Scientific
publications

OBJECTIVES: Antiobesity drug (AOD) prescribing in children and young people (CYP) in primary care is rising with high rates of discontinuation. Little is known about prescribing in this group in terms of patient demographics and comorbidities, reasons for initiation and discontinuation, or adherence to national guidelines. DESIGN: Questionnaire survey to general practitioners (GPs) identified using a nationally representative primary care database covering 6% of UK population. SETTING: UK-wide primary care. PARTICIPANTS: Patients were eligible if prescribed an AOD aged ≤18 years between 2010 and 2012. A total of 151 patients from 108 unique practices were identified via national prescribing database, with responses for 119 patients (79%) from 84 practices; 94 of 119 (79%) were eligible for inclusion. PRIMARY AND SECONDARY OUTCOMES: Survey of GP prescribing habits of AODs to CYP. We audited orlistat usage against the National Institute for Health and Care Excellence (NICE) guidance. RESULTS: 47% were prescribed metformin, 59% orlistat and 5% both drugs. Orlistat was largely prescribed by GPs independently (49/55 prescriptions, 89%) and metformin by GPs on specialist recommendation (12/44, 27%). Orlistat was largely prescribed in those over 16 years of age without physical comorbidities. Metformin was initiated for treatment of polycystic ovarian syndrome (70%), insulin resistance (25%) and impaired glucose control (9%). Median supply of metformin was 10.5 months (IQR 4-18.5 months) and 2.0 months (1.0-4.0) for orlistat (p≤0.001). Drug terminations were largely due to families not requesting repeat prescriptions. NICE guidance adherence was low; 17% of orlistat prescriptions were initiated by specialists, and 56% had evidence of obesity-related comorbidity. GPs reported lower confidence in prescribing AOD to CYP compared with adults (10-point Likert score median 3 vs 8, p<0.001). CONCLUSIONS: Prescribing of AOD in primary care is challenging with low adherence to NICE guidance. Further work is needed to better support GPs in the use of AOD in CYP.

BACKGROUND: Electronic health database (EHD) data is increasingly used by researchers. The major United Kingdom EHDs are the 'Clinical Practice Research Datalink' (CPRD), 'The Health Improvement Network' (THIN) and 'QResearch'. Over time, outputs from these databases have increased, but have not been evaluated. OBJECTIVE: This study compares research outputs from CPRD, THIN and QResearch assessing growth and publication outputs over a 10-year period (2004-2013). CPRD was also reviewed separately over 20 years as a case study. METHODS:  Publications from CPRD and QResearch were extracted using the Science Citation Index (SCI) of the Thomson Scientific Institute for Scientific Information (Web of Science). THIN data was obtained from University College London and validated in Web of Science. All databases were analysed for growth in publications, the speciality areas and the journals in which their data have been published. RESULTS: These databases collectively produced 1,296 publications over a ten-year period, with CPRD representing 63.6% (n=825 papers), THIN 30.4% (n=394) and QResearch 5.9% (n=77). Pharmacoepidemiology and General Medicine were the most common specialities featured. Over the 9-year period (2004-2013), publications for THIN and QResearch have slowly increased over time, whereas CPRD publications have increased substantially in last 4 years with almost 75% of CPRD publications published in the past 9 years. CONCLUSION: These databases are enhancing scientific research and are growing yearly, however display variability in their growth. They could become more powerful research tools if the National Health Service and general practitioners can provide accurate and comprehensive data for inclusion in these databases.

BACKGROUND: The hepatitis C virus (HCV) is a major cause of global morbidity and mortality, with conflicting evidence regarding a possible association with psoriasis. OBJECTIVE: To determine the prevalence of HCV in psoriasis patients, compared to controls, and to determine the incidence of hepatic decompensation in HCV+ psoriasis patients compared to HCV+ controls. METHODS: Cross-sectional and cohort studies were conducted in The Health Improvement Network (THIN). RESULTS: In fully adjusted models, a statistically significant increase in prevalence was seen in the adults with psoriasis (OR: 1.24, 95% CI 1.10-1.40). A "dose-response" of HCV prevalence with increasing psoriasis severity was not observed. HCV+ patients with psoriasis had a non-statistically significant increased incidence of hepatic decompensation compared to HCV+ individuals without psoriasis (aHR: 1.58, 95% CI: 0.90-2.77). The risk was highest and statistically significant, in those with moderate-to-severe psoriasis (aHR: 21.51, 95% CI: 7.58-61.03). CONCLUSIONS: These results demonstrate a higher prevalence of HCV in adults with psoriasis and a higher rate of hepatic decompensation in HCV+ individuals with moderate-severe psoriasis.

