Naturalistic comparison of clomethiazole and Diazepam treatment in alcohol withdrawal: effects on oxidative stress, inflammatory cytokines and hepatic biomarkers.

Ethanol is metabolized by alcohol dehydrogenase to acetaldehyde and induces cytochrome P450 2E1 (CYP2E1), which generates reactive oxygen species that cause inflammatory liver damage. Clomethiazole, a drug approved for alcohol withdrawal treatment (AWT) in some European countries, inhibits CYP2E1. We hypothesized that clomethiazole would lead to a faster reduction in oxidative stress, inflammatory cytokines, and liver enzymes compared to diazepam treatment. We analysed respective biomarkers in 50 patients undergoing AWT and 25 healthy individuals but found no statistical difference between the two medication groups over 3-5 days. Hence, our hypothesis was not confirmed during this observation period.

Protocolized screening and detection of occult alcohol use before and after liver transplant: Lessons learned from a quality improvement initiative.

INTRODUCTION: Detection of alcohol (ETOH) use with biomarkers provides an opportunity to intervene and treat patients with alcohol use disorder before and after liver transplant (LT). We describe our center's experience using urine ethyl glucuronide (EtG) and serum phosphatidylethanol (PEth) in alcohol screening protocols. METHODS: Single-center, retrospective review of patients presenting for LT evaluation, patients waitlisted for LT for alcohol-associated liver disease (ALD), and patients who received a LT for ALD over a 12-month period, from October 1, 2019 through September 30, 2020. Patients were followed from waitlisting to LT, or for up to 12 months post-LT. We monitored protocol adherence to screening for ETOH use- defined as completion of all possible tests over the follow-up period- at the initial LT visit, while on the LT waitlist and after LT. RESULTS: During the study period, 227 patients were evaluated for LT (median age 57 years, 58% male, 78% white, 54.2% ALD). Thirty-one patients with ALD were placed on the waitlist, and 38 patients underwent LT for ALD during this time period. Protocolized adherence to screening for alcohol use was higher for PEth for all LT evaluation patients (191 [84.1%] vs. 146 [67%] eligible patients, p < .001), in patients with ALD waitlisted for LT (22 [71%] vs. 14 (48%] eligible patients, p = .04) and after LT for ALD, 20 (33 [86.8%] vs. 20 [52.6%] eligible patients, p < .01). Few patients with a positive test in any group completed chemical dependency treatment. CONCLUSIONS: When screening for ETOH use in pre- and post-LT patients, protocol adherence is higher using PEth compared to EtG. While protocolized biomarker screening can detect recurrent ETOH use in this population, engagement of patients into chemical dependency treatment remains challenging.

Concordance of Ethyl Glucuronide, Blood Alcohol Content, and Self-Reported Alcohol Use in Russian Women with HIV and Hepatitis C Virus Co-Infection.

Problematic alcohol use is prevalent in Russia and is deleterious for individuals with HIV and Hepatitis C Virus (HCV). Ethyl glucuronide (EtG) and blood alcohol content (BAC) provide objective biomarkers of drinking that can be compared to self-reported alcohol use. This paper describes patterns of alcohol use measured by biomarkers and self-report along with concordance across measures. Participants were Russian women with HIV and HCV co-infection (N = 200; Mean age = 34.9) from two Saint Petersburg comprehensive HIV care centers enrolled in an alcohol reduction intervention clinical trial. Measures were: (a) urine specimen analyzed for EtG; (b) breathalyzer reading of BAC; and (c) self-reported frequency of drinking, typical number of drinks consumed, and number of standard drinks consumed in the past month. At baseline, 64.0% (n = 128) had a positive EtG (> 500 ng/mL) and 76.5% (n = 153) had a positive breathalyzer reading (non-zero reading). There was agreement between EtG and BAC (kappa = 0.66, p < .001; Phi coefficient = 0.69, p < .001); self-reported alcohol measures were positively correlated with positive EtG and BAC (p's < 0.001). There was concordance between EtG and BAC measures, which have differing alcohol detection windows. Most participants endorsed frequent drinking at high quantities, with very few reporting no alcohol consumption in the past month. Concordance between biomarkers and self-reported alcohol use suggests that underreporting of alcohol use was minimal. Results highlight the need for alcohol screening within HIV care. Implications for alcohol assessment within research and clinical contexts are discussed.

