Severe Alcohol Research Articles

Hydrogen cyanamide exposure: a case series from Pavia Poison Control Centre.

Hydrogen cyanamide is a plant growth regulator introduced in Italy as Dormex in 2000, but recalled from the market in 2008. It's currently not authorized in Europe. Inhalation/dermal contact may cause irritation/caustic burns, ingestion of severe organ damage and concomitant alcohol consumption disulfiram-like reaction due to aldehyde-dehydrogenase inhibition by hydrogen cyanamide. To study all exposure cases referred to our centre, evaluating temporal and geographic distribution and analysing clinical manifestations, including the ones after alcohol consumption. We retrospectively evaluated all hydrogen cyanamide exposures referred to our Poison Control Centre (January 2007-December 2021). For each case, age, sex, exposure route/year, geographical location, intent of exposure, alcohol co-ingestion, emergency department-admission Poison Severity Score, signs/symptoms and treatment were analysed. Thirty subjects were included. Median case/year was 1 [1; 2]: 79% occurred after market withdrawal, 92% in Sicily. All exposures were unintentional and work related; 41% of patients also co-ingested alcohol. Mean poison severity score at emergency department admission was 1.54, more severe when ingestion occurred. The most common signs/symptoms were flushing, secondary to peripheral vasodilation (41%), hyperaemia/erythema (29%), dyspnoea (25%), nausea (20%), vomiting (12%), oedema (12%), II-III degrees burns (12%) and pharyngodynia (12%). All patients were treated symptomatically and fully recovered. Hydrogen cyanamide exposure can lead to severe clinical manifestations. Despite its withdrawal from the Italian market, hydrogen cyanamide is still used: through PCC's crucial role in monitoring exposure to agricultural products efforts should be made to contrast illegal trade and increase awareness of its potential toxicity in those countries in which it's still legal.

44 A Case Study of Non-Alcoholic Wernicke’s Encephalopathy in a Young Man with Intractable Vomiting

Objective:Wernicke’s encephalopathy (WE) is an acute neurological condition caused by thiamine deficiency. The typical presentation is characterized by a triad of oculomotor abnormalities, gait ataxia, and altered mental status, though patients rarely present with all three symptoms. WE is a serious medical condition that is associated with high rates of morbidity and mortality if left untreated. It is most commonly seen in patients with severe alcohol use disorder; however, it has also been found in patients with thiamine deficiency due to other causes of malnutrition such as prolonged starvation, hyperemesis, dialysis, cancer, and geriatric surgery. Despite growing research demonstrating WE in non-alcoholic populations, it is frequently misdiagnosed in patients without an extensive alcohol-use history, particularly when they do not present with the typical clinical triad of symptoms. Thus, more knowledge about non-alcoholic WE is needed to improve diagnostic accuracy.Participants and Methods:We present a case of a 26-year-old male with an unremarkable alcohol use history, who was diagnosed with WE following a 6-week period of excessive nausea and vomiting of unclear etiology. He presented to the ED three times prior to his diagnosis, and was treated with intravenous hydration, Zofran, and Pepcid. He presented to the ED for the fourth time with altered mental status and gait ataxia and was diagnosed with WE based on MRI findings. He was admitted and treated with high doses of IV thiamine and folate. His clinical course was tracked over time via outpatient neurology examinations, and his cognitive functioning was assessed with an outpatient neuropsychological evaluation approximately six months post-discharge. Record review, including clinical notes, lab tests, and imaging results supplement his outpatient neuropsychological evaluation performance.Results:Data from a comprehensive outpatient neuropsychological evaluation approximately six months after WE diagnosis is presented. His cognitive profile was characterized by impaired performance on measures of verbal fluency and memory, including encoding and retention of verbal and visual information (with minimal benefit from cueing). Given these impairments and continued functional declines related to cognitive deficits, he met criteria for a Major Neurocognitive Disorder. These results demonstrate persistent cognitive deficits beyond the acute WE period.Conclusions:WE is a serious neurological condition that can have lasting cognitive effects if left untreated. This case demonstrates persistent cognitive impairments six months after WE diagnosis in a young patient with an unremarkable alcohol history. These findings highlight the necessity of increased diagnostic efficiency of WE in non-alcoholic patients, as immediate thiamine treatment is essential to the recovery process. Neuropsychological functioning at a longer interval will be useful in further elucidating cognitive prognosis as well as providing quality of life recommendations.

