Heavy Drinking Days Research Articles

A randomized trial testing digital medicine support models for mild-to-moderate alcohol use disorder

This paper reports the results of a hybrid effectiveness-implementation randomized trial that systematically varied levels of human oversight required to support the implementation of a digital medicine intervention for persons with mild-to-moderate alcohol use disorder (AUD). Participants were randomly assigned to three groups representing possible digital health support models within a health system: self-monitored use (SM; n = 185), peer-supported use (PS; n = 186), or a clinically integrated model CI; (n = 187). Across all three groups, the percentage of self-reported heavy drinking days dropped from 38.4% at baseline (95% CI [35.8%, 41%]) to 22.5% (19.5%, 25.5%) at 12 months. The clinically integrated group showed significant improvements in mental health and quality of life compared to the self-monitoring group (p = 0.011). However, higher attrition rates in the clinically integrated group warrant consideration in interpreting this result. Results suggest that making a self-guided digital intervention available to patients may be a viable option for health systems looking to promote alcohol risk reduction. This study was prospectively registered at clinicaltrials.gov on 7/03/2019 (NCT04011644).

The combination of donepezil and cognitive training for improving treatment outcomes for alcohol use disorder: Design of a randomized controlled trial

BackgroundThe development of alcohol use disorder (AUD) is a major concern in public health, and cognitive impairments caused by alcohol are involved in this process. Emerging neurobiological evidence suggests that donepezil, an anticholinesterase agent, may improve AUD treatment outcomes by enhancing neurocognitive functioning. Previous research has also suggested that cognitive remediation therapy (CRT) could potentially improve cognitive function and AUD treatment outcomes. We present the rationale and design of a trial to evaluate the combination of donepezil and cognitive remediation therapy (donepezil + CRT) as an intervention for AUD. MethodsWe propose a 13-week, randomized, double-blind, placebo-controlled, between-subjects trial comparing 4 groups (donepezil + CRT vs. donepezil alone vs. CRT alone vs. placebos) as an intervention for AUD. The main goal of the study is to evaluate if donepezil + CRT is superior to placebo in reducing heavy drinking days and improving neurocognitive functioning. A total of 160 patients (4 groups, 40 per each group) with AUD between the ages of 18–80 years will be recruited at Yale University and the VA Connecticut Healthcare System. Primary outcome measures include 1) heavy drinking by Timeline Follow Back (TLFB) over 13 weeks and 2) global neurocognitive functioning by a global index of neurocognitive function score at 7 and 13 weeks. DiscussionThis protocol paper describes the rationale and proposed methods for the randomized controlled trial for improving AUD treatment outcomes. This project has significant clinical potential to help patients suffering from AUD by improving their cognition and reducing alcohol consumption.Trial Registration:NCT05042102

A smartphone app-based intervention combined with face-to-face sessions for alcohol dependence at internal medicine clinics: A randomized controlled trial

BackgroundAddressing the limited access to treatments for alcohol dependence, we developed ALM-002, a therapeutic application to be “prescribed” for non-abstinence-oriented treatment in internal medicine settings. Our objective was to preliminarily assess the efficacy and safety of ALM-002. MethodsIn a multicenter, open-label randomized controlled trial, participants aged ≥20 with alcohol dependence and daily alcohol consumption exceeding 60 g for men and 40 g for women, without severe complications, were randomly assigned to either the intervention group using ALM-002 or the treatment-as-usual control group. Participant in both groups received individual face-to-face sessions by physicians at weeks 0, 4, 8, and 12. The primary endpoint was the change in heavy drinking days (HDDs) from week 0 to week 12. A mixed model for repeated measures was employed. ResultsWe enrolled 43 participants: 22 in the intervention group and 21 in the control group. A significant reduction in HDDs every 4 weeks from week 0 to week 12 was observed, with a between-group difference of −6.99 days (95% CI: −12.4 to −1.6 days, standardized mean difference: −0.80). ConclusionsThese results indicate the potential of ALM-002 as a viable treatment for alcohol dependence. Further studies are needed to evaluate the clinical potential of ALM-002.

Applying behavioral economics to understand changes in alcohol outcomes during the transition to adulthood: Longitudinal relations and differences by sex and race.