Formation of phosphatidylethanol and ethylglucuronide after low to moderate alcohol consumption in volunteers with a previous three-week alcohol abstinence.

AIMS: Phosphatidylethanol (PEth) is only formed when ethanol is present in blood. This direct alcohol marker has been widely discussed, including the minimum amount of ethanol being necessary to form as much PEth as to exceed the threshold of 20 ng/mL in previously PEth negative subjects. In order to corroborate hitherto existing results, a drinking study including 18 participants after a 3-week alcohol abstinence was performed. METHODS: They consumed a pre-calculated amount of ethanol to reach a blood alcohol concentration (BAC) of at least 0.6 g/kg. Blood was drawn before and periodically seven times after alcohol administration on day 1. Blood and urine were also collected the next morning. Dried blood spots (DBS) were prepared immediately from collected venous blood. BAC was determined by head space gas chromatography and the concentrations of both PEth (16:0/18:1, 16:0/18:2 and five additional homologues) and ethyl glucuronide (EtG) were analysed using liquid chromatography-tandem mass spectrometry. RESULTS: Out of 18, 5 participants had concentrations of PEth 16:0/18:1 above the threshold of 20 ng/mL, and 11 out of the 18 subjects had concentrations between 10 and 20 ng/mL. In addition, four persons had PEth 16:0/18:2 concentrations above 20 ng/mL the following morning. All test subjects tested positive for EtG in DBS (≥ 3 ng/mL) and urine (≥100 ng/mL) upon 20-21 h after alcohol administration. CONCLUSION: By combining both a lower cutoff of 10 ng/mL and the homologue PEth 16:0/18:2, the sensitivity to detect a single alcohol intake after a 3-week abstinence increases to 72.2%.

Rapid urine screening for ethyl glucuronide from pregnant women as a tool for detecting prenatal alcohol exposure.

BACKGROUND: An increasing prevalence of alcohol consumption is a major public health problem, which has also led to an increasing number of children who have been prenatally exposed to the toxic effects of ethanol. However, obtaining reliable information on prenatal alcohol exposure through maternal self-reports has proved difficult. AIMS: Our aim was to evaluate the potential for rapid screening test for measuring ethyl glucuronide (EtG), a specific alcohol metabolite, from urine samples of pregnant women. METHODS: Five hundred five urine samples of pregnant women were collected anonymously from five prenatal units in two Finnish cities: a tertiary specialist antenatal clinic for pregnant women with problematic substance use (HAL), a regular hospital antenatal clinic (LCH = Lahti Central Hospital), a prenatal screening unit and two community maternity clinics (USR = user self-recruiting units). All samples were screened using rapid EtG test strips, and all positive, uncertain, and randomly selected negative samples were confirmed by quantitative analyses. The samples were also screened for cotinine and use of cannabis. RESULTS: In this material an EtG cut-off of 300 ng/mL suggesting heavy alcohol drinking was exceeded by 7.4% (5/68) of the samples in the HAL clinic, 1.9% (4/202) in LCH, and 0.9% (2/225) in USR. A cut-off of 100 ng/mL was exceeded by 17.6% (12/68) of samples from HAL, 7.5% (16/212) from LCH, and 6.7% (15/225) from USR. Based on confirmatory quantitative analyses, there were no false negatives nor false positives in rapid EtG screening. However, 57 (11.3%) of test results were classified as uncertain. In these cases, confirmation by quantitative analyses resulted in 56.1% rate of positive values. 73% of the samples with EtG > 300 ng/mL showed positive cotinine results suggesting smoking co-occurring with alcohol intake. CONCLUSIONS: Rapid EtG tests may be an easy and inexpensive method, which may improve the possibilities for screening alcohol use among pregnant women during routine prenatal visits. Quantitative EtG analyses are recommended to confirm screening positive and uncertain cases. TRIAL REGISTRATION: NCT04571463 Date of Registration 11/05/2020.

