Recent Alcohol Consumption Research Articles

Pancreatic Cancer: A Review of Risk Factors.

Pancreatic adenocarcinoma is one of the most lethal types of gastrointestinal cancer despite the latest medical advances. Its incidence has continuously increased in recent years in developed countries. The location of the pancreas can result in the initial symptoms of neoplasia being overlooked, which can lead to a delayed diagnosis and a subsequent reduction in the spectrum of available therapeutic options. The role of modifiable risk factors in pancreatic cancer has been extensively studied in recent years, with smoking and alcohol consumption identified as key contributors. However, the few screening programs that have been developed focus exclusively on genetic factors, without considering the potential impact of modifiable factors on disease occurrence. Thus, fully understanding and detecting the risk factors for pancreatic cancer represents an important step in the prevention and early diagnosis of this type of neoplasia. This review reports the available evidence on different risk factors and identifies the areas that could benefit the most from additional studies.

Burden and Patterns of Electric Scooter-Related Injuries: Insights From 2 Polish Emergency Departments.

BACKGROUND The widespread adoption of electric scooters (e-scooters) as a mode of urban transportation has led to a notable upsurge in e-scooter-related injuries globally. Variations in e-scooter regulations across countries contribute to differences in injury patterns. This study sought to investigate the healthcare burden posed by e-scooter-related injuries on emergency departments (EDs) in Poland, and to delineate the epidemiological and clinical features of these injuries. MATERIAL AND METHODS Medical records of patients who presented to 2 distinct EDs - in Poznań and Bydgoszcz, Poland - with injuries directly linked to e-scooter use were collected and retrospectively analyzed. RESULTS A total of 633 patients were admitted to the EDs due to e-scooter injuries during the study period, and 413 of these patients were further analyzed. The majority were males (64.65%), with a median age of 27 years. Most admissions occurred in the afternoon and nighttime (71.94%), with a higher incidence in the summer (46.73%). Falls were the most frequent mechanism of injury (74.09%), with the head and upper and lower extremities being the most frequently affected locations (36.08%, 29.78%, and 21.07%, respectively). Twelve patients (2.91%) confirmed recent alcohol consumption. Hospitalization costs were higher in cases involving alcohol use and among males. CONCLUSIONS The findings of this study underscore the significant strain exerted by e-scooter-related injuries on EDs in Poland. Injuries, notably to the head and limbs, carry significant long-term implications and strain healthcare resources. Collaboration with policymakers is crucial to ensure the safety of e-scooter users and appropriate healthcare resource allocation.

An experimental investigation into the effect of negative affect on the behavioral economic demand for alcohol.

It is hypothesized that alcohol use is reinforcing when used as a strategy to cope with negative affect. Although the evidence for this hypothesis in observational data is weak, some experimental evidence suggests that the behavioral economic demand for alcohol increases immediately following a negative emotional event. We hypothesized that people show a higher demand for alcohol following negative (vs. neutral) mood inductions and that this effect is stronger in people who report heavier drinking compared to people who report lighter drinking as well as stronger on days characterized by higher coping motives and negative urgency. 309 college students who reported recent alcohol consumption (MAUDIT = 6.86) completed the alcohol purchase task after being subjected to 12 mood inductions (six negative, six neutral, order randomized) on 12 separate days. In our preregistered analyses, we found no evidence that the behavioral economic demand for alcohol was elevated following negative mood inductions. The mood inductions in our study were not as strong as has been reported in previous research, weakening the preregistered inferences. In exploratory analyses performed on a subset of the data in which the mood inductions worked as intended, demand was higher following negative mood inductions. The results of this study are not conclusive. In light of previous research, we consider these data to slightly increase our confidence that demand for alcohol is increased immediately following a negative emotional event. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Making decisions one drink at a time and the "just one drink" effect: A fuzzy-trace theory model of harmful drinking.

Understanding the decision factors that drive harmful alcohol use among young adults is of practical and theoretical importance. We apply fuzzy-trace theory (FTT) to investigate a potential danger that may arise from the arguably correct notion that a single drink carries no meaningful risk. Decisions that are mentally represented as one drink at a time could contribute to excessive drinking. College students (N = 351) made a series of decisions to take or decline eight hypothetical drinks presented one at a time. Outcome measures included each decision, recent alcohol consumption (weekly drinks, peak blood alcohol content, and binges), and alcohol-related harms (scores on the Brief Young Adult Alcohol Consequences Questionnaire and Alcohol Use Disorders Identification Test). Linear regression models predicted each outcome from sex, perceived risk of a single drink, perceived risk of heavy drinking, perceived consequences of drinking, and general health-related risk sensitivity. Consistent with FTT, decisions to have a first drink and up to four additional drinks in short succession were each associated with lower perceived risk of one drink-a "just-one drink" effect-independent of perceived risks of heavy drinking, perceived consequences of drinking, and general risk sensitivity. Similarly, all measures of recent alcohol consumption and consequent harms were associated with perceived risk of one drink. Participants reporting "zero risk" of a single drink had worse outcomes on all measures than those reporting at least "low risk." Results are consistent with the theoretically informed premise that consumption decisions are typically made one drink at a time rather than by deciding the total number of drinks to be consumed in a sitting. When decisions about alcohol use proceed one drink at a time, a perception of zero risk in a single drink may contribute to heavy drinking.

