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Screening to identify patients at risk for opioid misuse after trauma is recommended but not commonly used to guide perioperative opioid management interventions. The Multimodal Analgesic Strategies for Trauma trial demonstrated that an opioid-minimizing multimodal pain regimen reduced opioid exposure in a heterogeneous trauma patient population. Here, we assess the efficacy of the Multimodal Analgesic Strategies for Trauma multimodal pain regimen in a critical patient subgroup who screened at high risk for opioid misuse. The Multimodal Analgesic Strategies for Trauma trial compared an opioid-minimizing multimodal pain regimen (oral acetaminophen, naproxen, gabapentin, lidocaine patch, as-needed opioid) against an original multimodal pain regimen (intravenous followed by oral acetaminophen, 48-hour celecoxib and pregabalin, followed by naproxen and gabapentin, scheduled tramadol, as-needed opioid), in a randomized trial conducted from April 2018 to March 2019. A total of 631 enrolled patients were classified either as low- or high-risk via the Opioid Risk Tool. Bayesian analyses evaluated the moderating influence of Opioid Risk Tool risk (high/low) on the effect of Multimodal Analgesic Strategies for Trauma multimodal pain regimen (versus original) on opioid exposure (morphine milligram equivalents/day), opioids prescribed at discharge, and pain scores. Multimodal Analgesic Strategies for Trauma multimodal pain regimen effectively reduced morphine milligram equivalents/day in low- and high-Opioid Risk Tool risk groups. Moderation was observed for opioids at discharge and pain scores; Multimodal Analgesic Strategies for Trauma multimodal pain regimen was effective in the high-risk group only (opioids at discharge: 63% vs 77%, relative risk = 0.86, 95% Bayesian credible interval [0.66–1.08], posterior probability (relative risk <1) = 90%; pain scores: b = 3.8, 95% Bayesian credible interval [3.2–4.4] vs b = 4.0, 95% Bayesian credible interval [3.4–4.6], posterior probability (b <0) = 87%). This study is the first to show the moderating influence of opioid misuse risk on the effectiveness of an opioid-minimizing multimodal pain regimen. The Opioid Risk Tool was useful in identifying high-risk patients for whom the Multimodal Analgesic Strategies for Trauma multimodal pain regimen is recommended for perioperative pain management. [Display omitted] [ABSTRACT FROM AUTHOR]

Acute inflammation is associated with sickness behavior characterized by reduced motivation for pleasurable activities in humans. The current study investigated the effect of an experimentally induced inflammatory stimulus on motivational reward in people who remitted from depression. This randomized, double-blind crossover study involved 12 participants, 5 with remitted major depressive disorder (rMDD) and 7 healthy controls (HC), who received an injection of typhoid vaccine and placebo (or vice-versa) intramuscularly at least one week apart. At baseline and between 4 and 6 h post-injection on both days, participant mood was measured using the profile of mood states (POMS), and injection blood samples were collected for cytokines measurement. All participants completed the Effort Expenditure for Rewards Task (EEfRT), a behavioral paradigm measuring effort-based decision-making before and 4 h post-both injections. Generalized linear mixed modeling was used to evaluate group differences in choosing the hard over easy task to obtain a monetary reward. Typhoid vaccine increased IL-6 in all participants. On the EEfRT, a significant interaction between treatment condition (typhoid vs. placebo) and participant group (HC vs. rMDD) was found (p =.004). Analyses of simple effects within treatment conditions found that after placebo, HCs were more likely to choose the harder task than rMDD (OR = 3.21; p =.013). However, after the typhoid vaccine, no differences were found between rMDD and HC (p =.397). Analyses within participant groups found that the probability of choosing a hard task was higher after placebo for HC (OR = 1.37; p =.045), but not different within rMDD (p =.241). For HC at baseline, mood was significantly lower following injection with typhoid vaccine, relative to placebo (b = −1.03, p <.001); however, this effect should be considered coincidental, given that mood rating was taken prior to injection. For rMDD patients 4–6 h post-injection, mood was significantly lower following typhoid vaccine, relative to placebo (b = −0.981, p <.001 b = −0.77, p <.001). Finally, for HC receiving placebo, mood was significantly lower 4–6 h post-injection, relative to baseline (b = −1.76, p <.001). Our preliminary findings suggest persistent deficits in motivational reward processing function despite clinical improvement in remitted depressed patients. • Typhoid vaccine can be used as an immune challenge. • Typhoid vaccine can be used to study motivational behavior in depression. • Typhoid vaccine increased interleukin (IL6) and induced negative mood. • Depressed patients in remission show motivational deficits compared to control. • Motivational deficits persist in depressed patients despite remission. [ABSTRACT FROM AUTHOR]

