[Fertility preservation for transmen]. / Place de la préservation de la fertilité dans le parcours des hommes transgenres.

The evolution of medical techniques as well as legislative changes currently allow to propose fertility preservation strategies in the context of transidentity. During "female to male" transition, androgen therapy has an impact on gonadal function since it usually induces a blockage of ovulation with amenorrhea. Although this effect is reversible when treatment is stopped, the possible long-term effects of testosterone treatment on future fertility or health of future children are poorly known. In addition, transitional surgeries definitely compromise fecundity when they include bilateral ovariectomy and/or hysterectomy. Yet, although long ignored or poorly expressed, the desire for parenthood is a reality in transgender men. Fertility preservation options in FtM transition rely on oocyte or ovarian tissue cryopreservation. The purpose of this review is to provide an overview of the literature regarding fertility preservation in transgender men. Although series remain limited, the increase in the number of recently published articles reflects the interest in improving the management of fertility issues in transgender men.

Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens.

PURPOSE: This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme. METHODS: Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC0-24 h/MIC ratio ≥ 125. RESULTS: A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance. CONCLUSION: The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC0-24 h to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m2) in children < 40 kg would be needed for the strains with highest MIC (16% of Pseudomonas aeruginosa and 47% of Staphylococcus aureus). The oral recommended dose of 20 mg/kg q12h (not exceeding 750 mg) would cover bacteria with MICs ≤ 0.125 but may be insufficient for bacteria with higher MIC and a dose increase according bodyweight and eGFR would be needed. These doses should be prospectively confirmed, and a therapeutic drug monitoring could be used to refine them individually.

Population Pharmacokinetics of Intravenous Ganciclovir and Oral Valganciclovir in a Pediatric Population To Optimize Dosing Regimens.

Ganciclovir is indicated for curative or preventive treatment of cytomegalovirus (CMV) infections. This study aimed to characterize ganciclovir pharmacokinetics, following intravenous ganciclovir and oral valganciclovir administration, to optimize dosing schemes. All children aged <18 years receiving ganciclovir or valganciclovir were included in this study. Pharmacokinetics were described using nonlinear mixed-effect modeling. Monte Carlo simulations were used to optimize the dosing regimen to maintain the area under the concentration-time curve (AUC) in the preventive or therapeutic target. Among the 105 children (374 concentration-time observations) included, 78 received intravenous (i.v.) ganciclovir, 19 received oral valganciclovir, and 6 received both drugs. A two-compartment model with first-order absorption for valganciclovir and first-order elimination best described the data. An allometric model was used to describe the bodyweight (BW) effect. Estimated glomerular filtration rate (eGFR) and medical status of critically ill children were significantly associated with ganciclovir elimination. Recommended doses were adapted for prophylactic treatment. To obtain a therapeutic exposure, doses should be increased to 40 mg/kg of body weight/day oral or 15 to 20 mg/kg/day i.v. in children with normal eGFR and to 56 mg/kg/day oral or 20 to 25 mg/kg/day i.v. in children with augmented eGFR. These doses should be prospectively confirmed, and therapeutic drug monitoring could be used to refine them individually. (This study has been registered at ClinicalTrials.gov under identifier NCT02539407.).

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus.

OBJECTIVES: Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens. METHODS: We included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT > 4 ×MIC. RESULTS: Thirty-nine patients with a median (range) age of 7 (0.1-17) years and a BW of 21 (2.8-79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m2 were the best schemes to reach the PK target of 100% fT> 4 ×MIC. CONCLUSIONS: In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT > 4 ×MIC in children with normal and augmented renal function.

Population Pharmacokinetics of Intravenous and Oral Acyclovir and Oral Valacyclovir in Pediatric Population To Optimize Dosing Regimens.

Acyclovir is an antiviral currently used for the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. This study aimed to characterize the pharmacokinetics (PK) of acyclovir and its oral prodrug valacyclovir to optimize dosing in children. Children receiving acyclovir or valacyclovir were included in this study. PK were described using nonlinear mixed-effect modeling. Dosing simulations were used to obtain trough concentrations above a 50% inhibitory concentration for HSV or VZV (0.56 mg/liter and 1.125 mg/liter, respectively) and maximal peak concentrations below 25 mg/liter. A total of 79 children (212 concentration-time observations) were included: 50 were taking intravenous (i.v.) acyclovir, 22 were taking oral acyclovir, and 7 were taking both i.v. and oral acyclovir, 57 for preventive and 22 for curative purposes. A one-compartment model with first-order elimination best described the data. An allometric model was used to describe body weight effect, and the estimated glomerular filtration rate (eGFR) was significantly associated with acyclovir elimination. To obtain target maximal and trough concentrations, the more suitable initial acyclovir i.v. dose was 10 mg/kg of body weight/6 h for children with normal renal function (eGFR ≤ 250 ml/min/1.73 m2) and 15 to 20 mg/kg/6 h for children with augmented renal clearance (ARC) (eGFR > 250 ml/min/1.73 m2). The 20-mg/kg/8 h dose for oral acyclovir and valacyclovir produced effective concentrations in more than 75% of children; however, a 15-mg/kg/6 h dose, if possible, is preferred. These doses should be prospectively confirmed, and therapeutic drug monitoring could be used to refine them individually. (This study has been registered at ClinicalTrials.gov under identifier NCT02539407.).

