SMARCAL1 loss and alternative lengthening of telomeres (ALT) are enriched in giant cell glioblastoma.

Subsets of high-grade gliomas, including glioblastoma (GBM), are known to utilize the alternative lengthening of telomeres (ALT) pathway for telomere length maintenance. However, the telomere maintenance profile of one subtype of GBM-giant cell GBM-has not been extensively studied. Here, we investigated the prevalence of ALT, as well as ATRX and SMARCAL1 protein loss, in a cohort of classic giant cell GBM and GBM with giant cell features. To determine the presence of ALT, a telomere-specific fluorescence in situ hybridization assay was performed on 15 cases of classic giant cell GBM, 28 additional GBMs found to have giant cell features, and 1 anaplastic astrocytoma with giant cell features. ATRX, SMARCAL1, and IDH1 protein status were assessed in a proportion of cases by immunohistochemistry and were compared to clinical-pathologic and molecular characteristics. In the overall cohort of 44 cases, 19 (43%) showed evidence of ALT. Intriguingly, of the ALT-positive cases, only 9 (47.4%) displayed loss of the ALT suppressor ATRX by immunohistochemistry. Since inactivating mutations in SMARCAL1 have been identified in ATRX wild-type ALT-positive gliomas, we developed an immunohistochemistry assay for SMARCAL1 protein expression using genetically validated controls. Of the 19 ALT-positive cases, 6 (31.5%) showed loss or mis-localization of SMARCAL1 by immunohistochemistry. Of these cases, four retained ATRX protein expression, while two cases also displayed ATRX loss. Additionally, we assessed five cases from which multiple temporal samples were available and ALT status was concordant between both tumor biopsies. In summary, we have identified a subset of giant cell GBM that utilize the ALT telomere maintenance mechanism. Importantly, in addition to ATRX loss, ALT-positive tumors harboring SMARCAL1 alterations are prevalent in giant cell GBM.

5-HTTLPR moderates naltrexone and psychosocial treatment responses in heavy drinking men who have sex with men.

BACKGROUND: A functional polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene has been widely studied as a risk factor and moderator of treatment for a variety of psychopathologic conditions. To evaluate whether 5-HTTLPR moderates the effects of treatment to reduce heavy drinking, we studied 112 high-functioning European-American men who have sex with men (MSM). Subjects participated in a randomized clinical trial of naltrexone (NTX) and cognitive behavioral therapy (CBT) for problem drinking. METHODS: Subjects were treated for 12 weeks with 100 mg/d of oral NTX or placebo (PBO). All participants received medical management with adjusted brief behavioral compliance enhancement treatment (BBCET) alone or in combination with modified behavioral self-control therapy (MBSCT; an amalgam of motivational interviewing and CBT). Participants were genotyped for the tri-allelic 5-HTTLPR polymorphism (i.e., low-activity S' or high-activity L' alleles). RESULTS: During treatment, the number of weekly heavy drinking days (HDD; defined as 5 or more standard drinks per day) was significantly lower in subjects with the L'L' (N = 26, p = 0.015) or L'S' (N = 52, p = 0.016) genotype than those with the S'S' (N = 34) genotype regardless of treatment type. There was a significant interaction of genotype with treatment: For subjects with the S'S' genotype, the effects of MBSCT or NTX on HDD were significantly greater than the minimal intervention (i.e., BBCET or PBO, p = 0.007 and p = 0.049, respectively). In contrast, for subjects with 1 or 2 L' alleles, the effects of the more intensive psychosocial treatment (MBSCT) or NTX did not significantly differ from BBCET or PBO. CONCLUSIONS: These preliminary findings support the utility of the 5-HTTLPR polymorphism for personalizing treatment selection in problem drinkers.

Unpacking personalized feedback: an exploratory study of the impact of its components and the reactions it elicits among problem drinking men who have sex with men.