• The Metacognitions about Smoking Questionnaire (MSQ) demonstrated good psychometric soundness when measuring metacognitive factors associated with e-cigarette use. • Three distinct factors were identified in relation to e-cigarette use outcome expectancies: 'positive metacognitions about cognitive regulation' (PMCR), 'positive metacognitions about emotional regulation' (PMER), and 'negative metacognitions' (NM). • Participants with higher outcome expectancies for cognitive and emotional regulation, as well as negative outcomes, tended to use e-cigarettes more frequently, indicating a significant association between these metacognitive factors and e-cigarette use behavior. Metacognition can be understood as 'cognition of cognition' or 'thinking about thinking'. Metacognition research has primarily focused on cigarette smoking, while e-cigarette use has been relatively unexplored. The study sought to examine the properties of the Metacognitions about Smoking Questionnaire (MSQ), as it was adapted for use among adolescent and young adult e-cigarette users. Further, the study sought to examine the ability of the Metacognitions about Smoking Questionnaire (MSQ) to predict past 30-day e-cigarette use among adolescent and young adult e-cigarette users. The study analyzed data collected by the Texas Adolescent Tobacco and Marketing Surveillance System (TATAMS) in Spring 2020. The instrument consisted of 20 items found to have sound psychometric properties when validated among self-defined cigarette smokers in the UK. The instrument was adapted for e-cigarette use by providing a brief description before the items. Participants were asked "Which of the following products you use most often?", and those who selected "e-cigarettes" were included in the study. Participants were then presented with 20 statements about beliefs people hold about using e-cigarette and were instructed to determine their agreement with the statements on a four-point Likert scale with respect to e-cigarette use. Factors were extracted using Exploratory Factor Analysis (EFA) and factor structure was verified using Confirmatory Factor Analysis (CFA). Further, each of the extracted factors were used to predict past 30-day e-cigarette use frequency in the most frequent group, using conditional effects, holding the most frequent category of categorical covariates, mean of continuous covariates and the other two metacognitive factors as reference levels. Past 30-day e-cigarette use was measured as the number of days of use in the past 30-days. Participants who reported e-cigarette use in the past 30-days were included in this analysis (n = 244). Participants were in 10th grade (n = 46), 12th grade (n = 92) and two years beyond high school (n = 106). EFA was conducted and items were assessed with varimax rotation. CFA was conducted with multiple models (one factor, two factor and three factor solutions) and the 3-factor solution showed the best fit. Factors were named as 'positive metacognitions about cognitive regulation'(PMCR) (e.g. '...helps me think more clearly'), 'positive metacognitions about emotional regulation'(PMER) (e.g. '...helps me to relax when I am agitated'), and 'negative metacognitions'(NM) (e.g. 'It is hard to control my desire for e-cigarettes'). Cronbach's alpha showed high internal consistency (0.92, 0.90 and 0.91, respectively). The median score (range) was 7 (5–20), 10 (5–20), and 11 (10–40) on PMCR, PMER, and NM factors. Higher scores denote higher levels of outcome expectancies of that factor. Lowest and highest score on PMCR was associated with 15 and 20.4 days of e-cigarette use in the past 30-days, respectively. Similarly, lowest and highest score on PMER and NM were associated with 13.2 and 21 days, and 14.7 and 24.6 days, respectively. The results indicate that participants who reported highest outcome expectancies for cognitive regulation, emotional regulation, and negative outcomes, used e-cigarettes on average 5, 8 and 10 days more than those who reported lowest outcome expectancies for these factors. The MSQ showed good psychometric soundness for measuring metacognitive factors associated with e-cigarette use. For cigarette smoking, the original questionnaire distinguished negative cognitions of 'uncontrollability' and 'cognitive interference', which was not seen in e-cigarette users. This indicates a difference in cognitions of cigarette and e-cigarette users. The instrument can help understand the similar role of cognition in e-cigarette use behavior and further assess association with e-cigarette use. [ABSTRACT FROM AUTHOR]

