Health Improvement Network Database Research Articles

Generalizability and treatment with sodium-glucose co-trasporter-2 inhibitors (SGLT2i) among patients with type 2 diabetes: an assessment using an Italian primary care database.

This study aimed to assess the proportions of type 2 diabetes (T2D) subjects meeting cardiovascular outcome trials (CVOTs) criteria for sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and estimate SGLT2i utilization, along with associated demographic and clinical characteristics, in a primary care setting. T2D patients in Italy were selected between January 1, 2021, and December 31, 2022, from The Health Improvement Network (THIN®) database. Representativeness was determined by dividing patients meeting key inclusion criteria for four CVOTs (CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, VERTIS-CV) to the total T2D population. Demographic and clinical characteristics of eligible T2D subjects and SGLT2i users were compared, and logistic regression models assessed the likelihood of receiving SGLT2i. Out of 17,102 T2D patients, 8,828 met eligibility criteria for at least one CVOT. DECLARE-TIMI 58 exhibited the highest representativeness (51.1%), compared to CANVAS (21.1%), EMPA-REG OUTCOME (5.5%), and VERTIS-CV (4.9%) trials. Eligible CVOTs patients were older (74.6 vs. 68.3 years), with a longer disease duration (10.2 vs. 9.7 years), and higher established cardiovascular disease (CVD) prevalence (36.0 vs. 27.3%) compared to SGLT2i users. Less than 10% of eligible T2D patients received SGLT2i. Males (OR: 1.43; 95%CI: 1.24-1.66) were more likely to be prescribed SGLT2i than other antidiabetic drugs, while the elderly (80 + vs. 40-64 years, OR: 0.17; 95% CI: 0.14-0.22) were less likely. Eligible T2D patients with CVD reported an increased likelihood of receiving SGLT2is compared to other antidiabetics. This study highlights significant variability in the proportion of T2D subjects meeting SGLT2i CVOT inclusion criteria, with DECLARE-TIMI-58 being the most represented. Low SGLT2i prescription rates in the Italian primary care setting, along with substantial demographic and clinical differences between SGLT-2i users and T2D eligible patients, emphasize the need for targeted interventions to optimize the use of these medications in primary care settings.

Epidemiological, clinical and economic burden of alopecia areata in Spain: a real-world retrospective study. The PETALO study.

Alopecia areata (AA) is a chronic autoimmune disease that causes non-scarring hair loss. Data are lacking on the epidemiology and clinical and economic burden of AA in Spain. To estimate the prevalence and incidence of AA in Spain and describe sociodemographic and clinical characteristics, treatment patterns, healthcare resource utilization (HCRU) and associated costs. This was an observational, retrospective, descriptive study based on the Health Improvement Network (THIN®) database (Cegedim Health Data, Spain). Patients with ICD9-Code 704.01 for AA, registered between 2014 and 2021, were identified. Prevalence (%) and incidence rates per 1,000 patient-years (IR) of AA were calculated and clinical characteristics, treatment characteristics and HCRU/costs were assessed. A total of 5,488 patients with AA were identified. The point prevalence of AA in 2021 was 0.44 (95% confidence interval [CI]: 0.43-0.45) overall, 0.48 (0.47-0.49) in adults, and 0.23 (0.21-0.26) in children ≤12 years. The 2021 IR for AA in adults was 0.55 (0.51-0.60). Of 3,351 adults with AA, 53.4% were female, mean (standard deviation [SD]) age was 43.1 (14.7) years, and 41.6% experienced comorbidities. Among adults, 2.7% used systemic treatment (0.5% immunosuppressants, 2.5% oral corticosteroids, 0.3% both). Laboratory tests and health care professional visits were the principal drivers of cost, which was €821.2 (1065.6)/patient in the first year after diagnosis. The epidemiology of AA in Spain is comparable with that reported for other countries, being more prevalent among adults. There is a significant burden of comorbidities and cost for patients, with limited use of systemic treatments, suggesting an unmet treatment need in this population.

