Binge alcohol disrupts skeletal muscle core molecular clock independent of glucocorticoids.

Circadian rhythms are central to optimal physiological function, as disruption contributes to the development of several chronic diseases. Alcohol (EtOH) intoxication disrupts circadian rhythms within liver, brain, and intestines, but it is unknown whether alcohol also disrupts components of the core clock in skeletal muscle. Female C57BL/6Hsd mice were randomized to receive either saline (control) or alcohol (EtOH) (5 g/kg) via intraperitoneal injection at the start of the dark cycle [Zeitgeber time (ZT12)], and gastrocnemius was collected every 4 h from control and EtOH-treated mice for the next 48 h following isoflurane anesthetization. In addition, metyrapone was administered before alcohol intoxication in separate mice to determine whether the alcohol-induced increase in serum corticosterone contributed to circadian gene regulation. Finally, synchronized C2C12 myotubes were treated with alcohol (100 mM) to assess the influence of centrally or peripherally mediated effects of alcohol on the muscle clock. Alcohol significantly disrupted mRNA expression of Bmal1, Per1/2, and Cry1/2 in addition to perturbing the circadian pattern of clock-controlled genes, Myod1, Dbp, Tef, and Bhlhe40 (P < 0.05), in muscle. Alcohol increased serum corticosterone levels and glucocorticoid target gene, Redd1, in muscle. Metyrapone prevented the EtOH-mediated increase in serum corticosterone but did not normalize the EtOH-induced change in Per1, Cry1 and Cry2, and Myod1 mRNA expression. Core clock gene expression (Bmal, Per1/2, and Cry1/2) was not changed following 4, 8, or 12 h of alcohol treatment on synchronized C2C12 myotubes. Therefore, binge alcohol disrupted genes of the core molecular clock independently of elevated serum corticosterone or direct effects of EtOH on the muscle.NEW & NOTEWORTHY Alcohol is a myotoxin that impairs skeletal muscle metabolism and function following either chronic consumption or acute binge drinking; however, mechanisms underlying alcohol-related myotoxicity have not been fully elucidated. Herein, we demonstrate that alcohol acutely interrupts oscillation of skeletal muscle core clock genes, and this is neither a direct effect of ethanol on the skeletal muscle, nor an effect of elevated serum corticosterone, a major clock regulator.

Total Keratin-18 (M65) as a Potential, Early, Non-Invasive Biomarker of Hepatocyte Injury in Alcohol Intoxicated Adolescents-A Preliminary Study.

BACKGROUND: Underage drinking is associated with health risk behaviors. Serum keratin-18 (CK18) levels are increased in liver diseases and may be biomarkers of outcome. The purpose of this study was to determine if the total CK18 (M65) or caspase-cleaved CK18 (M30) levels were different in adolescents admitted to hospital because of alcohol intoxication and controls with excluded liver diseases. METHODS: A prospective study included 57 adolescents after alcohol use and 23 control subjects. The concentrations of M30 and M65 in the serum samples were evaluated using an enzyme-linked immunosorbent assay. RESULTS: The median age was 15 (14-17) years and 49% were male. There were significant differences in M65 levels between the study and control groups (p = 0.03). The concentrations of M30 and M65 were insignificant in adolescents divided into subgroups according to blood alcohol concentrations (BAC). Significant positive correlations were found between BAC and M65 levels (p = 0.038; r = 0.3). In receiver operating characteristic (ROC) analysis M65 (cut-off = 125.966 IU/l, Se = 70.2%, Sp = 43.5%) allowed to differentiate between patients with and without alcohol intoxication (AUC = 0.66, p = 0.03). CONCLUSION: M65 appears to be a promising non-invasive biomarker of hepatocyte injury during alcohol intoxication in adolescents. Moreover, a higher concentration of M65 may indicate early organ injury before the increase in the activity of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Pathophysiology and Biomarker Potential of Fatty Acid Ethyl Ester Elevation During Alcoholic Pancreatitis.