Epidemiology of alcohol use and alcohol use disorder among female sex workers in Mbeya City, Tanzania.

Alcohol misuse is a global concern, contributing to 5.3% of total deaths and 132.6 million disability-adjusted life years worldwide. In Sub-Saharan African countries, the prevalence of Alcohol Use Disorder (AUD) has risen, especially among female sex workers, due to increased availability and advertising. However, there are limited studies on alcohol use and AUD among female sex workers in Tanzania. This study aimed to determine the prevalence, patterns, and factors associated with alcohol use and AUD among sex workers in Mbeya city, Tanzania. In this cross-sectional study, 212 female sex workers in Mbeya city, Tanzania, seeking enrolment in the National Institute for Medical Research Mbeya Medical Research Centre's registration cohort from July to November 2022. Structured interviews covered socio-demographics, alcohol screening (AUDIT-C and Timeline Follow Back Calendar), and sexual behaviours data. Data were analysed using Stata version 17. Descriptive analysis assessed alcohol consumption and AUD prevalence. Factors associated with alcohol use and AUD at bivariate analysis were identified using Chi-square/Fisher's exact tests. All variables with p-value ≤ 0.20 were entered into a multivariable logistic regression model to identify factors associated with alcohol use and AUD. Among 212 participants, 86.6% reported alcohol use in the past 12 months, 85% in the past 30 days, and 98.5% met AUD criteria. Factors linked to recent alcohol consumption included primary education or higher, income above the median, and more than 10 sexual partners. Education level, marital status, income, and having dependents were significantly associated with heavy drinking episodes. The prevalence of AUD, alcohol use, and heavy episodic drinking were high among female sex workers in Mbeya city. Socio-demographic factors and risky sexual behaviours were associated with alcohol use and heavy episodic drinking highlighting the need for targeted interventions to combat alcohol abuse among female sex workers within the HIV program.

You can't handle the truth! Comparing serum phosphatidylethanol to self-reported alcohol intake in chronic liver disease patients

BackgroundSerum phosphatidylethanol (PEth) testing has emerged as a promising biomarker for assessing recent alcohol consumption, surpassing the limitations of self-reported data. Limited clinical data exists comparing PEth levels and patients' reported alcohol intake. AimsCompare PEth testing results with self-reported alcohol intake and assesses variables associated with underreporting. MethodsSingle-center retrospective cohort of patients with a diagnosis of chronic liver disease and serum PEth. A patient's first positive PEth (>/=10 ng/mL) and self-reported alcohol consumption was used. PEth results were categorized as mild (10–20), moderate (20–200), or heavy (>200). Severity measures between self-report and PEth were assessed using Bhapkar's test and Bonferroni-adjusted McNemar's tests. Demographic data was analyzed using Chi-Square tests. Results279 patients were included. 94 (33.7%) patients had consistency with self-report, and 185 patients had inconsistencies in their report (66.3%, p < 0.001). Of 279 patients, 161 (57.7%) underreported their alcohol consumption, and 55 (19.7%) heavy PEth patients underreported alcohol consumption as light. 58% of alcohol-related and 56.4% of non-alcohol-related cirrhotic patients underreported their alcohol use. ConclusionIn our cohort, only one third of self-reported alcohol consumption was consistent with the PEth level. Notably, 57.7% underreported alcohol intake. Our study reinforces the clinical importance of PEth testing as an objective clinical measure.

ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome

ABSTRACT Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 (ZSCAN25) and CDT strongly predicted severe AWS with ATS (p < 0.007) and cg07375256 (p < 6 × 10–5) methylation also predicting AWS associated seizures. We conclude that epigenetic methods can predict those likely to experience severe AWS and that the use of these or similar Precision Epigenetic approaches could better guide AWS management.

