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Coronavirus disease 2019 (COVID-19) first emerged in China in November 2019. Most governments have responded to the COVID-19 pandemic by imposing a lockdown. Some evidence suggests that a period of isolation might have led to a spike in alcohol misuse, and in the case of patients with alcohol use disorder (AUD), social isolation can favour lapse and relapse. The aim of our position paper is to provide specialists in the alcohol addiction field, in psychopharmacology, gastroenterology and in internal medicine, with appropriate tools to better manage patients with AUD and COVID-19,considering some important topics: (a) the susceptibility of AUD patients to infection; (b) the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) the reorganization of the Centre for Alcohol Addiction Treatment for the management of AUD patients in the COVID-19 era (group activities, telemedicine, outpatients treatment, alcohol-related liver disease and liver transplantation, collecting samples); (d) AUD and SARS-CoV-2 vaccination. Telemedicine/telehealth will undoubtedly be useful/practical tools even though it remains at an elementary level; the contribution of the family and of caregivers in the management of AUD patients will play a significant role; the multidisciplinary intervention involving experts in the treatment of AUD with specialists in the treatment of COVID-19 disease will need implementation. Thus, the COVID-19 pandemic is rapidly leading addiction specialists towards a new governance scenario of AUD, which necessarily needs an in-depth reconsideration, focusing attention on a safe approach in combination with the efficacy of treatment. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there are increases in the treatment gap and few new medications have been approved in the past 20 years. Recently, psychedelic‐assisted therapy with psilocybin and lysergic acid diethylamide has garnered significant attention in the treatment of AUD. Yet, they require significant amounts of therapist input due to prolonged subjective effects (~4–12 h) leading to high costs and impeding implementation. Accordingly, there is an increasing interest in the rapid and short‐acting psychedelic 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT). This paper offers a first look at potential therapeutic mechanisms for AUD by reviewing the current literature on 5‐MeO‐DMT. Primarily, 5‐MeO‐DMT is able to induce mystical experiences and ego‐dissolution together with increases in psychological flexibility and mindfulness. This could decrease AUD symptoms through the alleviation of psychiatric mood‐related comorbidities consistent with the negative reinforcement and self‐medication paradigms. In addition, preliminary evidence indicates that 5‐MeO‐DMT modulates neural oscillations that might subserve ego‐dissolution (increases in gamma), psychological flexibility and mindfulness (increases in theta), and the reorganization of executive control networks (increases in coherence across frequencies) that could improve emotion regulation and inhibition. Finally, animal studies show that 5‐MeO‐DMT is characterized by neuroplasticity, anti‐inflammation, 5‐HT2A receptor agonism, and downregulation of metabotropic glutamate receptor 5 with clinical implications for AUD and psychiatric mood‐related comorbidities. The paper concludes with several recommendations for future research to establish the purported therapeutic mechanisms of action. [ABSTRACT FROM AUTHOR]

Introduction and aims: There is emerging evidence that heavy long‐term alcohol consumption may alter the neuroimmune profile. We conducted a meta‐analysis of the association between alcohol use disorder (AUD) and the extent of neuroinflammation using cerebrospinal (CSF), PET (Positron Emission Tomography), and postmortem studies. Design and methods: A comprehensive search of electronic databases was conducted using the Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols (PRISMA‐P) for AUD‐related terms in combination with neuroinflammatory markers and cytokine‐ and chemokine‐related terms for CSF, PET, and postmortem studies. Participants had to meet established criteria for AUD and/or heavy alcohol consumption with dependence features and be compared with healthy controls. Papers retrieved were assessed for inclusion criteria and a critical appraisal was completed using the Newcastle‐Ottawa Scale. A meta‐analysis was conducted on postmortem and PET studies. Results: Eleven papers met the inclusion criteria with CSF, PET, and postmortem studies included in the final analysis. Postmortem studies demonstrate significant heterogeneity (푄 (14) = 62.02, 푝 < 0.001), with the alcohol group showing higher levels of neuroimmune markers than controls (푑 = 1.50 [95% CI 0.56, 2.45]). PET studies demonstrated a lower [11C] PBR28 total volume of distribution (VT) for translocator protein in the hippocampus (g = −1.95 [95% CI −2.72, −1.18], p < 0.001) of the alcohol group compared to controls. Conclusion: There is emerging evidence across multiple diagnostic modalities that alcohol impacts neuroimmune signaling in the human brain. [ABSTRACT FROM AUTHOR]

Background and aims: The ability to regulate emotions effectively has been associated with resilience to psychopathology. Individuals with substance use disorders (SUDs) have been shown to have higher levels of negative emotionality, with some evidence suggesting impairment in emotion regulation compared with individuals without SUDs. However, no previous attempt has been made to systematically review the literature to assess the magnitude of this difference. We aimed to assess the association between SUD diagnosis and emotion regulation as measured by the Difficulties in Emotion Regulation Scale (DERS) and Emotion Regulation Questionnaire (ERQ) through a systematic review and meta‐analysis of existing findings. Methods: The systematic review was conducted using PubMed, PsycINFO and Embase. We examined cross‐sectional studies that compared a SUD group with a control group and measured emotion regulation using the DERS or the ERQ. The primary analysis focused on papers using the DERS, as this was the predominant instrument in the literature. Results: Twenty‐two studies met our primary analysis criteria, representing 1936 individuals with a SUD and 1567 controls. Individuals with SUDs relative to controls had significantly greater DERS scores, with a mean difference of 21.44 [95% confidence interval (CI) = 16.49–26.40, P < 0.001] and Hedges' g = 1.05 (95% CI = 0.86–1.24, P < 0.001). The difference was robust, remaining significant after removing outliers and studies with high risk of bias. Individuals with SUDs demonstrated poorer emotion regulation on each subscale of the DERS, with the largest deficits in the Strategies and Impulse subscales. The ERQ analysis revealed greater use of expressive suppression in those with SUDs relative to controls (Hedges' g = 0.76, 95% CI = 0.25–1.28, P = 0.004). Conclusions: People with substance use disorders appear to have greater difficulties in emotion regulation than people without substance use disorders. [ABSTRACT FROM AUTHOR]

Background and aims: Population‐level alcohol use data are available from high‐income countries, but limited research has been conducted in sub‐Saharan Africa. This systematic review and meta‐analysis aimed to summarize population‐level alcohol use in sub‐Saharan Africa. Method: Databases searched included PubMed, EMBASE, PsycINFO and AJOL, without language restrictions. Searches were also conducted in the Global Health Data Exchange (GHDx) and Google Scholar. Search terms encompassed 'substance' or 'substance‐related disorders' and 'prevalence' and 'sub‐Saharan Africa'. We included general population studies on alcohol use (including any use, high‐risk alcohol use and alcohol use disorders) from 2018 onwards. Prevalence data for alcohol use among sub‐Saharan African adolescents (10–17) and adults (18+) were extracted. Analyses included life‐time and past 12‐ and 6‐month alcohol use. Results: We included 141 papers. Among adolescents, the life‐time prevalence of alcohol use was 23.3% [95% confidence interval (CI) = 11.3–37.1%], 36.2% (CI = 18.4–56.1%) in the past year and 11.3% (CI = 4.5–20.4%) in the past 6 months. Among adolescents, 12‐month prevalence of alcohol use disorder and alcohol dependence were 7.7% (CI = 0.0–27.8%) and 4.1% (CI = 1.4–7.9%), respectively. Among adults, the life‐time prevalence of alcohol use was 34.9% (CI = 17.7–54.1%), 27.1% (CI = 5.0–56.4%) in the past year and 32.2% (CI = 19.8–46.0%) in the past 6 months. Among adults, the 12‐month prevalence of alcohol use disorder and alcohol dependence were 9.5% (CI = 0.0–30.4%) and 4.3% (CI = 0.8–9.8%), respectively. The highest weighted life‐time prevalence of alcohol use, 86.4%, was reported in Tanzania among adults. The highest weighted past 6‐month prevalence of alcohol use, 80.6%, was found in Zambia among adolescents. Conclusion: Alcohol use patterns vary across countries and subregions within sub‐Saharan Africa, and comprehensive population‐level data on alcohol use remain scarce in numerous sub‐Saharan African countries. The prevalence of alcohol use disorder is common among adolescents in sub‐Saharan Africa. [ABSTRACT FROM AUTHOR]

Background and Aim: Mortality of alcohol‐related liver disease (ArLD) is increasing, and liver fibrosis stage is the best mortality predictor. Non‐invasive tests (NITs) are increasingly used to detect fibrosis, but their value as prognostic tests in chronic liver disease, and in particular in ArLD, is less well recognized. We aimed to describe the prognostic performance of four widely used NITs (Fibrosis 4 test [FIB4], Enhanced Liver Fibrosis [ELF] test, FibroScan, and FibroTest) in ArLD. Methods: Applying systematic review methodology, we searched four databases from inception to May 2020. Inclusion/exclusion criteria were applied to search using Medical Subject Heading terms and keywords. The first and second reviewers independently screened results, extracted data, and performed risk‐of‐bias assessment using Quality in Prognosis Studies tool. Results: Searches produced 25 088 articles. After initial screening, 1020 articles were reviewed independently by both reviewers. Eleven articles remained after screening for eligibility: one on ELF, four on FibroScan, four on FIB4, one on FIB4 + FibroScan, and one on FibroTest + FIB4. Area under the receiver operating characteristic curves for outcome prediction ranged from 0.65 to 0.76 for FibroScan, 0.64 to 0.83 for FIB4, 0.69 to 0.79 for FibroTest, and 0.72 to 0.85 for ELF. Studies scored low–moderate risk of bias for most domains but high risk in confounding/statistical reporting domains. The results were heterogeneous for outcomes and reporting, making pooling of data unfeasible. Conclusions: This systematic review returned 11 papers, six of which were conference abstracts and one unpublished manuscript. While the heterogeneity of studies precluded direct comparisons of NITs, each NIT performed well in individual studies in predicting prognosis in ArLD (area under the receiver operating characteristic curves >0.7 in each NIT category) and may add value to prognostication in clinical practice. [ABSTRACT FROM AUTHOR]

