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See detailA Simple Tiered Methodology for the Determination of Ambient Air Quality Guidelines
PIRARD, Catherine ULiege; Brouhon, Jean-Marc; Fourmeaux, Annick et al

in Clean : Soil, Air, Water (2016), 44(5), 464-473

Within the scope of the renewal of industrial operating permits in Belgium, the Walloon Agency for Air and Climate needed air quality criteria for a wide range of toxics. Due to the plethora of different ... [more ▼]

Within the scope of the renewal of industrial operating permits in Belgium, the Walloon Agency for Air and Climate needed air quality criteria for a wide range of toxics. Due to the plethora of different existing values for some compounds or the total lack for others, the development of a simple methodology was required to provide both quality and intervention criteria, corresponding respectively to a chemical concentration for which no adverse health effects are expected for a lifetime exposure, and the chemical concentration in air associated with a risk for human health deemed significant. The tiered methodology developed here allows the selection of air guidelines from available databases, and proposes, if needed, approaches based on well-proven procedures to derive air quality guidelines from occupational exposure limits, drinking water guidelines, tolerable daily intakes, or as a last resort acute lethal toxicity data if nothing else is available. If this method has been successfully applied to more than 550 compounds, all values produced should be validated according to the purpose of the guidelines, the technical feasibility of achieving the threshold produced, and the specificity of the environment conditions and the targeted population. Moreover, the criteria obtained from non-air-related data should be critically examined and handled with caution. [less ▲]

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See detailPoliteal vein blood sampling and the post-mortem redistribution of diazepam, methadone and morphine
Lemaire, Eric ULiege; Schmidt, Carl; DENOOZ, Raphael ULiege et al

in Journal of Forensic Sciences (2016)

Postmortem redistribution (PMR) refers to the site- and time-related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and ... [more ▼]

Postmortem redistribution (PMR) refers to the site- and time-related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and popliteal) concentrations of diazepam, methadone, and morphine. To our knowledge, popliteal blood has never been compared with other sites. Intracardiac blood (ICB), subclavian blood (SB), femoral blood (FB), and popliteal blood (PB) were sampled in 30 cases. To assess PMR, mean concentrations and ratios were compared. Influence of postmortem interval on mean ratios was also assessed. Results show that popliteal mean concentrations were lower than those for other sites for all three drugs, even lower than femoral blood; mean ratios suggested that the popliteal site was less subject to PMR, and estimated postmortem interval did not influence ratios except for diazepam and methadone FB/PB. In conclusion, our study is the first to explore the popliteal site and suggests that popliteal blood is less prone to postmortem redistribution. [less ▲]

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See detailPostmortem Concentration and Redistribution of Diazepam, Methadone and Morphine with Subclavian and Femoral Vein Dissection/Clamping
Lemaire, Eric ULiege; Schmidt, Carl; DENOOZ, Raphael ULiege et al

in Journal of Forensic Sciences (2016), 61(6), 1596-1603

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See detailValidation of a novel and rapid method for simultaneous determination of some phenolic organohalogens in serum by GC-MS
Dufour, Patrice ULiege; PIRARD, Catherine ULiege; Charlier, Corinne ULiege

in Journal of Chromatography. B : Analytical Technologies in the Biomedical & Life Sciences (2016), 1036

Over the last decades, more and more studies focused on the impact of endocrine disruptors on the environment and human health. Among them, phenolic organohalogens (POHs) are a particular concern because ... [more ▼]

Over the last decades, more and more studies focused on the impact of endocrine disruptors on the environment and human health. Among them, phenolic organohalogens (POHs) are a particular concern because of their structural resemblance with natural hormones. There are different methods that are known to quantify these compounds in human serum, however, the current extraction techniques are long, fastidious and using harmfull chemicals such as diazomethane and sulfuric acid. Consequently, we developed an alternative, sensitive and faster method to simultaneously quantify pentachlorophenol (PCP), tetrabromobisphenol A (TBBPA), 4 bromophenols, 7 hydroxypolychlorinated biphenyls (OH-PCBs) and 3 hydroxy-polybrominated diphenyl ether (OH-PBDEs) in human serum sample. The clean-up and the enrichment of the sample were performed in a single extraction step using strong anion-exchange solid phase cartridge. After a rapid liquid–liquid extraction step to remove acidic traces, the extract was derivatized using trimethylsilyldiazomethane (TMSD) and finally analyzed by a gas-chromatograph coupled with an electron negative capture chemical ionization source combined with a triple quadrupole mass spectrometer (GC-ENCI-MS) operating in single ion monitoring. The whole procedure was validated according to the total error approach. The inter and intra assay precision were demonstrated to be lower than 20% and the relative bias to be lower than 15% in the dosing range of concentrations. The limit of quantification (LOQ) ranged from 2 pg mL−1 and 5 pg mL−1, except for the PCP (44.6 pg mL−1) and for the 2,4,6-tribromophenol (49.6 pg mL−1). Finally, the method was successfully applied to measure the POH background contamination in serum samples collected from 20 Belgian blood donors recruited in CHU Mont-Godinne (Namur, Belgium) aged between 21 and 69 years old. [less ▲]

