SABINA + Hong Kong: a territory wide study of prescribing trends and outcomes associated with the use of short-acting ß2 agonists in the Chinese population.

BACKGROUND: Excessive use of short-acting ß2 agonists (SABA) in patients with asthma continues to be a notable concern due to its link to higher mortality rates. Global relevance of SABA overuse in asthma management cannot be understated, it poses significant health risk to patients with asthma and imposes burden on healthcare systems. This study, as part of global SABINA progamme, aimed to describe the prescribing patterns and clinical outcomes associated with SABA use in the Chinese population. METHODS: Retrospective cohort study was conducted using anonymized electronic healthcare records of Clinical Data Analysis and Reporting System (CDARS) from Hong Kong Hospital Authority (HA). Patients newly diagnosed with asthma between 2011 and 2018 and aged ≥12 years were included, stratified by SABA use (≤2, 3-6, 7-10, or ≥11 canisters/year) during one-year baseline period since asthma diagnosis date. Patients were followed up from one-year post-index until earliest censoring of events: outcome occurrence and end of study period (31 December 2020). Cox proportional regression and negative binomial regression were used to estimate the mortality risk and frequency of hospital admissions associated with SABA use respectively, after adjusting for age, sex, Charlson Comorbidity Index (CCI), and inhaled corticosteroid (ICS) dose. Outcomes include all-cause, asthma-related, and respiratory-related mortality, frequency of hospital admissions for any cause, and frequency of hospital admissions due to asthma. RESULTS: 17,782 patients with asthma (mean age 46.7 years, 40.8% male) were included and 59.1% of patients were overusing SABA (≥ 3 canisters per year). Each patient was prescribed a median of 5.61 SABA canisters/year. SABA overuse during baseline period was associated with higher all-cause mortality risk compared to patients with ≤2 canisters/year. Association was dose-dependent, highest risk in those used ≥11 canisters/year (adjusted hazard ratio: 1.42, 95% CI: 1.13, 1.79) and 3-6 canisters/year (adjusted hazard ratio: 1.22, 95% CI: 1.00, 1.50). Higher SABA prescription volume associated with increased frequency of hospital admissions with greatest risk observed in 7-10 canisters/year subgroup (adjusted rate ratio: 4.81, 95% CI: 3.66, 6.37). CONCLUSIONS: SABA overuse is prevalent and is associated with increased all-cause mortality risk and frequency of hospital admissions among the patients with asthma in Hong Kong.

Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry.

Rationale: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. Objectives: We hypothesized that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. Methods: We recruited 431 current smokers (median age, 39 yr; 16 pack-years smoked) and recorded symptoms using the COPD Assessment Test (CAT), spirometry, and quantitative thoracic computed tomography (QCT) scans at study entry. These scan results were compared with those from 67 never-smoking control subjects. Three hundred sixty-eight participants were followed every six months with measurement of postbronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age, and sex, was related to the initial QCT appearances and symptoms, measured using the CAT. Measurements and Main Results: There were no material differences in demography or subjective CT appearances between the young smokers and control subjects, but 55.7% of the former had CAT scores greater than 10, and 24.2% reported chronic bronchitis. QCT assessments of disease probability-defined functional small airway disease, ground-glass opacification, bronchovascular prominence, and ratio of small blood vessel volume to total pulmonary vessel volume were increased compared with control subjects and were all associated with a faster FEV1 decline, as was a higher CAT score. Conclusions: Radiological abnormalities on CT are already established in young smokers with normal lung function and are associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. Clinical trial registered with www.clinicaltrials.gov (NCT03480347).

Effectiveness and Respiratory Adverse Events Following Inactivated and mRNA COVID-19 Vaccines in Patients with COPD and Asthma: A Chinese Population-Based Study.