Background and aims: Alcohol consumption increased in the early phases of the COVID‐19 pandemic in the United States. Alcohol use disorder (AUD) and risky drinking are linked to harmful health effects. This paper aimed to project future health and cost impacts of shifts in alcohol consumption during the COVID‐19 pandemic. Design: An individual‐level simulation model of the long‐term drinking patterns for people with life‐time AUD was used to simulate 10 000 individuals and project model outcomes to the estimated 25.9 million current drinkers with life‐time AUD in the United States. The model considered three scenarios: (1) no change (counterfactual for comparison); (2) increased drinking levels persist for 1 year ('increase‐1') and (3) increased drinking levels persist for 5 years ('increase‐5'). Setting: United States. Participants: Current drinkers with life‐time AUD. Measurements: Life expectancy [life‐years (LYs)], quality‐adjusted life‐years (QALYs), alcohol‐related hospitalizations and associated hospitalization costs and alcohol‐related deaths, during a 5‐year period. Findings Short‐term increases in alcohol consumption (increase‐1 scenario) resulted in a loss of 79 000 [95% uncertainty interval (UI]) 26 000–201 000] LYs, a loss of 332 000 (104 000–604 000) QALYs and 295 000 (82 000–501 000) more alcohol‐related hospitalizations, costing an additional $5.4 billion ($1.5–9.3 billion) over 5 years. Hospitalizations for cirrhosis of the liver accounted for approximately $3.0 billion ($0.9–4.8 billion) in hospitalization costs, more than half the increase across all alcohol‐related conditions. Health and cost impacts were more pronounced for older age groups (51+), women and non‐Hispanic black individuals. Increasing the duration of pandemic‐driven increases in alcohol consumption in the increase‐5 scenario resulted in larger impacts. Conclusions: Simulations show that if the increase in alcohol consumption observed in the United States in the first year of the pandemic continues, alcohol‐related mortality, morbidity and associated costs will increase substantially over the next 5 years. [ABSTRACT FROM AUTHOR]

Introduction: Before COVID‐19, Native Hawaiians/Pacific Islanders (NH/PI) endured a heavy burden of alcohol, tobacco and other drug (ATOD) use in prior US data. Responding to reports that many NH/PI communities experienced severe COVID‐19 disparities that could exacerbate their ATOD burden, we partnered with NH/PI communities to assess the substance use patterns and treatment needs of diverse NH/PIs during COVID‐19. Methods: Collaborating with NH/PI community organisations across five states with large NH/PI populations, we conducted a large‐scale investigation of NH/PI ATOD use, mental health and treatment need during COVID‐19. Between April and November 2021, NH/PI‐heritage research staff from our community partners collected data involving 306 NH/PI adults using several community‐based recruitment methods (e‐mail, telephone, in‐person) and two survey approaches: online and paper‐and‐pencil. Multivariate regressions were conducted to examine potential predictors of NH/PI alcohol use disorder and need for behavioural health treatment. Results: During COVID‐19, 47% and 22% of NH/PI adults reported current alcohol and cigarette use, while 35% reported lifetime illicit substance use (e.g., cannabis, opioid). Depression and anxiety were high, and alcohol use disorder, major depression and generalised anxiety disorder prevalence were 27%, 27% and 19%, respectively. One‐third of participants reported past‐year treatment need with lifetime illicit substance use, COVID‐19 distress and major depression respectively associating with 3.0, 1.2, and 5.3 times greater adjusted odds for needing treatment. Conclusions: NH/PI adults reported heavy ATOD use, depression, anxiety and treatment need during COVID‐19. Targeted research and treatment services may be warranted to mitigate COVID‐19's negative behavioural health impact on NH/PI communities. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) is a major contributor to morbidity and mortality worldwide. Although there is a heritable component, the etiology of AUD is complex and can involve environmental exposures like trauma and can be associated with many different patterns of alcohol consumption. Epigenetic modifications, which can mediate the influence of genetic variants and environmental variables on gene expression, have emerged as an important area of AUD research. Over the past decade, the number of studies investigating AUD and DNA methylation, a form of epigenetic modification, has grown rapidly. Yet we are still far from understanding how DNA methylation contributes to or reflects aspects of AUD. In this paper, we reviewed studies of DNA methylation and AUD and discussed how the field has evolved. We found that global DNA and candidate DNA methylation studies did not produce replicable results. To assess whether findings of epigenome‐wide association studies (EWAS) were replicated, we aggregated significant findings across studies and identified 184 genes and 15 gene ontological pathways that were differentially methylated in at least two studies and four genes and three gene ontological pathways that were differentially methylated in three studies. These genes and pathways repeatedly found enrichment of immune processes, which is in line with recent developments suggesting that the immune system may be altered in AUD. Finally, we assess the current limitations of studies of DNA methylation and AUD and make recommendations on how to design future studies to resolve outstanding questions. [ABSTRACT FROM AUTHOR]

Background and aims: Solitary drinking in adolescents and young adults is associated with greater risk for alcohol problems, but it is unclear whether this association exists in older demographics. The current paper is the first meta‐analysis and systematic review, to our knowledge, to determine whether adult solitary drinking is associated with greater risk for alcohol problems. Methods: PsychINFO, PubMed and Google Scholar were searched following a pre‐registered International Prospective Register of Systematic Reviews (PROSPERO) protocol (CRD42019147075) and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) methodology. Following the methodology used in our recent systematic review and meta‐analysis on adolescent/young adult solitary drinking, we systematically reviewed solitary drinking measures/definitions, prevalence rates and associated demographic variables in adults. We then meta‐analyzed (using random‐effects models) associations between adult solitary drinking and alcohol use/problems, negative affect and negative/positive reinforcement‐related variables (e.g. drinking to cope or for enhancement). Results: Solitary drinking was defined as drinking while physically alone in nearly all studies, but measures varied. Prevalence rates were generally in the 30–40% range, with some exceptions. In general, males were more likely than females to report drinking alone, and married individuals were less likely than unmarried individuals to report drinking alone; racial/ethnic differences were mixed. Meta‐analytical results showed significant effects for the associations between solitary drinking and the following factors: alcohol consumption, r = 0.25, 95% confidence interval (CI) = 0.18, 0.33, k = 15, I2 = 97.41; drinking problems, r = 0.15, 95% CI = 0.10, 0.21, k = 14, I2 = 92.70; and negative reinforcement, r = 0.24, 95% CI = 0.14, 0.32, k = 11, I2 = 89.77; but not positive reinforcement, r = 0.02, 95% CI = 0.06, 0.09, k = 8, I2 = 76.18; or negative affect, r = 0.03, 95% CI = −0.02, 0.08, k = 8, I2 = 52.06. Study quality moderated the association between solitary drinking and negative affect (β = −0.07, P < 0.01) such that lower‐quality studies were significantly associated with larger effect sizes. Study quality was generally low; the majority of studies were cross‐sectional. Conclusions: Solitary drinking appears to have a small positive association with alcohol problems. [ABSTRACT FROM AUTHOR]

Background: Knowledge of how drinking motives are differentially associated with alcohol use (e.g., frequency, quantity) and drinking problems is critical in understanding risky drinking and the development of alcohol use disorder. The purpose of this paper was to use meta‐analytic techniques to answer 2 overarching questions: (a) Which types of drinking motives (i.e., enhancement, coping, social, conformity) are most strongly associated with alcohol use and drinking problems? and (b) What are the most likely mechanisms (alcohol use or drinking problems) through which motives may be indirectly associated with outcomes? Method: A comprehensive literature search identified 229 studies that met inclusion criteria (254 samples; N = 130,705) with a subset containing longitudinal data (k = 5; N = 6283). Data were analyzed using 2‐stage meta‐analytic structural equation modeling. Results: Results showed that both enhancement and coping motives were the strongest predictors of drinking problems, but only enhancement motives were the strongest predictor of alcohol use. Enhancement and social motives were indirectly associated with alcohol use through drinking problems and with drinking problems through alcohol use, whereas coping motives were only indirectly associated with alcohol use through drinking problems, although the results differed for cross‐sectional and longitudinal data. Conclusion: Overall, findings from this meta‐analysis provide evidence that drinking motives differentially predict alcohol use outcomes through unique direct and indirect pathways. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this paper is to provide an account of the history, current status and vision of the Korean Institute on Alcohol Problems (KIAP). In the context of increasing alcohol consumption, rising second-hand effects and industry-friendly government policy, the Korean College Alcohol Study (KCAS) was established in the Republic of Korea in 1999, and changed its name to the Korean Institute on Alcohol Problems (KIAP) in 2005. KIAP's mission is to decrease alcohol consumption and its related harms by promoting research, advocating policy, developing intervention programmes and preparing media communications. Since 1999, KIAP has published scientific papers and books in alcohol research and used the internet and other media for dissemination of specialized information to the general population. In the last decade, KIAP has trained front-line alcohol researchers, and advanced domestic and international networks to promote evidence-based alcohol control policy in Korea. The light of hope shines brightly as KIAP grows and establishes critical linkages to move forward in its mission. [ABSTRACT FROM AUTHOR]

Although most cognitive impairments induced by prolonged alcohol consumption tend to improve within the initial months of abstinence, there is evidence suggesting certain cognitive deficits may persist. This study aimed to investigate the impact of aerobic exercise on learning and memory in alcohol use disorder (AUD) mice following a period of abstinence from alcohol. We also sought to assess the levels of monoamine neurotransmitters in the hippocampus. To this end, we established an AUD mouse model through a two‐bottle choice (sucrose fading mode and normal mode) and chronic intermittent alcohol vapor (combined with intraperitoneal injection) and randomly allocated mice into exercise groups to undergo treadmill training. Learning and memory abilities were assessed through the Morris water maze test and spontaneous activity was evaluated using the open field test. The levels of dopamine, norepinephrine, serotonin, and brain‐derived neurotrophic factor in the hippocampus were quantified using enzyme‐linked immunoassay (ELISA) kits. The findings reveal that after cessation of alcohol consumption, learning and memory abilities in AUD mice did not completely return to normal levels. The observed enhancement of cognitive functions in AUD mice through aerobic exercise may be attributed to restoring levels of monoamine neurotransmitters in the hippocampus, boosting brain‐derived neurotrophic factor (BDNF) concentrations, and facilitating an increase in hippocampal mass. These results offer empirical evidence to support aerobic exercise as a viable therapeutic strategy to alleviate cognitive deficits associated with AUD. [ABSTRACT FROM AUTHOR]