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See detailA Simple tiered methodology for the determination of ambient air quality guidelines
PIRARD, Catherine ULiege; DUBOIS, Nathalie ULiege; BROUHON, Jean-Marc et al

Poster (2015, November)

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See detailTemporal variability of urinary concentrations of phthalate metabolites, parabens and benzophenone-3 in a belgian adult population
DEWALQUE, Lucas ULiege; PIRARD, Catherine ULiege; Vandepaer, Sarah et al

in Environmental Research (2015), 142

In the present study, we investigated the temporal within-person variability of the exposure biomarker for phthalates, parabens and benzophenone-3 (BP3) in 32 Belgian adults, each providing 11 urine spots ... [more ▼]

In the present study, we investigated the temporal within-person variability of the exposure biomarker for phthalates, parabens and benzophenone-3 (BP3) in 32 Belgian adults, each providing 11 urine spots during 4 months. We calculated the intraclass coefficient correlation (ICC), the sensitivity and the specificity to assess the temporal reproducibility and to investigate the predictive ability of the spot measurements for these classes of chemicals. Additionally, we explored the temporal variability of the estimation of the cumulative risk of exposure to phthalates (hazard index; HI). We observed fair ICC ranging from 0.55 to 0.68 for parabens, monoethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP) and BP3, but lower ICC, from 0.20 to 0.49, for monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MnBP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxo-hexyl phthalate (5-oxo-MEHP) and mono-2-ethyl-5-hydroxy-hexyl phthalate (5-OH-MEHP). The ICC estimated for HI (0.49) reflected a moderate reproducibility. The measurements in spot samples were moderate to good predictor of the 4-month level of exposure for parabens, MEP, MnBP, MiBP, BP3 and HI (sensitivity ranging from 0.67 to 0.77), but lower predictor for MEHP, 5-oxo-MEHP, 5-OH-MEHP and MBzP (sensitivity ranging from 0.58 to 0.63). The sensitivity could be increased when several spot urinary levels were averaged to predict the long-term level of exposure. Globally, our results indicate that a single spot measurement seems to correctly represent the long-term exposure for parabens, BP3, MEP, MiBP and HI. Additional spot samples seemed to be needed for the proper exposure assessment of the other target compounds. [less ▲]

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See detailHigh reactive oxygen species in fibrotic and non-fibrotic skin of Patients with diffuse cutaneous systemic sclerosis
BOURJI, Khalil; MEYER, Alain; CHATELUS, Emmanuel et al

in Free Radical Biology & Medicine (2015), 87

Systemic Sclerosis (SSc) is a chronic multisystemic connective tissue disease characterized by progressive fibrosis affecting skin and internal organs. Despite serious efforts to unveil the pathogenic ... [more ▼]

