Prescription drug use in Danish children and adolescents 2005-2023.

Continuous monitoring of pediatric drug utilization is important for ensuring rational use and prioritizing research. This study provides an overview of pediatric prescription drug use among Danish children and adolescents from 2005-2023. Using Danish nationwide individual-level dispensing data, we identified all redeemed prescriptions for individuals < 18 years from January 2005-December 2023.

Effects of atrial fibrillation screening according to thyroid function: Post-hoc analysis of the randomized LOOP study.

Purpose: Subclinical thyroid dysfunction is a marker for atrial fibrillation (AF) and stroke risk. This study explored the effects of AF screening according to thyroid-stimulating hormone (TSH) levels.

Methods: An AF screening trial (the LOOP study) was analyzed post-hoc according to baseline TSH.

Heart Failure Events After Long-term Continuous Screening for Atrial Fibrillation: Results From the Randomized LOOP Study.

Background: Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown.

Methods: The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in older individuals with additional stroke risk factors.

Rare and Common Genetic Variation Underlying Atrial Fibrillation Risk.

Importance: Atrial fibrillation (AF) has a substantial genetic component. The importance of polygenic risk is well established, while the contribution of rare variants to disease risk warrants characterization in large cohorts.

Objective: To identify rare predicted loss-of-function (pLOF) variants associated with AF and elucidate their role in risk of AF, cardiomyopathy (CM), and heart failure (HF) in combination with a polygenic risk score (PRS).

Proteomics couples electrical remodelling to inflammation in a murine model of heart failure with sinus node dysfunction.

Aims: In patients with heart failure (HF), concomitant sinus node dysfunction (SND) is an important predictor of mortality, yet its molecular underpinnings are poorly understood. Using proteomics, this study aimed to dissect the protein and phosphorylation remodelling within the sinus node in an animal model of HF with concurrent SND.

Methods And Results: We acquired deep sinus node proteomes and phosphoproteomes in mice with heart failure and SND and report extensive remodelling.

Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis.

We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism.

Loss of Cardiac Splicing Regulator Is Associated With Early-Onset Atrial Fibrillation.

We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 in 2 independent cohorts. In a rat model with loss of , we demonstrated altered splicing of sarcomere genes (, , , and ), and differential expression in key cardiac genes. We identified altered sarcomere and mitochondrial structure on electron microscopy imaging and found compromised mitochondrial function.

Epicardial adipose tissue and subclinical incident atrial fibrillation as detected by continuous monitoring: a cardiac magnetic resonance imaging study.

Epicardial adipose tissue (EAT) has endocrine and paracrine functions and has been associated with metabolic and cardiovascular disease. This study aimed to investigate the association between EAT, determined by cardiac magnetic resonance imaging (CMR), and incident atrial fibrillation (AF) following long-term continuous heart rhythm monitoring by implantable loop recorder (ILR). This study is a sub-study of the LOOP study.

Anticoagulation-Associated Bleeding in Patients Screened for Atrial Fibrillation versus Usual Care-A Post Hoc Analysis from the LOOP Study.

 Atrial fibrillation (AF) prevalence is rising; however, data on the bleeding risks associated with the detection of subclinical AF are needed.  Our objective was to determine the bleeding increment associated with implantable loop recorder (ILR) screening for subclinical AF and subsequent anticoagulation initiation compared with usual care.  This post hoc study utilized LOOP trial data from 6,004 elderly patients with stroke risks randomized to either ILR (  = 1,503) or usual care (  = 4,503).

PITX2 gain-of-function mutation associated with atrial fibrillation alters mitochondrial activity in human iPSC atrial-like cardiomyocytes.

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide; however, the underlying causes of AF initiation are still poorly understood, particularly because currently available models do not allow in distinguishing the initial causes from maladaptive remodeling that induces and perpetuates AF. Lately, the genetic background has been proven to be important in the AF onset. iPSC-derived cardiomyocytes, being patient- and mutation-specific, may help solve this diatribe by showing the initial cell-autonomous changes underlying the development of the disease.