Determination of ethyl glucuronide in hair and self-reported alcohol consumption in university students.

Young individuals constitute an intriguing population, as their drinking habits are notably shaped by their perception of their peers' alcohol consumption. Nonetheless, excessive alcohol intake can have detrimental effects on academic performance, interpersonal relationships, and the risk and severity of accidents. This study reported the first data involving students enrolled from three universities on a voluntary basis for alcohol consumption evaluation. Alcohol consumption was assessed through questionnaires and EtG quantification in hair (hEtG) carried out by liquid chromatography-mass spectrometry (LC-MS/MS) analysis after a solid-phase extraction (SPE) purification step. The results of our study demonstrated that 77.1% of samples tested negative for hEtG or displayed hEtG ≤ 5 pg/mg. Particularly, the student population was not characterized by samples with hEtG indicative of chronic excessive consumption (hEtG ≥ 30 pg/mg). No significant association was identified between biological sex, among the degree course/the year attended, nor in relation to BMI or smoking/coffee consumption. Among the obtained results, it was worth noting that the comparison of self-reporting abstinence from tobacco and coffee accounted for 65.3% and 16.7%, respectively, while only 2.8% of the total declared abstinence from alcohol. The current study has uncovered a significant level of interest among students in this analysis and its interpretation. This suggests that implementing public health promotion activities within a university setting could be beneficial.

Ethyl glucuronide in hair detects a high rate of harmful alcohol consumption in presumed non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) cannot reliably be distinguished by routine diagnostics, and the role of alcohol consumption in metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. We investigated alcohol consumption in patients with presumed NAFLD and ALD using novel objective alcohol markers. METHODS: In total, 184 consecutive patients were included in this prospective observational study. Alcohol intake was assessed by ethylglucuronide in hair (hEtG) and urine (uEtG); the utility of these measures for alcohol detection was compared to Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), carbohydrate deficient transferrin (CDT), mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT), and ALD/NAFLD index (ANI). Clinical characteristics of patients with NAFLD and ALD were re-assessed after reclassification based on repeated moderate (≥10 g <60 g EtOH/day) and excessive (≥60 g EtOH/day) alcohol consumption, and patients were retrospectively reclassified based on MAFLD criteria. RESULTS: Repeated moderate to excessive alcohol consumption was detected in 28.6%, 28.5%, and 25.0% of patients with presumed NAFLD, ALD or MAFLD, respectively. ANI score, AUDIT-C, uEtG, and hEtG showed AUCs of 0.628, 0.733, 0.754, and 0.927 for the detection of repeated moderate to excessive alcohol consumption, respectively. The indirect markers CDT, MCV and GGT were not reliable. Patients with repeated moderate or excessive alcohol consumption were significantly more often male, had a significantly lower BMI, and suffered significantly less often from type 2 diabetes or impaired glucose tolerance. CONCLUSIONS: In total, 28.6% of patients with presumed NAFLD, and 25.0% with MAFLD are at risk of alcohol-related liver damage. AUDIT-C, uEtG and hEtG should be used to screen for alcohol consumption in patients with fatty liver disease. LAY SUMMARY: Fatty liver disease can be caused by metabolic factors and/or alcohol consumption. The diagnosis of non-alcoholic fatty liver disease (NAFLD) is based on the exclusion of harmful alcohol consumption, while metabolic dysfunction-associated fatty liver disease (MAFLD), which has been proposed as a new name for NAFLD, is based on the presence of metabolic comorbidities and allows for alcohol consumption. Herein, we show that up to 29% of patients diagnosed with NAFLD and 25% with MAFLD are at risk of alcohol-related liver damage. We show that ethyl glucuronide (a metabolite of alcohol) in the hair and urine can accurately detect potentially harmful alcohol consumption in these patients - as such, these tests should be integrated into routine diagnostic work-up for patients with fatty liver disease.

