The Health Improvement Network Research Articles

Cost-effectiveness of two reduced pressure compression systems in treating newly diagnosed venous leg ulcers.

To assess the clinical outcomes and cost-effectiveness of using two different reduced pressure compression systems in treating newly diagnosed venous leg ulcers (VLUs) in clinical practice, from the perspective of the UK's National Health Service (NHS). This was a modelling study based on a retrospective cohort analysis of the case records of patients with a newly diagnosed VLU, randomly extracted from The Health Improvement Network (THIN) database, who were initially treated with a two-layer cohesive compression bandage (TLCCB Lite; Coban 2 Lite, 3M, US) or a two-layer compression system (TLCS Reduced; Ktwo Reduced, Urgo, France). No significant differences were detected between the groups. Nevertheless, analysis of covariance (ANCOVA) was performed to enable differences in patients' outcomes between the groups to be adjusted for any heterogeneity in baseline covariates. Clinical outcomes and cost-effectiveness of the alternative compression systems were estimated over 12 months after starting treatment. Time from wound onset to starting compression was a mean of two months. The probability of healing at 12 months was 0.59 in the TLCCB Lite group and 0.53 in the TLCS Reduced group. Patients in the TLCCB Lite group experienced a marginally better health-related quality of life (HRQoL) of 0.02 quality-adjusted life years (QALYs) per patient compared to those in the TLCS Reduced group. The 12-month NHS wound management cost was £3883 per patient treated with TLCCB Lite and £4235 per patient treated with TLCS Reduced. When the analysis was repeated without ANCOVA, the findings from the base case analysis remained unchanged (i.e., use of TLCCB Lite improved outcomes at lower cost). Within the study's limitations, treating newly diagnosed VLUs with TLCCB Lite instead of TLCS Reduced potentially affords a cost-effective use of NHS-funded resources in clinical practice, since it is expected to result in an increased healing rate, better HRQoL and a lower NHS wound management cost.

Trends in incidence of recorded diagnosis of osteoporosis, osteopenia, and fragility fractures in people aged 50 years and above: retrospective cohort study using UK primary care data

SummaryThis study used primary care data to estimate the incidence of recorded diagnosis of osteoporosis, osteopenia, and fragility fracture in the UK during 2000–2018 accounting for age, sex, calendar year and social deprivation. More than 3 million people aged 50–99 years were included. We found that men living in the most deprived areas had a 45% higher risk of being diagnosed with osteoporosis and 50% higher risk of fragility fracture compared to men living in the least deprived areas.Purposea) To estimate the incidence trends of a recorded diagnosis of osteoporosis, osteopenia, and fragility fracture in the UK over time; b) to describe differences according to age, sex, and social deprivation.MethodsThis is a longitudinal population-based cohort study using routinely collected primary care data obtained via IQVIA Medical Research Database (IMRD). All patients aged 50–99 years registered with a practice participating in THIN (The Health Improvement Network) between 2000–2018 were included. The first recorded diagnosis of osteoporosis, osteopenia, or fragility fracture was used to estimate incidence rates (IR) per 10,000 person-years at risk. Poisson regression was used to provide Incidence Rate Ratios (IRR) adjusted by age, sex, social deprivation, calendar year, and practice effect.ResultsThe year-specific adjusted IRR of recorded osteoporosis was highest in 2009 in women [IRR 1.44(95%CI 1.38–1.50)], whereas in men it was highest in 2013–2014 [IRR 1.94(95%CI 1.72–2.18)] compared to 2000. The year-specific adjusted IRR of fragility fracture was highest in 2012 in women [IRR 1.77(95%CI 1.69–1.85)], whereas in men it was highest in 2013 [IRR 1.64(95%CI 1.51–1.78)] compared to 2000. Men in the most deprived areas had a higher risk of being diagnosed with osteoporosis [IRR 1.45(95%CI 1.38–1.53)], osteopenia [IRR 1.17(95%CI 1.09–1.26)], and fragility fracture [IRR 1.50(95%CI 1.44–1.56)] compared to those living in the least deprived areas, but smaller differences were seen in women.ConclusionUse of fracture risk assessment tools may enhance the detection of osteoporosis cases in primary care. Further research is needed on the effect of social deprivation on diagnosis of osteoporosis and fractures.

Non-steroidal anti-inflammatory drugs-aspirin interactions and with risk of cardiovascular disease in patients osteoarthritis.