Population drinking trends show clear developmental periodicity, with steep increases in harmful alcohol use from ages 18 to 22 followed by a gradual decline across the 20s, albeit with persistent problematic use in a subgroup of individuals. Cross-sectional studies implicate behavioral economic indicators of alcohol overvaluation (high alcohol demand) and lack of alternative substance-free reinforcers (high proportionate alcohol-related reinforcement) as potential predictors of change during this developmental window, but longitudinal evidence is sparse. Using a sample of emerging adults (N = 497, Mage = 22.61 years, 62% female, 48.69% White, 40.44% Black), this study examined prospective, bidirectional relations between both past-week heavy drinking days (HDD) and alcohol problems and proportionate alcohol-related reinforcement (reinforcement ratio), alcohol demand intensity (consumption at zero price), alcohol demand Omax (maximum expenditure), and change in demand elasticity (rate of change in consumption across escalating price) over five assessments (every 4 months) using random intercept cross-lagged panel models. Alcohol problems and HDD decreased across assessments. Significant between-person effects indicated that each behavioral economic variable was associated with increased drinking risk. Change in reinforcement ratio was positively associated with decreases in alcohol problems. Multigroup invariance modeling revealed distinct risk pathways in that change in demand intensity and Omax predicted change in alcohol problems for male participants and change in intensity predicted change in alcohol problems for non-White participants. The study provides consistent support for proportionate alcohol-related reinforcement and mixed support for demand as within-person predictors of reductions in drinking. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Young adults' change talk within brief motivational intervention in the emergency department and booster sessions is associated with a decrease in heavy drinking over 1 year.

Investigate the effect of change talk (CT) within successive brief motivational interventions (BMIs) as a mechanism of change for alcohol use. We conducted a secondary analysis of data from a randomized controlled trial in which 344 young adults (18-35 years old) admitted to a Swiss emergency department with alcohol intoxication received either BMI (N = 171) or brief advice (N = 173). Participants with a baseline audio-recorded BMI were included (N = 140; median age 23 [Q1-Q3: 20-27], 72.9% men). Up to three booster sessions by phone were offered at 1 week, 1 month, and 3 months. Percent CT and CT Average Strength were used as predictor variables. The outcome was the number of heavy drinking days (HDD) over the 30 days prior to research assessments at 1-, 3-, 6-, and 12-month follow-up. A latent growth curve modeling framework was first used to estimate predictor and outcome variable growth parameters (i.e., intercept and slope) over time, and then to regress HDD growth parameters on CT growth parameters. CT increased specifically from baseline to the 1-week booster session and thereafter remained stable. Higher baseline CT was associated with lower HDD at 1 month (Percent CT: b = -0.04, 95% confidence interval [-0.06, -0.01]; Average Strength: b = -0.99 [-1.67, -0.31]). An increase in CT from baseline to the 1-week booster session was related to a decrease in HDD from 1 month to 12 months (Percent CT: b = -0.08 [-0.14, -0.03]; Average Strength: b = -2.29 [-3.52, -1.07]). Both baseline CT and CT trajectory over the first week are meaningful predictors of HDD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Internet-delivered therapy for alcohol misuse: engagement, satisfaction, and outcomes when patients select their preference for therapist- or self-guided treatment

