AEROfen: protocol for a phase I, open-label, randomised crossover study evaluating the efficiency of nebulised fentanyl in healthy volunteers - comparing facial versus intranasal administration via pharmacometric modelling.

Introduction: Pain accounts for approximately 80% of emergency department admissions. While intravenous morphine titration is commonly used for severe pain, non-invasive alternatives that bypass intravenous access are needed. Nebulised fentanyl, combined with pupillometry for objective monitoring of opioid impregnation, may offer a rapid and safe alternative for pain management.

Effect of Alternative Administrations on P2Y12 Receptor Inhibitors' Pharmacokinetics and Pharmacodynamics: Systematic Review and Meta-Analysis.

Alternative administrations methods, such as chewing or crushing tablets, have been proposed to improve P2Y receptor inhibitors' absorption in acute and chronic coronary syndromes. This study aimed to evaluate the impact of these alternative strategies on the pharmacokinetics and pharmacodynamics of clopidogrel, ticagrelor, and prasugrel. PubMed, the Cochrane Library, and Web of Science were searched until March 07, 2025 for trials comparing at least one P2Y receptor inhibitor alternative administration method to the standard administration (swallowed integral tablets).

Population pharmacokinetics of cefazolin in neurosurgical antibiotic prophylaxis.

In neurosurgery, cefazolin (CFZ) is typically recommended at a dose of 2-gram within 60 minutes prior to surgical incision. However, due to the reported poor cerebrospinal fluid (CSF) penetration of CFZ, we conducted a population pharmacokinetic study to assess the adequacy of a 2-gram CFZ dosing regimen against the most common pathogens found in neurosurgical patients. If necessary, alternative CFZ dosing strategies were identified to achieve effective CSF concentrations.

Plasma metabolomics signatures predict COVID-19 patient outcome at ICU admission comparable to clinical scores.

SARS-CoV-2 significantly impacts the human metabolome. This study aims to evaluate the predictive capability of a comprehensive module clustering approach in plasma metabolomics for identifying the risk of critical complications in COVID-19 patients admitted to intensive care units (ICUs). We conducted a prospective monocenter study, gathering blood samples within 24 h of ICU admission, alongside clinical, biological, and demographic patient characteristics.

Assessing the Impact of Multiple Imputation Algorithms on Pharmacokinetic Model Performance: A Simulation-Based Study.

This study compared multiple imputation (MI) algorithms in a one-compartment pharmacokinetic (PK) scenario with oral absorption. Four covariates (two continuous, two dichotomous) linked to PK parameters were randomly removed under a missing completely at random (MCAR) mechanism. The aim was to identify which algorithm best preserves covariate distributions and PK parameter estimates.

Dynamic functional luminal imaging probe analysis of the anal sphincter opening function during straining in healthy volunteers.

The objective of the present study was to introduce a novel method of assessing anal canal opening in healthy volunteers (HV) using the EndoFLIP system. By analyzing dynamic loops during push maneuvers, the study aimed to identify the most reliable markers of anal canal opening function during this maneuver. Forty HV women were recruited and underwent anal canal assessments with the EndoFLIP system, both at rest and during push maneuvers.

Unraveling Ceftriaxone Dosing: Free Drug Prediction, Threshold Optimization, and Model Validation.

Ceftriaxone is pivotal in treating severe infections; however, predicting unbound plasma ceftriaxone (CEF) from total ceftriaxone (CEF) remains challenging. This study aimed to (1) predict CEF from CEF, (2) determine optimal target for CEF trough concentration in plasma, (3) perform an external validation of published models, and (4) to ascertain whether the CEF dosing regimen was sufficient to achieve the therapeutic objectives. CEF predictions based on CEF were evaluated using previously published models.

Multiple sclerosis and bowel symptoms: Frequency and barriers to their management.

Background: The frequency of bowel symptoms (BSs) is still a matter for debate in multiple sclerosis (MS) patients. However, BSs have been shown to cause significant distress. Our study aimed to (i) investigate the frequency of BSs, particularly those that are not managed, (ii) identify potential predictors for help-seeking care for patients with BSs, and (iii) evaluate the ability of the Neurogenic Bowel Dysfunction (NBD) score to screen for BSs.

Changes in carotid arterial wall viscosity and carotid arterial stiffness in type 2 diabetes patients.

Background And Aims: Changes in arterial wall viscosity (AWW) and stiffness during type 2 diabetes (T2D) have been little investigated. We explored changes in carotid AWV considering change in arterial stiffness and loading conditions, in patients with T2D.

Methods: This cross-sectional, monocentric study compared 19 middle-aged patients with T2D to 30 non-diabetic (ND) controls.

Inhibition of Soluble Epoxide Hydrolase Does Not Promote or Aggravate Pulmonary Hypertension in Rats.