Non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of the pharmacologic management for relieving osteoarthritis (OA) pain and low-dose aspirin is often prescribed to OA patients who are at high risk of cardiovascular disease (CVD). We conducted cohort studies using data from The Health Improvement Network (THIN) database (2000-2019) to assess whether the relation of initiation of naproxen or ibuprofen vs. initiation of other NSAIDs (excluding both naproxen and ibuprofen), respectively, to the risk of CVD was modified by co-prescription of low-dose aspirin among the participants with OA. Among participants without co-prescription of aspirin, the risk of CVD was lower in naproxen initiators (10.3/1000 person-years) than in other NSAIDs initiators (13.2/1000 person-years) (hazard ratio (HR)=0.71, 95% confidence interval (CI): 0.60-0.85). Among participants with co-prescription of aspirin, however, the risk of CVD was higher in naproxen initiators (36.9/1000 person-years) than that in other NSAIDs initiators (34.8/1000 person-years) (HR=1.48, 95%CI:1.12-1.84). The association was significantly modified by co-prescription of aspirin (P<0.001). Similar findings were observed in the association of initiation of ibuprofen vs. other NSAIDs with the risk of CVD, which was significantly modified by co-prescription of aspirin (P<0.001). These findings suggest that OA patients and clinicians should be aware of the potential CVD risk of concurrently taking naproxen or ibuprofen and low-dose aspirin.

Genetic Validation of Psoriasis Phenotyping in UK Biobank Supports the Utility of Self-Reported Data and Composite Definitions for Large Genetic and Epidemiological Studies

Genetic Validation of Psoriasis Phenotyping in UK Biobank Supports the Utility of Self-Reported Data and Composite Definitions for Large Genetic and Epidemiological Studies

Relative cost-effectiveness of three compression bandages in treating newly diagnosed venous leg ulcers in the UK

To assess the clinical outcomes and cost-effectiveness of using a two-layer cohesive compression bandage (TLCCB; Coban 2, 3M, US) compared with a two-layer compression system (TLCS; KTwo, Urgo, France) and a cohesive inelastic bandage system (CIBR; Actico, L&R, Germany) in treating newly diagnosed venous leg ulcers (VLUs) in clinical practice, from the perspective of the UK's National Health Service (NHS). This was a modelling study based on a retrospective cohort analysis of the case records of patients with a newly diagnosed VLU randomly extracted from the The Health Improvement Network (THIN) database who were treated with TLCCB, TLCS or CIBR. No significant differences were detected between the groups. Nevertheless, analysis of covariance was performed to enable differences in patients' outcomes between the groups to be adjusted for any heterogeneity in baseline covariates. Clinical outcomes and cost-effectiveness of the alternative compression systems were estimated over 12 months after starting treatment. There were 250 patients in each group. Time from wound onset to starting compression was a mean of two months. The healing distribution of the TLCCB-treated patients was significantly different from that of the other two cohorts (p=0.003); the probability of healing at 12 months was 0.62, 0.51 and 0.49 in the TLCCB, TLCS and CIBR groups, respectively. Patients treated with TLCCB experienced better health-related quality of life (HRQoL) over 12 months (0.86 quality-adjusted life years (QALYs) per patient), compared with those treated with TLCS and CIBR (0.83 and 0.82 QALYs per patient, respectively). The 12-month NHS wound management cost was £3693, £4451 and £4399 per patient in the TLCCB, TLCS and CIBR groups, respectively. Within the model's limitations, treating newly diagnosed VLUs with TLCCB instead of the other two compression systems appears to afford a more cost-effective use of NHS-funded resources in clinical practice, since it is expected to result in increased healing, better HRQoL and a lower wound management cost for the NHS.

Risk of progression from pre-diabetes to type 2 diabetes in a large UK adult cohort.

People with pre-diabetes are at high risk of progressing to type 2 diabetes. This progression is not well characterised by ethnicity, deprivation and age, which we describe in a large cohort of individuals with pre-diabetes. A retrospective cohort study with The Health Improvement Network (THIN) database was conducted. Patients aged 18 years and over and diagnosed with pre-diabetes [HbA1c 42 mmol/mol (6.0%) to 48 mmol/mol (6.5%) were included]. Cox proportional hazards regression was used to calculate adjusted hazard rate ratios (aHR) for the risk of progression from pre-diabetes to type 2 diabetes for each of the exposure categories [ethnicity, deprivation (Townsend), age and body mass index (BMI)] separately. Of the baseline population with pre-diabetes (n=397,853), South Asian (aHR 1.31; 95% CI 1.26-1.37) or Mixed-Race individuals (aHR 1.22; 95% CI 1.11-1.33) had an increased risk of progression to type 2 diabetes compared with those of white European ethnicity. Likewise, deprivation (aHR 1.17; 95% CI 1.14-1.20; most vs. least deprived) was associated with an increased risk of progression. Both younger (aHR 0.63; 95% CI 0.58-0.69; 18 to <30 years) and older individuals (aHR 0.85; 95% CI 0.84-0.87; ≥65 years) had a slower risk of progression from pre-diabetes to type 2 diabetes, than middle-aged (40 to <65 years) individuals. South Asian or Mixed-Race individuals and people with social deprivation had an increased risk of progression from pre-diabetes to type 2 diabetes. Clinicians need to recognise the differing risk across their patient populations to implement appropriate prevention strategies.

