Dataset Information

Stability of Drinking Reductions and Long-term Functioning Among Patients with Alcohol Use Disorder.

ABSTRACT:

Background

The World Health Organization (WHO) categorizes alcohol consumption according to grams consumed into low-, medium-, high-, and very-high-risk drinking levels (RDLs). Although abstinence has been considered the ideal outcome of alcohol treatment, reductions in WHO RDLs have been proposed as primary outcomes for alcohol use disorder (AUD) trials.

Objective

The current study examines the stability of WHO RDL reductions and the association between RDL reductions and long-term functioning for up to 3 years following treatment.

Design and participants

Secondary data analysis of patients with AUD enrolled in the COMBINE Study and Project MATCH, two multi-site, randomized AUD clinical trials, who were followed for up to 3 years post-treatment (COMBINE: n?=?694; MATCH: n?=?806).

Measures

Alcohol use was measured via calendar-based methods. We estimated all models in the total sample and among participants who did not achieve abstinence during treatment.

Key results

One-level RDL reductions were achieved by 84% of patients at the end of treatment, with 84.9% of those individuals maintaining that reduction at a 3-year follow-up. Two-level RDL reductions were achieved by 68% of patients at the end of treatment, with 77.7% of those individuals maintaining that reduction at a 3-year follow-up. One- and two-level RDL reductions at the end of treatment were associated with significantly better mental health, quality of life (including physical quality of life), and fewer drinking consequences 3 years after treatment (p?< 0.05), as compared to no change or increased drinking.

Conclusion

AUD patients can maintain WHO RDL reductions for up to 3 years after treatment. Patients who had WHO RDL reductions functioned significantly better than those who did not reduce their drinking. These findings are consistent with prior reports suggesting that drinking reductions, short of abstinence, yield meaningful improvements in patient health, well-being, and functioning.

SUBMITTER: Witkiewitz K

PROVIDER: S-EPMC7878601 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Stability of Drinking Reductions and Long-term Functioning Among Patients with Alcohol Use Disorder.

Witkiewitz Katie K Kranzler Henry R HR Hallgren Kevin A KA Hasin Deborah S DS Aldridge Arnie P AP Zarkin Gary A GA Mann Karl F KF O'Malley Stephanie S SS Anton Raymond F RF

Journal of general internal medicine 20201112 2

<h4>Background</h4>The World Health Organization (WHO) categorizes alcohol consumption according to grams consumed into low-, medium-, high-, and very-high-risk drinking levels (RDLs). Although abstinence has been considered the ideal outcome of alcohol treatment, reductions in WHO RDLs have been proposed as primary outcomes for alcohol use disorder (AUD) trials.<h4>Objective</h4>The current study examines the stability of WHO RDL reductions and the association between RDL reductions and long-te ...[more]

PMID: 33180306

Similar Datasets

Project description:BackgroundReductions in the World Health Organization (WHO) risk drinking levels have been proposed as an alternative primary outcome for alcohol clinical trials. Yet, little is known about whether reductions in WHO risk drinking levels can be maintained over time. The current study examined whether reductions in WHO risk drinking levels were maintained for up to 1 year following treatment, and whether reductions over time were associated with improvements in functioning.MethodsSecondary data analysis of individuals with alcohol dependence (n = 1,226) enrolled in the COMBINE study, a multisite, randomized, placebo-controlled clinical trial. Logistic regression was used to examine the maintenance of end-of-treatment WHO risk level reductions and WHO risk level reductions at the 1-year follow-up. Repeated-measures mixed models were used to examine the association between WHO risk level reductions and functional outcomes over time.ResultsAchieving at least a 1- or 2-level reduction in risk by the end of treatment was significantly associated with WHO risk level reductions at the 1-year follow-up assessment (p < 0.001). Among individuals who achieved at least a 1-level reduction by the end of treatment, 85.5% reported at least a 1-level reduction at the 1-year follow-up. Among individuals who achieved at least a 2-level reduction by the end of treatment, 77.8% reported at least a 2-level reduction at the 1-year follow-up. WHO risk level reductions were associated with significantly lower alcohol consumption, better physical health (p < 0.01), and fewer alcohol-related consequences (p < 0.001) up to 1 year following treatment.ConclusionsOne- and 2-level reductions in WHO risk levels during alcohol treatment were maintained after treatment and associated with better functioning over time. These findings support the use of the WHO risk level reductions as an outcome measure that reflects clinically significant improvement in how individuals seeking treatment for alcohol use disorder feel and function.