Budget Impact Tool for Implementing Contingency Management for Co-occurring Alcohol Use Disorders and Serious Mental Illness.

Contingency management (CM) is a behavioral intervention in which tangible incentives are provided to patients when they achieve a desired behavior (e.g., reducing or abstaining from alcohol use). The authors sought to describe the resource requirements and associated costs of various CM versions (usual, high magnitude, and shaping) tailored to a high-risk population with co-occurring serious mental illness and severe alcohol use disorder. A microcosting analysis was conducted to identify the resource requirements of the different CM versions. This approach included semistructured interviews with site investigators, who also staffed the intervention. The resource costing method-multiplying the number of units of each resource utilized by its respective unit cost-was used to value the resources from a provider's perspective. All cost estimates were calculated in 2021 U.S. dollars. The cost of setting up a CM program was $6,038 per site. Assuming full capacity and 56% of urine samples meeting the requirement for receipt of the CM incentive, the average cost of 16 weeks of usual and shaping CM treatments was $1,119-$1,136 and of high-magnitude CM was $1,848-$1,865 per participant. A customizable tool was created to estimate the costs associated with various levels of treatment success and CM design features. After the trial, the tool will be updated and used to finalize per-participant cost for incorporation into a comprehensive economic evaluation. This costing tool will help a growing number of treatment providers who are interested in implementing CM with budgeting for and sustaining CM in their practices.

Severe alcohol use disorder after initiation of selective serotonin reuptake inhibitor therapy.

Severe alcohol use disorder after initiation of selective serotonin reuptake inhibitor therapy.

Diagnostic Criteria for Identifying Individuals at High Risk of Progression From Mild or Moderate to Severe Alcohol Use Disorder

Current Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) diagnoses of substance use disorders rely on criterion count-based approaches, disregarding severity grading indexed by individual criteria. To examine correlates of alcohol use disorder (AUD) across count-based severity groups (ie, mild, moderate, mild-to-moderate, severe), identify specific diagnostic criteria indicative of greater severity, and evaluate whether specific criteria within mild-to-moderate AUD differentiate across relevant correlates and manifest in greater hazards of severe AUD development. This cohort study involved 2 cohorts from the family-based Collaborative Study on the Genetics of Alcoholism (COGA) with 7 sites across the United States: cross-sectional (assessed 1991-2005) and longitudinal (assessed 2004-2019). Statistical analyses were conducted from December 2022 to June 2023. Sociodemographic, alcohol-related, psychiatric comorbidity, brain electroencephalography (EEG), and AUD polygenic score measures as correlates of DSM-5 AUD levels (ie, mild, moderate, severe) and criterion severity-defined mild-to-moderate AUD diagnostic groups (ie, low-risk vs high-risk mild-to-moderate). A total of 13 110 individuals from the cross-sectional COGA cohort (mean [SD] age, 37.8 [14.2] years) and 2818 individuals from the longitudinal COGA cohort (mean baseline [SD] age, 16.1 [3.2] years) were included. Associations with alcohol-related, psychiatric, EEG, and AUD polygenic score measures reinforced the role of increasing criterion counts as indexing severity. Yet within mild-to-moderate AUD (2-5 criteria), the presence of specific high-risk criteria (eg, withdrawal) identified a group reporting heavier drinking and greater psychiatric comorbidity even after accounting for criterion count differences. In longitudinal analyses, prior mild-to-moderate AUD characterized by endorsement of at least 1 high-risk criterion was associated with more accelerated progression to severe AUD (adjusted hazard ratio [aHR], 11.62; 95% CI, 7.54-17.92) compared with prior mild-to-moderate AUD without endorsement of high-risk criteria (aHR, 5.64; 95% CI, 3.28-9.70), independent of criterion count. In this cohort study of a combined 15 928 individuals, findings suggested that simple count-based AUD diagnostic approaches to estimating severe AUD vulnerability, which ignore heterogeneity among criteria, may be improved by emphasizing specific high-risk criteria. Such emphasis may allow better focus on individuals at the greatest risk and improve understanding of the development of AUD.