BACKGROUND & AIMS: The role of fatty acid ethyl esters (FAEEs) during human alcoholic pancreatitis is unknown. We compared FAEEs levels with their nonesterified fatty acids (NEFAs) precursors during alcohol intoxication and clinical alcoholic pancreatitis. The pathophysiology underlying FAEEs increase and their role as diagnostic biomarkers for alcoholic pancreatitis was investigated. METHODS: A prospective blinded study compared FAEEs, NEFAs, and ethanol blood levels on hospitalization for alcoholic pancreatitis (n = 31), alcohol intoxication (n = 25), and in normal controls (n = 43). Serum FAEEs were measured at admission for nonalcoholic pancreatitis (n = 75). Mechanistic cell and animal studies were done. RESULTS: Median FAEEs were similarly elevated during alcohol intoxication (205 nmol/L; 95% confidence interval [CI], 71.8-515 nmol/L, P < .001) and alcoholic pancreatitis (103.1 nmol/L; 95% CI, 53-689 nmol/L, P < .001) vs controls (1.7 nmol/L; 95% CI, 0.02-4.3 nmol/L) or nonalcoholic pancreatitis (8 nmol/L; 95% CI, 1.1-11.5 nmol/L). Alcoholic pancreatitis increased serum NEFAs (1024 ± 710 µmol/L vs 307 ± 185 µmol/L in controls, P < .05). FAEEs comprised 0.1% to 2% of the parent NEFA concentrations. FAEES correlated strongly with NEFAs independent of ethanol levels in alcoholic pancreatitis but not during alcohol intoxication. On receiver operating characteristic curve analysis for diagnosing alcoholic pancreatitis, the area under the curve for serum FAEEs was 0.87 (95% CI, 0.78-0.95, P < .001). In mice and cells, alcohol administration transiently increased all FAEEs. Oleic acid ethyl ester was the only FAEE with a sustained increase up to 24 hours after intraperitoneal oleic acid plus ethanol administration. CONCLUSIONS: The sustained, alcohol-independent, large (20- to 50-fold) increase in circulating FAEEs during alcoholic pancreatitis results from their visceral release and mirrors the 2- to 4-fold increase in parent NEFA. The large areas under the curve of FAEEs on receiver operating characteristic curve analysis supports their role as alcoholic pancreatitis biomarkers.

The Influence of Alcohol on the Base Excess Parameter in Trauma Patients.

BACKGROUND: The base excess (BE) parameter can be used as an indicator of mortality. However, study results on the influence of alcohol on the validity of BE as a prognostic parameter in alcohol-intoxicated patients are controversial. Thus, this study examined the hypothesis: An increasing blood alcohol level reduces the prognostic value of the BE parameter on mortality. PATIENTS AND METHODS: In a retrospective analysis of the multicenter database of the TraumaRegister DGU, patients from 2015 to 2017 were grouped depending on their blood alcohol level (BAL) into a BAL+ and BAL- group. The hypothesis was verified using logistic regression with an assumed significance level of 1% (P < 0.01). RESULTS: Eleven thousand eight hundred eighty-nine patients were included; 9,472 patients in the BAL- group and 2,417 patients in the BAL+ group. Analysis of the BE showed lower values in the BAL+ group (BAL-: -1.8 ±â€Š4.4 mmol/L vs. BAL+: -3.4 ±â€Š4.6 mmol/L). There is a trend toward lower BE levels when BAL increases. Assuming a linear relationship, then BE decreases by 0.6 points per mille alcohol (95% CI: 0.5-0.7; P < 0.001). The mortality rate was significantly lower in the BAL+ group (BAL-: 11.1% vs. BAL+: 7.9%). The logistic regression analysis showed a significant beneficial influence of BAL+ on the mortality rate (OR 0.706, 95% CI 0.530-0.941, P = 0.018). To analyze whether a low BE (≤-6 mmol/L) has different prognostic effects in patients with and without alcohol, logistic regression models were calculated. However, the effect of BE ≤ -6 mmol/L was similar in both models (regression coefficients in BAL-/+ patients: 0.379/0.393). CONCLUSIONS: The data demonstrate an existing influence of alcohol on the BE parameter; however, this does not negatively affect the BE as a prognostic parameter at a threshold of ≤ -6 mmol/L.

Impact of sex, strain, and age on blood ethanol concentration and behavioral signs of intoxication during ethanol vapor exposure.

Animal models of alcohol drinking and dependence are a critical resource for understanding the neurobiological mechanisms and development of more effective treatments for alcohol use disorder (AUD). Because most rat strains do not voluntarily consume large enough quantities of alcohol to adequately model heavy drinking, dependence, and withdrawal-related symptoms, researchers frequently turn to experimenter administered methods to investigate how prolonged and repeated exposure to large quantities of alcohol impacts brain and behavior. Vaporized ethanol is a common method used for chronically subjecting rodents to alcohol and has been widely used to model both binge and dependence-inducing heavy drinking patterns observed in humans. Rodent strain, sex, and age during exposure are all well-known to influence outcomes in experiments utilizing intraperitoneal or intragastric methods of repeated ethanol exposure. Yet, despite its frequent use, the impact of these variables on outcomes associated with ethanol vapor exposure has not been widely investigated. The present study analyzed data generated from over 700 rats across an eight-year period to provide a population-level assessment of variables influencing level of intoxication using vapor exposure. Our findings reveal important differences with respect to strain, sex, and age during ethanol exposure in the relationship between blood ethanol concentration and behavioral signs of intoxication. These data provide valuable scientific and practical insight for laboratories utilizing ethanol vapor exposure paradigms to model AUD in rats.

