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Background: The COVID-19 pandemic reportedly had a significant impact on drug and alcohol use. In this article, we determine positivity rates for urine drugs of abuse and blood alcohol in 5 emergency departments (ED) in the greater Boston metropolitan area over a 4-year period (pre-, during, and post-COVID-19 pandemic)., Methods: Positivity rates for the urine drug screening (UDS) panel and blood alcohol concentration (>80 mg/dL; over the legal limit in MA) were calculated in patients presenting to one of the 5 ED (2 academic hospitals in Boston, MA and 3 community hospitals outside Boston, MA) during each of the 4 different time periods: pre-COVID (January 1, 2019 to December 31, 2019), stay-at-home (March 24, 2020 to May 18, 2020), during COVID (May 19, 2020 to March 28, 2021), and post-COVID (May 12, 2023 to August 31, 2023). Trend analysis was performed. Additionally, positivity rates during and post-COVID were compared to pre-COVID to determine any significant changes in drug positivity., Results: Stimulant (amphetamines and cocaine), cannabinoid, and methadone positivity increased during the pandemic and cocaine, cannabinoid, and methadone positivity remains elevated. By contrast, benzodiazepine and opioid (opiates, fentanyl, oxycodone) positivity decreased and remains lower post-COVID compared to pre-COVID. Patients in the ED with blood alcohol over the legal limit decreased both during and post-COVID., Conclusion: Our study showed that the COVID-19 pandemic significantly affected drug and alcohol positivity rates in patients presenting to the ED in greater Boston area. We encourage other institutions to perform similar analyses to help determine local drug use patterns and appropriate composition of UDS panels., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: People regularly contact emergency medicine services concerned that they have been exposed to drink spiking, i.e., exposure to drugs without their knowledge or permission. We identified drugs in blood and urine samples from patients suspecting exposure to drink spiking, with special consideration for drugs not reported taken by the patient (unreported drugs)., Methods: From September 2018 to May 2019, we collected blood and urine samples from patients 16 years or older presenting at an emergency clinic in Oslo, Norway, within 48 hours of suspected exposure to drink spiking. We also collected information on ethanol ingestion and drugs taken. Blood samples were analyzed for 20 classical recreational drugs using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and an automated enzymatic method for ethanol. Urine samples were analyzed using immunoassay methods and a specific gas chromatography mass spectrometry (GCMS) method for gammahydroxybutyrate (GHB)., Results: From 100 included patients (median age 24 years, 62 females), we collected 100 blood samples and 72 urine samples. Median time since exposure was 5 hours. Unreported drugs were found in 15 patients. Unreported drugs in the blood samples were clonazepam in 3, methylenedioxymethamphetamine (MDMA) in 3, amphetamine in 2, tetrahydrocannabinol (THC) in 2, tramadol in 1, cocaine in 1, and methamphetamine in 1. Unreported drugs in the urine samples were cocaine in 5, amphetamine in 4, ecstasy in 3, and cannabis in 2. Ethanol was found in 69 patients, all reporting ethanol ingestion. Median blood ethanol concentration was higher in patients with no unreported drugs detected, 1.00‰ (interquartile range (IQR) 0-1.52) vs. 0‰ (IQR 0-0.46) (p<0.001). GHB was not detected., Conclusion: Unreported drugs, possibly used for drink spiking, were found in 15% of patients. Blood ethanol concentration was higher when no unreported drugs were found. GHB was not detected in any patient., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dalaker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: About 95% of consumed ethanol is metabolized by oxidative pathways. Less than 1% is metabolized via nonoxidative pathways: glucuronidation, sulfation, and the formation of fatty acid esters of ethanol. In neonates, the glucuronidation pathway has been reported to be underdeveloped but matures with age. This work compared the test results of patients' random urine samples submitted to our facility for ethyl glucuronide (EtG) and ethyl sulfate (EtS) measurements across pediatric and adult populations., Methods: Test results (n = 63 498) from urine samples tested for EtG and EtS by quantitative liquid chromatography-tandem mass spectrometry at our facility were utilized for this study. EtG and EtS concentrations were compared across the age partitions 0 to 17 years (pediatric), 18 to 80 years (adult), and 81 to 100 years (geriatric). Eight pediatric patients from a tertiary academic hospital contributed clinical context via abstracted clinical information., Results: Across the individual age partitions, 60% to 65% of patients had both EtG and EtS present in urine. Approximately 5% to 10% of patients had only EtG, and 25% to 35% had neither metabolite present. The lowest percentages (<1.5%) had EtS present in the absence of EtG. Markedly, no pediatric patients had only EtS present; compared to the adult population, this was statistically significant (Fisher exact test, P = 0.025)., Conclusions: From the data presented in this work, EtG is more prevalent relative to EtS in urine samples of patients assessed for ethanol exposure., (© Association for Diagnostics & Laboratory Medicine 2024.)

This article traces the historical development of various biomarkers of acute and/or chronic alcohol consumption. Much of the research in this domain of clinical and laboratory medicine arose from clinics and laboratories in Sweden, as exemplified by carbohydrate deficient transferrin (CDT) and phosphatidylethanol (PEth). Extensive studies of other alcohol biomarkers, such as ethyl glucuronide (EtG), ethyl sulfate (EtS), and 5-hydroxytryptophol (5-HTOL), also derive from Sweden. The most obvious test of recent drinking is identification of ethanol in a sample of the person's blood, breath, or urine. However, because of continuous metabolism in the liver, ethanol is eliminated from the blood at a rate of 0.15 g/L/h (range 0.1-0.3 g/L/h), so obtaining positive results is not always possible. The widow of detection is increased by analysis of ethanol's non-oxidative metabolites (EtG and EtS), which are more slowly eliminated from the bloodstream. Likewise, an elevated ratio of serotonin metabolites in urine (5-HTOL/5-HIAA) can help to disclose recent drinking after ethanol is no longer measurable in body fluids. A highly specific biomarker of hazardous drinking is CDT, a serum glycoprotein (transferrin), with a deficiency in its N-linked glycosylation. Another widely acclaimed biomarker is PEth, an abnormal phospholipid synthesized in cell membranes when people drink excessively, having a long elimination half-life (median ~6 days) during abstinence. Research on the subject of alcohol biomarkers has increased appreciably and is now an important area of drug testing and analysis., (© 2023 John Wiley & Sons Ltd.)