INTRODUCTION: Effectiveness and respiratory adverse events following coronavirus disease-2019 (COVID-19) vaccines have not been well investigated in Chinese patients with chronic obstructive pulmonary disease (COPD) and asthma. METHODS: Using electronic health care records in Hong Kong, we included adults with COPD or asthma or both and hospitalised for severe respiratory exacerbation in a self-controlled case series (SCCS) study between 23/02/2021 and 30/11/2022. Conditional Poisson regression models were used to estimate the incidence of outcomes within exposure periods (28 days after each dose) compared with baseline periods. Cox proportional hazard models evaluated vaccine effectiveness (VE) against COVID-related mortality, hospitalisation, and severe complications, including admission to intensive care units or ventilatory support. The VE assessment was based on vaccine types and the number of doses. RESULTS: In the SCCS, 343 CoronaVac recipients and 212 BNT162b2 recipients were included. No increased risk of outcomes was observed within the exposure periods. In the cohort study, 108,423 and 83,323 patients received ≥ 2 doses of CoronaVac and BNT162b2, respectively. The VE (95% CI) against COVID-related mortality, hospitalisation, and severe complications after two-dose CoronaVac was 77% (74-80%), 18% (6-23%), and 29% (12-43%), respectively, while for the two-dose regimen of BNT162b2, it was 92% (91-94%), 33% (30-37%), and 57% (45-66%), respectively. Higher VE against COVID-related mortality, hospitalisation, and severe complications was found for the three-dose regimen of CoronaVac (94%, 40%, and 71%) and BNT162b2 (98%, 65%, and 83%). Administering a fourth dose of either vaccine showed additional reductions in COVID-related outcomes. CONCLUSIONS: Among people with COPD and asthma, the COVID-19 vaccines CoronaVac and BNT162b2 did not increase severe exacerbations and achieved moderate-to-high effectiveness against COVID-related outcomes. COVID-19 vaccination remains essential and should be encouraged to protect this vulnerable population in future epidemic waves.

Influence of age on clinical characteristics, pharmacological management and exacerbations in children with asthma.

BACKGROUND: Asthma trials and guidelines often do not distinguish between adolescents and younger children. Using a large English data set, we evaluated the impact of age on asthma characteristics, management and exacerbations. METHODS: Primary care medical records, 2004-2021, were linked to hospital records. Children were categorised by age at diagnosis and followed until the next age bracket. Ages (based on management guidelines) were 5-8 years, 9-11 years and adolescents (12-16 years). Characteristics evaluated included body mass index, allergies and events before and after diagnosis (symptoms, medication). Exacerbation incidence was calculated. Multivariable Cox proportional hazards determined associations with exacerbations. RESULTS: 119 611 children were eligible: 61 940 (51.8%) 5-8 years, 32 316 (27.7%) 9-11 years and 25 355 (21.2%) adolescents. Several characteristics differed by age; children aged 5-8 years had the highest proportion with eczema, food/drug allergy and cough, but adolescents had the highest proportion with overweight/obesity, aeroallergen sensitisation, dyspnoea and short-acting-beta-agonist only use. Exacerbation rates were highest in the youngest children (per 100 person-years (95% CI): 5-8 years =13.7 (13.4-13.9), 9-11 years =10.0 (9.8-10.4), adolescents =6.7 (6.5-7.0)). Exacerbation risk factors also differed by age; 5-8 years: male, eczema and food/drug allergy were strongly associated, but for children ≥9 years old, obesity and aeroallergen sensitisation were strongly associated. For all children, higher socioeconomic deprivation was significantly associated with having an exacerbation. Delayed diagnosis was most common in children aged 5-8 years and was associated with increased exacerbations across all ages. CONCLUSION: Children's baseline characteristics and exacerbation rates varied according to their age group. Clinical guidelines should consider age at time of diagnosis more discretely than the broad range, 5-16 years, as this appears to impact on asthma severity and management.

Asthma and incident coronary heart disease: an observational and Mendelian randomisation study.

BACKGROUND: Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To overcome these, we applied a "triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings. METHODS: First, we conducted an observational study using UK medical records to match asthma patients 1:1, by age, sex and general practitioner (GP) practice, to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium (TAGC) and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium (CARDIoGRAM). Using 64 asthma single nucleotide polymorphisms, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy. RESULTS: In our observational study (n=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR 1.06, 95% CI 1.01-1.13); after accounting for healthcare behaviour, we found no association (model 2: HR 0.99, 95% CI 0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR 1.11, 95% CI 1.01-1.21; males: HR 0.91, 95% CI 0.84-0.98). Our MR study (n=589 875) found no association between asthma and CHD (OR 1.01, 95% CI 0.98-1.04) and no modification by sex. CONCLUSIONS: Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.

Neuropsychiatric events associated with montelukast in patients with asthma: a systematic review.