Development and validation of LCMS method for determination of Ethyl Glucuronide (EtG) in urine.

Background: Ethyl glucuronide (EtG) is a phase II metabolite of ethanol and is an upcoming biomarker for recent alcohol intake. Monitoring of alcohol intake in case of alcohol-dependent syndrome is very useful for early intervention and preventing harmful effects. EtG has also been identified as a very useful marker in differentiating antemortem ingestion of alcohol from postmortem production of alcohol. This study was undertaken with an objective of developing a sensitive and specific method for determination of EtG in urine. Methods: Triple quadruple Liquid Chromatography (LC)-Mass Spectrometry (MS) with Electrospray Ionization (ESI) negative mode has been used for developing the multiple reaction monitoring method by using the Polaris 3 C 18-Ether analytical column. A simple sample preparation method was adopted using the Bond Elute Plexa PAX SPE cartridge. The developed method was also tested on actual urine samples from 15 individuals after consumption of 60 and 90 ml of whiskey at different time intervals. Results: A simple method was developed for determination of EtG in urine, with a sensitivity of 100 ppb and a recovery of 75%. Validation of the method on urine samples revealed that EtG could be detected for up to 18 h in individuals who ingested 60 ml of whiskey and up to 24 h in those who ingested 90 ml of whiskey. Conclusion: The simple method was developed for determination of EtG in urine and validated on actual urine samples. This method can now be used in aircraft accident investigation to differentiate postmortem production of alcohol, and the method is also a very useful tool to monitor Alcohol dependent Syndrome (ADS) cases.

Significance and clinical impact of routinely tested urinary ethyl glucuronide after liver transplantation - development of a risk score.

Alcohol abuse after liver transplantation can seriously impact graft and patient survival. However, to date, there is no defined standard procedure to identify patients consuming alcohol after liver transplantation. The aim of this study was to analyze the diagnostic value and clinical impact of routinely measured urinary ethyl glucuronide (uEtG) - a metabolite of ethanol - in patients after liver transplantation. Data of 362 consecutive patients after liver transplantation who visited the University Hospital of Tuebingen for outpatient follow-up were analyzed. Forty-eight patients (13%) displayed positive uEtG results. The uEtG positive group contained significantly more patients with pretransplant alcoholic liver disease. However, two thirds of the uEtG positive patients had no history of pretransplant alcoholic liver disease. Several clinical parameters were significantly associated with positive uEtG. In order to enable a more cost-effective application of uEtG in the future, a clinical risk score was developed (specificity 0.95). In conclusion, routine testing for uEtG reveals a considerable percentage of patients practicing alcohol intake after liver transplantation. Application of our proposed risk score could help focusing uEtG testing on patients at risk.

Development and validation of a method for the simultaneous analysis of fatty acid ethyl esters, ethyl sulfate and ethyl glucuronide in neonatal meconium: application in two cases of alcohol consumption during pregnancy.

