The Health Improvement Network Research Articles

<p>Differences in Psychotropic Drug Prescribing Between Ethnic Groups of People with Dementia in the United Kingdom</p>

PurposeTo test hypotheses that minority ethnic people with dementia in the UK receive fewer anti-dementia drugs and more psychotropic and anticholinergic drugs associated with harms.Patients and MethodsWe analyzed UK primary care electronic health records from The Health Improvement Network (THIN) database (2014–2016), comparing psychotropic drug prescribing initiation and duration between people with dementia from White, Black, and Asian ethnic groups. We repeated analyses in people (aged 50+) without dementia, to explore whether any differences found reflected prescribing patterns in the general older population, or were specific to dementia.ResultsWe included 53,718 people with and 1,648,889 people without dementia. Among people with dementia, compared to White ethnic groups, Asian people were less likely to be prescribed anti-dementia drugs when they were potentially indicated (adjusted prevalence rate ratio 0.86 (95% Confidence Interval 0.76–0.98)), and received them for on average 15 days/year less. Compared to White groups, Asian and Black individuals with dementia were no more likely to take an antipsychotic drug, but those that had were prescribed them for 17 and 27 days/year more, respectively (190.8 (179.6–199.1) and 200.7 (191.1–206.5) days). Black people were less likely to be prescribed anxiolytics/hypnotics (0.60 (0.44–0.8)), but the duration these drugs were prescribed was similar across ethnic groups. Asian people were more likely to be prescribed anticholinergic drugs (1.43 (1.19–1.73)), in analyses unadjusted for cardiovascular comorbidities. Among people without dementia, those in the Asian and Black ethnic groups were less likely to be prescribed psychotropic drugs, relative to people from White groups.ConclusionAmong people with dementia, Asian groups received less potentially beneficial symptomatic treatments, and Asian and Black groups were prescribed antipsychotic drugs for longer than White ethnic groups. Our findings may indicate care inequalities.

Predictors of Bleeding in Patients with Symptomatic Peripheral Artery Disease: A Cohort Study Using the Health Improvement Network (THIN) in the UK

Introduction: Cardiovascular risk reduction guidelines recommend antiplatelets and statins for all individuals with symptomatic peripheral artery disease (PAD), and antihypertensives for those with concomitant hypertension. Antiplatelet use is associated with an increased bleeding risk. We aimed to assess potential risk factors for intracranial bleeding (ICB) and gastrointestinal bleeding (GIB) in patients with symptomatic PAD. Methods: Patients aged 50–89 years diagnosed with symptomatic PAD in 2000–2010 were identified using The Health Improvement Network (THIN) UK primary care database (N = 28 484). The main exclusion criteria were: dementia; ischaemic stroke; anticoagulant or dual antiplatelet therapy (past 3 months); and previous ICB or GIB (past 6 months). Patients were followed up until they reached an endpoint (ICB or GIB), death or end of follow-up (ICB: June 2013; GIB: March 2012). Follow-up for GIB was restricted to THIN practices linked to hospital episode statistics data. Potential comorbid, demographic and therapeutic risk factors for ICB (153 cases) and GIB (506 cases) were assessed using a nested case–control analysis, with 1000 controls for ICB and 5000 controls for GIB, case-matched by age, sex and calendar year. Odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders, were calculated. Results: The incidence of ICB was 7.9 (95% CI: 6.8–9.3) per 10 000 person-years (median follow-up: 6.4 years). Previous ICB was a major predictor of ICB (OR: 3.85; 95% CI: 1.33–11.13). Regarding other potential risk factors for ICB, the OR (95% CI) was 0.90 (0.61–1.34) for treated hypertension, 1.59 (0.65–3.87) for untreated hypertension, 1.38 (0.80–2.36) for current smoking, 0.73 (0.40–1.33) for body mass index (BMI) ≥ 30 kg/m2 and 2.20 (1.12–4.34) for BMI 15–19 kg/m2. Compared with patients not using acetylsalicylic acid (ASA), clopidogrel or warfarin in the previous year (49 patients), the OR (95% CI) for ICB was 0.78 (0.50–1.21) with ASA monotherapy (55 patients), 0.40 (0.09–1.82) with clopidogrel monotherapy (2 patients) and 1.27 (0.47–3.47) with warfarin monotherapy (8 patients). The incidence of GIB was 9.6 (95% CI: 8.8–10.5) per 1000 person-years (median follow-up: 6.0 years). Major predictors (OR; 95% CI) of GIB were peptic ulcer disease (1.40; 1.05–1.86), dual antiplatelet therapy (3.20; 1.81–5.64) and use of non-steroidal anti-inflammatory drugs (1.96; 1.46–2.64). Regarding other potential risk factors for GIB, the OR (95% CI) was 1.32 (1.05–1.65) for treated hypertension, 1.35 (0.77–2.35) for untreated hypertension, 0.98 (0.72–1.33) for smoking, 1.26 (0.92–1.72) for BMI ≥ 30 kg/m2 and 0.67 (0.44–1.01) for BMI 15–19 kg/m2. Compared with individuals not using ASA, clopidogrel or warfarin in the previous year (124 patients), the OR (95% CI) for GIB was 1.78 (1.39–2.30) with ASA monotherapy (245 patients), 2.03 (1.05–3.93) with clopidogrel monotherapy (15 patients) and 1.25 (0.72–2.16) with warfarin monotherapy (19 patients). Conclusion: Incidence of GIB was about 10-fold higher than incidence of ICB in patients with symptomatic PAD in UK primary care. Antiplatelet therapy increased the risk of GIB.

