Scientific
publications

BACKGROUND: Allergic rhinoconjunctivitis (ARC), asthma and eczema carry a substantial morbidity. These conditions often co-exist within the same individual and their prevalence can differ based on age, ethnicity and gender. OBJECTIVES: Using a UK primary care database, we estimated the trends in prevalence over the last decade for ARC, asthma and eczema and associated risk factors. METHODS: Longitudinal cohort analysis of the health improvement (THIN) database between 1st Jan 2010 and 1st Jan 2019. Logistic regression analysis was used to explore risk factors for diagnosis of these conditions. RESULTS: An average of 4.17 million records per year were analysed, 19.4% were children and 49.75% were male. There was an increase in prevalence of ARC, asthma and eczema amongst adults during the study period, whereas ARC and asthma prevalence amongst children has fallen. By 2018, 1:8 adults and 1:14 children had ARC; asthma was diagnosed in 1:7 adults and 1:10 children whereas eczema was diagnosed in 1:6 adults and 1:4 children respectively. There were regional discrepancies in allergy prevalence across the UK. Caucasians generally had the highest rates of asthma and lower rates of ARC compared with other ethnic groups. Having other allergies substantially increases the odds of having asthma, eczema and ARC. CONCLUSION: The population burden of ARC, asthma and eczema in the UK is substantial. These conditions are often associated with other allergies and can, therefore, be complex to manage. These data support calls for improvement of pathways of care for allergy patients in the UK.

INTRODUCTION: This study examines the association between the age of hypertension onset and the risks of cardiovascular diseases (CVD) and mortality. METHODS: Two retrospective cohort studies were conducted using electronic medical records from public healthcare systems in the UK and Hong Kong (HK). Adults (≥18 years) who attended public health services between January 1, 2008 and December 31, 2013 were included in the study. Patients diagnosed with CVD before baseline or who transferred out of practice before baseline in the UK cohort were excluded. Hypertension onset was defined as a diagnosis of hypertension (≥140/90 mmHg) or the prescription of anti-hypertensive medication. Patients were categorized based on hypertension onset and divided into 6 age groups based on onset age. Propensity score fine stratification weights were applied to ensure balance between groups. Multivariable Cox proportional hazards regression a was used to assess risks of CVD, cardiovascular mortality, and deaths. RESULTS: The UK cohort included 481 791 new-onset hypertension patients and 3 893 134 controls, while the HK cohort included 552 594 new-onset hypertension patients and 2 548 914 controls. Hypertension was associated with increased CVD and mortality risks, which decreased with older onset ages. In the UK cohort, hypertension onset at ≤39 years had the highest risks for CVD and deaths, with adjusted hazard ratios (HR = 4.30, 95% CI [3.98, 4.65] and HR = 2.86, 95% CI [2.64, 3.10]). For patients with hypertension onset at ≥80 years, risks were lower, with adjusted HR = 2.56, 95% CI [2.45, 2.68] for CVD and HR = 1.11, 95% CI [1.09, 1.14] for deaths. Similar trends were observed in the HK cohort. CONCLUSION: Younger age of hypertension onset is associated with higher risks for cardiovascular events and mortality, highlighting the need for early screening and intensive interventions in younger adults to improve long-term blood pressure control and reduce cardiovascular complications and deaths, alleviating the chronic disease burden on the public healthcare system over the long term.