Concurrent Use of Oral Anticoagulants and Sulfonylureas in Individuals With Type 2 Diabetes and Risk of Hypoglycemia: A UK Population-Based Cohort Study.

ObjectiveTo investigate the association of concurrent use of oral anticoagulants (OACs) and sulfonylureas and the risk of hypoglycemia in individuals with type 2 diabetes mellitus (T2DM).Research Design and MethodsA retrospective cohort study was conducted between 2001 and 2017 using electronic primary healthcare data from the IQVIA Medical Research Data (IMRD) that incorporates data supplied by The Health Improvement Network (THIN), a propriety database of Cegedim SA. Individuals with T2DM who received OAC prescription and sulfonylureas were included. We compared the risk of hypoglycemia with sulfonylureas and OACs using propensity score matching and Cox regression.Results109,040 individuals using warfarin and sulfonylureas and 77,296 using direct oral anticoagulants (DOACs) and sulfonylureas were identified and included. There were 285 hypoglycemia events in the warfarin with sulfonylureas group (incidence rate = 17.8 per 1,000 person-years), while in the sulfonylureas only, 304 hypoglycemia events were observed (incidence rate = 14.4 per 1,000 person-years). There were 14 hypoglycemic events in the DOACs with sulfonylureas group (incidence rates = 14.8 per 1,000 person-years), while in the sulfonylureas alone group, 60 hypoglycemia events were observed (incidence rate =23.7 per 1,000 person-years). Concurrent use of warfarin and sulfonylureas was associated with increased risk of hypoglycemia compared with sulfonylureas alone (HR 1.38; 95% CI 1.10–1.75). However, we found no evidence of an association between concurrent use of DOACs and sulfonylureas and risk of hypoglycemia (HR 0.54; 95% CI, 0.27–1.10) when compared with sulfonylureas only.ConclusionsWe provide real-world evidence of possible drug-drug interactions between warfarin and sulfonylureas. The decision to prescribe warfarin with coexistent sulfonylureas to individuals with T2DM should be carefully evaluated in the context of other risk factors of hypoglycemia, and availability of alternative medications.

Long term survival after a first transient ischaemic attack in England: A retrospective matched cohort study

ObjectiveTransient ischaemic attacks (TIA) serve as warning signs for future stroke, and the impact of TIA on long term survival is uncertain. We assessed the long-term hazards of all-cause mortality following a first episode of a transient ischaemic attack (TIA). DesignRetrospective matched cohort study. MethodsCohort study using electronic primary health care records from The Health Improvement Network (THIN) database in the United Kingdom. Cases born in or before 1960, resident in England, with a first diagnosis of TIA between January 1986 and January 2017 were matched to three controls on age, sex and general practice. The primary outcome was all-cause mortality. The hazards of all-cause mortality were estimated using a time-varying Double-Cox Weibull survival model with a random frailty effect of general practice, while adjusting for different socio-demographic factors, medical therapies, and comorbidities. Results20,633 cases and 58,634 controls were included. During the study period, 24,176 participants died comprising of 7,745 (37.5%) cases and 16,431(28.0%) controls. In terms of hazards of mortality, cases aged 39 to 60 years at the first TIA event had the highest hazard ratio (HR) of mortality compared to their 39-60 years matched controls (HR = 3.04 (2.91 - 3.18)). The HR for cases aged 61-70 years, 71-76 years and 77+ years were 1.98 (1.55 - 2.30), 1.79 (1.20 - 2.07) and 1.52 (1.15 - 1.97) compared to their same-aged matched controls. Cases aged 39-60 at TIA onset who were prescribed aspirin were associated with reduced HR of 0.93 (0.84 - 1.01), 0.90 (0.82 - 0.98) and 0.88 (0.80 - 0.96) at 5, 10 and 15 years respectively, compared to the same aged cases who were not prescribed any antiplatelet. Statistically significant reductions in hazard ratios were observed with aspirin at 10 and 15 years in all age groups. Hazard ratio point estimates for other antiplatelets (dipyridamole or clopidogrel) and dual antiplatelet therapy were very similar to aspirin at 5, 10 and 15 years but with wider confidence intervals that included 1. There was no survival benefit associated with antiplatelet prescription in controls. ConclusionsThe overall risk of death was considerably elevated in all age groups after a first-ever TIA event. Aspirin prescription was associated with a reduced risk. These findings support the use of aspirin in secondary prevention for people with a TIA. The results do not support the use of antiplatelet medication in people without TIA.

