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Worldwide, the prevalence of alcohol use disorder (AUD) is 20-30% in men and 10-15% in women, and cirrhosis due to alcohol-related liver disease (ALD) is responsible for 0.9% of global deaths and 47.9% of cirrhosis-related deaths. End-stage ALD (ESALD) is the final condition of alcohol-related cirrhosis, and severe acute alcohol-related hepatitis (SAAH) is a distinct clinical syndrome associated with the consumption of large amounts of alcohol. In some cases, ESALD, and SAAH may need liver transplantation (LT). Thus, the management of ESALD and SAAH in patients affected by AUD may be an essential part of the clinical skills for hepatologists. For these reasons, the national board of the Italian Society on Alcohol have reviewed the most recent data on the management of ESALD, SAAH and LT for ALD in patients with AUD, formulating a position paper with related recommendations regarding four issues of specific clinical interest in this field: (a) the management of hepatic encephalopathy in patients with AUD, and LT in patients with ESALD; (b) the management of SAAH; (c) the management of AUD in patients with ESALD and SAAH; (d) special populations: polydrug addicts.

This naturalistic study among patients with alcohol dependence examined whether routine blood biomarkers could help to identify patients with high risk for relapse after withdrawal treatment. In a longitudinal study with 6-month follow-up among 133 patients with alcohol dependence who received inpatient alcohol withdrawal treatment, we investigated the usefulness of routine blood biomarkers and clinical and sociodemographic factors for potential outcome prediction and risk stratification. Baseline routine blood biomarkers (gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT/GPT], aspartate aminotransferase [AST/GOT], mean cell volume of erythrocytes [MCV]), and clinical and sociodemographic characteristics were recorded at admission. Standardized 6 months’ follow-up assessed outcome variables continuous abstinence, days of continuous abstinence, daily alcohol consumption and current abstinence. The combined threshold criterion of an AST:ALT ratio > 1.00 and MCV > 90.0 fl helped to identify high-risk patients. They had lower abstinence rates (P = 0.001), higher rates of daily alcohol consumption (P P = 0.027) compared with low-risk patients who did not meet the threshold criterion. Regression analysis confirmed our hypothesis that the combination criterion is an individual baseline variable that significantly predicted parts of the respective outcome variances. Routinely assessed indirect alcohol biomarkers help to identify patients with high risk for relapse after alcohol withdrawal treatment. Clinical decision algorithms to identify patients with high risk for relapse after alcohol withdrawal treatment could include classical blood biomarkers in addition to clinical and sociodemographic items.

Multiple studies show an increased prevalence of gambling disorder among African Americans compared to whites. However, few studies take an analytic approach to understanding differences in risk factors by race/ethnicity. Income is inversely associated with gambling disorder; we hypothesized that this association would vary by race/ethnicity. The main objective was to evaluate whether the association between income and gambling disorder varies by race/ethnicity. With data from the baseline visit of a prospective cohort study, Prevention and Etiology of Gambling Addiction Study in the United States, we used multivariable logistic regression analysis to determine whether the association between income and gambling disorder varies by race/ethnicity. 1164 participants were included in the final analyses. Measures included: demographics (age, sex, race/ethnicity, education, employment, annual household income), veteran status, marital status, homelessness, smoking, substance abuse, alcohol abuse, marijuana use, and lifetime gambling disorder diagnosis as derived from Alcohol Use Disorder and Associated Disabilities Interview Schedule. There was no evidence of effect modification by race/ethnicity in the association between income and gambling disorder (global p value = 0.17). Income was associated with increased odds of gambling disorder, but only for those with low income (

Alcohol use disorder (AUD) is a chronic relapsing disease associated with malnutrition, metabolic disturbances, and gut microbiota alterations that are correlated with the severity of psychological symptoms. This study aims at supplementing AUD patients with prebiotic fiber during alcohol withdrawal, in order to modulate the gut microbiota composition and to evaluate its effect on gastrointestinal tolerance, metabolism, and patient’s behavior. A randomized, double-blind, placebo-controlled study included 50 AUD patients assigned to inulin versus maltodextrin daily supplementation for 17 days. Biological measurements (fecal microbial 16S rDNA sequencing, serum biology), dietary intake, validated psychological questionnaires, and gastrointestinal tolerance assessment were performed before and after the intervention. Inulin significantly decreased the richness and evenness and induced changes of 8 genera (q

Highlights • Examining the mechanisms underlying alcohol use in college students. • Interplay among temperament domains and alcohol use. • Positive affect (PA) linked with engagement in hazardous alcohol use. • Effortful control (EC) associated with reduced engagement in alcohol use broadly. • PA and EC temperament domains linked to alcohol use in college students., Alcohol use and alcohol use disorder (AUD) among young adults are important public health concerns. The high prevalence and negative effects of alcohol use suggests that there is a need for improved understanding of the mechanisms underlying alcohol use. The current study utilizes the model of adult temperament proposed by Evans and Rothbart (2007) as the framework with which to examine the interplay among temperament domains and alcohol use. Specifically, we examined individual and interactive associations among self-report ratings of positive affect, negative affect, effortful control, orienting sensitivity and alcohol use patterns, among a large sample of college students. ANOVA and linear regression analyses indicated that positive affect was associated with engagement in hazardous alcohol use and binge drinking. Furthermore, effortful control was associated with reduced engagement in overall alcohol use. These results corroborate and extend previous work which suggests that positive affect and effortful control temperament domains are linked to alcohol use patterns in college-age young adults. These findings may serve as an important step for informed decision-making about prevention and intervention efforts related to problematic alcohol use in young adults.