Systemic Sclerosis (SSc) is a chronic multisystemic connective tissue disease characterized by progressive fibrosis affecting skin and internal organs. Despite serious efforts to unveil the pathogenic mechanisms of SSc, they are still unclear. High levels of Reactive Oxygen Species (ROS) in affected patients have been shown, and ROS are suggested to play a role in fibrosis pathogenesis. In this study we evaluate ROS levels in non-fibrotic and fibrotic skin of patients with SSc and we compare them with those obtained from healthy controls. Patients and Methods We enrolled 9 SSc patients fulfilling the EULAR/ACR classification criteria and 7 healthy controls. Patients included were 4 men and 5 women with mean age of 46 ±10 yrs. Controls were matched by sex and age. All patients were affected by diffuse cutaneous form of SSc and the ANA pattern anti-Scl70. Mean disease duration was 7.5±5 yrs. Skin involvement was evaluated by modified Rodnan Skin Score (mRSS). Skin samples (4 mm punch biopsy) were taken from fibrotic skin and non-fibrotic skin of patients and from healthy controls as well. To detect ROS, specimens were analyzed immediately after sampling by electron paramagnetic resonance spectroscopy. Blood samples have been drawn from all patients and controls to assess oxidative stress biomarkers. Results ROS levels (expressed as median and range, unit of measurement was nmol/l/min/mg of dry weight) were 24.7 (10.9– 47.0) in fibrotic skin, 18.7 (7.3–34.0) in non-fibrotic skin and 7.7 (3.5–13.6) in healthy controls skin. ROS levels in Fibrotic and Non-fibrotic skin of SSc patients were significantly higher than in Healthy Controls (p=0.002 and p=0.009, respectively). ROS levels in fibrotic skin were raised in comparison to non-fibrotic skin, when samples related to each patient were compared (p=0.01). ROS levels in fibrotic skin were correlated with forced vital capacity (r= -0.75, p=0.02) and erythrocyte sedimentation rate (r=0.70, p=0.04). All other clinical and lab parameters showed no significant correlation. When compared to controls, blood from SSc patients showed lower ascorbate (vitamin C) levels (8 [3.8-9.8] vs. 10.5 [9-19.1] mg/L, p=0.004) and higher lipid peroxides (873.5 [342-1973] vs. 422 [105-576] μmol/L, p=0.004). Conclusion Our results indicate the presence of high oxidative stress both in non-fibrotic skin and fibrotic skin of SSc patients, but with higher tendency in the latter. Raised ROS levels in non-fibrotic skin of SSc patients might be a hint of early involvement in skin fibrogenesis. However, a longitudinal prospective study is necessary for such proof. [less ▲]

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See detailFish consumption patterns and hair mercury levels in children and their mothers in 17 EU countries
Castano, Argelia; Cutanda, Francisco; Esteban, Marta et al

in Environmental Research (2015), 141

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential ... [more ▼]

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-​levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-​child pairs from 17 European countries using a strictly harmonized protocol for mercury anal. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster anal. of consumption habits of the mother-​child pairs, the DEMOCOPHES cohort can be classified into two branches of approx. similar size: one with high fish consumption (H) and another with low consumption (L)​. All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-​child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concn. between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-​child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish contribute significantly to the mercury levels in hair. We conclude that addnl. studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster anal. also showed that 95​% of mothers who consume once per wk fish only, and no other marine products, have mercury levels 0.55 μg​/g. Thus, the 95th percentile of the distribution in this group is only around half the US-​EPA recommended threshold of 1 μg​/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an addnl. dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements. [less ▲]

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See detailDetermination of blood concentration levels of psychotrope medications in Rwandan patients
Hahirwa, Innocent; DENOOZ, Raphael ULiege; Karangwa, Charles et al

in Acta Clinica Belgica (2015)

OBJECTIVES: In Rwanda, no therapeutic monitoring of psychotropic drugs is done. This results in difficult treatment optimisation and exposition to a high risk of toxicity and drug ineffectiveness for ... [more ▼]

OBJECTIVES: In Rwanda, no therapeutic monitoring of psychotropic drugs is done. This results in difficult treatment optimisation and exposition to a high risk of toxicity and drug ineffectiveness for patients under treatment. This study aimed to determine blood concentration levels of psychotropic drugs in Rwandan patients and identify problems associated with the lack of therapeutic drug monitoring (TDM) of these drugs. METHODS: The analysis was performed on 1 ml of serum sample using prazepam as internal standard. Regarding the step of sample preparation, we used a liquid-liquid extraction with a mixture of organic solvents: diethyl ether/dichloromethane/hexane/n-amyl alcohol (50/30/20/0.5:V/V). A Waters Alliance 2695 was used for analysis. The chromatography was run on a Symmetry C8 column and as mobile phase acetonitrile and phosphate buffer (pH 3.8) were used. RESULTS: Concerning the results, serum samples from 128 patients were analysed. Twenty-one different psychotropic drugs belonging to various pharmacological classes were detected and quantified. Analytical results were put into three categories based upon therapeutic reference ranges (TRR) of various drugs: subtherapeutic, therapeutic and supratherapeutic. For a total of 237 analyses, results within TRR represented 46% while 47 and 8% of results were, respectively, below and above TRR. CONCLUSION: It was therefore concluded that patients under psychotropic treatment in Rwanda are exposed to both the risk of drug ineffectiveness and the risk of toxicity (54%) with only 46% of results within the TRR. Consequently, TDM is needed to optimise psychotropic treatment in Rwandan patients. [less ▲]