Although kombucha is a popular fermented beverage, the presence of alcohol markers has not been well studied despite being potential indicators of unintentional impairment. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) were measured in oral fluid and urine collected after consumption of regular or hard kombucha. Participants drank within 20 min and provided all urine voids for 12 h, the first urine voids on days 2 and 3 and oral fluid specimens at fixed time points for 48 h. Screening employed liquid chromatography-tandem mass spectrometry (LC-MS-MS; EtS, 25 ng/mL cutoff [oral]; 100 ng/mL cutoff [urine]; EtG, 500 ng/mL cutoff [urine] and immunoassay (IA; EtG, 500 ng/mL cutoff [urine]). After consuming regular kombucha (n = 12 participants), EtS was not detected in oral fluid but both markers were detected by LC-MS-MS in urine specimens within the first five voids from 83% of participants with median (range) concentrations of 240 (100-3,700) ng/mL for EtS and 830 (530-2,200) ng/mL for EtG. Neither marker was positive by IA nor LC-MS-MS after day 1. After consuming hard kombucha (n = 7 participants), 2 (2.8%) of the 70 collected oral fluid specimens tested positive for EtS 3 h after consumption; however, 21 (30%) had EtS levels above the limit of detection (LOD, 10 ng/mL) after 0.5-8 h. Both markers were detected in urine specimens from all participants with median (range) concentrations of 3,381 (559-70,250) ng/mL for EtS and 763 (104-12,864) ng/mL For EtG. Urine specimens were negative for EtG and EtS by the end of the 48-hour study., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The objective of the current study is to determine how alcohol and illicit substance use contributes to motorcycle crash fatalities by examining the relationship between toxicology levels found postmortem and the behavior of riders and passengers in fatal motorcycle crashes., Materials and Methods: All motorcycle fatalities in Miami-Dade County, FL, from 2009 to 2014 were reviewed using the Miami-Dade County Medical Examiner's toxicology reports and the corresponding crash reports., Results: Positive alcohol/illicit substance detection was found in 44% of our population of 227 fatalities. When compared with those with a negative alcohol/illicit substance detection, those with a positive alcohol/illicit substance detection were more likely to be found at fault of the crash (77% versus 50%, P < 0.001), more likely to be in a single-vehicle crash (47% versus 21%, P < 0.001) and less likely to wear a helmet (44% versus 64%, P = 0.002). However, there was no significant relationship between speeding and alcohol/illicit substance detection (29% versus 33%, P = 0.748). In addition, a regression analysis demonstrated that there was less helmet use and more single-vehicle crashes with higher blood alcohol concentration., Conclusions: In fatal motorcycle crashes, alcohol and illicit substance use had a significantly negative impact on the risk aversion of motorcycle fatalities in regard to fault, helmet use, and single-vehicle crashes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Infants in the neonatal intensive care unit may be exposed to ethanol via medications that contain ethanol as an excipient and through inhalation of ethanol vapor from hand sanitizers. We hypothesized that both pathways of exposure would result in elevated urinary biomarkers of ethanol., Methods: Urine samples were collected from infants in incubators and in open cribs. Two ethanol metabolites, ethyl sulfate (EtS) and ethyl glucuronide (EtG), were quantified in infants' urine., Results: A subset of infants both in incubators and open cribs had ethanol biomarkers greater than the cutoff concentration that identifies adult alcohol consumption. These concentrations were associated with the infant having received an ethanol-containing medication on the day of urine collection. When infants who received an ethanol-containing medication were excluded from analysis, there was no difference in ethanol biomarker concentrations between the incubator and crib groups., Conclusions: Some infants who received ethanol-containing medications had concentrations of ethanol biomarkers that are indicative of adult alcohol consumption, suggesting potential exposure via ethanol excipients., Impact: Infants and newborns in the neonatal intensive care unit are exposed to concerning amounts of ethanol. No one has shown exposure to ethanol in these infants before this study. The impact is that better understanding of the excipients in medications given to patients in the NICU is needed. When physicians order medications in the NICU, the amount of excipient needs to be indicated.

Alcohol Liver Disease (ALD) is one of the most prevalent conditions leading to liver transplantation for end-stage liver disease. There is lacking evidence of regular urine screening testing (RUST) impact on survival or liver transplantation of ALD patients. The aims of this study were to compare the sensitivity of RUST, to assess its impact on survival and liver transplantation, and to evaluate factors associated with adherence to RUST. We performed a single-centered retrospective study (N = 84) with ALD candidates for liver transplantation. Demographic, biochemical and clinical variables were recorded at baseline. Adherence to RUST was evaluated during follow-up. The sensitivity of both RUST and self-reports were calculated for all drugs. Multivariable logistic and survival regression analyses were performed to explore associated factors and the impact of adherence to RUST, and positive results on survival. RUST had high sensitivity for identifying active drinkers (76.9%), smokers (78.9%) and cannabis users (83.3%). High adherence to RUST was inversely associated with mortality during follow-up. Presence of personality disorders negatively impacted (OR 0.29, CI 95% 0.08-0.97) adherence to RUST. Both RUST and self-reports should be carried out in this setting. Professionals involved in liver transplantation programs must promote adherence to RUST, primarily in patients with personality disorders.

In Saudi Arabia, alcohol consumption is prohibited by law, but interpreting postmortem ethanol can be complicated by its postmortem production. This study developed and validated a method using headspace gas chromatography with flame ionization detection and liquid chromatography tandem mass spectroscopy to detect ethanol and its polar metabolites (ethyl glucuronide [EtG] and ethyl sulfate [EtS]) in postmortem blood and urine specimens, respectively. All calibration curves were linear with coefficients of determination greater than 0.999. The limits of detection ranged 4.5-5.0mg/dL for ethanol and 0.05-0.06mg/L for EtG and EtS. The limits of quantification were 10.0mg/dL for ethanol and 0.075mg/L for EtG and EtS. Within-run precision was less than 11% for all analytes of interest. Matrix effects for EtG and EtS ranged 3-47%. After excluding matrix effects, analytical recoveries ranged 72-100%. This validated method was then used for routine postmortem forensic toxicology analyses in 592 routine postmortem cases to distinguish between antemortem ethanol consumption and its postmortem microbial formation. Among them, 98 blood samples (17%) were positive for ethanol or its polar metabolites. Thirty-two of these cases (33%) were positive for EtG and EtS and therefore due to antemortem ethanol consumption. The remaining 66 (67%) cases were negative for both EtG and EtS and therefore due to postmortem ethanol synthesis. Because this is the first study to report the problem of alcohol consumption in Saudi Arabia, further studies are essential for validating these findings., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Claimed intake of alcohol after a traffic incident, called the hip-flask defence, can be objectively assessed by different methods. One of them is the use of two consecutive ethanol concentrations in urine and the ratio between ethanol concentrations in urine and blood. Another one is the concentrations of ethyl glucuronide (EtG) and ethyl sulphate (EtS) in blood and their ratio to ethanol. The experimental basis for both these models is from single dose studies only. The aim of this study was therefore to describe the kinetics of ethanol, EtG and EtS after ingestion of two repeated doses of ethanol and to investigate the usefulness of the different models for the assessment of the hip-flask defence., Methods: Thirty-five subjects ingested a first dose of 0.51 g of ethanol per kilo body weight, and two hours later a second dose (the hip-flask drink) of 0.25, 0.51 or 0.85 g of ethanol per kilo body weight. Ten urine and 17 blood samples were collected and analysed for ethanol, EtG and EtS using fully validated methods. It was investigated if all subjects fulfilled the criteria for recent drinking, according to the two different models, when using the samples collected 180-240 minutes after start of first dose drinking. According to the first model, increase in urinary ethanol concentrations and a ratio UAC/BAC below 1.3 indicated recent drinking. According to the second model, increase in blood EtG concentrations and a ratio ethanol (g/kg)/EtG (mg/L) above 1 indicated recent drinking., Results: All subjects in the high dose group fulfilled all criteria for recent drinking. One subject in the medium dose group and nine subjects in the low dose group failed to show increasing UAC and/or a UAC/BAC ratio below 1.3. One subject in the low dose group failed to show increasing concentrations of blood EtG, but all subjects showed a ratio ethanol/EtG above 1., Conclusions: The present study showed, by the use of experimental data, that both two models used to investigate the hip-flask defence can be used, but only when the hip-flask dose is sufficiently high., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Gamma-hydroxybutyric acid (GHB) is a recreational drug with central nervous system depressing effects that is often abused. A urine GHB point-of-care test can be of great diagnostic value. The objective of this prospective study was to determine the performance of the new DrugCheck GHB Single Test and the Viva-E GHB immunoassay for urine samples in emergency department patients., Methods: Patients presented to the emergency department of the OLVG hospital in Amsterdam with a Glasgow Coma Scale score <15 and potential drug of abuse intoxication were included in the study. Between June 2016 and October 2017, 375 patients were included. Using the DrugCheck GHB Single Test (Express Diagnostics Int'l, Blue Earth, MN) and the Viva-E GHB immunoassay (Siemens Healthineers, The Hague, the Netherlands), patients' urine samples were tested for GHB (cutoff for a positive result, 10 or 50 mcg/mL GHB). To ensure quality, the results obtained were compared with those generated using a validated gas chromatography method. The tests were considered reliable if specificity and sensitivity were both >90%. Possible cross-reactivity with ethanol was investigated by analyzing ethanol concentrations in patients' samples., Results: Seventy percentage of the included patients was men, and the median age was 34 years old. The DrugCheck GHB Single Test's specificity and sensitivity were 90.0% and 72.9%, respectively, and using 50 mcg/mL as a cutoff value, its specificity and sensitivity improved to 96.7% and 75.0%, respectively. Serum and urine ethanol levels in the false-positive group were significantly higher compared with those in the true-negative group. The specificity and sensitivity of the Viva-E GHB immunoassay (cutoff value of 50 mcg/mL and excluding samples with ethanol levels ≥2.0 g/L) were 99.4% and 93.5%, respectively., Conclusions: The DrugCheck GHB Single Test's specificity was sufficient, whereas its sensitivity was poor, making it unsuitable for use at point-of-care. Contrarily, using 50 mcg/mL as the cutoff value and excluding samples with ethanol levels ≥2.0 g/L, the Viva-E GHB immunoassay showed acceptable results to detect clinically relevant GHB intoxications.