Association Between Diseases and Symptoms Diagnosed in Primary Care and the Subsequent Specific Risk of Multiple Sclerosis.

Previous studies have reported a possible prodrome in multiple sclerosis (MS) defined by nonspecific symptoms including mood disorder or genitourinary symptoms and increased health care use detected several years before diagnosis. This study aimed to evaluate agnostically the associations between diseases and symptoms diagnosed in primary care and the risk of MS relative to controls and 2 other autoimmune inflammatory diseases with similar population characteristics, namely lupus and Crohn disease (CD). A case-control study was conducted using electronic health records from the Health Improvement Network database in the United Kingdom and France. We agnostically assessed the associations between 113 diseases and symptoms in the 5 years before and after diagnosis in patients with subsequent diagnosis of MS. Individuals with a diagnosis of MS were compared with individuals without MS and individuals with 2 other autoimmune diseases, CD and lupus. The study population consisted of patients with MS (n = 20,174), patients without MS (n = 54,790), patients with CD (n = 30,477), and patients with lupus (n = 7,337). Twelve ICD-10 codes were significantly positively associated with the risk of MS compared with controls without MS. After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, 5 ICD-10 codes remained significantly associated with MS: depression (UK: odds ratio 1.22, 95% CI 1.11-1.34), sexual dysfunction (1.47, 1.11-1.95), constipation (1.5, 1.27-1.78), cystitis (1.21, 1.05-1.39), and urinary tract infections of unspecified site (1.38, 1.18-1.61). However, none of these conditions was selectively associated with MS in comparisons with both lupus and CD. All 5 ICD-10 codes identified were still associated with MS during the 5 years after diagnosis. We identified 5 health conditions associated with subsequent MS diagnosis, which may be considered not only prodromal but also early-stage symptoms. However, these health conditions overlap with prodrome of 2 other autoimmune diseases; hence, they lack specificity to MS.

Assessing the cardiovascular effects of levothyroxine use in an ageing United Kingdom population (ACEL-UK) protocol: a cohort and target trial emulation study

BackgroundSubclinical hypothyroidism is diagnosed when serum thyroid stimulating hormone levels are higher whilst free thyroxine levels remain within their respective reference ranges. These reference ranges are uniformly applied in all adults, despite serum thyroid stimulating hormone levels naturally increasing with age. Research has found that mildly elevated thyroid stimulating hormone levels may be associated with some benefits in ageing patients, including reduced mortality and better cardiorespiratory fitness. Levothyroxine is typically prescribed to patients with hypothyroidism, but no conclusive evidence exists on whether levothyroxine therapy is beneficial or detrimental in older subclinical hypothyroid patients. Despite this, prescriptions for levothyroxine are increasing year-on-year. This study aims to determine if receiving levothyroxine affects the cardiovascular and bone health outcomes of subclinical patients in primary care aged 50 years and over.MethodsThis project includes a retrospective cohort analysis and a target trial emulation study using electronic patient records collected between 2006 and 2021 and recorded in The Health Improvement Network database. The primary outcome of this study is to compare the cardiovascular outcomes of subclinical hypothyroid patients aged over 50 years treated with levothyroxine compared to those untreated. Secondary outcomes are bone health and all-cause mortality outcomes. Descriptive and inferential statistics will both be employed to analyse the data. Secondary analysis will explore confounding factors, including age, sex, smoking status, body mass index, co-morbidities, and levothyroxine dosage.DiscussionThere needs to be a greater understanding of the potential risks of the current treatment for older patients with subclinical hypothyroidism in a primary care setting. We will investigate the clinical importance of this issue and whether older subclinical hypothyroid patients have poorer outcomes when treated. Clarifying this concern may help address the healthcare resource implications of ageing patients being misclassified as having mild hypothyroidism, as these patients are more likely to repeat their blood tests. This could reduce prescription wastage and improve patient outcomes and quality of life in the ageing population.Trial registrationNot applicable.