1071 INCIDENCE OF RECORDED OSTEOPOROSIS, OSTEOPENIA AND FRAGILITY FRACTURE IN OLDER PEOPLE: ANALYSIS OF UK PRIMARY CARE DATA

Abstract Introduction Osteoporosis is common in later life, leading to fragility fractures associated with increased mortality, disability, and costs. There is a surprising lack of data regarding the incidence of osteoporosis. We aimed to estimate the incidence of recorded diagnosis of osteoporosis, osteopenia, and fragility fracture in older people, explore time trends in diagnosis, and differences by age, sex, and social deprivation. Method We used de-identified patient data provided as part of routine primary care (IQVIA Medical Research Database (IMRD). All patients aged 50-99y registered with THIN (The Health Improvement Network) participating practices between 1/1/2000–31/12/2018 were included. Crude incidence rates (IR) were estimated per 10,000 person-years (PY). We used Poisson regression to calculate adjusted Incidence Rate Ratios (IRR) accounting for sex, age, calendar year and deprivation. Results The IR of osteoporosis was significantly higher in women, 84.32 (95%CI 83.81–84.83) vs. 16.66 (95%CI 16.43–16.90) in men per 10,000PY. In women, recorded IR of osteoporosis reached a peak in 2009. In the adjusted model, older men in most deprived areas had a higher IRR of osteoporosis [1.67 (95% 1.59–1.74)] compared to those in least deprived areas. Women were more likely to be diagnosed with osteopenia compared to men, at any age. Incidence of osteopenia diagnosis increased over time. In the adjusted model, men in most deprived areas had a higher IRR of osteopenia [1.44 (95%CI 1.35–1.53)] compared to least deprived areas. The IR of fragility fracture was higher in women, 84.97 (95%CI 84.45–85.48) vs. 31.15 (95%CI 30.83–31.48) in men per 10,000PY. In the adjusted model, men in most deprived areas had an increased IRR of fragility fracture [1.53 (95%CI 1.48–1.59)] compared to least deprived areas. Conclusion Community bone health interventions might be targeted at populations at higher risk of fragility fractures, including older men living in socially deprived areas.

Maternal Postnatal Depression and Completion of Infant Immunizations: A UK Cohort Study of 196,329 Mother-Infant Pairs, 2006-2015.

Objective: To examine the relationship between maternal postnatal depression and completion of infant vaccinations.Methods: We conducted a cohort study using data from The Health Improvement Network (THIN), a large UK primary care electronic health record database. We identified 196,329 mother-infant pairs in which the infant was born between 2006 and 2015. Postnatal depression was identified through antidepressant prescriptions or diagnoses or symptoms of depression in first year after childbirth. Primary outcome was completion of three 5-in-1 vaccination doses in infants before 1 year of age; this vaccine protects against diphtheria, tetanus, whooping cough, polio, and Haemophilus influenzae type b. We used Poisson regression models to compare likelihood of infant 5-in-1 vaccine uptake among children of women with a record of postnatal depression to likelihood among those without.Results: Of the 196,329 women, 20,802 (10.6%) had a record of postnatal depression and/or antidepressant prescription. There was no difference in infants' 5-in-1 vaccination completion between those of mothers with a record and those of mothers' without (adjusted incidence rate ratio [IRR] = 1.01; 95% CI, 0.99-1.02). Those from more socially deprived areas were less likely to complete infant vaccinations compared to those from the least deprived areas (IRR = 0.92; 95% CI, 0.90-0.93). Likelihood of completing infant vaccination decreased over time, comparing 2014-2015 to 2006-2007 (IRR = 0.90; 95% CI, 0.89-0.92).Conclusions: Among mothers who engage with primary care, maternal postnatal depression is not associated with lower rates of infant vaccination, though more research is needed to conclude if either more severe depression or unrecognized depression is associated with lower completion rates.