Alcohol consumption during pregnancy constitutes one of the leading preventable causes of birth defects and neurodevelopmental disorders in the exposed children. Fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG) and ethyl sulfate (EtS) have been studied as potential biomarkers of alcohol consumption. However, most analytical approaches proposed for their analysis in meconium samples consist of separated extraction procedures requiring the use of two meconium aliquots, which is costly in terms of both time and materials. Therefore, the aim of this study was to develop and validate a method for the simultaneous extraction of 9 FAEEs, EtG and EtS from one meconium aliquot. The sample was homogenized using methanol, and then FAEEs were extracted with hexane while EtG and EtS were isolated using acetonitrile. Then, extracts were applied to solid-phase extraction columns and analysed by gas chromatography mass spectrometry (FAEEs) and liquid chromatography tandem mass spectrometry (EtG and EtS). Calibration curves were linear with r values greater than 0.99. The LODs ranged from 0.8 to 7.5 ng/g for FAEEs and were 0.2 ng/g and 0.8 ng/g for EtS and EtG, respectively. LOQs ranged from 5 to 25 ng/g for FAEEs and were 1 ng/g and 2.5 ng/g for EtS and EtG, respectively. Accuracies and precisions were between 93.8 and 107% and between 3.5 and 9.7%, respectively. The recovery values ranged from 89.1 to 109%. The method proved to be sensitive, specific, simple and fast and allowed for the reduction of the amount of organic solvent used for extraction compared to other published data while higher recoveries were obtained. The method was used for analysis of meconium samples in two cases of mothers who were consuming alcohol during pregnancy.

The association between prenatal alcohol consumption and preschool child stress system disturbance.

BACKGROUND: Drinking alcohol during pregnancy is considered a risk factor for child development; however, child biomarkers of prenatal alcohol exposure have been rarely studied. We examined whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with child cortisol concentrations at primary school age. METHODS: For 137 children, prenatal alcohol exposure was operationalized by the meconium biomarker EtG and by maternal self-reports during pregnancy. Two EtG cut-offs (EtG ≥10 ng/g and EtG ≥112 ng/g) were applied. Cortisol concentrations were measured in saliva and hair samples. RESULTS: Children with EtG ≥10 ng/g showed significantly reduced hair cortisol concentrations (HCCs) (p = .050, ηp2  = 0.042). For children with EtG ≥112 ng/g, the cortisol awakening response (CAR) was significantly decreased (p = .025, ηp2  = 0.070). These effects were also present in correlational analyses with continuous EtG data, speaking for partly dose-dependent effects. Especially, within the EtG ≥112 ng/g group, the basal (CAR: rp  = -.642, p = .120) and cumulative (HCC: rp  = -.660, p = .107) cortisol parameters were associated with child emotional symptoms at medium effect size. CONCLUSIONS: The present study showed both the biological association of intrauterine alcohol exposure with the cortisol stress system, partly dose-dependent, and the functional association with emotional and behavioral symptoms.

Phosphatidylethanol Reliably and Objectively Quantifies Alcohol Consumption in Adolescents and Young Adults.

BACKGROUND: Alcohol contributes to numerous annual deaths and various societal problems not just in adult, but also in adolescent, populations. Therefore, it is vital to find methods for reliably detecting alcohol use for early preventative measures. Research has shown phosphatidylethanol (PEth) to be superior to self-report instruments and indirect biomarkers for alcohol consumption in adult populations. However, the transferability onto an adolescent population has not yet been investigated. METHODS: N = 106 adolescents and young adults aged between 13 and 21 years were included. PEth analysis using high-pressure liquid chromatography-tandem mass spectrometry was performed on dried blood spot samples. Self-report questionnaires for alcohol consumption (Alcohol Use Disorders Identification Test-Consumption, AUDIT-C, and Timeline Followback, TLFB) and drug and alcohol consumption (Detection of Alcohol and Drug Problems in Adolescents, DEP-ADO) were completed by each participant. RESULTS: AUDIT-C scores showed large correlations with PEth 16:0/18:1 (rs  = 0.732) and PEth 16:0/18:2 (rs  = 0.661) concentrations. AUDIT-C with a cutoff value ≥3 was largely correlated with PEth 16:0/18:1 (η = 0.411) and showed a medium-sized correlation with PEth 16:0/18:2 (η = 0.397) concentrations. Using an AUDIT-C cutoff value ≥5 showed large correlations with both PEth 16:0/18:1 (η = 0.510) and PEth 16:0/18:2 (η = 0.497) concentrations, respectively. ROC curves indicated higher PEth concentrations are a good model for detecting positive AUDIT-C cutoff values (AUROC range: 0.800 to 0.849). PEth concentrations showed medium to large correlations with DEP-ADO and TLFB subscales (range rs  = 0.469 to 0.746). CONCLUSION: The results suggest that PEth is a reliable and objective marker for quantifying alcohol consumption in adolescents and young adults. This could be of importance for early preventative measures against hazardous alcohol consumption, which is increasingly common at younger ages.