Background Opioid overdose (OD) and related deaths have significantly increased in the United States over the last 2 decades. Existing studies have mostly focused on demographic and clinical risk factors in noncritical care settings. Social and behavioral determinants of health (SBDH) are infrequently coded in the electronic health record (EHR) and usually buried in unstructured EHR notes, reflecting possible gaps in clinical care and observational research. Therefore, SBDH often receive less attention despite being important risk factors for OD. Natural language processing (NLP) can alleviate this problem. Objective The objectives of this study were two-fold: First, we examined the usefulness of NLP for SBDH extraction from unstructured EHR text, and second, for intensive care unit (ICU) admissions, we investigated risk factors including SBDH for nonfatal OD. Methods We performed a cross-sectional analysis of admission data from the EHR of patients in the ICU of Beth Israel Deaconess Medical Center between 2001 and 2012. We used patient admission data and International Classification of Diseases, Ninth Revision (ICD-9) diagnoses to extract demographics, nonfatal OD, SBDH, and other clinical variables. In addition to obtaining SBDH information from the ICD codes, an NLP model was developed to extract 6 SBDH variables from EHR notes, namely, housing insecurity, unemployment, social isolation, alcohol use, smoking, and illicit drug use. We adopted a sequential forward selection process to select relevant clinical variables. Multivariable logistic regression analysis was used to evaluate the associations with nonfatal OD, and relative risks were quantified as covariate-adjusted odds ratios (aOR). Results The strongest association with nonfatal OD was found to be drug use disorder (aOR 8.17, 95% CI 5.44-12.27), followed by bipolar disorder (aOR 2.69, 95% CI 1.68-4.29). Among others, major depressive disorder (aOR 2.57, 95% CI 1.12-5.88), being on a Medicaid health insurance program (aOR 2.26, 95% CI 1.43-3.58), history of illicit drug use (aOR 2.09, 95% CI 1.15-3.79), and current use of illicit drugs (aOR 2.06, 95% CI 1.20-3.55) were strongly associated with increased risk of nonfatal OD. Conversely, Blacks (aOR 0.51, 95% CI 0.28-0.94), older age groups (40-64 years: aOR 0.65, 95% CI 0.44-0.96; >64 years: aOR 0.16, 95% CI 0.08-0.34) and those with tobacco use disorder (aOR 0.53, 95% CI 0.32-0.89) or alcohol use disorder (aOR 0.64, 95% CI 0.42-1.00) had decreased risk of nonfatal OD. Moreover, 99.82% of all SBDH information was identified by the NLP model, in contrast to only 0.18% identified by the ICD codes. Conclusions This is the first study to analyze the risk factors for nonfatal OD in an ICU setting using NLP-extracted SBDH from EHR notes. We found several risk factors associated with nonfatal OD including SBDH. SBDH are richly described in EHR notes, supporting the importance of integrating NLP-derived SBDH into OD risk assessment. More studies in ICU settings can help health care systems better understand and respond to the opioid epidemic.

Background and Purpose: Alcohol and nicotine use disorders are commonly comorbid. Both alcohol and nicotine can activate opioid systems in reward-related brain regions, leading to adaptive changes in opioid signalling upon chronic exposure. The potential role of these adaptations for comorbidity is presently unknown. Here, we examined the contribution of mu and kappa-opioid receptors to nicotine-induced escalation of alcohol self-administration in rats. Experimental Approach: Chronic nicotine was tested on alcohol self-administration and motivation to obtain alcohol. We then tested the effect of the kappa antagonist CERC-501 and the preferential mu receptor antagonist naltrexone on basal and nicotine-escalated alcohol self-administration. To probe mu or kappa receptor adaptations, receptor binding and G-protein coupling assays were performed in reward-related brain regions. Finally, dopaminergic activity in response to alcohol was examined, using phosphorylation of DARPP-32 in nucleus accumbens as a biomarker. Key Results: Nicotine robustly induced escalation of alcohol self-administration and motivation to obtain alcohol. This was blocked by naltrexone but not by CERC-501. Escalation of alcohol self-administration was associated with decreased DAMGO-stimulated mu receptor signalling in the ventral tegmental area (VTA) and decreased pDARPP-32 in the nucleus accumbens shell in response to alcohol. Conclusions and Implications: Collectively, these results suggest that nicotine contributes to escalate alcohol self-administration through a dysregulation of mu receptor activity in the VTA. These data imply that targeting mu rather than kappa receptors may be the preferred pharmacotherapeutic approach for the treatment of alcohol use disorder when nicotine use contributes to alcohol consumption. Funding Agencies|Deutsche Forschungsgemeinschaft (DFG), German Research FoundationGerman Research Foundation (DFG) [402170461 - TRR 265]; Bundesministerium fur Bildung und Forschung (BMBF) SysMedSUDs - FKZFederal Ministry of Education & Research (BMBF) [01ZX1909]; Swedish Research CouncilSwedish Research Council [2013-07434]