BACKGROUND: The United States Food and Drug Administration issued a black box warning on the mental health adverse effects of montelukast in 2020. Age-related effects on the risk of developing specific neuropsychiatric events in montelukast users remain largely unknown. OBJECTIVE: To describe the risk of neuropsychiatric events associated with montelukast in adults and children with asthma. METHODS: A systematic search of all studies investigating neuropsychiatric events in montelukast users was performed in PubMed, the Cochrane Library and Embase from inception to 7 September 2022. Animal studies and conference abstracts were excluded. RESULTS: 59 studies (21 pharmacovigilance studies, four reviews from 172 randomised controlled trials, 20 observational studies, 10 case reports and four case series) evaluating neuropsychiatric events in patients with asthma on montelukast were reviewed. No significant association was shown between montelukast and suicide-related events in six of the observational studies. No association was found for depression as defined by the International Classification of Diseases 10th revision codes in three observational studies and a review of randomised clinical trials. However, findings from four studies using antidepressant prescriptions as the outcome identified significant associations. Consistent with nine pharmacovigilance studies, two large-scale observational studies revealed possible associations of montelukast with anxiety and sleeping disorders in adult patients with asthma, respectively. However, the results were not replicated in two observational studies on children. CONCLUSION: Montelukast is not associated with suicide- and depression-related events in asthma patients. Older adults may be particularly susceptible to anxiety and sleeping disorders.

The Effect of Inhaled Corticosteroids on Pneumonia Risk in Patients With COPD-Bronchiectasis Overlap: A UK Population-Based Case-Control Study.

BACKGROUND: Inhaled corticosteroids (ICS) increase the risk of pneumonia in COPD and commonly are used in patients with COPD-bronchiectasis overlap. RESEARCH QUESTION: Is the risk of pneumonia associated with ICS further heightened in COPD-bronchiectasis? STUDY DESIGN AND METHODS: Electronic health care records (from 2004-2019) were used to obtain a cohort of patients with COPD and a nested case-control group (age and sex matched 1:4). Analyses were conducted to determine the risk of hospitalization for pneumonia in COPD associated with ICS use in those with bronchiectasis. Findings were confirmed by several sensitivity analyses. Additionally, a smaller nested case-control group containing only patients with COPD-bronchiectasis overlap and those with recent blood eosinophil counts (BECs) was used to determine any association with BEC. RESULTS: Three hundred sixteen thousand six hundred sixty-three patients were eligible for the COPD cohort; bronchiectasis significantly increased the risk of pneumonia (adjusted hazard ratio, 1.24; 95% CI, 1.15-1.33). In the first nested case-control group of 84,316 patients with COPD, ICS was found to increase the odds of pneumonia (adjusted OR [AOR], 1.26; 95% CI, 1.19-1.32) only if used in the previous 180 days. However, bronchiectasis was a significant modifier such that ICS use did not augment further the already elevated bronchiectasis-associated pneumonia risk (COPD-bronchiectasis: AOR, 1.01; 95% CI, 0.8-1.28; no bronchiectasis: AOR, 1.27; 95% CI, 1.20-1.34). Several sensitivity analyses and a second smaller nested case-control group confirmed these findings. Finally, we found that BEC modified the ICS-associated pneumonia risk in COPD-bronchiectasis overlap, where lower BEC was associated significantly with pneumonia (BEC ≤ 3 × 109/L: AOR, 1.56; 95% CI, 1.05-2.31; BEC > 3 × 109/L: AOR, 0.89; 95% CI, 0.53-1.24). INTERPRETATION: ICS use does not augment further the already increased risk of hospitalization for pneumonia associated with concomitant bronchiectasis in patients with COPD.

Covid-19 pandemic and asthma: What did we learn?

This review addresses some of the major lessons we have learnt regarding asthma and the covid-19 pandemic, including susceptibility to SARS-CoV-2 infection and severe covid-19, potentially protective factors, comparison to other respiratory infections, changes in healthcare behaviour from the perspective of patients and clinicians, medications to treat or prevent covid-19, and post-covid syndrome.

Persistent isolated impairment of gas transfer following COVID-19 pneumonitis relates to perfusion defects on dual-energy computed tomography.