Background:  In order to reduce alcohol relapse after liver transplantation (LT), the German national guidelines for waiting-list maintenance and organ allocation demand a minimum 6-month period of alcohol abstinence pre-LT, confirmed by measuring urinary ethyl glucuronide (uEtG)., Methods:  Between January 2015 and June 2016, uEtG was measured at least once in 339 cirrhotic patients with an indication for LT at the University Medical Center Mainz. uEtG was measured with an enzyme-linked immunosorbent assay (ELISA) screening test (cutoff value: 500 µg/L). For uEtG values ≥ 500 µg/L, liquid chromatography-mass spectrometry (LC-MS/MS) was performed as a confirmatory assay. Data were collected prospectively in a transplant database., Results:  Of the 339 potential liver transplant candidates, uEtG was negative in 86.4 %. Most patients were male (64.3 %), with an average age of 56.42 ± 10.1 years. In the multivariate analysis, mean corpuscular volume (p = 0.001), urinary creatinine (p = 0.001), gamma-glutamyl transferase (p = 0.001), and hemoglobin (p = 0.003) were significantly associated with a positive uEtG test result. The sensitivity of the ELISA screening test was 100 % for uEtG values > 2000 µg/L, as confirmed by LC-MS/MS., Conclusion:  uEtG is an effective parameter to reveal alcohol consumption by patients on the waiting list for LT. The sensitivity of the ELISA is excellent for uEtG values > 2000 µg/L, for which LC-MS/MS confirmation could be omitted., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

This retrospective study sought to identify a regular pattern of limb bruising which occurs in association with suicidal or accidental hanging. Following exclusion of cases suspicious for homicide, 82 consecutive cases of hanging from a 10-year period were retrospectively reviewed to identify the pattern of traumatic limb injury in each case. Relevant information such as location, toxicology, and type of suspension was also noted. 72% of the reviewed cases had traumatic limb lesions, the majority of which occurred on the posterior upper limb and the anterior lower limb. Although the distribution of limb injury in our study mirrored that found in the literature, the incidence is much higher than in previous studies (7.4-20%). This could either be due to differences in confounding factors such as intoxication and location of hanging or differences in the practice of recording of limb trauma in hanging between centres. Neither type of suspension nor location of hanging were significantly associated with an increased incidence of traumatic limb injury. Positive toxicology was found to increase the likelihood of sustaining limb injury (p = .044084). In conclusion, the presence of this well documented pattern of traumatic limb lesions in cases of hanging should not always raise suspicion of foul play., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Background: We examined marijuana and alcohol use trends among drivers aged ≥16 years evaluated at Level I trauma centers before and after Arizona legalized medical marijuana in April 2011., Methods: We conducted interrupted time series (ITS) analysis of urine drug screens for marijuana metabolites and blood alcohol concentration (BAC) data from the 2008-2014 Arizona State Trauma Registry., Results: Among 30,083 injured drivers, 14,710 had marijuana test results, and 2590 were positive for marijuana; of these, 1087 (42%) also tested positive for alcohol. Among 23,186 drivers with BAC results, 5266 exceeded the legal limit for their age. Compared with prelaw trends (models if law had not been enacted), postlaw models showed small but significant annual increases in the proportions of drivers testing positive for either substance. By the end of 2014, the proportion of drivers testing positive for marijuana was 9.6% versus a projected 5.6% if the law had not been enacted, and the proportion of drivers with illegal BACs was 15.7% versus a projected 8.2%. When ITS was restricted to only substance-tested drivers, no significant differences were detected., Conclusions: Despite the small annual postlaw increases in the proportion of marijuana-positive drivers compared with the prelaw trend, alcohol-impaired driving remains a more prevalent threat to road safety in Arizona., (Published by Elsevier B.V.)

This study was conducted to understand alcohol kinetics for Koreans and to determine whether an individual is in absorption phase or elimination phase at the time of blood collection by analyzing of ethyl glucuronide and ethyl sulfate in blood. A total of 50 healthy adults was selected and assigned to drink 1g of ethanol per kg body weight of individual within 1h. Blood samples were then collected every 15min for the first 3h, 30min next 3h, and 1h last 9h. Urine samples were also collected from the individual, but not under the controlled environment. All samples were then analyzed by gas chromatography with a flame ionization detector (GC-FID) for alcohol and liquid chromatography-mass/mass spectrometry (LC-MS/MS) for EtG and EtS. The maximum BAC (Cmax) was 0.138% (g/100mL) in average under the controlled experimental condition. Alcohol elimination rates (β) in average were 0.020% for male and 0.024% for female, respectively. It was found that the ratio of UAC and BAC was less than 1 in the absorption phase and the average ratio of UAC and BAC was 1.47 in the elimination phase. The comparison of BAC (g/L) and EtG (mg/L) absorption and elimination curves showed that the intersection time was 3.9h in average. It is shown that the ratio of EtG (mg/L)/BAC (g/L) is higher than 1, the individual would be in elimination phase of BAC. At the time of Cmax, the ratio of EtG (mg/L)/BAC (g/L) was 0.255±0.132 (SD) in average., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Model cannons are usually considered to be harmless toys; therefore no legal regulations are required. Nevertheless, suicidal intentions or playful experimentation can turn this toy into a lethal weapon. This paper describes two cases of misuse of model cannons, leading to severe injuries and consequently death: the first case was the result of a suicidal intention, where the cannon caused a bullet injury into the forehead with marked signs of close-firing and intensive brain damage. The second case was an accidental event, where the cannon induced an entry wound at the left chest wall with surrounding carbonization and a fatal rupture of the heart. Circumstances of the lethal situations and mechanisms of the cannons leading to fatal injuries including ballistic considerations are described. The report is supported by a thorough literature research., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Driving under the influence of alcohol is a major problem for traffic-safety and a popular defence argument is alleged consumption after driving, commonly referred to as the hip-flask defence. Forensic toxicologists are often called as expert witnesses in drinking and driving cases where the suspect has claimed the hip-flask defence, to assess the credibility of the explanation. Several approaches to help the expert have been introduced but the scientific data used to support or challenge this is solely based on data from controlled single doses of ethanol administered during a short time and in abstinent subjects. In reality, we believe that even in drinking after driving cases, the subject many times has alcohol on board at time of the hip-flask drink. This questions the applicability of the data used as basis to investigate the hip-flask defence. To fill this knowledge gap, we aimed to investigate how blood and urine ethanol kinetics vary after an initial drinking session of beer and then a subsequent hip-flask drink of three different doses of whiskey. Fifteen subjects participated in the study and each provided 10 urine samples and 17 blood samples over 7h. The initial drink was 0.51g ethanol/kg and the second was either 0.25, 0.51, or 0.85g/kg. Our data suggested that the difference between the ethanol concentrations in two consecutive urine samples is a more sensitive parameter than the ratio between urine and blood alcohol to detect a recent intake when ethanol from previous intakes are already present in the body. Twelve subjects presented results that fully supported a recent intake using the criteria developed from a single intake of ethanol. Three subjects showed unexpected results that did not fully support a recent intake. We conclude that data from one blood sample and two urine samples provide good evidence for investigating the hip-flask defence even if alcohol was on board at the time of the hip-flask drink., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Urine ethanol is a common finding in urine drug-screening results. An unexpected finding of alcohol in urine can have serious implications for patients who have committed to pain-management contracts or are being counseled for substance abuse. Although laboratory screening for urine ethanol is highly specific and sensitive, the source of the ethanol can sometimes be unclear. This case report describes a 44-year-old Caucasian man with positive urine ethanol results who reported having abstained from alcohol. A test for urine ethyl-glucuronide and ethyl sulfate was used to validate the information in the patient history stating that the patient had not consumed alcohol for 1 year. Evaluation of the urinalysis results from the patient revealed fermentation in the context of glucosuria as the source of the urine ethanol.