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.

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.

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.

Impact of depression and antidepressant use on clinical outcomes of hepatitis B and C: a population-based study.

Depression is common in patients with chronic viral hepatitis. We evaluated the impact of major depressive disorder (MDD) and antidepressant use on survival among patients with HBV and HCV. We used The Health Improvement Network database, the largest medical database in the UK, to identify incident HBV (n=1401) and HCV (n=1635) in patients between 1986 and 2017. Our primary composite outcome was the development of decompensated cirrhosis or death. MDD and each class of antidepressants were assessed in multivariate Cox proportional hazards models. Models were adjusted for age, sex, and clinical comorbidities. The prevalence of MDD among HCV patients was higher compared with HBV patients (23.5% vs. 9.0%, p<0.001, respectively). Similarly, HCV patients were more likely to use antidepressants (59.6%) compared with HBV patients (27.1%), p>0.001. MDD was not an independent predictor for decompensated cirrhosis-free survival or mortality. However, the use of tricyclic and tetracyclic antidepressants (TCAs) was associated with poor decompensated cirrhosis-free survival in HBV and HCV cohorts (adjusted HR: 1.80, 95% CI, 1.00-3.26 and 1.56, 95% CI, 1.13-2.14, respectively). Both TCAs in the HBV cohort and selective serotonin reuptake inhibitors among the HCV cohort were associated with poor overall survival (adjusted HR: 2.18, 95% CI, 1.16-4.10; 1.48, 95% CI, 1.02-2.16, respectively). Although prevalent among viral hepatitis patients, MDD did not affect disease progression or survival in either HBV or HCV cohorts. TCA use was associated with poor decompensated cirrhosis-free survival. Therefore, its use should be further studied among viral hepatitis patients.

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.

Time trends in the incidence of essential tremor: Evidences from UK and France primary care data.

IntroductionAlthough essential tremor (ET) is considered a common adult movement disorder, evidence on its incidence is still scant. This study aims at estimating ET incidence in two European countries, namely, the UK and France.MethodsIncident cases of ET were identified within the Health Improvement Network (THIN®) database between 1st January 2014 and 31 December 2019. Yearly crude and standardized incidence rates (IR) were estimated across the study period for both countries. Poisson regression models were built to assess temporal trends in IRs and differences between sexes and age classes.ResultsIn total, 4,970 and 4,905 incident cases of ET were identified in the UK and France, respectively. The yearly average crude IR (per 100,000 person-years) was 18.20 (95%CI: 15.09–21.32) in UK and 21.42 (17.83–25.00) in France, whereas standardized ones were 19.51 (18.97–20.01) and 19.50 (18.97-20.05). Regression analyses showed slightly increasing trends in both countries, higher incidence among males, and a significant increase with age. Yearly average IR increased from 3.96 (0.95–6.97) and 5.28 (1.12–9.44) in subjects aged <20 years to 49.27 (26.29–72.24) and 51.52 (30.19–72.86) in those aged >80 year in UK and France.ConclusionsStandardized ET incidence was comparable in the UK and France, showing a slight increase in both countries, reporting a higher value among people aged 60 years and older. This study outlines the need to conduct future studies to estimate the burden of ET in terms of disease control and healthcare resource utilization.

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.

Association between tramadol use and risk of pneumonia in the middle‐aged and elderly populations: a propensity‐score matched cohort study