A novel iodine perfusion score correlates with breathlessness and D LCO in patients post-#COVID19 without obvious interstitial disease on CT, suggesting that lung perfusion assessment may be useful in patients without another cause of dyspnoea https://bit.ly/3U6E2f5.

Treatment Transitions in Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases.

INTRODUCTION: Previous studies have reported that more patients receive inhaled corticosteroid (ICS)-containing therapies than would be expected based on exacerbation history, suggesting overprescribing. We aimed to describe patterns of treatment switching from first (1MT) to second maintenance therapy (2MT) among COPD patients in the US and UK. METHODS: We used healthcare data from the US IBM® MarketScan® and UK Clinical Practice Research Datalink databases (2015 - 2018) to assess transitions between 1MT and 2MT among COPD patients. Patients with a recorded asthma diagnosis prior to 1MT were excluded. We assessed whether prescribed treatments (long-acting muscarinic antagonists [LAMA], long-acting ß2-agonists [LABA], inhaled corticosteroids [ICS], as monotherapy or in combination) were consistent with global and national recommendations for COPD, identified patient characteristics associated with treatment transitions, and evaluated treatment duration. RESULTS: Overall, 7028 patients in the US and 2461 in the UK initiated 2MT within a median (IQR) 160.0 (76.0; 335.0) and 218.0 (86.0; 428.0) days after 1MT, respectively. In the US, 33.6% of patients initiating 2MT had no recorded exacerbations in the previous year, whereas 23.1% had one and 43.3% had ≥ 2. In the UK, 54.9% of patients had no recorded exacerbations in the previous year, whereas 20.9% had one and 24.2% had ≥ 2. At 2MT, most patients switched to LAMA/LABA/ICS (26.1%) or LABA/ICS (25.8%) in the US, and LAMA/LABA (39.4%) or LAMA/LABA/ICS (27.8%) in the UK; 62.2% (US) and 47.5% of patients (UK) were prescribed ICS-containing regimens. The most common treatment transition from 1MT to 2MT was LABA/ICS to LAMA/LABA/ICS (13.0%) in the US; and LAMA to LAMA/LABA (32.5%) and LAMA to LAMA/LABA/ICS (14.3%) in the UK. CONCLUSIONS: At 2MT, the proportion of patients on LAMA/LABA/ICS was similar between the US and UK, but treatment pathways were different.

People with chronic obstructive pulmonary disease (COPD) take inhaled medication to control symptoms such as breathlessness and cough. There are two types of inhaler: 'reliever' inhalers for immediate symptom relief, and 'maintenance' inhalers for long-term disease control. Maintenance inhalers can be used on their own or together, and treatment is often escalated based on the persistence of symptoms or exacerbations (flare-ups), for which inhaled corticosteroids (ICS) are often prescribed. We wanted to see whether doctors' prescribing habits are in line with clinical guidelines, so we looked at data from COPD patients who switched from their first maintenance therapy (1MT) to a second, different maintenance therapy (2MT) between 2015 and 2018. Our data sources were a US health claims database (~ 7000 patients) and a UK general practice database (~ 2500 patients). We excluded people with a diagnosis of both COPD and asthma, as similar inhalers are used to treat these two conditions, although the clinical decisions for when to prescribe them differ. On average, the time between 1MT and 2MT was 160 days (US) and 218 days (UK). Overall, 50% (UK) and 60% of patients (US) were prescribed ICS as part of their treatment regimen at 2MT, and ICS use in both countries was higher than expected based on the guidelines, which recommend ICS only for patients with severe COPD who meet certain criteria. This means that some patients are being given medication without a known clinical benefit, which puts them at risk of side effects, possibly increasing unnecessary healthcare costs.

First Maintenance Therapy for Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases.