Obesity represents a major medical and public health problem worldwide. Efforts have been made to develop novel treatments, and among them bariatric surgery is used as an effective treatment to achieve significant, long-term weight loss and alleviate medical problems related to obesity. Alcohol use disorder (AUD) is also a leading cause of morbidity and mortality worldwide. Recent clinical studies have revealed a concern for bariatric surgery patients developing an increased risk for alcohol consumption, and for AUD. A better understanding of the relationship between bariatric surgery and potential later development of AUD is important, given the critical need of identifying patients at high risk for AUD. This paper reviews current clinical and basic science research and discusses potential underlying mechanisms. Special emphasis in this review is given to recent work suggesting that, alterations in alcohol metabolism/pharmacokinetics resulting from bariatric surgery are unlikely to be the primary or at least the only explanation for increased alcohol use and development of AUD, as changes in brain reward processing are also likely to play an important role. Additional studies are needed to clarify the potential role and mechanisms of how bariatric surgery may increase alcohol use and lead to AUD development. [ABSTRACT FROM AUTHOR]

Introduction and Aims Evidence of treatment effectiveness for alcohol use disorders ( AUD) have emerged predominantly from Western studies, using highly controlled trials that may not reflect real-world settings. This paper examines treatment outcome and its predictors among Asian problem drinkers participating in a treatment outcome monitoring program at an addiction treatment centre in Singapore. Design and Methods Data were collected at intake and 3, 6 and 12 months, although the focus of this paper is on reliable change at 3 months among the 70% who were followed up. Five hundred and forty-one AUD-diagnosed outpatients presenting for treatment, over a 2-year period, were assessed on drinking behaviours and administered the Addiction Severity Index- Lite, Personal Wellbeing Index ( PWI) and Treatment Perceptions Questionnaire. Results At 3 months, drinking days, alcohol units and alcohol use severity had more than halved and 69% were either abstinent or had reliably reduced their drinking days. Baseline drinking days and treatment satisfaction predicted 3-month drinking frequency but not severity. Positive alcohol outcomes observed at 3 months were sustained among those followed up until 12 months. Mean PWI score improved significantly and fell within the 'normal' range. Treatment satisfaction also emerged as the only significant predictor of reliable positive change in both drinking days and PWI score. Discussion and Conclusions Significant reductions in drinking frequency and severity are possible for Asian problem drinkers after 12 weeks of outpatient treatment. The identified predictors suggest that more frequent drinkers and patients with past/current psychiatric comorbidities may require a more intensive treatment approach to optimise treatment outcomes. [ABSTRACT FROM AUTHOR]

Introduction and Aims. The trajectory from alcohol use to alcohol use disorders in adolescence is yet to be understood. Momentary sampling may assist in capturing ‘real-time’ data on young people's alcohol use and associated motivational factors. This paper aims to review the feasibility and usefulness of a mobile phone momentary sampling program to capture data about alcohol use and related behaviours. Design and Methods. Two studies were conducted: a school-based study with 18 Year 9 and 11 students and a clinical study with eight high-risk adolescent drinkers. Participants answered questions about their daily activities, alcohol use, stressors and negative mood four times a day for 1 week using a mobile phone momentary sampling program. Results. In the school-based study, 61% of participants reported drinking alcohol. On drinking days participants spent less time studying (14% vs. 26%), more time sleeping or resting (35% vs. 12%) and more time hanging out (21% vs. 11%) than on non-drinking days. In the high-risk sample, 88% of participants reported drinking alcohol. On drinking days, these participants spent a greater proportion of their waking time with their boyfriend or girlfriend (19.2% vs. 6%) and generally had higher negative mood than on non-drinking days. Discussion and Conclusions. The current mobiletype program was well suited to capturing data on alcohol use in younger, school-attending adolescents. However, to capture alcohol use in older adolescents who lead less routine lives, it is necessary to make some amendments including targeting particular behaviours and symptoms. Recommendations for future studies are proposed.[Kauer SD, Reid SC, Sanci L & Patton GC. Investigating the utility of mobile phones for collecting data about adolescent alcohol use and related mood, stress and coping behaviours: Lessons and recommendations. Drug Alcohol Rev 2009;28:25–30] [ABSTRACT FROM AUTHOR]

Background Stress and anxiety are widely considered to be causally related to alcohol craving and consumption, as well as development and maintenance of alcohol use disorder ( AUD). However, numerous preclinical and human studies examining effects of stress or anxiety on alcohol use and alcohol-related problems have been equivocal. This study examined relationships between scores on self-report anxiety, anxiety sensitivity, and stress measures and frequency and intensity of recent drinking, alcohol craving during early withdrawal, as well as laboratory measures of alcohol craving and stress reactivity among heavy drinkers with AUD. Methods Media-recruited, heavy drinkers with AUD ( N = 87) were assessed for recent alcohol consumption. Anxiety and stress levels were characterized using paper-and-pencil measures, including the Beck Anxiety Inventory ( BAI), the Anxiety Sensitivity Index-3 ( ASI-3), and the Perceived Stress Scale ( PSS). Eligible subjects ( N = 30) underwent alcohol abstinence on the Clinical Research Unit; twice daily measures of alcohol craving were collected. On day 4, subjects participated in the Trier Social Stress Test; measures of cortisol and alcohol craving were collected. Results In multivariate analyses, higher BAI scores were associated with lower drinking frequency and reduced drinks/drinking day; in contrast, higher ASI-3 scores were associated with higher drinking frequency. BAI anxiety symptom and ASI-3 scores also were positively related to Alcohol Use Disorders Identification Test total scores and AUD symptom and problem subscale measures. Higher BAI and ASI-3 scores but not PSS scores were related to greater self-reported alcohol craving during early alcohol abstinence. Finally, BAI scores were positively related to laboratory stress-induced cortisol and alcohol craving. In contrast, the PSS showed no relationship with most measures of alcohol craving or stress reactivity. Conclusions Overall, clinically oriented measures of anxiety compared with perceived stress were more strongly associated with a variety of alcohol-related measures in current heavy drinkers with AUD. [ABSTRACT FROM AUTHOR]

Background The primary goals in conducting clinical trials of treatments for alcohol use disorders ( AUDs) are to identify efficacious treatments and determine which treatments are most efficacious for which patients. Accurate reporting of study design features and results is imperative to enable readers of research reports to evaluate to what extent a study has achieved these goals. Guidance on quality of clinical trial reporting has evolved substantially over the past 2 decades, primarily through the publication and widespread adoption of the Consolidated Standards of Reporting Trials statement. However, there is room to improve the adoption of those standards in reporting the design and findings of treatment trials for AUD. Methods This paper provides a narrative review of guidance on reporting quality in AUD treatment trials. Results Despite improvements in the reporting of results of treatment trials for AUD over the past 2 decades, many published reports provide insufficient information on design or methods. Conclusions The reporting of alcohol treatment trial design, analysis, and results requires improvement in 4 primary areas: (i) trial registration, (ii) procedures for recruitment and retention, (iii) procedures for randomization and intervention design considerations, and (iv) statistical methods used to assess treatment efficacy. Improvements in these areas and the adoption of reporting standards by authors, reviewers, and editors are critical to an accurate assessment of the reliability and validity of treatment effects. Continued developments in this area are needed to move AUD treatment research forward via systematic reviews and meta-analyses that maximize the utility of completed studies. [ABSTRACT FROM AUTHOR]

Background Over the past 60 years, the view that 'alcoholism' is a disease for which the only acceptable goal of treatment is abstinence has given way to the recognition that alcohol use disorders ( AUDs) occur on a continuum of severity, for which a variety of treatment options are appropriate. However, because the available treatments for AUDs are not effective for everyone, more research is needed to develop novel and more efficacious treatments to address the range of AUD severity in diverse populations. Here we offer recommendations for the design and analysis of alcohol treatment trials, with a specific focus on the careful conduct of randomized clinical trials of medications and nonpharmacological interventions for AUDs. Methods This paper provides a narrative review of the quality of published clinical trials and recommendations for the optimal design and analysis of treatment trials for AUDs. Results Despite considerable improvements in the design of alcohol clinical trials over the past 2 decades, many studies of AUD treatments have used faulty design features and statistical methods that are known to produce biased estimates of treatment efficacy. Conclusions The published statistical and methodological literatures provide clear guidance on methods to improve clinical trial design and analysis. Consistent use of state-of-the-art design features and analytic approaches will enhance the internal and external validity of treatment trials for AUDs across the spectrum of severity. The ultimate result of this attention to methodological rigor is that better treatment options will be identified for patients with an AUD. [ABSTRACT FROM AUTHOR]