Objective: Urine drug testing (UDT) is increasingly performed as a means of identifying aberrant behavior that may be grounds for discontinuation of long-term opioid therapy (LTOT). Little is known, however, about the ways in which positive UDT results may differentially inform decisions to discontinue LTOT based on the type of substance for which the UDT screened positive. The aim of this study was to examine the likelihood of clinician-initiated discontinuation of LTOT attributed to positive UDT results across three discrete categories of substances: (1) cannabis, (2) alcohol or illicit substances (excluding cannabis), and (3) controlled prescription medications that were not prescribed., Design: This retrospective study utilized the US Department of Veterans Affairs (VA) Health Care System. Corporate Data Warehouse to assemble a sample of 600 patients with substance use disorders and matched controls who were discontinued from LTOT in 2012. Comprehensive manual medical record review identified UDT results in the year prior to discontinuation and reason(s) for discontinuation., Patients, Participants: Patients with one or more UDTs positive for a single substance (N = 185) comprised the study sample., Main Outcome Measure(s): Likelihood of clinician-initiated discontinuation attributed to a positive UDT across the three categories., Results: Patients with one or more UDTs positive for cannabis were more likely to be discontinued from opioid therapy as a result of the positive UDT compared to those with one or more UDTs positive for nonprescribed prescription medication (adjusted odds ratio [OR] = 18.05, 95% CI = 7.29-44.66). Similarly, patients with UDTs positive for alcohol or illicit substances were more likely to be discontinued for the positive UDTs relative to patients who tested positive for nonprescribed prescription medications (adjusted OR = 13.10, 95% CI = 4.81-35.68). No difference in UDT-related discontinuation decisions was evident between patients with UDTs positive for alcohol/illicit substances versus cannabis (adjusted OR = 1.47, 95% CI = 0.57-3.77)., Conclusions: High odds of UDT-related discontinuation were found in patients who tested positive for cannabis, alcohol, or illicit substances, relative to nonprescribed prescription medications.

A recent update of the Italian Road Traffic Law (RTL 41/2016), established severe penal sanctions when drivers, driving under the influence of alcohol (DUI) or drugs (DUID), are involved in road accident that results in death or injuries. A study was carried out to assess the trends of consumption of alcohol, illicit drugs or pharmaceutical among injured drivers suspected for DUI or DUID from 2009 to 2016 in the region of Campania (Italy). Confirmation toxicological analyses were performed on 780 blood samples and 1017 urine samples collected from 1797 injured drivers. These drivers all tested positive for alcohol or drug use through immunoassay screening applied at hospital emergency units and their biological samples transferred to the Forensic Reference Laboratory (FRL) for confirmation analysis. The GC/HS-FID methodology was used to test Blood Alcohol Concentration (BAC). Qualitative and quantitative analyses for drugs were performed using the GC/MS or LC-MS/MS methodology. The BAC >0.5g/L was confirmed in 91.5% of drivers suspected for DUI cases and in 93% of DUID respectively. In DUI cases, results show an increasing incidence of road accidents involving drivers with BAC above 1.5g/L while at concentrations above 0.8g/L alcohol and drugs are both used. Among the suspected DUID cases, the intake of alcohol in association with drugs has consistently increased over time and positive results on blood samples was confirmed for multiple drugs (20%) or cannabis and cocaine alone (18%) followed by benzodiazepines (6%) and methadone (3.5%) respectively. The majority of injured drivers suspected for DUID (1017 cases) did not authorize blood sampling, therefore only urine was analyzed showing the prevalent use of cannabis, followed by multiple drug>cocaine>benzodiazepines>opiates. Among 1797 drivers, suspected at screening for DUI or DUID, 15.4% of cases (64 blood and 213 urine samples) were not confirmed by GC/HS, GC/MS or LC-MS/MS analysis. In forensic toxicological investigations, it is mandatory to satisfy the best quality standards, which is not achievable if immunochemical screening is only performed on urine. Therefore, only confirmed positive results of alcohol or drugs on blood samples can represent conclusive evidence to demonstrate the DUI or DUID related offences. An improvement of the protocols currently applied in Italy for the assessment of DUI or DUID crimes is needed and the confirmation analysis on blood should be considered mandatory., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) in hair are effective direct biomarkers of ethanol ingestion, whose analytical determination can be used to discriminate between chronic and occasional ethanol intake. Ethanol is a compound widely used in some workplaces (e.g., clinics, hospitals) and is present in considerable amounts in mouthwash for oral cleaning, medications, cosmetic products, hydro-alcoholic disinfectants and antiseptics for hands. This study examined the ethyl alcohol exposure derived from hand disinfectants (in gel form) by simulating the typical occupational situation of medical-health workers (healthcare workers, nurses, surgeons, etc.) who frequently wash their hands with antiseptic sanitizer. Two types of hand disinfectants with 62% w/w of ethanol content were daily applied to the hands of a teetotaler for 20 times a day, for 4 consecutive weeks, thus simulating a typical workplace situation and a cumulative dermal exposure to ethanol of ~1,100 g. Different matrices (head, chest and beard hair, urine) were regularly sampled and analyzed using a ultra high-performance liquid chromatography tandem massspectrometry validated method for EtG and a (HS)SPME-GC-MS validated technique for FAEEs. The data obtained showed that a significant dermal absorption and/or inhalation of ethanol occurred, and that the use of detergents produce urinary EtG concentrations both higher than the cut-offs normally used for clinical and forensic analyses (either 100 and 500 ng/mL, depending on the context). The concentrations of the ethanol metabolites in the keratin matrices were, respectively, below the cut-off of 7 pg/mg for EtG and below 0.5 ng/mg for FAAEs (0.35 ng/mg for ethyl palmitate). In conclusion, the regular use of alcohol-based hand sanitizers can affect the concentration of urinary EtG and lead to positive analytical results, particularly when specimens are obtained shortly after sustained use of ethanol-containing hand sanitizer. On the other hand, direct biomarkers of alcohol abuse in the keratin matrix are capable of distinguishing between ethanol consumption and incidental exposures.

Background: Efforts aimed at reducing alcohol-related harm include early detection of risky drinkers as well as detection of early relapse in patients with alcohol dependence. Ethyl glucuronide (EtG) has been proven to be a reliable biomarker for the detection of recent drinking; however, no randomized, diagnostic trial to date has tested its impact on drinking outcomes. The aim of this study was to assess, in a randomized design, the implications of EtG screening on alcohol outcomes, compared to screening with a low sensitivity biomarker such as ethanol., Methods: Alcohol dependent outpatients were randomized to either 24 weeks of continuous screening with EtG or ethanol. Patients were aware of screening methods and results. After 24 weeks, all participants were screened with EtG. Self-reports were also gathered. A logistic regression compared the rate of EtG positive results at study end between groups. Generalized estimating equations evaluated the descending monthly rate of EtG positive patients in the EtG group., Results: A total of 162 patients were randomized. During the study period, the ethanol group showed less patients with positive screens (19/64 (29.7%) vs 58/98 (59%)). After 24 weeks, the EtG group showed a greater number of patients having a negative screening test compared to ethanol subjects when they were all screened with EtG (5/62 (8.1%) vs 13/39 (33.3%)). A significant decrease in the rate of EtG positive patients was found for the first three months of the study., Conclusions: Routine screening with EtG seems to reduce drinking and improve abstinence rates in alcohol dependent outpatients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The study objective was to compare rates of alcohol use between urine ethanol testing and self- reporting (Method: 1) and Phosphatidylethanol (PEth) dried blood spot testing and self-reporting (Method: 2)., Methods: This was a prospective observational study in an obstetric clinic with universal alcohol screening., Results: Method: 1 identified 11 patients with alcohol use (5 urine and 6 self-reported); Method: 2 identified 28 (22 PEth and 6 self-reported) out of 315 patients (one patient positive for both urine and PEth). The six patients with self-reported use had negative urine and PEth testing. We had fair agreement between the two methods (282 negative and 7 positive; 289/314=92.0%; Kappa 0.32, p<0.001); method 2 identified significantly more women (McNemar, p<0.001). Combining methods: resulted in an alcohol detection rate of 10.2% (32/314)., Conclusion: Method: 2 identified more alcohol users than Method: 1. Combining both methods: identified the most alcohol consumption., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: It has been postulated that the hangover state starts when breath alcohol concentration is zero., Methods: Data from 2 studies that assessed ethanol in breath, blood and urine were compared., Results: The data revealed that ethanol may still be present in the blood and urine during the hangover state, despite breath analyser readings of zero., Discussion: As ethanol is still present in the body despite zero breath alcohol readings, the current consensus to postpone cognitive testing in hangover studies until breath alcohol concentration is zero should be reconsidered., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Phosphatidylethanol (PEth) is a new, highly specific alcohol marker. The aim of this study was to assess its diagnostic value in the liver transplant setting. In 51 pre- and 61 post-transplant patients with underlying alcoholic liver disease PEth, ethanol, methanol, carbohydrate-deficient transferrin (CDT), and ethyl glucuronide in urine (uEtG) and hair (hEtG) were tested and compared with patients' questionnaire reports. Twenty-eight (25%) patients tested positive for at least one alcohol marker. PEth alone revealed alcohol consumption in 18% of patients. With respect to detection of alcohol intake in the preceding week, PEth showed a 100% sensitivity. PEth testing was more sensitive than the determination of ethanol, methanol, CDT or uEtG alone [sensitivity 25% (confidence interval (CI) 95%, 7-52%), 25% (7-52%), 21% (6-45%) and 71% (41-91%), respectively], or ethanol, methanol and uEtG taken in combination with 73% (45-92%). Specificity of all markers was 92% or higher. Additional testing of hEtG revealed alcohol consumption in seven patients, not being positive for any other marker. Phosphatidylethanol was a highly specific and sensitive marker for detection of recent alcohol consumption in pre- and post-transplant patients. The additional determination of hEtG was useful in disclosing alcohol consumption 3-6 months retrospectively., (© 2017 Steunstichting ESOT.)