Background Previous research has highlighted the role of stress in substance misuse and addiction, particularly for relapse risk. Mobile health interventions that incorporate real-time monitoring of physiological markers of stress offer promise for delivering tailored interventions to individuals during high-risk states of heightened stress to prevent alcohol relapse. Before such interventions can be developed, measurements of these processes in ambulatory, real-world settings are needed. Objective This research is a proof-of-concept study to establish the feasibility of using a wearable sensor device to continuously monitor stress in an ambulatory setting. Toward that end, we first aimed to examine the quality of 2 continuously monitored physiological signals—electrodermal activity (EDA) and heart rate variability (HRV)—and show that the data follow standard quality measures according to the literature. Next, we examined the associations between the statistical features extracted from the EDA and HRV signals and self-reported outcomes. Methods Participants (N=11; female: n=10) were asked to wear an Empatica E4 wearable sensor for continuous unobtrusive physiological signal collection for up to 14 days. During the same time frame, participants responded to a daily diary study using ecological momentary assessment of self-reported stress, emotions, alcohol-related cravings, pain, and discomfort via a web-based survey, which was conducted 4 times daily. Participants also participated in structured interviews throughout the study to assess daily alcohol use and to validate self-reported and physiological stress markers. In the analysis, we first used existing artifact detection methods and physiological signal processing approaches to assess the quality of the physiological data. Next, we examined the descriptive statistics for self-reported outcomes. Finally, we investigated the associations between the features of physiological signals and self-reported outcomes. Results We determined that 87.86% (1,032,265/1,174,898) of the EDA signals were clean. A comparison of the frequency of skin conductance responses per minute with previous research confirmed that the physiological signals collected in the ambulatory setting were successful. The results also indicated that the statistical features of the EDA and HRV measures were significantly correlated with the self-reported outcomes, including the number of stressful events marked on the sensor device, positive and negative emotions, and experienced pain and discomfort. Conclusions The results demonstrated that the physiological data collected via an Empatica E4 wearable sensor device were consistent with previous literature in terms of the quality of the data and that features of these physiological signals were significantly associated with several self-reported outcomes among a sample of adults diagnosed with alcohol use disorder. These results suggest that ambulatory assessment of stress is feasible and can be used to develop tailored mobile health interventions to enhance sustained recovery from alcohol use disorder.

Highlights • We estimated prevalence of e-cigarette dual use among smokers with substance use disorders. • Dual e-cigarette users were more likely to have tried to quit in the past year. • Overall, participants preferred to use e-cigarettes in comparison to nicotine patches/gum. • E-cigarettes seem appealing to patients with substance use disorders. • E-cigarette use may be effective for harm reduction among patients in addiction treatment., Background We explored characteristics and beliefs associated with e-cigarette use patterns among cigarette smokers requiring inpatient detoxification for opioid and/or alcohol use disorder(s). Methods Adult cigarette smokers (≥18 years), admitted to inpatient detoxification for alcohol and/or opioid use disorder(s) in a safety-net tertiary referral center in New York City were surveyed in 2015 (n = 158). Descriptive statistics (proportions) were used to assess for demographic, clinical diagnosis, cigarette smoking patterns (exclusive and dual use of e-cigarettes). Chi-square, t-test statistics, and logistic regression models were used. Results Among our sample of combustible cigarette users, 13.9% (n = 22) reported dual use with electronic cigarettes. Dual use did not differ by demographic or clinical variables. Compared to exclusive smokers, dual users were more likely to have tried to quit in the past year (Adjusted Odds ratio = 8.59; CI: 2.58, 28.35; p

Objective: The authors used a decision tree classifier to reduce neuropsychological, behavioral and laboratory measures to a subset of measures that best predicted whether an individual with alcohol use disorder (AUD) seeks treatment. Method: Clinical measures (N = 178) from 778 individuals with AUD were used to construct an alternating decision tree (ADT) with 10 measures that best classified individuals as treatment or not treatment-seeking for AUD. ADT's were validated by two methods: using cross-validation and an independent dataset (N = 236). For comparison, two other machine learning techniques were used as well as two linear models. Results: The 10 measures in the ADT classifier were drinking behavior, depression and drinking-related psychological problems, as well as substance dependence. With cross-validation, the ADT classified 86% of individuals correctly. The ADT classified 78% of the independent dataset correctly. Only the simple logistic model was similar in accuracy; however, this model needed more than twice as many measures as ADT to classify at comparable accuracy. Interpretation: While there has been emphasis on understanding differences between those with AUD and controls, it is also important to understand, within those with AUD, the features associated with clinically important outcomes. Since the majority of individuals with AUD do not receive treatment, it is important to understand the clinical features associated with treatment utilization; the ADT reported here correctly classified the majority of individuals with AUD with 10 clinically relevant measures, misclassifying

Depression and alcohol use disorders are highly comorbid. Typically, alcohol use peaks in emerging adulthood (e.g., during university), and many people also develop depression at this time. Self-medication theory predicts that depressed emerging adults drink to reduce negative emotions. While research shows that depression predicts alcohol use and related problems in undergraduates, far less is known about the continuity of this association after university. Most emerging adults “mature out” of heavy drinking; however, some do not and go on to develop an alcohol use disorder. Depressed emerging adults may continue to drink heavily to cope with the stressful (e.g., remaining unemployed) transition out of university. Accordingly, using parallel process latent class growth modelling, we aimed to distinguish high- from low-risk groups of individuals based on joint patterns of depression and alcohol misuse following university graduation. Participants (N = 123) completed self-reports at three-month intervals for the year post-graduation. Results supported four classes: class 1: low stable depression and low decreasing alcohol misuse (n = 52), class 2: moderate stable depression and moderate stable alcohol misuse (n = 35), class 3: high stable depression and low stable alcohol misuse (n = 29), and class 4: high stable depression and high stable alcohol misuse (n = 8). Our findings show that the co-development of depression and alcohol misuse after university is not uniform. Most emerging adults in our sample continued to struggle with significant depressive symptoms after university, though only two classes continued to drink at moderate (class 2) and high (class 4) risk levels., Highlights • Co-patterns of depression and alcohol misuse were examined in emerging adults. • Four distinct classes were supported. • Co-patterns of depression and alcohol misuse were not uniform. • Some continue to struggle with alcohol misuse and depression after graduation.