INTRODUCTION: Inhaled corticosteroids (ICS) are often prescribed inappropriately alongside long-acting bronchodilators for chronic obstructive pulmonary disease (COPD). We aimed to investigate if prescribing habits in the US and UK differ from recommendations for initiation of COPD maintenance therapy. METHODS: We used healthcare data from the US IBM® MarketScan® and UK Clinical Practice Research Datalink databases to assess exacerbations and comorbidities in patients with COPD initiating first maintenance therapy (1MT) between 2015 and 2018. Patients with a recorded asthma diagnosis prior to initiation of 1MT were excluded. We evaluated time from recorded diagnosis of COPD until initiation of 1MT, and treatment regimen at 1MT (long-acting muscarinic antagonist [LAMA], long-acting ß2-agonist [LABA], ICS, as monotherapy or in combination). RESULTS: In the US and UK, median (IQR) time between recorded COPD diagnosis and 1MT was 158 (12; 839) and 29 (1; 521) days, respectively. Among the 53,473 US patients and 8786 UK patients who initiated 1MT, 50.9% and 32.4% had ≥ 1 exacerbation in the previous year. In the US, 20% of patients initiated LAMA, 1% LABA, 13% LAMA/LABA, and 66% an ICS-containing regimen (49% LABA/ICS, 13% ICS, and 4% LAMA/LABA/ICS). In the UK, 53% of patients initiated LAMA, 4% LABA, 16% LAMA/LABA, and 27% an ICS-containing regimen (14% LABA/ICS, 9% ICS, and 4% LAMA/LABA/ICS). CONCLUSIONS: At 1MT, two-thirds of patients in the US received ICS-containing therapies, with almost half on LABA/ICS. In contrast, less than one-third received ICS-containing therapy in the UK and more than half of patients received LAMA. In both countries, more patients received ICS-containing therapies at initiation of 1MT than would be expected based on their exacerbation history, suggesting overprescribing.

Chronic obstructive pulmonary disease (COPD), a smoking-related lung disease, restricts airflow in the lungs, causing symptoms such as breathlessness and coughing. To control symptoms, patients use one or more types of inhaled 'maintenance' medication, which can be prescribed alone or together. When patients have a short-term worsening of symptoms, doctors often prescribe inhaled corticosteroids (ICS). We wanted to see whether doctors' prescribing habits for maintenance inhalers are in line with clinical guidelines, so we analyzed data from a US health insurance database (~ 50,000 patients) and UK primary care medical records (~ 8000 patients). We focused on patients with a diagnosis of COPD who were prescribed their first maintenance therapy (1MT) between 2015 and 2018. We excluded people with a diagnosis of both COPD and asthma, as similar inhalers are used to treat these conditions, although the clinical decisions for when to prescribe them differ. The average time between COPD diagnosis and 1MT was longer in the US (158 days) than in the UK (29 days). A higher percentage of patients in the US (~ 65%) versus UK (~ 25%) were prescribed ICS as part of their treatment, and ICS use in both countries was higher than expected based on the guidelines, which recommend ICS only for patients with severe COPD who meet certain criteria. Our findings suggest overprescribing of ICS in both countries (particularly the US), meaning that some patients are being given medication without a known clinical benefit, which puts them at risk of side effects, possibly increasing unnecessary healthcare costs.

Hospitalization for Heart Failure in the United States, UK, Taiwan, and Japan: An International Comparison of Administrative Health Records on 413,385 Individual Patients.

BACKGROUND: Registries show international variations in the characteristics and outcome of patients with heart failure (HF), but national samples are rarely large, and case selection may be biased owing to enrolment in academic centers. National administrative datasets provide large samples with a low risk of bias. In this study, we compared the characteristics, health care resource use (HRU) and outcomes of patients with primary HF hospitalizations (HFH) using electronic health records (EHR) from 4 high-income countries (United States, UK, Taiwan, Japan) on 3 continents. METHODS AND RESULTS: We used electronic health record to identify unplanned HFH between 2012 and 2014. We identified 231,512, 10,991, 36,900, and 133,982 patients with a primary HFH from the United States, the UK, Taiwan, and Japan, respectively. HFH per 100,000 population was highest in the United States and lowest in Taiwan. Fewer patients in Taiwan and Japan were obese or had chronic kidney disease. The length of hospital stay was shortest in the United States (median 4 days) and longer in the UK, Taiwan, and Japan (medians of 7, 9, and 17 days, respectively). HRU during hospitalization was highest in Japan and lowest in UK. Crude and direct standardized in-hospital mortality was lowest in the United States (direct standardized rates 1.8, 95% confidence interval 1.7%-1.9%) and progressively higher in Taiwan (direct standardized rates 3.9, 95% CI 3.8%-4.1%), the UK (direct standardized rates 6.4, 95% CI 6.1%-6.7%), and Japan (direct standardized rates 6.7, 95% CI 6.6%-6.8%). The 30-day all-cause (25.8%) and HF (7.2%) readmissions were highest in the United States and lowest in Japan (11.9% and 5.1%, respectively). CONCLUSIONS: Marked international variations in patient characteristics, HRU, and clinical outcomes exist; understanding them might inform health care policy and international trial design.

