Data_Sheet_1_Adherence and persistence to oral anticoagulants in patients with atrial fibrillation: A Belgian nationwide cohort study.DOCX

BackgroundSince non-vitamin K antagonist oral anticoagulants (NOACs) do not require coagulation monitoring, concerns of lower adherence and persistence to NOACs than vitamin K antagonists (VKAs) have been raised. Moreover, little is known on the frequency of permanent cessation and switching between anticoagulants in patients with atrial fibrillation (AF). Therefore, persistence, reinitiation, switching and adherence to oral anticoagulants (OACs) were investigated.Materials and methodsAF patients with a first OAC prescription claim between 2013 and 2019 were identified in Belgian nationwide data. Persistence, reinitiation and switching were estimated using Kaplan-Meier analyses. Adherence was investigated using the proportion of days covered (PDC). Predictors for non-adherence and non-persistence were identified by multivariable logistic regression.ResultsAmong 277,782 AF patients, 69.6% NOAC and 37.2% VKA users were persistent after 1 year, whereas 44.3% and 18.9% after 5 years, respectively. After one year, 67.1% rivaroxaban, 68.1% dabigatran, 69.8% apixaban, and 76.9% edoxaban users were persistent. Among subjects having discontinued NOAC or VKA treatment, 75.4% and 46.1% reinitiated any OAC within 5 years, respectively. VKAs were more frequently switched to NOACs than vice versa (17.6% versus 2.5% after 1 year). After 1 year, a high PDC (≥ 90%) was observed in 87.8% apixaban, 88.6% dabigatran, 91.3% rivaroxaban, and 94.7% edoxaban users (90.2% NOAC users). Adherence and persistence were higher in older, female subjects, while lower in subjects with dementia or hyperpolypharmacy.ConclusionAdherence and persistence to NOACs were high. However, 10% of subjects were non-adherent after 1 year and one-fourth did not reinitiate anticoagulation within 5 years after NOAC discontinuation.</p

Additional file 1 of The AGE-RAGE axis associates with chronic pulmonary diseases and smoking in the Rotterdam study

Supplementary Material

Additional file 1 of In-hospital antibiotic use for severe chronic obstructive pulmonary disease exacerbations: a retrospective observational study

Additional file 1

Asthma exacerbations and eosinophilia in the UK Biobank: a genome-wide association study.

BackgroundAsthma exacerbations reflect disease severity, affect morbidity and mortality, and may lead to declining lung function. Inflammatory endotypes (e.g. T2-high (eosinophilic)) may play a key role in asthma exacerbations. We aimed to assess whether genetic susceptibility underlies asthma exacerbation risk and additionally tested for an interaction between genetic variants and eosinophilia on exacerbation risk.MethodsUK Biobank data were used to perform a genome-wide association study of individuals with asthma and at least one exacerbation compared to individuals with asthma and no history of exacerbations. Individuals with asthma were identified using self-reported data, hospitalisation data and general practitioner records. Exacerbations were identified as either asthma-related hospitalisation, general practitioner record of asthma exacerbation or an oral corticosteroid burst prescription. A logistic regression model adjusted for age, sex, smoking status and genetic ancestry via principal components was used to assess the association between genetic variants and asthma exacerbations. We sought replication for suggestive associations (p-6) in the GERA cohort.ResultsIn the UK Biobank, we identified 11 604 cases and 37 890 controls. While no variants reached genome-wide significance (p-8) in the primary analysis, 116 signals were suggestively significant (p-6). In GERA, two single nucleotide polymorphisms (rs34643691 and rs149721630) replicated (pConclusionsOur study has identified reproducible associations with asthma exacerbations in the UK Biobank and GERA cohorts. Confirmation of these findings in different asthma subphenotypes in diverse ancestries and functional investigation will be required to understand their mechanisms of action and potentially inform therapeutic development

Participant characteristics.