Background Alcohol misuse is common among Operation Enduring Freedom and Operation Iraqi Freedom veterans, yet barriers limit treatment participation. Mobile apps hold promise as means to deliver alcohol interventions to veterans who prefer to remain anonymous, have little time for conventional treatments, or live too far away to attend treatment in person. Objective This pilot study evaluated the usability and acceptability of Step Away, a mobile app designed to reduce alcohol-related risks, and explored pre-post changes on alcohol use, psychological distress, and quality of life. Methods This single-arm pilot study recruited Operation Enduring Freedom and Operation Iraqi Freedom veterans aged 18 to 55 years who exceeded National Institute on Alcohol Abuse and Alcoholism drinking guidelines and owned an iPhone. Enrolled veterans (N=55) completed baseline and 1-, 3-, and 6-month assessments. The System Usability Scale (scaled 1-100, ≥70 indicating acceptable usability) assessed the effectiveness, efficiency, and satisfaction dimensions of usability, while a single item (scaled 1-9) measured the attractiveness of 10 screenshots. Learnability was assessed by app use during week 1. App engagement (proportion of participants using Step Away, episodes of use, and minutes per episode per week) over 6 months measured acceptability. Secondary outcomes included pre-post change on heavy drinking days (men: ≥5 drinks per day; women: ≥4 drinks per day) and Short Inventory of Problems–Revised, Kessler-10, and brief World Health Organization Quality of Life Questionnaire scores. Results Among the 55 veterans enrolled in the study, the mean age was 37.4 (SD 7.6), 16% (9/55) were women, 82% (45/55) were White, and 82% (45/55) had an alcohol use disorder. Step Away was used by 96% (53/55) of participants in week 1, 55% (30/55) in week 4, and 36% (20/55) in week 24. Step Away use averaged 55.1 minutes (SD 57.6) in week 1 and Conclusions Operation Enduring Freedom and Operation Iraqi Freedom veterans found the usability of Step Away to be acceptable and engaged in the app over the 6-month study. Reductions were seen in heavy drinking days, alcohol-related problems, and Kessler-10 scores. A larger randomized trial is warranted to confirm our findings.

Background Alcohol use disorder (AUD) has been associated with diverse physical and mental morbidities. Among the main consequences of chronic and excessive alcohol use are cognitive and executive deficits. Some of these deficits may be reversed in specific cognitive and executive domains with behavioral approaches consisting of cognitive training. The advent of computer-based interventions may leverage these improvements, but randomized controlled trials (RCTs) of digital interactive-based interventions are still scarce. Objective The aim of this study is to explore whether a cognitive training approach using VR exercises based on activities of daily living is feasible for improving the cognitive function of patients with AUD undergoing residential treatment, as well as to estimate the effect size for this intervention to power future definitive RCTs. Methods This study consisted of a two-arm pilot RCT with a sample of 36 individuals recovering from AUD in a therapeutic community; experimental group participants received a therapist-guided, VR-based cognitive training intervention combined with treatment as usual, and control group participants received treatment as usual without cognitive training. A comprehensive neuropsychological battery of tests was used both at pre- and postassessments, including measurement of global cognition, executive functions, attention, visual memory, and cognitive flexibility. Results In order to control for potential effects of global cognition and executive functions at baseline, these domains were controlled for in the statistical analysis for each individual outcome. Results indicate intervention effects on attention in two out of five outcomes and on cognitive flexibility in two out of six outcomes, with effect sizes in significant comparisons being larger for attention than for cognitive flexibility. Patient retention in cognitive training was high, in line with previous studies. Conclusions Overall, the data suggest that VR-based cognitive training results in specific contributions to improving attention ability and cognitive flexibility of patients recovering from AUD. Trial Registration ClinicalTrials.gov NCT04505345; https://clinicaltrials.gov/show/NCT04505345

Highlights • Substantial growth in quality of life during the course of treatment. • Co-occurrence between mental distress and lower quality of life. • Higher patient satisfaction associated with higher quality of life trajectories. • Substance use at follow-up was not associated with quality of life., Aims The main study purpose was to investigate patient- and treatment-related factors associated with overall quality of life (OQOL) trajectories during and after inpatient alcohol use disorder (AUD) treatment. Design A large-scale prospective multicenter cohort study of patients with different substance use disorder (SUD) types who were consecutively admitted for inpatient SUD treatment. Data were obtained at treatment entry (T1), discharge (T2), three months after discharge (T3), and one year after discharge (T4). The inclusion criterion was that the patient be dependent solely on alcohol. OQOL data were collected at all four time points. Independent variables included demographics, mental distress, psychiatric disorders, substance use, treatment history, and patient satisfaction. Results Among the 611 patients available, 236 met the AUD inclusion criterion and completed T1 assessments. A linear mixed model showed substantial co-occurrence between higher mental distress and lower OQOL. Higher patient satisfaction with inpatient treatment (T2) was associated with higher trajectories of OQOL, whereas abstinence (T3) was not. There was a substantial increase in OQOL from T1 to T2, which then remained stable during the last two assessment time points. Conclusions Routine OQOL screening at treatment entry, and targeting mental distress both during and after inpatient treatment, may be associated with improved OQOL among individuals with AUD. Further research should investigate inpatient treatment factors that contribute to OQOL improvement and those that moderate the relationship between patient satisfaction and OQOL.