Positive findings of ethyl glucuronide in hair of young children from families with addiction background.

AIMS: Small children are expected to be abstinent from alcohol, and children's hair is frequently used as the blank matrix for calibration of the alcohol consumption marker ethyl glucuronide (EtG). The basal EtG concentrations of total abstainers were described to be 0.3-2.1 pg/mg (Pirro et al. 2013). It is examined whether this assumption is valid for children from families with addiction background. METHODS: In a social support system for families with drug and/or alcohol addicted parents, 161 hair samples from 126 children (age 1-14 years, hair segment 0-3 cm) were analyzed for EtG by a validated LC-MS/MS method (LOD 0.56 pg/mg, LLOQ 2.3 pg/mg). For comparison, ethyl palmitate (EtPa) was measured and hair samples from parents were included. EtG ≥ 3 pg/mg was considered as an alarming result for children. RESULTS AND DISCUSSION: EtG concentrations between 3.0 and 42.6 pg/mg (mean 9.55 pg/mg, median 6.40 pg/mg) were measured for 25 samples (15.5%, age 22 × 1-5 years, 3 × 9-11 years). Elevated EtPa (0.15-0.46 ng/mg) was found in 6 samples and cocaethylene (0.02-0.07 ng/mg) was detected in 5 samples with high cocaine findings. Hair results of one or both parents indicated drug abuse in 12 from 14 cases (85.7%) if both parents were tested. CONCLUSION: Although accidental or voluntary intake of alcoholic beverages cannot be excluded, the external contamination of children's hair by EtG-containing wine and sweat or urine of the alcohol abusing parents is assumed to be the most probable explanation for the positive EtG results in hair of 1-5-year-old children.

Urinary Ethyl Glucuronide Can Be Used as a Biomarker of Habitual Alcohol Consumption in the General Population.

BACKGROUND: Alcohol consumption is a frequently studied risk factor for chronic diseases, but many studies are hampered by self-report of alcohol consumption. The urinary metabolite ethyl glucuronide (EtG), reflecting alcohol consumption during the past 72 h, is a promising objective marker, but population data are lacking. OBJECTIVE: The objective of this study was to assess the reliability of EtG as a marker for habitual alcohol consumption compared with self-report and other biomarkers in the general population. METHODS: Among 6211 participants in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort, EtG concentrations were measured in 24-h urine samples. EtG was considered positive when concentrations were ≥100 ng/mL. Habitual alcohol consumption was self-reported by questionnaire (categories: no/almost never, 1-4 units per month, 2-7 units per week, 1-3 units per day or ≥4 units per day). Plasma HDL cholesterol concentration, erythrocyte mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltransferase (GGT) were determined as indirect biomarkers of alcohol consumption. Sensitivity, specificity, positive and negative predictive value, and proportions of agreement between reported consumption and EtG were calculated. To test the agreement of EtG concentration and alcohol consumption in categories, linear regression analysis was performed. In addition, the association between EtG concentrations and indirect biomarkers was analyzed. RESULTS: Mean age was 53.7 y, and 52.9% of participants men. Of the self-reported abstainers, 92.3% had an EtG concentration <100 ng/mL. Sensitivity was 66.3%, positive predictive value was 96.3%, and negative predictive value was 47.4%. The proportion of positive agreement was 78.5%, and the proportion of negative agreement was 62.7%. EtG concentrations were linearly associated with higher categories of alcohol consumption (P-trend < 0.001), adjusted for age, sex, and renal function. EtG was positively related to MCV, HDL cholesterol, and GGT but not to AST and ALT concentrations. CONCLUSIONS: This study shows that urinary EtG is in reasonable agreement with self-reported alcohol consumption and therefore can be used as an objective marker of habitual alcohol consumption in the general population.