PURPOSE: This retrospective study used medical records from The Health Improvement Network (THIN) and Hospital Episode Statistics (HES) database to evaluate endometriosis (incidence, treatment and need for recurrent invasive procedures) in the general UK population. MATERIALS AND METHODS: Women aged 12-54 years between January 2000 and December 2010, with a Read code for endometriosis, were identified in THIN. Cases were validated by manual review of free-text comments in medical records and responses to physician questionnaires. False-negative cases were identified among women with Read codes for hysterectomy or dysmenorrhea. Prescriptions of medical therapies for endometriosis were identified in THIN. Cases of single and recurrent invasive procedures were identified in women with medical records in both THIN and HES. RESULTS: Overall, 5087 women had a Read code for endometriosis, corresponding to an incidence of 1.02 (95% confidence interval [CI]: 0.99-1.05) per 1000 person-years. After case validation, the estimate was 1.46 (95% CI: 1.43-1.50) per 1000 person-years. Medical therapy was prescribed to 55.5% of women with endometriosis in the first year after diagnosis. In total, 48.3% of women received invasive treatment during the study period; approximately one-fifth of these women required further invasive treatment, mainly in the 3 years after the index procedure. CONCLUSIONS: Using Read codes as the only method to identify women with endometriosis underestimates incidence. Over half of women with recorded endometriosis are prescribed medical therapy in the first year after diagnosis. Women with diagnosed endometriosis are at risk of requiring recurrent invasive procedures.

Vitamin D has attracted considerable interest in recent years, with a marked increase in diagnosis of vitamin D deficiency seen among children in clinical practice in the UK. The economic implications of this change in diagnostic behaviour have not been explored. We performed a cohort study to examine longitudinal trends in healthcare expenditure arising from vitamin D testing and prescribing for children in primary care in England, using the electronic healthcare records of 722,525 children aged 0-17 years held in The Health Improvement Network database. Combined costs of vitamin D tests and prescriptions increased from £1647 per 100,000 person-years in 2008 (95% CI, £934 to £3007) to £28,913 per 100,000 person-years in 2014 (95% CI, £26,361 to £31,739). The total cost of vitamin D prescriptions and tests for children in primary care at the national level in England in 2014 was estimated to be £4.31 million (95% CI, £2.96-£6.48 million). CONCLUSION: There has been a marked increase in healthcare expenditure on vitamin D tests and prescriptions for children in primary care over the past decade. Future research should explore the drivers for this change in diagnostic behaviour and the reasons prompting investigation of vitamin D status in clinical practice. What is Known: • Vitamin D deficiency has attracted considerable interest in recent years, with a marked increase in diagnosis seen in children. • The economic implications of this change in diagnostic behaviour have not been explored. What is New: • There has been a large increase in healthcare expenditure on vitamin D tests and prescriptions for children in primary care in England over the past decade (> 15 fold between 2008 and 2013). • Screening of vitamin D status in children without specific risk factors or clinical features of deficiency may represent avoidable healthcare expenditure.