Background Detection of alcohol consumption in clients undergoing treatment for alcohol dependence can be difficult. The ethanol metabolites ethyl glucuronide and ethyl sulphate are detectable for longer in urine than either breath ethanol or urine ethanol. Our aim was to develop a liquid chromatography-tandem mass spectrometry method for urine ethyl glucuronide and ethyl sulphate for use in a routine clinical laboratory and define clinical cut-offs in a large population who had not consumed alcohol for at least two weeks. Methods Urine samples were diluted in 0.05% formic acid in HPLC grade water and then directly injected onto a Waters Acquity ultra high performance liquid chromatography coupled to a Waters TQ Detector. Eighty participants were recruited who had not consumed alcohol for at least two weeks to define cut-offs for urine ethyl glucuronide and ethyl sulphate. Samples and alcohol diaries were also collected from 12 alcohol-dependent clients attending a treatment programme. Results The assay was validated with a lower limit of quantitation of 0.20 mg/L for ethyl glucuronide and 0.04 mg/L for ethyl sulphate. Accuracy, precision, linearity and recovery were acceptable. Cut-offs were established for ethyl glucuronide, ethyl sulphate and ethyl sulphate/creatinine ratio (≤0.26 mg/L, ≤0.22 mg/L and ≤0.033 mg/mmol, respectively) in a non-drinking population. The validated cut-offs correctly identified clients in alcohol treatment who were continuing to drink alcohol. Conclusions A simple liquid chromatography-tandem mass spectrometry method for urine ethyl glucuronide and ethyl sulphate has been validated and cut-offs defined using 80 participants who had not consumed alcohol for at least two weeks. This is the largest study to date to define cut-offs for ethyl glucuronide, ethyl sulphate and ethyl sulphate/creatinine ratio.

Background: The aim of this study was to examine the relationship between urine ethanol concentration and alcohol hangover severity., Methods: N = 36 healthy social drinkers participated in a naturalistic study, comprising a hangover day and a control day. N = 18 of them have regular hangovers (the hangover group), while the other N = 18 claim to be hangover immune (hangover-immune group). On each test day at 9.30 am, urine samples were collected. Participants rated their overall hangover severity on a scale from 0 (absent) to 10 (extreme), as well as 18 individual hangover symptoms., Results: Urine ethanol concentration was significantly higher on the hangover day when compared to the control day (p = 0.006). On the hangover day, urine ethanol concentration was significantly lower in the hangover-immune group when compared to the hangover group (p = 0.027). In the hangover-immune group, none of the correlations of urine ethanol concentration with individual hangover symptoms was significant. In contrast, in the hangover group, significant correlations were found with a variety of hangover symptoms, including nausea, concentration problems, sleepiness, weakness, apathy, sweating, stomach pain, thirst, heart racing, anxiety, and sleep problems., Conclusion: Urine ethanol levels are significantly associated with the presence and severity of several hangover symptoms., Competing Interests: Compliance with ethical standards Declaration of interest This study was supported by the Utrecht University. Joris Verster has received grants/research support from the Dutch Ministry of Infrastructure and the Environment, Janssen Research and Development, Nutricia, Takeda, and Red Bull and has acted as a consultant for the Canadian Beverage Association, Centraal Bureau Drogisterijbedrijven, Coleman Frost, Danone, Deenox, Eisai, Janssen, Jazz, Purdue, Red Bull, Sanofi-Aventis, Sen-Jam Pharmaceutical, Sepracor, Takeda, Transcept, Trimbos Institute, and Vital Beverages. Karel Brookhuis has received grants/research support from NWO, the Dutch Ministry of Infrastructure and the Environment, European Commission, Wyeth, Sanofi, Schering, Nissan, JARI, Mercedes Benz, and Verbond van Verzekeraars. Johan Garssen is a part-time employee of Nutricia Research. The other authors have no potential conflicts of interest to disclose.

Introduction: The surging popularity of all-terrain vehicles (ATV) in the United States has caused an "epidemic of injuries and mortality." The U.S. Consumer Product Safety Commission reported 99,600 injuries and 426 fatalities from ATV accidents in 2013. The aim of this study was to examine the relationship between helmet use and positive toxicology screenings on outcomes in ATV accident victims., Methods: This is a retrospective study of patients admitted to a Level 1 Trauma Center in southwestern West Virginia following an ATV accident between 2005 and 2013. Data were obtained from the institution's Trauma Registry., Results: A total of 1,857 patients were admitted during the study period with 39 (1.9%) reported deaths. Positive serum alcohol and/or urine drug screens were obtained in 66.4% of the patients tested (n=1,293). Those with positive screenings were 9.5% less likely to utilize a helmet (13.2% vs. 22.7%, p<0.001); and the lack of helmet use was associated with an increase in traumatic brain injury (57.1% vs. 41.7%, p<0.001). Positivity for substances or the lack of helmet use was significantly associated with higher morbidity. Lack of helmet use resulted in a 3.94-fold increase in the risk of discharge in a vegetative state or death., Conclusions: Drugs and alcohol use may predispose riders to be less likely to wear helmets and significantly increase the risk of a poor clinical outcome following an ATV accident. Rigorous efforts should be made to enhance safety measures through educational endeavors and amendment of current regulations to promote safe and responsible use of ATVs., Practical Applications: Modification of regulatory requirements should be considered in order to mandate the wearing of helmets during ATV operation. In addition, expansion of safety programs should be considered in an effort to improve availability, affordability and awareness of safe ATV practices., (Copyright © 2016 Elsevier Ltd and National Safety Council. All rights reserved.)

The forensic utility of N-acetyltaurine (NAcT) in urine as a marker for ethanol intake was examined. A HILIC-based liquid chromatography method for the mass spectrometric determination of NAcT, taurine, and creatinine in urine was developed and validated to investigate NAcT formation and elimination in a drinking study. Thereby, eight subjects ingested 0.66 to 0.84 g/kg alcohol to reach a blood alcohol concentration (BAC) of 0.8 g/kg. Blood and urine were taken every 1.5-2 h, during the first 8 h. NAcT and taurine levels were measured and corrected for the urine's dilution by normalization to a creatinine concentration of 1 mg/mL. For the determination of NAcT and taurine, uncorrected lower limits of quantitation (LLOQs) were at 0.05 μg/mL of urine. In the drinking study, NAcT proved to be an endogenous compound, which is present at a range of 1.0 to 2.3 μg/mL in urine of alcohol-abstinent subjects. Maximum NAcT concentrations were reached in samples taken 3 to 6 h after the start of drinking, whereby an upregulation in N-acetyltaurine could be found for all the subjects. The mean peak concentrations (c̅ max) of 14 ± 2.6 μg/mL (range 9-17.5 μg/mL) were reached. Within 24 h, the NAcT levels declined to endogenous concentrations. The detectability of NAcT was found to be slightly shifted compared to BAC: When BAC was not detectable anymore, NAcT levels were still elevated. After 24 h, when ethyl glucuronide (EtG) and ethyl sulfate (EtS) were still detectable, NAcT concentrations showed endogenous levels again. Positive NAcT results can be used as an indicator for recent alcohol consumption. A direct relationship between NAcT and taurine concentrations could not be found. Graphical abstract N-acetyltaurine concentrations for eight subjects during the first 24 h after an alcohol consumption of 0.8 g/kg.

