Philippe Lehert

University of Melbourne | MSD · faculty of Medicine

Aims: Anaphylaxis guidelines recommend intramuscular adrenaline, commonly 300 μg administered using an auto-injector device. However, overweight/obese patients may require a higher adrenaline dose for adequate cardiovascular (CV) response. This study evaluated the pharmacokinetics (PK) and pharmacodynamic (PD) CV profile after a single 500 μg adre...

Aim: To study the effect of metformin on plasma levels of arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), indicators of the nitric oxide pathway. Materials and methods: In this post hoc analysis of the HOME trial, we analysed plasma levels of arginine, ADMA and SDMA during the 4.3-year follow-up (comparing the...

Purpose Anti-Müllerian hormone (AMH) and antral follicle count (AFC) are correlated with the ovarian response, but their reliability and reproducibility are questionable. This large multicenter study describes their distribution, inter-cycle and inter-center variability, and their correlation. Methods A total of 25,854 IVF cycles among 15,219 pati...

Background Metformin has favorable effects on cardiovascular outcomes in both newly onset and advanced type 2 diabetes, as previously reported findings from the UK Prospective Diabetes Study and the HOME trial have demonstrated. Patients with type 2 diabetes present with chronically elevated circulating cardiac troponin levels, an established predi...

Introduction Pitolisant, agent éveillant agoniste inverse des récepteurs H3 (histamine) est un traitement de la somnolence diurne excessive (SDE) de la narcolepsie. Cette méta-analyse en réseau a pour objectif de comparer pitolisant jusqu’à 18 mg (P18) et Solriamfetol jusqu’à 150 mg (S150) en termes d’efficacité, de tolérance et de rapport bénéfice...

Introduction Pitolisant (Pit), agent éveillant antagoniste/agoniste inverse des récepteurs H3 (histamine) est un traitement de la somnolence diurne excessive (SDE) de la narcolepsie. La synthèse de son efficacité et de sa tolérance à 18 mg est démontrée versus placebo (pcb) via une méta-analyse des données individuelles patients à partir de 2 étude...

Introduction: Early prediction of survival without bronchopulmonary dysplasia (BPD) at 36 weeks of postmenstrual age remains challenging for infants born extremely preterm. We aimed to provide a new predictive model including variables available only at or soon after birth based on the literature and existing models. Methods: We conducted a syst...

Study question: Can the Poor Responder Outcome Prediction (PROsPeR) score identify live birth outcomes in subpopulations of patients with poor ovarian response (POR) defined according to the ESHRE Bologna criteria (female age, anti-Müllerian hormone (AMH), number of oocytes retrieved during the previous cycle (PNO) after treatment with originator...

Background Beyond antihyperglycemic effects, metformin may improve cardiovascular outcomes. Patients with type 2 diabetes often have an elevated plasma level of N-terminal pro B-type as a marker of (sub) clinical cardiovascular disease. We studied whether metformin was associated with a reduction in the serum level of N-terminal pro B-type natriure...

Objectif Pitolisant (P), agent éveillant agoniste inverse des récepteurs H3 (histamine) est un traitement de la somnolence diurne excessive (SDE) de la narcolepsie. La synthèse de son efficacité, sa tolérance à 20 mg versus placebo (pl) est démontrée via une méta-analyse des données individuelles patient à partir de 2 études chez des patients souff...

The Outcome study examines the fate of 4083 patients beginning IVF in 41 IVF centres, between January 2010 and December 2013. Cumulative live birth rate per patient (CLBR), the best reflection of IVF efficacy, is rarely presented in publications as it requires long-term follow-up, including all successive cycles, and pregnancies outcome. Analysis o...

Research question The benefit of Luteinizing Hormone supplementation (LHS) to FSH alone during Controlled Ovarian Stimulation (COS) remains controversial. Meta-analyses provided some evidence that the LHS benefit is limited to Poor Ovarian Responders (POR). Our objective is the assessment of the effectiveness of LHS on Cumulative Live Birth rate (C...

Aim: To assess the non-inferiority of pitolisant, a new compound for the relief of excessive daytime sleepiness (EDS) and cataplexy in narcolepsy, compared with modafinil. Methods: Randomized controlled trials (RCTs) in narcolepsy were searched systematically. Network meta-analysis (NMA) compared the efficacy and safety of pitolisant and modafin...