Highlights • Psychopathological symptom profiles and trajectories were examined among AUD inpatients. • Three quantitatively different subgroups were identified in terms of psychopathological symptoms. • Classes were discriminated by different psychopathological symptom change trajectories. • Subgroups with more severe psychopathological symptoms used alcohol in a more harmful way. • Drinking of the more severely affected classes were more motivated by coping and conformity motives., Background Patients diagnosed with Alcohol Use Disorder (AUD) present an increased risk for experiencing severe internalizing and externalizing symptoms. Involvement in twelve-step based treatment programs, such as the Minnesota Model (MM), can contribute to improvement of an individual’s psychopathological symptom profile. The present study’s main objective was to examine profiles and change trajectories of psychopathological symptoms of AUD subgroups during an eight-week long period of MM treatment attendance. Method Inpatients with AUD (N = 303) who attended MM treatment programs participated in the present study. Latent Class Growth Analysis (LCGA) was used to evaluate the psychopathological symptom change trajectories assessed by using the Brief Symptom Inventory (BSI). Multiple comparisons and multinomial logistic regression were performed to validate the subgroups. Results Three subgroups were identified: low severity (48.5%), moderate severity (35.2%), and high severity (16.2%) symptomatic subgroups. The moderate severity class demonstrated the largest effect in terms of symptoms decrease. Higher severity classes showed significantly higher rates of harmful alcohol drinking and drinking motives. Conclusions The present study identified three severity-based subgroups which indicate that psychopathology sits on a spectrum of severity among AUD patients. The findings highlight the associations between AUD and internalizing symptoms, negative reinforcement drinking motives, and the symptomatic improvement that can occur among those participating in MM treatment programs.

BackgroundGay, bisexual and other men who have sex with men (GBMSM) are at increased risk of mental health disorders and drug use. In GBMSM taking pre-exposure prophylaxis (PrEP) for HIV, the proportion engaging in risk behaviors could increase due to decreased perception in HIV risk. In turn, this could leave them further susceptible to mental health disorders.MethodsThe AMsterdam PrEP study (AMPrEP) is a demonstration project offering a choice of daily PrEP or event-driven PrEP regimen at the STI clinic of the Public Health Service of Amsterdam. Eligible participants were HIV-negative GBMSM and transgender people at risk of HIV, aged ≥18 years. We assessed anxiety and depressive mood disorders (Mental Health Inventory 5), sexual compulsivity (Sexual Compulsivity Scale), alcohol use disorder (Alcohol Use Disorder Identification Test), and drug use disorder (Drug Use Disorder Identification Test) using yearly self-administered assessments (August 2015–September 2018). The proportion of mental health problems were analyzed and changes over time and between regimen were assessed using a logistic regression model. Variables associated with the development or recovery of disorders were assessed using a multistate Markov model.OutcomesOf 376 enrolled, we analyzed 341 participants with data at baseline and at least one follow-up visit. During a median follow-up of 2.5 years (IQR=2.3–2.7), the proportion assessed with sexual compulsivity decreased from 23% at baseline to 10% at the last visit (pp = 0.004). No changes occurred in proportion assessed with anxiety/depressive mood disorders (20% at baseline, 18% at last visit, p = 0.358) or alcohol use disorder (28% at baseline, 22% at the last visit, p = 0.106). During follow-up, participants reported significant less use of alcohol (pppInterpretationMental health disorders are prevalent among those initiating PrEP. We did not find increases in mental health disorders during PrEP use, but rather a decrease in sexual compulsivity and drug use disorders. The initial prevalence of mental health disorders in our study point at the continuous need to address mental health disorders within PrEP programs.FundingZonMw, H-TEAM, Internal GGD research funds, Aidsfonds, Stichting AmsterdamDiner Foundation, Gilead Sciences, Janssen Pharmaceutica, M A C AIDS Fund, and ViiV Healthcare.

Background Novel alcohol prevention strategies are needed for heavy-drinking young adults. Sleep problems are common among young adults who drink heavily and are a risk factor for developing an alcohol use disorder (AUD). Young adults, interested in the connection between sleep and alcohol, are open to getting help with their sleep. Therefore, sleep interventions may offer an innovative solution. This study evaluates social media advertising for reaching young adults and recruiting them for a new alcohol prevention program focused on sleep. Objective This study aims to evaluate the effectiveness and cost of using Facebook, Instagram, and Snapchat advertising to reach young adults who drink heavily for a sleep intervention; characterize responders’ sleep, alcohol use, and related concerns and interests; and identify the most appealing advertising content. Methods In study 1, advertisements targeting young adults with sleep concerns, heavy alcohol use, or interest in participating in a sleep program ran over 3 months. Advertisements directed volunteers to a brief web-based survey to determine initial sleep program eligibility and characterize the concerns or interests that attracted them to click the advertisement. In study 2, three advertisements ran simultaneously for 2 days to enable us to compare the effectiveness of specific advertising themes. Results In study 1, advertisements generated 13,638 clicks, 909 surveys, and 27 enrolled volunteers in 3 months across the social media platforms. Fees averaged US $0.27 per click, US $3.99 per completed survey, US $11.43 per volunteer meeting initial screening eligibility, and US $106.59 per study enrollee. On average, those who completed the web-based survey were 21.1 (SD 2.3) years of age, and 69.4% (631/909) were female. Most reported sleep concerns (725/909, 79.8%) and an interest in the connection between sleep and alcohol use (547/909, 60.2%), but few had drinking concerns (49/909, 5.4%). About one-third (317/909, 34.9%) were identified as being at risk for developing an AUD based on a validated alcohol screener. Among this subsample, 8.5% (27/317) met the final criteria and were enrolled in the trial. Some volunteers also referred additional volunteers by word of mouth. In study 2, advertisements targeting sleep yielded a higher response rate than advertisements targeting alcohol use (0.91% vs 0.56% click rate, respectively; P Conclusions Social media advertisements designed to target young adults with sleep concerns reached those who also drank alcohol heavily, despite few being concerned about their drinking. Moreover, advertisements focused on sleep were more effective than those focused on drinking. Compared with previous studies, cost-effectiveness was moderate for engagement (impressions to clicks), excellent for conversion (clicks to survey completion), and reasonable for enrollment. These data demonstrate the utility of social media advertising focused on sleep to reach young adults who drink heavily and recruit them for intervention.