(1)H NMR spectroscopy was employed to investigate the repercussion of Origanum dictamnus tea ingestion in several volunteers' urine metabolic profiles, among them two with chronic inflammatory bowel diseases (IBD), mild IBD and Crohn's disease. Herein, we demonstrate that the concentrations of a lot of urinary metabolites such as hippurate, trimethylamine oxide (TMAO), citrate, and creatinine are altered, which prompts the intestinal microflora function/content perturbation as well as kidney function regulation by dictamnus tea. Interestingly, our preliminary results showed that a high dose of dictamnus tea intake appeared to be toxic for a person with Crohn's disease, since it caused high endogenous ethanol excretion in urine. All subjects' metabolic effects caused by the dictamnus tea appeared to be reversible, when all volunteers stopped its consumption. Finally, we highlight that individuals' metabolic phenotype is reflected in their urine biofluid before and after the dictamnus tea effect while all individuals have some common and different metabolic responses to this tea, implying that each phenotype has a quite different response to this tea consumption.

Background: During hand antisepsis, health care workers (HCWs) are exposed to alcohol by dermal contact and by inhalation. Concerns have been raised that high alcohol absorptions may adversely affect HCWs, particularly certain vulnerable individuals such as pregnant women or individuals with genetic deficiencies of aldehyde dehydrogenase., Methods: We investigated the kinetics of HCWs' urinary concentrations of ethanol and its metabolite ethyl glucuronide (EtG) during clinical work with and without previous consumption of alcoholic beverages by HCWs., Results: The median ethanol concentration was 0.7 mg/L (interquartile range [IQR], 0.5-1.9 mg/L; maximum, 9.2 mg/L) during abstinence and 12.2 mg/L (IQR, 1.5-139.6 mg/L; maximum, 1,020.1 mg/L) during alcohol consumption. During abstinence, EtG reached concentrations of up to 958 ng/mL. When alcohol consumption was permitted, the median EtG concentration of all samples was 2,593 ng/mL (IQR, 890.8-3,576 ng/mL; maximum, 5,043 ng/mL). Although alcohol consumption was strongly correlated with both EtG and ethanol in urine, no significant correlation for the frequency of alcoholic hand antisepsis was observed in the linear mixed models., Conclusions: The use of ethanol-based handrub induces measurable ethanol and EtG concentrations in urine. Compared with consumption of alcoholic beverages or use of consumer products containing ethanol, the amount of ethanol absorption resulting from handrub applications is negligible. In practice, there is no evidence of any harmful effect of using ethanol-based handrubs as much as it is clinically necessary., (Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

It is reasonable to expect the presence of multiple drugs to present a complicated picture of toxicity. We report a fatal case involving a young man who purchased illicit drugs and knowingly consumed them. After consuming these drugs and going to sleep in his friend's car, he was found unresponsive the next morning with no signs of physical violence. Drugs found in the peripheral blood at autopsy were oxymorphone, methylone and ethanol at concentrations of 0.106, 0.50 and 130 mg/dL, respectively. The levels of oxymorphone and methylone in peripheral blood were comparable to those observed in other reported fatalities. Cocaine and benzoylecgonine were detected in the urine but not in the blood. Measureable concentrations were also observed for oxymorphone and methylone in urine, liver, kidney and bile. The physical findings at autopsy included pulmonary edema. This is the only reported fatal case involving this combination of drugs encountered in our laboratory., (Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Context: An increasing number of new psychoactive substances (NPS) of different chemical classes have become available through marketing and sale over the Internet. This report from the Swedish STRIDA project presents the prevalence, laboratory results, and clinical features in a series of intoxications involving the stimulant NPS α-pyrrolidinovalerophenone (α-PVP), a potent dopamine re-uptake inhibitor, over a 4-year period., Study Design: Observational case series of consecutive patients with admitted or suspected intake of NPS presenting to hospitals in Sweden from 2012 to 2015., Patients and Methods: In the STRIDA project, blood and urine samples are collected from intoxicated patients with admitted or suspected intake of NPS or unknown drugs presenting to hospitals over the country. Analysis of NPS is performed by mass spectrometry multicomponent methods. Clinical data are collected when caregivers consult the Swedish Poisons Information Centre (PIC), and retrieved from medical records. The severity of poisoning is graded retrospectively using the Poisoning Severity Score (PSS). The inclusion criteria for this study included absence of other stimulants than α-PVP., Results: During the 4-year study period, 23 intoxications were originally coded as "α-PVP related" out of a total 3743 NPS-related inquiries (0.6%) at the PIC. The present study covered 42 analytically confirmed cases in which α-PVP was the only stimulant detected. The age range of patients was 20-58 (median 32) years, of which 79% were males. The α-PVP concentration in serum was 4.0-606 (median 64; n = 42) ng/mL and 2.0-41,294 (median 1782; n = 25) ng/mL in urine. There was no statistically significant association between the serum α-PVP concentration and urinary α-PVP/creatinine ratio in 25 cases, where both sets of data were available. In 14/42 (33%) cases, α-PVP was the only psychoactive substance identified. In the remaining cases, additional substances comprised opioids, benzodiazepines, and ethanol. The main clinical manifestations were tachycardia (80%), agitation (70%), hypertension (33%), hallucinations (20%), and delirium (18%). Classification of poisoning severity yielded 25 (60%) moderate (PSS 2), 7 (17%) severe (PSS 3), and 2 fatal cases (PSS 4)., Conclusions: In analytically confirmed α-PVP intoxication cases involving no other stimulant drugs, the urine and serum concentrations showed high variability. The clinical features were consistent with a severe sympathomimetic toxidrome. The results further demonstrated that α-PVP prevailed as a drug of abuse after being classified as a narcotic substance, and despite a high incidence of severe poisonings and fatalities. However, the low prevalence of α-PVP cases registered at the PIC suggested that many were unaware of the actual substance they had taken.