Identifying People with Dementia in Electronic Primary Care Records in the UK

Abstract Background Many epidemiological questions need to be answered regarding dementia, including the causes, prognosis, comorbidities, and treatment of the condition and complications. A routine electronic primary care dataset provides a way of investigating some of the complicated factors with rich information. However, there has been concern regarding whether dementia is recorded well enough. Methods This study has therefore explored this by conducting a systematic review to understand how dementia has been identified previously in primary care databases in the UK, and added to this by exploring additional terms and symptoms, and medications that might be helpful in identifying people with dementia. The study estimated the prevalence and incidence rates of dementia in The Health Improvement Network (THIN) database and compared with other longitudinal studies using the comprehensive list of diagnostic codes. Results The estimated incidence rates per 1,000 person-years for the 60+ age group who had any of the first diagnosis among the Quality Outcomes Framework (QOF) defined codes, Other diagnoses, Dementia symptoms and Prescribed medications were 2.5, 4.7, and 15.9 in 1995, 2004, and 2015 respectively. The estimated prevalence were 2.8, 3.2, and 10.2 in 1995, 2004, and 2015 respectively. Conclusions The codes related to dementia symptoms (represented by mini-mental state examination, the six item cognitive impairment test, referral to memory clinic and behaviour assessment) seem to cover a broad definition of dementia or pre-existing dementia population in the UK primary care records. At least, using of the Other diagnoses (represented by dementia annual review, senile/presenile dementia and dementia monitoring) in addition to the QOF defined codes, and Prescribed medications were evidenced that will not missing out a number of people with dementia. Key messages The codes related to dementia symptoms seem to cover a broad definition of dementia or pre-existing dementia population in electronic primary care records in the UK. Nevertheless, the codes about non-specific or temporary symptoms may need to be used carefully as it is possible for memory or cognitive function to be impaired temporarily due to other factors.

Increasing Rates of Arthroplasty for Psoriatic Arthritis in the United Kingdom Between 1995 and 2010.

Arthroplasty requirements among patients with psoriatic arthritis (PsA) are not well known. This information is important to clinical and policy stakeholders for health-system planning and may serve as a surrogate for estimation of the efficacy of disease-modifying therapy. We utilized The Health Improvement Network (THIN), a large general practice medical records database in the UK, to assess rates of primary total arthroplasty among patients with PsA and the general population between the years 1995 and 2010. Linear regression was used to estimate arthroplasty rates for the 2 cohorts during the study period, and Poisson regression was used to determine age- and sex-adjusted incidence rate ratios (IRRs) between the PsA and general population cohorts. We identified 5,619 patients with incident PsA and 5,090,814 eligible patients from the general population between 1995 and 2010. In total, 187 primary total arthroplasties were documented in patients with PsA, and 80,163 primary total arthroplasties were documented in the general population. A trend of increasing arthroplasty rates was observed for both the PsA (R2 = 0.809; P < 0.0001) and general population (R2 = 0.890; P < 0.0001) cohorts during the study period. After adjustment for age and sex, patients with PsA had a first arthroplasty incidence rate that was twice that of the general population (IRR 2.01 [95% confidence interval 1.73-2.34]; P < 0.0001), notably beyond the year 2003 when biologic therapies were introduced. Both the general population and patients with PsA have experienced increasing rates of first arthroplasty from 1995 to 2010, although the overall incidence rate was significantly higher for those with PsA.

Circulating Folate Concentrations and Risk of Peripheral Neuropathy and Mortality: A Retrospective Cohort Study in the U.K.

Background: Folate deficiency may increase the risk of peripheral neuropathy but there is a paucity of data from large prospective studies examining this association. Methods: Longitudinal analysis of electronic health records in The Health Improvement Network (THIN), a U.K. primary care database including 594,338 patients aged 18–70 years with a folate measurement and without a history of peripheral neuropathy. Results: After a mean follow-up of 3.71 (standard deviation (SD) = 3.14) years, 1949 patients were diagnosed with peripheral neuropathy and 20,679 patients died. In those <40 years, compared to patients with folate ≥13.6 nmol/L, those with folate <6.8 (deficient) and 6.8–13.5 nmol/L (insufficient) had a hazard ratio (HR) for peripheral neuropathy of 1.83 (95% confidence intervals (CI) = 1.16–2.91) and 1.48 (95% CI = 1.04–2.08), respectively. There was no significant association between folate and peripheral neuropathy among those aged 41–70 years. Compared to patients with folate ≥ 13.6 nmol/L, folate <6.8 nmol/L was associated with a greater risk of death among all ages. Conclusion: Folate deficiency and insufficiency was associated with a greater risk of peripheral neuropathy among younger patients. This investigation should be replicated in other large datasets and it may be important to monitor peripheral neuropathy incidence after the introduction of mandatory folic acid fortification of flour in the U.K.