Co‐occurring BD and AUD associated with increased craving

Researchers studied reward circuitry dysfunction, which may be a mechanism of co‐occurring bipolar disorder (BD) and alcohol use disorder (AUD), using functional magnetic resonance imaging (fMRI). The objective was to find out how alcohol cue processing differs in people with co‐occurring BD and AUD compared with people who have either one of the disorders. They used a visual alcohol cue reactivity paradigm following one week or more of abstinence from alcohol and other drugs. They rated past‐week mood symptoms for depression and mania, as well as obsessive‐compulsive drinking and impulsiveness. Function MRI was analyzed focusing on the ventral striatum, dorsal striatum, and ventromedial prefrontal cortex. The researchers analyzed associations between cue reactivity and select behavioral correlates, namely, alcohol craving, impulsivity, maximum number of alcohol drinks on a single occasion and days since last alcohol drink). Of the 112 participants, 28 (25.0%) had BD and AUD, 26 (23.2%) had AUD alone, 31 (27.7%) had BD alone, and 27 (24.1%) were healthy controls. The mean age was 38.7 years, 50 (45.5%) were female, 33 (30%) were smokers, and 37 (34.9%) reported recent alcohol consumption. Individuals with BD and AUD exhibited reduced activation compared with all other groups. Other groups did not significantly differ from one another. The hypo‐activations were associated with increased impulsivity and obsessive‐compulsive alcohol craving exclusively among individuals with BD and AUD. The researchers concluded that the potential interaction between BD and AUD blunted the response to rewards and decreased inhibitory control. They added that reduced right inferior frontal gyrus and insula alcohol cue reactivity is a novel biomarker of comorbid BD and AUD that may respond to pharmacological interventions targeting impulsivity‐related neural mechanisms for improved executive control. The study, “Alcohol Cue Processing in Co‐Occurring Bipolar Disorder and Alcohol Use Disorder, is by William H. Mellick, Ph.D., and colleagues, and was conducted at the Medical University of South Carolina, Addiction Sciences Division and published Nov. 1 in JAMA Psychiatry.

Lyso-phosphatidylethanol detected by LC-MS/MS as a potential new marker for alcohol consumption.

Alcohol biomarkers are able to reflect the degree of recent or long-term alcohol consumption, covering different windows of detection. Phosphatidylethanols (PEths) are an emerging group of direct alcohol biomarkers that are widely applied in clinical and forensic applications. Their quantification can provide insight into an individual's drinking behaviour. Here, we present a new sub-class of yet unknown PEth species, LysoPEths, which are structurally related to PEth, but miss one fatty acyl chain. LysoPEths can be either a degradation product of PEth or a product of transesterification of lyso-phosphatidylcholine (LysoPC) with ethanol. To set up an analytical method, LysoPEth 16:0 was synthesised from PC 16:0/18:1 and characterised by LC-MS/MS, using an enzymatic method: phospholipase D (PLD), followed by phospholipase A2 (PLA2). Then, an LC-MS/MS method in MRM mode for LysoPEth 16:0 with additional LysoPEth species (LysoPEth 18:1, LysoPEth 18:2, and LysoPEth 20:4) and PEth 16:0/20:4 was developed. By incubation of freshly sampled venous blood of a teetotaller with ethanol at different concentrations, the formation of LysoPEth in parallel to PEth was investigated. With increasing ethanol concentrations, LysoPEth 16:0 was formed besides the known PEth species (PEth 16:0/18:1, PEth 16:0/18:2) for up to 72 h with LysoPEth concentrations being about three times lower than PEth concentrations. Storage of ethanol-free PEth-positive blood of an alcohol consumer at 37 °C showed that LysoPEth 16:0 concentrations increased, while PEth 16:0/18:1 concentrations decreased in the first 24 h for frozen/thawed blood, however not for freshly collected blood. Furthermore, LysoPEth 16:0 was detected in venous as well as lyophilised blood from clinical and forensic case work alongside with PEth 16:0/18:1, 16:0/18:2, and other PEth and LysoPEth species (PEth 16:0/20:4, LysoPEth 18:1, LysoPEth 18:2, and LysoPEth 20:4). LysoPEth 16:0 concentrations were found to be in linear correlation with PEth 16:0/18:1 (r2 = 0.75).

