnosis may be associated with partial response.

OBJECTIVE: To assess the association of compliance with treatment (medication and clinic appointments) and all-cause mortality in people with insulin-treated type 2 diabetes. RESEARCH DESIGN AND METHODS: Data were extracted from U.K. general practice records and included patients (N = 15,984) who had diagnostic codes indicative of type 2 diabetes or who had received a prescription for an oral antidiabetic agent and were treated with insulin. Records in the 30 months before the index date were inspected for clinical codes (recorded at consultation) indicating medication noncompliance or medical appointment nonattendance. Noncompliance was defined as missing more than one scheduled visit or having at least one provider code for not taking medications as prescribed. Relative survival postindex date was compared by determining progression to all-cause mortality using Cox proportional hazards models. RESULTS: Those identified as clinic nonattenders were more likely to be smokers, younger, have higher HbA(1c), and have more prior primary care contacts and greater morbidity (P < 0.001). Those identified as medication noncompliers were more likely to be women (P = 0.001), smokers (P = 0.014), and have higher HbA(1c), more prior primary care contacts, and greater morbidity (all P < 0.001). After adjustment for confounding factors, medication noncompliance (hazard ratio 1.579 [95% CI 1.167-2.135]), clinic nonattendance of one or two missed appointments (1.163 [1.042-1.299]), and clinic nonattendance of greater than two missed appointments (1.605 [1.356-1.900]) were independent risk factors for all-cause mortality. CONCLUSIONS: Medication noncompliance and clinic nonattendance, assessed during routine care by primary care physicians or their staff, were independently associated with increased all-cause mortality in patients with type 2 diabetes receiving insulin.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterised by the symptoms of inattention, impulsivity and hyperactivity. ADHD was once perceived as a condition of childhood only; however increasing evidence has highlighted the existence of ADHD in older adolescents and adults. Estimates for the prevalence of ADHD in adults range from 2.5-4%. Few data exist on the prescribing trends of the stimulants methylphenidate and dexamfetamine, and the non-stimulant atomoxetine in the UK. The aim of this study was to investigate the annual prevalence and incidence of pharmacologically treated ADHD in children, adolescents and adults in UK primary care. METHODS: The Health Improvement Network (THIN) database was used to identify all patients aged over 6 years with a diagnosis of ADHD/hyperkinetic disorder and a prescription for methylphenidate, dexamfetamine or atomoxetine from 2003-2008. Annual prevalence and incidence of pharmacologically treated ADHD were calculated by age category and sex. RESULTS: The source population comprised 3,529,615 patients (48.9% male). A total of 118,929 prescriptions were recorded for the 4,530 patients in the pharmacologically treated ADHD cohort during the 6-year study. Prevalence (per 1000 persons in the mid-year THIN population) increased within each age category from 2003 to 2008 [6-12 years: from 4.8 (95% CI: 4.5-5.1) to 9.2 (95% CI: 8.8-9.6); 13-17 years: from 3.6 (95% CI: 3.3-3.9) to 7.4 (95% CI: 7.0-7.8); 18-24 years: from 0.3 (95% CI: 0.2-0.3) to 1.1 (95% CI: 1.0-1.3); 25-45 years: from 0.02 (95% CI: 0.01-0.03) to 0.08 (95% CI: 0.06-0.10); >45 years: from 0.01 (95% CI: 0.00-0.01) to 0.02 (95% CI: 0.01-0.03). Whilst male patients aged 6-12 years had the highest prevalence; the relative increase in prescribing was higher amongst female patients of the same age - the increase in prevalence in females aged 6-12 years was 2.1 fold compared to an increase of 1.9 fold for their male counterparts. Prevalence of treated ADHD decreased with increasing age. Incidence (per 1000 persons at risk in the mid-year THIN population) was highest for children aged 6-12 years. CONCLUSIONS: A trend of increasing prescribing prevalence of ADHD drug treatment was observed over the period 2003-2008. Prevalence of prescribing to adult patients increased; however the numbers treated are much lower than published estimates of the prevalence of ADHD. This study has added to the limited knowledge on ADHD prescribing in primary care, particularly in the area of drug treatment in adulthood.