Impact of the introduction and withdrawal of financial incentives on the delivery of alcohol screening and brief advice in English primary health care: an interrupted time-series analysis.

To evaluate the impact of the introduction and withdrawal of financial incentives on alcohol screening and brief advice delivery in English primary care. Interrupted time-series using data from The Health Improvement Network (THIN) database. Data were split into three periods: (1) before the introduction of financial incentives (1January 2006-31March 2008); (2) during the implementation of financial incentives (1April 2008-31March 2015); and (3) after the withdrawal of financial incentives (1April 2015-31December 2016). Segmented regression models were fitted, with slope and step change coefficients at both intervention points. England. Newly registered patients (16+) in 500 primary care practices for 2006-16 (n=4 278 723). The outcome measures were percentage of patients each month who: (1) were screened for alcohol use; (2) screened positive for higher-risk drinking; and (3) were reported as having received brief advice on alcohol consumption. There was no significant change in the percentage of newly registered patients who were screened for alcohol use when financial incentives were introduced. However, the percentage fell (P<0.001) immediately when incentives were withdrawn, and fell by a further 2.96 [95% confidence interval (CI)=2.21-3.70] patients per 1000 each month thereafter. After the introduction of incentives, there was an immediate increase of 9.05 (95% CI=3.87-14.23) per 1000 patients screening positive for higher-risk drinking, but no significant further change over time. Withdrawal of financial incentives was associated with an immediate fall in screen-positive rates of 29.96 (95% CI=19.56-40.35) per 1000 patients, followed by a rise each month thereafter of 2.14 (95% CI=1.51-2.77) per 1000. Screen-positive patients recorded as receiving alcohol brief advice increased by 20.15 (95% CI=12.30-28.00) per 1000 following the introduction of financial incentives, and continued to increase by 0.39 (95% CI=0.26-0.53) per 1000 monthly until withdrawal. At this point, delivery of brief advice fell by 18.33 (95% CI=11.97-24.69) per 1000 patients and continued to fall by a further 0.70 (95% CI=0.28-1.12) per 1000 per month. Removing a financial incentive for alcohol prevention in English primary care was associated with an immediate and sustained reduction in the rate of screening for alcohol use and brief advice provision. This contrasts with no, or limited, increase in screening and brief advice delivery rates following the introduction of the scheme.

P4754Time to discontinuation of non-vitamin k antagonist oral anticoagulants in patients with non-valvular atrial fibrillation

Abstract Background Despite widespread use of non-vitamin K antagonist oral anticoagulants (NOACs), real-world data on time to discontinuation and time to re-initiation of the NOAC treatment are still scarce. Purpose To identify patterns of time to discontinuation as well as time to re-initiation of NOACs in patients with NVAF during the first year of treatment in UK primary care. Methods This population-based retrospective cohort study included 11,481 patients with NVAF, aged 18 and above, enrolled in The Health Improvement Network (THIN) with at least 1 year of follow-up after first recorded prescription of apixaban, dabigatran, or rivaroxaban between Jan 2012 to Dec 2016, and received two or more prescriptions of index NOAC. Discontinuation was defined as an interval greater than 30 days between the end of supply of the index NOAC and the date of the next prescription of the index NOAC. Discontinuers were further categorized as switchers, re-initiators or non-re-initiators. Re-initiators were patients who re-started OAC therapy after they discontinued treatment. Proportion of patients who discontinued NOAC treatment as well as mean duration (months) on treatment was calculated. Results The majority of patients were continuous users of their initial NOAC; discontinuation within the first year of treatment accounted for 26.1% of the apixaban cohort, 40.0% of the dabigatran cohort, and 29.6% of the rivaroxaban cohort. Time to discontinuation: Among discontinuers, the mean time patient stayed on initial treatment was the least for dabigatran (4.5 months), followed by apixaban (4.7 months) and highest for rivaroxaban (4.9 months). Discontinuers who did not later reinitiate any OAC therapy had a slightly longer time to discontinuation (mean 5.5 months) than those who later reinitiated OAC therapy (either on the same NOAC, a different NOAC or VKA; mean 4.6 months), or who switched treatment (4.0 months). Time to re-initiation: Among OAC reinitiators, no difference was seen in the time to re-initiation between NOACs (apixaban – 1.9 months, dabigatran – 2.1 months, and rivaroxaban – 2.0 months. Conclusion The proportion of discontinuation among new users of NOAC with NVAF in the first year was 30%. Average time on treatment for switchers, re-initiators and those who completely discontinued shows that such activities occurs around 4–5 months after initiating NOAC treatment, which is when further monitoring might be required. Once discontinued, re-initiation of NOAC treatment on average took 55–65 days. Acknowledgement/Funding The study is funded by Bayer AG

