Paracetamol Concentrations and Time-Course of Ductus Arteriosus Diameter in Extremely Preterm Neonates: A Population Pharmacokinetic-Pharmacodynamic Analysis.

Background: Patent ductus arteriosus is a common complication of extreme prematurity. Prophylactic treatment with indomethacin or ibuprofen has shown efficacy on ductus closure but without reducing mortality and morbidity. Prophylactic treatment by paracetamol could be a safer alternative.

Ceftazidime-Avibactam Pharmacokinetic Comparative In Vivo/In Vitro Study in a Critically Ill Children Under High-Volume Continuous Venovenous Hemodiafiltration.

Ceftazidime-avibactam is a novel cephalosporin/beta-lactamase inhibitor combination developed to address increasing antimicrobial resistance. This report presents a comparative study of the pharmacokinetics of ceftazidime and avibactam, utilizing in vitro data derived from two experiments with continuous venovenous hemodiafiltration (CVVHDF) simulation and a comparison with a previously published in vivo case report. The results highlight the importance of therapeutic drug monitoring and the need for higher dosing or continuous infusion of ceftazidime-avibactam in critically ill children under crontinuous renal replacement therapy (CRRT).

Drugs for Procedural Sedation and Analgesia in Children: A Systematic Review and Meta-analysis.

Background And Objectives: Performing medical procedures on children can often be challenging because of the anxiety that these procedures may induce, the need for immobility that they may require, or age-related development capabilities. We assessed the effects of procedural sedation and analgesia drugs for anxiety management in children during medical procedures.

Methods: We searched PubMed Medline, Cochrane Library, American Academy of Pediatrics, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.

Comparison of human transplacental transfer of escitalopram, sertraline and paroxetine: an ex vivo cotyledon perfusion study.

Introduction: Depression is common in pregnant women and the decision to treat must consider potential risk to the fetus. Since data on the transplacental transfer of serotonin reuptake inhibitors (SSRIs) remain sparse, we aimed to characterize and compare the transplacental transfer of three commonly used SSRIs in pregnant women: escitalopram, sertraline and paroxetine.

Methods: Ex vivo human placental perfusions in dual recirculating configuration were performed for these three antidepressants with and without albumin over 3 h of perfusion.

Pregnancy-Related Complications in Osteogenesis Imperfecta.

Objective: To evaluate obstetric and perinatal outcomes of pregnancies among patients with osteogenesis imperfecta using the French National Health Insurance Database.

Methods: We conducted a retrospective cohort study. Pregnancies were identified with an algorithm specifically developed for the French National Health Insurance Database to identify delivery stays using a combination of International Classification of Diseases, Tenth Revision (ICD-10) discharge codes and medical procedures.

Population pharmacokinetic modelling of prednisolone in systemic lupus erythematosus patients: Analysis of exposure and disease activity.

Aims: Prednisone is a widely used glucocorticoid in the treatment of lupus, although its dosing is often determined empirically. Prednisolone, the active metabolite of prednisone, is found in its free form in the serum. The goal of this study was to develop a population pharmacokinetic model in patients with systemic lupus erythematosus (SLE) to forecast free prednisolone concentrations and its association with disease activity.

Population Pharmacokinetics of Elexacaftor, Tezacaftor and Ivacaftor in a Real-World Cohort of Adults with Cystic Fibrosis.

Background And Objectives: Elexacaftor-tezacaftor-ivacaftor (ETI), a combination of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, has become the therapeutic standard of care for most people with cystic fibrosis (pwCF). People with cystic fibrosis exhibit differences in CFTR genotypes and have important differences in phenotypic characteristics including age, body weight, pancreatic status, disease severity, and comorbidities. While these differences predict large interindividual variability (IIV) in ETI exposure, there is a unique dose regimen recommended for adults.

Elexacaftor/Tezacaftor/Ivacaftor Population Pharmacokinetics in Pediatric Patients With Cystic Fibrosis.

Elexacaftor/tezacaftor/ivacaftor (ETI) significantly improves treatment outcomes for people with cystic fibrosis (pwCF) with at least one F508del allele. In 2023, the Food and Drug Administration approved ETI for children with CF aged 2-5 years. However, real-world pharmacokinetic-pharmacodynamic data for ETI in pediatric and adult populations are still limited.

Assessment of the steady-state drug-drug interactions between dolutegravir and ritonavir-boosted darunavir in adolescents.

Objectives: DTG is primarily metabolized by the UDP-glycosyltransferase (UGT) 1A1, and to a lesser extent by the cytochrome P450 (CYP) 3A4. Co-administration of DRV/r has been reported to decrease DTG plasma concentrations. Our aim was to distinguish the extent of the drug-drug interactions between DRV/r and DTG, and to evaluate the consequences of this interaction, in adolescents at steady state.

Safety of ifosfamide during pregnancy: A comprehensive analysis.

