Characterization of Biomarkers of Thrombo-Inflammation in Patients with First-Diagnosed Atrial Fibrillation.

Patients with first-diagnosed atrial fibrillation (FDAF) exhibit major adverse cardiovascular events (MACEs) during follow-up. Preclinical models have demonstrated that thrombo-inflammation mediates adverse cardiac remodeling and atherothrombotic events. We have hypothesized that thrombin activity (FIIa) links coagulation with inflammation and cardiac fibrosis/dysfunction.

Role of innovation in pharmaceutical regulation: A proposal for principles to evaluate EU General Pharmaceutical Legislation from the innovator perspective.

Because the EU General Pharmaceutical Legislation is under review, the EFPIA Innovation Board developed evaluation principles for the policy proposals and key considerations on how the regulatory framework can support innovation while ensuring only safe, efficacious and quality medicines are authorized. The evaluation principles are anchored on actions to promote: agile adoption of new methodologies with soft law tools; continued emphasis on regulatory science to inform policies; a cost/benefit assessment of the new regulation to ensure they have an overall positive impact; and mitigation of any negative externalities or unintended effects for any type of innovation or products. The evaluation principles are intended to guide the impact assessment of the pharmaceutical legislation in the EU but the principles can be applied globally.

Intestinal Barrier Dysfunction and Microbial Translocation in Patients with First-Diagnosed Atrial Fibrillation.

Background: According to the leaky gut concept, microbial products (e.g., lipopolysaccharide, LPS) enter the circulation and mediate pro-inflammatory immunological responses.

Cytotoxic CD8 T Cells Are Involved in the Thrombo-Inflammatory Response during First-Diagnosed Atrial Fibrillation.

Background: Atrial myopathy and atrial fibrillation (AF) accompany thrombo-inflammation. This facilitates disease progression and promotes major adverse cardiovascular events (MACEs). Thrombin receptor (protease-activated receptor 1, PAR1) signalling is central in mediating thrombo-inflammation.

New Approaches to Regulatory Innovation Emerging During the Crucible of COVID-19 : In Responding to a Global Health Crisis, Industry is Discovering New, Efficient Ways of Meeting Objectives.

The urgency and impact of the ongoing COVID-19 pandemic are changing global drug development and regulatory processes. The need for speed to understand the virus and develop new vaccines, medicines, and therapies for patients has provided unprecedented learning opportunities and revealed how the pharmaceutical industry can improve upon traditional processes. To stay competitive while remaining compliant with agency regulations and guidance, companies need to implement new process/tools that allow for more flexible work models, consider expanding the use of decentralized/hybrid trials, and capitalize on the use of real-world evidence (RWE) and cloud-based data systems.

Protease-activated receptor 2 deficiency mediates cardiac fibrosis and diastolic dysfunction.

Aims: Heart failure with preserved ejection fraction (HFpEF) and pathological cardiac aging share a complex pathophysiology, including extracellular matrix remodelling (EMR). Protease-activated receptor 2 (PAR2) deficiency is associated with EMR. The roles of PAR1 and PAR2 have not been studied in HFpEF, age-dependent cardiac fibrosis, or diastolic dysfunction (DD).

Clinical trials in neonates and children: Report of the pulmonary hypertension academic research consortium pediatric advisory committee.

Drug trials in neonates and children with pulmonary hypertensive vascular disease pose unique but not insurmountable challenges. Childhood is defined by growth and development. Both may influence disease and outcomes of drug trials.