"TO BE OR NOT TO BE" GWAS Ends the Controversy about the DRD2 Gene as a Determinant of Reward Deficiency Syndrome (RDS).

Since 1990, there have been thousands of published studies on addiction psychiatry. Several from Blum et al showed the clinical relevance of the Genetic Addiction Risk Severity (GARS) test in identifying risk for reward deficiency behaviors in cohorts from polysubstance abuse and pain clinics, post-surgical bariatrics, and DWI offenders facing prison time. Since Blum et al first published in JAMA (1990) concerning the association of the DRD2 gene polymorphism and severe alcoholism, reactions have been mixed. More recently, however, a meta-analysis of 62 studies showed a significant association between DRD2 rs1800497 and Alcohol Use Disorder (AUD). Other studies from Yale University showed that a haplotype block of the DRD2 gene A1 allele was associated with AUD and heroin dependence. GWAS studies of depression and suicide in 1.2 million veterans confirmed the first psychiatric candidate gene study finding from Blum et al 1990; a significant association between the minor DRD2 allele, Taq A1 and severe alcoholism. Additionally, the DRD2 rs1800497 is robustly associated with suicidal behaviors. Furthermore, DNA polymorphic alleles underlying substance use disorder (SUD) with multiple substances were mapped via chromatin refolding, revealing that the DRD2 gene and associated polymorphism(s) as the top gene signal. Based on these investigations, we conclude that GWAS should end the controversy about the DRD2 gene being one determinant of Reward Deficiency Syndrome (RDS) first reported in 1996.

Alcohol-associated sexual dysfunction: How much is the damage?

BackgroundThe existing literature on alcohol-induced sexual dysfunction has mainly deliberated on erectile dysfunction and premature ejaculation, ignoring other important domains of sexual dysfunctions (viz sexual pleasure, sexual desire, arousal, orgasmic function). This study was undertaken to assess the extent of alcohol-associated sexual dysfunction and to compare their severity with the severity of alcohol dependence in males. MethodsA cross-sectional descriptive study design recruited 78 male patients and an assessment was conducted using the Changes in sexual functioning questionnaire male clinical version, International index of erectile function scale, Severity of Alcohol Dependence Questionnaire, Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) and International Classification of Diseases-10 (ICD-10). A correlation between years of alcohol consumed and its effect on various domains of sexual dysfunction was also carried out using Pearson's correlation coefficient. ResultsSeventy-seven percent of the study population had complaints of sexual dysfunction in one or more domains, with reduced sexual pleasure (71.8%) as the most common followed by low sexual desire (in terms of frequency) in 61.5% and erectile dysfunction in 43.6%. The severity of the sexual dysfunction was found to be directly proportional to the severity of alcohol dependence with almost 100 percent of the patients with severe alcohol dependence having sexual dysfunction in all the domains. ConclusionThe most common sexual dysfunction reported in the current study was decreased sexual pleasure (71.8%) followed by low sexual desire 61.5% (in terms of frequency). These findings emphasize the fact, that alcohol significantly compromises almost all domains of sexual functioning in addition to erectile dysfunction.