UNLABELLED: Personalized feedback (PF) has demonstrated effectiveness in reducing drinking. Few studies have examined its effectiveness with adult problem drinkers or its potential mediators or moderators, including developing discrepancy. This study aimed to identify potential mediators and moderators of PF provided to adult problem drinking men who have sex with men (PDMSM). METHOD: An exploratory analysis of PF provided to PDMSM in the context of modified behavioral self-control therapy (N = 90). The association of individual items of PF, severity of PF, and independently rated, in-session participant reactions to PF with drinking outcomes (mean drinks per drinking day, MDDD) were examined using correlations and logistic and linear regression. RESULTS: Significant pre-post differences in MDDD emerged. Other drug risk, family risk, and having an abnormal liver enzyme test result were significantly associated with proxies for developed discrepancy in expected directions; however, no PF item or reaction to PF predicted drinking outcomes. Severity of PF was not associated with participant reactions or drinking outcome. CONCLUSIONS: PF may be an effective intervention for PDMSM. Further research is needed to identify potential mediators and moderators of PF among adults.

FRAMES Elements Associated With Alcohol Treatment Research Assessments and Related Behavior Change.

OBJECTIVE: Assessment reactivity research has contributed substantially to our understanding of alcohol treatment research protocols influencing clinical outcomes. The state of the science is such that relatively little is known about how alcohol treatment research participation influences behavior. The purpose of this study was twofold: (a) to determine the distribution of FRAMES elements (i.e., Feedback, personal Responsibility, Advice, a Menu of options, Empathic style of interaction, and support for Self-efficacy) contained in alcohol treatment research assessment interviews; and (b) to examine their association with subsequent alcohol use among a sample of clients presenting for alcohol use disorder treatment. METHOD: Audiotaped recordings of participant (n = 189) research assessment interviews were converted to digital recordings and reviewed for FRAMES elements using the FRAMES Checklist Instrument. RESULTS: Feedback, personal responsibility, empathic style of interaction, and support for self-efficacy were the more frequently occurring elements across follow-up periods. Alternatively, menu of options and advice occurred infrequently. Feedback and support for self-efficacy predicted subsequent alcohol use, although the association between feedback and alcohol use was unexpectedly positive. CONCLUSIONS: As part of the assessment interview process, alcohol treatment research participants receive multiple instances of feedback and support for self-efficacy specific to their alcohol use that are predictive of changes in alcohol use.

Alcohol Treatment Research Contributing to Changes in Substance Use Behavior and Related Negative Consequences.

OBJECTIVE: The purpose of this study was to investigate the extent to which two of the more salient characteristics of a treatment research assessment protocol (i.e., the comprehensiveness of the assessment battery and the frequency of its administration) for alcohol use disorder contribute to reductions in substance use and related negative consequences. METHOD: Study participants were recruited from two hospital-administered substance use disorder outpatient clinics. Two hundred thirty-five individuals presenting for outpatient alcohol treatment screened study eligible and provided informed consent. Study participants were randomized to one of four research assessment conditions (i.e., frequent-comprehensive, frequent-brief, infrequent-comprehensive, and infrequent-brief) based on the crossing of a 2 (i.e., assessment comprehensiveness: comprehensive vs. brief) by 2 (i.e., assessment frequency: frequent vs. infrequent) factorial design. RESULTS: Individuals assigned to the frequent assessment conditions reported greater reductions in substance use and substance use-related negative consequences relative to their counterparts assigned to the infrequent assessment conditions. In addition, a greater proportion of individuals assigned to the frequent assessment conditions reported abstinence from both alcohol and other substances. CONCLUSIONS: The improvements in substance use and related negative consequences associated with more frequent research assessments were statistically significant and clinically meaningful.

Development of the alcohol use discrepancy instrument (AUDI): An instrument for measuring a purported mechanism of behavior change underlying self-regulation theory.

