Shaping the future of pharmacoepidemiology in France: Recommendations from the SFPT Pharmacoepidemiology Working Group.

The drug authorization process is shifting towards a policy aimed at shortening time-to-market. While this policy facilitates early access to new treatments, it can also result in potentially insufficient knowledge of both efficacy and safety at the time of marketing. The latter is particularly true for long-term outcomes or in specific populations (e.

β-Lactam Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus Infective Endocarditis.

Importance: Infective endocarditis (IE) caused by Staphylococcus aureus is associated with high mortality, approximately 20% to 30%, mostly in the first month, with no improvement in recent decades. Current opinion is that antistaphylococcal penicillin and cefazolin are equally effective in treating methicillin-susceptible S aureus (MSSA) IE, and both are recommended as possible first-line treatments. Most MSSA strains carry the β-lactamase blaZ gene, and some blaZ-positive strains exhibit an inoculum effect, meaning increased minimum inhibitory concentrations at high inoculum.

Plasma clearance of 5-fluorouracil is more influenced by variations in glomerular filtration rate than by uracil concentration.

Objectives: The use of plasma uracil measurements to detect dihydropyrimidine dehydrogenase (DPD) deficiency is one of the methods for preventing toxicities associated with fluoropyrimidines, including 5-Fluorouracil (5-FU). Unfortunately, this measurement is subject to variations, that may lead to unnecessary dosage reductions and therefore to a reduced efficacy of treatment. Recently, new factors such as hepatic and renal impairment have been proposed as also influencing uracil concentration.

Determining the Relative Affinity of ORPs for Lipid Ligands Using Fluorescence and Thermal Shift Assays.

Lipid transfer proteins (LTPs) are specialized proteins that convey specific lipids across the cytosol to regulate the lipid composition of organelles and the plasma membrane. Quantifying to which extent these LTPs recognize and transfer various lipid species and subspecies is of prime interest to define their cellular role(s). Here, we describe how to measure in vitro the relative affinity of Osh6p, a yeast phosphatidylserine (PS)/phosphatidylinositol 4-phosphate (PI(4)P) exchanger belonging to the oxysterol-binding protein(OSBP)-related protein (ORP) family, for PS and phosphoinositide subspecies.

[Tirzepatide : overview of clinical studies SURPASS in type 2 diabetes and SURMOUNT in obesity].

Tirzepatide is a unimolecular dual agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, which has been developed as once-weekly injection first for the treatment of type 2 diabetes (T2DM), then for the treatment of obesity. Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, semaglutide 1 mg, basal insulin and preprandial boluses of insulin lispro in six studies of the SURPASS programme. In the SURMOUNT programme, tirzepatide showed a marked reduction in body weight, never reached before with a drug, among people with obesity or overweight associated with complications linked to excess weight.

Methodological expectations for demonstration of health product effectiveness by observational studies.

The issue of assessing the effectiveness of health technologies (drugs, devices, etc.) through observational studies is becoming increasingly important as registration and market access agencies consider them in their evaluation process. In this context, observational studies must be able to provide real demonstrations of a level of reliability comparable to those produced by the conventional randomized controlled trial (RCT) approach.

Evaluation of efficacy and safety of rituximab in patients with progressive interstitial lung disease (ILD) with inflammatory component (EvER-ILD2): A multicentre double-blind placebo-controlled randomized trial.

Introduction: Progressive interstitial lung diseases (ILDs) are rare but severe diseases, with high mortality and morbidity, with no effective pharmacological treatment allowing for long-term remission, and therefore no clear therapeutic recommendations. Several ILDs present inflammatory components (ILDic), which may justify the use of anti-inflammatory and immunosuppressive drugs, as first-step therapy. Except for systemic sclerosis (SSc)-ILD and sarcoidosis, the evidence in favor of this approach is very weak.

Impact of pediatric continuous renal replacement therapy parameters on meropenem, piperacillin, and tazobactam pharmacokinetics: an model.

Background: Limited data exist on how continuous renal replacement therapy (CRRT) affects antimicrobial dosing in pediatric patients. This study examined the impact of pediatric CRRT parameters on the pharmacokinetics (PK) of meropenem, piperacillin, and tazobactam using an in vitro CRRT model.

Research Design And Methods: An in vitro CRRT model with a pediatric ST60 circuit was used to assess antimicrobial clearance during continuous veno-venous hemodialysis (CVVHD) or hemofiltration (CVVH).

A nuclear protein quality control system for elimination of nucleolus-related inclusions.

The identification of pathways that control elimination of protein inclusions is essential to understand the cellular response to proteotoxicity, particularly in the nuclear compartment, for which our knowledge is limited. We report that stress-induced nuclear inclusions related to the nucleolus are eliminated upon stress alleviation during the recovery period. This process is independent of autophagy/lysosome and CRM1-mediated nuclear export pathways, but strictly depends on the ubiquitin-activating E1 enzyme, UBA1, and on nuclear proteasomes that are recruited into the formed inclusions.

[A 2024 inventory in oncology news].