Tramadol is a widely used weak opioid; however, the evidence for its safety profile in respiratory system needs additional information. We aimed to examine whether tramadol use is associated with an increased risk of pneumonia in the general population. We conducted five propensity-score (PS) matched cohort studies in The Health Improvement Network database. Participants aged ≥50-years initiated tramadol were compared with those initiated one of the following analgesics: codeine (n=144,506), naproxen (n=113,028), diclofenac (n=74,297), celecoxib (n=42,538), or etoricoxib (n=27,232). The outcome was incident pneumonia. During 6-month follow-up, 395 pneumonia (5.6/1000 person-years) occurred in the tramadol group and 414 pneumonia (5.9/1000 person-years) occurred in the PS matched codeine group. Compared with codeine group, the risk of pneumonia was lower in the tramadol group (hazard ratio [HR]=0.63, 95% confidence interval [CI]: 0.49-0.82) during the first 30-day follow-up, but comparable between groups over the entire 6-month follow-up (HR=0.95, 95%CI: 0.83-1.09). In addition, the risk of pneumonia was higher in the tramadol group than that in the PS matched naproxen (HR=1.68, 95%CI: 1.37-2.06), diclofenac (HR=1.63, 95%CI: 1.31-2.03), celecoxib (HR=1.64, 95%CI: 1.20-2.24) or etoricoxib (HR=1.61, 95%CI: 1.04-2.49) group. The present study indicated that tramadol initiators had a lower risk of incident pneumonia than codeine initiators during the short-time follow-up, but had a comparable pneumonia risk compared with codeine initiators and had a higher risk of pneumonia compared with NSAIDs initiators over the entire 6-month follow-up duration. Confirmation of the present findings and determination of the underlying mechanism will require more studies. Tramadol might not be a safer alternative analgesic to codeine or NSAIDs. Both of health-care providers and patients may need to be on alert for its safety profile in respiratory system in future clinical practice.

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.

Incidence of depression and antidepressant prescription in patients with COPD: A large UK population-based cohort study

BackgroundDepression is frequently reported in patients with Chronic Obstructive Pulmonary Disease (COPD). However, there is little information available on the incidence of depression following a COPD diagnosis. ObjectiveTo determine the incidence of a new diagnosis of depression or antidepressant prescription in people with and without a COPD diagnosis. MethodsA matched cohort study was conducted using The Health Improvement Network database. Patients with confirmed COPD diagnosis were matched to up to four subjects without a COPD diagnosis by age, sex and GP practice. Cox proportional hazards models were used to assess the incidence rates of depression and antidepressant prescription. Results44,362 patients with COPD and 124,140 subjects without COPD were included. The incidence rate of depression per 1000 person-years following COPD diagnosis was greater (11.4; 95% CI: 10.9–11.8) compared to subjects without COPD (5.7; 95% CI: 5.5–5.8) (p < 0.001). Patients with COPD were 42% more likely to have an incident depression (adjusted hazard ratio [aHR]: 1.42; 95% CI: 1.32–1.53; p < 0.001), and 40% more likely to be prescribed an antidepressant (aHR: 1.40; 95% CI: 1.35–1.45; p < 0.001). The incidence to either depression or antidepressant prescription was also greater for patients with COPD (aHR: 1.41; 95% CI: 1.36–1.46; p < 0.001). Patients with COPD and worse breathlessness had a higher risk of incident depression compared to patients with less breathlessness. ConclusionHealthcare providers managing patients with COPD should be alert to the existence of depression and aware of its symptoms and consequences.

Identifying health conditions associated with Alzheimer's disease up to 15 years before diagnosis: an agnostic study of French and British health records