BACKGROUND: Vascular dementia (VaD) is the second most common form of dementia. However, there were mixed evidences about the association between blood pressure (BP) and risk of VaD in midlife and late life and limited evidence on the association between pulse pressure and VaD. METHODS: This is a population-based observational study. 265,897 individuals with at least one BP measurement between the ages of 60 to 65 years and 211,116 individuals with at least one BP measurement between the ages of 70 to 75 years were extracted from The Health Improvement Network in United Kingdom. Blood pressures were categorized into four groups: normal, prehypertension, stage 1 hypertension, and stage 2 hypertension. Cases of VaD were identified from the recorded clinical diagnoses. Multivariable survival analysis was used to adjust other confounders and competing risk of death. All the analysis were stratified based on antihypertensive drug use status. Multiple imputation was used to fill in missing values. RESULTS: After accounting for the competing risk of death and adjustment for potential confounders, there was an association between higher BP levels in the age 60-65 cohort with the risk of developing VaD (hazard ratio [HR] 1.53 (95% confidence interval: 1.04, 2.25) for prehypertension, 1.90 (1.30, 2.78) for stage 1 hypertension, and 2.19 (1.48, 3.26) for stage 2 hypertension) in the untreated group. There was no statistically significant association between BP levels and VaD in the treated group in the age 60-65 cohort and age 70-75 cohort. Analysis on Pulse Pressure (PP) stratified by blood pressure level showed that PP was not independently associated with VaD. CONCLUSION: High BP between the ages of 60 to 65 years is a significant risk for VaD in late midlife. Greater efforts should be placed on early diagnosis of hypertension and tight control of BP for hypertensive patients for the prevention of VaD.

Over the last decades, an increase in antipsychotic (AP) prescribing and a shift from first-generation antipsychotics (FGA) to second-generation antipsychotics (SGA) among youth have been reported. However, most AP prescriptions for youth are off-label, and there are worrying long-term safety data in youth. The objective of this study was to assess multinational trends in AP use among children and adolescents. A repeated cross-sectional design was applied to cohorts from varied sources from Denmark, Germany, the Netherlands, the United Kingdom (UK) and the United States (US) for calendar years 2005/2006-2012. The annual prevalence of AP use was assessed, stratified by age group, sex and subclass (FGA/SGA). The prevalence of AP use increased from 0.78 to 1.03% in the Netherlands' data, from 0.26 to 0.48% in the Danish cohort, from 0.23 to 0.32% in the German cohort, and from 0.1 to 0.14% in the UK cohort. In the US cohort, AP use decreased from 0.94 to 0.79%. In the US cohort, nearly all ATP dispensings were for SGA, while among the European cohorts the proportion of SGA dispensings grew to nearly 75% of all AP dispensings. With the exception of the Netherlands, AP use prevalence was highest in 15-19 year-olds. So, from 2005/6 to 2012, AP use prevalence increased in all youth cohorts from European countries and decreased in the US cohort. SGA were favoured in all countries' cohorts.

BACKGROUND: Underuse of anticoagulants in atrial fibrillation (AF) is an international problem, which has often been attributed to the presence of contraindications to treatment. No studies have assessed the influence of contraindications on anticoagulant prescribing in the UK. AIM: To determine the influence of contraindications on anticoagulant prescribing in patients with AF in the UK. DESIGN AND SETTING: Cross-sectional analysis of primary care data from 645 general practices contributing to The Health Improvement Network, a large UK database of electronic primary care records. METHOD: Twelve sequential cross-sectional analyses were carried out from 2004 to 2015. Patients with a diagnosis of AF aged ≥35 years and registered for at least 1 year were included. Outcome measure was prescription of anticoagulant medication. RESULTS: Over the 12 study years, the proportion of eligible patients with AF with contraindications who were prescribed anticoagulants increased from 40.1% (95% confidence interval [CI] = 38.3 to 41.9) to 67.2% (95% CI = 65.6 to 68.8), and the proportion of those without contraindications prescribed anticoagulants increased from 42.1% (95% CI = 41.6 to 42.6) to 67.7% (95% CI = 67.2 to 68.1). In patients with a recent history of major bleeding or aneurysm, prescribing rates increased from 44.3% (95% CI = 42.2 to 46.5) and 34.8% (95% CI = 29.4 to 40.6) in 2004 to 71.7% (95% CI = 69.9 to 73.5) and 63.2% (95% CI = 58.3 to 67.8) in 2015, respectively, comparable with rates in patients without contraindications. CONCLUSION: The presence or absence of recorded contraindications has little influence on the decision to prescribe anticoagulants for the prevention of stroke in patients with AF. The study analysis suggests that, nationally, 38 000 patients with AF with contraindications are treated with anticoagulants. This has implications for patient safety.