The editorial board of the Bulletin du cancer has compiled a summary of the news from 2024 in oncology, based on the main results presented at international congresses or published over the past year. After a year marked by the success of the Olympic Games, the selection of data is presented and discussed in podiums of three main results by topic. Emphasis is placed on studies that have an immediate impact on practice and on data that raise important questions for the year 2025.

Mass Spectrometry-Based Workflow for the Identification and Quantification of Alternative and Canonical Proteins in Pancreatic Cancer Cells.

The identification of small proteins and proteins produced from unannotated open reading frames (called alternative proteins or AltProts) has changed our vision of the proteome and has attracted more and more attention from the scientific community. Despite several studies investigating particular AltProts in diseases and demonstrating their importance in such context, we are still missing data on their expression and functions in many pathologies. Among these, pancreatic ductal adenocarcinoma (PDAC) is a particularly relevant case to study alternative proteins.

[Emergence of antifungal resistance: A creeping environmental threat?].

Antifungal resistance in humans is a clinical reality of increasing incidence that raises problems for patient care. In this current event, we discuss the link that can be made between the presence of antifungals in the environment and the development of resistance in humans, as well as the ecotoxicology of antifungals. The presence of antifungals in the environment has a health, but also an ecological impact.

Patient reactions to proactive tobacco cessation counseling using a decision aid in primary care: A qualitative study.

Medications for smoking cessation can double quit rates but are underused in primary care. This qualitative study aimed to explore: (1) patients' perspectives regarding having their general practitioner (GP) use a proactive approach to smoking cessation treatment using an encounter decision aid (DA), and (2) their expectations regarding their GP's role. We conducted qualitative semi-structured interviews with participants of the FIRST randomized trial (adults who smoke daily with any level of motivation for tobacco quitting).

Cytokines reprogram airway sensory neurons in asthma.

Nociceptor neurons play a crucial role in maintaining the body's homeostasis by detecting and responding to potential environmental dangers. However, this function can be detrimental during allergic reactions, as vagal nociceptors contribute to immune cell infiltration, bronchial hypersensitivity, and mucus imbalance in addition to causing pain and coughing. Despite this, the specific mechanisms by which nociceptors acquire pro-inflammatory characteristics during allergic reactions are not yet fully understood.

Tracking fructose 1,6-bisphosphate dynamics in liver cancer cells using a fluorescent biosensor.

HYlight is a genetically encoded fluorescent biosensor that ratiometrically monitors fructose 1,6-bisphosphate (FBP), a key glycolytic metabolite. Given the role of glucose in liver cancer metabolism, we expressed HYlight in human liver cancer cells and primary mouse hepatocytes. Through , , and experiments, we showed HYlight's ability to monitor FBP changes linked to glycolysis, not gluconeogenesis.

Dynamic pre-structuration of lipid nanodomain-segregating remorin proteins.

Remorins are multifunctional proteins, regulating immunity, development and symbiosis in plants. When associating to the membrane, remorins sequester specific lipids into functional membrane nanodomains. The multigenic protein family contains six groups, classified upon their protein-domain composition.

Non-medical nitrous oxide misuse: From identifying a signal to unprecedented addictovigilance network communication.

Addictovigilance is a French health monitoring system, composed of 13 centres distributed across the national territory, that aims to monitor cases of abuse, misuse, or use disorders related to psychoactive substances. Fulfilling these missions requires a regional network that ensures efficient information flow, dissemination to health authorities, and subsequent downward communication to prevent risks. This was illustrated through the example of nitrous oxide misuse.

Prenatal Exposure to Proton Pump Inhibitors and Risk of Serious Infections in Offspring During the First Year of Life: A Nationwide Cohort Study.

Introduction And Objective: Proton pump inhibitor (PPI) use in children increases the risk of infections, prompting inquiry into the impact of prenatal PPIs exposure on serious infections in offspring. As a research gap in this area exists, this study aimed to address it by assessing the association between prenatal PPIs exposure and serious infections in infants during their first year of life.

Methods: Using the French health insurance data warehouse (SNDS) (2013-2018), we conducted a retrospective cohort study on singleton, full-term liveborn non-immunocompromised infants, stratified by PPI use during the first three months of life (early-life use).

Beta-Lactam Antibiotic Exposure During Pediatric Extracorporeal Membrane Oxygenation: Retrospective Cohort Analysis of Drug Levels Using Standard Dosing, 2018-2020.

Objectives: Children on extracorporeal membrane oxygenation (ECMO) are at high risk of infection that may worsen prognosis. Even though treatment with beta-lactam antibiotics is frequent, dosing is not adapted to altered pharmacokinetic and pharmacodynamic characteristics of children on ECMO. There is, therefore, a risk of inadequate drug levels when using standard dosing.

Targeting n-myristoyltransferases promotes a pan-Mammarenavirus inhibition through the degradation of the Z matrix protein.

Several Old World and New World Mammarenavirus are responsible for hemorrhagic fever in humans. These enveloped viruses have a bi-segmented ambisense RNA genome that encodes four proteins. All Mammarenavirus identified to date share a common dependency on myristoylation: the addition of the C14 myristic acid on the N-terminal G2 residue on two of their proteins.