Objectif Deux symptômes caractérisent la narcolepsie : la somnolence diurne excessive (SDE) évaluée par le score d’Epworth (ESS), le test de Maintien de l’Éveil (TME) et les crises de cataplexie (CC). Des analyses multi-traitement (TT) comparatives des TT furent faites sur la SDE, les CC et la tolérance via une MAR. Méthodes La MAR fut faite selon...

Background Domains encompassing emotional disorders in relapsing-remitting MS (RRMS) patients are still unclear. Methods We performed a 24-month, multicenter, single-arm, prospective study. RRMS patients started IFN-β treatment at baseline. The primary endpoint was lack of emotional control, measured using the “Echelle d'HumeurDépressive” (EHD) sc...

Objective: To evaluate the safety and efficacy of cholecalciferol in patients with relapsing-remitting MS (RRMS). Methods: In this double-blind, placebo-controlled parallel-group, 2-year study, 181 patients with RRMS were randomized 1:1. Key inclusion criteria were a low serum 25-hydroxy vitamin D (25OHD) concentration (<75 nmol/L), a treatment...

Research question Can previous reports of a decreased probability of success in stimulated IVF cycles with premature rise of progesterone, as determined by progesterone concentration on HCG day (PHCG), be confirmed? Design Retrospective, observational, single-centre cohort study conducted on 5447 IVF and intracytoplasmic (ICSI) cycles carried out...

Matériel et méthode Etudier l'évolution de la douleur moyenne avec et sans manipulation ostéopathique chez 223 sujets recrutés car présentant une dysfonction vertébrale thoracique douloureuse à la palpation. J0 : Test et mesure d'EVA 1 pour les 223 sujets + inclusion par randomisation en 4 groupes C : Contrôle P : Placebo R : Réel M : Mensonge Pas...

Study Objectives Randomised clinical trials (RCTs) that compared the safety and efficacy of medical treatments for narcolepsy were analysed using network meta-analysis. Methods The RCTs in narcolepsy were searched. Network meta-analysis compared efficacy and safety of multiple treatments, multi-arm studies, and multi-criteria treatment decisions,...

Background: Multiple Sclerosis (MS) affects quality of life (QoL). Pharmacological treatments demonstrated benefits on clinical endpoints without improving QoL. We evaluated the effects of a group Cognitive Behavioural Therapy (CBT) on QoL disease progression.Methods: One-year multi-centre controlled multivariate-matched study was organised on Rela...

Aim: To determine the influence of polymorphisms on the effects of metformin on HbA1c, daily dose of insulin and metformin plasma concentration. Methods: In a post hoc analysis of a 4.3 year placebo-controlled randomized trial with 390 patients with Type 2 diabetes already on insulin, we analyzed the influence of polymorphisms in genes coding for...

Aims Metformin prevents weight gain, but it also leads to malabsorption of B12 and decreased ileal reabsorption of bile acids. Little is known whether metformin affects absorption of fat‐soluble vitamins like vitamin D. Therefore, we studied the effects of metformin, as compared to placebo, on serum levels of vitamin D (25‐hydroxyvitamin D [25(OH)D...

Aims: The prevalence of insomnia ranges from 36% to 91% in alcohol-dependent patients and may persist after alcohol withdrawal. Acamprosate has been shown to decrease insomnia in abstinent patients. Based on a large clinical trial database, the aim of the present study is to assess the efficacy of acamprosate in reducing insomnia, and if indeed it...

Objectif La narcolepsie est une maladie rare pour laquelle peu de traitements ont démontré dans des études randomisées et contrôlées (ERC) une efficacité sur les principaux symptômes qui sont la somnolence diurne excessive (SDE) mesurée par le score d’Epworth (ESS) ou le Test de maintien de l’éveil (MWT) et les crises de cataplexie rapportées par l...

Research Question A number of live-birth predictive models are available. Despite clinical interest, these are rarely used, owing to poor performance. In addition, no predictive models specifically for poor ovarian responders (POR) are available. The aim of the current project was to develop a clinically applicable tool for predicting live birth in...

