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Introduction Craving is considered a central process to addictive behavior including cigarette smoking, although the clinical utility of craving relies on how it is defined and measured. Network analysis enables examining the network structure of craving symptoms, identifying the most central symptoms of cigarette craving, and improving our understanding of craving and its measurement. Aims and Methods This study used network analysis to identify the central symptoms of self-reported cigarette craving as measured by the Craving Experience Questionnaire, which assesses both craving strength and craving frequency. Data were obtained from baseline of a randomized controlled trial of mindfulness training for smoking cessation. Results The most central symptoms in an overall cigarette craving network were the frequency of imagining its smell, imagining its taste, and intrusive thoughts. The most central symptoms of both craving frequency and craving strength sub-networks were imagining its taste, the urge to have it, and intrusive thoughts. Conclusions The most central craving symptoms reported by individuals in treatment for cigarette smoking were from the frequency domain, demonstrating the value of assessing craving frequency along with craving strength. Central craving symptoms included multisensory imagery (taste, smell), intrusive thoughts, and urge, providing additional evidence that these symptoms may be important to consider in craving measurement and intervention. Findings provide insight into the symptoms that are central to craving, contributing to a better understanding of cigarette cravings, and suggesting potential targets for clinical interventions. Implications This study used network analysis to identify central symptoms of cigarette craving. Both craving frequency and strength were assessed. The most central symptoms of cigarette craving were related to craving frequency. Central symptoms included multisensory imagery, intrusive thoughts, and urge. Central symptoms might be targeted by smoking cessation treatment.

A recent study demonstrated that during a single sampling period, 0.1 mg of intravenous (IV) nicotine (vs. placebo) was found to be the threshold for subjective and physiological drug effects. The present study is a secondary analysis evaluating whether the threshold for subjective and physiological effects is similar when the subject has repeated opportunities to choose blinded doses of nicotine versus placebo. We also examined whether cigarette craving, withdrawal, and rate of nicotine metabolism affected nicotine reinforcement, defined by a greater number of nicotine choices than placebo. Young adult (

Binge-eating disorder, the most prevalent eating disorder, is a serious public health problem associated with obesity, psychiatric and medical comorbidities, and functional impairments. Binge-eating disorder remains underrecognized and infrequently treated, and few evidence-based treatments exist. The authors tested the effectiveness of naltrexone-bupropion and behavioral weight loss therapy (BWL), alone and combined, for binge-eating disorder comorbid with obesity.In a randomized double-blind placebo-controlled trial conducted from February 2017 to February 2021, using a 2×2 balanced factorial design, 136 patients with binge-eating disorder (81.6% women; mean age, 46.5 years; mean BMI, 37.1) were randomized to one of four 16-week treatments: placebo (N=34), naltrexone-bupropion (N=32), BWL+placebo (N=35), or BWL+naltrexone-bupropion (N=35). Overall, 81.7% of participants completed independent posttreatment assessments.Intention-to-treat binge-eating remission rates were 17.7% in the placebo group, 31.3% in the naltrexone-bupropion group, 37.1% in the BWL+placebo group, and 57.1% in the BWL+naltrexone-bupropion group. Logistic regression of binge-eating remission revealed that BWL was significantly superior to no BWL, and that naltrexone-bupropion was significantly superior to placebo, but there was no significant interaction between BWL and medication. Mixed models of complementary measures of binge-eating frequency also indicated that BWL was significantly superior to no BWL. The rates of participants attaining 5% weight loss were 11.8% in the placebo group, 18.8% in the naltrexone-bupropion group, 31.4% in the BWL+placebo group, and 38.2% in the BWL+naltrexone-bupropion group. Logistic regression of 5% weight loss and mixed models of percent weight loss both revealed that BWL was significantly superior to no BWL. Mixed models revealed significantly greater improvements for BWL than no BWL on secondary measures (eating disorder psychopathology, depression, eating behaviors, and cholesterol and HbABWL and naltrexone-bupropion were associated with significant improvements in binge-eating disorder, with a consistent pattern of BWL being superior to no BWL.