Alcohol Cue Processing in Co-Occurring Bipolar Disorder and Alcohol Use Disorder

Reward circuitry dysfunction is a candidate mechanism of co-occurring bipolar disorder and alcohol use disorder (BD + AUD) that remains understudied. This functional magnetic resonance imaging (fMRI) research represents the first evaluation of alcohol cue reward processing in BD + AUD. To determine how alcohol cue processing in individuals with BD + AUD may be distinct from that of individuals with AUD or BD alone. This cross-sectional case-control study (April 2013-June 2018) followed a 2 × 2 factorial design and included individuals with BD + AUD, AUD alone, BD alone, and healthy controls. A well-validated visual alcohol cue reactivity fMRI paradigm was administered to eligible participants following their demonstration of 1 week or more of abstinence from alcohol and drugs assessed via serial biomarker testing. Study procedures were completed at the Medical University of South Carolina. Analysis took place between June and August 2022. Past-week mood symptoms were rated by clinicians using the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. The Alcohol Dependence Scale, Obsessive-Compulsive Drinking Scale, and Barratt Impulsiveness Scale were included questionnaires. Functional MRI whole-brain data were analyzed along with percent signal change within a priori regions of interest located in the ventral striatum, dorsal striatum, and ventromedial prefrontal cortex. Exploratory analyses of associations between cue reactivity and select behavioral correlates (alcohol craving, impulsivity, maximum number of alcohol drinks on a single occasion, and days since last alcohol drink) were also performed. Of 112 participants, 28 (25.0%) had BD + AUD, 26 (23.2%) had AUD alone, 31 (27.7%) had BD alone, and 27 (24.1%) were healthy controls. The mean (SD) age was 38.7 (11.6) years, 50 (45.5%) were female, 33 (30%) were smokers, and 37 (34.9%) reported recent alcohol consumption. Whole-brain analyses revealed a BD × AUD interaction (F = 10.64; P = .001; η2 = 0.09) within a cluster spanning portions of the right inferior frontal gyrus and insula. Region of interest analyses revealed a main association of BD (F = 8.02; P = .006; η2 = 0.07) within the dorsal striatum. In each instance, individuals with BD + AUD exhibited reduced activation compared with all other groups who did not significantly differ from one another. These hypoactivations were associated with increased impulsivity and obsessive-compulsive alcohol craving exclusively among individuals with BD + AUD. The findings of this study suggest conceptualizing reward dysfunction in BD + AUD by the potential interaction between blunted reward responsivity and deficient inhibitory control may help guide treatment development strategies. To this end, reduced right inferior frontal gyrus and insula alcohol cue reactivity represents a novel candidate biomarker of BD + AUD that may respond to pharmacological interventions targeting impulsivity-related neural mechanisms for improved executive control.

The complementarity of phosphatidylethanol in whole blood and ethyl glucuronide in hair as biomarkers for the monitoring of alcohol use.

Monitoring long-term alcohol use and/or abstinence is essential in clinical and medico-legal cases. Analysis of ethyl glucuronide (EtG) in hair provides information on alcohol consumption over several months. However, there is a lag time between ethanol consumption, incorporation of EtG in the hair bulb and hair growing out of the scalp. Phosphatidylethanol (PEth) 16:0/18:1 analysis in whole blood has a detection window of 2-4 weeks, allowing for the detection of recent alcohol consumption. In this study, 2340 paired samples (of hair and venous whole blood from 1170 individuals) were analysed for EtG in hair (hEtG) and PEth 16:0/18:1 in venous whole blood. PEth 16:0/18:1 and hEtG results were subdivided into three categories according to the consensus of SoHT (hEtG) and PEth-NET (PEth): abstinence/low, moderate or excessive alcohol consumption. For hEtG analysis, 446 individuals presented abstinence/low alcohol consumption, of which 2% were classified as excessive alcohol users through PEth 16:0/18:1 analysis. This suggests excessive alcohol consumption in the weeks before sample collection. Out of 483 individuals classified as heavy alcohol users based on hEtG analysis, 14% showed abstinence/low alcohol consumption for PEth 16:0/18:1 analysis, implying that these subjects stopped drinking 2-4 weeks before sample collection. Our results show that the analysis of the two different biomarkers can lead to a more accurate categorisation of individuals. Therefore, we emphasize that for the retrospective investigation of alcohol use, it is necessary to include two alcohol use biomarkers with different detection windows.

Role of Biomarkers to Assess the Use of Alcohol.

Alcohol-associated liver disease has seen a significant rise in the last 2 decades, with an associated rise in the need for accurate alcohol use assessment. Alcohol use has been associated with poor outcomes in both the pre-liver transplant and post-liver transplant patients. Patients with alcohol use disorder often under-report their alcohol consumption because of varying factors, highlighting the need for objective assessment of alcohol use. Aside from the available self-report questionnaires, multiple serologic biomarkers are currently available to assist clinicians to assess recent alcohol consumption among patients with chronic liver disease, liver transplant candidates, and recipients. In this review, we will assess some of these alcohol biomarkers, discuss their strengths and weakness, and review-available data to discuss their role in pre-liver transplant and post-liver transplant population.

Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use: a single arm trial.

