An Update on Stiripentol Mechanisms of Action: A Narrative Review.

Stiripentol (Diacomit) (STP) is an orally active antiseizure medication (ASM) indicated as adjunctive therapy, for the treatment of seizures associated with Dravet syndrome (DS), a severe form of childhood epilepsy, in conjunction with clobazam and, in some regions valproic acid. Since the discovery of STP, several mechanisms of action (MoA) have been described that may explain its specific effect on seizures associated with DS. STP is mainly considered as a potentiator of gamma-aminobutyric acid (GABA) neurotransmission: (i) via uptake blockade, (ii) inhibition of degradation, but also (iii) as a positive allosteric modulator of GABA receptors, especially those containing α3 and δ subunits.

One last effort. Are high out-of-pocket payments at the end of life a fatality?

Only few studies outside of the US have addressed the issue of out-of-pocket payments (OOP) at the end of life because of a lack of data. We use an exclusive dataset from a major French health insurance company (MGEN), including claim data, both mandatory and voluntary health insurance details, income and individual characteristics, for individuals aged 65 or older who died in 2017. We address three main issues: (1) What is the magnitude of OOP in France at the end of life? (2) How are OOP distributed, and do they present a financial risk to patients? (3) What are the determinants of OOP and what health system reforms could reduce them? Our results indicate that OOP expenses increase in the last year of life and accelerate in the last trimester.

Mud-Based Construction Material: Promising Properties of French Gravel Wash Mud Mixed with Byproducts, Seashells and Fly Ash as a Binder.

The French gravel industry produces approximatively 6.5 million tons of gravel wash mud each year. This material offers very promising properties which require an in-depth characterization study before its use as a construction material, otherwise it is removed from value cycles by disposal in landfills.

A big-data approach to producing descriptive anthropometric references: a feasibility and validation study of paediatric growth charts.

Background: Both national and WHO growth charts have been found to be poorly calibrated with the physical growth of children in many countries. We aimed to generate new national growth charts for French children in the context of huge datasets of physical growth measurements routinely collected by office-based health practitioners.

Methods: We recruited 32 randomly sampled primary care paediatricians and ten volunteer general practitioners from across the French metropolitan territory who used the same electronic medical records software, from which we extracted all physical growth data for the paediatric patients, with anonymisation.

Are selection criteria for healthy pregnancies responsible for the gap between fetal growth in the French national Elfe birth cohort and the Intergrowth-21st fetal growth standards?

Background: The Intergrowth-21st (IG) project proposed prescriptive fetal growth standards for global use based on ultrasound measurements from a multicounty study of low-risk pregnancies selected using strict criteria. We examined whether the IG standards are appropriate for fetal growth monitoring in France and whether potential differences could be due to IG criteria for "healthy" pregnancies.

Method: We analysed data on femur length and abdominal circumference at the second and/or the third recommended ultrasound examination from 14 607 singleton pregnancies from the Elfe national birth cohort.

Parkinson disease male-to-female ratios increase with age: French nationwide study and meta-analysis.

Background: Parkinson's disease (PD) is 1.5 times more frequent in men than women. Whether age modifies this ratio is unclear.

Microorganisms linked to inflammatory bowel disease-associated dysbiosis differentially impact host physiology in gnotobiotic mice.

Studying host-microbiota interactions are fundamental to understanding the mechanisms involved in intestinal homeostasis and inflammation. In this work, we analyzed these interactions in mice that were mono-associated with six microorganisms that are representative of inflammatory bowel disease (IBD)-associated dysbiosis: the bacteria Bacteroides thetaiotaomicron, adhesive-invasive Escherichia coli (AIEC), Ruminococcus gnavus and Roseburia intestinalis; a yeast used as a probiotic drug, Saccharomyces boulardii CNCM I-745; and another yeast, Candida albicans. Extensive ex vivo analyses including colon transcriptomics, histology, immune response, bile acid metabolism and short-chain fatty acid production were studied.

Reassessment of stiripentol pharmacokinetics in healthy adult volunteers.