Introduction Count outcomes in tobacco research are often analyzed with the Poisson distribution. However, they often exhibit features such as overdispersion (variance larger than expected) and zero inflation (extra zeros) that violate model assumptions. Furthermore, longitudinal studies have repeated measures that generate correlated counts. Failure to account for overdispersion, zero inflation, and correlation can yield incorrect statistical inferences. Thus, it is important to familiarize researchers with proper models for such data. Aims and Methods Poisson and Negative Binomial models with correlated random effects with and without zero inflation are presented. The illustrative data comes from a study comparing a mindfulness training app (Craving to Quit [C2Q], n = 60) with a control app (experience sampling-only app, n = 66) on smoking frequency at 1, 3, and 6 months. Predictors include app, time, the app-by-time interaction, and baseline smoking. Each model is evaluated in terms of accounting for zero inflation, overdispersion, and correlation in the data. Emphasis is placed on evaluating model fit, subject-specific interpretation of effects, and choosing an appropriate model. Results The hurdle Poisson model provided the best fit to the data. Smoking abstinence rates were 33%, 32%, and 28% at 1, 3, and 6 months, respectively, with variance larger than expected by a factor >7 at each follow-up. Individuals on C2Q were less likely to achieve abstinence across time but likely to smoke fewer cigarettes if smoking. Conclusions The models presented are specifically suited for analyzing correlated count outcomes and account for zero inflation and overdispersion. We provide guidance to researchers on the use of these models to better inform nicotine and tobacco research. Implications In tobacco research, count outcomes are often measured repeatedly on the same subject and thus correlated. Such outcomes often have many zeros and exhibit large variances relative to the mean. Analyzing such data require models specifically suited for correlated counts. The presented models and guidelines could improve the rigor of the analysis of correlated count data and thus increase the impact of studies in nicotine and tobacco research using such outcomes.

We describe pain intensity and opioid prescription jointly over time in Veterans with back pain to better understand their relationship.We performed a retrospective cohort study on electronic health record data from 117 126 Veterans (mean age 49.2 years) diagnosed with back pain in 2015. We used latent class growth analysis to jointly model pain intensity (0-10 scores) and opioid prescriptions over 2 years to identify classes of individuals similar in their trajectory of pain and opioid over time. Multivariable multinomial logit models assessed sociodemographic and clinical predictors of class membership.We identified six trajectory classes: a "no pain/no opioid" class (22.2%), a "mild pain/no opioid" class (45.0%), a "moderate pain/no opioid" class (24.6%), a "moderate, decreasing pain/decreasing opioid" class (3.3%), a "moderate pain/high opioid" class (2.6%), and a "moderate, increasing pain/increasing opioid" class (2.3%). Among those in moderate pain classes, being white (vs. non-white) and older were associated with higher odds of being prescribed opioids. Veterans with mental health diagnoses had increased odds of being in the painful classes versus "no pain/no opioid" class.We found distinct patterns in the long-term joint course of pain and opioid prescription in Veterans with back pain. Understanding these patterns and associated predictors may help with development of targeted interventions for patients with back pain.

Although nicotine from cigarettes is delivered in puff-sized amounts, most preclinical and human intravenous (IV) nicotine studies have used bolus or continuous infusions.To determine the feasibility of a pulsed-nicotine infusion model in smokers.Following overnight abstinence, 12 adult smokers underwent 5 laboratory sessions. Using a crossover design, in each session, participants were assigned to 1 of 5 conditions: (1) high/fast: 1.0 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (2) high/slow: 1.0 mg nicotine delivered over 20 pulsed-infusions; (3) low/fast: 0.2 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (4) low/slow: 0.2 mg nicotine delivered over 20 pulsed-infusions; and (5) placebo: Saline delivered over 20 pulsed-infusions. Subjective drug effects, urges to smoke, nicotine withdrawal, and cognitive performance were measured in each session.Both the high/fast and high/slow conditions were associated with greater "head rush" and "high" (p 0.05). The high/fast condition also provided greater suppression of urges to smoke and nicotine withdrawal (p 0.05), indexed by the Questionnaire of Urges to Smoke-Brief, and the Minnesota Nicotine Withdrawal Scale, respectively. The high/fast and high/slow conditions produced greater increases in heart rate (p 0.01) than saline. Finally, there were no main effects of dosing conditions on cognitive performance, indexed by the continuous performance test.These findings demonstrate the feasibility of pulsed-nicotine infusions to model nicotine delivery by smoking. This model could inform future studies testing novel smoking cessation therapies and tobacco regulatory studies testing the impact of nicotine reduction approaches.

