Biomarqueurs métabolomiques en relation avec les problèmes de comportement auprès de jeunes Inuit du Nunavik

L’obésité et la résistance à l’insuline sont associées avec les troubles de l’humeur ainsi que des concentrations plasmatiques élevées en acides aminés ramifiés (BCAAs : isoleucine, leucine et valine) et en acides aminés aromatiques (AAAs : phénylalanine et tyrosine). Étant donné que les AAAs sont des précurseurs de neurotransmetteurs clés et que leur apport au cerveau est concurrentiel à celui des BCAAs en raison de leur transporteur commun, nous avons exploré la relation entre les biomarqueurs métabolomiques (BCAAs et AAAs) et les problèmes de comportement auprès de jeunes Inuit du Nunavik. L’analyse inclut 141 jeunes ayant participé au début du suivi (2005-2010) de la Nunavik Child Development Study et au suivi à l’adolescence (2013-2015). Les concentrations plasmatiques de BCAAs et AAAs ont été mesurées au début du suivi et catégorisées en tertiles du ratio des BCAAs sur les AAAs (BCAA/AAA). Les problèmes de comportement ont été évalués à l’adolescence à l’aide du Youth Self-Report (YSR) du Child Behavior Checklist (CBCL). La relation entre les tertiles de BCAA/AAA et les scores moyens des syndromes du YSR a été évaluée à l'aide de modèles linéaires généraux. Nous avons noté que les scores moyens des syndromes de problèmes internalisés (Ptendance = 0,05) et de plaintes somatiques (Ptendance = 0,01) tendent à augmenter avec l’élévation du ratio BCAA/AAA. Aucune relation statistiquement significative n’a été trouvée pour les scores de problèmes externalisés et d’attention. Nous avons observé que les scores de problèmes internalisés ainsi que les sous-scores de plaintes somatiques augmentent (Ptendance < 0,05) avec le ratio BCAA/AAA chez les jeunes de statut pondéral normal, mais non parmi ceux en surpoids ou en obésité. Nos résultats suggèrent qu’un ratio élevé de BCAA/AAA est associé aux problèmes de comportement chez les jeunes, essentiellement aux problèmes de type internalisés.Obesity and insulin resistance are associated with mood disorders and elevated plasma concentrations of branched-chain amino acids (BCAAs: isoleucine, leucine and valine), and aromatic amino acids (AAAs: phenylalanine and tyrosine). Because AAAs are precursors of key neurotransmitters and their uptake into the brain is competitive with respect to the uptake of BCAAs via their transport through the same carrier, we explored the relationship between metabolomic biomarkers (BCAAs and AAAs) and behavioral problems among young Inuit from Nunavik. The current analysis includes 141 youth who participated in the Nunavik Child Development Study baseline (2005-2010) and adolescent follow-up (2013-2015). BCAA and AAA plasma concentrations were measured at baseline and categorised in tertiles of the ratio of BCAAs to AAAs (BCAA/AAA). Behavioral problems were assessed during adolescence with the Youth Self-Report (YSR) from the Child Behavior Checklist (CBCL). The relationship between tertiles of BCAA/AAA and mean scores of YSR syndromes was assessed with general linear models. We noted a trend toward a higher mean scores of internalizing problems (Ptrend=0.05) and somatic complaints (Ptrend=0.01) syndromes with higher BCAA/AAA ratio. No statistically-significant relationship was noted for externalizing and attention problems scores. We observed higher (Ptrend < 0.05) internalizing problems and somatic complaints syndrome scores with a higher ratio of BCAA/AAA among normal weight participants, but not among overweight or obese. Our results suggest that an elevated BCAA/AAA ratio is associated with behavioral problems among youth, mainly internalizing problems

Exposure to toxic metals and polychlorinated biphenyls of adolescents and adults from two atolls in the Tuamotu Archipelago (French Polynesia)

International audienc

Nickel and associated metals in New Caledonia Exposure levels and their determinants

International audienceThe ultramafic massifs of the New Caledonian archipelago contain about 10% of the world's nickel reserves, which also contain significant but lower amounts of cobalt, chromium, and manganese. Natural erosion of these massifs and mining activities may contribute to the exposure of local populations to these metals through contamination of air, food, and water resources. We conducted a biomonitoring survey to evaluate exposure to these four metals and its main determinants by constructing a stratified sample of 732 adults and children (> 3 years old) from visitors to 22 health centers across the archipelago. Urine was collected and analyzed by inductively-coupled plasma mass spectrometry to determine metal concentrations. A face-to-face interview was conducted to document sociodemographic characteristics, lifestyle and dietary habits, and residence-mine distance. Environmental samples (soil, house dust, water, and foodstuffs) were collected from two areas (one with and one without mining activity) to delineate determinants of exposure in more detail. Nickel and chromium were metals with the highest concentrations found in urine, especially in children, at levels exceeding reference values derived from representative national surveys elsewhere throughout the world (for children 4.7 mu g/g creatinine for nickel and 0.50 mu g/g creatinine for chromium) 13% of children exceeded the reference value for nickel and 90% for chromium. Large variations were observed by region, age, and sex. In this geological setting, urinary and environmental nickel concentrations appear to be driven mainly by soil content. This is the first archipelago-wide survey of metal exposure in New Caledonia. The potential health consequences of this chronic high exposure need to be assessed