Children with chronic diseases face a higher risk of mental health disorders. However, the cognitive consequences of food allergies (FA), which are not classified as a chronic disease, remain insufficiently researched. The objective of this study is to examine the association between FA and mental health in children and adolescents, compared to children and adolescents without FA (controls) and those with other chronic conditions but no history of FA. This is a retrospective cohort study using IQVIA Medical Research Data from UK primary care practices. Five cohorts of children aged 0-18 between 2000 and 2021 were defined: FA, control, asthma, atopic dermatitis (AD), and type 1 diabetes (T1D). The study included 1,130,721 children without FA (control), 23,263 with FA, 136,453 with asthma, 207,575 with AD, and 4835 with T1D. Compared to control, FA patients had higher risks of eating disorders (hazard ratio (HR) 1.85, 95% CI 1.42-2.41), anxiety (HR 1.35, 95% CI 1.25-1.45), and depression (HR 1.24, 95% CI 1.11-1.39). FA patients had lower depression risk than asthma and T1D patients (HR 0.77, 95% CI 0.68-0.87, 0.64, 95% CI 0.54-0.76, respectively) and lower anxiety risk than asthma patients (HR 0.86, 95% CI 0.79-0.91). FA patients' risk of eating disorders was not significantly different from asthma and T1D patients (HR 1.17, 95% CI 0.88-1.55, 1.58, 95% CI 0.81-3.10, respectively) but was significantly higher than in the AD group (HR 1.43, 95% CI 1.07-1.90). CONCLUSION: This study indicates that children with FA face elevated risks of anxiety, depression, and eating disorders compared to children without FA, and that these risks vary when compared to children with other chronic conditions. These findings highlight the need for integrated mental health support in FA management and greater awareness of FA's psychological impact among healthcare providers. WHAT IS KNOWN: • Children with chronic illnesses such as asthma and diabetes are known to have an elevated risk of mental health disorders. However, research on the mental health impact of food allergies remains limited. WHAT IS NEW: • This study reveals that children with FA have significantly increased risks of anxiety, depression, and eating disorders compared to children without FA and provides comparative insights into the mental health risks of FA relative to other chronic conditions like asthma, atopic dermatitis, type 1 diabetes, and healthy controls.

BACKGROUND: Inconclusive findings regarding the association between suicidal ideation/suicide attempt and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been recently revealed in a small number of studies. METHODS: This was a multinational self-controlled case series analysis using Hong Kong's Clinical Data Analysis and Reporting System (2008-2023), Taiwan's National Health Insurance Research Database (2012-2020) and the UK's IQVIA Medical Research Database with The Health Improvement Network (2000-2021). A total of 642 suicide attempt or self-harm cases with GLP-1RA use were included to assess pooled incident rate ratios (IRRs) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment with their 95% CIs. RESULTS: The pooled IRR (95% CI) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment was 0.67 (0.51 to 0.88). The suicide attempt or self-harm risk varied with the time window of GLP-1RA use, with pooled IRRs (95% CIs) of 1.94 (0.86 to 4.37), 0.61 (0.23 to 1.63), 0.72 (0.37 to 1.41), 0.60 (0.32 to 1.09) and 0.63 (0.49 to 0.87) for the pretreatment period and Days 1-30, Days 31-90, Days 91-180 and Days>180 of GLP-1RA treatment, respectively. Subgroup analyses by age, sex and individual GLP-1RAs and sensitivity analyses showed no significant increase in the suicide attempt or self-harm risk associated with GLP-1RA use. The point estimate and CI of the E-value for suicide attempts or self-harm were 2.35 and 1.53, respectively. CONCLUSIONS: We found no increase in the risks of suicide attempts or self-harm following GLP-1RA treatment, and even in the long-term use of GLP-1RAs. Close monitoring of potential suicide attempts or self-harm and ensuring treatment tolerability during treatment initiation are required, and well-controlled or pragmatic trials remain warranted to validate our findings.

BACKGROUND: Hypoglycaemic drugs (sulfonylureas, glinides or insulins) are commonly prescribed for older adults with type 2 diabetes (T2D) but may carry risks of adverse events. Whether de-intensifying hypoglycaemic drugs is associated with clinical benefit in older adults remains unknown. OBJECTIVE: To evaluate the association between de-intensification of hypoglycaemic drugs and clinical outcomes in older adults with T2D. METHODS: Cohort study conducted with the target trial emulation approach, using data collected from 2000 French general practises between January 2010 and February 2019 (The Health Improvement Network-THIN database). Eligible participants were ≥75 years old, on stable hypoglycaemic drugs (no change in drug or dose) for at least 6 months, and had an HbA1c value <9%. Hypoglycaemic drug de-intensification (exposure) was defined as cessation or reduction of ≥50% of total dose. The primary outcome was a composite measure of all-cause death or hospital admissions within 3 months, and its association with exposure was assessed using multivariable logistic regression adjusted for potential baseline confounders. RESULTS: The study included 14 383 unique individuals corresponding to 177 314 trial emulation participants (mean age 80 years; 44.7% female). Of these, 6480 participants were allocated to de-intensification group, and 170 834 to the control group. At 3 months, the primary outcome occurred in 3.96% of the de-intensification group and 2.99% of controls [adjusted relative risk, 1.33 (95% CI, 1.22-1.43)]. Subgroup analyses showed consistent associations across most participants' profiles. CONCLUSIONS: In older adults with T2D, de-intensification of hypoglycaemic drugs was associated with a higher short-term risk of all-cause death or hospitalisation.