Isoniazid (INH) preventive therapy is recommended to prevent tuberculosis (TB) disease for persons with HIV (PWH), except for those with regular and heavy alcohol consumption, due to hepatotoxicity concerns. We aimed to quantify the incidence of severe INH-related toxicity among PWH with and without recent alcohol consumption. Prospective study of PWH receiving INH. We included PWH in southwest Uganda with recent (prior three months) (n = 200) or no (prior year) self-reported alcohol consumption (n = 101), on antiretroviral therapy, TB infected (≥5 mm on tuberculin skin test), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2x the upper limit of normal (ULN). Grade 3+ INH-related toxicity was ALT or AST ≥5x the ULN or severe symptoms; we stopped IPT upon detection. Grade 2 INH-related toxicity was ALT or AST 2-5x the ULN or moderate symptoms. The cumulative incidence of Grade 3+ INH-related toxicity was 8.3% (95% CI: 5.7-12.0); all resolved after INH cessation. Incidence was 6.0% (95% CI: 3.1-10.2) among those reporting recent alcohol use and 12.9% (95% CI: 7.0-21.0) of those reporting no prior year alcohol use. We found no differences by baseline phosphatidylethanol-confirmed alcohol severity. The cumulative incidence of Grade 2 toxicities (without Grade 3+) was 21.7% (95% CI: 17.2-27.0); 25.0% (95% CI: 19.0-31.8) among those with recent alcohol use and 14.8% (95% CI: 8.1-23.9) among those with no prior year alcohol use. Alcohol use does not appear to increase risk for serious INH-related toxicity among PWH without significant liver enzyme elevations at baseline (≤2x ULN).

Phosphatidylethanol and self-reported alcohol consumption among people living with HIV in Thai Nguyen, Vietnam.

Phosphatidylethanol (PEth) is a biomarker for recent alcohol consumption that would ideally validate self-reported alcohol consumption behaviors. We assessed the relationship between PEth and several self-reported alcohol consumption metrics among hazardous alcohol users living with HIV in Vietnam. Participants in a three-arm randomized controlled trial assessing two alcohol interventions reported recent alcohol consumption on a 30-day timeline follow-back interview and had a PEth assessment at enrollment, 3 months, and 12 months of the study follow-up. We examined the relationship between self-reported alcohol consumption and quantitative PEth results using Spearman rank correlation and receiver-operating characteristic (ROC) curves to calculate the area under the curve (AUC). We assessed associations between categorical PEth results and self-reported drinking behaviors using prevalence ratios calculated with regression models and generalized estimating equations. Among 1221 study visits (n = 439 participants; 425 (97%) men), the median PEth result was 71 ng/mL (Interquartile range (IQR): 20, 212), and participants reported a median of 11 (IQR: 4, 24) drinking days and 25 (IQR: 8, 71) standard drinks in the previous 28 days. Quantitative PEth results were moderately correlated with drinking days (ρ = 0.26-0.35) and standard drinks consumed (ρ = 0.23-0.38) in the same period. AUCs ranged from 0.54 (any binge drinking in the past 28 days) to 0.82 (any alcohol consumed in the past 21 days). Positive PEth results (≥50 ng/mL) were 2.24 (95% Confidence Interval [CI]: 1.49, 3.35) times as prevalent among participants who reported drinking in the previous 28 days compared with those who did not. Although PEth values and self-reported alcohol use were correlated, the observed associations were modest. Additional research into the dynamics of PEth production and elimination is warranted across diverse populations to better understand how PEth assessments can best be integrated into research and clinical care.

The association between alcohol consumption and intimate partner violence in young male perpetrators in Mwanza, Tanzania: a cross-sectional study

ABSTRACT Background Although alcohol consumption is a well-known risk factor for intimate partner violence (IPV) perpetration, few studies have been conducted among young males in low- and middle-income countries. Alcohol consumption and IPV are both complex phenomena, whose association requires more in-depth exploration regarding drinking patterns and the alcohol-related manifestation of five different forms of IPV. Objective In this study, we sought to explore the relationship between alcohol use and IPV in young Tanzanian men and to identify differences in the magnitude of past-year IPV perpetration among alcohol drinkers and abstainers. Furthermore, we aimed to assess the association between various drinking patterns with the perpetration of different forms of IPV. Methods A cross-sectional survey of 1002 young males residing in Mwanza, Tanzania, was conducted in 2021–2022. Data on alcohol consumption were collected using the alcohol use disorder identification test. IPV perpetration was assessed using an index total of 19 items on acts of physical, sexual, economic, emotional abuse, and controlling behaviour. Logistic regression models were conducted to estimate the relationship between alcohol use and the perpetration of each form of IPV. Results Among partnered respondents currently consuming alcohol (n = 189, 18.8%), the most and the least prevalent IPV forms in the past 12 months were controlling behaviour (84.1%) and physical IPV (25.4%), respectively. Those reporting recent alcohol consumption reported higher rates of all forms of past-year IPV perpetration compared to abstainers. While no form of IPV was associated with low-risk consumption versus abstention, all forms of IPV were associated with hazardous drinking. Conclusion Young men who drink alcohol, especially those drinking hazardously, are also more likely to report perpetrating IPV. An understanding of the different drinking patterns and manifestations of forms of IPV can contribute to better-tailored alcohol-related interventions and has the potential to improve young adults’ health and reduce IPV perpetration.

