Forensic confirmatory analysis of ethyl sulfate—a new marker for alcohol consumption—by liquid-chromatography/electrospray ionization/tandem mass spectrometry

Ethyl sulfate (EtS)—a new direct marker for ethanol intake besides ethyl glucuronide (EtG) and others—was detected in urine samples by electrospray ionization tandem mass-spectrometry (LC-ESI-MS/MS). Ethyl sulfate sodium salt was used for method development, yielding a precursor [M − H]− m/z 125 and product ions m/z 97 [HSO4]− and m/z 80 [SO3]−. Pentadeuterated EtS (D5-EtS) was synthesized by esterification of sulfuric acid with anhydrous hexadeutero ethanol ([M − H]− m/z 130, product ions m/z 98 [DSO4]− and m/z 80 [SO3]−). After addition of D5-EtS and D5-EtG, urine samples were analyzed by direct injection into the gradient LC-MS/MS system. Analysis was performed in accordance with forensic guidelines for confirmatory analysis using one precursor and two product ions. EtS has been detected (in addition to EtG) in the urine samples of nine volunteers after drinking sparkling wine containing between 9 and 49 g of ethanol. Both EtS and EtG could be detected up to 36 h after consumption of alcohol. The excretion profile was found to be similar to that of EtG. No EtS was found in teetotalers’ urine samples. Method validation parameters are presented. EtS was stable in urine upon storage up to twenty days at room temperature. In addition to EtG, EtS can be used to detect recent alcohol consumption, thus providing a second marker for the time range of up to approximately one day after elimination of ethanol from urine samples. The determination of EtS can be used in addition to EtG as proof of ethanol consumption in workplace monitoring programs

CANNABIS USE AMONG A SAMPLE OF 16 TO 18 YEAR-OLD STUDENTS IN SWITZERLAND

Background: The aim of this study was to estimate the prevalence of cannabis use among Swiss students and to assess their attitudes regarding health and safety issues associated with drug use. Subjects and methods: After a workshop, 173 students (23.1% male, 75.7% female; 44.4% age 16, 43.8% age 17 and 11.8% age 18) from a Swiss school were surveyed by questionnaire. Results: 59.3% (n=103) of all participants had tried cannabis, and 30.1% of those who reported cannabis use had consumed more than 100 joints. Of those 103 students with cannabis experience, 6.8% rated the risk of cannabis-related psychic effects as low, and 9.8% were not concerned about driving under the influence of cannabis. In cases of heavy cannabis use, the chance of increased tobacco, alcohol or other drug use is higher than for those with less or no cannabis use at all (odds ratios of 4.33-10.86). Conclusions: This paper deals primarily with cannabis prevalence data in adolescents from previous studies and sources, and shows that our findings deviate significantly - and surprisingly - from past research. Our data from a school survey indicates higher cannabis use than data from official drug policy studies. Additionally, our data shows that the students’ self-reported attitudes towards health and safety issues were mostly realistic. The examination of methodological issues that might impact prevalence estimates should be added to the cannabis literature

ETHYL GLUCURONIDE: A BIOMARKER TO IDENTIFY ALCOHOL USE BY HEALTH PROFESSIONALS RECOVERING FROM SUBSTANCE USE DISORDERS

Aims: Physicians recovering from substance-related disorders are usually allowed to return to practice if they agree to remain abstinent from drugs, including alcohol, and to undergo random urine testing. Over 9000 physicians are currently involved in such monitoring programs in the US. To date, it has been difficult to adequately monitor abstinence from alcohol due to the short half-life of alcohol and no other highly specific marker. Ethyl glucuronide (EtG), a direct metabolite of alcohol, offers an extended window for assessment of drinking status (up to 5 days). Our aim was to assess the potential value of EtG testing in abstinence-based monitoring programs. Patients and methods: Urine samples were obtained from 100 participants in a physician monitoring program and additional samples were subsequently obtained ‘for cause', ‘to verify positive urine alcohol, when drinking was denied' and ‘in high risk individuals'. All participants had signed contracts agreeing to remain abstinent from mood-altering drugs, including alcohol, and had agreed to random urine testing. EtG was determined using LC/MS-MS in addition to standard testing. The main outcome measure were urine specimens positive for EtG versus those positive based on standard testing for alcohol and other drugs. Results: Among the initial 100 random samples collected, no sample was positive for alcohol using standard testing; however, seven were positive for EtG (0.5-196 mg/l), suggesting recent alcohol use. Subsequent EtG testing was performed clinically during the course of monitoring. Of the 18 tests performed to date, eight of eight tests performed ‘for cause' were positive for EtG but negative for all other drugs including urine alcohol. All eight were confirmed positive by self reported drinking by the patient when confronted regarding the positive test result. Of six tests performed to ‘confirm a positive urine alcohol' two were positive for EtG and confirmed positive by self reported drinking. For the other four samples, especially as two are from a diabetic, in vitro fermentation of ethanol is discussed. Conclusions: These data suggest that physicians in monitoring programs have a higher rate of unrecognized alcohol use than previously reported. Incorporation of EtG testing into alcohol abstinence monitoring can strengthen these program