An Adolescent Porcine Model of Voluntary Alcohol Consumption Exhibits Binge Drinking and Motor Deficits in a Two Bottle Choice Test.

AIMS: Alcohol is the most commonly abused substance leading to significant economic and medical burdens. Pigs are an attractive model for studying alcohol abuse disorder due to the comparable alcohol metabolism and consumption behavior, which are in stark contrast to rodent models. This study investigates the usage of a porcine model for voluntary binge drinking (BD) and a detailed analysis of gait changes due to motor function deficits during alcohol intoxication. METHODS: Adolescent pigs were trained to drink increasing concentration (0-8%) of alcohol mixed in a 0.2% saccharin solution for 1 h in a two bottle choice test for 2 weeks. The training period was followed by a 3-week alcohol testing period, where animals were given free access to 8% alcohol in 0.2% saccharin solution and 0.2% saccharin water solution. Blood alcohol levels were tested and gait analysis was performed pre-alcohol consumption, last day of training, and Day 5 of each testing period. RESULTS: Pigs voluntarily consumed alcohol to intoxication at all timepoints with blood alcohol concentration (BAL) ≥80 mg/dl. Spatiotemporal gait parameters including velocity, cadence, cycle time, swing time, stance time, step time, and stride length were perturbed as a result of intoxication. The stratification of the gait data based on BAL revealed that the gait parameters were affected in a dose-dependent manner. CONCLUSION: This novel adolescent BD porcine model with inherent anatomical and physiological similarities to humans display similar consumption and intoxication behavior that is likely to yield results that are translatable to human patients.

[Comparative analysis of the incidence of alcohol intoxication in adolescents in a pediatric emergency department.] / Análisis comparativo de la incidencia de intoxicaciones etílicas en adolescentes en un servicio de Urgencias pediátricas.

OBJECTIVE: A retrospective study (2007-2012) of acute alcohol intoxication (AAI) in the paediatric Emergency Department (ED) (Hospital Sant Joan de Déu, Barcelona) demonstrated a decrease in the rates of AAI over the last two years. Aim: to determine if this decile continued during the following 5 years and to describe the profile and clinical management of these patients. METHODS: Descriptive, retrospective and observation study. Adolescents who presented to the ED (Hospital Sant Joan de Déu, Barcelona) with AAI were included (2007-2017). Patients were classified in two groups: mil and moderate/severe; we compared the differences in the clinical management (monitoring of vital signs, lab test and treatment). We defined the AAI incidence rate: number of AAI every 1000 ED adolescent consultations/year. RESULTS: We included 836 AII, incidence rate: 7.7;2007, 8.5;2008, 6.6;2009, 7.8;2010, 6.4;2011, 6.4;2012, 4.8;2013, 4.6;2014, 5.5;2015, 4.8;2016 and 3.4;2017. The mean age was 15.9 (SD 1.2) years, 54.9% (459) were women. 54.5% had mild AAI, 45.4% moderate/severe. The temperature was taken to 607 patients, capillary blood glucose to 573 and blood pressure to 633. We found no differences in the monitoring of vital signs regardless of the symptoms of the patients. Patients with moderate/severe AAI underwent blood test more frequently than those with mild AAI (ethanol levels 88.2% vs 50.4%; p<0.001; electrolytes 81.2% vs 48%, p<0.001; glucose levels 64.4% vs 37.1%, p<0.001). Four hundred and twelve patients (49.3%) received fluid therapy. Twenty-two patients were admitted. CONCLUSIONS: The incidence of AAI decreased over the last years. The profile of these patients remains unchanged (adolescents with moderate AAI during weekends). Even though lab test were performed more frequently to patients with moderate/severe AAI, clinical management should be improved by taking vital signs and capillary glycemia to all patients, keeping the blood analysis for moderate-severe AAI.