Significantly elevated phosphatidylethanol levels in recent suicide attempters, but not in depressed controls and healthy volunteers

IntroductionSuicide is a complex transdiagnostic phenomenon. It is strongly associated with, but not exclusive to major depressive disorder (MDD). Hazardous alcohol drinking has also been linked to an increased risk of suicidal behaviours, however, it is often underreported. The study aimed to evaluate whether an objective measure of chronic alcohol use, phosphatidylethanol (PEth) could be useful as a biomarker in clinical practice. Methodology. The present case-control multi-centric study recruited 156 participants into three study groups: 52 patients treated for major depressive disorder (MDD), 51 individuals immediately following a suicide attempt (SA), and 53 volunteers. Sociodemographic data, medical history, and laboratory data, including PEth concentrations and C-reactive protein levels, were collected from study participants. ResultsPEth concentrations were the highest in suicide attempters (232,54 ± 394,01 ng/ml), followed by patients with MDD (58,39 ± 135,82 ng/ml), and the control group (24,45 ± 70,83 ng/ml) (Kruskall Wallis χ2 = 12.23, df = 2, p = .002). In a multinomial logistic regression model with adjustments, PEth concentration was able to predict belonging to suicide attempters’ group, but not to depression group (p = .01). Suicide attempters were also more likely to underreport their recent alcohol consumption. LimitationsWe did not analyze SA methods, psychiatric comorbidity and several other factors that might be associated with PEth levels, such as body mass index, race, and haemoglobin levels. Sample recruited in hospital settings may not be representative of the whole population. The results of this adult-only study cannot be generalized to adolescents. ConclusionsPEth levels in recent suicide attempters significantly exceeded those of patients with MDD and controls. Suicide attempters also were more likely to underreport their alcohol consumption when questioned about their consuption. PEth might be an interesting biomarker to evaluate individuals at risk of SA.

ODP085 Denosumab Induced Severe Hypophosphatemia

Abstract Introduction Denosumab is a receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor used for treatment of osteoporosis and bone metastases in patients with solid tumors. Denosumab induced hypophosphatemia has been reported in less than 1% of patients, and in most cases described as mild to moderate in severity. We present a case of severe hypophosphatemia after denosumab treatment for diffuse bone metastases due to prostate cancer. Case report A 78-year-old male patient with history of diffuse bone metastases due to prostate cancer, schizophrenia on treatment and intermittent alcohol use, presented to the hospital with suicidal ideation and worsening fatigue. Patient was found to have a phosphorus levels of &amp;lt;1. 0 mg/dL (2.5-4.6 mg/dL), corrected calcium of 8.2 mg/dL (8.4-10.5 mg/dl), vitamin D 25 OH of 36.34 ng/mL (30-100 ng/mL), magnesium of 2.3 mg/dL (1.7-2.5 mg/dL), parathyroid hormone (iPTH) level of 379 pg/mL (10-65pg/mL) and serum creatinine of 1.1 mg/dL (0.5-1.2 mg/dL). Urinary studies showed 24 hour urinary phosphate 1282 mg/24h (360-1600 mg/24h), urine creatinine 1570 mg/24h (500-2150 mg/24h). There was no evidence of acidosis, chronic kidney disease, preexisting osteomalacia or vitamin D deficiency. The patient had no recent alcohol consumption and his alcohol level was undetectable. After reviewing the outside medical records it was noted that the patient had received denosumab 120 mg, 11 days prior to the hospital admission, as part of the management of bone metastases due to prostate cancer. The patient's baseline phosphorus prior to denosumab was in the low normal range. The severe hypophosphatemia and secondary hyperparathyroidism were attributed to denosumab administration. Patient was initially treated with intravenous phosphate and then transitioned to oral phosphate along with elemental calcium and calcitriol during the course of his hospitalization. Patient's phosphorus improved to 2.3 mg/dL by the time of discharge. Discussion In patients treated with denosumab, the primary concern is potential post-treatment hypocalcemia, however, our case brings attention to severe hypophosphatemia as a serious side effect to treatment with denosumab. Multiple specialties are involved in the treatment of osteoporosis and metastatic bone lesions, and each should be aware that denosumab can lead to lower serum phosphate levels due to its effects on bone resorption and reduction of proximal tubular reabsorption of the phosphate resulting in clinical symptoms of muscle weakness, bone pain, fractures and even stupor, coma and death. We therefore conclude that monitoring phosphate levels should be part of the pre- and post-treatment evaluation in patients who are candidates for treatment with denosumab, particularly high-dose denosumab. Presentation: No date and time listed

Determination of Ethyl Glucuronide and Ethyl Sulfate in Dried Blood Spots by UHPLC-MS-MS: Method Validation and Assessment of Ethanol Exposure in Postmortem Samples from Road Traffic Victims.