BACKGROUND: Although children are known to be at risk of developing long COVID, its economic burden is poorly described. We aimed to assess the all-cause healthcare resource utilization (HCRU) and associated direct medical costs of children with mild-to-moderate long COVID in France. METHODS: This retrospective cohort study utilized The Health Improvement Network (THIN) primary care electronic health records to identify children aged <18 years with confirmed/probable COVID-19 diagnoses during March 2020 to December 2022 who developed long COVID, identified per the World Health Organization as suggestive symptoms present ≥3 months following SARS-CoV-2 infection. Patient characteristics, all-cause HCRU and direct healthcare costs from a national health insurance perspective were summarized. HCRU and costs were stratified into healthcare encounters, medical procedures, retail pharmacy usage, testing, caregiver sick leave, medical transport, and medical device usage. RESULTS: Of 27,537 children diagnosed with acute COVID-19, 3,888 (14.1%) developed long COVID; mean age was 8.9 years, 49.2% were female and, among those with comorbidity, 24.5% had a Charlson Comorbidity Index score ≥1. During a mean post-diagnosis follow-up of 12.6 months, 93.6% of children had general practitioner consultations, 93.5% had pharmacy usage, and 61.0% had medical procedures. First-year costs were highest at €823 per patient per year; 4.3% of children required caregiver-related work absenteeism. Compared to children who did not develop long COVID, a long COVID diagnosis was associated with an incremental cost increase of €98 per patient per year. LIMITATIONS: Our findings only represent a national payer perspective. The true societal burden of long COVID in children is likely underestimated since long COVID-related indirect costs are not fully captured and access to care varies. CONCLUSION: Children living with long COVID managed in the community pose a non-neglectable burden on French health insurance, reinforcing the importance of managing long COVID with a multidisciplinary approach and optimizing resource allocation.

BACKGROUND: Several observational studies have reported epidemiologic associations between psoriasis and risk of some cancers, but systematic evidence is lacking. Our aim was to comprehensively estimate the association between psoriasis and the risk of 33 common cancers using systematical Mendelian randomization based on genetic data. METHOD: Forty-nine independent single-nucleotide polymorphisms (SNPs) significantly associated with psoriasis were extracted as instrumental variables from a large-scale meta-analysis study of genome-wide association study (GWAS) for psoriasis. Outcome GWAS data were obtained from the FinnGen consortium (n = 500,348), UK Biobank (n = 420,531), and other large-scale cancer datasets. The inverse-variance weighted (IVW) was used as the primary method to infer the association between psoriasis and risk of cancer, and finally the results from multiple databases were pooled by meta-analysis. RESULTS: In the UK Biobank, genetically predicted psoriasis had a suggestive association with colon (OR = 1.055, 95%CI: 1.001-1.113, P = 0.046) and uterine corpus cancer (OR = 0.922, 95%CI: 0.852-0.997, P = 0.042). In the FinnGen consortium, psoriasis had a suggestive association with vulvar cancer (OR = 1.182, 95%CI: 1.023-1.366, P = 0.024), uterine corpus cancer (OR = 0.937, 95%CI: 0.883-0.993, P = 0.028), and prostate cancer (OR = 0.973, 95%CI: 0.948-0.999, P = 0.045). In an additional large-scale cancer dataset, psoriasis also showed a suggestive association with prostate cancer (OR = 0.968, 95%CI:0.942-0.995, P = 0.020). The meta-analysis confirmed the suggestive association of psoriasis with uterine corpus (OR = 0.931, 95% CI: 0.889-0.976, P = 0.003) and prostate cancer (OR = 0.976, 95% CI: 0.955-0.997, P = 0.023). Whereas the effect of psoriasis on colon and vulvar cancer was not in the same direction across different populations. Furthermore, no association between genetically predicted psoriasis and other cancers were observed. CONCLUSIONS: This comprehensive MR study suggests that psoriasis may be a potential protective factor for uterine corpus cancer in women and prostate cancer in men.