Self-regulation theory (SRT) posits that individuals make decisions regarding behavior change based on a comparison of their actual (e.g., excessive alcohol use) and desired (e.g., abstinence) behaviors. This comparison must result in a discrepancy of sufficient magnitude to motivate an individual toward behavior change. It appears that this purported mechanism of behavior change (MOBC) has not been tested with regards to alcohol use disorder (AUD) treatment. Furthermore, there seems to be no psychometrically sound instrument for assessing such discrepancies in a clinical sample. The purpose of this study was to establish the psychometric properties of an instrument developed to assess actual versus desired alcohol use discrepancies that could be used to test this purported MOBC underlying SRT. The Alcohol Use Discrepancy Instrument (AUDI) was administered to 235 individuals participating in the Clifford et al. (2007) alcohol treatment outcome study that centered on research assessment exposure reactivity effects. Principal axis factor analysis yielded a unidimensional construct (Cronbach's α = 0.80). Baseline and six-month AUDI scores were correlated with concurrent alcohol use (proportion days abstinent, drinks per drinking day, and proportion heavy days, p < .01) in expected directions. Parallel process models provided further evidence of the AUDI's construct validity, as well as its potential as a measure of discrepancy as a MOBC. The AUDI has good psychometric properties and is likely to prove useful for assessing discrepancies between actual and desired alcohol use behavior, which, according to the principles of SRT, is essential for behavior change and maintenance.

Alcohol use post AUD treatment initiation as a predictor of later functioning.

OBJECTIVE: To replicate and extend the earlier work of Maisto and colleagues showing an association between early post-treatment alcohol use and later functioning (1, 2, 3). METHODS: The present study classified adults presenting for alcohol use disorders (AUD) treatment (n = 114) into one of three drinker groups (i.e., abstainer, moderate drinker, or heavy drinker) based upon alcohol use during the first 6-months following outpatient AUD treatment initiation, and examined the associations between drinker group classification and later alcohol use and psychosocial functioning. RESULTS: Study results showed that individuals classified within the heavy drinker group tended to have the poorest outcomes (i.e., greater alcohol use and poorer psychosocial functioning) relative to individuals classified within the abstainer or moderate drinker groups. CONCLUSIONS: Study findings are consistent with the prior work of Maisto and colleagues. In addition, it appears that alcohol use, particularly heavy alcohol consumption, during the early post-treatment initiation period may serve as a marker for later alcohol related problems and poorer overall psychosocial functioning.

Medication adherence and quality of life in pediatric inflammatory bowel disease.

OBJECTIVE: To examine the relationship between medication adherence and quality of life (QOL) in adolescent patients with inflammatory bowel disease (IBD) utilizing a multimethod adherence assessment approach. METHODS: Medication adherence in 36 adolescents with IBD was assessed via interviews, pill counts, and biological assays. QOL was assessed via patient and parent report. Pediatric gastroenterologists provided disease severity assessments. RESULTS: Hierarchical multiple regression analyses revealed that adherence contributed significant variance to patient-reported QOL but not parent-reported QOL. Nonadherence to 6-MP/azathioprine was related to poorer patient-reported physical health QOL. Greater self-reported 5-ASA adherence was related to poorer overall psychological health QOL, and particularly social functioning QOL. CONCLUSIONS: Results provide preliminary support for the negative effects of 6-MP/azathioprine nonadherence on QOL and an inverse relationship between 5-ASA adherence and QOL in this population. Adherence burden in patients and the utility of multimethod adherence assessment in research are discussed.

The utility of collateral informants in substance use research involving college students.

Collateral informants have been routinely included in substance abuse treatment research to corroborate subject self-reported alcohol and other drug use. However, only a few studies to date have examined subject-collateral correspondence with respect to non-clinical populations (e.g., college students). The purpose of the present study was to examine the associations between college students self-reported substance use and corresponding collateral (i.e., friends') reports. A total of 100 subject-collateral pairs were recruited from psychology courses at a large public university located in the Southeastern, United States. Subjects and collaterals provided information specific to their own, as well as their friend's, recent (i.e., last 90-days) substance use. Study data yielded moderate to good, statistically significant, correlations between subject-friend pairs for each type of substance use. Discrepancy analyses revealed that the majority of subjects reported greater substance use relative to their collateral reports. This pattern of response (i.e., subject reporting greater use) is consistent with the extant literature. In addition, the friend's personal substance use appeared to influence his/her report of the subject's alcohol and other drug use. It appears that college student self-reports regarding alcohol and other drug use are reasonably accurate.