Background Electronic health record (EHR)–based disease registries have aided health care professionals and researchers in increasing their understanding of chronic illnesses, including identifying patients with (or at risk of developing) conditions and tracking treatment progress and recovery. Despite excessive alcohol use being a major contributor to the global burden of disease and disability, no registries of alcohol problems exist. EHR-based data in Kaiser Permanente Northern California (KPNC), an integrated health system that conducts systematic alcohol screening, which provides specialty addiction medicine treatment internally and has a membership of over 4 million members that are highly representative of the US population with access to care, provide a unique opportunity to develop such a registry. Objective Our objectives were to describe the development and implementation of a protocol for assembling the KPNC Adult Alcohol Registry, which may be useful to other researchers and health systems, and to characterize the registry cohort descriptively, including underlying health conditions. Methods Inclusion criteria were adult members with unhealthy alcohol use (using National Institute on Alcohol Abuse and Alcoholism guidelines), an alcohol use disorder (AUD) diagnosis, or an alcohol-related health problem between June 1, 2013, and May 31, 2019. We extracted patients’ longitudinal, multidimensional EHR data from 1 year before their date of eligibility through May 31, 2019, and conducted descriptive analyses. Results We identified 723,604 adult patients who met the registry inclusion criteria at any time during the study period: 631,780 with unhealthy alcohol use, 143,690 with an AUD diagnosis, and 18,985 with an alcohol-related health problem. We identified 65,064 patients who met two or more criteria. Of the 4,973,195 adult patients with at least one encounter with the health system during the study period, the prevalence of unhealthy alcohol use was 13% (631,780/4,973,195), the prevalence of AUD diagnoses was 3% (143,690/4,973,195), and the prevalence of alcohol-related health problems was 0.4% (18,985/4,973,195). The registry cohort was 60% male (n=432,847) and 41% non-White (n=295,998) and had a median age of 41 years (IQR=27). About 48% (n=346,408) had a chronic medical condition, 18% (n=130,031) had a mental health condition, and 4% (n=30,429) had a drug use disorder diagnosis. Conclusions We demonstrated that EHR-based data collected during clinical care within an integrated health system could be leveraged to develop a registry of patients with alcohol problems that is flexible and can be easily updated. The registry’s comprehensive patient-level data over multiyear periods provides a strong foundation for robust research addressing critical public health questions related to the full course and spectrum of alcohol problems, including recovery, which would complement other methods used in alcohol research (eg, population-based surveys, clinical trials).

Background Few studies have focused on those who present to hospital with suicidal thoughts (suicidal ideation). The aim of this study was to establish the risk of repeat presentation to hospital following suicidal ideation and to identify factors which were associated with further ideation or subsequent self-harm. Methods Data were obtained from the Northern Ireland Registry of Self-harm. Risk of repeat presentation following hospital-presenting ideation was analysed using Kaplan Meier analyses, specifically cox proportional hazard models. Findings During the period April 2014 to March 2019, a total of 14,695 presentations to hospital due to suicidal ideation were made in Northern Ireland. The cumulative incidence of repeat presentation to hospital was 40·5% within five years, with an 18·3% risk of subsequent self-harm. Previous ideation had the strongest association with repeat presentation. There was evidence of recidivism considering further ideation, with an increased risk according to number of previous presentations. In contrast, risk of subsequent self-harm was highest after the first or second presentation. Male gender and alcohol were associated with further ideation, while females and young people were more likely to re-present with self-harm. Interpretation The findings indicate that individuals who present to hospital with suicidal ideation are at risk of repeat presentation and future self-harm, however clinical guidelines do not specifically address hospital-presenting ideation. The transition from ideation to suicidal behaviour is important to consider and research could inform effective screening and early intervention measures. Role of Funding The Northern Ireland Registry of Self-harm is funded by the Public Health Agency, Northern Ireland.

Background Animal data suggest a role of the gut-liver axis in progression of alcoholic liver disease (ALD), but human data are scarce especially for early disease stages. Methods We included patients with alcohol use disorder (AUD) who follow a rehabilitation program and matched healthy controls. We determined intestinal epithelial and vascular permeability (IP) (using urinary excretion of 51Cr-EDTA, fecal albumin content, and immunohistochemistry in distal duodenal biopsies), epithelial damage (histology, serum iFABP, and intestinal gene expression), and microbial translocation (Gram – and Gram + serum markers by ELISA). Duodenal mucosa-associated microbiota and fecal microbiota were analyzed by 16 S rRNA sequencing. ALD was staged by Fibroscan® (liver stiffness, controlled attenuation parameter) in combination with serum AST, ALT, and CK18-M65. Results Only a subset of AUD patients had increased 51Cr-EDTA and fecal albumin together with disrupted tight junctions and vasculature expression of plasmalemma Vesicle-Associated Protein-1. The so-defined increased intestinal permeability was not related to changes of the duodenal microbiota or alterations of the intestinal epithelium but associated with compositional changes of the fecal microbiota. Leaky gut alone did not explain increased microbial translocation in AUD patients. By contrast, duodenal dysbiosis with a dominance shift toward specific potential pathogenic bacteria genera (Streptococcus, Shuttleworthia, Rothia), increased IP and elevated markers of microbial translocation characterized AUD patients with progressive ALD (steato-hepatitis, steato-fibrosis). Conclusion Progressive ALD already at early disease stages is associated with duodenal mucosa-associated dysbiosis and elevated microbial translocation. Surprisingly, such modifications were not linked with increased IP. Rather, increased IP appears related to fecal microbiota dysbiosis.

