Recovery from alcohol use disorder: Reinforcer pathology theory, measurement, and methods.

Recovery from alcohol use disorder (AUD) is a dynamic process that often entails periods of drinking but has been defined primarily by abstinence. Recently, a broader interpretation of recovery was developed, including meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM) remission criteria and improved psychosocial functioning. This new understanding of recovery has facilitated the development of novel theories and methodologies. This paper reviews a new theoretical perspective of recovery, Reinforcer Pathology, and two novel methodological approaches in light of this broader view of recovery. Using this theoretical framework as a foundation, we propose an alternative perspective to explain the recovery process as it relates to environmental factors and valuation of the future; we suggest that changing the environment in which substances are available (e.g., increasing non-alcohol-related activities) and extending one's temporal window are associated with improved recovery outcomes (e.g., remission and quality of life). In this review, we discuss two novel methodological approaches. The first uses latent profile analysis to show that using a measure of Relative Reinforcement Value of Alcohol-Free Activities is associated with a greater likelihood of belonging to a high functioning/infrequent heavy drinking recovery profile. The second developed an online national sample and used an accelerated longitudinal design to study longer-term recovery of up to 12 years over a 5-year study period. Reinforcer Pathology theory, novel methods, and measures may further our understanding of recovery and begin to address critical questions for future studies. Subsequent randomized clinical trials should examine whether the suggested targets and interventions based on the theoretical model improve recovery outcomes prospectively. Measuring and promoting alcohol-free activity engagement may facilitate improved recovery outcomes, while novel methodologies permit an understanding of returning to use or remission across different recovery durations.

Negative Affect, Sensation Seeking, and Adolescent Substance Use Development: The Moderating Role of Executive Function.

It is unknown how the Addictions Neuroclinical Assessment markers-negative affect, sensation seeking, and executive function-contribute to substance use development. This study examined whether associations of negative affect and sensation seeking with substance use vary by executive function. Participants were 167 adolescents (47% female) who participated annually for four years (Mage = 14.07, SDage = 0.54 at Time 1). There were within-person bidirectional associations between higher negative affect and higher substance use for adolescents with lower executive function. Adolescents with higher sensation seeking at age 14 exhibited increasing substance use trajectories from age 14 to 17, regardless of executive function level. Negative affect and substance use influence each other within individuals, whereas sensation seeking predicts substance use between individuals.

Associations between delay discounting and unhealthy behaviors in substance use recovery.

BACKGROUND: Research on delay discounting (DD) is mixed on whether DD is a domain-specific component related to specific behaviors or a domain-general process that cuts across various behaviors. A pivotal group to test the associations between DD and unhealthy behaviors is individuals in recovery from substance use disorders (SUD), as they are moving away from a disorder toward a healthier state. METHODS: Individuals in SUD recovery (n = 317) completed the Temptation Scale, the Health Behaviors Questionnaire, and an Adjusting Delay Discounting Task. An exhaustive model space search was performed using linear regression to examine associations between DD with temptation, engagement in unhealthy behaviors, and the total number of unhealthy behaviors participants engage in. We also tested whether remission status is associated with the total number of unhealthy behaviors participants engage in. RESULTS: Results revealed that DD was positively associated with poor eating (p<.001), physical inactivity (p=.003), financial irresponsibility (p<.001), risky behaviors (p<.001), lack of personal development goals (p<.001), lack of household savings (p=.004), and lack of health behaviors (p=.003). DD was also positively associated with the total number of unhealthy behaviors participants engage in (p<.001). Participants who were not in remission engaged in more unhealthy behaviors compared to those who were in remission (p<.001). CONCLUSION: In a sample of individuals in recovery from SUD, DD is not domain-specific and undergirds engagement in several maladaptive health behaviors that can negatively impact recovery. Thus, DD can be a target for interventions aiming to reduce other maladaptive behaviors in SUD recovery.

Longitudinal Associations Among Socioeconomic Status, Delay Discounting, and Substance Use in Adolescence.