Peptic Ulcer Disease and Risk of Hip Fracture: A General Population-based Cohort Study.

Previous studies reported proton pump inhibitor (PPI) use may increase the risk of fracture; however, the findings may be susceptible to indication bias because peptic ulcer disease (PUD), 1 major indication for PPIs, may affect skeletal health. Determining whether PUD would increase hip fracture risk may help identify high-risk populations and explore risk factors. We conducted a cohort study using data from The Health Improvement Network (THIN) in the United Kingdom. THIN contains patient information such as disease diagnosis and medicine prescriptions. Up to 5 non-PUD individuals (n = 138 265) were matched to each case of incident PUD (n = 27 653) by age, sex, and body mass index. We examined the association between PUD and hip fracture by a multivariable Cox proportional hazard model. We repeated the same analysis among individuals with incident PUD and gastroesophageal reflux disease (GERD) (n = 27 160), another disease with similar indication for PPIs, as a positive control exposure. Over a mean of 5.6 years of follow-up, hip fracture occurred in 589 individuals with PUD and 2015 individuals without PUD (3.8 vs 2.6/1000 person-years), with a multivariable-adjusted hazard ratio (HR) being 1.44 (95% confidence interval [CI], 1.31-1.58). The association persisted among subgroups stratified by sex and age. In positive control exposure analysis, the hip fracture risk was also higher in PUD than GERD (3.8 vs 2.4/1000 person-years; multivariable-adjusted HR = 1.65; 95% CI, 1.45-1.7). This general population-based cohort study suggests, after controlling for acid-lowering medication and other potential risk factors, PUD is independently associated with an increased risk of hip fracture.

Risk of incident obstructive sleep apnoea in patients with type 1 diabetes: a population-based retrospective cohort study

Aims/hypothesisPeople with type 2 diabetes are at increased risk of developing obstructive sleep apnoea. However, it is not known whether people with type 1 diabetes are also at an increased risk of obstructive sleep apnoea. This study aimed to examine whether people with type 1 diabetes are at increased risk of incident obstructive sleep apnoea compared with a matched cohort without type 1 diabetes.MethodsWe used a UK primary care database, The Health Improvement Network (THIN), to perform a retrospective cohort study between January 1995 and January 2018 comparing sleep apnoea incidence between patients with type 1 diabetes (exposed) and without type 1 diabetes (unexposed) (matched for age, sex, BMI and general practice). The outcome was incidence of obstructive sleep apnoea. Baseline covariates and characteristics were assessed at the start of the study based on the most recent value recorded prior to the index date. The Cox proportional hazards regression model was used to estimate unadjusted and adjusted hazard ratios, based on a complete-case analysis.ResultsIn total, 34,147 exposed and 129,500 matched unexposed patients were included. The median follow-up time was 5.43 years ((IQR 2.19–10.11), and the mean BMI was 25.82 kg/m2 (SD 4.33). The adjusted HR for incident obstructive sleep apnoea in patients with type 1 diabetes vs those without type 1 diabetes was 1.53 (95% CI 1.25, 1.86; p<0.001). Predictors of incident obstructive sleep apnoea in patients with type 1 diabetes were older age, male sex, obesity, being prescribed antihypertensive or lipid-lowering drugs, atrial fibrillation and depression.Conclusions/interpretationIndividuals with type 1 diabetes are at increased risk of obstructive sleep apnoea compared with people without diabetes. Clinicians should suspect obstructive sleep apnoea in patients with type 1 diabetes if they are old, have obesity, are male, have atrial fibrillation or depression, or if they are taking lipid-lowering or antihypertensive drugs.Graphical abstract

A prospective evaluation of the fourth national Be Clear on Cancer 'Blood in Pee' campaign in England.

ObjectiveTo assess the impact of the fourth Be Clear on Cancer (BCoC) ‘Blood in Pee’ (BiP) campaign (July to September 2018) on bladder and kidney cancer symptom awareness and outcomes in England.MethodsIn this uncontrolled before and after study, symptom awareness and reported barriers to GP attendance were assessed using panel and one‐to‐one interviews. The Health Improvement Network (THIN), National Cancer Registration and Analysis Service (NCRAS) and NHS Cancer Waiting Times (CWT) data were analysed to assess the impact on GP attendances, urgent cancer referrals, cancer diagnoses and 1‐year survival. Analyses used Poisson, negative binomial and Cox regression.ResultsSymptom awareness and intention to consult a GP after one episode of haematuria increased following the campaign. GP attendance with haematuria (rate ratio (RR) 1.17, 95% confidence interval (CI): 1.07–1.28) and urgent cancer referrals (RR 1.18 95% CI: 1.08–1.28) increased following the campaign. Early‐stage diagnoses increased for bladder cancer (difference in percentage 2.8%, 95% CI: −0.2%–5.8%), but not for kidney cancer (difference −0.6%, 95% CI: −3.2%–2.1%).ConclusionsThe fourth BCoC BiP campaign appears to have been effective in increasing bladder cancer symptom awareness and GP attendances, although long‐term impacts are unclear.