Objective: Little is known regarding the safety of ifosfamide in pregnant women and some case reports were associated with oligohydramnios. In the study, we performed a comprehensive analysis of the available data regarding the safety of ifosfamide in pregnant women.

Material And Methods: First, we performed a case-by-case review of the cases related to ifosfamide use during pregnancy that were spontaneously reported in the French Pharmacovigilance Database.

Impact of clomiphene citrate on multiple gestation births and perinatal outcomes: a nationwide cohort study.

Objective: To evaluate the occurrence of multiple gestation birth and perinatal adverse outcomes in pregnancies resulting from clomiphene citrate (CC) treatment compared with nonexposed pregnancies.

Design: Nationwide cohort study in a university hospital-based research center.

Subjects: Pregnancies lasting >22 weeks of gestation, in women aged 18-43 years between 2013 and 2019, recorded in the French health data warehouse (Système National des Données de Santé).

Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease.

In sickle cell disease (SCD), the β6 substitution in the β-globin leads to red blood cell sickling. The transplantation of autologous, genetically modified hematopoietic stem and progenitor cells (HSPCs) is a promising treatment option for patients with SCD. We completed a Phase I/II open-label clinical trial (NCT03964792) for patients with SCD using a lentiviral vector (DREPAGLOBE) expressing a potent anti-sickling β-globin.

First real-world study of fetal therapy with CFTR modulators in cystic fibrosis: Report from the MODUL-CF study.

Background: We aimed to build a cohort of Maternal-Cystic Fibrosis (CF) fetal dyads treated in utero with Variant Specific Therapy (VST), to assess the efficacy on Meconium Ileus (MI) and potential adverse effects of treatment.

Methods: Dyads were included if the foetus had a genetic diagnosis of CF and carried at least one variant responsive to VST. Standardized assessment included pre-VST Magnetic Resonance Imaging (MRI), repeated ultrasound (US), and VST drug concentrations in cord blood, maternal and infant plasma.

CFTR modulators and pregnancy outcomes: Early findings from a nationwide cohort study.

Objectives: Recent therapeutic advances, mainly with the advent of CFTR modulators, have been associated with an increasing number of pregnancies in females with cystic fibrosis (fwCF). This study aimed to evaluate the safety of the use of CFTR modulators, specifically elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) during pregnancy.

Methods: A nationwide cohort study was conducted using the French health insurance data warehouse (SNDS), covering nearly all singleton pregnancies ending between January 2018 and December 2023.

Maternal and perinatal outcomes of sickle cell disease in pregnancy: A nationwide study in France.

This nationwide cohort study provides a comprehensive overview of maternal and perinatal outcomes associated with sickle cell disease (SCD) during pregnancy. Using the French national health database, all singleton pregnancy-related hospital discharges from 2013 to 2020 in women aged 15-55 (n = 5 752 080) were selected. Of these, 1022 births were to women with SCD, 308 of whom were on long-term treatment, that is, hydroxyurea (HU) and/or transfusion programme.

Risk of Neurodevelopmental Disorders in Children Exposed to HIV and Antiretrovirals In Utero: A National Cohort Study in France.

Background: The health of children exposed but uninfected by human immunodeficiency virus (HIV) requires long-term assessment, in particular in terms of neurological and cognitive development. Numerous confounding factors have hampered such assessment, and published data are contradictory.

Methods: Using data from the French National Health Data System from 2012 to 2022, we conducted a population-based matched cohort study on all live-born single children, including those born to mothers with HIV, all prenatally exposed to antiretrovirals (ARVs).

Quantification of maternal and fetal valaciclovir exposure in a pharmacokinetic study of cytomegalovirus-infected pregnant women treated to prevent vertical transmission.

Background: In cases of maternal primary infection with cytomegalovirus (CMV-MPI) maternal treatment with oral valaciclovir 8 g/day has been shown to reduce the risk of fetal infection. The pharmacological profile of this high dosage during pregnancy is not yet known.

Objectives: To quantify maternal-fetal exposure to valaciclovir 8 g/day in a population pharmacokinetic (popPK) study.

Birth defects reporting and the use of dydrogesterone: a disproportionality analysis from the World Health Organization pharmacovigilance database (VigiBase).

Study Question: Is there an association between dydrogesterone exposure during early pregnancy and the reporting of birth defects?

Summary Answer: This observational analysis based on global safety data showed an increased reporting of birth defects, mainly hypospadias and congenital heart defects (CHD), in pregnancies exposed to dydrogesterone, especially when comparing to progesterone.

What Is Known Already: Intravaginal administration of progesterone is the standard of care to overcome luteal phase progesterone deficiency induced by ovarian stimulation in ART. In recent years, randomized controlled clinical trials demonstrated that oral dydrogesterone was non-inferior for pregnancy rate at 12 weeks of gestation and could be an alternative to micronized vaginal progesterone.

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).

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.