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Finding success in failure: using latent profile analysis to examine heterogeneity in psychosocial functioning among heavy drinkers following treatment.

ABSTRACT: To estimate differences in post-treatment psychosocial functioning among treatment 'failures' (i.e. heavy drinkers, defined as 4+/5+ drinks for women/men) from two large multi-site clinical trials and to compare these levels of functioning to those of the purported treatment 'successes' (i.e. non-heavy drinkers).Separate latent profile analyses of data from two of the largest alcohol clinical trials conducted in the United States, COMBINE (Combined Pharmacotherapies and Behavioral Interventions) and Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity), comparing psychosocial outcomes across derived classes of heterogeneous treatment responders.Eleven US academic sites in COMBINE, 27 US treatment sites local to nine research sites in Project MATCH.A total of 962 individuals in COMBINE (69% male, 77% white, mean age: 44 years) treated January 2001 to January 2004 and 1528 individuals in Project MATCH (75% male, 80% white, mean age: 40 years) treated April 1991 to September 1994.In COMBINE, we analyzed health, quality of life, mental health symptoms and alcohol consequences 12 months post-baseline. In Project MATCH, we examined social functioning, mental health symptoms and alcohol consequences 15 months post-baseline.Latent profile analysis of measures of functioning in both samples supported a three-profile solution for the group of treatment 'failures', characterized by high-, average- and low-functioning individuals. The high-functioning treatment 'failures' generally performed better across measures of psychosocial functioning at follow-up than participants designated treatment 'successes' by virtue of being abstainers or light drinkers.Current United States Food and Drug Administration guidance to use heavy drinking as indicative of treatment 'failure' fails to take into account substantial psychosocial improvements made by individuals who continue occasionally to drink heavily post-treatment.

SUBMITTER: Wilson AD

PROVIDER: S-EPMC5218991 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Finding success in failure: using latent profile analysis to examine heterogeneity in psychosocial functioning among heavy drinkers following treatment.

Wilson Adam D AD Bravo Adrian J AJ Pearson Matthew R MR Witkiewitz Katie K

Addiction (Abingdon, England) 20160824 12

<h4>Aims</h4>To estimate differences in post-treatment psychosocial functioning among treatment 'failures' (i.e. heavy drinkers, defined as 4+/5+ drinks for women/men) from two large multi-site clinical trials and to compare these levels of functioning to those of the purported treatment 'successes' (i.e. non-heavy drinkers).<h4>Design</h4>Separate latent profile analyses of data from two of the largest alcohol clinical trials conducted in the United States, COMBINE (Combined Pharmacotherapies a ...[more]

PMID: 27367263

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Project description:Background: Alcohol-associated liver disease (ALD) is the most common disorder of prolonged drinking. Mechanisms underlying cirrhosis in such patients remain unclear. MicroRNAs play regulatory role in several diseases, are affected by alcohol and may be important players in alcohol use disorders, such as cirrhosis. Methods: We investigated serum samples from heavy chronic alcohol users (80 g/day (male) and 50 g/day (female) for ≥10 years) that were available from our previously reported GenomALC study. A subset of GenomALC drinkers with liver cirrhosis (cases, n = 24) and those without significant liver disease (drinking controls, n = 23) were included. Global microRNA profiling was performed using high-throughput real-time quantitative PCR to identify the microRNA signatures associated with cirrhosis. Ingenuity Pathway Analysis (IPA) software was utilized to identify target mRNAs of significantly altered microRNAs, and molecular pathways were analysed. Identified microRNAs were analysed for correlation with traditional liver disease biomarkers and risk gene variants previously reported from GenomALC genome-wide association study. Results: The expression of 21 microRNAs was significantly downregulated in cases compared to drinking controls (p < 0.05, ∆∆Ct > 1.5-fold). Seven microRNAs (miR-16, miR-19a, miR-27a, miR-29b, miR-101, miR-130a, and miR-191) had a highly significant correlation (p < 0.001) with INR, bilirubin and MELD score. Three microRNAs (miR-27a, miR-130a and miR-191) significantly predicted cases with AUC-ROC 0.8, 0.78 and 0.85, respectively (p < 0.020); however, INR performed best (0.97, p < 0.001). A different set of six microRNAs (miR-19a, miR-26a, miR-101, miR-151-3p, miR-221, and miR-301) showed positive correlation (ranging from 0.32 to 0.51, p < 0.05) with rs10433937:HSD17B13 gene variant, associated with the risk of cirrhosis. IPA analysis revealed mRNA targets of the significantly altered microRNAs associated with cell death/necrosis, fibrosis and increased steatosis, particularly triglyceride metabolism. Conclusions: MicroRNA signatures in drinkers distinguished those with liver cirrhosis from drinkers without liver disease. We identified mRNA targets in liver functions that were enriched for disease pathogenesis pathways.

Project description:BackgroundHeavy episodic drinking (HED) is a major public health problem among emerging adults (individuals 18 to 25), but with considerable heterogeneity in concurrent substance use and psychopathology. The current study used latent profile analysis (LPA) to detect discrete subgroups of HED based on alcohol, other drug severity, and concurrent psychopathology. A reinforcer pathology approach was used to understand motivational differences among the latent subgroups.MethodsParticipants were 2 samples of emerging adults reporting regular HED, 1 Canadian (n = 730) and 1 American (n = 602). Indicators for the LPA were validated dimensional self-report assessments of alcohol severity, cannabis severity, other drug severity, nicotine dependence, depression, anxiety, posttraumatic stress disorder, and attention-deficit/hyperactivity disorder. Reinforcer pathology indicators were measures of alcohol demand, proportionate substance-related reinforcement, and discounting of future rewards.ResultsThe LPA yielded parallel 3-class solutions in both samples. The largest subgroup was characterized by comparatively low substance severity and psychopathology (Low overall severity). The second largest subgroup was characterized by comparatively high alcohol and other drug severity (excluding tobacco) and high levels of psychopathology (Heavy alcohol & high psychiatric severity). The third subgroup exhibited high alcohol, smoking and intermediate levels of other substance use and psychopathology (Heavy alcohol, smoking, & intermediate psychiatric severity). The Heavy alcohol & high psychiatric severity and Heavy alcohol, smoking, & intermediate psychiatric severity subgroups exhibited significantly higher alcohol demand, greater proportionate substance-related reinforcement, and steeper delay discounting.ConclusionsParallel latent subgroups of emerging adults engaging in HED were present in both samples, and the high-risk subgroups were significantly differentiated by the reinforcer pathology indicators. These latent profiles may ultimately inform heterogeneity in the longitudinal course of HED in emerging adults.

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Finding success in failure: using latent profile analysis to examine heterogeneity in psychosocial functioning among heavy drinkers following treatment.

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Finding success in failure: using latent profile analysis to examine heterogeneity in psychosocial functioning among heavy drinkers following treatment.

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