It is unclear how delay discounting and substance use develop across adolescence and whether contextual factors alter their trajectories. The present study used a longitudinal design to examine whether socioeconomic status is related to developmental trajectories of delay discounting and substance use across adolescence. The sample included 167 adolescents (Mage = 14 at Time 1; 53% male) and their parents who participated annually across four years. Parents reported SES at Time 1 and adolescents completed delay discounting behavioral assessments and substance use questionnaires at Times 1 to 4. Bivariate latent growth curve modeling revealed that low SES was related to steeper increases in substance use from age 14 through 17, mediated through elevated delay discounting at age 14. The findings clarify the mediating role of delay discounting in linking family economic environment to the progression of substance use.

Selective Reduction of Socioeconomic Disparities in the Experimental Tobacco Marketplace: Effects of Cigarette and E-cigarette Flavor Restrictions.

INTRODUCTION: Cigarette smoking accounts for >30% of the socioeconomic gap in life expectancy. Flavored restrictions claim to promote equity; however, no previous studies have compared the effect of cigarette and e-cigarette flavor restrictions among individuals who smoke with lower and higher socioeconomic status (SES). AIMS AND METHODS: In a between-group within-subject design, individuals with lower (n = 155) and higher (n = 125) SES completed hypothetical purchasing trials in the experimental tobacco marketplace (ETM). Conditions were presented in a 2 × 2 factorial design (cigarette flavors restricted or unrestricted and e-cigarette flavors restricted or unrestricted) with increasing cigarette prices across trials. RESULTS: Results show (1) SES differences in cigarette, e-cigarette, and NRT purchases under unrestricted policies, with lower SES showing higher cigarette demand and lower e-cigarette and NRT substitution than higher SES, (2) cigarette restrictions decreased cigarette and increased NRT purchases among lower SES, but no significant changes among higher SES, (3) decreased SES differences in cigarette demand under cigarette restrictions, but persistence under e-cigarette restrictions or their combination, (4) persistence of SES differences in e-cigarette purchases when all restrictions were enforced, and (5) waning of SES differences in NRT purchasing under all restrictions. CONCLUSIONS: Flavor restrictions differentially affected individuals based on SES. Within-group comparisons demonstrated restrictions significantly impacted lower SES, but not higher SES. Between-group comparisons showed SES differences in cigarette purchasing decreased under cigarette restrictions, but persisted under e-cigarette-restrictions or their combination. Additionally, SES differences in NRT substitution decreased under flavor restrictions. These findings highlight the utility of the ETM to investigate SES disparities. IMPLICATIONS: With increasing trends of socioeconomic differences in smoking prevalence and cessation rates, smoking-related health disparities are expected to continue to widen. Restricting menthol flavor in cigarettes while enhancing the availability and affordability of NRT have the potential to alleviate SES disparities in tobacco use, therefore, positively impacting health equity. However, this effect may depend on flavor availability in other tobacco products.

A multicentre survey investigating the knowledge, behaviour, and attitudes of surgical healthcare professionals to frailty assessment in emergency surgery: DEFINE(surgery).

PURPOSE: Screening for frailty in people admitted with emergency surgical pathology can initiate timely referrals to enhanced perioperative services such as intensive care and geriatric medicine. However, there has been little research exploring surgical healthcare professionals' opinions to frailty assessment, or accuracy in identification. This study aimed to assess the knowledge, behaviour, and attitudes of healthcare professionals to frailty assessment in emergency surgical admissions. METHODS: We designed a cross-sectional multicentre study developed by a multiprofessional team of surgeons, geriatricians, and supported by patients. A semi-structured survey examined attitudes and behaviours. Knowledge was assessed by comparing respondents' accuracy in scoring twenty-two surgical case vignettes using the Clinical Frailty Scale. RESULTS: Eleven hospitals across England, Wales, and Scotland participated. Two hundred and eleven clinicians responded-20.4% junior doctors, 43.6% middle grade doctors, 24.2% senior doctors, 11.4% nurses and physician associates. Respondents strongly supported perioperative frailty assessment. Most were already assessing for frailty, although frequently not using a standardised tool. There was a strong call for more frailty education. Participants scored 2175 vignettes with 55.4% accurately meeting the gold standard; accuracy improved to 87.3% when categorised into "not frail/mildly frail/severely frail" and 94% when dichotomised to "not frail/frail". CONCLUSION: Frailty assessment is well supported by healthcare professionals working in surgery. However, standardised tools are not routinely being used, and only half of respondents could accurately identify frailty. Better education around frailty assessment is needed for healthcare professionals working in surgery to improve perioperative pathway for people living with frailty.