Trends in the incidence of Parkinson's disease between 2006 and 2016: Analysis of a large primary care database

Objective To investigate trends in the incidence of Parkinson’s disease (PD) between 2006 and 2016. Design Cohort study in The Health Improvement Network (THIN): a large UK primary care database. Study participants Individuals actively registered with a practice within THIN aged 50 years and over. Measures of outcome The incidence of Parkinson’s disease between 2006 and 2016 using different case definitions: 1) PD diagnostic Read code; 2) PD diagnostic Read code OR symptom Read code; 3) PD diagnostic Read code OR symptom Read code and OR at least 1 antiparkinsonian drug prescription; 4) PD diagnostic Read code OR symptom Read code plus at least 2 antiparkinsonian drug prescription. The effect of age and sex on these measures were investigated. Results The overall crude incidence of PD for people over 50 years has increased in recent years. The rates increased with increasing age and as expected, higher in men. Using the broadest case definition (3), incidence rate of PD between 2006 and 2016 in men was 190 per 100,000 person years (95% CI 187–193) and in women was 176 per 100,000 person years (95% CI 173–178). Incidence of PD was highest at age 90 (496 per 100,000 95% CI 471–522). Conclusion There is increasing diagnosis of PD in primary care setting.

The burden of mental ill health associated with childhood maltreatment in the UK, using The Health Improvement Network database: a population-based retrospective cohort study

Childhood maltreatment is a global public health, human rights, and moral issue that is associated with a substantial mental health burden. We aimed to assess the association between childhood maltreatment and the development of mental ill health and the initiation of new prescriptions for mental ill health. In this population-based, retrospective, open cohort study, we used a dataset from individuals in The Health Improvement Network (THIN) database. THIN database comprises UK electronic medical records taken from 787 general practices throughout the UK. We used read codes in these records to identify exposed patients (those with a read code identifying officially confirmed childhood maltreatment or a maltreatment-related concern) and up to two unexposed patients (those without such read codes) from the same general practice, who were matched by age and sex. We evaluated the risk of developing depression, anxiety, or serious mental illness (a composite mental ill health outcome) or initiation of a prescription drug used to treat mental ill health, and the odds ratio of these events at baseline, in the exposed versus unexposed patients. The first possible date for cohort entry (the study start date) was Jan 1, 1995, and patients could enter the cohort until the study end date, Dec 31, 2018. During the study period, 11 831 850 patients were eligible to participate. Of these patients, we identified 217 758 (1·8%) patients with any recorded childhood maltreatment. These patients were matched to 423 410 unexposed control patients with no recorded exposure to childhood maltreatment. The exposed group were followed up for a median of 1·8 years (IQR 0·6-4·3) versus 3·2 years (1·3-6·1) in the unexposed group. During the study period, 11 665 (5·9%) new diagnoses of mental ill health were made in the exposed group, giving an incidence rate of 16·8 events per 1000 person-years versus 15 301 (3·7%) new recorded diagnoses at an incidence rate of 8·3 events per 1000 person-years in the unexposed cohort, giving an adjusted IRR of 2·14 (95% CI 2·08-2·19). 30 911 (14·8%) patients in the exposed group received a new prescription for any type of mental ill health (incidence rate 46·5 events per 1000 person-years) versus 36 390 (8·9%) patients in the unexposed group (20·5 per 1000 person-years) resulting in an adjusted IRR of 2·44 (95% CI 2·40-2·48). Childhood maltreatment is thought to affect one in three children globally; therefore, a doubled risk of developing mental ill health among these individuals represents a substantial contribution to the mental ill health burden in the UK. It is imperative that public health approaches, including those aimed at preventing and detecting childhood maltreatment and its associated negative consequences, are implemented to prevent mental ill health. None.

Non-linear associations of 25-hydroxyvitamin D concentrations with risk of cardiovascular disease and all-cause mortality: Results from The Health Improvement Network (THIN) database

BackgroundThere is increasing evidence that vitamin D supplementation may only be beneficial in people with vitamin D deficiency, and the lack of sufficient people with very low vitamin D levels could explain the lack of protection against cardiovascular disease (CVD) reported in recent clinical trials of vitamin D supplementation. The aim of this study was to assess associations of low to moderate circulating concentrations of 25-hydroxyvitamin D (25(OH)D with risk of incident CVD and all-cause mortality, as well as the risk of ischaemic heart disease (IHD), cerebrovascular disease, and heart failure separately. Methods and ResultsLongitudinal analysis of electronic health records in The Health Improvement Network (THIN), a UK primary care database. The analysis included 180,263 patients age 18 years and older without a history of CVD and with circulating concentrations of 25(OH)D. After a mean follow-up of 2.2 (SD 1.7) years, there were 3747 patients diagnosed with CVD and 3912 patients died. Compared to patients in the highest quintile of 25(OHD) (≥ 67.5 nmol/L), those in the lowest 25(OH)D quintile (<23.1 nmol/L) had a hazard ratio (HR) of 1.24 (95% CI 1.12–1.38, P < 0.001) for CVD and 1.71 (1.55–1.88, P < 0.001) for mortality. The HR for both outcomes associated with 25(OH)D concentration was non-linear, being significantly increased in patients with 25(OH)D <35 nmol/L, and highest in those with 25(OH)D <25 nmol/L, although increased for mortality at 25(OH)D ≥100 nmol/L. The increased CVD HR in the lowest 25(OH)D quintile was more from IHD (1.35, 95% CI 1.13–1.60) and heart failure (1.38, 95% CI 1.08–1.77), than from cerebrovascular disease (1.13, 95% CI 0.97–1.31). ConclusionLow 25(OH)D are associated with highest risk of CVD and mortality, and are consistent with accumulating evidence that increased risk of these diseases occurs primarily in people with vitamin D deficiency.

