Impact of Pharmacovigilance Interventions Targeting Fluoroquinolones on Antibiotic Use in the Netherlands and the United Kingdom.

Purpose: Fluoroquinolones are antibiotics associated with adverse events that prompted the European Medicines Agency to implement risk minimization measures (RMMs) in 2018/19 and 2020. Our aim is to assess the RMMs' impact on antibiotic prescriptions in primary care during 2014-2023.

Methods: We assessed antibiotic prescriptions using CPRD GOLD (the United Kingdom, UK) and PHARMO (the Netherlands, NL).

INSIGHT: A Tool for Fit-for-Purpose Evaluation and Quality Assessment of Standardized Observational Data Sources for Real World Evidence on Medicine and Vaccine Safety.

Purpose: To describe the development of INSIGHT, a real-world data quality tool to assess completeness, consistency, and fitness-for-purpose of observational health data sources.

Methods: We designed a three-level pipeline with data quality assessments (DQAs) to be performed in ConcePTION Common Data Model (CDM) instances. The pipeline has been coded using R.

Core Concepts: Self-Controlled Designs in Pharmacoepidemiology.

One of the key challenges in pharmacoepidemiological studies is that of uncontrolled confounding, which occurs when confounders are poorly measured, unmeasured or unknown. Self-controlled designs can help address this issue, as their key comparison is not between people, but periods of time within the same person. This controls for all time-stable confounders (genetics) and in the absence of time-varying confounding negates the need for an external control group.

Burden of RSV infections among young children in primary care: a prospective cohort study in five European countries (2021-23).

Background: The majority of respiratory syncytial virus (RSV) infections in young children are managed in primary care, however, the disease burden in this setting remains poorly defined.

Methods: We did a prospective cohort study in primary care settings in Belgium, Italy, Spain, the Netherlands, and the UK during the RSV seasons of 2020-21 (UK only; from Jan 1, 2021), 2021-22, and 2022-23. Children aged younger than 5 years presenting to their general practitioner or primary care paediatrician with symptoms of an acute respiratory tract infection were eligible for RSV testing.

Evaluation of an interprofessional education program involving medical and pharmacy students: a mixed-method study.

Background: Effective pharmacotherapy requires strong collaboration between physicians and pharmacists, highlighting the need for interprofessional education (IPE) in university curricula. This study evaluated the impact of an IPE program on medical and pharmacy students, focusing on their perceived development of interprofessional collaborative competencies, perceived learning outcomes, and clinical collaboration perceptions.

Methods: A mixed-method approach was employed to evaluate an IPE program that consisted of three mandatory activities with increased complexity and autonomy, that were integrated into the medical and pharmacy students' curricula.

Individual patient and donor seroprofiles in convalescent plasma treatment of COVID-19 in REMAP-CAP clinical trial.

Objectives: Convalescent plasma (CP) treatment of COVID-19 has shown significant therapeutic effect only when administered early. We investigated the importance of patient and CP seroprofiles on treatment outcome in REMAP-CAP CP trial.

Methods: We evaluated neutralising antibodies (nAb), anti-spike (S) IgM, IgG, IgG avidity, IgG fucosylation and respiratory viral loads in a sub-set of patients (n=80) and controls (n=51) before and after transfusion, comparing them to those in the CP units (n=157) they received.

Does ruminating about the previous night's drinking during a hangover predict changes in heavy episodic drinking? A two-wave, 30-day prospective study.

Objective: We examined whether hangover-related rumination-repeatedly dwelling on negative aspects of yesterday's drinking while hungover the following morning-predicts changes in three dimensions of heavy episodic drinking (HED) over time.

Method: = 334 emerging adults (aged 19-29) from three Eastern Canadian universities who had recently experienced a hangover completed online self-report questionnaires at baseline (Wave 1) and 30 days later (Wave 2; 71.6% retention).

Multiple Perspectives on the Need for Real-World Evidence to Inform Regulatory and Health Technology Assessment Decision-Making: Scoping Review and Stakeholder Interviews.

Purpose: Real-world evidence (RWE) is increasingly considered in regulatory and health technology assessment (HTA) decision-making, though perspectives on its relevance may vary. Expanding on a recent review regarding regulatory decisions, this study aimed to identify factors influencing the need for RWE in HTA decision-making, confirm and enrich factors with stakeholder views, and evaluate similarities and differences between regulatory and HTA needs.

Methods: Previous scoping review methodology was used to identify factors influencing the need for RWE in HTA decision-making.

Mouse strain-specific responses along the gut-brain axis upon fecal microbiota transplantation from children with autism.

Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD.

The Lebanese health economic evaluation guideline.

Background: Economic evaluation guidelines (EEGs) serve as a valuable tool to assist appraisers in making consistent and transparent recommendations, standardize EE studies, enhance their quality, and minimize methodological uncertainties. As other LMICs, Lebanon aims for UHC where EEG is a necessity. This paper aims to report on the Lebanese health EEG (LEEG) and its reference case, including the intermediate results leading to the final decisions.

NAC regulates metabolism and cell fate in intestinal stem cells.