BACKGROUND: Vitiligo is an acquired skin depigmentation disorder often accompanied by leukoderma and leukotrichia. Half of vitiligo patients experience episodes of stress. METHODS: We established a chronic unpredictable mild stimulation (CUMS) model in C57BL/6 J mice to simulate chronic mental stress-induced leukoderma and leukotrichia. Single-cell RNA sequencing was performed to determine the immune landscape and to characterize the relationship between immune-stromal cells. Immunohistochemistry was employed for validation. RESULTS: We discovered a similar pro-inflammatory micro-environment composed of keratinocytes and fibroblasts similar to that in human vitiligo. Macrophages in CUMS mice expressed high levels of inflammatory factors and were inclined to an M1 pro-inflammatory phenotype. Two distinct clusters of melanocytes were also identified: Mel2, defined as melanocyte stem cells, and Mel3, defined as mature melanocytes. Mel2 cells were prone to pyroptosis and necroptosis, while Mel3 cells were susceptible to oxidative stress, mitochondrial dysfunction, and ferroptosis. Compared with control mice, higher expression of CXCL16 on dendritic cells and of the CXCL16 ligand, CXCR6, on γδT cells were observed in leukoderma. Dendritic cells and natural killer T cells in the CUMS mouse spleen exhibited elevated levels of CXCL16 and CXCR6, respectively. Activation of the CXCL16-CXCR6 axis and a non-specific immune response in our CUMS model might imitate chronic mental stress-induced vitiligo in humans better than CD8 + cytotoxic T lymphocyte-mediated models. CONCLUSIONS: We discovered two melanocyte clusters with distinct fates and a pro-inflammatory micro-environment with CXCL16-CXCR6 axis activation of antigen-presenting cells and other innate immunocytes that might provide new insights into the pathogenesis of stress-induced vitiligo.

ABATRACT: BACKGROUND: Information on the survival of people living with dementia over time and across systems can help policymakers understand the real-world impact of dementia on health and social care systems. This multinational cohort study examines the trends in relative mortality risk following a dementia diagnosis. METHODS: A common protocol was applied to population-based data from the UK, Germany, Finland, Canada (Ontario), New Zealand, South Korea, Taiwan and Hong Kong. Individuals aged 60+ with an incident dementia diagnosis recorded between 2000 and 2018 were followed until death or the end of the study period. Cox proportional hazards regression was used to assess the association of mortality in dementia patients with the year of dementia diagnosis. RESULTS: Data from 1,272,495 individuals, with the mean age at diagnosis ranging from 76.8 years (South Korea) to 82.9 years (Germany), show that the overall median length of survival following recorded diagnosis ranges from 2.4 years (New Zealand) to 7.9 years (South Korea). Hazard ratios (HRs) estimated from Cox proportional hazard models decline consistently over the study period in the UK, Canada, South Korea, Taiwan and Hong Kong, which accounted for 84% of all participants. For example, the HR decreases from 0.97 (95% CI: 0.92-1.02) in 2001 to 0.72 (0.65-0.79) in 2016 in comparison to year 2000 in the UK. CONCLUSIONS: This study shows a steady trend of decreasing risk of mortality in five out of eight databases, which signals the potential positive effect of dementia plans and associated policies and provides reference for future policy evaluation.