The determination of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in blood has been proposed in clinical and forensic applications to identify recent alcohol consumption. Also, there is a growing interest on the use of dried blood spots (DBS) in toxicological analysis, allowing increased stability of the analytes and simplifying sample transportation and storage. This study presents the development and validation of a method for quantifying EtG and EtS in DBS using ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS). The DBS samples were extracted with a mixture of methanol and acetonitrile (80:20 v/v) and analyzed using UHPLC-MS-MS with electrospray source in negative mode, after separation with a fluoro-phenyl stationary phase. Validation was performed according to the Scientific Working Group for Forensic Toxicology (SWGTOX) guidelines, with calibrations ranging from 0.10 to 18 µg/mL for EtG and 0.02 to 6 µg/mL for EtS. The analytes were stable in DBS stored from -20 to 45°C for 21 days. The method was successfully applied to capillary and venous DBS samples from 20 volunteers after ethanol ingestion and to DBS samples from 99 fatal victims of road traffic injuries. Capillary DBS was comparable to venous DBS and fresh whole blood in Passing-Bablok and Bland-Altman analysis, with correlation coefficients >0.91 (P < 0.001) for all comparisons. In postmortem application, the DBS EtG and EtS analysis indicated positive exposure to ethanol in 72.7% of the cases (EtG: 0.10-24.0 µg/mL and EtS: 0.03-4.11 µg/mL). The identification of ethanol consumption from blood alcohol concentrations (BACs) and EtG/EtS in DBS was in agreement in 98.6% of positive and 96.3% of negative cases (kappa 0.877, P < 0.001), indicating a high level of concordance with BAC in assessing alcohol use in postmortem samples.

Added value evidences of a simultaneous determination of two phosphatidylethanol isoforms and ethylglucuronide in dried blood spots in forensic contexts

In clinical or postmortem forensic medicine, acute or chronical alcohol abuse are of main concern and direct/indirect biomarkers are widely use in order to assess recent or retrospective alcohol abuse. We aim to illustrate that a simultaneous determination of 3 directs ethanol biomarkers [two phosphatidylethanol isoforms, 16:0/18:1 (PEth18:1) and 16:0/20:4 (PEth20:4), and ethylglucuronide (EtGB)] using dried blood spot (DBS) can be a useful additional tool in many situations. (Case#1) Sexual assault of a 17-year-old girl with negative urine and blood ethanol concentration (BAC) (but urine EtG concentration was 10 mg/L) sampled 19 hours after the facts. (Case#2) Only blood sampling (negative BAC) was performed 14 hours after a 36-year-old man (with heavy psychiatric disorders) tried to kill 3 persons. He was reported drunk at the time of the attack by witnesses. (Case#3) A 27-year-old man was implicated in a car-related fatality that occurred 11 days before sampling. Blood and hair sampling were performed in order to investigate his alcoholic status: hair EtG concentration was < 5 pg/mg. (Case#4) The alcoholic status of a 43-year-old woman killed in a car accident had to be established. BAC was 140 mg/L in the postmortem peripheral blood (only available biological sample; sampled less than one hour after death and kept refrigered until time of analysis, 2 days later). (Case#5) A low BAC (70 mg/L) was found in postmortem cardiac blood (only sample available) sampled on the corps of a 42-year-old man found submerged in the sea. (Case#6) Peripheral blood sampling (for BAC determination) and direct DBS sampling (MitraTM) were performed at the time of discovery of the 36-year-old man corpse, allegedly heavy drinker according to the testimonies (BAC was 2810 mg/L). Blood samples can alternatively consist in 10 μL from usual blood sampling tubes (e.g. fluoride preserved) transferred on DBS card, or direct DBS sampling using Volumetric Absorptive MicroSampling devices (VAMS; HemaxisTM, MitraTM). These DBS are analyzed using a LC-MS/MS (routinely used in clinical toxicology) method (LLOQ: 2 μg/L for the 3 analytes). Results (μg/L; PEth18:1, PEth20:4 and EtGB, respectively) were: – (Case#1) 22, 2 and 300, in coherence with both a recent alcohol intake hypothesis [EtGB above the 45 μg/L threshold supported an alcohol consumption [> 2 standard units (SU)] in the last 24 to 48 hours] and that this girl was not an excessive drinker [owing to the low PEths concentrations]; – (Case#2) 98, 103 and 71, consistent with an alcohol intake hypothesis arround the time of the attack by this man who had a significant consumption of alcohol in the last 10 days as PEth 20:4 concentration was similar to the PEth18:1 one; – (Case#3) 9, < 2 and < 2, and did not contradict the negative EtG hair result as these low values were, at most, compatible with an “occasional” or “social drinker” status (< 14 SU per week); – (Case#4) 817, 44 and 130. EtGB positive result supported a recent alcohol consumption and the very high PEth18:1 value strongly suggested chronic excessive alcohol consumption; – (Case#5) negative (< 2 μg/L) for the 3 analytes in postmortem cardiac blood, in agreement with both the hypothesis of a light postmortem ethanol production, and a probable “abstinent” or “occasional consumer” status of the victim; – (Case#6) 3470, 1030 and 13,400, supporting the massive alcohol intoxication hypothesis close to the death of a heavy drinker. This analytical tool is of high interest when only blood samples are available, although postmortem use (due to PEths neoformation issues) should be limited to cases with negative BAC, or when blood sampling is performed close to death using a VAMS or a refrigerated preserved (< 4 days) tube.