Introduction E-cigarette liquid nicotine concentrations typically are labeled as mg/mL or percent, which poorly convey nicotine strength to users. We evaluated whether four novel nicotine concentration labels better convey information about nicotine strength and addictiveness. Methods Adolescents and young adults (N = 826) completed an online survey in 2020. Participants rated nicotine concentrations (3, 6, 18, 30, 40, and 50 mg/mL) from “no nicotine” to “very high nicotine” communicated using current market labels (mg/mL, percent) and four new labels (text-based, caution sign-shaped, horizonal stoplight, vertical thermometer) which used color, symbols, and verbal strength descriptors. Participants reported on perceived addictiveness for all labels viewed and rank-ordered labels on perceived ability to convey information accurately. Results Participants ranked the vertical (77%) and horizontal (70%) labels in first or second place and mg/mL (59.1%) and percent (47.2%) in last or second-to-last place. All new labels conveyed nicotine strength more accurately than did market labels (M[SD] correct of 6: percent = 1.50[1.08]; mg/mL = 2.14[1.52]; caution = 5.23[1.37]; vertical thermometer = 5.28[1.51]; text = 5.33[1.36]; horizontal stoplight = 5.47[1.14]), with the horizontal label also outperforming the thermometer and caution labels. Underestimating nicotine strength was uncommon among all new labels (4.7–6.8%). The new labels also were associated with increased perceived addictiveness at higher concentrations (30, 40, and 50 mg/mL), although the thermometer label underperformed the others. When considering perceived nicotine strength, rates of strength underestimates, perceived addictiveness, and rank ordering, the horizontal stoplight label performed best. Conclusions Novel labeling could improve understanding of nicotine strength and e-cigarette-related risk. Implications Extending prior research showing that adolescents and young adults who use Electronic Nicotine Delivery Systems (ENDS) have difficulty understanding nicotine concentrations labeled using mg/mL and percent nicotine, the current study demonstrates that novel nicotine concentration labels can improve understanding of nicotine strength and influence perceptions of addictiveness among young ENDS users. While four novel labels were tested, each outperforming current market labeling, the novel label that resembles a horizontal stoplight performed best. The study provides proof-of-concept that creating an easy-to-understand nicotine concentration label is possible and that new labeling better conveys information about nicotine strength and addictiveness.

This study tested the efficacy of repeated intravenous ketamine doses to reduce symptoms of posttraumatic stress disorder (PTSD). Veterans and service members with PTSD (n = 158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo (n = 54), low dose (0.2 mg/kg; n = 53) or standard dose (0.5 mg/kg; n = 51) ketamine. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS). There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5. The standard ketamine dose ameliorated depression measured by the MADRS significantly more than placebo. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration. There was no evidence of differential treatment discontinuation by ketamine dose, consistent with good tolerability. This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms. Secondary analyses suggested that the standard dose exerted rapid antidepressant effects. Further studies are needed to determine the role of ketamine in PTSD treatment. ClinicalTrials.gov identifier: NCT02655692.

Working memory (WM) is a crucial resource for temporary memory storage and the guiding of ongoing behavior. N-methyl-D-aspartate glutamate receptors (NMDARs) are thought to support the neural underpinnings of WM. Ketamine is an NMDAR antagonist that has cognitive and behavioral effects at subanesthetic doses. To shed light on subanesthetic ketamine effects on brain function, we employed a multimodal imaging design, combining gas-free calibrated functional magnetic resonance imaging (fMRI) measurement of oxidative metabolism (CMRO2), resting-state cortical functional connectivity assessed with fMRI, and WM-related fMRI. Healthy subjects participated in two scan sessions in a randomized, double-blind, placebo-controlled design. Ketamine increased CMRO2and cerebral blood flow (CBF) in prefrontal cortex (PFC) and other cortical regions. However, resting-state cortical functional connectivity was not affected. Ketamine did not alter CBF-CMRO2coupling brain-wide. Higher levels of basal CMRO2were associated with lower task-related PFC activation and WM accuracy impairment under both saline and ketamine conditions. These observations suggest that CMRO2and resting-state functional connectivity index distinct dimensions of neural activity. Ketamine’s impairment of WM-related neural activity and performance appears to be related to its ability to produce cortical metabolic activation. This work illustrates the utility of direct measurement of CMRO2via calibrated fMRI in studies of drugs that potentially affect neurovascular and neurometabolic coupling.

