Interventions for hyperhidrosis in secondary care : a systematic review and value-of-information analysis

Background: Hyperhidrosis is uncontrollable excessive sweating that occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. The management of hyperhidrosis is uncertain and variable. Objective: To establish the expected value of undertaking additional research to determine the most effective interventions for the management of refractory primary hyperhidrosis in secondary care. Methods: A systematic review and economic model, including a value-of-information (VOI) analysis. Treatments to be prescribed by dermatologists and minor surgical treatments for hyperhidrosis of the hands, feet and axillae were reviewed; as endoscopic thoracic sympathectomy (ETS) is incontestably an end-of-line treatment, it was not reviewed further. Fifteen databases (e.g. CENTRAL, PubMed and PsycINFO), conference proceedings and trial registers were searched from inception to July 2016. Systematic review methods were followed. Pairwise meta-analyses were conducted for comparisons between botulinum toxin (BTX) injections and placebo for axillary hyperhidrosis, but otherwise, owing to evidence limitations, data were synthesised narratively. A decision-analytic model assessed the cost-effectiveness and VOI of five treatments (iontophoresis, medication, BTX, curettage, ETS) in 64 different sequences for axillary hyperhidrosis only. Results and conclusions: Fifty studies were included in the effectiveness review: 32 randomised controlled trials (RCTs), 17 non-RCTs and one large prospective case series. Most studies were small, rated as having a high risk of bias and poorly reported. The interventions assessed in the review were iontophoresis, BTX, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland (e.g. laser, microwave). There is moderate-quality evidence of a large statistically significant effect of BTX on axillary hyperhidrosis symptoms, compared with placebo. There was weak but consistent evidence for iontophoresis for palmar hyperhidrosis. Evidence for other interventions was of low or very low quality. For axillary hyperhidrosis cost-effectiveness results indicated that iontophoresis, BTX, medication, curettage and ETS was the most cost-effective sequence (probability 0.8), with an incremental cost-effectiveness ratio of £9304 per quality-adjusted life-year. Uncertainty associated with study bias was not reflected in the economic results. Patients and clinicians attending an end-of-project workshop were satisfied with the sequence of treatments for axillary hyperhidrosis identified as being cost-effective. All patient advisors considered that the Hyperhidrosis Quality of Life Index was superior to other tools commonly used in hyperhidrosis research for assessing quality of life. Limitations: The evidence for the clinical effectiveness and safety of second-line treatments for primary hyperhidrosis is limited. This meant that there was insufficient evidence to draw conclusions for most interventions assessed and the cost-effectiveness analysis was restricted to hyperhidrosis of the axilla. Future work: Based on anecdotal evidence and inference from evidence for the axillae, participants agreed that a trial of BTX (with anaesthesia) compared with iontophoresis for palmar hyperhidrosis would be most useful. The VOI analysis indicates that further research into the effectiveness of existing medications might be worthwhile, but it is unclear that such trials are of clinical importance. Research that established a robust estimate of the annual incidence of axillary hyperhidrosis in the UK population would reduce the uncertainty in future VOI analyses

Identification of biologically active peptides derived from enzymatically treated porcine matrices