Testing Cross-Sectional and Prospective Mediators of Internalized Heterosexism on Heavy Drinking, Alcohol Problems, and Psychological Distress Among Heavy Drinking Men Who Have Sex With Men.

OBJECTIVE: Minority stress theory is one of the primary theories used to understand substance use among lesbian, gay, and bisexual populations. This study tested whether drinking to cope with stress (DTC), loneliness, and gay community participation (GCP) mediated the relationship between one type of minority stress (i.e., internalized heterosexism) and behavioral health outcomes. METHOD: Using secondary data analysis and the PROCESS procedure, relationships between internalized heterosexism, the mediators (DTC, loneliness, and GCP), and outcomes (heavy drinking, alcohol problems, and psychological distress) were explored, both cross-sectionally and in a lagged manner, among both treatment-seeking and non-treatment-seeking problem drinking men who have sex with men. Problem drinkers (N = 187) were assessed, provided brief normative feedback about their drinking, given the choice to receive brief alcohol use disorder treatment or change on their own, and then followed for 9 months. RESULTS: Cross-sectional findings revealed that internalized heterosexism was significantly associated with heavy drinking, alcohol problems, and psychological distress. DTC emerged as a significant mediator of internalized heterosexism for all the health outcomes. Loneliness and GCP were significant mediators of internalized heterosexism for alcohol problems and psychological distress. Multiple mediation models reveal that all three mediators significantly contribute to internalized heterosexism's effect on health outcomes. Lagged analyses did not yield any significant indirect effects. CONCLUSIONS: DTC, loneliness, and GCP all play an integral, mediational role in the relationship between internalized heterosexism and alcohol problems and psychological distress. Findings underscore the necessity of addressing internalized heterosexism in psychosocial interventions along with coping skills training, emphasizing culturally relevant social support and loneliness.

Drinking in the year after treatment as a predictor of three-year drinking outcomes.

OBJECTIVE: Previous research suggests that abstinence from alcohol during the first year posttreatment for alcohol-use disorders (AUDs) is an important, independent predictor of longer-term alcohol consumption and related functioning. The purpose of this study was to test the hypothesis that abstinence during the first year posttreatment initiation predicts alcohol use at Months 37-39. A second aim of this study was to explore the relationship between "moderate" drinking in the first year and drinking at Months 37-39. METHOD: Secondary data analyses were conducted on the outpatient Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) sample (N = 952 at baseline and 802 at Months 37-39). For these analyses, participants were classified first as abstainers, moderate drinkers, or heavy drinkers based on their alcohol use in the first year posttreatment initiation. RESULTS: Analyses of covariance showed that the first-year drinker classification predicted both percentage of days abstinent and drinks per drinking day at Months 37-39. Subsequent analyses showed that the abstainers functioned significantly better than (1) both of the other drinker groups combined and (2) either of the other two groups, which did not differ from each other on either measure of alcohol use. A third set of exploratory analyses evaluated first-year abstinence and heavy drinking as continuous variables and showed an essentially linear relationship between them and drinking at 3 years. CONCLUSIONS: This study confirmed the strong relationship between first-year abstinence and later drinking but did not show that participants who engaged in moderate drinking during the first year had positive alcohol-use outcomes at 3 years. The clinical implications of the findings, their generalizability to different populations of individuals presenting for specialty alcohol treatment, and future research directions are discussed.

Ascertaining the relationships between the trajectories of specific categories of alcohol-related negative consequences and subsequent drinking behavior.