Ethnopharmacological Relevance: Eurycoma longifolia (Tongkat Ali, TA) roots have been ethnically used as a remedy to boost male sexual desire, libido, energy and fertility., Aim of the Study: The study evaluated the effect of TA extracts with different quassinoid levels on rats sperm count and examined corresponding post-treatment urinary metabolic changes., Materials and Methods: Twenty-four male Sprague-Dawley rats, categorized into 4 groups of 6 rats each, were orally administered for 48 days with water for the control (group 1), 125mg/kg of TA water extract (TAW, group 2), 125mg/kg of TA quassinoid-poor extract (TAQP, group 3) and 21mg/kg of TA quassinoid-rich extract (TAQR, group 4). Upon completion of the 48-day treatment, the urine samples were analyzed by NMR and the animals were subsequently sacrificed for sperm count analysis. The urine profiles were categorized according to sperm count level., Results: The results showed that the sperm count in TAW- and TAQR-treated groups was significantly higher compared to the TAQP-administered and control groups. The orthogonal partial least squares discriminant analysis (OPLS-DA) model indicated a clear separation among the urine profiles with respect to sperm count level. Urine (1)H-NMR profiles of the high-sperm count group contained higher concentrations of trigonelline, alanine, benzoic acid and higher intensity of a signal at 3.42ppm, while ethanol was at higher concentration in the normal-sperm count group., Conclusions: The results proved the efficacy of quassinoids on sperm count increase in rats and provided quantitative markers in urine suitable for analysis of sperm profile and male fertility status., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Urine drug screens are commonly performed to identify drug use or monitor adherence to drug therapy. The purpose of this retrospective study was to evaluate the true positive and false positive rates of one of our in-house urine drug screen panels. The urine drugs of abuse panel studied consists of screening by immunoassay then positive immunoassay results were confirmed by mass spectrometry. Reagents from Syva and Microgenics were used for the immunoassay screen. The screen was performed on a Beckman AU5810 random access automated clinical analyzer. The percent of true positives for each immunoassay was determined. Agreement with previously validated GC-MS or LC-MS-MS confirmatory methods was also evaluated. There were 8,825 de-identified screening results for each of the drugs in the panel, except for alcohol (N = 2,296). The percent of samples that screened positive were: 10.0% for amphetamine/methamphetamine/3,4-methylenedioxy-methamphetamine (MDMA), 12.8% for benzodiazepines, 43.7% for opiates (including oxycodone) and 20.3% for tetrahydrocannabinol (THC). The false positive rate for amphetamine/methamphetamine was ∼14%, ∼34% for opiates (excluding oxycodone), 25% for propoxyphene and 100% for phencyclidine and MDMA immunoassays. Based on the results from this retrospective study, the true positive rate for THC drug use among adults were similar to the rate of illicit drug use in young adults from the 2013 National Survey; however, our positivity rate for cocaine was higher than the National Survey., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Ethyl Glucoronide (EtG) and Ethyl Sulfate (EtS) have shown promise as biomarkers for alcohol and may be sensitive enough for use with pregnant women in whom even low-level alcohol use is important. However, there have been reports of over-sensitivity of EtG and EtS to incidental exposure to sources such as alcohol-based hand sanitizer. Further, few studies have evaluated these biomarkers among pregnant women, in whom the dynamics of these metabolites may differ., Objectives: This study evaluated whether commercial EtG-EtS testing was vulnerable to high levels of environmental exposure to alcohol in pregnant women., Methods: Two separate samples of five nurses-one pregnant and the other postpartum, all of whom reported high levels of alcohol-based hand sanitizer use-provided urine samples before and 4-8 hours after rinsing with alcohol-based mouthwash and using hand sanitizer. The five pregnant nurses provided urine samples before, during, and after an 8-hour nursing shift, during which they repeatedly cleansed with alcohol-based hand sanitizer (mean 33.8 uses). The five postpartum nurses used hand sanitizer repeatedly between baseline and follow-up urine samples., Results: No urine samples were positive for EtG-EtS at baseline or follow-up, despite use of mouthwash and-in the pregnant sample-heavy use of hand sanitizer (mean of 33.8 uses) throughout the 8-hour shift., Conclusions/importance: Current, commercially available EtG-EtS testing does not appear vulnerable to even heavy exposure to incidental sources of alcohol among pregnant and postpartum women.

Alcohol consumption during pregnancy may lead to severe foetal damage, such as foetal alcohol spectrum disorders. It is known that pregnant women under-report to questionnaires about alcohol consumption. It is therefore necessary to determine alcohol consumption during pregnancy objectively. We present 2 pregnant women with negative urine tests for ethyl glucuronide (EtG) and alcohol. However, analysis of two other biomarkers, phosphatidylethanol (PEth) in blood and fatty acid ethyl esters (FAEE) in meconium, revealed alcohol consumption during pregnancy by both women. Analysis of PEth can yield additional information alongside EtG testing. This is due to the much longer half-life of PEth. Meconium testing for FAEE provides relevant information about alcohol consumption during the second and third trimesters. Both PEth and meconium analysis can help identify women who have consumed alcohol during pregnancy. Appropriate counselling and follow-up can be given to these mothers and their children.

This study disproves the reliability of n-propanol as a biomarker to establish whether the ethanol found in postmortem blood is derived from antemortem ingestion or postmortem putrefactive processes. Two groups of rats were given ethanol or normal saline solution, respectively, and sacrificed 1.5 h later. After putrefaction, blood and, in a few cases, urine samples from the rats were analyzed for ethanol and n-propanol by head-space gas chromatography equipped with flame ionization detection. Although the concentration ratios of ethanol/n-propanol in the postmortem blood collected from the bodies without prior alcohol consumption were expected to be <20 (as per limited case reports and previous in vitro studies), in samples from several rats that were on saline solution, this ratio was found to exceed 20. In conclusion, the concentration ratio of ethanol/n-propanol in postmortem blood does not allow for the discernment between antemortem ingestion and the postmortem synthesis of ethanol., (© 2015 American Academy of Forensic Sciences.)

Aims: To test the screening performance of urinary ethyl glucuronide (EtG) under routine clinical conditions in a sample of alcohol-dependent outpatients, comparing it against urinary ethanol, self reports and clinical judgment., Methods: A cross-sectional study under routine conditions was conducted in February 2015, where 613 consecutive urinary samples, provided by 188 outpatients with alcohol use disorders, were analyzed for ethanol and EtG (cut-off level = 500 ng/ml). Clinical variables such as the presence of aversive medication, comorbidities and clinician judgment were also collected. The discrepancy between the number of alcohol and EtG positives was recorded. A logistic regression analysis including clinical variables was conducted to assess for predictors of EtG positivity., Results: Urinary alcohol yielded 9 positives (1.5% of all urine samples) belonging to 8 patients. EtG yielded 136 positives (22% of all urine samples) belonging to 74 patients. Of these, 93.4% (127 of 136) were negative for alcohol. All urinary alcohol positives resulted in EtG positives. The clinician judged 48 samples from 26 patients as belonging to not abstinent patients and 550 samples from 178 patients as belonging to abstinent patients. She was unsure in 15 samples from 15 patients. When comparing it against EtG as the gold standard, the area under the curve was 0.592. Self reports were extremely unreliable in this study, with only 5 patients reporting drinking in a total of 6 urine samples. In the logistic regression model, only aversive medications (OR 2.1, 95% CI 1.3-3.3) and clinician judgment (OR 2, 95% CI 1.4-2.9) resulted in significant effects., Conclusions: EtG performed largely better than ethanol for urine screening in alcohol outpatients, detecting an extra 20.4% (125 out of 613) of positives. It means that for each alcohol-positive sample, there were 15 EtG-positive samples. Although better than ethanol, clinician judgment was also not performed efficiently. If routinely implemented in the screening of alcohol outpatients, EtG might bring relevant changes that merit further research., (© 2016 S. Karger AG, Basel.)

Humans liberally use ethanol for its facilitating effects on social interactions but its effects on central nervous system function remain underexplored. We have recently described that very low doses of ethanol abolish long-term potentiation (LTP)-like plasticity in human cortex, most likely through enhancement of tonic inhibition [Lücke et al, 2014, Neuropsychopharmacology 39:1508-18]. Here, we studied the effects of low-dose ethanol on long-term depression (LTD)-like plasticity. LTD-like plasticity was induced in human motor cortex by paired associative transcranial magnetic stimulation (PASLTD), and measured as decreases of motor evoked potential input-output curve (IO-curve). In addition, sedation was measured by decreases in saccade peak velocity (SPV). Ethanol in two low doses (EtOH<10mM, EtOH<20mM) was compared to single oral doses of alprazolam (APZ, 1mg) a classical benzodiazepine, and zolpidem (ZLP, 10 mg), a non-benzodiazepine hypnotic, in a double-blinded randomized placebo-controlled crossover design in ten healthy human subjects. EtOH<10mM and EtOH<20mM but not APZ or ZLP enhanced the PASLTD-induced LTD-like plasticity, while APZ and ZLP but not EtOH<10mM or EtOH<20mM decreased SPV. Non-sedating low doses of ethanol, easily reached during social drinking, enhance LTD-like plasticity in human cortex. This effect is most likely explained by the activation of extrasynaptic α4-subunit containing gamma-aminobutyric type A receptors by low-dose EtOH, resulting in increased tonic inhibition. Findings may stimulate cellular research on the role of tonic inhibition in regulating excitability and plasticity of cortical neuronal networks.