BackgroundAlcohol misuse is common and causes substantial harm. Internet-delivered cognitive behaviour therapy (ICBT) is effective in reducing alcohol misuse; however, the literature investigating how treatment outcomes are impacted by patients’ preferences for therapist- versus self-guided ICBT for alcohol misuse is sparse.MethodsIn this preference trial, 74 eligible patients (who reported ≥ 14 drinks in the previous week and obtained scores suggesting hazardous or harmful drinking) chose between enrolling in either therapist- or self-guided ICBT for alcohol misuse. We investigated whether those who chose therapist- versus self-guided ICBT differed in their (a) drinking outcomes—as measured by Timeline Follow-Back (TLFB) and heavy drinking days (HDD) at post-treatment and 3-month follow-up—and (b) post-treatment ICBT engagement and satisfaction.ResultsThe majority (81.1%) of eligible patients chose therapist-guided ICBT. These patients reported higher psychotropic medication use, drinking difficulties, and anxiety symptoms. For both the therapist- and self-guided patients, a modified intention-to-treat analysis revealed large within-group treatment effects for TLFB (β = − 2.64, SE 0.66; p < 0.001) and HDD (β = − 0.34, SE 0.07; p < 0.001), with large pre-to-post-treatment Cohen’s effect sizes of d = 0.97 (95% CI [0.49, 1.45]) for TLFB and d = 1.19 (95% CI [0.69, 1.68]) for HDD. The interaction comparing the effects of therapist- to self-guided ICBT over time was not significant for TLFB (p = 0.34) or HDD (p = 0.06). With treatment, for both therapist- and self-guided patients, there was a significant improvement in drinking difficulties, cravings, and confidence with controlling cravings, as well as in anxiety, depression, and functional impairment. Further, the majority (75.7%) of patients completed five or more lessons, as well as reported overall satisfaction with the treatment (88.9%) and increased confidence in managing their symptoms (86.7%); these outcomes also did not differ between therapist- and self-guided patients.ConclusionsThe current study shows that ICBT for alcohol misuse is associated with reduced drinking and comorbid mental health difficulties over time, irrespective of whether patients chose to complete the course on their own or with therapist guidance.Trial registration number: NCT04611854 (https://clinicaltrials.gov/ct2/show/NCT04611854).

Measurement invariance and other psychometric properties of the Short Inventory of Problems (SIP-2R) across racial groups in adults experiencing homelessness and alcohol use disorder.

People experiencing homelessness are disproportionately impacted by alcohol-related harm. Racially minoritized groups are disproportionately represented in the homeless population and are likewise disproportionately impacted by alcohol-related harm. Most alcohol outcome measures have not been adequately psychometrically studied in this marginalized population and across racial groups. This study documents psychometric properties, including measurement invariance, reliability, and convergent validity, of a measure of alcohol-related harm, the Short Inventory of Problems (SIP-2R), across Black, North American Indigenous (NAI), and White adults experiencing homelessness and alcohol use disorder (AUD). Adults experiencing homelessness and AUD who had participated in one of two randomized controlled trials of harm-reduction treatment (N = 493; NAI = 205, Black = 125, and White = 163) were included in this psychometric study of the 15-item SIP-2R. Multigroup confirmatory factor analysis (MGCFA) indicated that a model comprising one general alcohol-related harm factor overarching five factors, showed close fit and partial scalar invariance, χ²(329, N = 493) = 624.902, p < .001, comparative fit index (CFI) = .966, root-mean-square error of approximation (RMSEA) = .074, 90% CI [.066, .083], standardized root-mean-square residual (SRMR) = .063, confirming acceptable measurement equivalence across racial groups. The SIP-2R showed internal consistency (α = .94, ω = .95) and convergent validity, that is, positive correlation between the total SIP-2R score and the number of drinks consumed the heaviest drinking day, ρ(490) = .30, p < .001. This study provided support for the internal consistency, convergent validity, and cross-group measurement equivalence of the SIP-2R for NAI, Black, and White adults experiencing homelessness with AUD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Treatment responder status and time to response as a function of hazardous drinking among active-duty military receiving variable-length cognitive processing therapy for posttraumatic stress disorder.

A common concern is whether individuals with posttraumatic stress disorder (PTSD) and hazardous drinking will respond to PTSD treatment or need a higher dose. In a sample of active-duty military, we examined the impact of hazardous drinking on cognitive processing therapy (CPT) outcomes and whether number of sessions to reach good end-state or dropout differed by drinking status. Participants included 127 service members participating in a clinical trial of variable-length CPT. The Quick Drinking Screen was used to characterize drinking. Participants were categorized as treatment responders when they reached good end-state (<20 on the PTSD Checklist for DSM-5) or nonresponders if they completed 24 sessions or 18 weeks of treatment without good end-state. Survival analyses were used to compare time to dropout or good end-state between those with and without hazardous drinking. Those with hazardous drinking were as likely as those without to reach good end-state and no more likely to drop out. There were no differences in number of sessions to reach good end-state or dropout. On a gold-standard assessment, those with hazardous drinking evidenced more PTSD symptom reduction than those without. The overall proportion of participants with hazardous drinking decreased (30.7% to 18.6%), as did mean number of drinks per drinking day and drinks on the heaviest drinking day among those initially drinking hazardously. Results support using CPT for military personnel with PTSD and hazardous drinking and indicate that those with hazardous drinking can benefit from PTSD treatment without additional treatment sessions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A Bayesian meta-analysis of topiramate's effectiveness for individuals with alcohol use disorder.