Effect of Bariatric Surgery on Cardiovascular Events and Metabolic Outcomes in Obese Patients with Insulin-Treated Type 2 Diabetes: a Retrospective Cohort Study.

To compare non-fatal cardiovascular (CV) events and metabolic outcomes, among obese patients with insulin-treated type 2 diabetes who underwent bariatric surgery compared with a propensity-matched non-bariatric cohort. A retrospective cohort study was conducted among 11,125 active patients with type 2 diabetes from The Health Improvement Network (THIN) database. Propensity score matching (up to 1:6 ratio) was used to identify patients who underwent bariatric surgery (N = 131) with a non-bariatric cohort (N = 579). Follow-up was undertaken for 10years (9686 person-years) to compare differences in metabolic outcomes and CV risk events that included the following: acute myocardial infarction (AMI), stroke, coronary heart disease (CHD), heart failure (HF) and peripheral artery disease (PAD). Cox proportional regression was used to compute the outcomes between groups. The mean age was 52 (SD 13) years (60% female); the baseline weight and BMI were 116 (SD 25) kg and 41 (SD 9) kg/m2, respectively. Significant reductions in weight and BMI were observed in bariatric group during 10years of follow-up. Bariatric surgery had a significant cardioprotective effect by reducing the risk of non-fatal CHD (adjusted hazard ratio [aHR] 0.29, 95% CI 0.16-0.52, p < 0.001) and PAD events (aHR 0.31, 95% CI 0.11-0.89, p = 0.03). However, the surgery had no significant effect on AMI (aHR 0.98, p = 0.95), stroke (HR 0.87, p = 0.76) and HF (HR 0.89, p = 0.73) risks. Bariatric surgery had favourable effects on insulin independence, HbA1c and BP. Among obese insulin-treated patients with type 2 diabetes, bariatric surgery is associated with significant reductions in non-fatal CHD and PAD events, lower body weight, HbA1c, BP and a greater likelihood of insulin independency during 10years of follow-up.

A Novel Approach to Visualize Risk Minimization Effectiveness: Peeping at the 2012 UK Proton Pump Inhibitor Label Change Using a Rapid Cycle Analysis Tool.

Evaluation of risk minimization (RM) actions is an emerging area of regulatory science, often without tools to rapidly and systematically assess their effectiveness. The aim of this study was to evaluate whether chronographs, typically used for rapid signal detection in observational longitudinal databases, could be used to visualize RM effectiveness. We evaluated the UK Medicines and Healthcare products Regulatory Agency (MHRA) 2012 proton-pump inhibitors (PPIs) class-wide label change that warned of increased risk of bone fracture, advocated to limit duration of use, and recommended to treat those at risk for osteoporosis according to clinical guidelines. The cohort consisted of adults aged 18years and above prescribed one of the five PPIs available in the UK The Health Improvement Network (THIN) database through September 2015. Four chronographs were compared using drug episodes that started before (PRE) and after (POST) the 20 April 2012 MHRA warning; fracture and osteoporosis were evaluated separately. Chronographs show a measure of observed/expected events, the Information Component (IC) and 95% credibility interval (CI), calculated at monthly time intervals relative to the start date of a prescription, and summed to estimate IC over a 3-year period; IC > 0 indicates observed > expected events. We hypothesized that chronographs may assess RM effectiveness if stratified by PRE/POST an RM intervention such as a label change. There were 1,588,973 and 664,601 PPI users in the PRE and POST periods, respectively. We observed a 4.6% reduction in the proportion of long-term PPI episodes and a 4.1% reduction in the overall proportion of the THIN population using PPIs. Compared with the PRE chronographs, when both visually comparing and when examining the summed ICs for fracture in the POST period, a significant reduction was observed overall (IC = 0.024 [95% CI 0.015 to 0.33] PRE vs - 0.141 [95% CI - 0.162 to - 0.120] POST), suggesting less observed events than expected, and prior to PPI start, suggestive of strong channeling (IC = - 0.027 [95% CI - 0.037 to - 0.017] PRE vs - 0.291 [95% CI - 0.308 to - 0.274] POST). Results were qualitatively similar for osteoporosis. This pilot demonstrated a novel application of a visual, rapid analysis technique to assess RM effectiveness, and supported a hypothesis that prescribers altered some behaviors after the MHRA label change, such as channeling patients at risk of fracture or osteoporosis away from PPI use and potentially reducing fracture outcomes. Limitations include lack of confounding control and outcomes defined only by diagnosis code. Results demonstrate the potential to use large healthcare databases with chronographs to rapidly assess RM effectiveness, similar to signal detection in pharmacovigilance, and may help design more comprehensive RM evaluation studies.