The identification of modifiable risk factors for Alzheimer's disease is paramount for early prevention and the targeting of new interventions. We aimed to assess the associations between health conditions diagnosed in primary care and the risk of incident Alzheimer's disease over time, up to 15 years before a first Alzheimer's disease diagnosis. In this agnostic study of French and British health records, data from 20 214 patients with Alzheimer's disease in the UK and 19 458 patients with Alzheimer's disease in France were extracted from The Health Improvement Network database. We considered data recorded from Jan 1, 1996, to March 31, 2020 in the UK and from Jan 4, 1998, to Feb 20, 2019, in France. For each Alzheimer's disease case, a control was randomly assigned after matching for sex and age at last visit. We agnostically tested the associations between 123 different diagnoses of the International Classification of Diseases, 10th revision, extracted from health records, and Alzheimer's disease, by running a conditional logistic regression to account for matching of cases and controls. We focused on three time periods before diagnosis of Alzheimer's disease, to separate risk factors from early symptoms and comorbidities. Unadjusted odds ratios (ORs) and 95% CIs for the association between Alzheimer's disease and various health conditions were estimated, and p values were corrected for multiple comparisons. In both the British and French studies, ten health conditions were significantly positively associated with increased Alzheimer's disease risk, in a window of exposure from 2-10 years before Alzheimer's disease diagnosis, comprising major depressive disorder (UK OR 1·34, 95% CI 1·23-1·46; France OR 1·73, 1·57-1·91), anxiety (UK OR 1·36, 1·25-1·47; France OR 1·50, 1·36-1·65), reaction to severe stress and adjustment disorders (UK OR 1·40, 1·24-1·59; France OR 1·83, 1·55-2·15), hearing loss (UK OR 1·19, 1·11-1·28; France OR 1·51, 1·21-1·89), constipation (UK OR 1·31, 1·22-1·41; France OR 1·59, 1·44-1·75), spondylosis (UK OR 1·26, 1·14-1·39; France OR 1·62, 1·44-1·81), abnormal weight loss (UK OR 1·47, 1·33-1·63; France OR 1·88, 1·56-2·26), malaise and fatigue (UK OR 1·23, 1·14-1·32; France OR 1·59, 1·46-1·73), memory loss (UK OR 7·63, 6·65-8·76; France OR 4·41, 3·07-6·34), and syncope and collapse (UK OR 1·23, 1·10-1·37; France OR 1·57, 1·26-1·96). Depression was the first comorbid condition associated with Alzheimer's disease, appearing at least 9 years before the first clinical diagnosis, followed by anxiety, constipation, and abnormal weight loss. These results from two independent primary care databases provide new evidence on the temporality of risk factors and early signs of Alzheimer's disease that are observable at the general practitioner level. These results could guide the implementation of new primary and secondary prevention policies. Agence Nationale de la Recherche.

Exposure to immediate-release tramadol in children 6 years and under – a nationwide French poison control center study

Introduction Data regarding immediate-release (IR)-tramadol exposures in children remain sparse. We aimed to investigate the incidence of IR-tramadol exposures in ≤6-year-old children, to describe the characteristics and resulting outcome of ingestions involving IR-tramadol alone, and to estimate a clinically relevant toxic dose in this population. Methods Retrospective analysis of IR-tramadol exposures in ≤6-year-old children, collected by the French Poison Control Centers (PCCs) in 2003–2019. The incidence was estimated using IR-tramadol prescription data from the Health Improvement Network database (the French version of THIN). The Poison severity score (PSS) was used to grade severity. Results We found 1260 IR-tramadol exposures in ≤6-year-old children. The number of cases per 100,000 IR-tramadol-treated patients increased over time (p < .0001). One hundred forty-five cases involving IR-tramadol alone were analyzed. The median age was 3.0 years (IQR: 1.9, 4.0), the M/F ratio was 1.5 and the median dose was 5.0 mg/kg (IQR 3.3–11.1). Half of the children (49.7%) remained asymptomatic (PSS0) while 29.6% and 14.5% developed minor (PSS1) or moderate-to-severe (PSS2–PSS3) neurological symptoms, respectively. Twelve children developed respiratory depression. No seizures and no fatality were reported. All symptomatic children recovered within 24 h. The ingested IR-tramadol dose was positively correlated with the PSS (p < .0001). Using a receiver operating characteristic (ROC) curve approach (area under the curve, 0.92; p < .001), ingestion of ≥7.4 mg/kg IR-tramadol was appropriate to recommend hospital referral (sensitivity, 100% [95% confidence interval (CI), 85–100]; specificity, 73% [95% CI, 64–80]; predictive positive value, 39% [95% CI, 35–57]; negative predictive value, 100% [95% CI, 96–100]). Children who ingested <7.4 mg/kg IR-tramadol developed no (n = 68) or minor (n = 22) neurological symptoms. Conclusions Despite increasing tramadol prescriptions in adults during the study period in France, oral exposure to IR-tramadol in ≤6-year-old children was rare but possibly responsible for severe toxicity. Children with no underlying disease and concomitant medication ingesting <7.4 mg/kg IR-tramadol alone could be observed at home. However, given the observed variability in the onset of seizures after tramadol ingestion, which can occur at ingested tramadol doses below 7.4 mg and even at therapeutic doses, parents or guardians should be specifically warned about the risk of seizures.