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See detailApplication of the characteristic function to evaluate and compare analytical variability in an external quality assessment scheme for serum ethanol
Coucke, Wim; Charlier, Corinne ULiege; Lambert, Willy et al

in Clinical Chemistry (2015), 61

As a cornerstone of quality management in the laboratory, External Quality Assessment (EQA) schemes are used to assess laboratory and analytical method performance. The characteristic function is used to ... [more ▼]

As a cornerstone of quality management in the laboratory, External Quality Assessment (EQA) schemes are used to assess laboratory and analytical method performance. The characteristic function is used to describe the relation between the target concentration and the EQA standard deviation, which is an essential part of the evaluation process. The characteristic function is also used to compare the variability of different analytical methods. We fitted the characteristic function to data from the Belgian External Quality Assessment program for serum ethanol. Data included results from headspace gas chromatography and the enzymatic methods of Abbott, Roche, Siemens, and Ortho-Clinical Diagnostics. We estimated the characteristic function with weighted nonlinear regression. By introducing dummy variables, we rewrote the original formula of the characteristic function to assess statistical inference for comparing the variability of the different analytical methods. The characteristic function fitted the data precisely. Comparison between methods showed that there was little difference between the estimated variability for low concentrations, and that the increase in SD with increasing target concentration was slower for Abbott and Roche than for the other methods. The characteristic function can successfully be introduced in clinical schemes, although its applicability to fit the data should always be assessed. Because of its easy parameterization, it can be used to assess differences in performance between analytical methods and to assess laboratory performance. The characteristic function also offers an alternative framework for coefficients of variation to describe variability of analytical methods. [less ▲]

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See detailLe dosage du cobalt dans le sang par ICP-MS : application aux patients porteurs de prothèses de hanche en métal
MISTRETTA, Virginie ULiege; Charlier, Corinne ULiege

in Toxicologie Analytique & Clinique (2015), 27(2), 91-98

Objectif Les patients porteurs de prothèse de hanche à couple métal-métal (PHM) présentent un taux de cobalt circulant supérieur à celui de la population générale. Chez ces patients, le dosage du cobalt ... [more ▼]

Objectif Les patients porteurs de prothèse de hanche à couple métal-métal (PHM) présentent un taux de cobalt circulant supérieur à celui de la population générale. Chez ces patients, le dosage du cobalt permet d’apprécier le risque toxique éventuel de l’implant et peut servir d’indicateur de révision ou de remplacement de cette prothèse. A cette fin, une méthode de dosage a été validée et appliquée à des patients porteurs de PHM. Méthode Le dosage du cobalt est réalisé sur 500 μL de sang total, après dilution dix fois dans une solution aqueuse acide et après ajout de 100 μL d’une solution de standard interne titrée à 500 μg/L de germanium. L’échantillon est ensuite analysé par un spectromètre de masse avec source d’ionisation par plasma induit haute fréquence (ICP-MS). La méthode décrite a été validée par l’approche de l’erreur totale au moyen du logiciel e•noval (Arlenda®). Résultats La méthode de dosage a été validée avec succès. Elle est linéaire de 0,5 à 50 μg/L. L’inexactitude et l’imprécision intra- et inter-essais sont inférieures à 5 % et 8 %, respectivement. L’incertitude de mesure est inférieure à 17 %. La concentration sanguine moyenne de cobalt estimée sur une période de 1 an à partir de 107 prélèvements de patients porteurs de PHM est de 2,61 μg/L (nombre de patients : 98 ; âge moyen : 60 ans ; ratio hommes/femmes : 38/60). Ce résultat est inférieur au seuil recommandé dans ces populations, fixé à 7 μg/L de cobalt sanguin. Conclusion La méthode analytique présentée permet de doser le cobalt sanguin, notamment chez les patients porteurs de PHM. Ce dosage est recommandé pour le suivi de ces patients, en association avec un examen clinique et radiologique. [less ▲]

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See detailEstimation du délai entre la consommation d'héroïne et le prélèvement de sang chez des consommateurs chroniques
DUBOIS, Nathalie ULiege; Charlier, Corinne ULiege

in Toxicologie Analytique & Clinique (2015, June), S27(2), 43

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See detailEvaluation d'une trousse de dépistage de l'éthylène glycol par méthode enzymatique
DEVILLE, Marine ULiege; HALENG, Jeanine ULiege; Henrad, Valérie et al

in Toxicologie Analytique et Clinique (2015, June), S27(2), 60-61

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See detailProfession : toxicologue médicolégal
CHARLIER, Corinne ULiege