BACKGROUND Family history of alcohol use disorder; AUD (FH +) and impulsivity-related traits are known risk factors for problem drinking that have been investigated in predominately White samples. This cross-sectional study examined whether these risk factors vary by sex in the overall, majority White sample and in a Black subsample. METHOD A model building regression procedure was used to investigate the combined effect of FH + and impulsivity-related traits on alcohol quantity, frequency, and problems by sex (overall sample: N = 757, 50% female, 73% White, agemean = 33.74, SD = 11.60; Black subsample: n = 138, 47% female, agemean = 33.60, SD = 9.87). RESULTS Overall Sample. No sex differences were found in the compounding effects of FH + and impulsivity-related traits on alcohol outcomes. Males reported more physical, social, and overall alcohol-related problems than females. FH + was positively associated with all alcohol-related consequences. Poor self-regulation was the only trait associated with all alcohol outcomes. Black Subsample: A three-way interaction suggested a negative association between inhibition and frequency of alcohol use among FH + males only. A two-way interaction also suggested impulse control was associated with more interpersonal alcohol-related problems among males only. Main effects were also found in the expected direction such that higher impulsivity and FH + were associated with poorer alcohol outcomes. CONCLUSION These findings suggest no sex differences in the overall sample in the interactive effects of established risk factors for AUD on alcohol outcomes, and that poor self-regulation may be key for personality-targeted alcohol prevention and intervention programs. Preliminary findings of sex differences in the Black subsample should be replicated. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

E-cigarettes are popular among adolescents. Given that flavors enhance e-cigarette appeal, this study examined the influence of flavors on nicotine in e-cigarettes. Youth e-cigarette users (average 26.2 days [SD = 3.6] in past 28 days) were randomized to use e-cigarettes containing 6 or 12 mg/mL of freebase nicotine and completed 4 test sessions. During the first 3 test sessions, participants completed 3 fixed puffing bouts (1 puffing bout = 10 puffs, 3 s each, 30-s interval), using menthol, green-apple, and unflavored e-liquids (50 propylene glycol [PG]/50 vegetable glycerin [VG]) with their assigned nicotine concentration in a random order using a ∼5.5-W V2 e-cigarette device. After each puffing bout, participants assessed subjective effects of nicotine and flavor. In the 4th test session, participants used any of the e-liquids they had tried in the earlier sessions, ad libitum for 60 min and the amount of e-liquid used for each flavor and the number of puffs was assessed. Participants (n = 49; 6 mg/mL [n = 24]; 12 mg/mL [n = 25]) were 63.3% male, 65.3% non-Hispanic White with an average age of 18.7 (SD = 0.9). Mixed models analysis revealed that green apple and 6 mg/mL of nicotine independently increased liking of e-cigarette taste. In addition, green apple produced higher ratings of fruitiness, sourness, sweetness, and menthol produced higher ratings of coolness. We did not observe any interactions between nicotine and flavor. Youth liked the taste of e-liquids containing green-apple flavor or low nicotine concentration which highlights the appeal of fruit flavors in e-cigarettes to adolescents. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Loss-of-control (LOC)-eating postoperatively predicts suboptimal longer-term outcomes following bariatric surgery. This study examined longer-term effects through 24-month follow-ups after completing treatments in a randomized controlled trial testing guided-self-help treatments (cognitive-behavioral therapy [gshCBT] and behavioral weight-loss [gshBWL]) and control (CON) delivered postoperatively for LOC-eating.140 patients with LOC-eating 6 months after bariatric surgery were randomized (5:5:2 ratio) to 3-months of gshCBT (n = 56), gshBWL (n = 60), or CON (n = 24) delivered by trained allied-health clinicians. Independent assessments were performed throughout/after treatments and at 6-, 12-, 18-, and 24-month follow-ups; 83% of patients were assessed at 24-month follow-up.Intention-to-treat analyses comparing the three groups (gshCBT vs. gshBWL vs. CON) in LOC-eating abstinence at posttreatment (30%, 27%, 38%), 12-month follow-up (34%, 32%, 42%), and 24-month follow-up (45%, 32%, 38%) revealed no significant differences. Mixed-models revealed significantly reduced LOC-eating frequency through posttreatment, no significant changes in LOC-eating frequency during follow-up, and no differences between the three groups. Weight reduced significantly, albeit modestly, through posttreatment but increased significantly and substantially during follow-ups, with no differences between groups.Overall, the 12-week scalable guided-self-help treatments did not differ from each other or control, were associated with significantly reduced frequency of LOC-eating and modest weight loss at posttreatment but were followed by significant weight gain during the 24-month follow-up. Weight gain was substantial and nearly universal whereas the frequency of LOC-eating did not change over time (i.e., LOC-eating reductions and abstinence rates were well maintained through 24-moth follow-ups). Patients with postoperative LOC-eating require more intensive adjunctive treatments.Loss-of-control (LOC) eating postoperatively predicts poorer bariatric surgery outcomes and the longer-term effects of postoperative adjunctive postoperative interventions for LOC eating are unknown. In this 24-month follow-up of a controlled study of scalable guided-self-help treatments and a control condition, improvements in LOC-eating frequency, eating-disorder psychopathology, and depression during treatment were maintained well, with no differences between the three groups. Proportion of patients achieving abstinence from LOC-eating at the 24-month follow-up ranged from 38% to 45% across the three groups. In contrast, weight increased significantly during the 24-month follow-ups, with no differences between the three groups. Findings suggest LOC-eating following bariatric surgery might represent a "marker" for a subgroup of patients that are at risk for substantial weight gains over time. LOC eating following bariatric surgery is challenging to treat with low-intensity scalable treatments and may require more intensive specialist treatments.