OBJETIVO: Una revisión retrospectiva (período 2007-2012) de las intoxicaciones etílicas agudas (IEA) en el Servicio de Urgencias Pediátrico (SUP) del Hospital San Joan de Déu, de Barcelona, evidenció un descenso de las visitas por IEA los últimos dos años. El objetivo de este trabajo fue comprobar si este descenso se había mantenido los 5 años posteriores, así como describir el perfil y manejo de estos pacientes. METODOS: Se realizó un estudio descriptivo, retrospectivo y observacional. Se incluyeron consultas de adolescentes en el SUP del Hospital San Joan de Déu, de Barcelona, por IEA (período 2007-2017). Se dividieron los pacientes en IEA leve y moderada-grave. Se valoraron las diferencias en su manejo (toma de constantes, analítica y tratamiento.) Se definió la tasa de incidencia de IEA cada 1.000 visitas a Urgencias de adolescentes/año. RESULTADOS: Se incluyeron 836 IEA. Las tasas de incidencia por años fueron: 7,7% (2007); 8,5% (2008); 6,6% (2009); 7,8% (2010); 6,4% (2011); 6,4% (2012); 4,8% (2013); 4,6% (2014); 5,5% (2015); 4,8% (2016) y 3,4% (2017). La edad media fue de 15,9 (DE 1,2) años, siendo mujeres el 54,9%. Presentó IEA leve un 54,5% y moderada-grave un 45,4%. Se determinó temperatura a 607, glicemia capilar a 573 y tensión arterial a 633. No hubo diferencias significativas en la determinación de las tres constantes según la clínica de intoxicación. A los pacientes con IEA moderada-grave se les realizó analítica sanguínea con mayor frecuencia que a los de IEA leve (niveles de etanol del 88,2% frente al 50,4%; p<0,001 / EAB-ionograma del 81,2% contra el 48%, p<0,001 / glicemia venosa del 64,4% respecto al 37,1%, p<0,001). Se administró sueroterapia a 412 (49,3%). Precisaron ingreso 22 pacientes. CONCLUSIONES: La incidencia de IEA en SUP disminuye. Se mantiene el perfil de adolescentes (IEA moderadas el fin de semana). Aunque se realizó analítica con mayor frecuencia a los pacientes con IEA moderada, el manejo de las IAE presenta aspectos mejorables, debiendo preconizar la toma de constantes y la glicemia capilar en todos los pacientes, reservando la analítica para los pacientes moderados-graves.

No effect of moderate alcohol intake on the detection of concealed identity information in the laboratory.

The Concealed Information Test (CIT) enables the detection of certain (e.g., crime-relevant or personal) information, even if participants aim to conceal their knowledge. The current preregistered study investigated whether previously observed impairing effects of alcohol intoxication on participants' performance in a reaction time CIT (RT CIT) field study also translate to a laboratory environment. In contrast to the previous study of Suchotzki and Gamer (Sci Rep 8:7825, 2018) in which alcohol consumption was voluntary and self-administered, the current study used a randomized assignment of participants to either an alcohol group (n = 88; receiving a drink with 3 cl alcohol) or a sober control group (n = 89; receiving a drink with just some alcohol drops to hide group assignment). After drink administration, participants completed an RT CIT, in which they were instructed to hide knowledge of their own identity. Blood alcohol concentration (BAC) was estimated via breath alcohol ratio. In contrast to the previous field study, results revealed no differences in CIT-performance between intoxicated and sober participants. Aside from questioning the robustness of the result of the previous field study, our results also point to a number of interesting theoretical explanations for the discrepancy between both results, which are elaborated in the discussion.

Does Level of Blood Alcohol Content Affect Clinical Outcomes After Trauma in Older Adult Patients?

INTRODUCTION: Preinjury alcohol use and older age have independently been associated with poor outcomes. This study examined whether higher levels of blood alcohol concentration (BAC) correlated with an increased likelihood of poor outcomes in older trauma patients. METHODS: This was a retrospective cohort study of injured patients ≥65 years with BAC testing presenting to a Level 1 trauma center between 2015 and 2018. Patients were stratified by BAC at 4 thresholds of intoxication: BAC ≧10 mg/dL, BAC ≧80 mg/dL, BAC ≧150 mg/dL, and BAC ≧200 mg/dL. Propensity score matching using inverse probability of treatment weighting was used to estimate outcomes. Logistic and Poisson regression models were performed for each threshold of the BAC level with the matched cohort to assess clinical outcomes. RESULTS: Of all older patients (n = 3112), 32.5% (n = 1012) had BAC testing. In the matched cohort of 883 patients (76.7 ± 8.2 years; 48.1% female), 111 (12.5%) had BAC ≧10 mg/dL, 83 (74.8%) had BAC ≧80 mg/dL, 60 (54.1%) had BAC ≧150 mg/dL, and 37 (33.3%) had BAC ≧200 mg/dL. Falls (60.5%) and motor vehicle crashes (28.9%) were the most common mechanisms of injury. Median (IQR) of Injury Severity Score (ISS) was 5 (1-10). The risk of severe injury (ISS ≧15) was similar between alcohol-positive and alcohol-negative patients (9.9% vs 15.0%, P = .151). BAC ≧10 g/dL was not associated with length of stay, intensive care unit admission, or in-hospital complication, nor was any of the other 3 analyzed BAC thresholds. CONCLUSION: Overall, any detectable BAC along and increasing thresholds of BAC was not associated with poor in-hospital outcomes of older patients after trauma. Alcohol screening was low in this population, and intoxication may bias injury assessment, leading to mistriage of older trauma patients.