A randomized controlled trial of intermittent theta burst stimulation to the medial prefrontal cortex for tobacco use disorder: Clinical efficacy and safety.

OBJECTIVE: This study aimed to evaluate the clinical efficacy and safety of administering intermittent theta burst stimulation (iTBS) to the medial prefrontal cortex for tobacco use disorder. METHODS: A randomized sham-controlled trial was conducted, with 38 participants receiving 28 sessions of active (n=25) or sham (n=13) iTBS (2 sessions/day, 600 pulses/session, 110% resting motor threshold, AFz target) along with smoking cessation education (Forever Free © booklets) over 14 visits. Primary outcomes included self-reported cigarette consumption and abstinence, verified by urinary cotinine tests. Secondary outcomes included symptoms of tobacco use disorder, negative mood, and safety/tolerability. RESULTS: Both active and sham groups reported reduced cigarette consumption (ß = -0.12, p = 0.015), cigarette craving (ß = -0.16, p = 0.002), and tobacco withdrawal symptoms (ß = -0.05, p < 0.001). However, there were no significant time x group interaction effects for any measure. Similarly, the two groups had no significant differences in urinary cotinine-verified abstinence. Adverse events occurred with similar frequency in both groups. CONCLUSION: There were no differences in cigarette consumption between the active and sham iTBS groups, both groups decreased cigarette consumption similarly. Further research is needed to compare iTBS to standard high-frequency rTMS and explore the potential differences in efficacy. Despite limitations, this study contributes to experimental design considerations for TMS as a novel intervention for tobacco and other substance use disorders, emphasizing the need for a more comprehensive understanding of the stimulation parameters and target sites.

The phenotype of recovery XI: associations of sleep quality and perceived stress with discounting and quality of life in substance use recovery.

PURPOSE: Sleep and stress show an interdependent relationship in physiology, and both are known risk factors for relapse in substance use disorder (SUD) recovery. However, sleep and stress are often investigated independently in addiction research. In this exploratory study, the associations of sleep quality and perceived stress with delay discounting (DD), effort discounting (ED), and quality of life (QOL) were examined concomitantly to determine their role in addiction recovery. DD has been proposed as a prognostic indicator of SUD treatment response, ED is hypothesized to be relevant to the effort to overcome addiction, and QOL is an important component in addiction recovery. METHOD: An online sample of 118 individuals recovering from SUDs was collected through the International Quit and Recovery Registry. Exhaustive model selection, using the Bayesian Information Criterion to determine the optimal multiple linear model, was conducted to identify variables (i.e., sleep quality, perceived stress, and demographics) contributing to the total variance in DD, ED, and QOL. RESULTS: After model selection, sleep was found to be significantly associated with DD. Stress was found to be significantly associated with psychological health, social relationships, and environment QOL. Both sleep and stress were found to be significantly associated with physical health QOL. Neither sleep nor stress was supported as an explanatory variable of ED. CONCLUSION: Together, these findings suggest sleep and stress contribute uniquely to the process of addiction recovery. Considering both factors when designing interventions and planning for future research is recommended.

Latent profiles of regulatory flexibility in alcohol use disorder: Associations with delay discounting and symptoms of depression, anxiety, and stress.