Acceptance and mindfulness processes indicating psychological flexibility may be important mechanisms in chronic pain adaptation; however, their association with opioid analgesic misuse (OA) risk is unclear. The present study investigated the extent to which psychological flexibility is associated with OA misuse risk within a chronic low back pain population on long-term opioid therapy. Participants were 156 patients presenting for treatment at an academic pain clinic. Aspects of psychological flexibility were assessed using the Mindfulness Attention Awareness Scale (MAAS) and the Acceptance and Action Questionnaire II (AAQ II). The Current Opioid Misuse Measure (COMM) determined heightened risk of opioid analgesic misuse. Participants were 59% female, 48.3 years old on average (SD = 9.8), and largely White, Hispanic. Nested multiple linear regression indicated that the higher mindfulness levels predicted opioid misuse risk while controlling for pain severity, pain-related interference, pain anxiety, and acceptance. The full regression model predicted 54% of the variance in OA misuse risk. Results suggest that psychological flexibility, particularly mindfulness processes, may be important in predicting and mitigating OA misuse risks among chronic pain patients. Non-pharmacological interventions are critical to addressing the current opioid misuse crisis. • More than half of chronic pain patients were at high risk for opioid misuse. • Pain severity, pain anxiety and mindfulness were predictive of opioid misuse. • The regression model predicted 54% of the variance of opioid misuse. [ABSTRACT FROM AUTHOR]

• First examination of the orexin system in human psychostimulant users. • Results supported evidence for a signal of suvorexant in several target domains. • Orexin may be a favorable target for relapse-prevention in cocaine use disorder. Rationale. Current evidence and literature reviews provide a strong justification for examining the orexin receptor (OXR) system as a therapeutic target in substance use disorders, including cocaine and other psychostimulants. Objectives. In this preliminary, proof-of-concept examination of orexin modulation in humans with cocaine use disorder, we measured changes in domains tied to relapse: stress, sleep, cue reactivity, and inhibitory control. Additionally, mood symptoms (anxiety, depression), medication compliance, and side effects were assessed. Methods. Twenty non-treatment seeking subjects with cocaine use disorder (CUD) received either the OX 1 R / OX 2 R antagonist suvorexant PO or placebo at 10 PM daily for two weeks (10 mg week 1, 20 mg week 2). Using psychometrics, smart-watch actigraphy, a cold-pressor stress challenge, and eye-tracking technology, the following domains were examined: sleep, stress/anxiety, cue-reactivity (attentional bias, craving), and inhibitory control. Psychometric data were collected every M/W/F (7 time points). Laboratory data were collected weekly (3 time points). Results. Bayesian and frequentist generalized linear models were employed in parallel to examine the effects of suvorexant compared to placebo, with a Bayesian posterior probability threshold >80% as evidence of a signal for suvorexant. Notable results favoring suvorexant over placebo included fewer total anti-saccade errors, improved sleep actigraphy (sleep/awake periods), pre/post cold-pressor change in heart rate and salivary cortisol (all posterior probabilities >94%), and craving (posterior probability >87%). Conclusions. Initial but restricted evidence is provided supporting the orexin system as a modulator of relapse-related processes in cocaine use disorder. Baseline differences in the main outcome variables were not experimentally controlled and differences in craving were observed at baseline. This, in combination with a limited sample size, constrain the nature of the project. The results may serve to inform more comprehensive future research. [ABSTRACT FROM AUTHOR]