Metadehumanization, fundamental needs and coping strategies: A comparison of drinkers at low versus high risk of alcohol use disorder

The interpersonal difficulties documented in chronic excessive drinking might foster the progression toward severe alcohol use disorder (SAUD). Characterizing these interpersonal difficulties and their commonalities with patients already presenting a diagnosed SAUD is needed to develop targeted prophylactic interventions. Patients with SAUD present metadehumanization (i.e., the perception of being considered as less than human by others), which is associated with deleterious consequences (e.g., reduced fundamental needs satisfaction, increased negative emotions, reduced self-esteem, disrupted coping strategies) involved in the persistence of this disorder. No study has investigated metadehumanization among individuals not diagnosed with SAUD but at high risk of alcohol use disorder. We measured metadehumanization, emotions, self-esteem, coping strategies, and fundamental needs threat among such high-risk drinkers (N = 86; AUDIT score higher than 15), and matched low-risk drinkers (N = 100, AUDIT score <8). Compared to low-risk drinkers, high-risk drinkers felt more dehumanized and reported increased fundamental needs threat, negative emotions, anxiety, depression, and more frequent use of both adaptive and maladaptive coping strategies, including alcohol use. Mediation analyses controlling for anxiety/depression revealed that the differences in emotions and coping strategies were explained by metadehumanization and fundamental needs threat. Despite not being diagnosed with SAUD and being untreated, high-risk drinkers are more similar to patients with SAUD than to low-risk drinkers. In view of its links with factors favoring SAUD, metadehumanization should be considered in experimental studies among high-risk drinkers and treated by specific interventions.

People who binge drink show neuroendocrine tolerance to alcohol cues that is associated with immediate and future drinking- results from a randomized clinical experiment.

Neuroendocrine tolerance to alcohol, i.e., a blunted cortisol response to alcohol, has been linked to Ventromedial Prefrontal Cortex (VmPFC) alcohol cue reactivity and relapse risk in severe Alcohol Use Disorders (AUDs), but its role in the development of AUDs is not clear. Recent work suggests that blunted cortisol responses to alcohol cues in individuals who engage in binge drinking (BD) may play a role in motivation to consume larger amounts of alcohol, but the link between this dysregulated endocrine response and BD's neural responses to alcohol cues remains unclear. To examine this, two groups of participants were recruited based on their recent drinking history. Thirty-three BD and 31 non-binging, social drinkers (SD) were exposed to alcohol cues and water cues in two separate 7 T functional magnetic resonance imaging (fMRI) scans. Each scan was followed by the Alcohol Taste Test (ATT) of implicit motivation for alcohol and a post-experiment, one-month prospective measurement of their "real world" drinking behavior. During each scan session, blood plasma was collected repeatedly to examine the separate effects of alcohol cues and alcohol consumption on cortisol levels. Relative to water cues and SD, BD demonstrated blunted cortisol cue reactivity that was negatively associated with VmPFC cue reactivity. In BD, both blunted cortisol and greater VmPFC cue reactivity were related to immediate and future alcohol consumption in the month following the scans. Thus, neuroendocrine tolerance in BD may be associated with increased incentive salience of cues and contribute mechanistically to increased alcohol consumption seen in the development of AUDs.

Craving modulates attentional bias towards alcohol in severe alcohol use disorder: An eye-tracking study.