BACKGROUND: Regulatory flexibility (RF) involves three distinct components of self-regulation: context sensitivity, repertoire, and feedback responsiveness. Subgroups based on differences in RF have been identified in a general sample and are differentially associated with symptoms of anxiety and depression. However, potential RF profiles have not been examined in individuals with substance use disorders. This study examined RF subtypes in individuals with alcohol use disorder (AUD) and their associations with psychosocial outcomes (i.e., depression, anxiety, and stress) and delay discounting (a core feature of addiction). METHODS: Individuals (n = 200) with an Alcohol Use Disorders Identification Test score of >16 (mean = 24.12 (±6.92)) were recruited from Amazon Mechanical Turk (mean = 37.26 years old (±11.41); 94 (47%) women). Participants completed the Context Sensitivity Index, the Flexible Regulation of Emotional Expression Scale, and the Coping Flexibility Scale to assess RF. Participants also completed an Adjusting Amount Delay Discounting Task and the Depression, Anxiety, and Stress Scale (DASS-21). Latent profile analyses (LPA) were used to identify patterns in RF deficits. Kruskal-Wallis and Dunn's tests were performed to examine differences in discounting rates and symptoms of depression, anxiety, and stress across RF profiles. RESULTS: The LPA revealed a 2-profile characterization, including (1) context sensitive regulators (CSR; n = 39) and (2) moderate flexibility regulators (MFR; n = 161). CSR demonstrated significantly lower symptoms of depression (p = 0.004), anxiety (p < 0.001), and stress (p < 0.001) than MFR. CSR also displayed significantly lower AUDIT scores (p = 0.031). CONCLUSIONS: Findings illustrate that among individuals with moderate-severe AUD, those high in context sensitivity coupled with moderate abilities in repertoire and feedback responsiveness have fewer symptoms of depression, anxiety, and stress. Together, context sensitivity may be an important and protective component of RF among individuals with AUD.

Expanding on cross-price elasticity: Understanding tobacco product demand and substitution from the cross-price purchase task.

We examine whether cigarettes serve as substitutes for electronic nicotine delivery systems (ENDS) among ENDS users and demonstrate methodological extensions of data from a cross-price purchase task to inform policies and interventions. During a clinical laboratory study, n = 19 exclusive ENDS users and n = 17 dual cigarette/ENDS users completed a cross-price purchase task with cigarettes available at a fixed price while prices of own-brand ENDS increased. We estimated cross-price elasticity using linear models to examine substitutability. We defined five additional outcomes: nonzero cross-price intensity (purchasing cigarettes if ENDS were free), constant null demand (not purchasing cigarettes at any ENDS price), cross-product crossover point (first price where participants purchased more cigarettes than ENDS), dual-demand score (percentage of prices where both products were purchased), and dual-use break point (minimum relative price to force complete substitution). The cross-price elasticity results indicated that cigarettes could serve as substitutes for ENDS among ENDS users on average, but this average effect masked substantial heterogeneity in profiles of demand (here, a measure of the drug's reinforcement potential). Policies and regulations that increase ENDS prices appear unlikely to steer most exclusive ENDS users toward cigarette use, as most would not purchase cigarettes at any ENDS price, but they could prompt some dual users to substitute cigarettes completely while others remain dual users. This heterogeneity in consumer responses suggests additional indices of cross-product demand are useful to characterize the anticipated and unanticipated effects of tobacco price policies more fully.

Glucose response to sugar challenge moderates the effect of insulin resistance on reinforcing value of sugar-sweetened yogurt.