Background In the ever-growing and technologically advancing world, an increasing amount of social interaction takes place through the Web. With this change, loneliness is becoming an unprecedented societal issue, making youth more susceptible to various physical and mental health problems. This societal change also influences the dynamics of addiction. Objective Employing the cognitive discrepancy loneliness model, this study aimed to provide a social psychological perspective on youth addictions. Methods A comprehensive survey was used to collect data from American (N=1212; mean 20.05, SD 3.19; 608/1212, 50.17% women), South Korean (N=1192; mean 20.61, SD 3.24; 601/1192, 50.42% women), and Finnish (N=1200; mean 21.29, SD 2.85; 600/1200, 50.00% women) youths aged 15 to 25 years. Perceived loneliness was assessed with the 3-item Loneliness Scale. A total of 3 addictive behaviors were measured, including excessive alcohol use, compulsive internet use, and problem gambling. A total of 2 separate models using linear regression analyses were estimated for each country to examine the association between perceived loneliness and addiction. Results Loneliness was significantly related to only compulsive internet use among the youth in all 3 countries (P Conclusions The findings reveal existing differences between youths who spend excessive amounts of time online and those who engage in other types of addictive behaviors. Experiencing loneliness is consistently linked to compulsive internet use across countries, although different underlying factors may explain other forms of addiction. These findings provide a deeper understanding in the mechanisms of youth addiction and can help improve prevention and intervention work, especially in terms of compulsive internet use.

Background Binge drinking, defined as consuming five or more standard alcoholic drinks for men (four for women) within a 2-hour period, is common among young adults and is associated with significant alcohol-related morbidity and mortality. To date, most research on this problem in young adults has relied upon retrospective questionnaires or costly laboratory-based procedures. Smartphone-based ecological momentary assessment (EMA) may address these limitations by allowing researchers to measure alcohol use and related consequences in real time and in drinkers’ natural environments. To date, however, relatively less research has systematically examined the utility of this approach in a sample of young adults targeting real-world heavy drinking episodes specifically. Objective This study aimed to evaluate the feasibility, acceptability, and safety of a smartphone-based EMA method targeting binge drinking and related outcomes in heavy drinking young adults during real-world drinking occasions. Methods Young adult binge drinkers in the smartphone group (N=83; mean 25.4 (SD 2.6) years; 58% (48/83) male; bingeing on 23.2% (6.5/28) days in the past month) completed baseline measures of alcohol use and drinking-related consequences, followed by up to two smartphone-based EMA sessions of typical drinking behavior and related outcomes in their natural environments. They also completed next-day and two-week follow-up surveys further assessing alcohol use and related consequences during the EMA sessions and two weeks after study participation, respectively. A separate demographic- and drinking-matched safety comparison group (N=25) completed the baseline and two-week follow-up surveys but did not complete EMA of real-world drinking behavior. Results Most participants (71%, 59/83) in the smartphone group engaged in binge drinking during at least one 3-hour EMA session, consuming 7.3 (SD 3.0) standard alcoholic drinks. They completed 87.2% (507/581) system-initiated EMA prompts during the real-world drinking episode, supporting the feasibility of this approach. The procedure was acceptable, as evidenced by high participant ratings for overall satisfaction with the EMA software and study procedures and low ratings for intrusiveness of the mobile surveys. Regarding safety, participants endorsed few drinking-related consequences during or after the real-world drinking episode, with no adverse or serious adverse events reported. There were no differences between the groups in terms of changes in drinking behavior or consequences from baseline to two-week follow-up. Conclusions This study provided preliminary support for the feasibility, acceptability, and safety of a smartphone-based EMA of real-time alcohol use and related outcomes in young adult heavy drinkers. The results suggest that young adults can use smartphones to safely monitor drinking even during very heavy drinking episodes. Smartphone-based EMA has strong potential to inform future research on the epidemiology of and intervention for alcohol use disorder by providing researchers with an efficient and inexpensive way to capture large amounts of data on real-world drinking behavior and consequences.

Background Cue exposure therapy (CET) is a psychological approach developed to prepare individuals with alcohol use disorder (AUD) for confronting alcohol and associated stimuli in real life. CET has shown promise when treating AUD in group sessions, but it is unknown whether progressing from group sessions to using a mobile phone app is an effective delivery pathway. Objective The objectives of this study were to investigate (1) whether CET as aftercare would increase the effectiveness of primary treatment with cognitive behavior therapy, and (2) whether CET delivered through a mobile phone app would be similarly effective to CET via group sessions. Methods A total of 164 individuals with AUD were randomized to one of three groups: CET as group aftercare (CET group), CET as fully automated mobile phone app aftercare (CET app), or aftercare as usual. Study outcomes were assessed face-to-face at preaftercare, postaftercare, and again at 6 months after aftercare treatment. Generalized mixed models were used to compare the trajectories of the groups over time on drinking, cravings, and use of urge-specific coping skills (USCS). Results In all, 153 of 164 individuals (93%) completed assessments both at posttreatment and 6-month follow-up assessments. No differences in the trajectories of predicted means were found between the experimental groups (CET group and app) compared with aftercare as usual on drinking and craving outcomes over time. Both CET group (predicted mean difference 5.99, SE 2.59, z=2.31, P=.02) and the CET app (predicted mean difference 4.90, SE 2.26, z=2.31, P=.02) showed increased use of USCS compared to aftercare as usual at posttreatment, but this effect was reduced at the 6-month follow-up. No differences were detected between the two experimental CET groups on any outcomes. Conclusions CET with USCS delivered as aftercare either via group sessions or a mobile phone app did not increase the effectiveness of primary treatment. This suggests that CET with USCS may not be an effective psychological approach for the aftercare of individuals treated for AUD. Trial Registration ClinicalTrials.gov NCT02298751; https://clinicaltrials.gov/ct2/show/NCT02298751