The first year following alcohol use disorder (AUD) treatment has been identified as a period of high risk for relapse and an important timeframe for enquiry regarding alcohol-related behavior change and its maintenance. In addition, at least among individuals with AUD, alcohol use and negative consequences have been shown to be reciprocally related. A commonly used measure of alcohol-related negative consequences is the Drinker Inventory of Consequences (DrInC). Investigations of specific categories of alcohol-related negative consequences and their trajectories, however, have been lacking. Given this background, the purpose of this study was to: follow the course of the 5 DrInC categories of alcohol-related negative consequences over the first year post-AUD treatment initiation; investigate whether these trajectories varied by gender, age, and/or treatment condition; examine the relationships between these trajectories and subsequent drinking behavior; and investigate whether these relationships varied by gender, age, and/or treatment condition, via secondary data analyses. Data from the outpatient arm of Project MATCH (n = 952) were utilized. Study results revealed that the trajectory of each DrInC category was indicative of improved alcohol-related problems across the first year posttreatment initiation. Specific DrInC categories varied as a function of gender, age, and treatment condition, and the trajectories were predictive of subsequent drinking behavior. Specifically, higher intercepts during the treatment period were associated with poorer drinking behavior 1 year later. Alternatively, steeper negative slopes were associated with improved drinking behavior. Some of these relationships were modified by gender, age, and treatment condition. It was concluded that assessing alcohol-related negative consequences during the first year posttreatment initiation period has clinical utility. (PsycINFO Database Record

Site-directed mutagenesis of rat α-parvalbumin: replacement of canonical CD-site residues with their non-consensus counterparts from rat ß-parvalbumin.

Rat ß-parvalbumin (ß-PV) displays low divalent-ion affinity. Its CD site is distinguished by six non-consensus residues--the "CD-loop residues"--at positions 49, 50, 57-60. Additionally, leucine occupies position 85, rather than phenylalanine, the ß-lineage-consensus residue. Replacement of the CD-loop residues in rat ß with the canonical residues was previously found to have little effect on divalent-ion affinity, unless L85 is replaced by phenylalanine. Herein, we replace the canonical CD-loop residues in rat α-PV with their rat ß-PV counterparts. Although the mutations have a generally modest impact on affinity, E59D confers Ca(2+)-specificity on the CD site, in the presence or absence of the other mutations. Despite their minimal impact on ΔG, several CD-loop mutations markedly alter ΔH, evidently by perturbing the apo-protein conformation. The L85F mutation was also examined. In wild-type rat α, L85F increases EF-site Ca(2+) affinity. In the CD-loop variants, the mutation leaves the ΔG for Ca(2+)-binding largely unaffected. However, several variants display highly exothermic binding enthalpies, indicative of ligation-linked protein-folding. Consistent with that idea, scanning-calorimetry data confirm that L85F has significantly destabilized those proteins.

Variation in Mu-Opioid Receptor Gene (OPRM1) as a Moderator of Naltrexone Treatment to Reduce Heavy Drinking in a High Functioning Cohort.

BACKGROUND: It is well known that naltrexone, an FDA-approved medication for treatment of alcohol dependence, is effective for only a subset of individuals. Recent studies have examined the utility of a functional A118G single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1) as a predictor of naltrexone treatment response. Although the findings to date have generally been consistent with a moderating effect of the SNP, further evaluation of this hypothesis is warranted. OBJECTIVE: To evaluate whether problem drinkers with one or two copies of the 118G allele respond better to naltrexone treatment. The treatment goal in this cohort of high functioning men who have sex with men (MSM) was to reduce heavy drinking, rather than to promote abstinence. METHOD: 112 subjects of European ancestry from a randomized clinical trial of naltrexone and behavioral therapy for problem drinking MSM were included in the analysis. Subjects were treated for 12 weeks with 100 mg/day of oral naltrexone hydrochloride. All participants received medical management with a modified version of the Brief Behavioral Compliance Enhancement Treatment (BBCET), alone or in combination with Modified Behavioral Self-control Therapy (MBSCT). RESULTS: Naltrexone-treated subjects with one or two 118G alleles had a significantly greater percentage of non-hazardous drinking (NoH) (p < 0.01) than those treated with placebo or A118 homozygotes in either medication group. CONCLUSIONS: These results are consistent with a modest moderating effect of the OPRM1 118G allele on the reduction of heavy drinking by naltrexone treatment.

Alcohol treatment research assessment exposure: a critical review of the literature.