Context, acute tolerance, and subjective response affect alcohol-impaired driving decisions.

RATIONALE: Alcohol intoxication produces effects that can impair judgment and increase engagement in risky behaviors, including alcohol-impaired driving (AID). Real-world AID decisions are informed by contextual circumstances and judgments of associated risk. How individuals vary in their AID decision-making across contexts and whether subjective alcohol responses (stimulation, sedation, acute tolerance) differentially affect AID decisions are critical, but under-studied research questions. OBJECTIVES: We systematically investigated predictors of AID decisions at different hypothetical driving distances across the blood alcohol concentration (BAC) curve. METHODS: Young adults (n = 40; 55% female) completed two laboratory sessions in a within-subjects alcohol/placebo design. At multiple points along the BAC curve (M peak BAC = 0.101 g%), participants rated their subjective intoxication, stimulation, sedation, and perceived dangerousness of driving prior to indicating their willingness to drive distances of 1, 3, and 10 miles. Multilevel mixed models assessed within- and between-person predictors of the maximum distance participants were willing to drive at matched BACs on the ascending and descending limb. RESULTS: Under intoxication (but not placebo), participants were willing to drive greater distances on the descending versus ascending limb. At the momentary level, participants were willing to drive further when they felt less intoxicated, stimulated, and sedated, and perceived driving as less dangerous. CONCLUSIONS: Individuals differed in the distance they were willing to drive as a function of indicators of intoxication, implicating driving distance as an important contextual factor relevant to AID decisions. Individuals may simultaneously perceive themselves as "unsafe" to drive, but "safe enough" to drive short distances, particularly when BAC is falling.

Intubation in acute alcohol intoxications at the emergency department.

BACKGROUND: Guidelines recommend endotracheal intubation in trauma patients with a Glasgow coma scale (GCS) < 9 because of the loss of airway reflexes and consequential risk of airway obstruction. However, in patients with acute alcohol intoxication guidelines are not clear. Thus, we aimed to determine the proportional incidence of intubation in alcohol intoxication and compare the clinical characteristics of intubated and non-intubated patients, as well as reasons for intubation in all patients and in the subgroup of patients with reduced GCS (< 9) but without traumatic brain injury. METHODS: We performed a retrospective analysis of all consultations to an urban ED in Switzerland that presented with an acute alcohol intoxication between 1st June 2012 and 31th Mai 2017. Patient and emergency consultations' characteristics, related injuries, intubation and reason for intubations were extracted. As a subgroup analysis, we analysed the patients with a GCS < 9 without a traumatic brain injury. RESULTS: Of 3003 consultations included from 01.06.2012 to 31.05.2017, 68 were intubated, leading to a proportional incidence of 2.3% intubations in alcohol-intoxication. Intubated patients had a lower blood alcohol concentration (1.3 g/kg [IQR 1.0-2.2] vs. 1.6 g/kg [IQR1.1-2.2], p = 0.034) and less often suffered from chronic alcohol abuse (1183 [39.4%] patients vs. 14 [20.6%], p = 0.001) than non-intubated patients. Patients with trauma were intubated more often (33 patients [48.5%] vs. 742 [25.3%], p < 0.001). In subgroup analysis, 110/145 patients (74.3%) were not intubated; again, more intubated patients had a history of trauma (9 patients [25.7%] vs. 10 [9.1%], p = 0.011). CONCLUSIONS: Intubation in alcohol-intoxicated patients is rare and, among intoxicated patients with GCS < 9, more than two thirds were not intubated in our study - without severe complications. Trauma in general, independent of the history of a traumatic brain injury, and a missing history of chronic alcohol abuse are associated with intubation, but not with blood alcohol concentration. Special caution is required for intoxicated patients with trauma or other additional intoxications or diseases.