Objective A substantial proportion of patients with binge-eating disorder (BED) do not derive sufficient benefits from available evidence-based psychological interventions. We examined depression scores as predictors and moderators of response to cognitive-behavioral therapy (CBT) and behavioral weight-loss (BWL) for BED. We explored associations between changes in depression scores and changes in treatment outcomes. Method Ninety adults with BED with obesity were randomized to CBT or BWL (6 months) and were evaluated independently throughout treatment, at posttreatment, and 12-month follow-up after treatments (18 months post-randomization). Pre-treatment depression scores, early changes in depression, and changes in depression from pre- to post-treatment were tested as predictors/moderators of outcomes (binge-eating frequency and eating-disorder psychopathology). Results Baseline depression scores did not predict nor moderate outcomes at post-treatment or 12-month follow-up. Changes in depression scores (both early and throughout treatment) were not associated significantly with changes in binge-eating frequency or eating-disorder psychopathology at post-treatment or 12-month follow-up. Discussion Findings suggest depression scores do not predict nor moderate acute- or longer-term outcomes in patients with BED receiving CBT or BWL. Findings reinforce need to improve treatments for BED overall, although they provide confidence that patients with elevated depression scores derive benefits from existing CBT and BWL interventions.

Objective Recent findings have examined the factor structure and associated correlates of three neurofunctional domains, Executive Function, Incentive Salience, and Negative Emotionality in the development and maintenance of alcohol use disorders in a clinical sample. The current study sought to replicate and extend prior work by testing this three-factor model, utilizing both exact and similar phenotypic measures, as well as novel measures, in a non-treatment seeking sample. Methods Self-report measures of alcohol addiction, impulsivity, behavior, and exposure to early-life stress were collected as part of baseline assessments for alcohol imaging and pharmacotherapy studies in 335 individuals. Confirmatory factor analysis (CFA) was used to examine model structure and fit. A multiple indicators, multiple causes (MIMIC) model identified predictors of latent factors identified by CFA. Results Results supported an intercorrelated model with three factors: Executive Function, Incentive Salience, and Emotionality. All factors were associated with current AUD and Incentive Salience was uniquely associated with past 30-day drinking frequency. MIMIC results identified multiple significant predictors of these latent factors, including history of alcohol use disorder, positive family history of alcohol dependence, earlier age of first drink, and a history of childhood emotional abuse and physical neglect. Conclusions Our results support an intercorrelated three-factor model of neurofunctional domains in alcohol use models, consistent with published findings (Kwako et al., 2019). Because childhood physical neglect was a significant predictor of all latent factors, these results also highlight the significant negative impact of childhood neglect on later addiction development.