<p>TRV = tricuspid regurgitation peak velocity; RAP = right atrial pressure; ePASP = pulmonary artery systolic pressure; RVEDD = right ventricular end-diastolic diameter; FS = left ventricular fractional shortening; LV = left ventricle; COPD = chronic obstructive pulmonary disease.</p><p>Participant characteristics.</p

Prevalence of echocardiographic-defined pulmonary hypertension, alternative diagnostic criteria.

<p>Data are shown as prevalences (95% confidence interval)</p><p>RAP = right atrial pressure; TRV = tricuspid regurgitation velocity; ePASP = pulmonary artery systolic pressure, calculated as 4*TRV² + RAP. If RAP could not be estimated, the case definition was based on TRV > 3.0 m/s and 3.4 m/s to correspond to ePASP > 40 mmHg and 50 mmHg, respectively</p><p>Participants with absent or too-small-to-measure TRV were included as non-cases.</p><p>Prevalence of echocardiographic-defined pulmonary hypertension, alternative diagnostic criteria.</p

Prevalence of echocardiographic pulmonary hypertension, overall and in subgroups.

<p>COPD = chronic obstructive pulmonary disease; LV = left ventricle; ePH = pulmonary hypertension.</p><p>Prevalence of echocardiographic pulmonary hypertension, overall and in subgroups.</p

Associations with pulmonary artery systolic pressure in linear regression models in 1945 participants in whom ePASP could be estimated.

<p>Dependent variable is ePASP (mmHg).</p><p>LV = left ventricular; COPD = chronic obstructive pulmonary disease; 95%CI = 95% confidence interval.</p><p>In model A, each variable is adjusted for age and sex.</p><p>In model B, adjustments were made for all the variables which had p < 0.05 in model A.</p><p>Associations with pulmonary artery systolic pressure in linear regression models in 1945 participants in whom ePASP could be estimated.</p

Distribution of pulmonary artery systolic pressure in 1945 participants in whom it could be estimated.

<p>Distribution of pulmonary artery systolic pressure in 1945 participants in whom it could be estimated.</p

Image_1_A Genome-Wide Linkage Study for Chronic Obstructive Pulmonary Disease in a Dutch Genetic Isolate Identifies Novel Rare Candidate Variants.pdf

<p>Chronic obstructive pulmonary disease (COPD) is a complex and heritable disease, associated with multiple genetic variants. Specific familial types of COPD may be explained by rare variants, which have not been widely studied. We aimed to discover rare genetic variants underlying COPD through a genome-wide linkage scan. Affected-only analysis was performed using the 6K Illumina Linkage IV Panel in 142 cases clustered in 27 families from a genetic isolate, the Erasmus Rucphen Family (ERF) study. Potential causal variants were identified by searching for shared rare variants in the exome-sequence data of the affected members of the families contributing most to the linkage peak. The identified rare variants were then tested for association with COPD in a large meta-analysis of several cohorts. Significant evidence for linkage was observed on chromosomes 15q14–15q25 [logarithm of the odds (LOD) score = 5.52], 11p15.4–11q14.1 (LOD = 3.71) and 5q14.3–5q33.2 (LOD = 3.49). In the chromosome 15 peak, that harbors the known COPD locus for nicotinic receptors, and in the chromosome 5 peak we could not identify shared variants. In the chromosome 11 locus, we identified four rare (minor allele frequency (MAF) <0.02), predicted pathogenic, missense variants. These were shared among the affected family members. The identified variants localize to genes including neuroblast differentiation-associated protein (AHNAK), previously associated with blood biomarkers in COPD, phospholipase C Beta 3 (PLCB3), shown to increase airway hyper-responsiveness, solute carrier family 22-A11 (SLC22A11), involved in amino acid metabolism and ion transport, and metallothionein-like protein 5 (MTL5), involved in nicotinate and nicotinamide metabolism. Association of SLC22A11 and MTL5 variants were confirmed in the meta-analysis of 9,888 cases and 27,060 controls. In conclusion, we have identified novel rare variants in plausible genes related to COPD. Further studies utilizing large sample whole-genome sequencing should further confirm the associations at chromosome 11 and investigate the chromosome 15 and 5 linked regions.</p