We have shown insulin resistance is associated with the choice of sugar-sweetened over monk fruit sweetened yogurt. This study extends this research by assessing the association between insulin resistance and reinforcing value for sugar versus monk fruit-sweetened yogurt, and testing the hypothesis that this effect is moderated by greater blood glucose response in people with insulin resistance. Eighteen people with overweight/obesity (BMI = 35.8 kg/m2, range 26.2-48.5) with varying degrees of insulin resistance (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) = 2.6, range of 0.6-8.0) had blood glucose measured for 2 h after a sugar challenge. Over six days, they consumed, in a double-blind fashion, novel flavored-colored sugar or monk fruit-sweetened yogurts, and the reinforcing value of sugar or monk fruit-sweetened yogurts and delay discounting (DD) were measured. HOMA-IR (r = 0.62, p = .006) and insulin (r = 0.51, p = .03) were related to the reinforcing value of sugar-sweetened, but not monk fruit-sweetened yogurt (r = -0.07, -0.10, respectively). The blood glucose area under the curve moderated the relationship between HOMA-IR and the reinforcing value of sugar-sweetened yogurt (p = .02). People with greater HOMA-IR and greater blood glucose excursions responded the most for sugar-sweetened yogurt. These results extend previous research and confirm the hypothesis that individual differences in response to sugar may activate brain reward centers and condition people to prefer high-sugar foods. DD was related to sugar reinforcement (r = -0.46, p = .03), consistent with the idea that those with high sugar reinforcement desire immediate gratification, and DD moderated the relationship between HOMA-IR and the reinforcing value of sugar-sweetened yogurt (p < .001). Research should test whether reducing insulin resistance would permit people with insulin resistance to choose lower-sugar foods.

Illegal product purchasing in the experimental tobacco marketplace: Effects of menthol cigarette and cigarette ventilation ban.

BACKGROUND: Tobacco regulations may increase demand for illegal cigarettes. We use the Experimental Tobacco Marketplace to estimate the impact of banning menthol cigarettes (Experiment 1) and decreasing allowable cigarette filter ventilation levels (Experiment 2). METHODS: Crowdsourced participants were randomized into one of four groups (2×2 factorial design). Experiment 1 included menthol availability (yes/no) by purchasing option (legal only vs illegal available). Experiment 2 included filter-vented cigarettes availability (yes/no) by purchasing option (legal only vs illegal available). Participants were given an individualized budget to purchase tobacco. Percent budget spent was the outcome measure. RESULTS: Experiment 1, with a legal marketplace only, non-menthol cigarette purchasing was lower (p=0.010) and electronic-cigarette purchasing was higher (p=0.016), when cigarettes were banned compared to when they were available. With an illegal marketplace, switching to legal non-menthol cigarettes was less likely (p<0.001) and purchasing illegal menthol cigarettes was higher (p<0.001), when cigarettes were banned compared to when they were available. Experiment 2, with a legal marketplace only, cigarette purchasing was lower (p=0.010), when the participant's filtered vented cigarettes were banned compared to when they were available. With an illegal marketplace, purchasing the legal low-ventilated cigarette option was lower (p<0.001) and significant differences in illegal filter-vented cigarette purchasing were not observed, when their filter-vented cigarettes were banned compared to when they were available legally. CONCLUSIONS: Without an illegal option, both restrictions decreased cigarette purchasing, but the menthol ban increased e-cigarette purchasing. With an illegal option, a menthol ban increased illegal cigarette purchasing, but decreasing filter ventilation did not.

Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity.

Alcohol Use Disorder (AUD) contributes significantly to global mortality. GLP-1 (Glucagon-like peptide-1) and GLP-1/GIP (Glucose-dependent Insulinotropic Polypeptide) agonists, FDA-approved for managing type 2 diabetes and obesity, where the former has shown to effectively reduce the consumption of alcohol in animal models but no reports exist on the latter. In this report, we conducted two studies. In the first study, we conducted an analysis of abundant social media texts. Specifically, a machine-learning based attribution mapping of ~ 68,250 posts related to GLP-1 or GLP-1/GIP agonists on the Reddit platform. Secondly, we recruited participants (n = 153; current alcohol drinkers; BMI ≥ 30) who self-reported either taking Semaglutide (GLP-1 agonist), Tirzepatide (the GLP-1/GIP combination) for ≥ 30 days or, as a control group; no medication to manage diabetes or weight loss for a within and between subject remote study. In the social media study, we report 8 major themes including effects of medications (30%); diabetes (21%); and Weight loss and obesity (19%). Among the alcohol-related posts (n = 1580), 71% were identified as craving reduction, decreased desire to drink, and other negative effects. In the remote study, we observe a significantly lower self-reported intake of alcohol, drinks per drinking episode, binge drinking odds, Alcohol Use Disorders Identification Test (AUDIT) scores, and stimulating, and sedative effects in the Semaglutide or Tirzepatide group when compared to prior to starting medication timepoint (within-subjects) and the control group (between-subjects). In summary, we provide initial real-world evidence of reduced alcohol consumption in people with obesity taking Semaglutide or Tirzepatide medications, suggesting potential efficacy for treatment in AUD comorbid with obesity.