Prevalence of anal fistula in the United Kingdom.

BACKGROUNDAnal fistula is a pathological connection between the anal canal and perianal skin, which most commonly develops from an infected anal crypt. While the majority of anal fistulas are idiopathic, they are also associated with Crohn’s disease (CD) and other inflammatory conditions. The prevalence of anal fistula is estimated to be 1-2 per 10000 patients, but population-based studies on anal fistula epidemiology are limited and outdated.AIMTo assess the prevalence of anal fistula and relevant comorbidities, with and without CD in the United Kingdom and Europe.METHODSA retrospective population-representative observational cohort study was performed in The Health Improvement Network (THIN), a United Kingdom primary care database. Mid-year point prevalence of anal fistula was calculated on the first of July for each year between 2014 and 2017. Estimates were calculated for anal fistula overall and by CD status and standardized to the United Kingdom and European population. Prevalence of relevant comorbidities including lymphogranuloma venereum, hidradenitis suppurativa, anal presentation of sexually transmitted diseases, diabetes mellitus, and radiation in the pelvic area was reported.RESULTSThe United Kingdom-standardized overall point prevalence of anal fistula was 1.80 (95%CI: 1.65-1.94) per 10000 patients in 2017, while the Europe standardized estimate was 1.83 (95%CI: 1.68-1.98) per 10000 patients. Both these standardized point prevalence estimates ranged from 1.89 to 2.36 between 2014-2016. The United Kingdom-standardized point prevalence of anal fistula without CD was 1.35 (95%CI: 1.23-1.48) per 10000 patients, while the Europe-standardized estimate was 1.39 (95%CI: 1.26-1.52) per 10000 patients. In contrast, the standardized point prevalence estimate of anal fistula with CD was lower for both United Kingdom and Europe (0.44; 95%CI United Kingdom: 0.37-0.52, 95%CI Europe: 0.37-0.51) per 10000 patients in 2017. In 2017, 19% of anal fistula patients without CD and 13% of anal fistula patients with CD had at least one relevant comorbidity. These results show that anal fistulas are infrequent in the general population. 24.5% of prevalent anal fistulas are associated with CD, but other potentially etiological comorbidities are rare.CONCLUSIONThis real-world evidence study estimated the United Kingdom-standardized prevalence of anal fistula was 1.80 per 10000 patients in 2017. Approximately 25% of cases may be associated with CD, while other comorbidities are rare.

Evaluating Glycemic Control in Patients with Type 2 Diabetes Suboptimally Controlled on Basal Insulin: UK ATTAIN Real-World Study.

IntroductionThis retrospective, observational cohort study evaluated the effect of therapy intensification on change in glycated hemoglobin (HbA1c) at 6 and 12 months post intensification in patients with type 2 diabetes (T2D) suboptimally controlled on basal insulin (BI) (i.e., HbA1c ≥ 7.5% [≥ 58 mmol/mol]).MethodsPatients with T2D with suboptimal glycemic control using BI were identified from The Health Improvement Network (THIN) database. Patients who underwent therapy intensification (intensifiers) within 12 months of index 1 (the date of the first incidence of suboptimally controlled HbA1c) were matched (1:1) to patients who did not intensify therapy (non-intensifiers). Index 2 was the date of therapy intensification for intensifiers, or a pseudo date for non-intensifiers that resulted in the same duration from index 1 to index 2 as their matched intensifier patient. Primary outcomes were HbA1c change and proportion of patients achieving the HbA1c target at 6 and 12 months post index 2.ResultsA total of 1342 patients (n = 646 intensifiers; n = 696 non-intensifiers) were included in the analysis. At post index 2, mean HbA1c change was substantially greater at 6 months for intensifiers than for non-intensifiers (− 0.81% vs. − 0.35%), with no additional benefit at 12 months (− 0.81% vs. − 0.49%, respectively). Compared with non-intensifiers, a greater proportion of intensifiers achieved target HbA1c at 6 months (25.1% vs. 18.8%) and at 12 months (33.4% vs. 28.2%).ConclusionsMany real-world patients with T2D suboptimally controlled with BI do not have their therapy intensified. The results of this study suggest that in this patient population, therapy intensification achieves significant reductions in HbA1c at 6 months post intensification, with little additional clinical benefit at 12 months. This suggests that, for patients who fail to achieve their glycemic targets at 6 months, since no meaningful additional clinical benefit is observed at 12 months when continuing the same therapy, further therapy intensification or change should be promptly considered.FundingThis study and the Rapid Service Fees were funded by Sanofi.Trial registration17THIN068.