225P Impact of potential drug-drug interactions (PDDI) on adherence to endocrine therapy (ET) among patients with breast cancer (BC) in the Health Improvement Network (THIN)

ET represents a cornerstone in the treatment of early and late hormone receptors-positive (HR+) BC. However, adherence to ET is a major issue that can substantially impact survival outcomes. We explored whether PDDI with ET impact adherence.

Does hydrochlorothiazide increase the incidence of skin, lip and oral cancer in a UK population?

Data sources Data was from The Health Improvement Network (THIN) database from January 1999 to May 2016.Study selection This was a series of population-based, case-control studies looking to evaluate the association between hydrochlorothiazide (HCTZ) exposure and skin, lip and oral cancer in the UK population.Case/control selection Using the THIN database, patients with the following outcomes were grouped: squamous cell carcinoma (SCC) skin cancer; basal cell carcinoma (BCC) skin cancer; melanoma; lip cancer and oral cancer. Patients within the lip cancer and oral cancer groups were accepted with a history of non-melanoma skin cancer (NMSC). Patients in the SCC and BCC groups were not accepted with a history of cancer. Patients with a history of organ transplantation, human immunodeficiency virus (HIV) or immunosuppressant drug use before the index date were not accepted, due to the risk of predisposition to cancer. Controls were randomly selected using incidence density sampling. Up to 100 controls were randomly selected, matched on sex, exact year of birth and calendar year of cohort entry for lip cancer. However, for the remaining outcomes, only 20 controls were matched as above. Adults with incident NMSC, melanoma, lip cancer and oral cancer were matched to controls. Incidence rate ratios (IRRs) for the aforementioned outcomes were calculated for every cumulative HCTZ exposure.Data analysis Odds ratios were calculated using conditional logistic regression. Associations were presented using a two-year HCTZ exposure lag-time and a five-year HCTZ exposure lag-time. Associations were evaluated using sensitivity analysis, restricted to patients with at least ten years' follow-up. There was adjustment for smoking status and BMI. Published incidence rates were used to calculate the absolute risk estimate for SCC as the incidence of SCC in the cohort was less than expected. For high-dose cumulative HCTZ exposure, the number of patients needed to treat to cause one additional cancer (number needed to harm) per year overall was estimated using rate differences. Analysis was carried out using SAS Enterprise Guidev7.1 and STATAv15.Results Relative incidence of SCC, BCC and lip cancer was significantly elevated with every use of HCTZ. Relative incidence of melanoma and oral cancer was not significantly elevated with HCTZ exposure. Smoking was inversely associated with BCC and melanoma risk, but significantly increased the risk of lip and oral cavity cancers. SCC risk was not strongly associated with smoking. Significantly reduced risk of SCC, BCC melanoma and oral cavity cancer was associated with a BMI ≥30 kg/m2.Conclusions The risk of NMSC and lip cancer in a UK population is increased with cumulative high-dose HCTZ exposure. It is therefore important for dentists to note as it may increase suspicion of lesions in patients taking these medications.

Evaluating the performance of temporal pattern discovery: new application using statins and rhabdomyolysis in OMOP databases