Summary: Background: Alcohol use is the most important factor in determining the prognosis of patients with alcohol‐related cirrhosis and alcohol‐associated hepatitis. Aim: To conduct a systematic review of interventions for alcohol use disorder specific to patients with cirrhosis or alcohol‐associated hepatitis. Methods: We searched five databases between inception and November 2022. The primary outcomes were abstinence, hepatic decompensation and mortality. We included randomised and non‐randomised studies. Risk of bias was assessed using validated tools. Where possible, meta‐analysis was performed. Results: Twenty‐three studies met the inclusion criteria including six randomised trials and 17 non‐randomised studies of interventions. These included 104,298 patients with a mean/median age range from 44 to 65, of whom 75% were male. Interventions included psychological therapy, pharmacological therapies, specialist clinics, patient education and low alcohol drinks. Baclofen was the only intervention to demonstrate a statistically significant impact on the primary outcomes in a randomised trial (abstinence OR: 6.3, 95% CI: 2.4–16.1). Three non‐randomised studies reported reductions in episodes of hepatic decompensation that were significant in multivariate models. This was in response to psychological therapy, use of any pharmacotherapy, and use of any treatment. A meta‐analysis of non‐randomised studies that examined the impact of psychological therapies revealed statistically non‐significant improvements in abstinence (4 studies, OR: 1.87, 95% CI: 0.38–9.23) and mortality (4 studies, OR: 0.47, 95% CI: 0.12–1.77). Conclusions: Baclofen is the only intervention with randomised trial evidence for significant benefit in patients with cirrhosis. Non‐randomised studies also point to non‐pharmaceutical interventions possibly improving clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Previous studies have yielded mixed results on the association between gender and alcohol use disorder (AUD) treatment outcomes. Thus, additional research is needed to determine the effect of gender on AUD treatment outcomes, including quality of life (QoL), particularly among older adults. Aims: In a clinical sample of older adults with DSM‐5 AUD, we examined changes in QoL from the beginning of AUD treatment through 1 year of follow‐ups. We also examined the effect of gender and explored interaction effects with gender on QoL. Methods: We utilized data from the "Elderly Study," a multi‐national, single‐blind, randomized, controlled trial of 693 adults aged 60+ with DSM‐5 AUD. Alcohol use was assessed with the Form‐90, and QoL with the brief version of the World Health Organization QoL measure. Information was collected at treatment initiation and at 4‐, 12‐, 26‐, and 52‐week follow‐ups. Multilevel mixed‐effects logistic and linear regression models were used to examine QoL changes and the effect of gender on changes in QoL. Results: Following treatment, small, but significant improvements were seen over time in overall perceived health (p < 0.05). Improvements that persisted over the 1‐year follow‐up period were seen in the QoL domains of physical health (β: 2.6, 95% CI: 1.4–3.9), psychological health (β: 3.5, 95% CI: 3.3–3.8), social relationships (β: 4.0, 95% CI: 2.5–5.6), and environmental health (β: 1.4, 95% CI: 0.4–2.4). No significant changes were seen over time in overall perceived QoL (p = 0.58). Gender was not associated with changes in any of the QoL outcome measures (all p ≥ 0.05). Conclusions: Among 60+ year‐old adults receiving treatment for DSM‐5 AUD, improvements in QoL were achievable and maintained over time, but were not associated with gender. [ABSTRACT FROM AUTHOR]

Background: Concerns regarding symptom severity and the risk of relapse among people seeking recovery from alcohol use disorder (AUD) have been raised since the onset of the COVID‐19 pandemic. Owing to preventive measures implemented during the pandemic (social distancing or lockdown), self‐help group (SHG) meetings were restricted. However, the impact of deprivation of onsite recovery meetings on drinking behavior and risk among SHG members with AUD remains unclear. We examined the proportion of SHG members who reported drinking and their reasons for drinking during the early stages of the pandemic and the effect of nonattendance at onsite recovery meetings on drinking behavior during the early pandemic period, stratified by gender. Methods: A national cross‐sectional survey of Japanese SHG members was conducted to measure self‐reported alcohol consumption, sociodemographic characteristics, AUD diagnosis, treatment status, SHG meeting attendance, membership duration, psychological distress, and health‐related variables. Of 6478 SHG members, 2955 (male: n = 2678; female: n = 277; response rate: 46.7%) responded, and the responses were analyzed using a gender‐stratified multivariate logistic regression model. Results: Most participants reported having abstained from alcohol use, while 6% of the respondents reported having consumed alcohol during the early stages of the pandemic. The proportion of "drinkers" among women (10.5%) was significantly higher than that among men (5.9%; p = 0.012). Through multivariate model analysis, the factors associated with drinking during the pandemic were identified as psychological distress (among men and women) and not attending onsite recovery meetings (among men). Conversely, a longer duration of SHG membership was associated with less drinking during the pandemic for both genders. Conclusions: Most SHG members appear to have remained abstinent during the early stages of the COVID‐19 pandemic. However, psychological distress in both genders and the inability to attend recovery meetings among men may have influenced drinking behavior. [ABSTRACT FROM AUTHOR]

Background and Aims: Alcohol use is increasing among women in mid‐life concurrently with societal changes in timing of parenthood and changing cultural norms, which may influence alcohol use. The aim of this study was to determine if age of first parenting was associated with excessive drinking [i.e. past 2‐week binge drinking and past 5‐year alcohol use disorder (AUD) symptoms] among women during mid‐life in the United States and to determine if there were pronounced cohort effects influencing these relationships. Design: This was a retrospective cohort, longitudinal study. Setting, Participants and Measurements: Data were drawn from the Monitoring the Future survey, an annual ongoing survey of high school students' substance use behaviors in the United States. Participants were women who completed the age 35 survey between 1993 and 2019, corresponding to high school senior years 1976–2002 (n = 9988). Past 2‐week binge drinking and past 5‐year AUD symptoms were self‐reported. Age of first parenting was self‐reported. Findings Binge drinking and AUD symptoms were higher among women in recent than in older cohorts. Women from the 2018–19 cohort had increased odds of binge drinking [odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.41–2.12] and AUD symptoms (OR = 1.51, CI = 1.27–1.80) relative to women from the 1993–97 cohort. Throughout cohorts, there was an inverse association between transition to parenthood and excessive drinking outcomes (e.g. range for ORs for binge drinking among those without children compared with those who had had children between the ages of 18 and 24: 1.22–1.55). Simultaneously, there was a population shift towards delaying parenting in recent cohorts (i.e. 54% of women in the 1993–97 cohort had children before age 30 compared with 39% in the two recent cohorts), increasing the size of the group at highest risk for excessive drinking. Conclusions: In the United States, subgroups of women at highest risk of excessive drinking appear to be expanding, probably supported in part by a trend towards delayed parenting. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) and related health conditions result from a complex interaction of genetic, neural and environmental factors, with differential impacts across the lifespan. From its inception, the Collaborative Study on the Genetics of Alcoholism (COGA) has focused on the importance of brain function as it relates to the risk and consequences of alcohol use and AUD, through the examination of noninvasively recorded brain electrical activity and neuropsychological tests. COGA's sophisticated neurophysiological and neuropsychological measures, together with rich longitudinal, multi‐modal family data, have allowed us to disentangle brain‐related risk and resilience factors from the consequences of prolonged and heavy alcohol use in the context of genomic and social‐environmental influences over the lifespan. COGA has led the field in identifying genetic variation associated with brain functioning, which has advanced the understanding of how genomic risk affects AUD and related disorders. To date, the COGA study has amassed brain function data on over 9871 participants, 7837 with data at more than one time point, and with notable diversity in terms of age (from 7 to 97), gender (52% female), and self‐reported race and ethnicity (28% Black, 9% Hispanic). These data are available to the research community through several mechanisms, including directly through the NIAAA, through dbGAP, and in collaboration with COGA investigators. In this review, we provide an overview of COGA's data collection methods and specific brain function measures assessed, and showcase the utility, significance, and contributions these data have made to our understanding of AUD and related disorders, highlighting COGA research findings. [ABSTRACT FROM AUTHOR]

Background and Purpose: Chronic pain is considered a key factor contributing to alcohol use disorder (AUD). The mechanisms responsible for chronic pain associated with chronic alcohol consumption are unknown. We evaluated the development of chronic pain in a mouse model of alcohol dependence and investigate the role of neuroinflammation. Experimental Approach: The chronic‐intermittent ethanol two‐bottle choice CIE‐2BC paradigm generates three groups: alcohol‐dependent with escalating alcohol intake, nondependent (moderate drinking) and alcohol‐naïve control male and female mice. We measured mechanical allodynia during withdrawal and after the last voluntary drinking. Immunoblotting was used to evaluate the protein levels of IBA‐1, CSFR, IL‐6, p38 and ERK2/1 in spinal cord tissue of dependent and non‐dependent animals. Key Results: We found significant escalation of drinking in the dependent group in male and female compared with the non‐dependent group. The dependent group developed mechanical allodynia during 72 h of withdrawal, which was completely reversed after voluntary drinking. We observed an increased pain hypersensitivity compared with the naïve in 50% of non‐dependent group. Increased IBA‐1 and CSFR expression was observed in spinal cord tissue of both hypersensitivity‐abstinence related and neuropathy‐alcohol mice, and increased IL‐6 expression and ERK1/2 activation in mice with hypersensitivity‐related to abstinence, but not in mice with alcohol‐evoked neuropathic pain. Conclusions and Implications: The CIE‐2BC model induces two distinct pain conditions specific to the type of ethanol exposure: abstinence‐related hypersensitivity in dependent mice and alcohol‐evoked neuropathic pain in about a half of the non‐dependent mice. [ABSTRACT FROM AUTHOR]