Introduction Engaging individuals, suffering from alcohol use disorder (AUD), in a physical activity can be a challenge, and often it is a limitation of the quality of studies on the topic. The aim of the present study is to investigate differences between participants and non-participants in a randomized controlled trial on the effect of physical exercise as add-on to treatment as usual (TAU) to treatment for alcohol use disorder, thereby identifying potential factors that may predict lack of willingness or ability to consider increasing the level of physical activity. Method The Healthy Lifestyle Study was a randomized controlled trial with three arms, of which two included adding physical activities to treatment for AUD as usual. All patients from an outpatient alcohol treatment clinic were invited to participate in the study. 172 accepted participation, and 384 patients either did not show up for information about the study or declined to participate. All patients in the treatment clinic were assessed by means of European Addiction Severity Index (EuropASI). Results The only predictor of participation in the study was the drinking pattern. Patients, who had been drinking every day for the last 6 months were less likely to participate in the study (OR 0.7 CI 0.4–0.9). Neither somatic nor psychiatric health seemed to impact whether or not the patients participated in the study. Conclusion Non-participants did not differ from participants in this study except in their drinking pattern., Highlights • No psychological or social differences between participants and non-participants • Non-participants drink alcohol on a daily base. • Non-participants are affected by something else than health and social problems.

Alcohol abuse is one of the most important risk factors for health and is a major cause of death and morbidity. Despite this, only about one-tenth of individuals with alcohol abuse disorders receive therapeutic intervention and specific rehabilitation. Among the various dichotomies that limit an effective approach to the problem of alcohol use disorder treatment, one of the most prominent is integrated treatment versus harm reduction. For years, these two divergent strategies have been considered to be opposite poles of different philosophies of intervention. One is bound to the search for methods that aim to lead the subject to complete abstinence; the other prioritizes a progressive decline in substance use, with maximum reduction in the damage that is correlated with curtailing that use. Reduction of alcohol intake does not require any particular setting, but does require close collaboration between the general practitioner, specialized services for addiction, alcohology services and psychiatry. In patients who reach that target, significant savings in terms of health and social costs can be achieved. Harm reduction is a desirable target, even from an economic point of view. At the present state of neuroscientific knowledge, it is possible to go one step further in the logic that led to the integration of psychosocial and pharmacological approaches, by attempting to remove the shadows of social judgment that, at present, are aiming for a course of treatment that is directed towards absolute abstention.

Background Resistance to alcohol hangover may be a risk factor for alcohol use disorder. Previous research to establish the prevalence of hangover resistance in a drinking population has either not used comparable intoxication levels or has considered hangover resistance over a limited time frame. The purpose of this study was to examine the prevalence of lifetime hangover negative (LHN) drinkers across comparable eBAC values ranging from 0 to 500 mg/dl. Methods Students at an eastern Canadian university were surveyed about their heaviest drinking episode in the past month and indicated whether they had ever experienced a hangover in their lifetime (LHN) and, if they had, the hangover severity they experienced the next day. eBACs were calculated and the percentage of LHN drinkers was computed at each 10 mg/dl eBAC increment from 0 to 500 mg/dl. Results Most LHN drinkers (58% female, 71% male) had an eBAC on their heaviest drinking occasion below 80 mg/dl. Above eBACs of 80 mg/dl, 5.8% of female and 5.1% of male drinkers were lifetime hangover negative. Conclusions The results suggest that only a small percentage of heavy drinkers lay claim to being lifetime hangover negative., Highlights • The estimated BAC of more than half of male and female lifetime hangover negative drinkers was below 80 mg%. • Approximately 5% of drinkers registering estimated BAC’s beyond 80 mg% claim to be lifetime hangover negative. • Biological and psychological hypotheses are proposed to explain why heavy drinkers may be lifetime hangover negative.

Problem gambling attracts considerable public stigma, with deleterious effects on mental health and use of healthcare services amongst those affected. However, no research has examined the extent of stigma towards problem gambling within the general population. This study aimed to examine the stigma-related dimensions of problem gambling as perceived by the general public compared to other health conditions, and determine whether the publicly perceived dimensions of problem gambling predict its stigmatisation. A sample of 2000 Australian adults was surveyed, weighted to be representative of the state population by gender, age and location. Based on vignettes, the online survey measured perceived origin, peril, concealability, course and disruptiveness of problem gambling and four other health conditions, and desired social distance from each. Problem gambling was perceived as caused mainly by stressful life circumstances, and highly disruptive, recoverable and noticeable, but not particularly perilous. Respondents stigmatised problem gambling more than sub-clinical distress and recreational gambling, but less than alcohol use disorder and schizophrenia. Predictors of stronger stigma towards problem gambling were perceptions it is caused by bad character, is perilous, non-recoverable, disruptive and noticeable, but not due to stressful life circumstances, genetic/inherited problem, or chemical imbalance in the brain. This new foundational knowledge can advance understanding and reduction of problem gambling stigma through countering inaccurate perceptions that problem gambling is caused by bad character, that people with gambling problems are likely to be violent to other people, and that people cannot recover from problem gambling. Financial support for this research was provided by the Victorian Research Gambling Foundation. The funding body had no role in the creation of the study design; in the collection, analysis and interpretation of data; in the writing of articles; and in the decision to submit this article for publication.