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BACKGROUND: Hypoglycemia in neonates is common and contributes to 4.0–5.8% of neonatal intensive care unit (NICU) admissions. In utero nicotine exposure is underexplored as a potential contributor to neonatal hypoglycemia. Rat models have shown that in utero nicotine exposure can be associated with a reduction in pancreatic beta cell mass, leading to glucose dysregulation. The primary aim of this work is to study the risk of developing hypoglycemia after birth in a population of in utero nicotine-exposed neonates. METHODS: We conducted a retrospective matched cohort study that augmented an existing dataset of neonates admitted to a level IV NICU with household-based in utero nicotine exposure (N = 335). Neonates in the control group parents denied household smoking (N = 325), were born within a 6-month timeframe, and were within a birthweight of 50 grams of a nicotine-exposed neonate. Data reviewed included gestational age, growth parameters, maternal history of diabetes, and glucose levels within the first three hours of life per unit protocol. RESULTS: 660 neonates were included in the analysis. In utero nicotine exposure demonstrated a 94.3% posterior probability (PP) for greater hypoglycemia risk (RR = 1.185, 95% CrI = [0.953, 1.445]). A 94.6% PP was demonstrated when neonates who were small for gestational age, intrauterine growth-restricted, and born to diabetic mothers were excluded (n = 482; RR = 1.271, 95% CrI = [0.946, 1.669]). CONCLUSION: Nicotine exposure in utero was found to be a potential risk factor for developing hypoglycemia after birth. Mechanisms of action should be explored, and additional research on in utero nicotine exposure risks should follow. [ABSTRACT FROM AUTHOR]

Purpose: The growing homeless population in the U.S.A. is disproportionately impacted by poor mental and physical health status, including a higher incidence of acute and chronic health problems, increased hospitalizations, and premature mortality compared to the general population. This study examined the association between demographic, social, and clinical factors and perceptions of general health status among the homeless population during admission to an integrated behavioral health treatment program. Methods: The study sample included 331 adults experiencing homelessness with a serious mental illness or co-occurring disorder. Participants were enrolled in services at a day program for unsheltered homeless adults, a residential substance use treatment program for males experiencing homelessness, a psychiatric step-down respite program for those experiencing homelessness following psychiatric hospitalization, permanent supportive housing for formerly chronically homeless adults, a faith-based food distribution program, and homeless encampment sites in a large urban area. Participants were interviewed using The Substance Abuse and Mental Health Services Administration's National Outcome Measures tool and a validated health-related quality of life measurement tool, SF-36. Data were examined using in elastic net regression. Results: The study found seven factors to be particularly strong predictors of SF-36 general health scores. Male gender, "other" sexual identity, stimulant use, and Asian race were all associated with better perceptions of health status, while transgender status, inhalant use, and number of times arrested were associated with poorer perceptions. Conclusion: This study suggests targeted areas for health screening within the homeless population; however, more studies are necessary to demonstrate generalizability of the results. [ABSTRACT FROM AUTHOR]

Following a stressful life event, there is considerable variation in how individuals respond and adapt. Multiple models of risk and resilience show that adverse childhood experiences may be associated with an individual's response to stress later in life. While there is considerable support that early adversity can sensitize the stress response system and lead to adverse outcomes later in life, there is mounting evidence that in adolescence and young adulthood, certain biological predispositions to stress may be associated with resilience in the context of subsequent stressors. In this study, we evaluated how individual differences in vagally mediated heart rate variability moderated the relationship between childhood maltreatment and grief among a sample of individuals experiencing a stressful life event (i.e., spousal bereavement) over time. Data were collected at approximately 3, 4.5, and 6.5 months after the death of a spouse (n = 130). Heart rate variability moderated the relationship between childhood maltreatment and grief symptoms over time (b = −0.03, p <.001), such that among individuals with more severe experiences of childhood maltreatment, those with higher heart rate variability had a faster recovery from grief than those with low heart rate variability. This research highlights an overall pattern of resilience among older adult's following spousal bereavement, as well as the relationships between childhood maltreatment, heart rate variability, and differential responses to grief following the loss of a spouse. Public Significance Statement: Childhood maltreatment and heart rate variability may be related to differential responses to grief among bereaved spouses over time. Among bereaved spouses with a history of childhood maltreatment, those with higher heart rate variability experienced faster recovery from grief symptoms than bereaved spouses with lower heart rate variability. These findings suggest a pathway to intervention may include increased heart rate variability to mitigate the relationship between adverse childhood experiences and adjustment to stressors later in life, particularly among older adults. [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]