Discounting of delayed rewards: Missing data imputation for the 21- and 27-item monetary choice questionnaires.

The Monetary Choice Questionnaire (MCQ) is a widely used behavioral task that measures the rate of delay discounting (i.e., k), the degree to which a delayed reward loses its present value as a function of the time to its receipt. Both 21- and 27-item MCQs have been extensively validated and proven valuable in research. Different methods have been developed to streamline MCQ scoring. However, existing scoring methods have yet to tackle the issue of missing responses or provide clear guidance on imputing such data. Due to this lack of knowledge, the present study developed and compared three imputation approaches that leverage the MCQ's structure and prioritize ease of implementation. Additionally, their performance was compared with mode imputation. A Monte Carlo simulation was conducted to evaluate the performance of these approaches in handling various missing responses in each observation across two datasets from prior studies that employed the 21- and 27-item MCQs. One of the three approaches consistently outperformed mode imputation across all performance measures. This approach involves imputing missing values using congruent non-missing responses to the items corresponding to the same k value or introducing random responses when congruent answers are unavailable. This investigation unveils a straightforward method for imputing missing data in the MCQ while ensuring unbiased estimates. Along with the investigation, an R tool was developed for researchers to implement this strategy while streamlining the MCQ scoring process.

Can delay discounting predict vaccine hesitancy 4-years later? A study among US young adults.

Despite being a major threat to health, vaccine hesitancy (i.e., refusal or reluctance to vaccinate despite vaccine availability) is on the rise. Using a longitudinal cohort of young adults (N = 1260) from Los Angeles County, California we investigated the neurobehavioral mechanisms underlying COVID-19 vaccine hesitancy. Data were collected at two time points: during adolescence (12th grade; fall 2016; average age = 16.96 (±0.42)) and during young adulthood (spring 2021; average age = 21.33 (±0.49)). Main outcomes and measures were delay discounting (DD; fall 2016) and tendency to act rashly when experiencing positive and negative emotions (UPPS-P; fall 2016); self-reported vaccine hesitancy and vaccine beliefs/knowledge (spring 2021). A principal components analysis determined four COVID-19 vaccine beliefs/knowledge themes: Collective Responsibility, Confidence and Risk Calculation, Complacency, and Convenience. Significant relationships were found between themes, COVID-19 vaccine hesitancy, and DD. Collective Responsibility (ß = -1.158[-1.213,-1.102]) and Convenience (ß = -0.132[-0.185,-0.078]) scores were negatively associated, while Confidence and Risk Calculation (ß = 0.283[0.230,0.337]) and Complacency (ß = 0.412[0.358,0.466]) scores were positively associated with COVID-19 vaccine hesitancy. Additionally, Collective Responsibility (ß = -0.060[-0.101,-0.018]) was negatively associated, and Complacency (ß = -0.063[0.021,0.105]) was positively associated with DD from fall 2016. Mediation analysis revealed immediacy bias during adolescence, measured by DD, predicted vaccine hesitancy 4 years later while being mediated by two types of vaccine beliefs/knowledge: Collective Responsibility (ß = 0.069[0.022,0.116]) and Complacency (ß = 0.026[0.008,0.044]). These findings provide a further understanding of individual vaccine-related decision-making among young adults and inform public health messaging to increase vaccination acceptance.