RATIONALE: Reducing nicotine content of inhaled tobacco products may prevent nicotine addiction, but the threshold for nicotine reinforcement has not been systematically evaluated in controlled human laboratory studies. OBJECTIVES: The current study uses a novel double-blind placebo-controlled intravenous (IV) nicotine self-administration (NSA) model to determine threshold for subjective effects of nicotine and nicotine reinforcement using a forced choice self-administration procedure. METHODS: Young adults (n = 34) had 5 laboratory sessions after overnight nicotine abstinence. In each session, participants sampled and rated the subjective effects of an IV dose of nicotine (0.0125, 0.025, 0.05, 0.1, or 0.2 mg nicotine/70 kg bodyweight) versus saline (placebo), then were given a total of 10 opportunities to self-administer either the IV dose of nicotine or placebo. RESULTS: Mixed effect models revealed a significant effect of nicotine dose for positive (i.e., “stimulatory” and “pleasurable”; p < .0001) effects, but not “aversive” effects during sampling period. Post hoc comparisons showed that higher doses (i.e., 0.1 and 0.2 mg) were associated with greater stimulatory, pleasurable, and physiological effects than placebo and lower doses. Mixed effect models revealed that only the highest dose (i.e., 0.2 mg) was consistently preferred over placebo. Sex differences were generally weak (p = .03–.05). CONCLUSIONS: Using our IV nicotine NSA model, the threshold for detecting positive effects of nicotine in young adult smokers is about 0.1 mg, but a higher dose of nicotine, 0.2 mg, is required to produce a consistent nicotine reinforcement. Regarding the regulatory impact, our findings further support the value of nicotine reinforcement threshold as a tobacco regulatory target.

Objective Loss-of-control (LOC) eating postoperatively is a consistent predictor of suboptimal longer-term bariatric surgery outcomes. This randomized controlled trial examined the effectiveness of two guided self-help treatments (cognitive behavioral therapy [gshCBT] and behavioral weight loss [gshBWL]) compared with a control (CON) for reducing LOC eating and weight. Methods A total of 140 patients with recurrent LOC eating approximately 6 months after bariatric surgery were randomly assigned (5:5:2 ratio) to one of three conditions: gshCBT (n = 56), gshBWL (n = 60), or CON (n = 24). Three-month treatments were delivered by trained allied health clinicians to increase generalizability to bariatric surgery settings. Independent assessments were performed by doctoral research-clinicians using established interviews/measures; posttreatment outcomes were obtained for 89% of patients. Results Mixed models revealed significant improvements for LOC eating frequency and weight loss but no significant differences between treatments; race neither predicted (main effect) nor moderated (interaction effect) treatment outcomes. Intent-to-treat categorical analyses of abstinence from LOC eating (30% for gshCBT, 27% for gshBWL, 38% for CON) and proportion attaining 5% weight loss (20%, 22%, 17%) revealed no significant differences between treatments; non-White participants had a higher proportion achieving LOC eating abstinence but a lower proportion attaining 5% weight loss compared with White participants. Conclusions In this 12-week randomized controlled trial following bariatric surgery, significant LOC eating reductions and weight loss did not differ significantly between treatments. Race was associated with posttreatment categorical outcomes.