CONCENTRATION OF FATTY ACID ETHYL ESTERS IN HAIR OF ALCOHOLICS: COMPARISON TO OTHER BIOLOGICAL STATE MARKERS AND SELF REPORTED-ETHANOL INTAKE

Aims: In a variety of clinical and forensic situations long term use of alcohol must be monitored. In this project we explore the utility of fatty acid ethyl esters (FAEE) in this regard. Additionally, we propose a cut-off value of FAEE to distinguish teetotallers/moderate/social drinkers from alcoholics or individuals drinking at harmful levels. Patients and methods: FAEE levels from 18 alcohol-dependent patients in detoxification were contrasted with those of 10 social drinkers and 10 teetotallers. FAEE in hair were determined, using headspace solid phase microextraction and gas chromatography mass spectrometry. CFAEE, as sum of the concentrations of four esters, was compared to a major FAEE, ethyl palmitate. PEth was measured in heparinized whole blood with a high pressure liquid chromatography (HPLC) method. Drinking validation criteria include self reports, phosphatidyl ethanol (PEth) in whole blood as well as the traditional markers of heavy drinking, gamma glutamyl transpeptidase (GGT), mean corpuscular volume (MCV) and carbohydrate deficient transferrin (CDT). Results: Receiver-operating characteristic (ROC) curve analysis for CFAEE, indicated a sensitivity of 100% and a specificity of 90% for a cut-off of 0.29 ng/mg. By using a cut-off of 0.4 ng/mg, CFAEE identified 94.4% correctly. CFAEE and ethyl palmitate were significantly associated (r = 0.945; P < 0.001) as were CFAEE and PEth (r = 0.527; P = 0.025). No significant correlation was found between CFAEE and total grams of ethanol consumed last month, blood-alcohol concentration at admission to the hospital, CDT, MCV, or GGT. Among the serum and blood markers, %CDT identified 47.1%, MCV 38.8% and GGT 72.2% of patients with chronic intake of higher amounts of ethanol correctly, whereas PEth achieved 100% accuracy. Conclusions: The data suggest that CFAEE is a potentially valuable marker of chronic intake of high quantities of ethanol. Furthermore, the results indicate that a reasonable and provisional FAEE cut-off to distinguish between social/moderate and heavy drinking/alcoholism in hair is 0.4 ng/m

Phosphatidylethanol (PEth) for Monitoring Sobriety in Liver Transplant Candidates: Preliminary Results of Differences Between Alcohol-Related and Non-Alcohol-Related Cirrhosis Candidates.

BACKGROUND Monitoring sobriety is mandatory for liver transplant (LT) candidates with alcohol-related cirrhosis in Germany. Prior to listing, abstinence of 6 months is required. However, little is known about biomarker performance in alcohol-related cirrhosis. Routine testing of ethyl glucuronide in urine (uEtG) or hair (hEtG) is prone to manipulation or is unfeasible in anuria. Phosphatidylethanol (PEth) in dried-blood spots is a promising alternative. We compared PEth with routine parameters and self-reports in alcohol-related and non-alcohol-related cirrhosis at our transplant center. MATERIAL AND METHODS All patients received self-report questionnaires (AUDIT & TLFB). Blood, urine and hair samples, as well as PEth dried-blood spots were drawn at baseline. In addition, survival analyses were conducted. RESULTS Out of 66 patients, 53 were listed for LT and 13 were candidates not listed so far. An alcohol-use disorder was found in 25 patients. Positive results for uEtG, hEtG, and PEth were found in 5/65, 9/65, and 34/66 cases, respectively. PEth positivity was found in 52% of patients with alcohol-related cirrhosis, while 53% of patients with other liver diseases were positive. While uEtG, hEtG, and TLFB correlated with higher PEth values, active waiting list status was significantly correlated with negative PEth values. During the mean follow-up of 41.15 months, 23 patients were transplanted (34.9%). None of the biomarkers significantly predicted survival. CONCLUSIONS PEth can importantly assist abstinence monitoring in LT candidates due to its high validity and objectivity. The high percentage of patients with alcohol consumption in the non-alcoholic liver disease cohort underscores the importance of testing all transplant candidates