Background: The administration of adrenaline is a life-saving intervention for anaphylactic reactions. However, it has been questioned whether the needle length of the autoinjectors is sufficient to achieve genuine intramuscular delivery and optimal bioavailability. Objective: To assess the adequacy of Anapen, which has a relatively short needle...

Aims: Metformin treatment is associated with a decrease of serum vitamin B12, but whether this reflects tissue B12 deficiency is controversial. We studied the effects of metformin on serum levels of methylmalonic acid (MMA), a biomarker for tissue B12 deficiency, and on onset or progression of neuropathy. Methods: In the HOME trial, 390 insulin-...

In this trial, 390 insulin-treated patients with type 2 diabetes were randomized to either placebo or metformin. Fasting levels of glucose, insulin and C peptide were determined at baseline, after 4 months and yearly thereafter for 4 years to assess fasting estimates of beta cell function. The primary endpoint was the fasting C peptide-to-glucose r...

[This corrects the article DOI: 10.1371/journal.pone.0173603.].

Metformin prevents weight gain in patients with type 2 diabetes (T2D). However, the mechanisms involved are still unknown. In this post-hoc analysis of the HOME trial, we aimed to determine whether metformin affects energy intake. Patients with T2D were treated with 850 mg metformin or placebo (1-3 times daily) added to insulin for 4.3 years. Dieta...

Objectives Vascular disease remains a leading cause of death. There are several vascular risk factors identified that can mitigate development of disease in ageing. We examine reported rates of modifiable risk factors in women responding to an online health questionnaire advertised by popular media. Methods A sample of 26 620 women aged over 18 wa...

Odds ratios–Likelihoods of not meeting different national guidelines based on risk category for other factors. Data are presented as: odds ratio (95% confidence interval). Non-significance is denoted by “NS”. Cells containing increased likelihoods are shaded. The odds ratios represent the likelihood of not meeting national guidelines for row elemen...

Objectif Evaluation de l’efficacite et la tolerance de pitolisant, antagoniste/agoniste inverse selectif du recepteur histamine H3 chez des patients narcoleptiques avec cataplexie. Methodes Patients adultes narcoleptiques (Epworth sleepiness scale (ESS) score ≥ 12) avec ≥ 3 cataplexies/semaine ont ete randomises et traites par pitolisant ou placebo...

Introduction Alors qu’une hypovitaminose D est un facteur de risque connu de developper une, l’utilisation de la Vitamine D (VitD) dans le traitement de la SEP n’est supportee par aucune evidence clinique. Objectifs Evaluer le benefice d’une supplementation en Vitamine D3 100 kUI chez des patients atteints d’une SEP-R avec un taux serique de VitD ≤...

Background: Histaminergic neurons are crucial to maintain wakefulness, but their role in cataplexy is unknown. We assessed the safety and efficacy of pitolisant, a histamine H3 receptor inverse agonist, for treatment of cataplexy in patients with narcolepsy. Methods: For this randomised, double-blind, placebo-controlled trial we recruited patien...

Unfortunately, the original version of this article [1] contained an error due to a typographical error in the computer code used. This meant the percentage improvement over baseline of the endpoints CMTNS,ONLS, 9HPT and DML was slightly increased. Therefore some of the values in Tables 3, 4, Additional file 4: Table S4 and Fig. 4 are incorrect. Ho...

Treatment of steroid-resistant acute graft-versus-host disease (GVHD) remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase 2 trials. This phase 3 randomized, open-label, multicenter trial compared inolimomab vs usual care in adult patients with steroid-refractory acute GVHD. Patients were...

Objective Multiple sclerosis (MS) severely affect quality of life (QoL). Pharmacological treatments demonstrated benefits on clinical endpoints, however, without proving a significant effect on QoL, we test the effect of a cognitive behavioural therapy (CBT) on QoL and investigate the association between QoL and illness progression. Materials/pati...

Background: Abnormalities in brain structure and function can occur several decades prior to the onset of cognitive decline. It is in the preceding decades that an intervention is most likely to be effective, when informed by an understanding of factors contributing to the disease prodrome. Few studies, however, have sufficient longitudinal data o...