Alcohol treatment researchers have speculated about the benefits of research participation (e.g., research follow-up interviews functioning as aftercare) for more than 4 decades (Gallen, 1974). Alternatively, research participation can decrease study design sensitivity and hamper the interpretability of research findings. To the extent that the typical alcohol treatment trial is characterized by frequent and comprehensive data collection, accounting for potential research assessment-related effects is essential for proper interpretation of study findings. Given this background, the purpose of this article is to review the alcohol treatment research literature on assessment exposure resulting in subject reactivity. In addition, interventions that use data collection activities to inform clinical practice are receiving increased attention, and such interventions share common characteristics with research assessment-related clinical improvements. Therefore, a second purpose of this article is to compare and contrast these 2 influences of behavior change. Study findings indicate that during and posttreatment data collection activities (i.e., both research and clinical data) positively influence clinical outcomes, although there appears to be important differences in regard to the mechanisms by which these 2 data collection activities exert their influence. Understanding of mechanisms of behavior change, effect boundaries, and the conditions under which clinical improvement is most likely to occur is only at a rudimentary level.

Objective versus subjective assessment of oral medication adherence in pediatric inflammatory bowel disease.

BACKGROUND: The objective was to examine the prevalence and frequency of oral medication nonadherence using a multimethod assessment approach consisting of objective, subjective, and biological data in adolescents with inflammatory bowel disease (IBD). METHODS: Medication adherence was assessed via pill counts, patient/parent interview, and 6-thioguanine nucleotide (6-TGN)/6-methylmercaptopurine nucleotide (6-MMPN) metabolite bioassay in 42 adolescents with IBD. Pediatric gastroenterologists provided disease severity assessments. RESULTS: The objective nonadherence prevalence was 64% for 6-MP/azathioprine (AZA) and 88% for 5-aminosalicylate (5-ASA) medications, whereas subjective nonadherence prevalence was 10% for 6-MP/AZA and 2% for 5-ASA. The objective nonadherence frequency was 38% for 6-MP/AZA and 49% for 5-ASA medications, and subjective nonadherence frequency was 6% for 6-MP/AZA and 3% for 5-ASA. The bioassay data revealed that only 14% of patients had therapeutic 6-TGN levels. CONCLUSIONS: The results indicate that objectively measured medication nonadherence prevalence is consistent with that observed in other pediatric chronic illness populations, and that objective nonadherence frequency is considerable, with 40%-50% of doses missed by patients. Subjective assessments appeared to overestimate adherence. Bioassay adherence data, while compromised by pharmacokinetic variation, might be useful as a cursory screener for nonadherence with follow-up objective assessment. Nonadherence in 1 medication might also indicate nonadherence in other medications. Clinical implications and future research directions are provided.

Factors mediating the association between drinking in the first year after alcohol treatment and drinking at three years.

OBJECTIVE: Previous research has shown a significant relationship between alcohol consumption in the first year following alcohol treatment admission and longer term functioning. This finding is clinically important and pertains to the clinical course of alcohol-use disorders(AUDs). This study investigated mediators of these relationships, focusing on the first year after treatment admission and alcohol consumption 3 years later. METHOD: Analyses were conducted on the outpatient Project MATCH (Matching Alcohol Treatment to Client Heterogeneity) sample at baseline (N=952) and at Months 37-39 after treatment admission (n=802; hereafter referred to as 3 years). Participants were classified as first-year "abstainer," "moderate drinker," or "heavy drinker." A model featuring three latent variables (psychosocial functioning, self-efficacy, and treatment experiences) whose indicators were collected at 15 months after treatment admission was initially tested for its fit to the data. The 3-year outcomes were percentage of days abstinent and drinks per drinking day. Each model was run on randomly split subsamples and then cross-validated on the remaining participants. RESULTS: Model tests by use of structural equation modeling methods showed poor model fit, owing primarily to problems involving the psychosocial-functioning variable. Consequently, a reduced model was tested that dropped the psychosocial factor. Initial tests of this model showed an excellent fit to the data that replicated across subsamples and 3-year drinking variables at the overall model and individual path levels. There was strong support for the hypothesis that the total effects of first-year alcohol use on 3-year drinking is mediated in part (31% and 23% for the two drinking outcomes) through self-efficacy to abstain from alcohol at 15 months. CONCLUSIONS: First-year posttreatment admission alcohol use predicts longer term (3-year) alcohol use, and a substantial portion of this relationship seems to be mediated through self-efficacy at 15 months to abstain from alcohol use. The apparent benefit of sustained abstinence in the first year may be in part the result of facilitation in the rate or strength of the acquisition of self-efficacy. Discussed are the clinical implications of these findings as well as directions for future research involving longitudinal studies of alcohol use, treatment experiences, psychosocial factors, and their interaction both within the first year and afterward in the determination of the clinical course of alcohol-use disorders.