Treatment patterns in UK adult patients with atopic dermatitis treated with systemic immunosuppressants: data from The Health Improvement Network (THIN)

Background: There is limited understanding on patterns of systemic treatment in adults with moderate-to-severe atopic dermatitis (AD) in the UK.Objective: To characterize treatment patterns in adult AD patients prescribed immunosuppressants (IMMs) in the primary care setting.Results: Six hundred and fifty-six patients with AD (6.6%) were prescribed IMM in the analysis (mean age 52.1 years; 59.1% female; age-adjusted Charlson comorbidity index 1.4). Most prevalent (>5%) conditions at baseline were depression (10.8%), contact dermatitis (10.7%), rheumatological disease (7.9%), skin/subcutaneous tissue disorders (6.4%), upper respiratory disease (5.8%), and psoriasis (5.2%). At baseline, up to 50% of patients were prescribed ≥1 IMM. During follow-up, 42.7% of patients were prescribed oral corticosteroids (OCSs), increasing in line with IMM exposure. The most commonly prescribed IMM was methotrexate (43.3%). Ciclosporin, the only approved IMM for AD, was prescribed to 16.9% of patients.Conclusions: The prevalence of comorbidities and high rate of IMM prescriptions demonstrate the impact of AD on quality of life. The frequency of OCS prescribing in AD patients treated with IMMs suggests a lack of disease control with existing therapies, and an unmet need for safe and effective targeted agents for long-term disease control.

Association Between Idiopathic Intracranial Hypertension and Risk of Cardiovascular Diseases in Women in the United Kingdom

Cardiovascular disease (CVD) risk has not been previously evaluated in a large matched cohort study in idiopathic intracranial hypertension (IIH). To estimate the risk of composite cardiovascular events, heart failure, ischemic heart disease, stroke/transient ischemic attack (TIA), type 2 diabetes, and hypertension in women with idiopathic intracranial hypertension and compare it with the risk in women, matched on body mass index (BMI) and age, without the condition; and to evaluate the prevalence and incidence of IIH. This population-based matched controlled cohort study used 28 years of data, from January 1, 1990, to January 17, 2018, from The Health Improvement Network (THIN), an anonymized, nationally representative electronic medical records database in the United Kingdom. All female patients aged 16 years or older were eligible for inclusion. Female patients with IIH (n = 2760) were included and randomly matched with up to 10 control patients (n = 27 125) by BMI and age. Adjusted hazard ratios (aHRs) of cardiovascular outcomes were calculated using Cox regression models. The primary outcome was a composite of any CVD (heart failure, ischemic heart disease, and stroke/TIA), and the secondary outcomes were each CVD outcome, type 2 diabetes, and hypertension. In total, 2760 women with IIH and 27 125 women without IIH were included. Age and BMI were similar between the 2 groups, with a median (interquartile range) age of 32.1 (25.6-42.0) years in the exposed group and 32.1 (25.7-42.1) years in the control group; in the exposed group 1728 women (62.6%) were obese, and in the control group 16514 women (60.9%) were obese. Higher absolute risks for all cardiovascular outcomes were observed in women with IIH compared with control patients. The aHRs were as follows: composite cardiovascular events, 2.10 (95% CI, 1.61-2.74; P < .001); heart failure, 1.97 (95% CI, 1.16-3.37; P = .01); ischemic heart disease, 1.94 (95% CI, 1.27-2.94; P = .002); stroke/TIA, 2.27 (95% CI, 1.61-3.21; P < .001); type 2 diabetes, 1.30 (95% CI, 1.07-1.57; P = .009); and hypertension, 1.55 (95% CI, 1.30-1.84; P < .001). The incidence of IIH in female patients more than tripled between 2005 and 2017, from 2.5 to 9.3 per 100 000 person-years. Similarly, IIH prevalence increased in the same period, from 26 to 79 per 100 000 women. Incidence increased markedly with BMI higher than 30. Idiopathic intracranial hypertension in women appeared to be associated with a 2-fold increase in CVD risk; change in patient care to modify risk factors for CVD may reduce long-term morbidity for women with IIH and warrants further evaluation.

Increased risk of non-alcoholic fatty liver disease in women with gestational diabetes mellitus: A population-based cohort study, systematic review and meta-analysis