OBJECTIVE: To examine the mental ill health burden associated with allergic and atopic disorders, in a UK primary care cohort. DESIGN: Population-based retrospective open cohort study. SETTING: United Kingdom. PARTICIPANTS: 2 491 086 individuals with primary-care recorded atopic disorder (food allergy, drug allergy, anaphylaxis, urticaria, allergic rhino-conjunctivitis) diagnosis were matched by sex, age (± 2 years), and socio-economic deprivation (Townsend quintile score) at index to 3 120 719 unexposed individuals. The mean age of exposed patients at cohort entry was 39.42 years (SD (SD) 23.65) compared with 35.81 years (SD 22.17) for unexposed patients. MAIN OUTCOME MEASURES: The primary outcome was a composite of mental ill health (severe mental illness, anxiety, depression, eating disorders, obsessive-compulsive disorder (OCD), and self-harm), identified using Read codes. Cox regression was used to estimate adjusted hazard ratios with 95% confidence intervals for the composite mental ill health outcome and each of the individual mental health disorders. Covariates adjusted for were age, sex, alcohol use, smoking status, body mass index (BMI), Townsend deprivation quintile score, asthma exposure, and eczema exposure at baseline. RESULTS: Between first January 1995 to 31st January 2022, a total of 2 491 086 eligible individuals were identified with a primary care recorded diagnosis of atopic disease and were matched to 3 120 719 unexposed individuals. 229 124 exposed individuals developed a mental ill health outcome during the study period (incidence ratio (IR) 144.13 per 10 000 person-years) compared with 203 450 in the unexposed group (IR 117.82 per 10 000 person-years). This translated to an adjusted hazard ratio (aHR) of 1.16 (95% CI 1.15 to 1.17). Notably, the risk of anxiety was greatest, aHR 1.22 (95% CI 1.21 to 1.23). Our findings were robust to a sensitivity analysis, where individuals were also matched for asthma and eczema. CONCLUSION: There is an increased risk of mental ill health disorders among patients with diagnosis of an allergic and atopic disorders. There is a need to consider dual delivery of allergy and psychology services to optimise mental well-being among this cohort.

AIMS: To compare the effects of low-dose aspirin and clopidogrel on the risk of incident type 2 diabetes among patients with ASCVD. METHODS: This target trial emulation study was performed usingthe IQVIA Medical Research Data UK primary care database, including adults with an incident first ASCVD event who initiated low-dose aspirin or clopidogrel between 2004 and 2021. We applied an overlap weighting approach to balance treatment groups. The observational analogues of intention-to-treat and per-protocol effects were estimated using pooled logistic regression. RESULTS: A total of 111,292 ASCVD patients who initiated aspirin (n = 78,012) or clopidogrel (n = 33,280) were included. In intention-to-treat analyses, aspirin and clopidogrel had similar risks of diabetes (Hazard ratio [HR] 1.02, 95 % Confidence interval [CI] 0.96 to 1.07), cardiovascular events (1.00, 0.95 to 1.05), and bleeding events (1.02, 0.97 to 1.08). In per-protocol analyses, risks remained comparable for diabetes (1.06, 0.97 to 1.15), cardiovascular events (0.96, 0.89 to 1.03), and bleeding events (1.01, 0.92 to 1.10). CONCLUSIONS: Aspirin and clopidogrel have similar risks of incident diabetes, cardiovascular events, and bleeding events among patients with ASCVD. The choice between these agents may thus be influenced more by factors like cost, patient preference, or tolerance than by clinical outcomes alone.

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.