Alcohol treatment research assessment exposure subject reactivity effects: part I. Alcohol use and related consequences.

OBJECTIVE: There has been increasing recognition among alcohol treatment researchers that research assessment exposure subject reactivity effects can contribute to clinical outcomes, decrease study design sensitivity, and confound research findings. The present study is an experimental investigation of two of the more salient components of the research assessment interview (i.e., frequency and comprehensiveness) and their effects on clinical outcomes (Part I: Alcohol Use and Related Consequences) and treatment participation (Part II: Treatment Engagement and Involvement). METHOD: The study design was a 2 (Frequency of Assessment) x 2 (Comprehensiveness of Assessment) completely randomized factorial, and study participants were randomly assigned, using an urn randomization procedure, to one of the resulting four experimental research assessment exposure conditions: (1) frequent-comprehensive, (2) frequent-brief, (3) infrequent-comprehensive, and (4) infrequent-brief. Study participants were recruited from one of two hospital-based outpatient alcohol- and other substance-abuse clinics. Two hundred thirty-five subjects were randomly assigned to one of the four research assessment exposure conditions. RESULTS: Research assessment exposure subject reactivity effects were related significantly to alcohol use and related negative consequences, such that subjects assigned to the infrequent-brief research assessment exposure condition reported the poorest outcomes. CONCLUSIONS: The research protocols used to study alcohol treatments have clinical efficacy and can alter the outcomes (e.g., alcohol use) under investigation. It is important for researchers to control/account for subject reactivity effects when conducting alcohol treatment outcome trials. Accurate interpretation of data derived from clinical trials of alcohol treatments necessitates taking research assessment exposure subject reactivity effects into consideration.

Alcohol treatment research assessment exposure subject reactivity effects: part II. Treatment engagement and involvement.

OBJECTIVE: This is the second of two articles in this issue on participant reactivity to alcohol treatment research assessment protocols. In the first article, Clifford et al. presented experimental evidence that the combination of less frequent and less comprehensive assessment results in the least assessment reactivity, as measured by alcohol use and related consequences at 1 year after admission for adult outpatient treatment for alcohol problems. In addition, Part I revealed that the presence of either frequent or comprehensive research assessment tends to result in a greater degree of reactivity. This article extends the analyses by Clifford et al. to treatment for substance use-disorders engagement and involvement across a 1-year follow-up. METHOD: The design, participants, and procedures were identical to those described in Clifford et al. Treatment data were obtained from hospital records and participants' self-reports as part of the Timeline Followback interview. RESULTS: Analyses revealed several effects of frequency of assessment and comprehensiveness of assessment on treatment engagement or involvement. The reactivity effect observed varied with the dependent variable, which included if a participant presented for outpatient treatment (more likely in the comprehensive groups), the number of days of outpatient substance use-disorders treatment during follow-up (no reactivity effects), if a participant engaged in intensive treatment for substance-use disorders during follow-up (more likely for the frequent groups in Months 1-6, but the reverse in Months 7-12, and overall more likely in the brief conditions), and the number of days of intensive treatment for substance-use disorders during follow-up (more days in the frequent groups in Months 1-6, no frequency differences in Months 7-12, and overall more days in the brief groups), respectively. Additional analyses showed that treatment participation did not mediate the reactivity effects on alcohol use and related consequences reported by Clifford et al. CONCLUSIONS: Data provide experimental evidence for a causal relationship between frequency of assessment and comprehensiveness of assessment on substance abuse-treatment engagement and involvement. Future research should be directed at understanding the factors in the assessment process that determine reactivity effects.