Objective: To evaluate a hospital-initiated intervention to reduce tobacco smoke exposure in infants in the neonatal intensive care unit.Study Design: A randomized, controlled trial compared motivational interviewing plus financial incentives with conventional care on infant urine cotinine at 1 and 4 months' follow-up. Mothers of infants in the neonatal intensive care unit (N = 360) who reported a smoker living in the home were enrolled. Motivational interviewing sessions were delivered in both the hospital and the home. Financial incentives followed session attendance and negative infant cotinine tests postdischarge.Results: The intervention effect on infant cotinine was not significant, except among mothers who reported high baseline readiness/ability to protect their infant (P ≤ .01) and mothers who completed the study within 6 months postdischarge (per protocol; P ≤ .05). Fewer mothers in the motivational interviewing plus financial incentives condition were smoking postdischarge (P ≤ .01). More mothers in the motivational interviewing plus financial incentives group reported a total home and car smoking ban at follow-up (P ≤ .05).Conclusions: Motivational interviewing combined with financial incentives reduced infant tobacco smoke exposure in a subset of women who were ready/able to protect their infant. The intervention also resulted in less maternal smoking postpartum. More robust interventions that include maternal and partner/household smoking cessation are likely needed to reduce the costly effects of tobacco smoke exposure on children and their families.Trial Registration: ClinicalTrials.gov: NCT01726062. [ABSTRACT FROM AUTHOR]

• Non-drinkers displayed a larger feedback-related negativity to aversive outcomes compared to rewards. • Drinkers had a blunted feedback-related negativity to aversive outcomes compared to non-drinkers. • College drinkers are less sensitive to aversive outcomes, which could contribute to alcohol use. The current study compared electrophysiological responses (the feedback-related negativity [FRN]) to appetitive and aversive outcomes between a group of college drinkers and non-drinkers. 50 undergraduate students completed a passive, slot machine-like task while their electroencephalographic data was recorded to extract the FRN to unexpected appetitive and aversive outcomes. In the appetitive condition, participants could expectedly or unexpectedly win $1 or not win $1 and in the aversive condition participants could expectedly or unexpectedly be exposed to a loud noise burst or silence. The FRN was recorded in response to a cue indicating the outcome. Participants also reported on the number of drinks they consumed in a typical week to establish drinking status (drinker/non-drinker). Results showed that non-drinkers had a larger FRN in the aversive task compared to the appetitive task while drinkers had similar FRNs between the tasks. Drinkers had a significantly smaller aversive outcome related FRN compared to non-drinkers. Neural sensitivity to aversive outcomes might be a marker of decreased punishment sensitivity in college drinkers compared to non-drinkers, contributing to unhealthy drinking behavior. [ABSTRACT FROM AUTHOR]

• Interpheron-alpha treatment in patients with chronic medical illness was associated with a reduction in plasma tryptophan levels. • Interferon-alpha treatment was associated with an increase in plasma kynurenine levels and kynurenine/tryptophan ratio activity. • Interpheron-alpha treatment was associated with increase in depression symptoms over time. Dysregulated kynurenine (KYN) pathway has been implicated in the pathophysiology of depression. In this systematic review, we examined the relationship between kynurenine pathway metabolites (KYN, kynurenic acid KYNA, tryptophan TRP, quinolinic acid QUIN, KYN/TRP ratio) and depression symptoms in the context of pro-inflammatory activation and immune response. Out of 5,082 articles, fifteen studies were suitable; ten studies (N = 315 medically ill patients treated with interferon-alpha IFN-α) reported baseline and post-intervention plasma KYN, TRP and KYN/TRP ratios which were included in quantitative meta-analysis. Data from five studies were summarized (IFN-α, interferon-beta IFN-β, and lipopolysaccharide LPS). We found that IFN-α treatment in patients with chronic illnesses was associated with decreased TRP, increased levels of KYN and KYN/TRP ratio and depression scores from baseline to follow-up at both 4 and 24 weeks. Our findings suggest that increased risk of depression observed after immune-activating agents in patients with chronic medical illnesses is likely mediated by the kynurenine pathway. Further prospective studies are required to investigate the exact pathophysiology of the KYN pathway in depression. [ABSTRACT FROM AUTHOR]