Conference given outside the academic context (2015)

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See detailEfficacy of heroin-assisted treatment in Belgium: a randomised controlled trial
Demaret, Isabelle ULiege; Quertemont, Etienne ULiege; Litran, Géraldine et al

in European Addiction Research (2015), 21(4), 179-187

Background/Aims: Heroin-assisted treatment (HAT) can improve the condition of heroin addicts still using street heroin after a methadone treatment. In Belgium, a new trial compared the efficacy of a HAT ... [more ▼]

Background/Aims: Heroin-assisted treatment (HAT) can improve the condition of heroin addicts still using street heroin after a methadone treatment. In Belgium, a new trial compared the efficacy of a HAT to existing methadone maintenance treatment. Methods: In this randomised controlled trial, HAT was limited to 12 months. Participants were assessed every 3 months. They were responders if they showed improvement on the level of street heroin use, health or criminal involvement. Results: 74 participants were randomised in the trial. The experimental group (n=36) counted 30% of responders more than the control group (n=38) at each assessment point (p<0.05), except at 12 months where the difference (11%) was no longer significant (p=0.35). Still, after 12 months, participants in the experimental group reported significantly greater improvements (p<0.05) than the control group on the level of street heroin use and on the level of physical and mental health. Both groups reported significantly less criminal facts after 12 months (p<0.001), but with no significant difference between the groups. Conclusions: This trial confirms the short-term efficacy of HAT for severe heroin addicts, who already failed methadone treatment. [less ▲]

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See detailToxicomanies : nouvelles substances, nouveaux usages
CHARLIER, Corinne ULiege

Conference given outside the academic context (2015)

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See detailEstimation of the Time Interval between the Administration of Heroin and the Sampling of Blood in Chronic Inhalers
DUBOIS, Nathalie ULiege; HALLET, Claude ULiege; SEIDEL, Laurence ULiege et al

in Journal of Analytical Toxicology (2015)

To develop a model for estimating the time delay between last heroin consumption and blood sampling in chronic drug users. Eleven patients, all heroin inhalers undergoing detoxification, were included in ... [more ▼]

To develop a model for estimating the time delay between last heroin consumption and blood sampling in chronic drug users. Eleven patients, all heroin inhalers undergoing detoxification, were included in the study. Several plasma samples were collected during the detoxification procedure and analyzed for the heroin metabolites 6-acetylmorphine (6AM), morphine (MOR), morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), according to a UHPLC/MSMS method. The general linear mixed model was applied to time-related concentrations and a pragmatic four-step delay estimation approach was proposed based on the simultaneous presence of metabolites in plasma. Validation of the model was carried out using the jackknife technique on the 11 patients, and on a group of 7 test patients. Quadratic equations were derived for all metabolites except 6AM. The interval delay estimation was 2–4 days when only M3G present in plasma, 1–2 days when M6G and M3G were both present, 0–1 day when MOR, M6G and M3G were present and <2 h for all metabolites present. The ‘jackknife’ correlation between declared and actual estimated delays was 0.90. The overall precision of the delay estimates was 8–9 h. The delay between last heroin consumption and blood sampling in chronic drug users can be satisfactorily predicted from plasma heroin metabolites. [less ▲]

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See detailBlood alcohol concentration in drivers of Liege aera (Belgium) : a 5-year analysis
DEVILLE, Marine ULiege; Charlier, Corinne ULiege

in Acta Clinica Belgica (2015), 00

Objectives: The objective of the present study was to describe the results of the blood alcohol determinations made on drivers from the Liege area between July 2007 and December 2012. Methods: The results ... [more ▼]

Objectives: The objective of the present study was to describe the results of the blood alcohol determinations made on drivers from the Liege area between July 2007 and December 2012. Methods: The results were interpreted according to the sex, to the age, to the circumstances and temporal variation of the blood test. Statistical analysis was performed using R® software. Results: During this 5-years period, 2725 determinations were done, mainly in the context of road crashes. The mean blood alcohol concentration (BAC) was 1.69 g/L, and 2132 drivers were above the legal threshold. A large majority of offenders (77%) were men, but the mean BAC did not differ significantly between men (1.69 g/L) and women (1.67 g/L). A statistically significant correlation between age and mean BAC can be observed, if we only consider the positive cases. Concerning the temporal variation of the results, lowest mean BACs are observed during the daytime while highest mean BACs are measured during the night. In both cases, no statistically significant difference can be observed if we compare the week and the weekend. Finally, no statistically significant difference in BAC was observed over years. [less ▲]

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