OBJECTIVE: To evaluate the performance of the QRISK2-2011 score for predicting the 10 year risk of cardiovascular disease in an independent UK cohort of patients from general practice and to compare it with earlier versions of the model and a National Institute for Health and Clinical Excellence version of the Framingham equation. DESIGN: Prospective cohort study to validate a cardiovascular risk score with routinely collected data between June 1994 and June 2008. SETTING: 364 practices from the United Kingdom contributing to The Health Improvement Network (THIN) database. PARTICIPANTS: Two million patients aged 30 to 84 years (11.8 million person years) with 93,564 cardiovascular events. MAIN OUTCOME MEASURE: First diagnosis of cardiovascular disease (myocardial infarction, angina, coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records. RESULTS: Results from this independent and external validation of QRISK2-2011 indicate good performance data when compared with the NICE version of the Framingham equation. QRISK2-2011 had better ability to identify those at high risk of developing cardiovascular disease than did the NICE Framingham equation. QRISK2-2011 is well calibrated, with reasonable agreement between observed and predicted outcomes, whereas the NICE Framingham equation seems to consistently over-predict risk in men by about 5% and shows poor calibration in women. CONCLUSIONS: QRISK2-2011 seems to be a useful model, with good discriminative and calibration properties when compared with the NICE version of the Framingham equation. Furthermore, based on current high risk thresholds, concerns exist on the clinical usefulness of the NICE version of the Framingham equation for identifying women at high risk of developing cardiovascular disease. At current thresholds the NICE version of the Framingham equation has no clinical benefit in either men or women.

PURPOSE: When using electronic medical record data to study drug use, hospitalizations are markers of severe outcomes. To identify events within a specified time window, it is important to validate hospitalization diagnoses and dates. Our objective was to validate pneumonia hospitalizations and their dates identified using hospitalization codes in The Health Improvement Network (THIN), a UK primary care electronic medical record. METHODS: This cross-sectional study used a cohort of THIN adult visits for acute nonspecific respiratory infections from June 1985 to August 2006. Pneumonia hospitalizations within 30 days after the visit were identified using THIN diagnosis and hospitalization codes; 60 participants were randomly selected for validation. Patients' general practitioners (GPs) returned de-identified hospital summaries and consultants' letters regarding overnight hospitalizations within a 180-day window around the THIN hospitalization. Positive predictive value (PPV) was the number of GP-validated hospitalizations divided by THIN documented hospitalizations. RESULTS: GPs returned 59 of 60 patient records; 52 had confirmed hospitalizations. PPV of THIN hospitalization documentation was 88% (95%CI = 77-95). One admission was not for pneumonia; PPV of THIN-documented pneumonia admission was 86% (95%CI = 75-94). Of 52 valid THIN hospitalizations, 50 were actually admitted within 14 days of the documented THIN date (range = -2 to +18). The absolute median difference between THIN and validated admission dates was +0.5 days, and the absolute mean difference was +3.1 days. In 16 of 52 admitted patients, the THIN admission date was the actual discharge date. CONCLUSIONS: THIN hospitalization codes performed well in identifying acute pneumonia hospitalizations and their timing. Admission date validity might be better for conditions associated with shorter versus longer hospitalizations.

OBJECTIVE:   To estimate the cost-effectiveness of using an extensively hydrolysed formula (eHF; Nutramigen) compared with an amino acid formula (AAF; Neocate) as first-line treatment for cow milk allergy (CMA) in the UK, from the perspective of the National Health Service (NHS). METHOD:   A decision model was constructed depicting the treatment paths and associated resource use attributable to first-line management of CMA with the two formulae. The model was based on the case records of 145 AAF-treated infants and 150 matched eHF-treated patients from The Health Improvement Network (THIN) database [a nationally representative database of patients registered with general practitioners (GPs) in the UK]. The model estimated the costs and consequences of patient management over 12 months following their initial GP visit for CMA. RESULTS:   Patients presenting with a combination of gastrointestinal symptoms and eczema accounted for 44% of all patients in both groups. Those with gastrointestinal symptoms alone and eczema alone accounted for up to a further 39% and 13%, respectively. Those with urticaria and faltering growth accounted for <5% and ≤6% of all patients, respectively. Patients' age and weight at presentation was a mean 2.6-2.8 months and 4.4 kg, respectively. It took a mean 2.2 months to start a formula after initially seeing a GP. Time to symptom resolution following the start of treatment was 1.2 months in both groups; hence, the mean number of symptom-free months during the 12 months following the initial GP visit was estimated to be 8.6 months in both groups. Patients treated with an eHF had a mean 13.1 GP visits over the 12 months compared to 17.5 visits made by AAF-treated patients (p < 0.001). The NHS cost of managing a CMA infant over the first 12 months following initial presentation to a GP was estimated to be £1853 and £3161 for an eHF-treated and AAF-treated patient, respectively. CONCLUSION:   Starting treatment for CMA with an eHF was the cost-effective option, as there were no significant differences in clinical outcomes between the two groups. A prospective, randomized controlled trial would allow a definitive confirmation of these findings.