Project description:Purpose: To determine whether previously observed behavioral differences in alcoholic human patients after fecal microbiota transplantation (FMT) could be transferred to mice. Methods: Fecal microbiota samples from a previously published phase 1, double-blind, randomized clinical trial of AUD-related cirrhosis patients were used to colonize germ-free mice. Fecal material was transferred to 10-15-week-old GF C57BL/6 male mice by daily gavage for 3 day. The mice were housed in sterile individually filtered cages for 15 days after which stool was collected and then they underwent the alcohol preference experiment using 2-bottle choice drinking (water and 20% ethanol v/v). Microbial DNA was isolated from stool samples by sequencing the V1 and V2 variable regions of the bacterial 16S rRNA gene were sequenced using Multitag fusion primers and sequenced on an Ion Torrent PGM next-generation sequencer. Intestinal mucosa, liver, and prefrontal cortex tissue was collected from mice at time of sacrifice. RNAseq was used to measure gene expression in pre-FMT and post-FMT samples. RNAseq data were aligned to the mouse genome (GRCm39) using STAR (version 2.7.9a) and counts were generated with HTSeq (version 0.13.5). Genes with very low counts across the study (defined as fewer than 10 counts in more than 2 samples) were eliminated before differential expression analysis. Low count genes were determined separately for each tissue type. The DESeq2 package for R was then used to measure differential expression between pre-FMT and post-FMT mice in the intestine, liver, and PFC. Benjamini and Hochberg False Discovery Rate (FDR) was used to correct for multiple testing with FDR ≤ 0.2 considered significant. Results: Mice colonized with post-FMT stool significantly reduced ethanol acceptance, intake and preference versus pre-FMT colonized mice. Microbial taxa that were higher in post-FMT humans were also associated with lower alcohol intake and preference in mice. RNAseq further showed that differential gene expression, post-FMT, occurred in the intestine rather than the liver and prefrontal cortex. Conclusions: FMT leads to significant change in gut microbiome population, which in turn alters gene expression in the intestine. FMT also significantly affects alcohol consumption. The microbiotal-intestinal interface may alter gut-liver-brain axis and reduce alcohol consumption in humans.

Project description:BackgroundAbstinence and no heavy drinking days are currently the only Food and Drug Administration-approved end points in clinical trials for alcohol use disorder (AUD). Many individuals who fail to meet these criteria may substantially reduce their drinking during treatment, and most individuals with AUD prefer drinking reduction goals. One- and two-level reductions in World Health Organization (WHO) drinking risk levels have been proposed as alternative end points that reflect reduced drinking and are associated with reductions in drinking consequences, improvements in mental health, and reduced risk of developing alcohol dependence. The current study examined the association between WHO drinking risk level reductions and improvements in physical health and quality of life in a sample of individuals with alcohol dependence.MethodsSecondary data analysis of individuals with alcohol dependence (n = 1,142) enrolled in the longitudinal, prospective COMBINE study, a multi site randomized placebo-controlled clinical trial, examining the association between reductions in WHO drinking risk levels and change in blood pressure, liver enzyme levels, and self-reported quality of life following treatment for alcohol dependence.ResultsOne- and two-level reductions in WHO drinking risk level during treatment were associated with significant reductions in systolic blood pressure (p < 0.001), improvements in liver enzyme levels (all p < 0.01), and significantly better quality of life (p < 0.001).ConclusionsOne- and two-level reductions in WHO drinking risk levels predicted significant improvements in markers of physical health and quality of life, suggesting that the WHO drinking risk level reduction could be a meaningful surrogate marker of improvements in how a person "feels and functions" following treatment for alcohol dependence. The WHO drinking risk levels could be useful in medical practice for identifying drinking reduction targets that correspond with clinically significant improvements in health and quality of life.

Project description:Many studies have found that earlier drinking initiation predicts higher risk of later alcohol and substance use problems, but the causal relationship between age of initiation and later risk of substance use disorder remains unknown.We use a "natural experiment" study design to compare the 12-month prevalence of Diagnostic and Statistical Manual, Fourth Edition, alcohol and substance use disorders among adult subjects exposed to different minimum legal drinking age laws minimum legal drinking age in the 1970s and 1980s. The sample pools 33,869 respondents born in the United States 1948 to 1970, drawn from 2 nationally representative cross-sectional surveys: the 1991 National Longitudinal Alcohol Epidemiological Survey (NLAES) and the 2001 National Epidemiological Study of Alcohol and Related Conditions. Analyses control for state and birth year fixed effects, age at assessment, alcohol taxes, and other demographic and social background factors.Adults who had been legally allowed to purchase alcohol before age 21 were more likely to meet criteria for an alcohol use disorder [odds ratio (OR) 1.31, 95% confidence intervals (95% CI) 1.15 to 1.46, p < 0.0001] or another drug use disorder (OR 1.70, 95% CI 1.19 to 2.44, p = 0.003) within the past-year, even among subjects in their 40s and 50s. There were no significant differences in effect estimates by respondent gender, black or Hispanic ethnicity, age, birth cohort, or self-reported age of initiation of regular drinking; furthermore, the effect estimates were little changed by inclusion of age of initiation as a potential mediating variable in the multiple regression models.Exposure to a lower minimum legal purchase age was associated with a significantly higher risk of a past-year alcohol or other substance use disorder, even among respondents in their 40s or 50s. However, this association does not seem to be explained by age of initiation of drinking, per se. Instead, it seems plausible that frequency or intensity of drinking in late adolescence may have long-term effects on adult substance use patterns.

Dataset Information

Stability of Drinking Reductions and Long-term Functioning Among Patients with Alcohol Use Disorder.

Background

Objective

Design and participants

Measures

Key results

Conclusion

Publications

Stability of Drinking Reductions and Long-term Functioning Among Patients with Alcohol Use Disorder.

Similar Datasets

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