Intestinal stem cells (ISCs) face the challenge of integrating metabolic demands with unique regenerative functions. Studies have shown an intricate interplay between metabolism and stem cell capacity; however, it is still not understood how this process is regulated. Combining ribosome profiling and CRISPR screening in intestinal organoids, we identify the nascent polypeptide-associated complex (NAC) as a key mediator of this process.

Variable Assembly and Procapsid Binding of Bacteriophage P22 Terminase Subunits in Solution.

Concatemeric viral DNA is packaged into bacteriophage P22 procapsids via a headful packaging mechanism mediated by a molecular machine consisting of small (gp3) and large (gp2) terminase subunits. Although a negative stain reconstruction exists for the terminase holoenzyme, it is not clear how this complex binds the dodecameric portal protein located at a 5-fold mismatch vertex. Herein, we describe new assemblies for the holoenzyme.

Intestinal Cells-on-Chip for Permeability Studies.

Background: To accurately measure permeability of compounds in the intestine, there is a need for preclinical in vitro models that accurately represent the specificity, integrity and complexity of the human small intestinal barrier. Intestine-on-chip systems hold considerable promise as testing platforms, but several characteristics still require optimization and further development.

Methods: An established intestine-on-chip model for tissue explants was adopted for intestinal cell monolayer culture.

'We need to be part of the solution': lessons from the 2024 PPRI Conference on ensuring access to affordable medicines through innovative policies.

On 25-26 April 2024, the 5th PPRI (Pharmaceutical Pricing and Reimbursement Information) Conference on ensuring equitable access to affordable medicines took place in Vienna (Austria). Twenty-four accepted contributions were presented either as oral presentations or posters, adding to invited keynote lectures, stakeholder debates and workshops. The global multi-stakeholder audience discussed a range of approaches in pharmaceutical policies, which have the potential to successfully and sustainably address current and future challenges in ensuring patient access to affordable medicines globally.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Revising EU pharmaceutical legislation: will it foster drug repurposing?

Repurposing off-patent drugs can be a potential source of low-cost treatments for patients with unmet medical needs. Here, we review the proposed new European Union (EU) pharmaceutical legislation in which two articles address drug repurposing. We find certain barriers hindering the adoption of these new incentives by academic and not-for-profit stakeholders, including lack of knowledge on regulatory aspects, pharmacovigilance, and restrictions in data protection.

Fostering moral reflectivity in community pharmacists through moral case deliberation using the dilemma method.

Background: Moral case deliberation has been successfully implemented in multidisciplinary groups of secondary care professionals to support ethical decision making. It has not yet been reported for community pharmacists.

Aim: This study investigated whether moral case deliberation fosters moral reflectivity in community pharmacists.

Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria.

Protective immunity to malaria depends on acquisition of parasite-specific antibodies, with Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) being one of the most important target antigens. The effector functions of PfEMP1-specific IgG include inhibition of infected erythrocyte (IE) sequestration and opsonization of IEs for cell-mediated destruction. IgG glycosylation modulates antibody functionality, with increased affinity to FcγRIIIa for IgG lacking fucose in the Fc region (Fc-afucosylation).

Multi-tiered proteome analysis displays the hyper-permeability of the rheumatoid synovial compartment for plasma proteins.

Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and cartilage/bone destruction. RA affects the synovial joints, the synovial lining and the permeability of the synovium. As the latter is of central relevance for the distribution of systemically delivered therapeutics into synovial fluid (SF), we here assessed the protein composition of paired plasma and SF of patients diagnosed with RA at three distinct levels of depth using mass spectrometric approaches: the "total" proteome, the "total" IgG1 antibody repertoire and the RA-specific ACPA IgG1 autoantibody repertoire.

Understanding Parkinson's: The microbiome and machine learning approach.

Objective: Given that Parkinson's disease is a progressive disorder, with symptoms that worsen over time, our goal is to enhance the diagnosis of Parkinson's disease by utilizing machine learning techniques and microbiome analysis. The primary objective is to identify specific microbiome signatures that can reproducibly differentiate patients with Parkinson's disease from healthy controls.

Methods: We used four Parkinson-related datasets from the NCBI repository, focusing on stool samples.

Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction.

The lack of a robust system to reproducibly propagate HRV-C, a family of viruses refractory to cultivation in standard cell lines, has substantially hindered our understanding of this common respiratory pathogen. We sought to develop an organoid-based system to reproducibly propagate HRV-C, and characterize virus-host interaction using respiratory organoids. We demonstrate that airway organoids sustain serial virus passage with the aid of CYT387-mediated immunosuppression, whereas nasal organoids that more closely simulate the upper airway achieve this without any intervention.

Trends in initial pharmacological COPD treatment in primary care (2010-2021): a population-based study using the PHARMO Data Network.

Background: Pharmacological treatment is a cornerstone of chronic obstructive pulmonary disease (COPD) management, with general practitioners providing the most care. However, the lack of data on prescribing trends in initial pharmacotherapy in primary care hinders the understanding of how scientific and technical developments impact patient care and may also perpetuate suboptimal practices. Hence, this study aims to analyze trends in the initial pharmacological treatment of newly diagnosed COPD patients in Dutch primary care from 2010 to 2021.