Alcohol markers in hair: an issue of interpretation.

Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) are metabolites of alcohol that when detected in hair can provide evidence of a person's drinking behavior. The analysis of these compounds in hair has become commonplace in recent years and has been used as evidence in legal proceedings. Despite the routine use of such toxicological analysis, the correct interpretation of alcohol biomarker hair testing can be complex, and there may be debate as to the significance of the data. This paper considers whether the accepted norm of applying interpretative cut-off values to EtG and FAEE concentrations from hair samples is appropriate, and asks whether Bayesian theory, using a likelihood ratio approach may offer greater insight as to the strength of evidence. In addition to the complexity of result interpretation in this field, the sensitivity of alcohol biomarkers in hair to distinguish low level drinking from abstinence also represents a significant challenge. The use of fingernail EtG testing as an alternative to hair analysis is explored in this paper and it is proposed that fingernails may in theory show a higher uptake of EtG than hair, and thus show potential as a useful alternative matrix to document long-term low to moderate alcohol consumption.

Effects of prenatal alcohol consumption on cognitive development and ADHD-related behaviour in primary-school age: a multilevel study based on meconium ethyl glucuronide.

BACKGROUND: Alcohol intake during pregnancy is considered to be a risk factor for child development. Child biomarkers of intrauterine alcohol exposure have been rarely studied. We investigated whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with cognitive development, ADHD-related behaviour and neurophysiological markers of attention and executive control of children at primary-school age. METHODS: Mothers provided self-report on prenatal alcohol consumption during their 3rd trimester. Meconium samples were collected at birth. A total of 44 children with a meconium EtG above the detection limit (≥10 ng/g) and 44 nonexposed matched controls were compared. A second threshold (≥154 ng/g) was applied to study the dose effects. When children reached primary-school age, mothers rated ADHD-related behaviour, child cognitive development was measured using an IQ test battery, and event-related potentials were recorded during a cued go/nogo task. RESULTS: Children in both EtG-positive groups allocated fewer attentional resources than controls to the go/nogo task (reduced P3 component in go-trials). Children with a meconium EtG above 154 ng/g were also found to have an IQ that was six points lower than the other groups. Within the EtG ≥ 154 ng/g group, there was a positive correlation between EtG value and ADHD-related behaviour. These significant effects were not observed in relation to the maternal self-report data. CONCLUSIONS: Associations between EtG and cognitive deficits, attentional resource capacity and ADHD-related behaviour could be documented with effects that were partially dose-dependent. In addition to maternal self-reports, this biomarker of intrauterine alcohol exposure may be considered as a predictor of child development.

Point-of-Care Urine Ethyl Glucuronide Testing to Detect Alcohol Use Among HIV-Hepatitis B Virus Coinfected Adults in Zambia.

In an HIV-hepatitis B virus (HIV-HBV) coinfection cohort in Zambia, we piloted a qualitative point-of-care (POC) test for urine Ethyl glucuronide (uEtG), assessed concordance between uEtG and alcohol use disorders identification test-consumption (AUDIT-C), and identified epidemiological factors associated with underreporting (defined as uEtG-positivity with last reported drink > 7 days prior). Among 211 participants (40.8% women), there were 44 (20.8%) lifetime abstainers, 32 (15.2%) former drinkers, and 135 (64.0%) current drinkers, including 106 (50.2%) with unhealthy drinking per AUDIT-C. Eighty-seven (41.2%) were uEtG-positive including 64 of 65 (98.5%) who drank ≤ 3 days prior and 17 of 134 (12.7%) underreported, all of whom admitted to recent drinking when results were discussed. uEtG was moderately concordant with AUDIT-C. Past drinking (versus lifetime abstinence) and longer time on antiretrovirals (≥ 12 months) were associated with underreporting. These data support further use of POC alcohol biomarkers in HIV and hepatitis research and clinical settings.