[Communication, information, and roles of parents in the pediatric intensive care unit: A review article]. / Communication, informations et place des parents en réanimation polyvalente pédiatrique : revue de la littérature.

Pediatric intensive care units (PICUs), whose accessibility to parents raises controversy, often operate under their own rules. Patients are under critical and unstable conditions, often in a life-threatening situation. In this context, the communication with the parents and their participation in the unit may be difficult. Information is a legal, deontological, and moral duty for caregivers, confirmed by the parents' needs. But the ability to enforce them is a challenge, and there is a gap between the theory and the reality. The communication between the parents and the physicians starts at the admission of the child with a family conference. According to the Société de réanimation de langue française (SRLF), the effectiveness of the communication is based on three criteria: the patients' comprehension, their satisfaction and their anxiety and depression. It has been shown that comprehension depends on multiple factors, related on the parents, the physicians, and the medical condition of the child. Regarding the parents' participation in the organization of the service, the parents' presence is becoming an important factor. In the PICU, the parents' status has evolved. They become a member of the care team, as a partner. The best interest of the child is always discussed with the parents, as the person knowing the best their child. This partnership gives them a responsibility, which is complementary to the physician's one, but does not substitute it.

[Blood transfusion and homosexuality: Ethical considerations]. / Transfusion et homosexualité : enjeux éthiques.

Since the context of the contaminated blood affair in 1983, the homosexual male were excluded from the blood donation in France. This exclusion is often called into question in several countries and is an actual lively debate. In France, reform process is ongoing for a practical change. Three issues make up the discussion: the infectious risk bound to sexual behavior, the feasibility of the powerful biological tests but having a silent window and the protection of the blood recipient. The infectious risk in the homosexual male is higher for the human immunodeficiency virus (HIV) than in the rest of the population. Even if every person has his/her own individual risk depending on his/her habits, everyone is confronted to the same law. The challenge is to build a consensus, along with the precautionary principle, the non-discrimination policy, and the individual and collective responsibilities.

[The practices of withdrawing artificial nutrition and hydration in the neonatal intensive care unit: a preliminary study]. / Étude pilote sur les pratiques de l'arrêt de la nutrition/hydratation artificielle en réanimation néonatale.

INTRODUCTION: Prematurity is one of the etiologies for severe neurological complications. Decisions to withdraw therapeutics, including artificial nutrition and hydration (ANH), are sometimes discussed. But can one withdraw ANH if the patient is a child suffering from severe neurological conditions, based on his best interests? The aim of this study was to further the understanding of the complexity of the withdrawal of ANH and its implementation in the neonatal intensive care unit (NICU). METHOD: This qualitative preliminary study based on a questionnaire was conducted on the staff in the NICU of the Pontoise medical center (France) in February 2012. The results were compared with the current knowledge on this issue and sociological data. RESULTS: Ten of the hospital staff members responded to the questionnaire: 60% considered ANH as a treatment, but the status of ANH (i.e., treatment or care) remained undefined for several respondents. Comparison with the withdrawal of mechanical ventilation or adult practices seemed to be inadequate. The staff had little experience in the domain and therefore few certainties on practices. Half of the respondents indicated that terminal sedation needed to be used. For the other half, it depended on the patient's pain. Timing was also an important notion given that the newborn is a being developing and evolving each in its own way. CONCLUSION: The withdrawal of ANH remains controversial in the NICU. Humanity, culture, and the relationship to others are ever present in the decision-making process, creating a moral opposition above and beyond ethical reflection.

First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene.

Major advances in the identification of genes implicated in idiopathic epilepsy have been made. Generalized epilepsy with febrile seizures plus (GEFS+), benign familial neonatal convulsions and nocturnal frontal lobe epilepsy, three autosomal dominant idiopathic epilepsies, result from mutations affecting voltage-gated sodium and potassium channels, and nicotinic acetylcholine receptors, respectively. Disruption of GABAergic neurotransmission mediated by gamma-aminobutyric acid (GABA) has been implicated in epilepsy for many decades. We now report a K289M mutation in the GABA(A) receptor gamma2-subunit gene (GABRG2) that segregates in a family with a phenotype closely related to GEFS+ (ref. 8), an autosomal dominant disorder associating febrile seizures and generalized epilepsy previously linked to mutations in sodium channel genes. The K289M mutation affects a highly conserved residue located in the extracellular loop between transmembrane segments M2 and M3. Analysis of the mutated and wild-type alleles in Xenopus laevis oocytes confirmed the predicted effect of the mutation, a decrease in the amplitude of GABA-activated currents. We thus provide the first genetic evidence that a GABA(A) receptor is directly involved in human idiopathic epilepsy.

[Essay about lacrymal proteins during sicca syndromes (author's transl)]. / Etude des protéines lacrymales au cours des syndromes secs.

Most of sicca syndromes are expressed in a modification of specifically lacrimal proteins. These modifications are involving:--perturbations in tears-electrophoresis, residing in a more or less important decrease of one or several lacrimal proteins,--a frequent sinking in rate of total lacrimal proteins,--a slump of antimicrobial property in tears. The electrophoretic modifications could serve for base to biological classification of sicca syndromes.