La biomasse animale issue de la filière porcine, qui est faiblement valorisée, nécessite la mise en œuvre de nouveaux procédés de diversification. L’identification de peptides bioactifs (PBs) est une voie prometteuse pour la valorisation de cette biomasse. Cela permet d’un point de vue environnemental de mieux rentabiliser les consommations en ressources naturelles (surface de culture, eau, énergie) ayant servi à l’alimentation des porcs, en fournissant un débouché économiquement intéressant à ces sous-produits. D’autre part, la génération de peptides bioactifs utilisables dans les domaines de la pharmacologie, la cosmétique, ou l’alimentation s’inscrit dans la demande croissante des consommateurs pour l’élaboration de molécules plus naturelles. L’objectif de ce projet est d’identifier des conditions d’hydrolyse optimales permettant de générer, à partir de sous-produits porcins, de nouvelles molécules bioactives à visée nutritionnelle ou médicale. Une étude de potentialité in silico est menée sur quatre matrices porcines (cœur, foie, poumon et muscle) afin d’évaluer leur capacité à générer des PBs, après hydrolyse enzymatique. De plus, la stabilité des peptides générés est testée en condition de digestion gastro-intestinale via l’utilisation d’un modèle statique. Finalement, le développement de la méthode à l’échelle pilote est réalisé. Les études in silico ont permis de sélectionner le couple d’enzymes papaïne/subtilisine présentant une forte potentialité dans la génération de peptides avec une activité antioxydante, antidiabétique (iDPP4) et antihypertensive (iECA) pour les quatre matrices d’étude. La validation in vitro, a confirmé la présence des activités antioxydante et iDPP4 dans les quatre hydrolysats générés avec la papaïne et la subtilisine. Il est noté que l’activité biologique des hydrolysats de cœur, de foie et de poumon est exacerbée au cours de la digestion gastro-intestinale. Les expérimentations sur la digestion d’un palet de porc supplémenté en hydrolysat de cœur ont montré que i) la température de cuisson (70°C ou 90°C) impacte peu le niveau des activités iDPP4 et antioxydante au cours de la digestion, ii) la supplémentation permet d’augmenter significativement l’activité iDPP4 par rapport à un échantillon témoin. Un effet plus modeste de cette supplémentation sur l’activité antioxydante a été observé et iii) l’activité antioxydante des palets de porc supplémentés augmente significativement (+40%) entre le compartiment gastrique et intestinal. Enfin, la méthodologie de génération des peptides bioactifs est transposable à l’échelle pilote moyennant l’utilisation d’enzymes commerciales et de paramètres d’hydrolyse adaptés. Les fractions peptidiques présentant une bioactivité significative pourront être valorisées comme ingrédients aromatiques et servir pour supplémenter des produits alimentaires dans le but d’obtenir des allégations de santé.The poorly valorized animal biomass from the pig sector requires the implementation of new recovery processes. The identification of bioactive peptides (BPs) is a promising way to valorize this biomass. From an environmental point of view, it is possible to reduce the consumption of natural resources (surface of culture, water, energy) having used for the feeding of the pigs, by providing an economically interesting outlet to these by-products. On the other hand, the generation of bioactive peptides that can be used in the fields of pharmacology, cosmetics or food is part of the growing consumer demand for the development of more natural molecules. The objective of this project is to identify optimal hydrolysis conditions allowing generating, from porcine by-products, new bioactive molecules for nutritional or medical purposes. An in silico potency study is conducted on four porcine products (heart, liver, lung and muscle) to evaluate their ability to generate PBs, based on the use of different enzymes. In addition, the stability of the generated peptides is evaluated in the gastrointestinal tract using an in vitro static model. Finally, the method for the generation of BPs is developed at a pilot scale. In silico studies allowed to select the papain / subtilisin pair of enzymes for the generation of the highest number of peptides with antioxidant, antidiabetic (DPP4i) and antihypertensive (ACEi) activities. In vitro validation confirmed the presence of antioxidant and DPP4i activities in the four hydrolysates generated with papain and subtilisin. The biological activity of heart, liver and lung hydrolysates increases during gastrointestinal digestion. Experiments on the digestion of a pork patty supplemented with heart hydrolysate have shown that i) the cooking temperature (70°C or 90°C) slightly modulates iDPP4 and antioxidant activities during digestion, ii) supplementation significantly increases iDPP4 activity compared to a control sample. A moderate effect of this supplementation on the antioxidant activity was observed and iii) the antioxidant activity of the supplemented pork patty increases significantly (+ 40%) between the gastric and intestinal compartment. In addition, the methodology for the generation of bioactive peptides is possible on a pilot scale with commercial enzymes and adapted hydrolysis parameters. Peptide fractions with significant bioactivity can be valued as aromatic ingredients and to supplement a food product for obtaining health claims