Contingency management intervention targeting co-addiction of alcohol and drugs among American Indian adults: Design, methodology, and baseline data.

BACKGROUND/AIMS: American Indian adults have some of the highest alcohol abstinence rates compared to the overall US population. Despite this, many American Indian people are more likely to concurrently use alcohol and illicit drugs and are less likely to participate and remain in outpatient treatment for alcohol and other drug use compared to the general US population. There is limited knowledge about effective interventions targeting alcohol and drug co-addiction among American Indian adults. Contingency management is a behavioral intervention designed to increase drug abstinence by offering monetary incentives in exchange for drug and alcohol negative urine samples. We aim to evaluate and describe a culturally tailored contingency management intervention to increase alcohol and other drug abstinence among American Indian adults residing in a Northern Plains reservation. METHODS: This 2 × 2 factorial, randomized controlled trial currently includes 114 American Indian adults with alcohol and/or drug dependence who are seeking treatment. Participants were randomized into one of four groups that received (1) contingency management for alcohol, (2) contingency management for other drug, (3) contingency management for both substances, or (4) no contingency management for either substance. We present descriptive, baseline data to characterize the sample and describe the modified contingency management approach that is specific to the community wherein this trial was being conducted. RESULTS: The sample is 49.1% male, with an average age of 35.8 years (standard deviation = 10.4 years). At baseline, 43.0% of the sample tested positive for ethyl glucuronide, 50.9% of participants self-reported methamphetamine as their most used drug, 36.8% self-reported cannabis, and 12.3% self-reported prescription opiates as their most used drug. Among randomized participants, 47.4% tested positive for cannabis, 28.1% tested positive for methamphetamine, 16.7% tested positive for amphetamines, and 2.1% tested positive for opiates. CONCLUSION: This is the first study to examine a culturally tailored contingency management intervention targeting co-addiction of two substances among American Indian adults. By establishing a tribal-university partnership to adapt, implement, and evaluate contingency management, we will increase the literature on evidence-based addiction treatments and research, while improving trust for addiction interventions among American Indian communities through ongoing collaboration. Moreover, results have implications for the use of contingency management as an intervention for co-addiction in any population.

[The development and validation of the method for the identification of ethyl glucuronide and ethyl sulfate as the markers of the consumption of ethyl alcohol during one's lifetime]. / Razrabotka i validatsiia metodiki opredeleniia étilgliukuronida i étilsul'fata kak markerov prizhiznennogo upotrebleniia étilovogo spirta.

The objective of the present study was the development and validation of the rapid reproducible method for the identification of ethyl glucuronide and ethyl sulfate allowing to store and transport the study specimens without the loss of the substances of interest by placing the samples on the paper. We have developed the validated technique for the detection and quantitative determination of ethyl glucuronide and ethyl sulfate in the cadaveric blood and urine by means of low-resolution tandem mass-spectroscopy with the use of deuterated derivatives of these substances as the internal standards. The low threshold for quantitative determination of both above substances is 50 ng/ml for the blood and 100 ng/ml for the urine. The method is characterized by the accuracy and precision with the coefficient of variation below 15% and the influence of the matrix with the coefficient of variation below 15%. The evaluation of stability of the two analytes in blood when stored in the dry condition on the paper carrier during 2 weeks showed that the coefficient of variation did not exceed 6.4%. The comparative study of ethyl glucuronide and ethyl sulfate in the samples of cadaveric blood and urine containing from 0 to 5.2% of ethyl alcohol was carried out. The methods for the transportation of the biological fluids and for the extraction of ethyl glucuronide and ethyl sulfate placed on the paper carrier (Whatman 903) have been proposed. The possibility has been demonstrated to use ethyl glucuronide and ethyl sulfate as the markers of the consumption of ethyl alcohol during one's lifetime for the purpose of investigation of the putrifactive changes of the blood components.