Topiramate (TPM) has the potential to become one of the most prominent treatment options for alcohol use disorder (AUD). We investigated the efficacy of TPM for AUD treatment, considering new randomized controlled trials carried out since the publication of four prior investigations. We searched six major databases, comparing TPM to placebo for AUD treatment. We performed a Bayesian meta-analysis. We conducted a meta-regression, analyzing the effect of age, TPM dosage, duration of treatment, gender, and attrition rate on the outcomes measured. The protocol is registered with PROSPERO: CRD42021286266. TPM reduced heavy drinking days (d = 0.401, Bayes factor (BF) = 23.088) and weeks (d = 0.461, BF = 3.784), lowered alcohol craving (d = 0.477, BF = 107.749), prolonged abstinence throughout the duration of trials (d = 0.505, BF = 54.998), and decreased the amount of gamma-glutamyl transferase in the blood (d = 0.345, BF = 39.048). The analysis pointed out that TPM could reduce anxiety (d = 0.517, BF = 5.993). TPM's efficacy in relieving alcohol withdrawal, minimizing relapse, and decreasing depressive symptoms was inconclusive. There was evidence of a meta-regression effect of attrition rate on heavy drinking days and craving and length of treatment on abstinence. TPM has the potential to become a key pharmacological agent in the treatment of AUD.

The Effect of the First UK COVID-19 Lockdown on Users of the Drink Less App: Interrupted Time Series Analysis of Sociodemographic Characteristics, Engagement, and Alcohol Reduction.

The first UK COVID-19 lockdown had a polarizing impact on drinking behavior and may have impacted engagement with digital interventions to reduce alcohol consumption. We examined the effect of lockdown on engagement, alcohol reduction, and the sociodemographic characteristics of users of the popular and widely available alcohol reduction app Drink Less. This was a natural experiment. The study period spanned 468 days between March 24, 2019, and July 3, 2020, with the introduction of UK lockdown measures beginning on March 24, 2020. Users were 18 years or older, based in the United Kingdom, and interested in drinking less. Interrupted time series analyses using generalized additive mixed models (GAMMs) were conducted for each outcome variable (ie, sociodemographic characteristics, app downloads and engagement levels, alcohol consumption, and extent of alcohol reduction) for existing (downloaded the app prelockdown) and new (downloaded the app during the lockdown) users of the app. Among existing users of the Drink Less app, there were increases in the time spent on the app per day (B=0.01, P=.01), mean units of alcohol recorded per day (B>0.00 P=.02), and mean heavy drinking (>6 units) days (B>0.00, P=.02) during the lockdown. Previous declines in new app downloads plateaued during the lockdown (incidence rate ratio [IRR]=1.00, P=.18). Among new app users, there was an increase in the proportion of female users (B>0.00, P=.04) and those at risk of alcohol dependence (B>0.00, P=.01) and a decrease in the proportion of nonmanual workers (B>-0.00, P=.04). Among new app users, there were step increases in the mean number of alcohol units per day (B=20.12, P=.03), heavy-drinking days (B=1.38, P=.01), and the number of days the app was used (B=2.05, P=.02), alongside a step decrease in the percentage of available screens viewed (B=-0.03, P=.04), indicating users were using less of the intervention components within the app. Following the first UK lockdown, there was evidence of increases in engagement and alcohol consumption among new and existing users of the Drink Less app.

Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial.