Dried blood spot (DBS) for ethyl glucuronide (EtG) and ethyl sulfate (EtS) determination in blood with a new design of “volumetric” DBS filter paper card

Determination of EtG in blood can be performed from capillary blood with high sensitivity and detection limits of down to 1 ng/mL for EtG–and in addition to phosphatidyl ethanol (PEth) determination, EtG concentrations can be used for interpretation of consumption habits of patients in maintenance therapy. Sampling of capillary blood is a crucial preanalytical step–and different methods have been suggested for collection of a defined volume (VAMS, Capitainer, HemaXis, and capillaries for collection of samples). We used and validated a new volumetric capillary blood sampling card (DBSv cards, Protzek, Lörrach/Germany) which can be used either for self-sampling of dried blood spots (up to 4 times 20 microliter of blood) on filter paper with convenient handling by the patients or also in laboratory work. In contrast to standard DBS cards with printed circles on a filter paper, a newly designed card with a paper comb with four teeth per card, which allows a volumetric collection of 20 microlitres of blood per tooth, was used. Venous blood was pipetted on the teeth of DBSv cards, dried, and one paper tooth was ripped off and extracted by adding 490 microliter of methanol and 10 microliter of ISTD (400 ng/ml D5-EtG and 400 ng/ml D5-EtS). The samples were then vortexed for 5 minutes and centrifuged for 10 minutes. After transferring them into vials, the solutions were evaporated under a stream of nitrogen and reconstituted in 80 microliter of a water/0.1% formic acid. The samples were shaken and 10 μL were injected onto the LC column. A previously published LC-MS/MS method was adapted for a QTrap 5500 triple-quadrupole ion trap mass spectrometer (Sciex, Toronto, Canada) with an Acquity C18 HSS T3 column (Waters, Wexford, Ireland) and detection of EtG, D5-EtG, EtS and D5-EtS was performed according to forensic guidelines using one precursor and two product ions. Lower limits of quantification were 10 ng/mL for EtG and 20 ng/mL for EtS–with linear ranges of 10 to 5000 ng/mL for EtG and (50 to 2500 ng/mL for EtS. Traces of EtS were found in HPLC grade solvent, and a solvent selection between products of different manufacturers had to be performed. One brand methanol showed the lowest baseline level of EtS, which was in the range of 20 ng/mL. Thus, for determination of EtS, a lower limit of quantitation of 50 ng/mL was defined, whereas EtG could be quantified at concentrations above 10 ng/mL. A validation with spiked blood samples was performed. Samples from forensic cases and from drinking studies, where DBS were collected for the analysis of alcohol biomarkers (PEth and EtG/EtS) have been analyzed. The dried blood spot sample collection in laboratory or by self-sampling (of capillary blood) can be used to detect EtG and EtS at very low levels. The results show the potential of DBS analysis for alcohol markers EtG and EtS–which can be used for abstinence monitoring by very low limits of detection, especially for EtG, or for the detection of a recent alcohol consumption, when ethanol has already been eliminated from the body. A contamination of pure HPLC-grade solvent methanol was found for EtS determination, this has to be kept in mind, and needs further optimization for detection of EtS at lower concentrations in biological samples.