Because children who have been receiving stiripentol for the treatment of Dravet syndrome for more than 10 years are now becoming young adults, it is important to accurately characterize stiripentol pharmacokinetics in this age range. A double-blind placebo-controlled dose ranging study was therefore conducted to investigate the pharmacokinetics and tolerability of stiripentol in 12 healthy volunteers. Each subject received 3 single doses of stiripentol (500, 1000, and 2000 mg) separated by a wash-out period of 1 week.

Stiripentol in Dravet syndrome: results of a retrospective U.S. study.

Purpose: To review the efficacy and tolerability of stiripentol in the treatment of U.S. children with Dravet syndrome.

Adjustment disorder with anxiety in old age: comparing prevalence and clinical management in primary care and mental health care.

Purpose: Adjustment disorder with anxiety (AjD-A) is a common cause of severe anxiety symptoms, but little is known about its prevalence in old age.

Methods: This cross-sectional study examined the prevalence of AjD-A in outpatients over the age of 60 who consecutively consulted 34 general practitioners and 22 psychiatrists during a 2-week period. The diagnosis of AjD-A was obtained using the optional module for diagnostic of adjustment disorder of the Mini International Neuropsychiatric Interview (MINI).

Saccharomyces boulardii does not prevent relapse of Crohn's disease.

Background & Aims: Saccharomyces boulardii is a probiotic yeast that has been shown to have beneficial effects on the intestinal epithelial barrier and digestive immune system. There is preliminary evidence that S boulardii could be used to treat patients with Crohn's disease (CD). We performed a randomized, placebo-controlled trial to evaluate the effects of S boulardii in patients with CD who underwent remission during therapy with steroids or aminosalicylates.

[Adjustment disorders with anxiety. Clinical and psychometric characteristics in patients consulting a general practitioner].

Background: The DSM-IV and ICD-10 descriptions of adjustment disorders are broadly similar. Their main features are the following: the symptoms arise in response to a stressful event; the onset of symptoms is within 3 months (DSM-IV) or 1 month (ICD-10) of exposure to the stressor; the symptoms must be clinically significant, in that they are distressing and in excess of what would be expected by exposure to the stressor and/or there is significant impairment in social or occupational functioning (the latter is mandatory in ICD-10); the symptoms are not due to another axis I disorder (or bereavement in DSM-IV); the symptoms resolve within 6 months, once the stressor or its consequences are removed. Adjustment disorders are divided into subgroups based on the dominant symptoms of anxiety, depression or behaviour.

Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle.

Citrulline malate (CM; CAS 54940-97-5, Stimol®) is known to limit the deleterious effect of asthenic state on muscle function, but its effect under healthy condition remains poorly documented. The aim of this longitudinal double-blind study was to investigate the effect of oral ingestion of CM on muscle mechanical performance and bioenergetics in normal rat. Gastrocnemius muscle function was investigated strictly non-invasively using nuclear magnetic resonance techniques.

Nefopam pharmacokinetics in patients with end-stage renal disease.

Background: Treatment of intense postoperative pain in patients with end-stage renal disease (ESRD) is a recurrent problem for anesthesiologists because of the risk of accumulation of numerous molecules and their metabolites. Nefopam is a potent analgesic metabolized by the liver and weakly eliminated intact in urine that may offer advantages for use in patients with ESRD because it lacks respiratory-depressive effects. However, the effects of renal failure on nefopam disposition have never been investigated.

[Pascal's disease in 1647].

Blaise Pascal's serious physiological disorders could be the consequence of a long exposition to mercury fumes as he was studying the first device of vacuum. Weakness headache, paralysis of the lower limbs were described by his sisters. Probably such were the causes of his bad health and of the disorders which hit him until his death.

Beneficial effects of citrulline malate on skeletal muscle function in endotoxemic rat.

Although citrulline malate (CM; CAS 54940-97-5, Stimol) is used against fatigue states, its anti-asthenic effect remains poorly documented. The objective of this double-blind study was to evaluate the effect of oral ingestion of CM on a rat model of asthenia, using in situ (31)Phosphorus magnetic resonance spectroscopy ((31)P-MRS). Muscle weakness was induced by intraperitoneal injections of Klebsiella pneumoniae endotoxin (lipopolysaccharides at 3 mg/kg) at t(0) and t(0)+24 h.