BackgroundAlcohol use disorder (AUD) is a chronic, relapsing brain disorder that accounts for 5% of deaths annually, and there is an urgent need to develop new targets for therapeutic intervention. The glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduces alcohol consumption in rodents and nonhuman primates, but its efficacy in patients with AUD is unknown.MethodsIn a randomized, double-blinded, placebo-controlled clinical trial, treatment-seeking AUD patients were assigned to receive exenatide (2 mg subcutaneously) or placebo once weekly for 26 weeks, in addition to standard cognitive-behavioral therapy. The primary outcome was reduction in number of heavy drinking days. A subgroup also completed functional MRI (fMRI) and single-photon emission CT (SPECT) brain scans.ResultsA total of 127 patients were enrolled. Our data revealed that although exenatide did not significantly reduce the number of heavy drinking days compared with placebo, it significantly attenuated fMRI alcohol cue reactivity in the ventral striatum and septal area, which are crucial brain areas for drug reward and addiction. In addition, dopamine transporter availability was lower in the exenatide group compared with the placebo group. Exploratory analyses revealed that exenatide significantly reduced heavy drinking days and total alcohol intake in a subgroup of obese patients (BMI > 30 kg/m2). Adverse events were mainly gastrointestinal.ConclusionThis randomized controlled trial on the effects of a GLP-1 receptor agonist in AUD patients provides new important knowledge on the effects of GLP-1 receptor agonists as a novel treatment target in addiction.Trial registrationEudraCT: 2016-003343-11. ClinicalTrials.gov (NCT03232112).FundingNovavi Foundation; Research Foundation, Mental Health Services, Capital Region of Denmark; Research Foundation, Capital Region of Denmark; Ivan Nielsen Foundation; A.P. Moeller Foundation; Augustinus Foundation; Woerzner Foundation; Grosserer L.F. Foghts Foundation; Hartmann Foundation; Aase and Ejnar Danielsen Foundation; P.A. Messerschmidt and Wife Foundation; and Lundbeck Foundation.

THE TROJAN HORSE: A CASE OF HEMORRHAGIC PANCREATITIS

THE TROJAN HORSE: A CASE OF HEMORRHAGIC PANCREATITIS

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder

Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy. In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD. Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy. The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance. A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin. Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD. ClinicalTrials.gov Identifier: NCT02061293.

Effectiveness of Varenicline and Cytisine for Alcohol Use Reduction Among People With HIV and Substance Use

Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking but are unproven for alcohol, and clinical trials rarely include individuals with HIV, substance use, and mental health conditions. To compare the effects on drinking and smoking of nicotinic acetylcholine receptor partial agonists varenicline and cytisine with those of NRT. This 4-group randomized, double-blinded, placebo-controlled clinical trial was conducted from July 2017 to December 2020 in St Petersburg, Russia. Included participants were 400 individuals with HIV who engaged in risky drinking (≥5 prior-month heavy-drinking days [HDDs]) and daily smoking; they were followed up for 12 months after enrollment. Data were analyzed from May 2021 through June 2022. Participants received alcohol and tobacco counseling, 1 active medication, and 1 placebo in 1 of 4 groups: active varenicline and placebo NRT (group 1), placebo varenicline and active NRT (group 2), active cytisine and placebo NRT (group 3), or placebo cytisine and active NRT (group 4). The primary outcome was number of prior-month HDDs at 3 months. Secondary outcomes included biochemically validated abstinence from alcohol at 3 months and smoking at 6 months. Among 400 participants (263 [65.8%] men; mean [SD] age, 39 [6] years), 97 individuals (24.3%) used opioids and 156 individuals (39.1%) had depressive symptoms. These individuals had a mean (SD) CD4 count of 391 (257) cells/mm3, smoked a mean (SD) of 21 [8] cigarettes/d, and reported a mean (SD) of 9.3 (5.8) HDDs in the prior 30 days. At 3 months, the mean (SD) number of HDDs was decreased vs baseline across all groups (group 1: 2.0 [3.8] HDDs vs. 9.5 [6.1] HDDs; group 2: 2.1 [4.3] HDDs vs 9.3 [5.7] HDDs; group 3: 1.5 [3.3] HDDs vs 8.9 [5.0] HDDs; group 4: 2.4 [5.2] HDDs vs 9.6 [6.3] HDDs). There were no significant differences at 3 months between groups in mean (SD) HDDs, including group 1 vs 2 (incident rate ratio [IRR], 0.94; 95% CI, 0.49-1.79), 3 vs 4 (IRR, 0.60; 95% CI, 0.30-1.18), and 1 vs 3 (IRR, 1.29; 95% CI, 0.65-2.55). There were no significant differences at 6 months between groups in smoking abstinence, including group 1 vs 2 (15 of 100 individuals [15.0%] vs 17 of 99 individuals [17.2%]; odds ratio [OR],0.89; 95% CI, 0.38-2.08), 3 vs 4 (19 of 100 individuals [19.0%] vs 19 of 101 individuals [18.8%]; OR, 1.00; 95% CI, 0.46-2.17), and 1 vs 3 (OR, 0.79; 95% CI, 0.35-1.78). Post hoc analyses suggested lower mean (SD) HDDs (eg, at 3 months: 0.7 [1.8] HDDs vs 2.3 [4.6] HDDs) and higher alcohol abstinence (eg, at 3 months: 30 of 85 individuals [35.3%] vs 54 of 315 individuals [17.1%]) among those who quit vs continued smoking. This study found that among individuals with HIV who engaged in risky drinking and smoking, varenicline and cytisine were not more efficacious than NRT to treat risky drinking and smoking but that behavior change rates were high in all groups. ClinicalTrials.gov Identifier: NCT02797587.