Alcohol cue exposure is a widely used experimental paradigm for screening pharmacotherapies for alcohol use disorder (AUD). Medication‐related reductions in cue‐reactivity signal early efficacy and inform medications development. Yet, across trials, the design of cue exposure, parameter testing, and outcome reporting is heterogeneous. This systematic review is a quantitative synthesis of trial methodologies and effect size estimation for AUD medication‐related craving and psychophysiological outcomes under the cue exposure paradigm. A PubMed search was conducted on January 3, 2022 based on identified pharmacotherapies for peer‐reviewed articles reported in English. Study‐level characteristics, including sample descriptors, paradigm design, analytic approach, and Cochrane Risk of Bias, along with descriptive statistics for cue‐exposure outcomes, were coded by two independent raters. Study‐level effect sizes were estimated for craving and psychophysiological outcomes separately and sample‐level effect sizes were calculated for each medication. Thirty‐six trials, comprising 1640 participants and testing 19 different medications satisfied eligibility criteria. All studies reported on biological sex (71% male participants on average). The exposure paradigms implemented used in vivo (n = 26), visual (n = 8), and audio script (n = 2) cues. Some trials included means for craving by medication condition in text (k = 7) or figures (k = 18). The quantitative synthesis included 63 effect sizes (craving kes = 47; psychophysiological kes = 16) from 28 unique randomized trials testing 15 medications for effects on cue reactivity. For cue‐induced craving, eight medications (kes range: 1–12) demonstrated small‐to‐medium effects (Cohen's d range: |0.24–0.64|) compared to placebo, with individuals randomized to receive medication reporting lower craving following cue exposure. Recommendations are provided to promote further consilience, so that the utility of cue exposure paradigms can be maximized in the development of effective AUD pharmacotherapies. Future work should explore the predictive utility of medication‐related reductions in cue‐reactivity on clinical outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims: Experiencing higher rates of stigma, marginalization and discrimination puts transgender individuals at risk for alcohol use and associated harms. Measures of harmful drinking were designed with cisgender people in mind, and some rely on sex‐ and gender‐based cut‐offs. The applicability of these measures for gender diverse samples remains unknown. The present study had two aims: (i) identify gender‐non‐inclusive language and cut‐offs in measures of harmful drinking, and (ii) systematically review research reporting psychometric properties of these measures in transgender individuals. Methods: We reviewed 22 measures of harmful drinking for gendered language and sex‐ and gender‐based cut‐off values and provided suggestions for revision when warranted. We also conducted a systematic narrative review, including eight eligible studies, summarizing the psychometric properties of measures of harmful drinking in transgender populations. Results: Six of 22 measures of harmful drinking were not gender inclusive, because of gendered language in the measure itself or use of sex‐ or gender‐based cut‐off scores. Only eight published studies reported psychometric data for these measures in transgender people. Apart from in one study, the Alcohol Use Disorders Identification Test (AUDIT) and Alcohol Use Disorders Identification Test Consumption (AUDIT‐C) appear reliable for transgender adults (Cronbach's α: AUDIT [0.81–0.87] and AUDIT [0.72–0.8)]). There is initial support for using uniform cut‐offs for transgender people for the AUDIT‐C (≥3) and binge drinking (≥5 drinks in a sitting). Conclusions: Most existing measures of harmful drinking appear to be gender inclusive (containing gender neutral language and uniform cut‐off scores across sex and gender groups) and some that are not easily adapted to be gender inclusive. [ABSTRACT FROM AUTHOR]

Background: The basis for familial alcohol use disorder (AUD) remains an enigma due to various biological and societal confounds. The present study used three of the most adopted and documented rat models, combining the alcohol‐preferring/non‐alcohol‐preferring (P/NP) lines and high alcohol‐drinking/low alcohol‐drinking (HAD/LAD) replicated lines, of AUD as examined through the lens of whole genomic analyses. Methods: We used complete genome sequencing of the P/NP lines and previously published sequences of the HAD/LAD replicates to enhance the discovery of variants associated with AUD and to remove confounding with genetic background and random genetic drift. Specifically, we used high‐order statistical methods to search for genetic variants whose frequency changes in whole sets of gene ontologies corresponded with phenotypic changes in the direction of selection, that is, ethanol‐drinking preference. Results: Our first finding was that in addition to variants causing translational changes, the principal genetic changes associated with drinking predisposition were silent mutations and mutations in the 3′ untranslated regions (3′UTR) of genes. Neither of these types of mutations alters the amino acid sequence of the translated protein but they influence both the rate and conformation of gene transcription, including its stability and posttranslational events that alter gene efficacy. This finding argues for refocusing human genomic studies on changes in gene efficacy. Among the key ontologies identified were the central genes associated with the Na+ voltage–gated channels of neurons and glia (including the Scn1a, Scn2a, Scn2b, Scn3a, Scn7a, and Scn9a subtypes) and excitatory glutamatergic secretion (including Grm2 and Myo6), both of which are essential in neuroplasticity. In addition, we identified "Nociception or Sensory Perception of Pain," which contained variants in nociception (Arrb1, Ccl3, Ephb1) and enlist sodium (Scn1a, Scn2a, Scn2b, Scn3a, Scn7a), pain activation (Scn9a), and potassium channel (Kcna1) genes. Conclusion: The multi‐model analyses used herein reduced the confounding effects of random drift and the "founders" genetic background. The most differentiated bidirectionally selected genes across all three animal models were Scn9a, Scn1a, and Kcna, all of which are annotated in the nociception ontology. The complexity of neuroplasticity and nociception adds strength to the hypothesis that neuroplasticity and pain (physical or psychological) are prominent phenotypes genetically linked to the development of AUD. [ABSTRACT FROM AUTHOR]

Impairment in autonomic self‐regulatory functioning reflected by reduced heart rate variability (HRV) is a common feature of alcohol use disorder (AUD) and is believed to heighten AUD relapse risk. However, to date, no study has explored associations between in natura HRV and subsequent alcohol use among individuals seeking AUD recovery. In this study, 42 adults in the first year of a current AUD recovery attempt were monitored for 4 days using ambulatory electrocardiogram, followed by 90 days of alcohol use monitoring using timeline follow‐back. HRV indices (independent variables) reflecting autonomic neurocardiac engagement were calculated from electrocardiogram recordings. Alcohol use (dependent variable) was calculated from timeline follow‐back and expressed as per cent days abstinent (PDA). The sample was 73.81% White/European American, 19.05% Black/African American, 4.76% Asian, and 2.38% Other race/Mixed race. As predicted, higher parasympathetically mediated HRV and lower heart rate were associated with greater PDA over 90‐day follow‐up. Additionally, interactions between these measures and baseline PDA indicated higher parasympathetically mediated HRV and lower heart rate mitigated the deleterious positive association between baseline and follow‐up alcohol use. Including factors known to influence alcohol use and/or HRV in the models did not meaningfully alter their results. Findings are consistent with psychophysiological theories implicating autonomic self‐regulatory functioning in AUD treatment outcomes and suggest that select HRV indices may have utility as indicants of risk for alcohol use lapse in individuals in early AUD recovery. Findings provide theoretical support for HRV Biofeedback for this population, which exercises the psychophysiological systems that support self‐regulation. [ABSTRACT FROM AUTHOR]

Background and aims: Alcohol use disorder is comorbid with numerous other forms of psychopathology, including externalizing disorders (e.g. conduct disorder) and, to a lesser extent, internalizing conditions (e.g. depression, anxiety). Much of the time, overlap among alcohol use disorder and other conditions is explored at the disorder level, assuming that criteria are co‐equal indicators of other psychopathology, even though alcohol use disorder criteria span numerous varied domains. Emerging evidence suggests that there are symptom clusters within the construct of alcohol use disorder that relate differentially with important external criteria, including psychopathology and allied personality traits (e.g. impulsivity, novelty‐seeking). The present study mapped individual alcohol use disorder criteria onto internalizing and externalizing dimensions. Design and participants: We used multivariate and factor analytical modeling and data from two large nationally representative samples of past year drinkers (n = 25 604; 19 454). Setting: United States. Measurements: Psychopathology was assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule, yielding alcohol use disorder criteria, internalizing diagnoses (i.e. major depressive disorder, dysthymia, social anxiety disorder, generalized anxiety disorder, specific phobia, agoraphobia and panic disorder) and externalizing diagnoses and symptoms (i.e. antisocial personality disorder, conduct disorder and three impulsivity items drawn from borderline personality disorder criteria). Alcohol consumption was assessed in terms of past‐year drinking frequency, usual amount of alcohol consumed on drinking days, binge drinking frequency, intoxication frequency, and maximum number of drinks in a 24‐hour period. Findings Four different patterns emerged. First, several alcohol use disorder criteria were relatively weakly associated with externalizing and internalizing. Secondly, withdrawal was associated with internalizing, but this association was not specific to distress. Thirdly, there was a general lack of specificity between alcohol use disorder criteria and narrower forms of internalizing, despite what might be predicted by modern models of addiction. Fourthly, recurrent use in hazardous situations reflected higher degrees of externalizing and lower internalizing liability. Conclusions: Different symptom combinations appear to yield differential expressions of alcohol use disorder that are disorder‐specific, or reflect broader tendencies toward externalizing, internalizing or both. [ABSTRACT FROM AUTHOR]

Preclinical and clinical work suggests that mifepristone may be a viable treatment for alcohol use disorder (AUD). This was a Phase 1/2, outpatient, cross‐over, randomized, double‐blind, placebo‐controlled trial with non‐treatment‐seeking individuals with AUD (N = 32). We assessed safety, alcohol craving and consumption, after 1‐week mifepristone 600 mg/day administration, in a human laboratory study comprised of a single oral yohimbine administration (32.4 mg), a cue‐reactivity procedure and alcohol self‐administration. Safety was monitored by adverse events and hemodynamic parameters, alcohol craving by alcohol craving questionnaire and cue‐induced saliva output. During the alcohol self‐administration, we assessed alcohol pharmacokinetics, subjective effects and consumption. Outcomes were assessed using Generalized Estimating Equations and mediation analysis. Mild‐moderate adverse events were reported in both conditions. There was no statistically significant difference between mifepristone and placebo in alcohol pharmacokinetics and subjective effects. Furthermore, blood pressure increased only in the placebo condition after the stress‐induced laboratory procedures. Mifepristone, compared to placebo, significantly reduced alcohol craving and increased cortisol levels. Mifepristone‐induced cortisol increase was not a mediator of alcohol craving. Mifepristone, compared to placebo, did not reduce alcohol consumption in the laboratory or in a naturalistic setting. This study successfully translated a developed preclinical procedure to a human laboratory study, confirming the safety of mifepristone in people with AUD and providing evidence to its role in reducing alcohol craving under stress procedures. The lack of effects on alcohol drinking may be related to the selection of non‐treatment seekers and suggests future treatment‐oriented trials should investigate mifepristone in people with AUD. [ABSTRACT FROM AUTHOR]

Calcium/calmodulin‐dependent kinase II (CaMKII) is a key enzyme at the glutamatergic synapses. CAMK2A gene variants have been linked with alcohol use disorder (AUD) by an unknown mechanism. Here, we looked for the link between αCaMKII autophosphorylation and the AUD aetiology. Autophosphorylation‐deficient heterozygous αCaMKII mutant mice (T286A+/−) were trained in the IntelliCages to test the role of αCaMKII activity in AUD‐related behaviours. The glutamatergic synapses morphology in CeA was studied in the animals drinking alcohol using 3D electron microscopy. We found that T286A+/− mutants consumed less alcohol and were more sensitive to sedating effects of alcohol, as compared to wild‐type littermates (WT). After voluntary alcohol drinking, T286A+/− mice had less excitatory synapses in the CeA, as compared to alcohol‐naive animals. This change correlated with alcohol consumption was not reversed after alcohol withdrawal and not observed in WT mice. Our study suggests that αCaMKII autophosphorylation affects alcohol consumption by controlling sedative effects of alcohol and preventing synaptic loss in the individuals drinking alcohol. This finding advances our understanding of the molecular processes that regulate alcohol dependence. [ABSTRACT FROM AUTHOR]