This study explored anhedonia (lack of interest or pleasure in non-drug rewards) as a potentially modifiable individual difference associated with the effectiveness of Contingency Management (CM). It also tested the hypothesis that a dopaminergic drug, levodopa (L-DOPA), would improve the effectiveness of CM, particularly in individuals high in anhedonia. The study was a single-site, randomized, double-blind, parallel group, 12-week trial comparing L-DOPA with placebo, with both medication groups receiving voucher-based CM targeting cocaine-negative urines. Participants were N=85 treatment-seeking adults with CUD. Anhedonia was measured at baseline using a validated self-report measure and a progressive ratio behavioral measure. Treatment Effectiveness Score (TES) was defined as the total number of cocaine-negative urines submitted. Analyses based on Frequentist general linear models were not significant, but Bayesian analyses indicated a high probability (92.6%) that self-reported anhedonia was associated with poor treatment outcomes (lower TES). L-DOPA did not significantly improve outcomes, nor was the effect of L-DOPA moderated by anhedonia. While the study failed to replicate positive findings from previous studies of L-DOPA in combination with CM, it does provide preliminary evidence that anhedonia may be a modifiable individual difference associated with poorer CM outcomes. [ABSTRACT FROM AUTHOR]

Material and methods Brain volumetric measures were obtained for 82 children and adolescents including 18 unaffected BD offspring (10.50 ± 3.37 years), 19 BD offspring suffering from psychiatric disorders (12.87 ± 3.28 years) and 45 healthy controls (HC-10.50 ± 3.37 years). Clinical diagnoses were established according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Cortical reconstruction and volumetric segmentation were performed with the Freesurfer image analysis suite. Profile analyses compared frontolimbic volumes across groups. Age, gender, testing site, ethnicity and intracranial volume were entered as covariates. Results The right amygdala was significantly larger in unaffected BD offspring compared to BD offspring with psychiatric disorders and HC. Volumes of striatal, hippocampal, cingulate, and temporal regions were comparable across groups. Discussion The size of the amygdala may be a marker of disease susceptibility in offspring of BD parents. Longitudinal studies are needed to examine rates of conversion to BD as related to specific pre-morbid brain abnormalities. [ABSTRACT FROM AUTHOR]

Background: Out-of-hospital cardiac arrest (OHCA) data debriefing and clinical research often require the retrospective analysis of large datasets containing defibrillator files from different vendors and clinical annotations by the emergency medical services.Aim: To introduce and evaluate a methodology to automatically extract cardiopulmonary resuscitation (CPR) quality data in a uniform and systematic way from OHCA datasets from multiple heterogeneous sources.Methods: A dataset of 2236 OHCA cases from multiple defibrillator models and manufacturers was analyzed. Chest compressions were automatically identified using the thoracic impedance and compression depth signals. Device event time-stamps and clinical annotations were used to set the start and end of the analysis interval, and to identify periods with spontaneous circulation. A manual audit of the automatic annotations was conducted and used as gold standard. Chest compression fraction (CCF), rate (CCR) and interruption ratio were computed as CPR quality variables. The unsigned error between the automated procedure and the gold standard was calculated.Results: Full-episode median errors below 2% in CCF, 1 min-1 in CCR, and 1.5% in interruption ratio, were measured for all signals and devices. The proportion of cases with large errors (>10% in CCF and interruption ratio, and >10 min-1 in CCR) was below 10%. Errors were lower for shorter sub-intervals of interest, like the airway insertion interval.Conclusions: An automated methodology was validated to accurately compute CPR metrics in large and heterogeneous OHCA datasets. Automated processing of defibrillator files and the associated clinical annotations enables the aggregation and analysis of CPR data from multiple sources. [ABSTRACT FROM AUTHOR]