Asthma Phenotypes and COVID-19 Risk: A Population-based Observational Study.

Rationale: Studies have suggested some patients with asthma are at risk of severe coronavirus disease (COVID-19), but they have had limited data on asthma phenotype and have not considered if risks are specific to COVID-19. Objectives: To determine the effect of asthma phenotype on three levels of COVID-19 outcomes. Compare hospitalization rates with influenza and pneumonia. Methods: Electronic medical records were used to identify patients with asthma and match them to the general population. Patient-level data were linked to Public Health England severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test data, hospital, and mortality data. Asthma was phenotyped by medication, exacerbation history, and type 2 inflammation. The risk of each outcome, adjusted for major risk factors, was measured using Cox regression. Measurements and Main Results: A total of 434,348 patients with asthma and 748,327 matched patients were included. All patients with asthma had a significantly increased risk of a General Practice diagnosis of COVID-19. Asthma with regular inhaled corticosteroid (ICS) use (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01-1.61), intermittent ICS plus add-on asthma medication use (HR, 2.00; 95% CI, 1.43-2.79), regular ICS plus add-on use (HR, 1.63; 95% CI, 1.37-1.94), or with frequent exacerbations (HR, 1.82; 95% CI, 1.34-2.47) was significantly associated with hospitalization. These phenotypes were significantly associated with influenza and pneumonia hospitalizations. Only patients with regular ICS plus add-on asthma therapy (HR, 1.70; 95% CI, 1.27-2.26) or frequent exacerbations (HR, 1.66; 95% CI, 1.03-2.68) had a significantly higher risk of ICU admission or death. Atopy and blood eosinophil count were not associated with severe COVID-19 outcomes. Conclusions: More severe asthma was associated with more severe COVID-19 outcomes, but type 2 inflammation was not. The risk of COVID-19 hospitalization appeared to be similar to the risk with influenza or pneumonia.

Under-recognition of heart failure in patients with atrial fibrillation and the impact of gender: a UK population-based cohort study.

BACKGROUND: Patients with atrial fibrillation (AF) complicated by heart failure (HF) have a poor prognosis. We investigated whether long term loop-diuretic therapy in patients with AF and no known diagnosis of HF, as a potential surrogate marker of undiagnosed HF, is also associated with worse outcomes. METHODS: Adults with incident AF were identified from UK primary and secondary care records between 2004 and 2016. Repeat prescriptions for loop diuretics, without a diagnosis of HF or documented non-cardiac indication, were classified as 'isolated' loop diuretic use. RESULTS: Amongst 124,256 people with incident AF (median 76 years, 47% women), 22,001 (17.7%) had a diagnosis of HF, and 22,325 (18.0%) had isolated loop diuretic use. During 2.9 (LQ-UQ 1-6) years' follow-up, 12,182 patients were diagnosed with HF (incidence rate 3.2 [95% CI 3.1-3.3]/100 person-years). Of these, 3999 (32.8%) had prior isolated loop diuretic use, including 31% of patients diagnosed with HF following an emergency hospitalisation. The median time from AF to HF diagnosis was 3.6 (1.2-7.7) years in men versus 5.1 (1.8-9.9) years in women (p = 0.0001). In adjusted models, patients with isolated loop diuretic use had higher mortality (HR 1.42 [95% CI 1.37-1.47], p < 0.0005) and risk of HF hospitalisation (HR 1.60 [95% CI 1.42-1.80], p < 0.0005) than patients with no HF or loop diuretic use, and comparably poor survival to patients with diagnosed HF. CONCLUSIONS: Loop diuretics are commonly prescribed to patients with AF and may indicate increased cardiovascular risk. Targeted evaluation of these patients may allow earlier HF diagnosis, timely intervention, and better outcomes, particularly amongst women with AF, in whom HF appears to be under-recognised and diagnosed later than in men.

Development of a fixed module repertoire for the analysis and interpretation of blood transcriptome data.

As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via:  https://drinchai.shinyapps.io/BloodGen3Module/ .