METEXPO : Niveaux d'imprégnation et déterminants de l'exposition humaine aux métaux. Tome Nickel et Santé

Environ un tiers de la superficie de la Nouvelle-Calédonie est recouverte de formationsgéologiques riches en métaux d’intérêt tels que le nickel (Ni) et le cobalt (Co), maiségalement le chrome (Cr) et le manganèse (Mn).La présence de ces formations constitue une source potentielle d’exposition des populationscalédoniennes à ces éléments traces métalliques (ETM), notamment à proximité des zonesoù le couvert végétal est dégradé voire absent.Au droit de ces zones, les processus d’érosion chimique et mécanique sont particulièrementactifs et conduisent à la libération des ETM qui sont ensuite dispersés dans l’environnementpar voie aérienne (vent) ou par les écoulements d’eau de surface.Ces ETM sont donc susceptibles de se retrouver dans :- l’eau des creeks et rivières, contaminant les captages d’eau destinée à laconsommation humaine, mais également certains produits de la pêche (crevettesde creek et poissons),- l’eau du lagon contaminant les produits de la pêche lagonaire (coquillages,poissons et crustacés),- les sols alluvionnaires cultivés contaminant les cultures qui y sont produites,- les poussières qui se déposent dans les habitations ou à proximité susceptiblesd’être inhalées ou avalées.Toutes ces voies sont susceptibles de contribuer à l’exposition à ces ETM des populationscalédoniennes. Et ce d’autant plus que l’intégrité du couvert végétal des massifsultramafiques calédoniens subit depuis plusieurs décennies différents types de pressions quicontribuent à sa dégradation. Les trois principales pressions à l’origine de ces dégradationssont les feux de brousse, les ongulés envahissants (cerfs et cochons sauvages), ainsi quel’activité minière. Cette dernière pression, outre le fait qu’elle participe à l’accentuation desprocessus d’érosion, est également susceptible d’amplifier les émissions aériennes depoussières chargées en ETM via les travaux d’excavation, le roulage des engins miniers, lesactivités de concassage et criblage effectuées sur site ou au travers les émissionsatmosphériques des usines métallurgiques.A ce jour aucune étude n’avait été menée pour évaluer le risque potentiel d’exposition despopulations calédoniennes aux ETM. Il n’existe a priori aucune donnée quant aux niveauxd’imprégnation de la population générale néo-calédonienne à ces quatre métaux

Niveaux d'imprégnation et déterminants de l'exposition humaine aux métaux en Nouvelle-Calédonie. Rapport scientifique final

- Ce rapport du programme Métexpo « Niveaux d’imprégnation et déterminants de l’exposition humaine aux métaux » constitue le volume 3 (sur 4) du programme intégré « Dispersion et exposition humaine aux métaux en Nouvelle-Calédonie » composé de 3 projets (DMML, Dynamine, Métexpo) étudiant les métaux et leur toxicité.- Le programme Métexpo a proposé une étude de biosurveillance visant à : - (i) évaluer l’exposition de la population néo-calédonienne aux quatre métaux cibles Ni, Cr, Co et Mn ; - (ii) évaluer l’existence d’une surexposition à ces éléments traces métalliques (ETM) des populations vivant au sein des régions ultramafiques du territoire ; - (iii) évaluer l'influence des exploitations minières sur ces niveaux d’exposition.- L’étude comportait deux phases : la première phase consistait à obtenir une « photographie » du niveau d’exposition de la population générale de Nouvelle-Calédonie au Ni, Co, Cr et Mn. La seconde phase cherchait à identifier les principales sources de contamination de la population générale vivant dans des zones sur sites ultramafiques avec ou sans activité minière à proximité.- A ce jour aucune étude n’avait été menée pour évaluer le risque potentiel d’exposition des populations calédoniennes aux ETM. Il n’existe a priori aucune donnée quant aux niveaux d’imprégnation de la population générale néo-calédonienne à ces quatre métaux

Overweight and obesity prevalence among school-aged Nunavik Inuit children according to three BMI classification systems

Purpose Little is known about the suitability of three commonly used body mass index (BMI) classification system for Indigenous children. This study aims to estimate overweight and obesity prevalence among school-aged Nunavik Inuit children according to International Obesity Task Force (IOTF), Centers for Disease Control and Prevention (CDC), and World Health Organization (WHO) BMI classification systems, to measure agreement between those classification systems, and to investigate whether BMI status as defined by these classification systems is associated with levels of metabolic and inflammatory biomarkers. Methods Data were collected on 290 school-aged children (aged 8–14 years; 50.7% girls) from the Nunavik Child Development Study with data collected in 2005–2010. Anthropometric parameters were measured and blood sampled. Participants were classified as normal weight, overweight, and obese according to BMI classification systems. Weighted kappa (¿w) statistics assessed agreement between different BMI classification systems, and multivariate analysis of variance ascertained their relationship with metabolic and inflammatory biomarkers. Results The combined prevalence rate of overweight/obesity was 26.9% (with 6.6% obesity) with IOTF, 24.1% (11.0%) with CDC, and 40.4% (12.8%) with WHO classification systems. Agreement was the highest between IOTF and CDC (¿w = .87) classifications, and substantial for IOTF and WHO (¿w = .69) and for CDC and WHO (¿w = .73). Insulin and high-sensitivity C-reactive protein plasma levels were significantly higher from normal weight to obesity, regardless of classification system. Among obese subjects, higher insulin level was observed with IOTF. Conclusions Compared with other systems, IOTF classification appears to be more specific to identify overweight and obesity in Inuit children