Adults experiencing homelessness are more likely to have an alcohol use disorder compared to adults in the general population. Although shelter-based treatments are common, completion rates tend to be poor, suggesting a need for more effective approaches that are tailored to this understudied and underserved population. One barrier to developing more effective treatments is the limited knowledge of the triggers of alcohol use among homeless adults. This paper describes the use of ecological momentary assessment (EMA) to identify predictors of "imminent drinking" (i.e., drinking within the next 4 h), among a sample of adults experiencing homelessness and receiving health services at a homeless shelter. A total of 78 mostly male (84.6%) adults experiencing homelessness (mean age = 46.6) who reported hazardous drinking completed up to five EMAs per day over 4 weeks (a total of 4557 completed EMAs). The study used machine learning techniques to create a drinking risk algorithm that predicted 82% of imminent drinking episodes within 4 h of the first drink of the day, and correctly identified 76% of nondrinking episodes. The algorithm included the following 7 predictors of imminent drinking: urge to drink, having alcohol easily available, feeling confident that alcohol would improve mood, feeling depressed, lower commitment to being alcohol free, not interacting with someone drinking alcohol, and being indoors. The research team used the results to develop intervention content (e.g., brief tailored messages) that will be delivered when imminent drinking is detected in an upcoming intervention phase. Specifically, we created three theoretically grounded message tracks focused on urge/craving, social/availability, and negative affect/mood, which are further tailored to a participant's current drinking goal (i.e., stay sober, drink less, no goal) to support positive change. To our knowledge, this is the first study to develop tailored intervention messages based on likelihood of imminent drinking, current drinking triggers, and drinking goals among adults experiencing homelessness. [ABSTRACT FROM AUTHOR]

The objective of the current meta-analysis was to assess the effect size of the Late Positive Potential (LPP) to drug and emotional cues in substance users compared to controls. The secondary objective was to test for moderation by: age, gender, years of use, use status, and substance type. Search was performed in August 2021 using PubMed. Inclusion criteria were: substance use disorder/dependence or validated self-report, LPP means, healthy control comparison, non-acute drug study, data available, peer-reviewed journal, English, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. Results (k = 11) indicated LPP to drug cues was larger in substance use compared to control group, with a large effect size (Hedges' g =1.66, 95%CI [0.64,2.67], p = 0.005). There were no overall differences for emotional cues. Though threats of selection bias were not severe, inclusion of more studies with larger sample sizes in future meta-analyses will allow more robust tests of publication bias and more accurate measures of effect size. • Late Positive Potential (LPP) represents the motivational relevance of a stimulus. • Meta-analysis estimated effect size of LPP in substance users compared to controls. • LPP to drug and alcohol cues was larger in substance users with a large effect size. • Findings highlight utility of LPP as biomarker of motivated attention to drug cues. [ABSTRACT FROM AUTHOR]

Cocaine use continues to be a significant public health problem with limited treatment options and no approved pharmacotherapies. Cognitive-behavioral therapy (CBT) remains the mainstay treatment for preventing relapse, however, people with chronic cocaine use display cognitive impairments that are associated with poor response to CBT. Emerging evidence in animal and human studies suggests that the peroxisome proliferator-activated receptor-gamma (PPAR- γ) agonist, pioglitazone, improves white matter integrity that is essential for cognitive function. This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from cocaine use disorder. This paper describes the design of a mechanism-focused phase 2 randomized clinical trial that aims first to evaluate the effects of pioglitazone on targeted mechanisms related to white matter integrity, cognitive function, and cocaine craving; and second, to evaluate the extent to which improvements on target mechanisms predict CBT response. Positive results will support pioglitazone as a potential cognitive enhancing agent to advance to later stage medication development research. [ABSTRACT FROM AUTHOR]