Endocrine effects of the novel ghrelin receptor inverse agonist PF-5190457: Results from a placebo-controlled human laboratory alcohol co-administration study in heavy drinkers.

Both animal and human work suggests that the ghrelin system may be involved in the mechanisms that regulate the development and maintenance of alcohol use disorder. Previously, in a Phase 1b study, we tested pharmacological blockade of the growth hormone secretagogue receptor 1a (GHS-R1a, also known as the ghrelin receptor), in heavy drinking individuals with PF-5190457, an orally bioavailable, potent and selective GHS-R1a inverse agonist. We report here the effects of PF-5190457 on endocrine blood concentrations of amylin, gastric inhibitory polypeptide, glucagon-like peptide 1, insulin, leptin, pancreatic polypeptide, peptide YY, thyroid stimulating hormone, free triiodothyronine (T3), thyroxine (T4), cortisol, prolactin, and glucose during PF-5190457 dosing, as compared to placebo, in absence of alcohol as well as during an alcohol challenge when PF-5190457 was on steady-state. Blood hormone levels were largely unaffected by PF-5190457, both during dosing and in the context of alcohol challenge. The safety-related relevance of these findings to further develop PF-5190547 in alcohol use disorder is discussed. CLINICALTRIALS.GOV: NCT02039349. This article is part of the special issue on 'Neuropeptides'.

Intoxicated aggression: Do alcohol and stimulants cause dose-related aggression? A review.

RATIONALE: Violence and drug use are significant public health challenges that are strongly linked. It is known that alcohol plays a major role in the causation of unnatural deaths and that stimulants like cocaine and amphetamine are often implicated in aggressive acts or violence. However, a clear causal relationship between these substances and aggression, and more specifically a blood concentration threshold at which intoxicated aggression emerges is lacking. In case of a crime and subsequent law enforcement, knowledge about dose-response relationships could be of pivotal importance when evaluating the role of alcohol and drugs in aggressive offences. AIMS: The present review aimed to determine whether there is a causal relation between intoxication with these psychoactive substances and aggression, and to define blood concentration thresholds above which these substances elicit aggression. METHODS: Empirical articles published between 2013 and 2017 and review papers containing the predefined search strings were identified through searches in the PubMed and Embase databases and additional reference list searches. The complete search query yielded 1578 publications. Initially all articles were manually screened by title and abstract. Articles with irrelevant titles, given the selected search terms and review aims were discarded. Remaining articles were carefully studied and those that did not comply with the main objectives of this review were discarded. At the end of this process, 167 titles were found eligible for review. FINDINGS AND CONCLUSION: While placebo-controlled experimental studies clearly showed a causal link between alcohol and aggression, it is evident that such a link has not yet been established for cocaine and amphetamines. In case of alcohol, it is clear that there are various individual and contextual factors that may contribute to the occurrence of an aggressive act during intoxication. A clear threshold blood alcohol concentration has not been defined yet for alcohol, but a statistically significant increase of aggression has been demonstrated at a dose of 0.75 g/kg and higher. Future studies into intoxicated aggression should include multiple doses of alcohol and stimulants and take into account individual and contextual factors.

The utility of S100B level in detecting mild traumatic brain injury in intoxicated patients.

BACKGROUND: S100B is a serum protein known to elevate in patients with brain injury, but it is unknown whether it can predict intracranial pathology in intoxicated patients following mild traumatic brain injury (MTBI). We performed a systematic review and meta-analysis of the English language literature to address this question. MAIN OUTCOMES AND RESULTS: Four prospective cohort trials of serum S100B levels on acutely intoxicated patients with MTBI were included in this meta-analysis. Prevalence of intracranial pathology in the pooled cohort of the intoxicated MTBI patients was 10%, lower than the 15-30% reported in the literature for the general MTBI population. Standard mean difference of serum S100B levels between patients with and without intracranial pathology on CT was 0.73 µg/L (Z = 18.33, P < 0.001). Following sensitivity analysis and hierarchical summary receiver-operating characteristic models, three remaining articles were used for pooled estimates that found that S100B had a sensitivity of 0.96 (95% CI: 0.84-1.00, I2 = 0%) and specificity of 0.63 (95% CI: 0.58-0.68, I2 = 86.8%) with a high negative predictive value (100%, 95% CI: 95.14-100, I2 = 0%) and a negative LR of 0.06 (95% CI: 0.01-0.31). CONCLUSIONS: Serum S100B levels may have utility in ruling out intracranial pathology in intoxicated patients, however more study and comparison with other serum biomarkers of brain injury are necessary before this becomes the accepted standard of care.