BACKGROUND: Opioid use for chronic non-cancer pain (CNCP) is consistently higher in menopausal and postmenopausal women than in younger women or men, elevating their risk of opioid-related adverse health outcomes. Since pain severity increases with hormonal changes accompanying menopause, these women should be a focus of opioid stewardship efforts. AIM: To examine opioid prescribing trends for CNCP in menopausal and postmenopausal women diagnosed with a musculoskeletal condition. DESIGN & SETTING: Population-based drug utilisation study, which was undertaken with data from IQVIA Medical Research Data UK. METHOD: Annual opioid prescribing incidence, prevalence, and average duration of use were calculated for a cohort of women aged 50-79 years with musculoskeletal conditions newly diagnosed between 2010 and 2021. Specific results were stratified by age, pain indication, and Townsend score. RESULTS: From 2010-2021, incident prescribing rates of opioids increased in women aged 50-54 years (161.4 [95% confidence interval {CI} = 149.7 to 174.0] per 1000 person-years at risk [PYAR] in 2010 to 239.6 [95% CI = 211.7 to 271.2] per 1000 PYAR in 2021); these women discontinued opioid use faster (<1 year) than older age groups (~2 years). Overall, opioid prescribing prevalence decreased from 23% in 2010 to 14% in 2021, and average opioid use duration decreased from 3 years to 1 year (2010-post-2017) in women aged 50-79 years. CONCLUSION: The overall observed decrease in prevalence and average duration of opioid use is encouraging. Incident prescriptions are rising in women aged 50-54 years and those with fibromyalgia while remaining steady in women aged 55-79 years. Understanding the impact of menopause and post-menopause on opioid use trends is important for effective opioid stewardship.

BACKGROUND: Depression and anxiety coexist with Alzheimer's disease (AD) and Parkinson's disease (PD), yet their progression trajectories vary, necessitating a thorough examination of prescription patterns for antidepressants and anti-anxiety drugs pre- and post-diagnosis. OBJECTIVES: To systematically compare the prescriptions of antidepressant and anti-anxiety drugs across AD and PD over 10 years before and after initial diagnosis in the UK and France. METHODS: Data on 19,954 patients with AD, 25,267 with PD from the UK, 17,463 with AD, 10,333 with PD from France were extracted from The Health Improvement Network database. For both countries, we compared the odds of prescribed antidepressants and anti-anxiety drugs for each diagnosis group, over 10 years before and after diagnosis, using logistic regressions adjusting for age, sex, and drug prescriptions for chronic diseases. RESULTS: Antidepressant prescriptions showed a significant rise from 25 % 5-10 years before the initial AD diagnosis to 50 % within the first 5 years post-diagnosis. AD Patients were more likely to be prescribed antidepressants than PD patients [Odds ratios ranging from 1.02 to 1.13 in the UK and 1.09-1.36 in France] and conversely PD patients were more likely to be prescribed anti-anxiety drugs [0.83-0.84 in the UK and 0.85-0.90 in France] several years before their diagnosis. AD patients sustained elevated antidepressant prescriptions up to 5 years after diagnosis. CONCLUSION: These findings offer insights into disease-specific psychological impacts and underscore the necessity for further investigation into prescription patterns and their implications on patient outcomes.

CONTEXT: Thyrotropin (TSH) levels tend to rise with age, but standard reference intervals do not reflect this, potentially leading to overdiagnosis of subclinical hypothyroidism (SCH) and excessive levothyroxine (LT4) prescriptions in older adults. OBJECTIVE: This work aimed to compare outcomes in adults older than 50 years with SCH who were either prescribed or not prescribed LT4. METHODS: A retrospective cohort study was conducted using data from UK Primary Care patients from the Health Improvement Network. The primary outcome was cardiovascular (CV) events (angina, myocardial infarction, peripheral vascular disease, stent procedures, or stroke). Secondary outcomes included bone events (fragility fractures or osteoporosis) and all-cause mortality. Time-varying hazard ratios (HRs) adjusted for relevant factors were estimated. RESULTS: This study included 53 899 patients (baseline median age 67 years (interquartile range [IQR]: 59-76 years); 68.5% female; median TSH 4.6 mU/L (IQR: 4.1-5.4 mU/L). Median follow-up duration was 10 years (IQR: 5.5-10.0 years). Of these, 19 952 (37%) received LT4 and 33 947 (63%) did not. LT4 therapy showed a protective effect against CV events (HR: 0.91; 95% CI, 0.87-0.97; P < .001) but increased risk of bone events (HR: 1.21; 95% CI, 1.14-1.28; P < .001) and all-cause mortality (HR: 1.17; 95% CI, 1.13-1.22; P < .001). CONCLUSION: Our data suggest that LT4 therapy in older individuals with SCH is associated with a trade-off between the potentially beneficial effect on CV risk and the deleterious relationship with bone health and mortality risk. These risks need to be considered, mitigated, and discussed when LT4 therapy is being deliberated in older patients with SCH.