Competing models disagree on three theoretical questions regarding alcohol-related attentional bias (AB), a key process in severe alcohol use disorder (SAUD): (1) is AB more of a trait (fixed, associated with alcohol use severity) or state (fluid, associated with momentary craving states) characteristic of SAUD; (2) does AB purely reflect the over-activation of the reflexive/reward system or is it also influenced by the activity of the reflective/control system and (3) does AB rely upon early or later processing stages? We addressed these issues by investigating the time-course of AB and its modulation by subjective craving and cognitive load in SAUD. A free-viewing eye-tracking task, presenting pictures of alcoholic and non-alcoholic beverages, combined with a concurrent cognitive task with three difficulty levels. A laboratory setting in the detoxification units of three Belgian hospitals. We included 30 patients with SAUD self-reporting craving at testing time, 30 patients with SAUD reporting a total absence of craving and 30 controls matched on sex and age. All participants from SAUD groupsmet the DSM-5 criteria for SAUD. We assessed AB through early and late eye-tracking indices. We evaluated the modulation of AB by craving (comparison between patients with/without craving) and cognitive load (variation of AB with the difficulty level of the concurrent task). Dwell time measure indicated that SAUDpatients with craving allocated more attention towards alcohol-related stimuli than patients without craving (P < 0.001, d = 1.093), resulting in opposite approach/avoidance AB according to craving presence/absence. SAUD patients without craving showed a stronger avoidance AB than controls (P = 0.003, d = 0.806). AB did not vary according to cognitive load (P = 0.962, η2 p = 0.004). The direction of alcohol-related attentional bias (approach/avoidance) appears to be determined by patients' subjective craving at testing time and does not function as a stable trait of severe alcohol use disorder. Alcohol-related attentional bias appears to rely on later/controlled attentional stages but is not modulated by the saturation of the reflective/control system.

Predictors of Escalation to Intensive Care Unit Level of Care Among Admissions for Alcohol Withdrawal.

According to the 2019 National Survey on Drug Use and Health, 14.5 million people ages 12 and older had alcohol abuse disorder. Alcohol withdrawal syndrome (AWS) can be defined as a collection of physical symptoms experienced due to abrupt cessation of alcohol after long-term dependence. In instances where regular inpatient management fails to control AWS symptoms, patients are shifted to intensive care units (ICUs) for closer monitoring and prevention of life-threatening complications like withdrawal seizures and delirium tremens (DTs), labeled as severe alcohol withdrawal syndrome (SAWS). Although this represents a significant healthcare burden, minimal studies have been conducted to determine objective predictors. In this study, we aim to determine the effect of patient demographics, socio-economic status, biochemical parameters, and clinical factors on the need for escalation to ICU level of care among admissions for AWS. Our study showed that factors such as a history of DTs or alcohol-related seizures, the initial protocol of management, degree of reported alcohol usage, activation of rapid response teams, mean corpuscular value, alcohol level on admission, highest Clinical Institute Withdrawal Assessment Alcohol Revised (CIWA-Ar) scored during the hospital stay, and the total amount of sedatives used were significantly associated with escalation to ICU level of care. Clinicians must use these objective parameters to identify high-risk patients and intervene early. We encourage further studies to establish a scoring algorithm incorporating biochemical parameters to tailor management algorithms that might better suit high-risk patients.

Insular volumetry in severe alcohol use disorder and Korsakoff's syndrome through an anatomical parcellation: Let us go back to basics.

Functional neuroimaging has demonstrated the key role played by the insula in severe alcohol use disorder (sAUD), notably through its involvement in craving and body signals processing. However, the anatomical counterpart of these functional modifications in sAUD patients with and without neurological complications remains largely unexplored, especially using state-of-the-art parcellation tools. We thus compared the grey matter volume of insular subregions (form anterior to posterior: anterior inferior cortex, anterior short gyrus, middle short gyrus, posterior short gyrus, anterior long gyrus, posterior long gyrus) in 50 recently detoxified patients with sAUD, 19 patients with Korsakoff's syndrome (KS) and 36 healthy controls (HC). We used a mixed linear model analysis to explore group differences in the six subregions grey matter volume and lateralization differences. Insular macrostructure was globally affected to the same extent in sAUD with and without KS, indicating that these brain abnormalities may be related to alcohol consumption per se, rather than to the presence of alcohol-related neurological complications. Insular atrophy showed a right-sided lateralization effect and was especially marked in the posterior insula, a region associated with visceral information processing and the embodiment effect of a substance, from which craving arises. Anatomical damages might thus underlie the previously reported altered insular activations and their behavioural counterparts.

Supplements Are Not a Synonym for Safe: Suspected Liver Injury From Ashwagandha.