During the COVID‐19 pandemic, many potential risk groups have been identified, such as those with obesity, diabetes, preexisting organ injuries, and several other conditions. Smoking is the most reported substance use disorder linked to increased COVID‐19 hospitalization rate and disease severity. In relation to smoking, we discuss the impairment of the innate and the adaptive immune systems as being among the main potential reasons for increased COVID‐19 infection risk and severity. Chronic alcohol consumption and alcohol use disorder (AUD) also have a negative impact on the immune system, but when it comes to COVID‐19 risk, they produce diverse outcomes. Some studies provide evidence that chronic alcohol consumption and AUD increase the risk of COVID‐19 infection and severe disease progression, while others report reduced hospitalization and death rates. In this review, we summarize the current state of epidemiological and molecular data concerning alcohol consumption and AUD as risk factors for COVID‐19 infection, hospitalization, and mortality. [ABSTRACT FROM AUTHOR]

Dopamine receptor D2 (DRD2) and ankyrin repeat and kinase domain‐containing protein 1 (ANKK1) genes have received considerable attention for their involvement in alcohol use disorder (AUD), but many questions remain on their exact role. We conducted a population‐based case–control and genetic association study in a large sample of young adults. Our aim was to assess the association between DRD2 and ANKK1 single nucleotide polymorphisms (SNPs) and harmful alcohol use, disentangling associated and possible intermediate factors. A total of 1841 college students from the French region Champagne‐Ardennes, aged between 18 and 21 years and who reported at least one lifetime alcohol consumption, were included in this study. Allele frequencies were analysed according to harmful alcohol use (assessed through the Alcohol Use Disorder Identification Test [AUDIT] questionnaire). Different substance use disorders, including nicotine and cannabis dependences, were also assessed through questionnaires, as was a list of potential associated factors (e.g., major depressive episode, conduct disorder, attention‐deficit/hyperactivity disorder [ADHD], school failure, sugar consumption, sexual trauma, parents' use of alcohol, tobacco or cannabis). We found that DRD2 rs1800498 was associated with harmful alcohol use. Many factors were detected, but a global path analysis revealed that DRD2 rs1800498 had a significant direct effect on harmful alcohol use and that early age at first alcohol consumption and depressive symptoms moderated this effect. This study suggests an interplay between harmful alcohol use, DRD2 genotypes and other risk factors that, with a full understanding, could be useful for preventive purposes. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol use disorder (AUD) is associated with a significant disease burden in France, where alcohol use is deeply rooted in culture. However, the treatment gap is large because of several barriers, including stigmatisation and drinkers' apprehension about total abstinence. However, standardised and evidence‐based interventions based on controlled‐drinking for people with AUD are lacking. We aimed to assess the effectiveness of a novel community‐based French therapeutic patient education (TPE) program for people with AUD named Choizitaconso. Methods: A before‐after non‐randomised quasi‐experimental study, named ETHER, was designed and implemented with people living with AUD, over a period of 6 months. The primary outcome was percentage change in the number of alcohol‐related harms experienced. Secondary outcomes were percentage changes in psycho‐social patient‐reported and community‐validated outcomes. Participants in the intervention group (n = 34) benefited from the 10‐week TPE program Choizitaconso, while the comparison group (n = 58) received standard care. The Kruskall–Wallis and chi‐squared or Fisher's exact tests were used to compare before‐after changes in variables in both groups. Linear regression models were used to test for the effect of study group on each outcome and to test for the effect of alcohol consumption as a confounder. Results: At 6 months, all outcomes but one either remained stable or numerically improved in both groups. Internalised stigma significantly improved in the intervention group (p = 0.026) but not in the comparison group (p = 0.207), with a significant group effect (p = 0.014). Discussion and Conclusions: This study demonstrates the effectiveness of the Choizitaconso TPE program on community‐validated outcomes, especially internalised stigma. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancer patients are at risk for malnutrition, which can impact postoperative outcomes. This study evaluates the Malnutrition Universal Screening Tool (MUST) to predict outcomes in major head and neck surgeries. Methods: A retrospective chart review included 275 major surgical procedures performed on 242 patients over the age of 18 years between May 2015 and May 2020. Results: The majority of patients had a MUST score of zero (68.7%). Just under 17% scored 2 or greater indicating malnourishment. Having a MUST score of 2 or higher was associated with occurrence of a postoperative complication (p < 0.001). Patients with alcohol use disorder or depression were 5.2 (CI: 2.0–13.7, p = 0.001) and 2.75 (CI 1.1–7.0; p = 0.033) times more likely to develop a postoperative complication, respectively. Conclusions: Malnutrition and comorbidities were associated with complications in our surgical cohort. MUST is a novel tool to identify patients who may benefit from nutritional interventions. [ABSTRACT FROM AUTHOR]

Background: Chronic alcohol consumption and alcohol use disorder have a tremendous impact on the patient's psychological and physiological health. There is evidence that chronic alcohol consumption influences SARS‐CoV2 infection risk, but so far, the molecular mechanism underlying such an effect is unknown. Methods: We generated the expression data of SARS‐CoV2 infection‐relevant genes (Ace2, Tmprss2, and Mas) in different organs in rat models of chronic alcohol exposure and alcohol dependence. Ace2 and Tmprss2 represent the virus entry point, whereas Mas activates the anti‐inflammatory response once the cells are infected. Results: Across three different chronic alcohol test conditions, we found a consistent upregulation of Ace2 gene expression in the lung, which has been shown to be the most affected organ in COVID‐19 patients. Other organs such as liver, ileum, kidney, heart, and brain also showed upregulation of Ace2 and Mas gene expression but less consistently across the different animal models, while Tmprss2 expression was unaffected in all conditions. Conclusions: We conclude that alcohol‐induced upregulation of Ace2 gene expression can lead to an elevated stochastic probability of virus entry into cells and may thus confer a molecular risk for SARS‐CoV2 infection. [ABSTRACT FROM AUTHOR]

Aberrant limbic circuit reactivity to negative stimuli might be related to alterations in emotion processing and regulation in alcohol use disorder (AUD). The current study tested for the first time in AUD the hypothesis of aberrant amygdala habituation to repeated aversive stimuli—a robust and reliable neuroimaging marker for emotion processing. We explored the link between deficits in habituation to adverse childhood experience (ACE), a common risk factor for impaired emotion regulation and AUD. AUD individuals (N = 36) and healthy controls (HC; N = 26) participated in an observational case–control functional magnetic resonance imaging (fMRI) study. An established habituation index was used to investigate processing of aversive emotional faces of the amygdala. AUD individuals showed an overall deficit in amygdala habituation (right: t = 4.26, pFWE = 0.004; left: t = 4.79, pFWE ≤ 0.001). Amygdala habituation was significantly related to increased exposure to ACE in HC (t = 3.88, pFWE = 0.012), whereas this association was not observed in AUD individuals (T = 1.80, pFWE = 0.662). Further, a significant association between higher alcohol consumption and reduced amygdala habituation (right: R2 = −0.356, F = 8.736, p = 0.004; left: R2 = −0.309, F = 6.332, p = 0.015) was observed. We found novel evidence for neural alterations in emotion processing in AUD individuals, indexed by deficient amygdala habituation to negative emotional content. We replicated a prior report on a link between ACE and amygdala habituation, a well‐established environmental risk factor for mental disorders and emotion dysregulation, in our control sample. Additionally, deficient amygdala habituation related to the amount of alcohol consumption in the overall sample might indicate a short‐term substance effect. [ABSTRACT FROM AUTHOR]

Gene expression studies offer promising opportunities to better understand the processes underlying alcohol use disorder (AUD). As cell types differ in their function, gene expression profiles will typically vary across cell types. When studying bulk tissue, failure to account for this cellular diversity has a detrimental impact on the ability to detect disease associations. We therefore assayed the transcriptomes of 32,531 individual nuclei extracted from the nucleus accumbens (NAc) of nine donors with AUD and nine controls (72% male). Our study identified 17 clearly delineated cell types. We detected 26 transcriptome‐wide significant differentially expressed genes (DEGs) that mainly involved medium spiny neurons with both D1‐type and D2‐type dopamine receptors, microglia (MGL) and oligodendrocytes. A higher than expected number of DEGs replicated in an existing single nucleus gene expression study of alcohol dependence in the prefrontal cortex (enrichment ratio 1.91, p value 0.019) with two genes remaining significant after a Bonferroni correction. Our most compelling result involved CD53 in MGL that replicated in the same cell type in the prefrontal cortex and was previously implicated in studies of DNA methylation, bulk gene expression and genetic variants. Several DEGs were previously reported to be associated with AUD (e.g., PER1 and MGAT5). The DEGs for MSN.3 seemed involved in neurodegeneration, disruption of circadian rhythms, alterations in glucose metabolism and changes in synaptic plasticity. For MGL, the DEGs implicated neuroinflammation and immune‐related processes and for OLI, disruptions in myelination. This identification of the specific cell‐types from which the association signals originate will be key for designing proper follow‐up experiments and, eventually, novel clinical interventions. [ABSTRACT FROM AUTHOR]