BACKGROUND: Budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) single inhaler triple therapy became available to prescribe to patients with severe chronic obstructive pulmonary disease (COPD) in France in 2021. The characteristics of patients prescribed BUD/GLY/FOR triple therapy and guideline adherence have not been previously described in France. OBJECTIVE: To describe the characteristics of COPD patients initiated on BUD/GLY/FOR triple therapy, assess adherence to COPD management guidelines, and explore any differences by prescribing physician. MATERIALS AND METHODS: A cross-sectional study using data from The Health Improvement Network (THIN ) France database was conducted. Patients with ≥2 recorded diagnostic codes for COPD were included. Demographic characteristics, comorbidities, management, COPD-related characteristics, and guideline adherence (Société de Pneumologie de Langue Française (SPLF); Haute Autorité de Santé (HAS)), stratified by initiating physician speciality (general practitioner (GP) or pulmonologist) were described. RESULTS: A total of 263 patients initiating BUD/GLY/FOR triple therapy were included. Mean (SD) age was 68.8 (11.8) years; 53.6% were male. Mean (SD) COPD duration was 6.4 (5.5) years. Comorbidities were common, with slightly more cardiometabolic and mental health conditions recorded in the GP-initiated group, and more comorbid respiratory conditions recorded in the pulmonologist-initiated group. About 77.2% (n=203) of patients had at least one moderate or severe exacerbation in the 12 months before initiation. About 86.3% had a previous record of dual (n=117, 44.5%) or triple (n=110, 41.8%) therapy. About 68.8% had been initiated on BUD/GLY/FOR triple therapy in line with SPLF guidelines (62.4% and 72.4% in the GP- and pulmonologist-initiated groups, respectively); among those with a record of COPD severity, 75.2% were initiated in line with HAS guidelines (69.2% and 76.3% in the GP- and pulmonologist-initiated groups, respectively). CONCLUSION: The majority of COPD patients are prescribed BUD/GLY/FOR triple therapy in accordance with current treatment guidelines, irrespective of whether the therapy is prescribed by a general practitioner or a pulmonologist.

BACKGROUND AND AIMS: Mineralocorticoid receptor antagonists (MRAs) reduce mortality and hospitalisation in heart failure with reduced ejection fraction (HFrEF) but are underused, despite recommendation in key guidelines. Identifying the factors contributing to underuse and addressing adherence are key components of a learning health system. We aimed to evaluate MRA prescription in people with HFrEF who would benefit, based on the UK National Institute for Health and Care Excellence (NICE) HFrEF guideline. METHODS: We used clinical code lists to identify people with HFrEF in primary care electronic health record (EHR) data from The Health Improvement Network database. For each calendar year 2014-2020, we identified individuals who met the NICE guideline criteria for MRA therapy. We fitted mixed effects logistic regression models to determine the factors contributing to MRA prescription. RESULTS: Among 24 135 people with HFrEF studied between 2014 and 2020, 12 150 person-years were eligible for MRA treatment. The MRA prescription rate increased from 41% to 55%. MRA prescription was inversely associated with age (OR per 1 SD, 95% CI) (0.02 (0.01, 0.03)), increasing glomerular filtration rate (0.37 (0.25, 0.55)), hypertension (0.21 (0.40, 0.78)) and prescription of antihypertensives (0.03 (0.02, 0.07)). MRA prescription was associated with male gender (6.31 (3.20, 12.4)), dilated cardiomyopathy (25.9 (7.48, 89.4)), calendar year (2.17 (1.85, 2.54) per year after study start) and prescription of sacubitril/valsartan (214 (56, 823)). CONCLUSIONS: MRAs are underused in people with HFrEF in the UK. Although prescribing increased between 2014 and 2020, half of the cohort still did not receive the therapy. Older age, gender, comorbidities and co-prescriptions were linked to MRA underuse. Understanding the factors contributing to underprescribing at a population level should be used to inform quality improvement strategies.