As patients look more to alternative herbal and dietary supplements to boost energy and mood, reports are increasing of unintended adverse effects, particularly to the liver. We report a case of a 48-year-old man with a history of severe alcohol use disorder who presented to the emergency department with a cholestatic pattern of liver injury in the setting of alcohol and use of a testosterone-boosting supplement containing ashwagandha. Drug-induced liver damage should be considered in patients with alcohol use disorder who present with a cholestatic pattern of liver injury. Although many natural substances are well tolerated, others can have unanticipated and harmful adverse effects and drug interactions. Future research should identify not only potentially harmful substances, but also which patients may be at greatest risk.

Evaluation of Atherosclerotic Risk by Oxidative Contributors in Alcohol Use Disorder.

Alcohol Use Disorder (AUD) is a condition described as the inability to control or stop alcohol consumption. The patients with AUD have an increased risk of developing atherosclerosis-related diseases. The present study aimed to evaluate oxidative contributors of atherosclerotic risk factors in patients with AUD. The male subjects diagnosed with AUD (n = 45) and the male subjects as control (n = 35) were enrolled in this study. All participants were undergone psychiatric evaluation and sociodemographic tests. Also, serum oxidative contributors of atherosclerosis including myeloperoxidase (MPO), ferroxidase, catalase (CAT), and lipid hydroperoxides (LOOH) were measured. Additionally, serum lipid profile tests and atherogenic indicators including atherogenic index of plasma (AIP) and non-high-density lipoprotein (HDL) cholesterol were also analyzed. The AUD subject had significantly elevated MPO activity and LOOH levels with decreased antioxidant capacity. AIP and non-HDL cholesterol levels, the atherogenic indicators, were also higher in AUD group compared to the control group. We found the MPO activity and LOOH levels were positively correlated with AIP, non-HDL cholesterol levels, and amount of alcohol consumption. Additionally, CAT activity was negatively correlated with duration of alcohol consumption. Our results revealed that MPO and LOOH levels were elevated by severe alcohol intake and the atherogenic indicators, AIP and non-HDL cholesterol, were significantly correlated alcohol induced elevated oxidative risk factors. Therefore, it can be suggested that MPO activity and LOOH levels may be useful to determine jeopardy of atherosclerotic and the therapeutic interventions that reduce oxidative load could be taken into account to prevent atherosclerotic diseases before clinical manifestation.

Acceptability of Personal Sensing Among People With Alcohol Use Disorder: Observational Study.

Personal sensing may improve digital therapeutics for mental health care by facilitating early screening, symptom monitoring, risk prediction, and personalized adaptive interventions. However, further development and the use of personal sensing requires a better understanding of its acceptability to people targeted for these applications. We aimed to assess the acceptability of active and passive personal sensing methods in a sample of people with moderate to severe alcohol use disorder using both behavioral and self-report measures. This sample was recruited as part of a larger grant-funded project to develop a machine learning algorithm to predict lapses. Participants (N=154; n=77, 50% female; mean age 41, SD 11.9 years; n=134, 87% White and n=150, 97% non-Hispanic) in early recovery (1-8 weeks of abstinence) were recruited to participate in a 3-month longitudinal study. Participants were modestly compensated for engaging with active (eg, ecological momentary assessment [EMA], audio check-in, and sleep quality) and passive (eg, geolocation, cellular communication logs, and SMS text message content) sensing methods that were selected to tap into constructs from the Relapse Prevention model by Marlatt. We assessed 3 behavioral indicators of acceptability: participants' choices about their participation in the study at various stages in the procedure, their choice to opt in to provide data for each sensing method, and their adherence to a subset of the active methods (EMA and audio check-in). We also assessed 3 self-report measures of acceptability (interference, dislike, and willingness to use for 1 year) for each method. Of the 192 eligible individuals screened, 191 consented to personal sensing. Most of these individuals (169/191, 88.5%) also returned 1 week later to formally enroll, and 154 participated through the first month follow-up visit. All participants in our analysis sample opted in to provide data for EMA, sleep quality, geolocation, and cellular communication logs. Out of 154 participants, 1 (0.6%) did not provide SMS text message content and 3 (1.9%) did not provide any audio check-ins. The average adherence rate for the 4 times daily EMA was .80. The adherence rate for the daily audio check-in was .54. Aggregate participant ratings indicated that all personal sensing methods were significantly more acceptable (all P<.001) compared with neutral across subjective measures of interference, dislike, and willingness to use for 1 year. Participants did not significantly differ in their dislike of active methods compared with passive methods (P=.23). However, participants reported a higher willingness to use passive (vs active) methods for 1 year (P=.04). These results suggest that active and passive sensing methods are acceptable for people with alcohol use disorder over a longer period than has previously been assessed. Important individual differences were observed across people and methods, indicating opportunities for future improvement.

