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International audience; Background: The European study MetaCardis aims to investigate the role of the gut microbiota in health and cardiometabolic diseases in France, Germany, and Denmark. To evaluate long-term diet-disease relationships, a food frequency questionnaire (FFQ) was found to be the most relevant dietary assessment method for the MetaCardis study.Objective: The objectives of this study were to describe the development of three semiquantitative online FFQs used in the MetaCardis study-one FFQ per country-and to assess the relative validity of the French MetaCardis FFQ.Design: The layout and format of the MetaCardis FFQ was based on the European Prospective Investigation of Cancer (EPIC)-Norfolk FFQ and the content was based on relevant European FFQs. Portion size and nutrient composition were derived from national food consumption surveys and food composition databases. To assess the validity of the French MetaCardis FFQ, a cross-sectional study design was utilized.Participants/setting: The validation study included 324 adults recruited between September 2013 and June 2015 from different hospitals in Paris, France.Main outcome measures: Food intakes were measured with both the French MetaCardis FFQ and 3 consecutive self-administered web-based 24-hour dietary recalls (DRs).Statistical analyses performed: Several measures of validity of the French MetaCardis FFQ were evaluated: estimations of food groups, energy, and nutrient intakes from the DRs and the FFQ, Spearman and Pearson correlations, cross-classification, and Bland-Altman analyses.Results: The French MetaCardis FFQ tended to report higher food, energy, and nutrient intakes compared with the DRs. Mean correlation coefficient was 0.429 for food, 0.460 for energy, 0.544 for macronutrients, 0.640 for alcohol, and 0.503 for micronutrient intakes. Almost half of participants (44.4%) were correctly classified within tertiles of consumption, whereas 12.9% were misclassified in the opposite tertile. Performance of the FFQ was relatively similar after stratification by sex.Conclusions: The French MetaCardis FFQ was found to have an acceptable level of validity and may be a useful instrument to rank individuals based on their food and nutrient intakes.

We present a fatal drug poisoning case involving venlafaxine (VEN). The deceased took his medication regularly (including 150 mg VEN twice daily), and nothing in the case or autopsy findings pointed towards suicide. The toxicological assessment concluded that the cause of death was most likely due to a poisoning with a combination of VEN, oxycodone and ethanol, and the manner of death was considered to be an accident. The blood concentration of VEN was high (4.5 mg/kg), and the ratio of the VEN metabolite O-desmethylvenlafaxine (ODV) to VEN was exceptionally low (0.006). Mechanistic pharmacokinetic simulations suggested that the low metabolite ratio was the result of combined poor metabolizer (PM) status of cytochrome P450 (CYP) 2C19 and CYP2D6. This hypothesis was confirmed by genetic analysis. Simulations revealed that it was likely that the combined missing CYP2D6 and CYP2C19 activity would cause higher concentrations of VEN, but the simulations also suggested that there could be additional reasons to explain the high VEN concentration found in this case. Thus, it seems likely that the potentially toxic VEN concentration was caused by reduced metabolic capacity. The simulations combined with genotyping were considered very useful in this fatal drug poisoning case. Keywords CYP2D6; CYP2C19; Venlafaxine; Poor metabolizer; Drug poisoning; Mechanistic pharmacokinetic simulation -------------------------------------------------------------------------------- We present a fatal drug poisoning case involving venlafaxine (VEN). The deceased took his medication regularly (including 150mg VEN twice daily), and nothing in the case or autopsy findings pointed towards suicide. The toxicological assessment concluded that the cause of death was most likely due to a poisoning with a combination of VEN, oxycodone and ethanol, and the manner of death was considered to be an accident. The blood concentration of VEN was high (4.5mg/kg), and the ratio of the VEN metabolite O-desmethylvenlafaxine (ODV) to VEN was exceptionally low (0.006). Mechanistic pharmacokinetic simulations suggested that the low metabolite ratio was the result of combined poor metabolizer (PM) status of cytochrome P450 (CYP) 2C19 and CYP2D6. This hypothesis was confirmed by genetic analysis. Simulations revealed that it was likely that the combined missing CYP2D6 and CYP2C19 activity would cause higher concentrations of VEN, but the simulations also suggested that there could be additional reasons to explain the high VEN concentration found in this case. Thus, it seems likely that the potentially toxic VEN concentration was caused by reduced metabolic capacity. The simulations combined with genotyping were considered very useful in this fatal drug poisoning case.

Introduction et but de l’etude Le but de l’etude europeenne MetaCardis est d’evaluer les relations qui existent entre les maladies cardiometaboliques et le microbiote intestinal. Sachant que l’alimentation module la composition du microbiote intestinal d’une part, et influe sur les risques de maladies cardiometaboliques d’autre part, les apports alimentaires des sujets francais, allemands et danois de l’etude MetaCardis ont ete mesures grâce a trois questionnaires de frequence alimentaire specialement developpes pour cette etude. Le but de ce travail etait d’evaluer la validite relative du questionnaire de frequence alimentaire developpe pour les sujets francais. Materiel et methodes Le questionnaire MetaCardis, developpe pour les sujets francais, se compose de 159 items qui mesurent les frequences de consommations d’aliments et de boissons sur les 12 derniers mois. Trois enregistrements de 24 heures auto-administres en ligne, completes a la meme periode que le questionnaire, ont servi de methode de reference (MR) pour l’etude de validite relative. Les apports alimentaires, energetiques et nutritionnels ont ete estimes a partir du questionnaire et de la MR, puis ont ete transformes, corriges et ajustes si necessaire. Les differences d’estimations d’apports entre les deux methodes ont ete evaluees selon le test t de Student ou le test des rangs signes de Wilcoxon. L’accord entre les apports alimentaires, energetiques et nutritionnels a ete evalue grâce aux correlations de Spearman et Pearson ainsi que la methode de Bland-Altman. Le taux d’erreurs de classification a ete evalue en calculant les tertiles et quintiles de distribution des apports nutritionnels. Resultats et analyse statistique Les analyses ont ete realisees a partir des donnees collectees aupres de 202 sujets de l’etude MetaCardis dont les recueils alimentaires ont ete juges valides. Les estimations d’apports alimentaires, energetiques et nutritionnels derivees du questionnaire etaient generalement plus elevees que celle derivees de la MR. Les coefficients de correlation moyens etaient de 0,43 pour les aliments, 0,37 pour l’energie, 0,49 pour les macronutriments, 0,63 pour l’alcool et 0,48 pour les micronutriments. Les analyses de Bland-Altman ont confirme la surestimation generale des apports estimes par le questionnaire. En moyenne, 44 % des sujets etaient correctement classes dans le meme tertile et 13 % etaient classes dans le tertile oppose. Les resultats obtenus en stratifiant par le sexe etaient similaires. Conclusion Le questionnaire de frequence alimentaire developpe pour les sujets francais de l’etude MetaCardis a montre avoir un niveau acceptable de validite. La surestimation des apports alimentaires et nutritionnels devra etre prise en compte lors de l’interpretation des resultats. Financement MetaCardis est un projet finance par le programme cadre de recherche europeen FP7 (HEALTH-F4-2012-305312), http://www.metacardis.net . Le promoteur du programme clinique est l’APHP.