A previous highly controlled pilot study revealed that body mass index (BMI) predicts outcome of in‐patients with alcohol use disorder (AUD) in a sex‐specific manner. We here provide translational evidence from a daily clinical routine setting and investigated whether BMI and sex interact to predict 24‐month readmission risk in four naturalistic cohorts of a specialized addiction clinic (i.e., all patients admitted to the clinic from 2016 to 2020): (i) in‐patients (443 males and 197 females) and (ii) day clinic patients (241 males and 103 females) with a primary diagnosis of AUD; (iii) in‐patients (175 males and 98 females) and (iv) day clinic patients (174 males and 64 females) with a primary substance use disorder (SUD) other than alcohol. In the in‐patients with AUD, BMI interacted with sex to predict the 24‐month readmission risks (p = 0.008; after adjustment for age and liver enzyme activities: p = 0.012); with higher BMI, the risk increases significantly in males, whereas for females, the risk tends to decrease. In the group of overweight in‐patients, we found higher readmission rates in males relative to females with an odds ratio of 1.8 (p = 0.038). No such significant effects were found in the other cohorts. This study's findings support previous results, suggesting that the easily accessible BMI may serve as a predictive and sex‐sensitive biomarker for outcome in in‐patients with AUD. Future studies are necessary to elucidate the underlying aetiopathological mechanisms. [ABSTRACT FROM AUTHOR]

Background and aims: Alcohol use disorder (AUD) is a chronic disorder with high relapse rates. There are currently few clinical trials of high frequency repetitive transcranial magnetic stimulation (HF‐rTMS) to reduce alcohol use among AUD patients, and results are mixed. The current study tested the effect of 10 add‐on sessions of HF‐rTMS over the right dorsolateral pre‐frontal cortex (DLPFC) on alcohol use and craving. Design: Single‐center, single blind sham‐controlled parallel‐group RCT (n = 80), with 3 and 6 months follow‐up. Setting: Clinical treatment center in Amsterdam, the Netherlands. Participants: Eighty detoxified and abstinent AUD inpatients in clinical treatment (20 females, average age = 44.35 years). Intervention: Ten sessions of active or sham HF‐rTMS (60 10 Hz trains of 5 sec at 110% motor threshold) over the right DLPFC on 10 consecutive work‐days. Measurements The primary outcome measure is the number of abstinent days over 6‐month follow‐up (FU). Secondary outcome measures are craving over 6‐month FU (alcohol urge questionnaire and obsessive‐compulsive drinking scale), time to first relapse over 6‐month FU and grams of alcohol consumed over 6‐month FU. Additional outcome measures: full abstinence over 6‐month FU and treatment success over 12‐month FU. Findings HF‐rTMS did not affect the number of abstinent days over 6 months FU [sham = 124 ± 65.9 days, active = 115 ± 69.8 days, difference: 9 days, 95% confidence interval (CI) = Poisson model: 0.578–3.547]. Moreover, HF‐rTMS did not affect craving (AUQ/OCDS) (sham = 15.38/5.28, active = 17.48/4.75, differences = 2.1/−0.53, 95% CI mixed‐effects model = −9.14 to 2.07/−1.44 to 2.40). Conclusions: There was no clear evidence that high‐frequency repetitive transcranial magnetic stimulation over the right dorsolateral pre‐frontal cortex treatment has a long‐term positive effect on alcohol use or craving as add‐on treatment for alcohol use disorder. High treatment response at 6‐month follow‐up could have limited the possibility to find an effect. [ABSTRACT FROM AUTHOR]

Background and aims: Tolerance to the effects of alcohol is an important element in the diagnosis of alcohol use disorders (AUD); however, there is ongoing debate about its utility in the diagnosis AUD in adolescents and young adults. This study aimed to refine the assessment of tolerance in young adults by testing different definitions of tolerance and their associations with longitudinal AUD outcomes. Design: Prospective cohort study. Settings Australia. Participants: A contemporary cohort of emerging adults across Australia (n = 565, mean age = 18.9, range = 18–21 at baseline). Measurements: Clinician‐administered Structured Clinical Interview for DSM‐IV Research Version (SCID‐IV‐RV) assessed for AUD criteria across five interviews, at 6‐month intervals over 2.5 years. Tolerance definitions were operationalized using survey‐type response (yes/no), clinician judgement (SCID‐IV‐RV), different initial drinking quantity and percentage increase thresholds and average heavy consumption metrics. AUD persistence was operationalized by the number of times AUD was present across the 2.5‐year study period (n = 491), and new‐onset AUD was operationalized as any new incidence of AUD during the follow‐up period (n = 461). Findings The (i) SCID‐IV‐RV clinician judgement [odds ratio (OR) = 2.50, P = 0.005], (ii) an initial drinking quantity threshold of four to five drinks and 50% minimum increase (OR = 2.48, P = 0.007) and (iii) 50% increase only (OR = 2.40, P = 0.005) were the tolerance definitions more strongly associated with any new onset of AUD throughout the four follow‐up time‐points than other definitions. However, these definitions were not associated with persistent AUD (Ps > 0.05). Average heavy consumption definitions of tolerance were most strongly associated with persistent AUD (OR = 6.66, P = 0.001; OR = 4.65, P = 0.004) but not associated with new‐onset AUD (Ps > 0.05). Conclusions: Initial drink and percentage change thresholds appear to improve the efficacy of change‐based tolerance as an indicator for new‐onset alcohol use disorder diagnosis in self‐report surveys of young adults. When predicting persistent alcohol use disorder, average heavy consumption‐based indicators appear to be a better way to measure tolerance than self‐reported change‐based definitions. [ABSTRACT FROM AUTHOR]

Background and aims: Approach bias modification (ApBM) targeting alcohol approach bias has been previously shown to reduce likelihood of relapse during the first 2 weeks following inpatient withdrawal treatment (IWT). We tested whether ApBM's effects endure for a longer period by analysing alcohol use outcomes 3, 6 and 12 months post‐discharge. Design: A double‐blind, sham‐controlled randomized controlled trial. Setting: Four IWT units in Melbourne, Australia. Participants: Three hundred alcohol IWT patients (173 men, 126 women, 1 non‐binary; mean age 43.5 years) were recruited between 4 June 2017 and 14 July 2019. Follow‐up data collection was completed on 22 September 2020. Intervention and control training: Four ApBM sessions were delivered during IWT. ApBM trained participants (n = 147) to avoid alcohol and approach non‐alcohol beverage cues. Controls (n = 153) responded to the same stimuli, but without approach/avoidance training. Measurements Date of first lapse was recorded for non‐abstinent participants to determine time to first lapse. Time‐line follow‐back interviews assessed past‐month alcohol consumption at each follow‐up, with participants reporting no alcohol consumption classified as abstinent. In analyses of past‐month abstinence, non‐abstinence was assumed in participants lost to follow‐up. Number of past‐month drinking days, standard drinks and heavy drinking days (five or more standard drinks for women or non‐binary; six or more standard drinks for men) were calculated for non‐abstinent participants at each follow‐up. Findings ApBM significantly delayed time to first lapse [ApBM median: 53 days, 95% confidence interval (CI) = 21–61; controls = 12 days, 95% CI = 9–21, P = 0.045]. Past‐month abstinence rates at 3‐, 6‐ and 12‐month follow‐ups were 33/153 (21.6%), 30/153 (19.6%), and 24/153 (15.7%) in controls; and 51/147 (34.7%), 30/147 (20.4%) and 29/147 (19.7%) in the ApBM group, respectively. Past‐month abstinence was significantly more likely in ApBM participants than controls at the 3‐month follow‐up [odds ratio (OR) = 1.93, 95% CI = 1.16–3.23, P = 0.012], but not at 6‐ or 12‐month follow‐ups (6‐month OR = 1.05, 95% CI = 0.60–1.95, P = 0.862; 12‐month OR = 1.32, 95% CI = 0.73–2.40, P = 0.360). No significant group differences were found for indices of alcohol consumption in non‐abstinent participants. Conclusions: Approach bias modification for alcohol delivered during inpatient withdrawal treatment helps to prevent relapse, increasing rates of abstinence from alcohol for at least 3 months post‐discharge. [ABSTRACT FROM AUTHOR]

Aims: To (1) measure the aggregated effect size of empathy deficits in individuals with alcohol use disorder (AUD) compared with healthy controls, (2) measure the aggregated effect sizes for associations between lower empathy and heavier alcohol consumption and more alcohol problems in non‐clinical samples and (3) identify potential moderators on the variability of effect sizes across studies in these meta‐analyses. Method: PsycINFO, PubMed and Google Scholar were searched following a pre‐registered International Prospective Register of Systematic Reviews (PROSPERO) protocol (CRD42021225392) and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) methodology. We meta‐analyzed (using random‐effects models) mean differences in empathy between individuals with AUD compared with healthy controls and associations between empathy and alcohol consumption and alcohol problems in non‐clinical samples. A total of 714 participants were included in the meta‐analysis on clinical samples; 3955 were included in the meta‐analyses on non‐clinical samples. Results: Individuals with AUD reported significantly lower empathy than healthy controls [Hedges' g = −0.53, 95% confidence interval (CI) = −0.91, –0.16, k = 9, P < 0.01, Q = 40.09, I2 = 80.04]. Study quality [Q = 1.88, degrees of freedom (d.f.) = 1, P = 0.17] and gender (β = −0.006, Z = −0.60, P = 0.55) were not moderators. Increases in age corresponded to an increase in effect size (β = 0.095, Z = 3.34, P < 0.001). Individuals with AUD (versus healthy controls) had significantly lower cognitive (Hedges' g = −0.44, CI = −0.79, –0.10, P < 0.05), but not affective empathy (Hedges' g = −0.19, CI = −0.51, 0.14, P = 0.27), and the difference between these was significant (Z = 2.34, k = 6, P < 0.01). In non‐clinical samples, individuals with lower (versus higher) empathy reported heavier alcohol consumption (r = −0.12, CI = −0.15, –0.09, k = 11, P < 0.001, Q = 9.68, I2 = 0.00) and more alcohol problems (r = −0.08, CI = −0.14, –0.01, k = 7, P = 0.021, Q = 6.55, I2 = 8.34). There was no significant heterogeneity across studies. Conclusion: Individuals with alcohol use disorder appear to show deficits in empathy compared with healthy controls. Deficits are particularly pronounced for older individuals and for cognitive (versus affective) empathy. In non‐clinical samples, lower empathy appears to be associated with heavier alcohol consumption and more alcohol problems. [ABSTRACT FROM AUTHOR]