Inhibitors of soluble epoxide hydrolase (sEH), which catalyzes the hydrolysis of various natural epoxides to their corresponding diols, present an opportunity for developing oral drugs for a range of human cardiovascular and inflammatory diseases, including, among others, diabetes and neuropathic pain. However, some evidence suggests that their administration may precipitate the development of pulmonary hypertension (PH). We thus evaluated the impact of chronic oral administration of the sEH inhibitor TPPU (N-[1-(1-Oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl]-urea) on hemodynamics, pulmonary vascular reactivity, and remodeling, as well as on right ventricular (RV) dimension and function at baseline and in the Sugen (SU5416) + hypoxia (SuHx) rat model of severe PH.

Population Pharmacokinetics of Levosimendan and its Metabolites in Critically Ill Neonates and Children Supported or Not by Extracorporeal Membrane Oxygenation.

Background: Levosimendan (LVSMD) is a calcium-sensitizer inotropic and vasodilator agent whose use might have a beneficial effect on the weaning of venoarterial extracorporeal membrane oxygenation (VA-ECMO). In light of LVSMD pharmacological characteristics, we hypothesized that ECMO may induce major pharmacokinetic (PK) modifications for LVSMD and its metabolites.

Objective: The aim of this study was to investigate the PK of LVSMD and its metabolites, and to assess the effects of ECMO on PK parameters.

CRISPR/Cas9-mediated inactivation of the phosphatase activity of soluble epoxide hydrolase prevents obesity and cardiac ischemic injury.

Introduction: Although the physiological role of the C-terminal hydrolase domain of the soluble epoxide hydrolase (sEH-H) is well investigated, the function of its N-terminal phosphatase activity (sEH-P) remains unknown.

Objectives: This study aimed to assess in vivo the physiological role of sEH-P.

Methods: CRISPR/Cas9 was used to generate a novel knock-in (KI) rat line lacking the sEH-P activity.

Relationship between anal functional lumen imaging probe (EndoFLIP®) results and the clinical presentation of faecal incontinence.

Aim: Faecal incontinence (FI) subtypes (urge, passive, mixed) are linked to the physiopathological mechanism of FI. Previous studies have failed to demonstrate a consistent relationship between FI subtype and anal sphincter dysfunction. Our aim was to evaluate the relationship between anal sphincter function, assessed using the new EndoFLIP® technology, and FI subtype.

Adaptation of Arterial Wall Viscosity to the Short-Term Reduction of Heart Rate: Impact of Aging.

Background Changes in arterial wall viscosity, which dissipates the energy stored within the arterial wall, may contribute to the beneficial effect of heart rate (HR) reduction on arterial stiffness and cardiovascular coupling. However, it has never been assessed in humans and could be altered by aging. We evaluated the effect of a selective HR-lowering agent on carotid arterial wall viscosity and the impact of aging on this effect.

Pharmacokinetic modeling of morphine and its glucuronides: Comparison of nebulization versus intravenous route in healthy volunteers.

Intravenous (i.v.) morphine is a safe, robust, and recommended treatment for severe pain using the titration principle.

Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension?

Cardiovascular diseases (CVD) are the leading cause of premature death and disability in humans that are closely related to lipid metabolism and signaling. This study aimed to assess whether circulating lysophospholipids (LPL), lysophosphatidic acids (LPA) and monoacylglycerols (MAG) may be considered as potential therapeutic targets in CVD. For this objective, plasma levels of 22 compounds (13 LPL, 6 LPA and 3 MAG) were monitored by liquid chromatography coupled with tandem mass spectrometry (HPLC/MS) in different rat models of CVD, i.

Fostering global data sharing: highlighting the recommendations of the Research Data Alliance COVID-19 working group.

The systemic challenges of the COVID-19 pandemic require cross-disciplinary collaboration in a global and timely fashion. Such collaboration needs open research practices and the sharing of research outputs, such as data and code, thereby facilitating research and research reproducibility and timely collaboration beyond borders. The Research Data Alliance COVID-19 Working Group recently published a set of recommendations and guidelines on data sharing and related best practices for COVID-19 research.

Preservation of epoxyeicosatrienoic acid bioavailability prevents renal allograft dysfunction and cardiovascular alterations in kidney transplant recipients.

This study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia-reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery.

Pharmacogenetics of Direct Oral Anticoagulants: A Systematic Review.

Dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban are direct oral anticoagulants (DOACs). Their inter-individual variability in pharmacodynamics and pharmacokinetics (transport and metabolism) is high, and could result from genetic polymorphisms. As recommended by the French Network of Pharmacogenetics (RNPGx), the management of some treatments in cardiovascular diseases (as antiplatelet agents, oral vitamin K antagonists, and statins) can rely on genetic testing in order to improve healthcare by reducing therapeutic resistance or toxicity.

Ten-year Evaluation of a Large Retrospective Cohort Treated by Sacral Nerve Modulation for Fecal Incontinence: Results of a French Multicenter Study.

Objective: The aim of this study was to assess the effectiveness of sacral nerve modulation (SNM) in a large cohort of patients implanted for at least 10 years, quantify adverse event rates, and identify predictive factors of long-term success.

Summary Background Data: Few studies have evaluated the long-term success of SNM.

Methods: Data collected prospectively from patients implanted for fecal incontinence (FI) in 7 French centers between January 1998 and December 2008 were retrospectively analyzed.