A simple, cost-effective headspace gas chromatography (GC) method coupled with GC with flame ionization detection for simultaneous determination of methanol, ethanol and formic acid was developed and validated for clinical and toxicological purposes. Formic acid was derivatized with an excess of isopropanol under acidic conditions to its volatile isopropyl ester while methanol and ethanol remained unchanged. The entire sample preparation procedure is complete within 6 min. The design of the experiment (the face-centered central composite design) was used for finding the optimal conditions for derivatization, headspace sampling and chromatographic separation. The calibration dependences of the method were quadratic in the range from 50 to 5,000 mg/L, with adequate accuracy (89.0-114.4%) and precision (<12%) in the serum. The new method was successfully used for determination of selected analytes in serum samples of intoxicated patients from among those affected by massive methanol poisonings in the Czech Republic in 2012., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In postmortem cases where the cause of death is hanging, toxicological analyses may be considered unnecessary by some medical examiners, toxicologists, and other persons involved in medico-legal investigations because the cause of death seems "obvious." To ascertain if toxicological analyses are necessary when the cause of death is hanging, all 102 hanging cases (25 females; 77 males) from 2011 to 2013 that came under the jurisdiction of the San Francisco Office of the Chief Medical Examiner were examined from a total of 3912 sudden, unexpected, or violent death cases in the same period. Suicide was the manner of death in 99 of these cases, with two accidental and one undetermined death. The average age of decedents was 43.9 years (median 41), the youngest was an 11-year old male and the oldest was an 86-year old female. Of the 102 cases, 33 had negative toxicology while 69 cases had at least one positive toxicology result. Females were equally likely to have negative or positive results (12 and 13 cases respectively), but males were 37.5% more likely to have positive toxicology (n=56) rather than negative toxicology (n=21). For females, alcohol, mirtazapine, venlafaxine, and trazodone were the top psychoactive substances in peripheral blood while THC, cocaine, hydrocodone, bupropion, olanzapine, doxylamine, quetiapine and dextromethorphan were also reported. For males, alcohol, THC, cocaine, amphetamine, methamphetamine, bupropion, and diphenhydramine were the top psychoactive substances in blood, but several other drugs were also found in individual cases. Our study of hanging cases over a 3-year period support the idea that complete postmortem toxicology investigation of hangings should be performed, even when the "obvious" cause of death is asphyxia due to hanging. Many of these cases involved psychoactive substances (most often alcohol and cannabis), and having such knowledge provides a better understanding of the circumstances surrounding the decedent's death, their possible state of impairment, including the possibility of a staged suicide if the decedent was too impaired to perform a self-hanging., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Spinal cord injuries result after diving into shallow water, often after incautious jumps head first into water of unknown depth during recreational or sport activities. Mortality is generally due to upper cervical trauma. The authors present a case of a diving-related death in a young woman who underwent medicolegal investigations. The measured water depth at the supposed dive site was 1.40 m. Postmortem radiology and autopsy revealed fractures of the body and the posterior arch of the fifth cervical vertebra, a fracture of the right transverse process of the sixth cervical vertebra and hemorrhages involving the cervical paraspinal muscles. Neuropathology showed a posterior epidural hematoma involving the whole cervical region and a symmetric laceration of the spinal cord located at the fourth and fifth cervical vertebra level, surrounded by multiple petechial hemorrhages. Toxicology revealed the presence of ethanol in both blood and urine samples. The death was attributed to cervical spine fracture (C5-C6), spinal cord contusion, and subsequent drowning. This case highlights the usefulness of postmortem radiology, examination of the deep structures of the neck, toxicology, neuropathology, and a detailed research of signs of drowning to formulate appropriate hypotheses pertaining to the cause and mechanism of death.

In a large number of forensic autopsies (N = 28,184) the concentrations of ethanol in femoral blood and bladder urine were determined and the urine-to-blood concentration ratios of ethanol were calculated. Based on the differences in ethanol concentration between urine and blood, the deaths were classified as having occurred during the absorptive, the peak or the post-absorptive phase of the blood–alcohol curve. Most people died in the post-absorptive phase, N = 24,223 (86%), whereas 1538 individuals (5.5%) were still absorbing alcohol and 2423 (8.6%) were at or close to the peak BAC at time of death. Both blood–alcohol concentration (BAC) and urine–alcohol concentration (UAC) were significantly higher in the post-absorptive phase (p < 0.001). The proportions of people dying in the absorptive and peak phases increased with advancing age. The cause of death (CoD) and manner of death (MoD) according to death certificates were compared with phase of the blood–alcohol curve using a multinomial regression model with and without making adjustment for possible effects of age, gender and BAC. The relative risk (RR) and relative risk ratios (RRR) showed some associations between CoD and phase of the blood–alcohol curve. Undetermined MoD was significantly higher in the absorptive phase compared with the post-absorptive phase (RRR = 2.12). Deaths related to esophagus, stomach and duodenum (RRR = 2.04) and alcoholic liver diseases (RRR = 1.85) were significantly higher at or close to peak phase compared to the post-absorptive phase. Road-traffic fatalities were more prevalent in the peak BAC phase (RRR = 1.33) and deaths by accidental falls were less in the absorptive phase (RRR = 0.58) compared with the post-absorptive phase. The phase of alcohol intoxication seems relevant to consider by forensic experts when alcohol-related deaths are investigated.

The "STRIDA" project monitors the occurrence and trends of new psychoactive substances (NPS; "Internet drugs/designer drugs/legal highs") in Sweden, and collects information about their clinical symptoms, toxicity and associated health hazards. The initial results of the project documented a widespread use of many different NPS by mainly adolescents and young (age range 13-63 years, median 20), male (79%) adults, among cases of drug intoxications presenting at emergency departments and intensive care units across the country. The new substances were identified in samples of urine and blood by a multi-component LC-MS/MS method, and the severity of clinical symptoms were graded by the Poisoning Severity Score (PSS). Of the initial 189 samples submitted for laboratory investigation, 156 (83%) tested positive for at least one drug. Besides classical substances such as ethanol, cannabis and amphetamines, many NPS were detected comprising synthetic cannabinoid receptor agonists ("Spice"), piperazines, substituted phenethylamines, synthetic cathinones, hallucinogenic tryptamines, piperidines, opioid related substances, ketamine and related substances, and GABA analogues (in total more than 50 substances). About half of the cases were demonstrated to be multiple drug intoxications, sometimes making it hard to associate the clinical presentations with one specific substance. In conclusion, the STRIDA project has documented use of a broad variety of NPS among mainly young people all over Sweden., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Postmortem ethanol formation is a well-known problem in forensic toxicology. The aim of this study was to interpret findings of ethanol in blood, in a large collection of forensic autopsy cases, by use of the nonoxidative ethanol metabolites, ethyl glucuronide (EtG), and ethyl sulfate (EtS). In this study, according to previously published literature, antemortem ethanol ingestion was excluded in EtS-negative cases. Among 493 ethanol-positive forensic autopsy cases, collected during the study period, EtS was not detected in 60 (12 %) of the cases. Among cases with a blood alcohol concentration (BAC) of ≤ 0.54 g/kg, antemortem ethanol ingestion was excluded in 38 % of the cases, while among cases with a BAC of ≥ 0.55 g/kg, antemortem ethanol ingestion was excluded in 2.2 % of the cases. For all cases where ethanol was measured at a concentration >1.0 g/kg, EtS was detected. The highest blood ethanol concentration in which EtS was not detected was 1.0 g/kg. The median concentrations of EtG and EtS in blood were 9.5 μmol/L (range: not detected (n.d.) 618.1) and 9.2 μmol/L (range: n.d. 182.5), respectively. There was a statistically significant positive correlation between concentration levels of ethanol and of EtG (Spearman's rho=0.671, p<0.001) and EtS (Spearman's rho=0.670, p<0.001), respectively. In conclusion, this study showed that in a large number of ethanol-positive forensic autopsy cases, ethanol was not ingested before the time of death, particularly among cases where ethanol was present in lower blood concentrations. Routine measurement of EtG and EtS should therefore be recommended, especially in cases with BAC below 1 g/kg.

Objective: To improve the results of treatment of children with severe alcohol poisoning as a result of investigation of water sectors of the body., Methods: The study included 54 patients aged from 13 to 15 years with a diagnosis of acute severe alcohol poisoning. All patients were divided into three groups. At the initial examination was determined the concentration of alcohol in saliva using Express-test "Alkoskan." Bioimpedance analysis was performed; water sectors of the body were investigated by analyzer of the balance of water sectors ABC-01 "Medass." The study was conducted at the time of admission, after 12, 24 and 48 hours., Results: In severe alcohol poisoning at the time of admission, it was revealed a reduction of the fluid in all studied sectors. The most effective compensation of liquid was observed in groups, where was used combination therapy included intravenous fluids based 4.0 ml/kg/hour., Conclusion: The treatment of severe alcohol poisoning should include fluid resuscitation about 4 ml/kg/hour. This capacity of medical care give the ability to correct adequately the water-sectoral disturbances already in the first 12 hours of hospitalization, and the inclusion to the basic therapy reamberine can contribute more effective replenishment of water sectors.