BACKGROUND: Data from trials of medications for alcohol use disorder (AUD) can be used to identify predictors of drinking outcomes regardless of treatment, which can inform the design of future trials with heterogeneous populations. Here, we identified predictors of abstinence, no heavy drinking days, and a 2-level reduction in World Health Organization (WHO) drinking levels during treatment for AUD in the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) Study. METHODS: We utilized data from the COMBINE Study, a randomized placebo- controlled trial evaluating the efficacy of naltrexone and acamprosate, both alone and in combination, for AUD (n = 1168). A tree-based machine learning algorithm was used to construct classification trees predicting abstinence, no heavy drinking days, and a 2-level reduction in WHO drinking levels in the last 4 weeks of treatment, based on 89 baseline variables. RESULTS: The final tree for predicting abstinence had one split based on consecutive days abstinent prior to randomization, with a higher proportion of subjects achieving abstinence among those classified as abstinent for >2 versus ≤2 consecutive weeks prior to randomization (66% vs. 29%). The final tree for predicting no heavy drinking days in the last 4 weeks of treatment had three splits based on consecutive days abstinent, age, and total Alcohol Dependence Scale score at baseline. Seventy-three percent of the subjects classified as abstinent for >2 consecutive weeks prior to randomization had no heavy drinking days in the last 4 weeks of treatment. Among those classified as abstinent ≤2 consecutive weeks prior, three additional splits showed that younger subjects (age ≤44 years; 37%), and older subjects (age >44) with a total Alcohol Dependence Scale score >13 and complete abstinence (56%) or other drinking goals (35%), were less likely to have no heavy drinking days than older subjects with a total Alcohol Dependence Scale score ≤13 (67%). The final tree for predicting a 2-level reduction in WHO levels had no splits. CONCLUSIONS: Consecutive days abstinent prior to randomization may predict absti- nence and no heavy drinking days and total Alcohol Dependence Scale score and age may predict no heavy drinking days. The 2-level reduction in WHO levels outcome may be less likely to discriminate based on multiple patient characteristics.

BACKGROUND: There is a need for novel alcohol biosensors that are accurate, able to detect alcohol close in time to consumption, and feasible and acceptable for many clinical and research applications. We evaluated the field accuracy and tolerability of a novel (BACTrack Skyn) and established (Alcohol Monitoring Systems SCRAM CAM) alcohol biosensor. METHODS: The sensor and diary data were collected in a larger study of a biofeedback intervention but compared observationally in the present sub-study. Participants (high-risk drinkers, 40% female; median age 21) wore both Skyn and SCRAM CAM sensors for 1 to 6 days and were instructed to drink as usual. Data from the first cohort of participants (N=27; 101 person-days) were used to find threshold values of transdermal alcohol that classified each day as meeting or not meeting defined levels of drinking (heavy, above-moderate, any). These values were used to develop scoring metrics that were subsequently tested using the second cohort (N = 20; 57 person-days). Data from both biosensors were compared to mobile diary self-report to evaluate sensitivity and specificity in relation to a priori standards established in the literature. RESULTS: Skyn classification rules for Cohort #1 within 3 months of device shipment showed excellent sensitivity for heavy drinking (94%) and exceeded expectations for above-moderate and any drinking (78%/69%), while specificity met expectations (91%). However, classification worsened when Cohort #1 devices ≥3 months from shipment were tested (area under curve for receiver operator characteristic .87 vs .79) and the derived classification threshold when applied to Cohort #2 was inadequately specific (70%). Skyn tolerability metrics were excellent and exceeded the SCRAM CAM (p ≤.001). CONCLUSIONS: Skyn tolerability was favorable and accuracy rules were internally derivable but did not yield useful scoring metrics going forward across device lots and months of usage.

Objective This study aimed to examine longer-term effects of behavioral weight loss (BWL) and Stepped Care for binge-eating disorder and obesity through 12-month follow-up after completing treatments. Methods A total of 191 patients with binge-eating disorder/obesity were randomized to 6 months of BWL (n = 39) or Stepped Care (n = 152). Within Stepped Care, patients began BWL (1 month), treatment responders continued BWL, nonresponders switched to cognitive behavioral therapy, and all were randomized (double-blind) to weight-loss medication or placebo (5 months). Patients were independently assessed throughout/after treatment and at 6- and 12-month follow-ups. Results Intent-to-treat analyses of remission rates revealed that BWL and Stepped Care did not differ significantly at posttreatment (74.4% vs. 66.5%), 6-month follow-up (38.2% vs. 33.3%), or 12-month follow-up (44.7% vs. 41.0%). Mixed models of binge-eating frequency indicated significant reductions through posttreatment but no significant changes or differences between BWL and Stepped Care during follow-up. Mixed models revealed significant weight loss with no differences between BWL and Stepped Care (5.1% vs. 5.8%) at posttreatment and significant time effects (larger percent weight loss at 6-month than at 12-month follow-up) with no differences between BWL and Stepped Care (-5.1% vs. -5.2% and -3.4% vs. -5.0%, respectively). Conclusions Binge-eating improvements and weight loss produced by BWL and adaptive Stepped Care did not differ significantly 12 months after completing treatments.