Background & aims: Elafibranor is an agonist of the peroxisome proliferator activated receptor-α (PPARA) and peroxisome proliferator activated receptor-δ (PPARD). Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. We assessed the safety and efficacy of elafibranor in an international, rand...

A number of health and lifestyle factors are thought to contribute to cognitive decline associated with age but cannot be easily modified by the individual patient. We identified 12 individually modifiable interventions that can be implemented during midlife or later with the potential to ameliorate cognitive aging. For ten of these, we used PubMed...

Objective To describe sexual function of women in the late postmenopause and to investigate change from early postmenopause. Methods Cross sectional analysis of 2012/13 and longitudinal analysis from 2002/04 of the population based, Australian cohort of the Women’s Healthy Aging Project (WHAP), applying validated instruments: Short Personal Experi...

CMT1A is the most common inherited peripheral neuropathy. There is currently no approved treatment. We performed a meta-analysis including four randomized, double-blind, Placebo-controlled clinical trials to assess the disease progression after one year under Placebo, Ascorbic Acid (AA) or PXT3003, a combination of three repurposed drugs. We observ...

To validate the Sustained Attention to Response Task (SART) as a treatment effect measure in narcolepsy, and to compare the SART with the Maintenance of Wakefulness Test (MWT) and the Epworth Sleepiness Scale (ESS). Validation of treatment effect measurements within a randomized controlled trial (RCT). Ninety-five patients with narcolepsy with or w...

Sleep disturbance constitutes a major risk factor for drinking relapse after alcohol withdrawal and necessitates regular follow-up. We reported previously that the sum-score of the 4 sleep items of the Hamilton Anxiety and Depression Scales (the Short Sleep Index [SSI]) constitutes a valid and simple sleep measurement tool. The objective of this st...

Background Charcot-Marie-Tooth type 1A disease (CMT1A) is a rare orphan inherited neuropathy caused by an autosomal dominant duplication of a gene encoding for the structural myelin protein PMP22, which induces abnormal Schwann cell differentiation and dysmyelination, eventually leading to axonal suffering then loss and muscle wasting. We favour th...

Objective: We assessed the predictive value added by Anti-Mullerian Hormone (AMH) to currently validated live birth (LB) prediction models. Methods: Based on recent data from our center, we compared the external validity of the Templeton Model (TM) and its recent improvement (TMA) to select our model of reference. The added predictive value of A...

Multiple sclerosis (MS) has a major impact on quality of life (QoL). Coping strategies which may influence QoL have not been identified. Furthermore, there is no coping scale designed to measure coping in MS patients and concise enough for routine medical practice. We used 46 items and 7 coping dimensions; we successively reduced the minimum number...

Metformin is known to prevent weight gain and to improve insulin resistance. Its effects on beta-cell function are assumed to be neutral. To evaluate the effect of metformin on endogenous insulin secretion, we analyzed the plasma concentrations of C peptide ( immuno-assay) at baseline, after 4 months and yearly for 4 years in a placebo-controlled,...

IntroductionThere is a paucity of longitudinal studies assessing sexual function of women in the late postmenopause.AimThis study aims to describe sexual function of women in the late postmenopause and to investigate change from early postmenopause.Methods Cross-sectional analysis of 2012/13 and longitudinal analysis from 2002/04 of the population...

To determine the impact of the time interval from the end of sperm preparation (TSP) to intrauterine insemination (IUI) on the outcome. Prospective multicentre cohort study. Seven French centers (assisted reproduction group in northeastern France, four academic centers, and three clinics). Eight hundred sixty-two IUI cycles (709 patients) managed b...

The potential benefit of adding recombinant human luteinizing hormone (r-hLH) to recombinant human follicle-stimulating hormone (r-hFSH) during ovarian stimulation is a subject of debate, although there is evidence that it may benefit certain subpopulations, e.g. poor responders. A systematic review and a meta-analysis were performed. Three databas...

Narcolepsy is characterised by excessive daytime sleepiness (EDS) and cataplexy. Histamine neurons are crucial to maintain wakefulness. We assessed the safety and efficacy of pitolisant (previously called BF2.649), a selective histamine H3 receptor inverse agonist that activates these neurons, in patients with narcolepsy. For this double-blind, ran...