Significant decrease in the rate of fatal alcohol poisonings in Finland validated by blood alcohol concentration statistics.

BACKGROUND: Alcohol may cause death directly by acute poisoning, as well as induce illnesses or accidents that lead to death. Our research question was whether the current decreasing trend in acute fatal alcohol poisonings in Finland is a real phenomenon or an artefact caused by possible changes in the process of determining the cause of death. METHODS: All cases in the national post-mortem toxicology database in which the underlying cause of death was acute alcohol poisoning in 1987-2018 were investigated in terms of blood alcohol concentration (BAC), age and gender. The number of acute alcohol poisonings was compared to the number of deaths from alcohol induced illness in the post-mortem toxicology database. RESULTS: A total of 12 126 acute alcohol poisoning cases were retrieved. Between 2004 and 2017 the number of acute alcohol poisonings decreased 60.1 %. At the same time the number of alcohol induced illnesses in the study material remained stable or decreased marginally. The median BAC in all acute alcohol poisonings was 3.2 g/kg. The annual median BAC values showed a small but significant decrease over the study period. The proportion of women in acute alcohol poisonings increased significantly over the study period, from 17.1%-22.3%. Women were on average 2.5 years older than men. CONCLUSIONS: On grounds of the BAC statistics and supporting evidence, we conclude that the significant decrease in the number of fatal alcohol poisonings is true and likely reflects changes in the overall consumption of alcohol.

Involuntary movements in an adolescent: what are the causes?

Involuntary movements can be a troublesome condition and represent a real challenge for emergency doctors, particularly for patients of paediatric age. We report a case of a 17-year-old boy with painful involuntary movements mostly affecting his mouth and lower limbs, but also the trunk. After reviewing the patient's history, it was revealed that the adolescent had had acute alcohol intoxication with severe acute agitation and therefore was given a single dose of 10 mg intravenous haloperidol. The concealment of the recent event posed serious difficulties in reaching the diagnosis. When the diagnosis of haloperidol-induced acute dystonia was made, 3 mg of intravenous biperiden was promptly administered with complete clinical resolution in 15 min.

Alcohol Intoxication as a Stroke Mimic and the Incidence of Acute Alcohol Intoxication in Stroke.

BACKGROUND AND AIM: Alcohol intoxication can be a posterior circulation stroke mimic as they share symptoms such as dysarthria, gait disturbances and nystagmus. We describe alcohol intoxication as a stroke mimic and the frequency of acute alcohol intoxication among stroke patients. METHODS: Prospective observational single-center study (2014-2017, Haga Ziekenhuis, the Hague). In all patients older than 16 years presenting as possible acute stroke less than 6 hours of onset, blood ethanol was measured; greater than 0.1 blood alcohol concentration (BAC) was considered elevated. RESULTS: In total 974 patients were included: 60 (6%) had elevated blood ethanol (mean: 1.3 BAC). In 180 of 974 patients (18%) a stroke mimic was diagnosed: 12 were due to alcohol intoxication (1% of total cohort, 7% of stroke mimic, mean ethanol level: 2.2 BAC). Half of these patients denied or downplayed their alcohol consumption. Stroke and concurrent alcohol intoxication occurred in 38 of 794 strokes (5%, mean ethanol level: 1.1 BAC). Compared to other stroke patients, these 38 patients presented more often after working hours (mean 6.38pm versus 2.23pm) and received alteplase and endovascular therapy less often (24% versus 43%, P = .018 and 3% versus 10%, P = .241, respectively). CONCLUSIONS: Of all patients presenting as possible acute stroke, 6% also drank alcohol. 18% of the whole cohort was diagnosed with a stroke mimic. Acute alcohol intoxication as sole diagnosis was diagnosed in 1% of the total cohort and 7% of stroke mimics, 50% denied or downplayed their alcohol consumption. 5% of all stroke patients also drank alcohol, they were significantly less likely to receive alteplase or endovascular treatment.

Exploring the Effect of Driving Factors on Traffic Crash Risk among Intoxicated Drivers: A case Study in Wujiang.