Differential susceptibility theory (DST) posits that individuals differ in their developmental plasticity: some children are highly responsive to both environmental adversity and support, while others are less affected. According to this theory, “plasticity” genes that confer risk for psychopathology in adverse environments may promote superior functioning in supportive environments. We tested DST using a broad measure of child genetic liability (based on birth parent psychopathology), adoptive home environmental variables (e.g., marital warmth, parenting stress, and internalizing symptoms), and measures of child externalizing problems (n = 337) and social competence (n = 330) in 54-month-old adopted children from the Early Growth and Development Study. This adoption design is useful for examining DST because children are placed at birth or shortly thereafter with nongenetically related adoptive parents, naturally disentangling heritable and postnatal environmental effects. We conducted a series of multivariable regression analyses that included Gene × Environment interaction terms and found little evidence of DST; rather, interactions varied depending on the environmental factor of interest, in both significance and shape. Our mixed findings suggest further investigation of DST is warranted before tailoring screening and intervention recommendations to children based on their genetic liability or “sensitivity.”

Introduction Evaluations of multiple tobacco product use and temporal changes in patterns of use are complicated by a large number of combinations and transitions. Visualization tools could easily identify most common patterns and transitions. Methods Set intersection bar plots describe ever use of five tobacco products among 12–17 years old youth in wave 1 of the Population Assessment of Tobacco and Health (PATH) study (N = 11 497). Heat maps visualize unweighted frequencies of transitions from ever use at wave 1 (2013–2014) to past 12-month use at wave 2 (2014–2015). Weighted calibrated heat maps assess differences in relative frequencies of transitions by pattern at wave 1 and identify differences in transitions by sex. Results The most common tobacco product ever use patterns in wave 1 were of cigarettes only, e-cigarettes only or hookah only, followed by ever use of both cigarettes and e-cigarettes. Initiation of use between waves was uncommon. The most frequent transition among those who reported use at wave 2 but not at wave 1 (N = 971) was to e-cigarette use (N = 301). However, among e-cigarette-only ever users at wave 1 (N = 260), about half did not report any product use at wave 2. Use of three or more products remained stable. Adolescent girls compared to boys appeared more likely to report hookah use at both waves. Conclusion Set intersection bar plots and heat maps are useful for visualizing tobacco product use patterns and transitions, especially for multiple products. Both techniques could identify common problematic tobacco use patterns across and within populations. Implications Given the growing complexity of the youth tobacco use landscape, approaches to efficiently communicate patterns of multiple tobacco product use should be used more often. This study introduces set intersection bar plots and modified versions of heat maps to the tobacco product literature and illustrates their use in the PATH youth sample. These techniques are useful for visualizing absolute and relative frequencies of multiple possible patterns and transitions. They also suggest targets for subsequent statistical inference such as sex differences in hookah use. The methods can be applied more generally for data visualization wherever large number of combinations occurs.

ObjectivesCombined smoking and heavy drinking is a significant health burden. Varenicline, an efficacious tobacco pharmacotherapy that also shows promise for drinking, has yielded mixed results among heavy-drinking smokers. This pilot study investigated integrated tobacco and alcohol counselling plus varenicline for this vulnerable group.DesignTwelve-week parallel, randomized controlled pilot trial of two behavioural interventions in combination with open-label varenicline. Participants were randomized using computer-generated tables, stratified by sex.SettingOutpatient academic medical centre research clinic.ParticipantsVolunteers who reported smoking and heavy drinking and sought tobacco or alcohol treatment (N = 26).Intervention(1) Integrated tobacco + alcohol counselling (INT; n = 13) or (2) counselling focused on their presenting concern (i.e., tobacco or alcohol) (SINGLE; n = 13), plus varenicline (2 mg) for 12 weeks.Main outcomesFeasibility/acceptability, smoking quit rates and heavy drinking.ResultsINT feasibility/acceptability was high among men but not women. More participants quit smoking in INT than SINGLE. This outcome was only in men, not significant, but had a medium effect size. Both conditions yielded significant drinking reductions.ConclusionIntegrated tobacco and alcohol behavioural counselling plus varenicline may be feasible and promote smoking cessation among men who smoke and drink heavily, but a larger sample is needed to replicate this finding.