Stimulating development of innovative medicines in the European Union: does a new definition for unmet medical need add value?

The European Commission (EC) has proposed to redefine 'unmet medical need' to steer pharmaceutical innovation and link the definition to incentives and regulatory tools and procedures. A multistakeholder meeting of the Regulatory Science Network Netherlands (RSNN) discussed the impact of this proposal. Four principles were highlighted (flexibility, feasibility, fairness, and sensitivity to risk) that were not considered sufficiently addressed.

Relevance of therapeutic prescription modifications in Dutch community pharmacies.

Objectives: Community pharmacists modify prescriptions to solve or prevent drug-related problems. To assess the relevance of prescription modifications, they are usually judged on clinical outcomes only, overlooking their humanistic and economic impact. This study aims to evaluate therapeutic prescription modifications performed by Dutch community pharmacists in terms of clinical outcome, along with the humanistic aspect "usability" and economic aspect "efficiency.

Inceptor binds to and directs insulin towards lysosomal degradation in β cells.

Blunted first-phase insulin secretion and insulin deficiency are indicators of β cell dysfunction and diabetes manifestation. Therefore, insights into molecular mechanisms that regulate insulin homeostasis might provide entry sites to replenish insulin content and restore β cell function. Here, we identify the insulin inhibitory receptor (inceptor; encoded by the gene IIR/ELAPOR1) as an insulin-binding receptor that regulates insulin stores by lysosomal degradation.

Impact of Regulatory Risk Communication on Thrombosis With Thrombocytopenia Syndrome for COVID-19 Adenovirus Vector Vaccines on European Healthcare Professionals.

Purpose: The European Medicines Agency (EMA) issued regulatory actions and communications in 2021 on thrombosis with thrombocytopenia syndrome (TTS) associated with adenovirus vector vaccines Vaxzevria or Jcovden. This study aimed to evaluate the impact of these actions on awareness, knowledge and implementation in practises of healthcare professionals (HCP).

Methods: Web-based cross-sectional surveys were conducted on HCPs engaged in the vaccination, monitoring or counselling about the vaccines.

Fc-Afucosylation of VAR2CSA-Specific Immunoglobulin G and Clinical Immunity to Placental Plasmodium falciparum Malaria.

Background: Acquired immunity to Plasmodium falciparum malaria is mainly mediated by immunoglobulin G (IgG) targeting erythrocyte membrane protein 1 (PfEMP1). These adhesins mediate infected erythrocyte (IE) sequestration, protecting IEs from splenic destruction. PfEMP1-specific IgG is therefore thought to protect mainly by inhibiting IE sequestration.

Evaluating the effectiveness of the Smart About Meds (SAM) mobile application among patients discharged from hospital: protocol of a randomised controlled trial.

Introduction: Almost half of patients discharged from hospital are readmitted or return to the emergency department (ED) within 90 days. Non-adherence to medication changes made during hospitalisation and the use of potentially inappropriate medications (PIMs) both contribute to postdischarge adverse events. We developed Smart About Meds (SAM), a patient-centred mobile application that targets medication non-adherence and PIMs use.

Constitutive activity of an atypical chemokine receptor revealed by inverse agonistic nanobodies.

Chemokine stimulation of atypical chemokine receptor 3 (ACKR3) does not activate G proteins but recruits arrestins. It is a chemokine scavenger that indirectly influences responses by restricting the availability of CXCL12, an agonist shared with the canonical receptor CXCR4. ACKR3 is upregulated in numerous disorders.

Challenges in the Implementation of EU Risk Minimisation Measures for Medicinal Products in Clinical Practice Guidelines: Mixed Methods Multi-Case Study.

Introduction: Risk minimisation measures (RMMs) aim to ensure safe use of medicines, but their implementation in clinical practice is complicated by the diversity of stakeholders whose clinical decision making they seek to inform. Clinical practice guidelines (CPGs) are considered integral in clinical decision making.

Objectives: To determine the extent to which RMMs are included in the relevant CPGs and to describe factors that determine RMM inclusion.

Genipin rescues developmental and degenerative defects in familial dysautonomia models and accelerates axon regeneration.

The peripheral nervous system (PNS) is essential for proper body function. A high percentage of the world's population suffers from nerve degeneration or peripheral nerve damage. Despite this, there are major gaps in the knowledge of human PNS development and degeneration; therefore, there are no available treatments.

Efficacy of Chitosan-N-Arginine Chitosomes in mRNA Delivery and Cell Viability Enhancement.

Cationic lipid-based carriers are recognized for their ability to complex with mRNA and effectively deliver the mRNA for vaccination and therapeutic purposes. However, the significant cytotoxicity of these carriers often restricts their practical application. In the present study, polymer-lipid hybrid nanoparticles, termed chitosomes, incorporating chitosan-N-arginine (CSA) with the DOTAP cationic lipid and the DOPE helper lipid, were synthesized and evaluated.

A systematic review and risk of bias analysis of in vitro studies on trophoblast response to immunological triggers.

An increasing amount of evidence suggests that immune responses may affect trophoblast functioning, which in turn may play a role in gestational disorders and fetal development. This systematic review offers the first summary of in vitro studies on the trophoblast response to immunological triggers, in conjunction with a risk of bias analysis. A search in Pubmed and Embase yielded 110 relevant studies.