AimsNon-Alcoholic Fatty Liver Disease (NAFLD) is one of the leading causes of liver transplantation in the West. This study seeks to examine whether women with gestational diabetes mellitus (GDM) are at increased risk of developing NAFLD compared to women without GDM. MethodsWe conducted a population-based retrospective matched-controlled cohort study utilising The Health Improvement Network (THIN), a large primary care database representative of the United Kingdom population, between 01/01/1990 to 31/05/2016 followed by systematic review of available literature. The study population included 9640 women with GDM and 31,296 controls without GDM, matched for age, body mass index (BMI) and time of pregnancy. All study participants were free from NAFLD diagnosis at study entry. Patients with GDM and patients developing NAFLD were identified by clinical codes. ResultsThe median (range) follow-up duration was similar in women with and without GDM (2.95 (1.21–6.01) vs 2.85 (1.14–5.75) years respectively). Unadjusted incidence rate ratio (IRR) for NAFLD development in women with vs without GDM was 3.28 (95% CI 2.14–5.02), which remained significant after adjustment for wide range of potential confounders (IRR 2.70; 95% CI 1.744–4.19). The risk of NAFLD in GDM remained high (IRR 2.46: 95% CI 1.51–4.00) despite women being censored after they developed type 2 diabetes. The meta-analysis of 3 studies (including the current study) showed increased NAFLD risk in women with vs without GDM (OR 2.60; 95% CI 1.90–3.57, I2 = 0%). As our study is based on routine clinical diagnosis of NAFLD, this study could potentially have underestimated the risk of NAFLD development. ConclusionsWomen with GDM are at increased risk of developing NAFLD in their later life compared to women without GDM regardless of the development of type 2 diabetes. Clinicians should have a low threshold to investigate women with history of GDM for the presence of NAFLD. Further studies to identify screening strategies are needed.

Thiazide diuretics and risk of knee replacement surgery among patients with knee osteoarthritis: a general population-based cohort study

Thiazide diuretic use is associated with higher bone mineral density (BMD) and possibly lower serum magnesium levels than loop diuretic use, and both high BMD and low serum magnesium have been linked to high prevalent knee osteoarthritis. This study aimed to compare the risk of a clinically relevant endpoint, knee replacement (KR) surgery, among initiators of thiazide and loop diuretics. Among patients aged ≥50 years with a diagnosis of knee osteoarthritis in The Health Improvement Network (THIN) in United Kingdom, we conducted a propensity score-matched cohort study to examine the relation of thiazide diuretic initiation vs loop diuretic initiation to the risk of KR over 5years. Among thiazide and loop diuretic initiators (n=3,488 for each group; mean age: 73 years; female ratio: 59%), 359 (28.6/1,000 person-years) and 283 (24.1/1,000 person-years) KRs occurred during the follow-up period, respectively. The hazard ratio (HR) of KR for thiazide diuretic initiation vs loop diuretic initiation was 1.26 (95% confidence interval [CI]: 1.08-1.47). The adherence-adjusted HR of KR for continuous use of thiazide diuretics was 1.44 (95% CI: 1.21-1.72). In this population-based cohort of patients with knee osteoarthritis, thiazide diuretic use was associated with a higher risk of KR than loop diuretic use. This association may potentially be due to thiazide diuretics' effect on BMD and serum magnesium.

Trends in the incidence of testing for vitamin D deficiency in primary care in the UK: a retrospective analysis of The Health Improvement Network (THIN), 2005–2015

ObjectiveTo investigate trends in the incidence of testing for vitamin D deficiency and the prevalence of patients with circulating concentrations of 25-hydroxyvitamin D (25(OH)D) indicative of deficiency (<30 nmol/L) between...

255-OR: Temporal Trend in the Prevalence and Incidence of Depression and Antidepressant Usages in Incident Type 2 Diabetes from U.S. and UK

Aim: Temporal trend in the prevalence and incidence of depression (DP), any mental illness (AMI) and use of anti-depressants (ADM) in incident T2DM pts is not well known. We evaluate these trends and the risk of developing DP in young pts in real world settings from U.S. and UK. Method: Adults with diagnosis (Dx) of T2DM from 2000 from Centricity Electronic Medical Records of U.S. and The Health Improvement Network (THIN) database of UK were examined. Results: In U.S. (n= 1,395,572)/UK (n= 343,714) cohorts, the age at T2DM Dx was 59/58 years, 2/8% had Dx of DP but were not on ADM, 16/10% were on ADM without DP or AMI Dx, 9/15% were using ADM with Dx of DP. The prevalence of DP, AMI and ADM use increased exponentially in UK since 2000 (Figure B), while an increasing prevalence in AMI and ADM use was seen in U.S. (Figure A). Between 2000-2016, the use of ADM without Dx of DP or AMI increased from 16-26%/5-41% in U.S./UK cohort. Incidence rates of DP and ADM use were significantly higher in the U.S. cohort compared to UK (Figures C and D). Among pts without a co-morbid condition at T2DM Dx, younger U.S./UK pts (≤ 50 years) had 28%/18% significantly higher risks of developing DP compared to older pts (≥ 60 years); among pts with existing co-morbidity, the risks were higher by 46%/33%. Conclusion: In incident T2DM pts in UK and U.S., a striking rise in the prevalence of DP and the ADP use without Dx of AMI is seen, with younger pts having higher risk of developing DP. Disclosure J. Dibato: None. D. Koye: None. W. Polonsky: Consultant; Self; Abbott, Bigfoot Biomedical, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Johnson &amp; Johnson Diabetes Institute, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi, Servier. O. Montvida: None. S.K. Paul: Consultant; Self; AstraZeneca, Roche Pharma. Research Support; Self; Roche Pharma.