Intoxicated driving is a threat to both drivers and other road users. Exploring the association between intoxicated driving factors and traffic crashes is essential for taking effective countermeasures. Most previous works have studied the relation between intoxicated driving and traffic crash based on some large-sized cities. The current study aims to evaluate the effect of driving factors on traffic crashes among intoxicated drivers in a small-sized city in China. Descriptive statistics and binary logistic regression analysis are performed to guide the study, and the data (N=1010) for the period 2016-2017 in Wujiang (i.e., a small-sized city in China) are employed as the target samples. The results demonstrate age, years of driving experience, road position, week, hour and blood alcohol concentration (BAC) are associated with traffic crashes in Wujiang. Specifically, the age of "18-25", the years of driving experience of "≤2", the "road intersection", the "weekend", the period of "0:00-6:59" and the BAC of "above 150 mg/100 mL" are more likely to cause traffic crashes among intoxicated drivers. The findings can be referred to make some targeted policies or measures to relieve Wujiang's intoxicated driving situation and reduce the number of crashes caused by intoxicated driving.

Critical Evaluation of the Association Between Elevated Mean Corpuscular Volume and Alcohol-Related Traffic Accidents: A Retrospective Study on 6244 Car Crash Cases.

BACKGROUND: Erythrocyte mean corpuscular volume (MCV) has been used for decades as a biomarker of chronic alcohol abuse and in the treatment of alcohol dependence. More recently, it has also been adopted to investigate the fitness of subjects to hold the driving license to prevent traffic accidents. So far, however, the studies on the association of MCV with an increased risk of alcohol-associated car accidents are extremely scarce, if not totally absent. To the best of our knowledge, the present work is the first specifically aimed at studying a plausible association between elevated MCV and crash accidents correlated with alcohol abuse. METHODS: A total of 6,244 drivers involved in traffic accidents underwent mandatory laboratory analyses including blood alcohol concentration (BAC) determination and MCV analysis. BAC and MCV determinations were performed by headspace gas chromatography and complete blood count, respectively. RESULTS: The chi-square test evaluating the proportions of subjects with elevated MCVs (>95 fl) yielded a highly significant result (χ2  = 68.0; p < 0.001) in the blood samples where the BAC was above the legal limit (i.e., >0.5 g/l). However, when considering only drivers showing BACs in the range of 0.51 to 1.5 g/l, the frequencies of elevated MCV values are fairly comparable (χ2  = 0.062, p = 0.80). In contrast, limiting the evaluation to BACs > 1.5 g/l, the frequency of elevated MCVs raised to 19.1% (χ2  = 58.9, p value < 0.001 vs. the group with BAC within the legal limits). CONCLUSIONS: The present observations show that MCV increases are typically associated with drivers involved in accidents only if driving under severe alcohol intoxication, leading to a preliminary conclusion that, in the context of the certification of the fitness to the driving license, MCV fails to reveal individuals at risk who tend to drive in a condition of low-to-moderate alcohol intoxication.

Effects of Phyllanthus amarus PHYLLPROTM leaves on hangover symptoms: a randomized, double-blind, placebo-controlled crossover study.

CONTEXT: Phyllanthus amarus Schumach. and Thonn. (Euphorbiaceae) is traditionally known to improve general liver health. However, its effect on hangover is unknown. OBJECTIVE: This study evaluated PHYLLPRO™, a standardized ethanol extract of P. amarus leaves for protection against oxidative stress and recovery from hangover symptoms. MATERIAL AND METHODS: Ten days daily oral supplementation of 750 mg/day followed by intoxication was evaluated in a randomized placebo-controlled (containing only excipient), crossover study in 15 subjects (21-50 years old), for oxidative stress, liver damage, alleviating hangover symptoms (Hangover Severity Score: HSS) and mood improvement (Profile-of-Mood-Scores: POMS). RESULTS: PHYLLPRO™ was able to remove blood alcohol in the active group while the placebo group still had 0.05% at 12 h post-intoxication (p < 0.0001). For HSS, the active group showed reduced hangover symptoms while there were higher levels of nausea, headache, anorexia, tremulousness, diarrhoea and dizziness in the placebo group (p < 0.05) at hour 10 post-intoxication. Increased fatigue at hour 2 and tension (p > 0.05) from baseline to hour 22 was reported in the placebo group using POMS. Significant anti-inflammatory group effect favouring the active group, by the upregulation of cytokines IL-8 (p = 0.0014) and IL-10 (p = 0.0492) and immunomodulatory effects via IL-12p70 (p = 0.0304) were observed. The incidence of adverse events was similar between groups indicating the safety of PHYLLPRO™. DISCUSSION AND CONCLUSION: Preliminary findings of PHYLLPRO™ in managing hangover, inflammation and liver functions following intoxication, is demonstrated. Future studies on PHYLLPRO™ in protecting against oxidative stress and hangover in larger populations is warranted.