Education and Training in Addiction Medicine and Psychology across Europe: A EUFAS Survey

Introduction: Training in addiction medicine and addiction psychology is essential to ensure the quality of treatment for patients with substance use disorders. Some earlier research has shown varying training between countries, but no comprehensive study of addiction training across Europe has been performed. The present study by the European Federation for Addiction Societies (EUFAS) aimed to fill this gap. Methods: A Delphi process was used to develop a questionnaire on specialist training in addiction treatment in 24 European countries. The final questionnaire consisted of 14 questions on either addiction medicine or addiction psychology, covering the nature and content of the training and institutional approval, the number of academic professorial positions, and the estimated number of specialists in each country. Results: Information was not received from all countries, but six (Belgium, Denmark, Ireland, Italy, Poland, and Romania) reported no specialized addiction medicine training, while 17 countries did. Seven countries (Belgium, France, Ireland, Italy, Russia, Switzerland, and the Netherlands) reported no specialized addiction psychology training, while 14 countries did. Training content and evaluation methods varied. Approval was given either by governments, universities, or professional societies. Eighteen countries reported having professorships in addiction medicine and 12 in addiction psychology. The number of specialists in addiction medicine or psychology varied considerably across the countries. Discussion: The survey revealed a large heterogeneity in training in addiction medicine and addiction psychology across Europe. Several countries lacked formal training, and where formal training was present, there was a large variation in the length of the training. Harmonization of training, as is currently the case for other medical and psychology specializations, is warranted to ensure optimal treatment for this under-served patient group

Optimal inference with suboptimal models:Addiction and active Bayesian inference

When casting behaviour as active (Bayesian) inference, optimal inference is defined with respect to an agent's beliefs - based on its generative model of the world. This contrasts with normative accounts of choice behaviour, in which optimal actions are considered in relation to the true structure of the environment - as opposed to the agent's beliefs about worldly states (or the task). This distinction shifts an understanding of suboptimal or pathological behaviour away from aberrant inference as such, to understanding the prior beliefs of a subject that cause them to behave less 'optimally' than our prior beliefs suggest they should behave. Put simply, suboptimal or pathological behaviour does not speak against understanding behaviour in terms of (Bayes optimal) inference, but rather calls for a more refined understanding of the subject's generative model upon which their (optimal) Bayesian inference is based. Here, we discuss this fundamental distinction and its implications for understanding optimality, bounded rationality and pathological (choice) behaviour. We illustrate our argument using addictive choice behaviour in a recently described 'limited offer' task. Our simulations of pathological choices and addictive behaviour also generate some clear hypotheses, which we hope to pursue in ongoing empirical work

Qualidade dos investimentos brasileiros: papel e limitações do BNDES

XX Encontro Nacional de Economia Política: desenvolvimento Latino-Americano, Integração e Inserção Internacional - UNILA, Foz do Iguaçu, 26 a 29 de maio de 2015O BNDES é a principal instituição de estímulo ao desenvolvimento nacional, responsável por realizar a alocação de uma parte signifi cativa da poupança para setores estratégicos. A hipótese testada é que a taxa de crescimento limitada do PIB não se deve apenas à baixa taxa de investimento, mas à baixa qualidade dos investimentos nacionais e dos recursos liberados pelo BNDES, destinados a setores que possuem baixos ganhos de produtividade. A análise da evolução histórica do BNDES mostra que ele não é imune a pressão política, a qual resulta em uma mudança frequente nos objetivos perseguidos, comprometendo os objetivos de longo prazo relacionados ao desenvolvimento nacional. Os fi nanciamentos do BNDES exercem uma pressão seletiva sobre a estrutura produtiva nacional, induzindo uma especialização regressiva, que benefi cia setores que geram menor crescimento no PIB e menor nível de rendaBanco Nacional de Desenvolvimento Econômico e Social (BNDES); Usina Hidrelétrica de Itaipu (ITAIPU); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e Universidade Federal da Integração Latino-Americana (UNILA

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