This population-based retrospective cohort study sought to determine if anorexia nervosa (AN) is associated with a higher risk of urolithiasis. Nine thousand three hundred two females with AN were compared to 92 959 randomly selected age-matched and practice-matched females. Cox regression was used to estimate the hazard ratio (HR) for urolithiasis and evaluate effect modification by age. Twenty-three participants with AN (0.25%) developed urolithiasis compared with 154 unexposed participants (0.17%) over a median of 4 years of observation. The risk of urolithiasis varied significantly with age (interaction p = 0.02). AN was associated with a more than threefold higher risk of urolithiasis in females ≤25 years of age (HR 3.49, 95% CI: 1.56-7.81; p = 0.002), but not in females over 25 years (HR 1.18, 95% CI: 0.69-2.02; p = 0.54). The distribution of diagnosis codes for urolithiasis differed between groups (p = 0.04), with a higher proportion of codes for uric acid urolithiasis in the AN (16.2%) versus unexposed group (5.0%). Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

BACKGROUND: Evidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease. METHODS: We investigated the risk of CRC among new-users of low-dose aspirin (75-300 mg), including risk by stage at diagnosis. Using The Health Improvement Network, we conducted a cohort study with nested case-control analysis. Two cohorts (N = 170,336 each) aged 40-89 years from 2000 to 2009 and free of cancer were identified: i) new-users of low-dose aspirin, ii) non-users of low-dose aspirin, at start of follow-up, matched by age, sex and previous primary care practitioner visits. Patients were followed for up to 12 years to identify incident CRC. 10,000 frequency-matched controls were selected by incidence density sampling where the odds ratio is an unbiased estimator of the incidence rate ratio (RR). RRs with 95% confidence intervals were calculated. Low-dose aspirin use was classified 'as-treated' independent from baseline exposure status to account for changes in exposure during follow-up. RESULTS: Current users of low-dose aspirin (use on the index date or in the previous 90 days) had a significantly reduced risk of CRC, RR 0.66 (95% CI 0.60-0.74). The reduction in risk was apparent across all age groups, and was unrelated to dose, indication, gender, CRC location or case-fatality status. Reduced risks occurred throughout treatment duration and with all low-dose aspirin doses. RRs by aspirin indication were 0.71 (0·63-0·79) and 0.60 (0.53-0.68) for primary and secondary cardiovascular protection, respectively. Among cases with staging information (n = 1421), RRs for current use of low-dose aspirin were 0.94 (0.66-1.33) for Dukes Stage A CRC, 0.54 (0.42-0.68) for Dukes B, 0.71 (0.56-0.91) for Dukes C, and 0.60 (0.48-0.74) for Dukes D. After 5 years' therapy, the RR for Dukes Stage A CRC was 0.53 (0.24-1.19). CONCLUSIONS: Patients starting low-dose aspirin therapy have a reduced risk of Stages B-D CRC, suggesting a role for low-dose aspirin in the progression of established CRC; a substantial reduction in the risk of Dukes A CRC may occur after 5 years' therapy.

Bipolar disorder and schizophrenia are associated with increased mortality relative to the general population. There is an international emphasis on decreasing this excess mortality. To determine whether the mortality gap between individuals with bipolar disorder and schizophrenia and the general population has decreased. A nationally representative cohort study using primary care electronic health records from 2000 to 2014, comparing all patients diagnosed with bipolar disorder or schizophrenia and the general population. The primary outcome was all-cause mortality. Individuals with bipolar disorder and schizophrenia had elevated mortality (adjusted hazard ratio (HR) = 1.79, 95% CI 1.67-1.88 and 2.08, 95% CI 1.98-2.19 respectively). Adjusted HRs for bipolar disorder increased by 0.14/year (95% CI 0.10-0.19) from 2006 to 2014. The adjusted HRs for schizophrenia increased gradually from 2004 to 2010 (0.11/year, 95% CI 0.04-0.17) and rapidly after 2010 (0.34/year, 95% CI 0.18-0.49). The mortality gap between individuals with bipolar disorder and schizophrenia, and the general population is widening.