Predicting severe alcohol use disorders in primary care using number of heavy drinking days.

Although screening for unhealthy alcohol use is becoming more common, severe alcohol use disorders (AUDs) associated with the most severe medical and socio-economic sequelae still often go unidentified in primary care. To improve identification of severe AUDs and aid clinical decision-making, we aimed to identify a threshold of heavy drinking days (HDDs) associated with severe AUDs. This cohort study analyzed electronic health record data of 138 765 adults who reported ≥ 1 HDD (4+ drinks/occasion for women and men aged ≥ 65 years, 5+ for men aged 18-64 years) during a 3-month period at a routine alcohol screening in primary care in a large Northern California, USA health-care system from 2014 to 2017. Our sample was 66.5% male, 59.7% white, 11.0% Asian/Pacific Islander, 5.0% black, 17.4% Latino/Hispanic and 7.0% other/unknown race/ethnicity; the mean age was 40.6years (standard deviation = 15.2). We compared sensitivity and specificity of different thresholds of the reported number of HDDs during a 3-month period for predicting severe AUD diagnoses in the following year, in the full sample and by sex and age. The prevalence of severe AUD diagnoses in the year after the screening was 0.6%. The optimal threshold predicting future severe AUD diagnoses in the full sample was ≥ 5 HDDs during a 3-month period [sensitivity = 68.9%, 95% confidence interval (CI) = 65.9, 72.0; specificity = 63.2%, 95% CI = 62.9, 63.4], but varied by sex and age. Women had a lower threshold than men (4 versus 6 HDDs), which decreased as women aged (from 5 HDDs among 18-24 years to 4 HDDs ≥ 25 years), but increased as men aged (from 5 HDDs among 18-24 years to 6 HDDs among 25-64 years, to 7 HDDs ≥ 65 years). Five or more heavy drinking days in a 3-month period may indicate heightened risk of future severe alcohol use disorder in an adult primary care population. The optimal thresholds are lower for women than for men, and thresholds decrease as women age but increase as men age.

Theragnostic Efficacy of K18 Response in Alcohol Use Disorder with Clinically Significant Fibrosis Using Gut-Liver Axis.

(1) Background: Fibrosis in early-stage alcohol-associated liver disease (ALD) is commonly under-diagnosed in routine clinical practice. This study characterized the liver-injury and cell death response in alcohol use disorder (AUD) patients with ALD who also exhibited fibrosis and assessed the efficacy of standard of care (SOC) treatment in the improvement in liver injury. (2) Methods: Forty-eight heavy-drinking AUD patients aged 21–65 yrs. without clinical manifestations of liver injury were grouped by Fibrosis-4 (FIB-4) score, as negative (Gr.1 < 1.45, n = 21) or positive (Gr.2 ≥ 1.45, n = 27). Patients received 2-weeks (2 w) inpatient SOC. Data on demographics, drinking patterns, liver-injury, immune markers, and liver cell death (K18s) markers were analyzed at baseline (BL) and after 2 w SOC. (3) Results: Lifetime drinking (LTDH, yrs.) and acute heavy drinking (Heavy Drinking Days Past 90 Days [HDD90]) markers were significantly higher in Gr.2 vs. Gr.1. BL ALT, AST, AST:ALT and K18M65 were considerably higher in Gr.2. Dysregulated gut dysfunction and elevated immune activity were evident in Gr.2 characterized by TNF-α, IL-8 and LPS levels. After SOC, Gr.2 showed improvement in AST, ALT, AST/ALT ratio; and in the K18M65, K18M30 and K18M65/M30 ratio vs. Gr.1. The true positivity of BL IL-8 response to predict the improvement in K18M65 to normal levels among Gr.2 patients against those who did not have improvement after 2 w SOC was very high (AUROC = 0.830, p = 0.042). (4) Conclusions: Gut dysfunction, elevated cytokine response and necrotic liver cell death were elevated in AUD patients with early-stage ALD. K18 showed promise as a predictive theragnostic factor to differentiate among the AUD patients with early-stage ALD and baseline fibrosis who had improvement in liver injury against those who did not, by the levels of baseline IL-8.