A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.

Development of severe alcohol related liver disease over four decades in Iceland: impact of increased access and use of alcohol

Objective Limited data exist on the association between per capita alcohol consumption and incidence of alcohol related liver disease (ARLD). The aims were to analyse this relationship and assess prevalence of ARLD in Iceland and among patients treated for alcohol use disorder (AUD) and its impact on outcomes. Methods A retrospective study on all patients diagnosed with severe ARLD: alcohol related cirrhosis (ARC) and alcohol related hepatitis (ARH) in Iceland 1984–2020. Medical records were scrutinized for clinical features, severity of ARLD, proportion undergoing treatment for AUD, data on abstinence and long-term outcomes. Results A total of 314 patients, males 76%, median age 56 years, fulfilled the predetermined criteria for ARLD. Median MELD was 17, 73% with Child-Pugh B/C and 70/314 (22%) who had ARH. Incidence of ARLD increased from 0.77 cases per 100 000 inhabitants annually 1984–2000 to 6.1 per 100 000 in 2016–2020. Per capita alcohol consumption increased from 4.3 Liters to 7.5 L in in the same time periods. Overall 220/314 (70%) with ARLD had undergone treatment for AUD. Of all individuals who had AUD treatment during the study period (n = 21.845), 1% were diagnosed with ARLD. Patients who underwent treatment for AUD after the ARLD diagnosis had better prognosis than those who had treatment prior to ARLD diagnosis (hazard ratio 2.5 [95% CI 1.3–5.0]). Conclusions The incidence of ARLD increased 8-fold during the study period coinciding with 74% increase in per capita alcohol consumption. Patients with prior diagnosis of AUD had worse prognosis that needs special attention.

Predictors of polysubstance use in patients with severe alcohol use disorder: the role of reward craving

BackgroundDifferent craving typologies (i.e., reward, relief, obsessive) have been identified in alcohol use disorder (AUD) but have been less investigated in specific populations like AUD patients with polysubstance use (PSU). The role of dysfunctional personality traits and reward pathways has been reported in both AUD and PSU. We hypothesized that patients with AUD-PSU might show a prevalent reward craving, alongside specific sociodemographic, clinical, and personality features, and aimed at investigating differences in 423 severe AUD outpatients with and without PSU. MethodsOne hundred fifteen patients (27.1% of the sample, 67% males, 42 ± 11.6 years old) displayed PSU. Sociodemographic, clinical features and psychopathological/personality dimensions were assessed through: Craving Typologies Questionnaire (CTQ); Obsessive–Compulsive Drinking Scale (OCDS); UPPS-P Impulsive Behavior Scale (S-UPPS-P); Difficulties in Emotion Regulation Scale (DERS). A binomial logistic regression explored factors associated with PSU. ResultsWe found higher CTQ ‘reward’ scores (p < 0.001) in AUD-PSU patients, and a significant association between reward craving and PSU through logistic regression (OR:1.13; p = 0.005). Earlier AUD onset (p < 0.001), greater rates of binge drinking (p = 0.029), more legal problems (p = 0.015), but no significantly higher S-UPPS-S and DERS scores, were detected in AUD-PSU patients. ConclusionsReward craving was associated with increased risk for PSU in severe AUD patients. Given AUD-PSU participants greater severity and detrimental treatment responses imputed to PSU, identifying prevalent craving types among risk factors for PSU in AUD may help to implement therapeutic strategies. Addressing neurobiological and behavioral mechanisms through combined psychotherapies, pharmacological and neuromodulation treatments could support tailored interventions with better long-term outcome.