Episodic future thinking in type 2 diabetes: Further development and validation of the Health Information Thinking control for clinical trials.

Episodic Future Thinking (EFT) reduces delay discounting and may have the potential as a clinical tool to increase the likelihood of health-promoting behaviors. However, evaluations of EFT in clinical settings require control conditions that match the effort and frequency of cue generation, as well as participants' expectations of improvement. The Health Information Thinking (HIT) control addresses these issues, but how this control affects delay discounting in individuals with diabetes and obesity when utilizing diabetes-management specific health-information vignettes is unknown. Moreover, little research has explored whether EFT reduces delay discounting in individuals with type 2 diabetes. To this end, we examined the impact of EFT, HIT, and a secondary no-cue control condition (NCC; assessments as usual) on delay discounting in 434 adults with self-reported type 2 diabetes and obesity recruited using Amazon Mechanical Turk. After completing an initial screening questionnaire, eligible participants reported demographics, then were randomized to EFT, HIT, or NCC conditions. Following the generation of seven EFT or HIT cues, participants assigned to EFT or HIT conditions completed a delay discounting task while imagining EFT or HIT cues; no-cue participants completed the task without cues. EFT participants demonstrated significantly lower delay discounting levels than HIT or NCC participants; no differences in delay discounting between HIT and NCC participants were observed. These results suggest that engaging in EFT, but not diabetes-specific HIT, results in lower delay discounting in adults with type 2 diabetes and obesity. This provides further evidence for the appropriateness of the HIT control for clinical trials examining the effect of EFT on delay discounting in adults with self-reported type 2 diabetes.

The Phenotype of Recovery X: Associations between delay discounting, regulatory flexibility, and remission from substance use disorder.

INTRODUCTION: Delay discounting (DD) and self-regulation are important predictors of substance use disorder (SUD) outcomes. Further, regulatory flexibility (RF; i.e., selecting, monitoring, and adapting coping techniques based on contextual demands) is related to psychological resilience. However, studies have yet to examine associations among DD, RF, and remission from SUDs among individuals in recovery. METHODS: Individuals (N = 148) in SUD recovery completed the Context Sensitivity Index (CSI), the Flexible Regulation of Emotional Expression (FREE) Scale, and the Perceived Ability to Cope with Trauma (PACT) Scale to assess RF and, an $1000 hypothetical reward Adjusting Amount Delay Discounting Task. The study considered individuals to be in remission from SUD if they did not endorse any SUD DSM-5 symptom other than craving (except tobacco use disorder) in the past three months. The study team used t-tests to examine differences in RF and DD by remission status. Univariate linear regressions were used to examine the relationship between RF and DD. Finally, mediation models examined the dynamic relationship among DD, RF, and remission status. RESULTS: Remitted individuals (n = 82) had significantly lower DD (i.e., greater preference for larger, later rewards) rates (p < .001) and higher context sensitivity (p < .001) and coping flexibility (p < .001). The study found significant negative associations between DD and context sensitivity (p = .008), coping flexibility (p = .002), and emotion regulation flexibility (p < .001). Finally, context sensitivity (p = .023) and coping flexibility (p = .009) mediated the relationship between DD and SUD remission. CONCLUSIONS: Results suggest that individuals in recovery with broader temporal windows can better identify contextual demands and flexibly cope, contributing to improved SUD recovery outcomes.

Struggling With Recovery From Opioids: Who Is at Risk During COVID-19?