BackgroundTemporal pattern discovery (TPD) is a method of signal detection using electronic healthcare databases, serving as an alternative to spontaneous reporting of adverse drug events. Here, we aimed to replicate and optimise a TPD approach previously used to assess temporal signals of statins with rhabdomyolysis (in The Health Improvement Network (THIN) database) by using the OHDSI tools designed for OMOP data sources.MethodsWe used data from the Truven MarketScan US Commercial Claims and the Commercial Claims and Encounters (CCAE). Using an extension of the OHDSI ICTemporalPatternDiscovery package, we ran positive and negative controls through four analytical settings and calculated sensitivity, specificity, bias and AUC to assess performance.ResultsSimilar to previous findings, we noted an increase in the Information Component (IC) for simvastatin and rhabdomyolysis following initial exposure and throughout the surveillance window. For example, the change in IC was 0.266 for the surveillance period of 1–30 days as compared to the control period of − 180 to − 1 days. Our modification of the existing OHDSI software allowed for faster queries and more efficient generation of chronographs.ConclusionOur OMOP replication matched the we can account forwe can account for of the original THIN study, only simvastatin had a signal. The TPD method is a useful signal detection tool that provides a single statistic on temporal association and a graphical depiction of the temporal pattern of the drug outcome combination. It remains unclear if the method works well for rare adverse events, but it has been shown to be a useful risk identification tool for longitudinal observational databases. Future work should compare the performance of TPD with other pharmacoepidemiology methods and mining techniques of signal detection. In addition, it would be worth investigating the relative TPD performance characteristics using a variety of observational data sources.

P652 The burden of mental illness, including deliberate self-harm, before and after a diagnosis of IBD, a UK population study

Abstract Background The burden of mental illness among IBD patients is recognised to be greater than among their healthy peers. Due to the bi-directional influence of the gut-brain axis,mental health may be linked to IBD outcomes and vice versa. The aim of this study was to use population level data to describe the incidence of anxiety, depression, insomnia, severe mental illness and deliberate self-harm in patients with IBD. Methods A retrospective cohort study was conducted using The Health improvement Network (THIN) database to estimate the incidence rates of anxiety, depression, insomnia, severe mental illness and deliberate self harm in patients with IBD between 1995 to 2021 and matched controls with no pre-existing mental health illness.The prevalence of pre-existing depression, anxiety and insomnia prior to IBD diagnosis was assessed for IBD patients and matched controls.The association between deliberate self harm and incident mental health diagnoses following IBD diagnosis were estimated using Cox regression analysis. Results We identified 59,613 incident cases of IBD,34,615 (58.1%) had UC and 25,000 (41.9%) had Crohn’s disease. The median age was;41.5 (IQR 29.6–57.5) years,with an equal proportion of males and females with IBD (49.2% vs 50.8%). Patients with a diagnosis of IBD had an increased prevalence of anxiety 10 years (3.0% vs 2.5%,p&amp;lt;0.001) and 2 years prior to diagnosis (6.2% and 5.3%,p&amp;lt;0.001). A similar pattern was seen for insomnia at 10 years (1.0% vs 0.9%, p=0.028) and 2 years (3.4% vs 3.0%, p&amp;lt;0.001) and for depression at 10 years (3.7% vs 4.5%, p&amp;lt;0.001) and 2 years (8.1% vs 9.6%, p&amp;lt;0.001). The incidence of mental illness was higher in IBD patients than controls for; anxiety [6.1 vs 5.3 per 1000 patient years,HR 1.14(1.09–1.20),p&amp;lt;0.001], depression [11.3 vs 7.5 per 1000 patient years,HR 1.34 (1.28–1.39),p&amp;lt;0.001], insomnia [9.6 vs 6.0 per 1000 patient years,HR 1.54(1.5–1.6),p&amp;lt;0.001] and DSH [1.6 vs 1.2 per 1000 patient years,HR 1.20(1.07–1.35),p&amp;lt;0.001]. Associations of deliberate self harm in this patient groups included: IBD (HR 1.20(1.07–1.35),p=0.002),female gender (HR 1.06(1.35–1.60),p&amp;lt;0.001),age quintile &amp;lt;27.4 years (HR 4.48(3.95–5.93),p&amp;lt;0.001) compared to &amp;gt;61.3 years,anxiety (HR 1.57(1.35–1.82),p&amp;lt;0.001),depression (HR 5.97(5.33–6.69),p&amp;lt;0.001),insomnia (HR 2.32(2.02–2.66),p&amp;lt;0.001), and severe mental illness (HR 5.74(4.56–7.22),p&amp;lt;0.001). Conclusion There is an additional burden of mental illness in patients who are later diagnosed with IBD. Following diagnosis,the incidence of depression, anxiety, insomnia and deliberate self harm is higher in individuals with IBD than controls.Patients who develop mental illness in the setting of IBD are at particularly high risk of deliberate self-harm.

What can GP data tell us about the treatment of onychomycosis in the UK?