Impact of the policy environment on substance use among sexual minority women

BackgroundSexual minority women (SMW) are at greater risk for heavy episodic drinking, frequent marijuana use, and tobacco use than heterosexual women. Because past research has suggested the political and social environment may influence disparities in substance use by sexual orientation, this study examined associations of the U.S. state-level policy environment on substance use by SMW. MethodsA total of 732 SMW participants were recruited from two national online panels: a general population panel (n = 333) and a sexual minority-specific panel (n = 399). Past year substance use was defined by number of days of heavy episodic drinking (HED; 4+ drinks in a day), weekly tobacco use (once a week or more vs. less or none), and weekly marijuana use (once a week or more vs. less or none). Comprehensive state policy protection was defined by enactment of five policies protecting rights of sexual minorities. Regression models compared substance use outcomes for SMW living in states with comprehensive policy protections to SMW living in states with fewer or no protections. Models also assessed the impact of state policies related to alcohol (state monopoly on alcohol wholesale or retail sales), tobacco (state enactment of comprehensive smoke-free workplace laws) and marijuana (legalization of purchase, possession, or consumption of marijuana for recreational use). ResultsComprehensive policy protections were associated with fewer HED days. Recreational marijuana legalization was associated with higher odds of weekly use. ConclusionsFindings underscore the importance of policy protections for sexual minorities in reducing substance use, particularly HED, among SMW.

Effect of Combination Treatment With Varenicline and Nicotine Patch on Smoking Cessation Among Smokers Who Drink Heavily

The concurrent use of both tobacco and alcohol causes substantial disease and early mortality, and smokers who drink heavily tend to be less successful in smoking cessation than smokers who do not. Although varenicline combined with nicotine replacement therapy for smoking cessation has been examined among smokers who do not drink heavily, this combination treatment has not yet been examined among smokers who drink heavily. To determine whether combined treatment with varenicline tartrate and nicotine patch improves continuous abstinence from cigarette smoking among smokers who drink heavily. This double-blind, placebo-controlled, superiority randomized clinical trial evaluated combined treatment with varenicline and nicotine patch compared with placebo and nicotine patch for smoking cessation (primary outcome) and drinking behavior (secondary outcome) among smokers who drink heavily. The clinical trial was conducted at 2 outpatient sites in Chicago, Illinois, with enrollment from March 26, 2018, to February 14, 2020. The 122 participants were recruited from the community via social media and public transit advertisements and equally randomized to the 2 treatment groups, which were stratified by sex and smoking behavior. Eligible participants smoked between 5 and 30 cigarettes per day and drank heavily (>14 drinks per week for men or >7 drinks per week for women and ≥1 heavy drinking day [defined as >5 drinks per occasion for men or >4 drinks per occasion for women] per month for the past year) and had a desire to quit smoking. Varenicline tartrate, 1.0 mg, twice daily or matching placebo pills twice daily for 12 weeks. Nicotine patch at manufacturer-recommended doses for 10 weeks and brief individual smoking cessation counseling the week before the quit date and on the quit date. The primary outcome was self-reported continuous cigarette abstinence through weeks 9 to 12; abstinence was biochemically confirmed at the week 12 study visit. Secondary outcomes were the frequency of weekly drinking and weekly heavy drinking during the study period. Among 122 participants (mean [SD] age, 44.0 [12.4] years; 67 men [54.9%]), 61 were randomly assigned to receive combined treatment with varenicline and nicotine patch (varenicline group), and 61 were randomly assigned to receive placebo and nicotine patch (placebo group). A total of 54 participants (44.3%) self-identified as Black, 56 (45.9%) as White, and 12 (9.8%) as other races (including American Indian or Alaska Native, Asian, >1 race, and unspecified race). A total of 8 participants (6.6%) self-identified as Hispanic and 114 (93.4%) as non-Hispanic ethnicity. Study retention to 12 weeks was 89%. The intention-to-treat analyses showed higher smoking cessation rates during weeks 9 to 12 in the varenicline group vs the placebo group (27 participants [44.3%] vs 17 participants [27.9%]; odds ratio, 2.20; 95% CI, 1.01-4.80; P = .047) and lower likelihood of relapse throughout treatment in the varenicline group relative to the placebo group (hazard ratio, 0.62; 95% CI, 0.40-0.96; P = .03). Both treatments were well tolerated; however, compared with participants in the placebo group, those in the varenicline group experienced more adverse effects, with 5 participants in the varenicline group discontinuing medication due to adverse effects. In this study, combined treatment with varenicline and nicotine patch was more effective than placebo and nicotine patch for smoking cessation among smokers who drink heavily. The combination treatment had no effect on alcohol consumption, with both groups showing significant reductions. Combination treatment with varenicline and nicotine patch may be a viable option for smokers who drink heavily. ClinicalTrials.gov Identifier: NCT02859142.