Endotoxemia does not limit energy supply in exercising rat skeletal muscle.

Although depletion in high-energy phosphorylated compounds and mitochondrial impairment have been reported in septic skeletal muscle at rest, their impact on energy metabolism has not been documented during exercise. In this study we aimed to investigate strictly gastrocnemius muscle function non-invasively, using magnetic resonance techniques in endotoxemic rats. Endotoxemia was induced by injecting animals intraperitoneally at t(0) and t(0) + 24 h with Klebsiella pneumoniae lipopolysaccharides (at 3 mg kg(-1)).

Endotoxemia causes a paradoxical intracellular pH recovery in exercising rat skeletal muscle.

In resting skeletal muscle, endotoxemia causes disturbances in energy metabolism that could potentially disturb intracellular pH (pH(i)) during muscular activity. We tested this hypothesis using in situ (31)P-magnetic resonance spectroscopy in contracting rat gastrocnemius muscle. Endotoxemia was induced by injecting rats intraperitoneally at t(0) and t(0) + 24 h with Klebsiella pneumoniae endotoxin (lipopolysaccharides at 3 mg/kg) or saline vehicle.

Efficacy of etifoxine compared to lorazepam monotherapy in the treatment of patients with adjustment disorders with anxiety: a double-blind controlled study in general practice.

Adjustment Disorders With Anxiety (ADWA) account for almost 10% of psychologically motivated consultations in primary care. The aim of this double-blind randomised parallel group study was to compare (non-inferiority test) the efficacies of etifoxine, a non-benzodiazepine anxiolytic drug, and lorazepam, a benzodiazepine, for ADWA outpatients followed by general practitioners. 191 outpatients (mean age: 43, female: 66%) were assigned to receive etifoxine (50 mg tid) or lorazepam (0.

Randomized prospective study of the analgesic effect of nefopam after orthopaedic surgery.

Background: Balanced postoperative analgesia combines non-narcotic drugs and opioids. We organized a large study to evaluate nefopam analgesia and tolerance in combination with morphine for patient-controlled analgesia (PCA) after orthopaedic surgery.

Methods: Two hundred and one patients scheduled to undergo hip arthroplasty were included in this multicentre (n=24), double-blind, randomized study comparing nefopam (20 mg every 4 h for 24 h) with placebo, the first dose being infused peroperatively.

Comparative pharmacokinetics and pharmacodynamics of intravenous and oral nefopam in healthy volunteers.

To determine the pharmacokinetic, subjective effects of a single 20 mg dose of nefopam administered either intravenously or orally in healthy volunteers, twenty-four healthy Caucasian men received 20 mg nefopam orally+placebo intravenous infusion and placebo orally+intravenous infusion of 20 mg nefopam with one week interval, in a double-blind, double-dummy cross-over study. Nefopam and desmethyl-nefopam plasma concentrations were measured by HPLC with UV detection up to 48 hr after drug administration. Self-rating questionnaires (Mood and vigilance Visual Analogue Scales, Addiction Research Centre Inventory) and drug safety were investigated.

Effect of route of administration on the pharmacokinetic behavior of enantiomers of nefopam and desmethylnefopam.

Nefopam hydrochloride is a non-narcotic analgesic used parenterally and orally as a racemic mixture for the relief of postoperative pain. However, no information is presently available on the oral kinetics of (+) and (-) nefopam in humans. Also, nefopam is metabolized by N-demethylation but it is not known whether the desmethylnefopam enantiomers (DES1 and DES2) are present in plasma following intravenous (I.

Citrulline/malate promotes aerobic energy production in human exercising muscle.

Background: Previous studies have shown an antiasthenic effect of citrulline/malate (CM) but the mechanism of action at the muscular level remains unknown.

Objective: To investigate the effects of CM supplementation on muscle energetics.

Methods: Eighteen men complaining of fatigue but with no documented disease were included in the study.