BackgroundTreatment of onychomycosis is challenging, and there is much literature on optimal treatment strategies. In contrast, information on how onychomycosis is actually treated in primary care is scarce. Information on practice is important as it can reveal much, such as, to what extent national guidelines are followed and which population groups seek/receive treatment or do not do so.ObjectivesTo describe the pattern of onychomycosis treatment in primary care in the UK, by patient's gender and age.MethodsA population‐based retrospective cross‐sectional study was conducted. The Health Improvement Network (THIN) database was used to calculate incidence rates of onychomycosis in the years 2001–2017. The prescription of oral and topical anti‐fungal drugs to patients with onychomycosis was reviewed.ResultsTHIN data showed an onychomycosis incidence rate of about 50 per 100,000. More males than females (52% vs. 48%), and more people aged 50–59 years had received treatment for onychomycosis. Oral terbinafine was the most commonly prescribed drug, followed by topical amorolfine, although terbinafine was used more commonly by men and amorolfine by women. Patients with onychomycosis were also prescribed other antifungals, including itraconazole, griseofulvin, tioconazole, ketoconazole shampoo, fluconazole and clotrimazole. A greater proportion of women, compared to men, were prescribed fluconazole.ConclusionsOnychomycosis treatment in primary care in the UK is broadly in concordance with national guidelines.

90-Day all-cause mortality can be predicted following a total knee replacement: an international, network study to develop and validate a prediction model

PurposeThe purpose of this study was to develop and validate a prediction model for 90-day mortality following a total knee replacement (TKR). TKR is a safe and cost-effective surgical procedure for treating severe knee osteoarthritis (OA). Although complications following surgery are rare, prediction tools could help identify high-risk patients who could be targeted with preventative interventions. The aim was to develop and validate a simple model to help inform treatment choices.MethodsA mortality prediction model for knee OA patients following TKR was developed and externally validated using a US claims database and a UK general practice database. The target population consisted of patients undergoing a primary TKR for knee OA, aged ≥ 40 years and registered for ≥ 1 year before surgery. LASSO logistic regression models were developed for post-operative (90-day) mortality. A second mortality model was developed with a reduced feature set to increase interpretability and usability.ResultsA total of 193,615 patients were included, with 40,950 in The Health Improvement Network (THIN) database and 152,665 in Optum. The full model predicting 90-day mortality yielded AUROC of 0.78 when trained in OPTUM and 0.70 when externally validated on THIN. The 12 variable model achieved internal AUROC of 0.77 and external AUROC of 0.71 in THIN.ConclusionsA simple prediction model based on sex, age, and 10 comorbidities that can identify patients at high risk of short-term mortality following TKR was developed that demonstrated good, robust performance. The 12-feature mortality model is easily implemented and the performance suggests it could be used to inform evidence based shared decision-making prior to surgery and targeting prophylaxis for those at high risk.Level of evidenceIII.

The effect of hormone replacement therapy on the survival of UK women: a retrospective cohort study 1984-2017.

ObjectiveTo estimate the effect of estrogen‐only and combined hormone replacement therapy (HRT) on the hazards of overall and age‐specific all‐cause mortality in healthy women aged 46–65 at first prescription.DesignMatched cohort study.SettingElectronic primary care records from The Health Improvement Network (THIN) database, UK (1984−2017).Population105 199 HRT users (cases) and 224 643 non‐users (controls) matched on age and general practice.MethodsWeibull‐Double‐Cox regression models adjusted for age at first treatment, birth cohort, type 2 diabetes, hypertension and hypertension treatment, coronary heart disease, oophorectomy, hysterectomy, body mass index, smoking and deprivation status.Main outcome measuresAll‐cause mortality.ResultsA total of 21 751 women died over an average of 13.5 years follow‐up per participant, of whom 6329 were users and 15 422 non‐users. The adjusted hazard ratio (HR) of overall all‐cause mortality in combined HRT users was 0.91 (95% CI 0.88−0.94), and in estrogen‐only users was 0.99 (0.93−1.07), compared with non‐users. Age‐specific adjusted HRs for participants aged 46–50, 51–55, 56–60 and 61–65 years at first treatment were 0.98 (0.92−1.04), 0.87 (0.82−0.92), 0.88 (0.82−0.93) and 0.92 (0.85−0.98) for combined HRT users compared with non‐users, and 1.01 (0.84−1.21), 1.03 (0.89−1.18), 0.98 (0.86−1.12) and 0.93 (0.81−1.07) for estrogen‐only users, respectively.ConclusionsCombined HRT was associated with a 9% lower risk of all‐cause mortality and estrogen‐only formulation was not associated with any significant changes.Tweetable abstractEstrogen‐only HRT is not associated with all‐cause mortality and combined HRT reduces the risks.