From Vision to Reality: The EU's Pharmaceutical Reforms and the Path to Improved Access.

Disparities in access to oncology medicines in European Union (EU) member states can impact patient outcomes profoundly, with availability and timely access varying significantly across and within member states. This paper discusses the intersection of the new European Health Technology Assessment Regulation (HTAR), the provisions of the proposed pharmaceutical legislation and their potential impacts on access to oncology medicines across EU member states. The HTAR, seeking to standardise the clinical evaluation of new medicines, has the potential to streamline the evaluation process but also risks oversimplifying diverse national healthcare needs.

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

Neurophysiological gradient in the Parkinsonian subthalamic nucleus as a marker for motor symptoms and apathy.

Sensing-based deep brain stimulation should optimally consider both the motor and neuropsychiatric domain to maximize quality of life of Parkinson's disease (PD) patients. Here we characterize the neurophysiological properties of the subthalamic nucleus (STN) in 69 PD patients using a newly established neurophysiological gradient metric and contextualize it with motor symptoms and apathy. We could evidence a STN power gradient that holds most of the spectral information between 5 and 30 Hz spanning along the dorsal-ventral axis.

Neurostatus-SMARTCARE clinical trial: Enabling health care professionals to assess EDSS for decentralized trials in multiple sclerosis.

Background: Neurostatus-Expanded Disability Status Scale (EDSS) is the standard measure used to assess impairment and disability in multiple sclerosis (MS) trials but requires trained expert neurologists.

Objectives: This study aims to evaluate the concordance of Neurostatus-EDSS assessments from specially trained health care professionals (HCPs) and standardized trained neurologists.

Methods: A Swiss multicenter, randomized, cross-over study with 100 people with MS.

Combining sequential extractions with bulk and micro X-ray spectroscopy to elucidate iron and phosphorus speciation in sediments of an iron-treated peat lake.

In shallow lakes, mobilization of legacy phosphorus (P) from the sediments can be the main cause for persisting eutrophication after reduction of external P input. In-lake remediation measures can be applied to reduce internal P loading and to achieve ecosystem recovery. The eutrophic shallow peat lake Terra Nova (The Netherlands) was treated with iron (Fe) to enhance P retention in the sediment.

Routine Spironolactone in Acute Myocardial Infarction.

Background: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain.

Methods: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo.

Impact of donor age ≥65 years on graft survival in large lung transplant cohorts.

Background: Although the demand for allografts continuously surpasses the supply, the majority of lungs offered for transplant are declined based on various factors, including donor age. This in turn sustains the wait-list mortality of patients with end-stage pulmonary disease.

Methods: In this single-center, observational cohort study, we investigated the impact of donor age on graft survival.

Activity-based contracting for optimization of the mass distribution of insecticide-treated nets in the Democratic Republic of Congo: pilot implementation in Kwilu province.

Background: Promoting the use of insecticide-treated mosquito nets (ITNs) is one of the main strategies for reducing malaria-related morbidity. An innovative activity-based contracting (ABC) approach has been implemented in Kwilu Province, Democratic Republic of Congo to optimize ITN mass distribution campaigns, with payments based on contractually defined programmatic outcomes for key campaign activities following independent verification of results.

Methods: This internal evaluation was carried out using a mixed methods approach combining qualitative and quantitative document and content analysis from a series of three workshops: validation workshops for campaign results at provincial level for the 2021 and 2022 campaigns; internal evaluation workshop for the Kwilu campaign as part of the ABC approach organized by "Santé pour tous en milieu rural" (SANRU) with its sub-contractors; and national campaign evaluation workshop organized by the National Malaria Control Program.

A First-Passage Model of Intravitreal Drug Delivery and Residence Time-Influence of Ocular Geometry, Individual Variability, and Injection Location.

Purpose: Standard of care for various retinal diseases involves recurrent intravitreal injections. This motivates mathematical modeling efforts to identify influential factors for ocular drug residence time, aiming to minimize administration frequency. We sought to describe the vitreal diffusion of therapeutics in nonclinical species frequently used during drug development assessments.

Adaptive Trials in Stroke: Current Use and Future Directions.

Inclusion of adaptive design features in a clinical trial provides preplanned flexibility to dynamically modify a trial during its conduct while preserving validity and integrity. Adaptive trials are needed to accelerate the conduct of more efficient, informative, and ethical clinical research in the field of neurology. Stroke is a natural candidate for adoption of these innovative approaches to trial design.

Extra-osseous Roles of the RANK-RANKL-OPG Axis with a Focus on Skeletal Muscle.

Purpose Of Review: This review aims to consolidate recent observations regarding extra-osseous roles of the RANK-RANKL-OPG axis, primarily within skeletal muscle.

Recent Findings: Preclinical efforts to decipher a common signalling pathway that links the synchronous decline in bone and muscle health in ageing and disease disclosed a potential role of the RANK-RANKL-OPG axis in skeletal muscle. Evidence suggests RANKL inhibition benefits skeletal muscle function, mass, fibre-type switching, calcium homeostasis and reduces fall incidence.

Visualisation and quantification of subcutaneous injections of different volumes, viscosities and injection rates: An ex-vivo micro-CT study.

The effects of subcutaneous (SC) injection parameters such as drug formulation volume, viscosity and injection rate on therapeutic performance and tolerability have not been established for any drug product. In this study four groups of SC injections were performed on fresh ex vivo minipig abdominal tissue samples, varying volume (0.5-1 mL), viscosity (1-11 cP) and rate (0.

Asundexian versus Apixaban in Patients with Atrial Fibrillation.

Background: Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding.

Methods: In a phase 3, international, double-blind trial, we randomly assigned high-risk patients with atrial fibrillation in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban.

Specific Reversal Agents for Direct Oral Anticoagulants in Acute Stroke.

Direct oral anticoagulants (DOACs) changed stroke prevention and decreased the risk of ischemic and hemorrhagic complications in patients on oral anticoagulation (OAC) therapy. The numbers of patients prescribed DOACs has increased rapidly. Availability of specific reversal agents opened new avenues in the prevention and management of DOAC complications.

PITX2 deficiency leads to atrial mitochondrial dysfunction.

Aims: Reduced left atrial PITX2 is associated with atrial cardiomyopathy and atrial fibrillation (AF). PITX2 is restricted to left atrial cardiomyocytes (aCMs) in the adult heart. The links between PITX2 deficiency, atrial cardiomyopathy, and AF are not fully understood.

Atrial fibrillation rhythm management: a matter of timing.

Rhythm control in patients with atrial fibrillation (AF) has evolved dramatically in the last decades. Several studies have informed us of the benefits of an early rhythm control strategy and primary rhythm control by catheter ablation (CA). Similarly, several studies have investigated the effects of CA in patients with longer AF duration and more comorbidities, especially heart failure.