Clinical moderators of response to nalmefene in a randomized-controlled trial for alcohol dependence: An exploratory analysis

BackgroundNalmefene is the only medication marketed to reduce the consumption of alcohol in patients with alcohol dependence, but it remains unclear which patients could most benefit from it. This study aimed to identify clinical moderators that affect treatment response to nalmefene in patients with alcohol dependence. MethodsIn a multicenter, randomized, controlled, double-blind, phase 3 study of nalmefene on Japanese patients with alcohol dependence, the relationship between the reduction of heavy drinking days (HDD) and total alcohol consumption (TAC) at 12 and 24 weeks of treatment and baseline variables of the participants were analyzed in a linear regression and multiple adjusted analysis. ResultsAge < 65, no family history of problem drinking, age at onset of problem drinking ≥ 25, and not currently smoking were possible positive moderators. Nalmefene showed a significant HDD reduction in patients with age < 65 or no family history of problem drinking, and a significant TAC reduction in patients with age at onset of problem drinking ≥ 25 or who were not currently smoking. After multiple adjusted analyses, age < 65 (p = .028), no family history of problem drinking (p = .047), and age at onset of problem drinking ≥ 25 (p = .030) were statistically significant. Not currently smoking (p = .071) was marginally significant. In combination, these moderators indicated synergistic effects. ConclusionsAlcohol-dependent patients with favorable prognostic factors such as non-smoking status, no family history of problem drinking, and a late-onset of problem drinking selectively benefit from nalmefene. Further research is needed to validate these exploratory results.

Neurofilament Light Chain as a Biomarker for Monitoring the Efficacy of Transcranial Magnetic Stimulation on Alcohol Use Disorder.

ObjectiveThis study assessed the effects of repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) on serum neurofilament light chain (NfL) levels, alcohol consumption, craving, and psychological impairment in participants with alcohol use disorder (AUD).MethodsParticipants with AUD were randomly assigned to receive one of two treatments (active or sham rTMS). All participants received 10 daily active or sham rTMS sessions over the left DLPFC for 2 weeks, with follow-up visits at baseline and immediately after the completion of the treatments. Serum samples were obtained before and after the intervention. Days of heavy drinking, visual analog scale (VAS) scores, and mental health component scores (MCSs) of the Medical Outcomes Study 36-Item Short Form Health Survey were used to assess the effects of rTMS.ResultsActive rTMS had a significant effect on reducing days of heavy drinking, alcohol craving, and serum NfL levels, and improved social functioning and mental health. The improvement with active rTMS was significantly greater than that with sham rTMS. Correlation analysis revealed that the reduction in the baseline drinking level was positively correlated with declines in the VAS and NfL levels but not with psychological scores.ConclusionRepetitive transcranial magnetic stimulation of the left DLPFC was associated with reducing alcohol consumption and craving in patients with AUD and positively impacted neuropsychological and social function. Serum NfL levels may be useful as an early serological indicator of alcohol-induced brain injury.