Le pharmacien d'officine vu par les adolescents (image, rôles attribués, attente, enquête réalisée dans la région nancéienne en 2005)

NANCY1-SCD Pharmacie-Odontologie (543952101) / SudocSudocFranceF

Improving Dietary Exposure Models by Imputing Biomonitoring Data through ABC Methods

International audienc

PBPK and population modelling to interpret urine cadmium concentrations of the French population

International audienc

New tools for evidence-based risk assessment of chemical mixtures

Risk assessment of chemical mixture has brought a number of scientific challenges, e.g. with respect to relevant data collection and robust quantitative methods to assess risks in humans. In this talk, the challenges will be presented in both regulatory and scientific viewpoints. Then, new tools for evidence-based risk assessment of chemical mixtures will be discussed in the context of the application of the systematic review methodology and meta-analysis to integrate metabolic interactions and toxicodynamic interactions for substances of priority in the food safety area. Examples of application and perspectives for embedding such techniques in routine risk assessment bodies will be presented

Identification of the main pesticide residue mixtures to which the French population is exposed

Owing to the intensive use of pesticides and their potential persistence in the environment, various pesticide residues can be found in the diet. Consumers are therefore exposed to complex pesticide mixtures which may have combined adverse effects on human health. By modelling food exposure to multiple pesticides, this paper aims to determine the main mixtures to which the general population is exposed in France. Dietary exposure of 3337 individuals from the INCA2 French national consumption survey was assessed for 79 pesticide residues, based on results of the 2006 French food monitoring programmes. Individuals were divided into groups with similar patterns of co-exposure using the clustering ability of a Bayesian nonparametric model. In the 5 groups of individuals with the highest exposure, mixtures are formed by pairs of pesticides with correlations above 0.7. Seven mixtures of 2-6 pesticides each were characterised. We identified the commodities that contributed the most to exposure. Pesticide mixtures can either be components of a single plant protection product applied together on the same crop or be from separate products that are consumed together during a meal. Of the 25 pesticides forming the mixtures, two-DDT and Dieldrin are known persistent organic pollutants. The approach developed is generic and can be applied to all types of substances found in the diet in order to characterise the mixtures that should be studied first because of their adverse effects on health. (C) 2013 Elsevier Inc. All rights reserved

Table ronde : Intégration de la biostimulation dans les itinéraires culturaux en combinaison avec les différents leviers de la transition agroécologique

National audienc

Inhalable delivery of AAV-based MRP4/ABCC4 silencing RNA prevents monocrotaline-induced pulmonary hypertension

International audienceThe ATP-binding cassette transporter MRP4 (encoded by ABCC4) regulates membrane cyclic nucleotides concentrations in arterial cells including smooth muscle cells. MRP4/ABCC4 deficient mice display a reduction in smooth muscle cells proliferation and a prevention of pulmonary hypertension in response to hypoxia. We aimed to study gene transfer of a MRP4/ABCC4 silencing RNA via intratracheal delivery of aerosolized adeno-associated virus 1 (AAV1.shMRP4 or AAV1.control) in a monocrotaline-induced model of pulmonary hypertension in rats. Gene transfer was performed at the time of monocrotaline administration and the effect on the development of pulmonary vascular remodeling was assessed 35 days later. AAV1.shMRP4 dose-dependently reduced right ventricular systolic pressure and hypertrophy with a significant reduction with the higher doses (i.e., >1011 DRP/animal) as compared to AAV1.control. The higher dose of AAV1.shMRP4 was also associated with a significant reduction in distal pulmonary arteries remodeling. AAV1.shMRP4 was finally associated with a reduction in the expression of ANF, a marker of cardiac hypertrophy. Collectively, these results support a therapeutic potential for downregulation of MRP4 for the treatment of pulmonary artery hypertension