Introduction: Exercise is a promising treatment option for individuals with alcohol use disorder, but qualitative studies are lacking. Our aim was to explore experiences of yoga and aerobic exercise among non‐treatment‐seeking adults with alcohol use disorder. Methods: Semi‐structured qualitative interviews (face‐to‐face or telephone) with 12 participants from a randomised controlled trial. Qualitative content analysis was used to analyse data. Results: One main category was identified, motivating and maintaining a lifestyle change, including four generic categories: (i) Initiating factors for lifestyle change, which describes how the concept of a lifestyle change initiated participants change; (ii) Influencing lifestyle change, explains how mood‐enhancing effects from exercise influence exercise behaviours; (iii) Influencing physical and mental health, which describes how improvements in physical and mental health influence self‐confidence and self‐esteem; and (iv) Influencing alcohol consumption, which describes how exercise reduced alcohol cravings and that success in changing exercise behaviours made participants take healthier decisions regarding their alcohol intake. Discussion and Conclusions: Exercise may help reduce alcohol intake, especially when presented in the context of a lifestyle change. Being able to self‐select the type of exercise may increase compliance and optimise these benefits. Intentional planning and positive results from exercise may strengthen the individual's self‐efficacy and increase the motivation to change behaviours associated with alcohol consumption. [ABSTRACT FROM AUTHOR]

Background and aims: For most treatment‐seeking patients with severe Alcohol Use Disorder (AUD), abstinence is the clinically indicated goal. Existing AUD motivation scales are non‐specific about treatment consumption goals, which limit their effectiveness. Desires and mental imagery are relevant in the motivation for AUD treatment engagement. The Motivational Thought Frequency Scale for an abstinence goal (MTF‐A) was adapted from the MTF for controlled drinking (MTF‐CD). This study psychometrically evaluated the MTF‐A in an alcohol‐dependent sample engaged in treatment with a goal of abstinence. To enhance the clinical utility of the scale, a secondary aim was to evaluate a psychometrically equivalent short version of the MTF‐A. Method: A sample N of 329 treatment‐seeking patients with AUD (mean age of 44.44 years, SD = 11.89 years, 72% male) who were undertaking a cognitive behavioral treatment (CBT) program for abstinence completed the Motivational Thought Frequency Scale for Abstinence (MTF‐A) and the Severity of Alcohol Dependence Questionnaire (SADQ). The MTF‐A measured motivation for abstinence through four factors: intensity, self‐efficacy imagery, incentives imagery, and availability. Confirmatory factor analyses (CFAs) were conducted to examine factor structure and model fit. Cronbach's alpha assessed internal consistency. Predictive validity was determined by logistic regression predicting first‐session treatment non‐attendance and alcohol consumption between baseline assessment and commencement of treatment, controlling for potential confounds. Results: A four‐factor structure provided the best fit for the MTF‐A, compared with one‐ and three‐factor models. A shortened 9‐item MTF‐A scale (S‐MTF‐A) provided better fit than the 13‐item MTF‐A scale. Both MTF‐A and S‐MTF‐A displayed good internal consistency. Although both MTF‐A and S‐MTF‐A successfully predicted first‐session treatment non‐attendance, neither predicted alcohol consumption between the baseline assessment and commencement of treatment. Conclusions: The model fit of the four‐factor, 9‐item S‐MTF‐A was superior to the original 13‐item MTF‐A. Both scales were predictive of participation of AUD treatment. Desires and mental imagery play an important role in AUD treatment motivation. [ABSTRACT FROM AUTHOR]

In Dec. 2019‐January 2020, a pneumonia illness originating in Wuhan, China, designated as coronavirus disease 2019 (COVID‐19) was shown to be caused by a novel RNA coronavirus designated as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). People with advanced age, male sex, and/or underlying health conditions (obesity, type 2 diabetes, cardiovascular disease, hypertension, chronic kidney disease, and chronic lung disease) are especially vulnerable to severe COVID‐19 symptoms and death. These risk factors impact the immune system and are also associated with poor health, chronic illness, and shortened longevity. However, a large percent of patients without these known risk factors also develops severe COVID‐19 disease that can result in death. Thus, there must exist risk factors that promote exaggerated inflammatory and immune response to the SARS‐CoV‐2 virus leading to death. One such risk factor may be alcohol misuse and alcohol use disorder because these can exacerbate viral lung infections like SARS, influenza, and pneumonia. Thus, it is highly plausible that alcohol misuse is a risk factor for either increased infection rate when individuals are exposed to SARS‐CoV‐2 virus and/or more severe COVID‐19 in infected patients. Alcohol use is a well‐known risk factor for lung diseases and ARDS in SARS patients. We propose that alcohol has three key pathogenic elements in common with other COVID‐19 severity risk factors: namely, inflammatory microbiota dysbiosis, leaky gut, and systemic activation of the NLRP3 inflammasome. We also propose that these three elements represent targets for therapy for severe COVID‐19. [ABSTRACT FROM AUTHOR]

Background: In a previous study, ondansetron, a serotonin 5‐HT3 receptor antagonist, reduced drinking intensity (drinks/drinking day [DPDD]) among European‐ancestry (EA) participants with moderate‐to‐severe alcohol use disorder (AUD) and variants in genes encoding the serotonin transporter (SLC6A4) and 5‐HT3A (HTR3A), and 5‐HT3B (HTR3B) receptors. We tested whether (1) ondansetron reduces DPDD among individuals of either European or African ancestry (AA), and (2) that reductions in DPDD are greatest among ondansetron‐treated individuals with population‐specific combinations of genotypes at SLC6A4, HTR3A, and HTR3B. Methods: In this 16‐week, double‐blind, placebo‐controlled, parallel‐group clinical trial, adults with AUD were randomized to receive low‐dose oral ondansetron (0.33 mg twice daily) or placebo stratified by "responsive" versus "nonresponsive" genotype defined using population‐specific genotypes at the three genetic loci. Generalized estimating equation regression models and a modified intent‐to‐treat analysis were used to compare the treatment groups on the primary outcome—DPDD—and two secondary outcomes—heavy drinking days per week [HDD] and drinks per day [DPD] across the 16 weeks of treatment. Results: Of 296 prospective participants screened, 95 (58 EA and 37 AA) were randomized and received at least one dose of study medication. In the modified intent‐to‐treat analysis, the ondansetron group averaged 0.40 more DPDD (p = 0.51), 1.35 times as many HDD (p = 0.16), and 1.06 times as many DPD (p = 0.59) as the placebo group. There were no significant interactions with genotype. There were no study‐related serious adverse events (AEs) and similar proportions of participants in the two treatment groups experienced AEs across organ systems. Conclusions: We found no evidence that low‐dose oral ondansetron is beneficial in the treatment of AUD, irrespective of genotype, thus failing to confirm prior study findings. However, the study was underpowered to identify medication by genotype interactions. [ABSTRACT FROM AUTHOR]

Background: Ongoing alcohol use is strongly associated with progressive liver damage and higher mortality in patients with alcohol‐related liver disease (ArLD). Reduction in alcohol use is therefore the cornerstone of treatment to improve the long‐term outcome of these patients. However, a large proportion of patients continue to use alcohol and do not access or engage with alcohol treatment services after a diagnosis of ArLD. We reviewed the literature on factors associated with ongoing alcohol consumption among patients with ArLD to identify barriers or facilitators to their accessing alcohol treatment. Methods: A search of MEDLINE and EMBASE was conducted using search strategies relating to ArLD and the psychosocial factors hypothesized to influence alcohol reduction and/or abstinence. Results: There were few relevant studies pertinent to this population group. Several studies reported a high prevalence of mental health diagnoses associated with the severity of alcohol dependence. Social and environmental factors were shown to be important determinants of alcohol use. Common themes perceived as barriers to treatment from qualitative interviews with ArLD patients across studies included poor communication between the clinical team and patient, lack of symptoms recognized by patients themselves, and perceived loss of control over their condition. Conclusions: We recommend that future clinical studies of patient cohorts with ArLD include detailed psychosocial assessments to capture information on mental health and social factors. Qualitative studies are required to explore the patient journey pre and post hospital admission, which should focus on identifying facilitators and barriers to accessing treatment. Well‐designed, controlled studies are needed to identify patient, social, and environmental factors associated with relapse to alcohol use after a diagnosis of ArLD. These data will enable us to adapt our support for patients to enhance engagement with services and improve long‐term outcomes. [ABSTRACT FROM AUTHOR]

Ibudilast, a neuroimmune modulator, shows promise as a pharmacotherapy for alcohol use disorder (AUD). In vivo administration of ibudilast reduces the expression of pro-inflammatory cytokines in animal models, but its effects on markers of inflammation in humans are unknown. This preliminary study examined the effect of ibudilast on peripheral and potential central markers of inflammation in individuals with AUD. This study also explored the predictive relationship of neurometabolite markers with subsequent drinking in the trial. Non-treatment-seeking individuals with an AUD (n = 52) were randomized to receive oral ibudilast (n = 24) or placebo (n = 28) for 2 weeks. Plasma levels of peripheral inflammatory markers were measured at baseline and after 1 and 2 weeks of medication. At study mid-point, proton magnetic resonance spectroscopy was performed to measure potential neurometabolite markers of inflammation: choline-compounds (Cho), myo-inositol (MI) and creatine + phosphocreatine (Cr) in frontal and cingulate cortices from 43 participants (ibudilast: n = 20; placebo: n = 23). The treatment groups were compared on peripheral and central markers. Ibudilast-treated participants had lower Cho in superior frontal white matter and nominally lower MI in pregenual anterior cingulate cortex. Ibudilast-treated participants had nominally lower C-reactive protein levels at visit 2 and nominally lower TNF-α/IL-10 ratios, relative to placebo. C-reactive protein and Cho levels were correlated, controlling for medication. Superior frontal white matter Cho predicted drinking in the following week. Micro-longitudinal ibudilast treatment may induce peripheral and putative central anti-inflammatory responses in patients with AUD. The neurometabolite responses may be associated with reduction in drinking, suggesting an anti-inflammatory component to the therapeutic action of ibudilast. [ABSTRACT FROM AUTHOR]