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.

Proton pump inhibitor therapy and risk of knee replacement surgery: a general population-based cohort study

Proton pump inhibitors (PPIs) are among the most commonly used medications for patients with osteoarthritis (OA). Various types of PPIs have different impacts on lowering serum magnesium level that may affect knee OA progression. We aimed to compare the risk of clinically relevant endpoint of knee replacement (KR) among initiators of five different PPIs with that among histamine-2 receptor antagonist (H2RA) initiators. Among patients with knee OA (≥50 years) in The Health Improvement Network database in the UK we conducted five sequential propensity-score matched cohort studies to compare the risk of KR over 5-year among patients who initiated omeprazole (n=2,672), pantoprazole (n=664), lansoprazole (n=3,747), rabeprazole (n=751), or esomeprazole (n=827) with those who initiated H2RA. The prevalence of PPI prescriptions among participants with knee OA increased from 12.7% in 2000-44.0% in 2017. Two-hundred-and-seventy-four KRs (30.8/1,000 person-years) occurred in omeprazole initiators and 230 KRs (25.4/1,000 person-years) in H2RA initiators. Compared with H2RA initiators, the risk of KR was 21% higher in omeprazole initiators (hazard ratio [HR]=1.21,95% confidence interval [CI]:1.01-1.44). Similar results were observed when pantoprazole use was compared with H2RA use (HR=1.38,95%CI:1.00-1.90). No such an increased risk of KR was observed among lansoprazole (HR=1.06,95%CI:0.92-1.23), rabeprazole (HR=0.97,95%CI:0.73-1.30), or esomeprazole (HR=0.83,95%CI:0.60-1.15) initiators compared with that among H2RA initiators. In this population-based cohort study, initiation of omeprazole or pantoprazole use was associated with a higher risk of KR than initiation of H2RA use. This study raises concern regarding an unexpected risk of omeprazole and pantoprazole on accelerating OA progression.

Association of Metformin Use With Risk of Venous Thromboembolism in Adults With Type 2 Diabetes: A General-Population-Based Cohort Study.

Metformin is hypothesized to protect against the risk of venous thromboembolism (VTE); however, there is a paucity of data supporting this hypothesis. Among individuals aged 40-90 years with a diagnosis of type 2 diabetes in the Health Improvement Network database (2000-2019), we compared the risks of incident VTE, pulmonary embolism, and deep vein thrombosis among metformin initiators with those among sulfonylurea initiators. Individuals were followed from their first prescription refill to an incident VTE, drug discontinuation, switching or augmenting, plan disenrollment, or the end of the study, whichever occurred first. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox model, adjusting for confounders using inverse probability of treatment weighting. Among 117,472 initiators of metformin and 13,835 initiators of sulfonylureas, 555 (1.3/1,000 person-years) and 75 (2.1/1,000 person-years) VTE cases occurred in each group, respectively. The multivariable-adjusted HR was 0.65 (95% CI: 0.51, 0.84). The corresponding risks for pulmonary embolism (adjusted HR=0.71, 95% CI: 0.50, 1.01) and deep vein thrombosis (adjusted HR=0.64, 95% CI: 0.48, 0.87) were also lower in metformin initiators than in sulfonylurea initiators. Our study provided empirical evidence to support a lower risk of VTE after initiation of metformin as compared with sulfonylureas among patients with type 2 diabetes.