OBJECTIVES: Individuals in recovery from opioid use disorder (OUD) are vulnerable to the impacts of the COVID-19 pandemic. Recent findings suggest increased relapse risk and overdose linked to COVID-19-related stressors. We aimed to identify individual-level factors associated with COVID-19-related impacts on recovery. METHODS: This observational study (NCT04577144) enrolled 216 participants who previously partook in long-acting buprenorphine subcutaneous injection clinical trials (2015-2017) for OUD. Participants indicated how COVID-19 affected their recovery from substance use. A machine learning approach Classification and Regression Tree analysis examined the association of 28 variables with the impact of COVID-19 on recovery, including demographics, substance use, and psychosocial factors. Ten-fold cross-validation was used to minimize overfitting. RESULTS: Twenty-six percent of the sample reported that COVID-19 had made recovery somewhat or much harder. Past-month opioid use was higher among those who reported that recovery was harder compared with those who did not (51% vs 24%, respectively; P < 0.001). The final classification tree (overall accuracy, 80%) identified the Beck Depression Inventory (BDI-II) as the strongest independent risk factor associated with reporting COVID-19 impact. Individuals with a BDI-II score ≥10 had 6.45 times greater odds of negative impact (95% confidence interval, 3.29-13.30) relative to those who scored <10. Among individuals with higher BDI-II scores, less progress in managing substance use and treatment of OUD within the past 2 to 3 years were also associated with negative impacts. CONCLUSIONS: These findings underscore the importance of monitoring depressive symptoms and perceived progress in managing substance use among those in recovery from OUD, particularly during large-magnitude crises.

Predictors of smoking cessation outcomes identified by machine learning: A systematic review.

This systematic review aims to characterize the utility of machine learning to identify the predictors of smoking cessation outcomes and identify the machine learning methods applied in this area. In the current study, multiple searches occurred through December 9, 2022 in MEDLINE, Science Citation Index, Social Science Citation Index, EMBASE, CINAHL Plus, APA PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, and the IEEE Xplore were performed. Inclusion criteria included various machine learning techniques, studies reporting cigarette smoking cessation outcomes (smoking status and the number of cigarettes), and various experimental designs (e.g., cross-sectional and longitudinal). Predictors of smoking cessation outcomes were assessed, including behavioral markers, biomarkers, and other predictors. Our systematic review identified 12 papers fitting our inclusion criteria. In this review, we identified gaps in knowledge and innovation opportunities for machine learning research in the field of smoking cessation.

Movement of cerebrospinal fluid tracer into brain parenchyma and outflow to nasal mucosa is reduced at 24 h but not 2 weeks post-stroke in mice.

BACKGROUND: Recent data indicates that cerebrospinal fluid (CSF) dynamics are disturbed after stroke. Our lab has previously shown that intracranial pressure rises dramatically 24 h after experimental stroke and that this reduces blood flow to ischaemic tissue. CSF outflow resistance is increased at this time point. We hypothesised that reduced transit of CSF through brain parenchyma and reduced outflow of CSF via the cribriform plate at 24 h after stroke may contribute to the previously identified post-stroke intracranial pressure elevation. METHODS: Using a photothrombotic permanent occlusion model of stroke in C57BL/6 adult male mice, we examined the movement of an intracisternally infused 0.5% Texas Red dextran throughout the brain and measured tracer efflux into the nasal mucosa via the cribriform plate at 24 h or two weeks after stroke. Brain tissue and nasal mucosa were collected ex vivo and imaged using fluorescent microscopy to determine the change in CSF tracer intensity in these tissues. RESULTS: At 24 h after stroke, we found that CSF tracer load was significantly reduced in brain tissue from stroke animals in both the ipsilateral and contralateral hemispheres when compared to sham. CSF tracer load was also reduced in the lateral region of the ipsilateral hemisphere when compared to the contralateral hemisphere in stroke brains. In addition, we identified an 81% reduction in CSF tracer load in the nasal mucosa in stroke animals compared to sham. These alterations to the movement of CSF-borne tracer were not present at two weeks after stroke. CONCLUSIONS: Our data indicates that influx of CSF into the brain tissue and efflux via the cribriform plate are reduced 24 h after stroke. This may contribute to reported increases in intracranial pressure at 24 h after stroke and thus worsen stroke outcomes.