Learning from others' experience: Social fear conditioning deficits in patients with severe alcohol use disorder.

Alcohol use disorder (AUD) is a significant public health problem. A better understanding of the psychosocial factors contributing to AUD is important for developing public health policy. The purpose of this study was to identify social mechanisms involved in AUD and, more specifically, to determine whether vicarious learning deficits are related to the disorder. A secondary objective was to evaluate the role of empathy in social fear conditioning. Patients with severe AUD (n = 30) and healthy participants (n = 30) performed a social fear learning (SFL) task. The task assesses how an association between a stimulus and an aversive consequence is acquired through social means. Specifically, participants observed a person receiving an electric shock (unconditioned stimulus; US) that was associated (conditioned stimulus; CS+) or not (CS-) with a neutral CS. The skin conductance response was used to measure the effect of learning. Individuals with severe AUD showed a deficit in SFL, indicating that they had difficulty learning from another's negative experience. Patients also evaluated the emotional experience as less unpleasant than healthy participants. This study is the first to show that patients with severe AUD have social learning deficits. The findings suggest that these individuals do not learn from another's negative experience. At a fundamental level, the findings demonstrate the importance of understanding the role of social mechanisms in AUD. At a clinical level, the study highlights the potential for using social learning enhancement to prevent relapse in individuals with severe AUD.

Integrating an addiction team into the management of patients transplanted for alcohol-associated liver disease reduces the risk of severe relapse

Background & AimsLiver transplantation (LT) is a last resort treatment for patients at high risk of mortality from end-stage liver disease. Over the past years, alcohol-associated liver disease has become the most frequent indication for LT in the world. The outcomes of LT for alcohol-associated liver disease are good, but return to alcohol use is detrimental for medium-term survival because of cancer development, cardiovascular events, and recurrent alcohol-associated cirrhosis. Several strategies have been developed to prevent return to alcohol use during the pre- or post-LT period, but there are no specific recommendations. Therefore, the main objective of this study was to investigate if the integration of an addiction team in a LT unit affected the rate of severe alcohol relapse after LT. The secondary objectives were to assess the effects of addiction follow up on cardiovascular events, cancer, and overall survival. MethodsThis study was a retrospective comparison between centres with or without addiction monitoring. ResultsThe study included 611 patients of which 79.4% were male with a mean age of 55.4 years at the time of LT, 190 were managed by an integrated addiction team. The overall alcohol relapse rate was 28.9% and the rate of severe relapse was 13.0%. Patients with addiction follow-up had significantly less frequent severe alcohol relapse than those in the control group (p = 0.0218). Addiction follow up (odds ratio = 0.19; p = 0.001) and age at LT (odds ratio = 1.23; p = 0.02) remained significantly associated with post-LT cardiovascular events. ConclusionsOur study confirms the benefits of integrating an addiction team to reduce return to alcohol use after LT. Clinical Trials registrationThis study is registered at ClinicalTrials.gov (NCT 04964687). Impact and implicationsThe main indication for liver transplantation is alcohol-associated cirrhosis. There are currently no specific recommendations on the addiction monitoring of transplant candidates, although severe return to alcohol use after liver transplantation has a negative impact on long-term survival of patients. In this study, we explored the impact of a systematic addiction intervention on the return to alcohol use rates. In our transplantation centre, we demonstrated the interest of an addiction follow up to limit the severe alcohol relapses rate. This information should be further investigated in prospective studies to validate these data.