Regional variation in the potentially inappropriate first-line use of fluoroquinolones in Canada as a key to antibiotic stewardship? A drug utilization review study

Background Serious adverse effects of fluoroquinolone antibiotics have been described for more than decade. Recently, several drug regulatory agencies have advised restricting their use in milder infections for which other treatments are available, given the potential for disabling and possibly persistent side effects. We aimed to describe variations in fluoroquinolone use for initial treatment of urinary tract infection (UTI), acute bacterial sinusitis (ABS), and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the outpatient setting across Canada. Methods Using administrative health data from six provinces, we identified ambulatory visits with a diagnosis of uncomplicated UTI, uncomplicated AECOPD or ABS. Antibiotic exposure was determined by the first antibiotic dispensed within 5 days of the visit. Results We identified 4,303,144 uncomplicated UTI events among 2,170,027 women; the proportion of events treated with fluoroquinolones, mostly ciprofloxacin, varied across provinces, ranging from 18.6% (Saskatchewan) to 51.6% (Alberta). Among 3,467,678 ABS events (2,087,934 patients), between 2.2% (Nova Scotia) and 11.2% (Ontario) were dispensed a fluoroquinolone. For 1,319,128 AECOPD events among 598,347 patients, fluoroquinolones, mostly levofloxacin and moxifloxacin, ranged from 5.8% (Nova Scotia) to 35.6% (Ontario). The proportion of uncomplicated UTI and ABS events treated with fluoroquinolones declined over time, whereas it remained relatively stable for AECOPD. Conclusions Fluoroquinolones were commonly used as first-line therapies for uncomplicated UTI and AECOPD. However, their use varied widely across provinces. Drug insurance formulary criteria and enforcement may be a key to facilitating better antibiotic stewardship and limiting potentially inappropriate first-line use of fluoroquinolones.Pharmaceutical Sciences, Faculty ofNon UBCAnesthesiology, Pharmacology and Therapeutics, Department ofReviewedFacult

Validity of an algorithm to identify cardiovascular deaths from administrative health records: a multi-database population-based cohort study

Background Cardiovascular death is a common outcome in population-based studies about new healthcare interventions or treatments, such as new prescription medications. Vital statistics registration systems are often the preferred source of information about cause-specific mortality because they capture verified information about the deceased, but they may not always be accessible for linkage with other sources of population-based data. We assessed the validity of an algorithm applied to administrative health records for identifying cardiovascular deaths in population-based data. Methods Administrative health records were from an existing multi-database cohort study about sodium-glucose cotransporter-2 (SGLT2) inhibitors, a new class of antidiabetic medications. Data were from 2013 to 2018 for five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, Quebec) and the United Kingdom (UK) Clinical Practice Research Datalink (CPRD). The cardiovascular mortality algorithm was based on in-hospital cardiovascular deaths identified from diagnosis codes and select out-of-hospital deaths. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for the cardiovascular mortality algorithm using vital statistics registrations as the reference standard. Overall and stratified estimates and 95% confidence intervals (CIs) were computed; the latter were produced by site, location of death, sex, and age. Results The cohort included 20,607 individuals (58.3% male; 77.2% ≥70 years). When compared to vital statistics registrations, the cardiovascular mortality algorithm had overall sensitivity of 64.8% (95% CI 63.6, 66.0); site-specific estimates ranged from 54.8 to 87.3%. Overall specificity was 74.9% (95% CI 74.1, 75.6) and overall PPV was 54.5% (95% CI 53.7, 55.3), while site-specific PPV ranged from 33.9 to 72.8%. The cardiovascular mortality algorithm had sensitivity of 57.1% (95% CI 55.4, 58.8) for in-hospital deaths and 72.3% (95% CI 70.8, 73.9) for out-of-hospital deaths; specificity was 88.8% (95% CI 88.1, 89.5) for in-hospital deaths and 58.5% (95% CI 57.3, 59.7) for out-of-hospital deaths. Conclusions A cardiovascular mortality algorithm applied to administrative health records had moderate validity when compared to vital statistics data. Substantial variation existed across study sites representing different geographic locations and two healthcare systems. These variations may reflect different diagnostic coding practices and healthcare utilization patterns.Pharmaceutical Sciences, Faculty ofNon UBCAnesthesiology, Pharmacology and Therapeutics, Department ofReviewedFacultyResearche

Additional file 1 of Characteristics of new users of recent antidiabetic drugs in Canada and the United Kingdom

Additional file 1