BACKGROUND: Previous studies have been unclear about the cardiovascular risks for metabolically healthy obese individuals. OBJECTIVES: This study examined the associations among metabolically healthy obese individuals and 4 different presentations of incident cardiovascular disease in a contemporary population. METHODS: We used linked electronic health records (1995 to 2015) in The Health Improvement Network (THIN) to assemble a cohort of 3.5 million individuals, 18 years of age or older and initially free of cardiovascular disease. We created body size phenotypes defined by body mass index categories (underweight, normal weight, overweight, and obesity) and 3 metabolic abnormalities (diabetes, hypertension, and hyperlipidemia). The primary endpoints were the first record of 1 of 4 cardiovascular presentations (coronary heart disease [CHD], cerebrovascular disease, heart failure, and peripheral vascular disease). RESULTS: During a mean follow-up of 5.4 years, obese individuals with no metabolic abnormalities had a higher risk of CHD (multivariate-adjusted hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.45 to 1.54), cerebrovascular disease (HR: 1.07; 95% CI: 1.04 to 1.11), and heart failure (HR: 1.96; 95% CI: 1.86 to 2.06) compared with normal weight individuals with 0 metabolic abnormalities. Risk of CHD, cerebrovascular disease, and heart failure in normal weight, overweight, and obese individuals increased with increasing number of metabolic abnormalities. CONCLUSIONS: Metabolically healthy obese individuals had a higher risk of coronary heart disease, cerebrovascular disease, and heart failure than normal weight metabolically healthy individuals. Even individuals who are normal weight can have metabolic abnormalities and similar risks for cardiovascular disease events.

BACKGROUND: Primary care data gathered from Electronic Health Records are of the utmost interest considering the essential role of general practitioners (GPs) as coordinators of patient care. These data represent the synthesis of the patient history and also give a comprehensive picture of the population health status. Nevertheless, discrepancies between countries exist concerning routine data collection projects. Therefore, we wanted to identify elements that influence the development and durability of such projects. METHODS: A systematic review was conducted using the PubMed database to identify worldwide current primary care data collection projects. The gray literature was also searched via official project websites and their contact person was emailed to obtain information on the project managers. Data were retrieved from the included studies using a standardized form, screening four aspects: projects features, technological infrastructure, GPs' roles, data collection network organization. RESULTS: The literature search allowed identifying 36 routine data collection networks, mostly in English-speaking countries: CPRD and THIN in the United Kingdom, the Veterans Health Administration project in the United States, EMRALD and CPCSSN in Canada. These projects had in common the use of technical facilities that range from extraction tools to comprehensive computing platforms. Moreover, GPs initiated the extraction process and benefited from incentives for their participation. Finally, analysis of the literature data highlighted that governmental services, academic institutions, including departments of general practice, and software companies, are pivotal for the promotion and durability of primary care data collection projects. CONCLUSION: Solid technical facilities and strong academic and governmental support are required for promoting and supporting long-term and wide-range primary care data collection projects.

OBJECTIVES: To determine the cost-effectiveness of two bespoke severe mental illness (SMI)-specific risk algorithms compared with standard risk algorithms for primary cardiovascular disease (CVD) prevention in those with SMI. SETTING: Primary care setting in the UK. The analysis was from the National Health Service perspective. PARTICIPANTS: 1000 individuals with SMI from The Health Improvement Network Database, aged 30-74 years and without existing CVD, populated the model. INTERVENTIONS: Four cardiovascular risk algorithms were assessed: (1) general population lipid, (2) general population body mass index (BMI), (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those considered high risk ( 10%) were assumed to be prescribed statin therapy while others received usual care. PRIMARY AND SECONDARY OUTCOME MEASURES: Quality-adjusted life years (QALYs) and costs were accrued for each algorithm including no algorithm, and cost-effectiveness was calculated using the net monetary benefit (NMB) approach. Deterministic and probabilistic sensitivity analyses were performed to test assumptions made and uncertainty around parameter estimates. RESULTS: The SMI-specific BMI algorithm had the highest NMB resulting in 15 additional QALYs and a cost saving of approximately £53 000 per 1000 patients with SMI over 10 years, followed by the general population lipid algorithm (13 additional QALYs and a cost saving of £46 000). CONCLUSIONS: The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of an SMI-specific BMI algorithm (blood tests not required) makes it an attractive algorithm to implement in clinical settings.