Background: Apathy is among the neuropsychiatric symptoms frequently observed in people with cognitive impairment. It has been postulated to be a potential predictor of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Objective: To detect conversion rates from MCI to AD, and to determine the effect of apathy on the progression to AD in patients with MCI enrolled in the Texas Alzheimer's Research and Care Consortium (TARCC) cohort. Methods: Apathy was determined by a positive response to the respective item in the Neuropsychiatric Inventory –Questionnaire (NPI-Q) completed by family members or caregivers. The final dataset included 2,897 observations from 1,092 individuals with MCI at the baseline. Kaplan-Meier survival curves were estimated to provide indices of the probability of conversion to AD over time across all individuals as well as between those with and without apathy. Cox proportional hazards regression measured the hazard associated with apathy and several other predictors of interest. Results: Over a period of 8.21 years, 17.3% of individuals had conversion from MCI to AD (n = 190 of 1,092 total individuals) across observations. The median time-to-conversion across all participants was 6.41 years. Comparing individuals with apathy (n = 158) versus without apathy (n = 934), 36.1% and 14.2% had conversion to AD, respectively. The median time-to-conversion was 3.79 years for individuals with apathy and 6.83 years for individuals without apathy. Cox proportional hazards regression found significant effects of several predictors, including apathy, on time-to-conversion. Age and cognitive performance were found to moderate the relationship between apathy and time-to-conversion. Conclusions: Apathy is associated with progression from MCI to AD, suggesting that it might improve risk prediction and aid targeted intervention delivery. [ABSTRACT FROM AUTHOR]

• Bipolar disorder is associated with increased GrimAge acceleration. • GrimAge acceleration is associated with different blood cell proportions. • Higher GrimAge acceleration is associated with cognitive impairment in patients. • Smoking is associated with GrimAge acceleration in patients with bipolar disorder. Bipolar disorder (BD) has been previously associated with clinical signs of premature aging, including accelerated epigenetic aging in blood and brain, and a steeper age-related decline in cognitive function. However, the clinical drivers and cognitive correlates of epigenetic aging in BD are still unknown. We aimed to investigate the relationship between multiple measures of epigenetic aging acceleration with clinical, functioning, and cognitive outcomes in patients with BD and controls. Blood genome-wide DNA methylation levels were measured in BD patients (n = 153) and matched healthy controls (n = 50) with the Infinium MethylationEPIC BeadChip (Illumina). Epigenetic age estimates were calculated using an online tool, including the recently developed lifespan predictor GrimAge, and analyzed with generalized linear models controlling for demographic variables and blood cell proportions. BD was significantly associated with greater GrimAge acceleration (AgeAccelGrim, β=0.197, p = 0.009), and significant group-dependent interactions were found between AgeAccelGrim and blood cell proportions (CD4+ T-lymphocytes, monocytes, granulocytes, and B-cells). Within patients, higher AgeAccelGrim was associated with worse cognitive function in multiple domains (short-term affective memory (β=-0.078, p = 0.030), short-term non-affective memory (β=-0.088, p = 0.018), inhibition (β=0.064, p = 0.046), and problem solving (β=-0.067, p = 0.034)), age of first diagnosis with any mood disorder (β=-0.076, p = 0.039) or BD (β=-0.102, p = 0.016), as well as with current non-smoking status (β=-0.392, p < 0.001). Overall, our findings support the contribution of epigenetic factors to the aging-related cognitive decline and premature mortality reported in BD patients, with an important driving effect of smoking in this population. [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]

Background: The response time speed-accuracy trade-off (SATO) is an established index of information processing ability, but rarely examined as a variable in association with treatment of substance use disorder (SUD).Aim: The purpose of this study was to test baseline information-processing ability differences between individuals who respond to treatment for cocaine use disorder v. those who do not.Methods: Eighty patients enrolled in a clinical trial for cocaine use disorder completed a baseline drug-specific eye-tracking (anti-saccade) assessment prior to treatment, which included trials with both cocaine-related and neutral stimuli. SATO functions were computed for treatment responders v. non-responders.Results: Unexpectedly, responders demonstrated statistically different SATO functions, showing poorer accuracy when executing faster response times. This difference was present on trials that presented cocaine stimuli only.Conclusions: SATO during performance of an eye-movement task may be useful for predicting differential response to substance use disorder treatment. However, in the present study, results were specific to cocaine cues rather than an overall SATO performance decrement. [ABSTRACT FROM AUTHOR]

Tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) studies have consistently shown diminished white matter (WM) integrity for individuals with cocaine use disorder (CUD). The present study used seed-based d mapping (SDM) to determine the extent to which a systematic difference in the WM integrity of cocaine users may exist (as compared with that of healthy controls). Articles from 2006 (when TBSS was first developed) to present were reviewed, with eight selected for inclusion. Meta-analysis found lower fractional anisotropy (FA) in the genu of the corpus callosum for cocaine users, with a small-to-moderate peak effect size (Hedge's g = -0.331). Sensitivity analyses mostly supported the robustness of the obtained difference. Differences detected at exploratory thresholds for significance suggested insult to WM integrity extending beyond the corpus callosum. The present results compliment a previous region-of-interest (ROI)-based meta-analysis of DTI studies in individuals with CUD. These findings have significant implications for the potential role of neuroprotective agents in the treatment of CUD and merit additional iteration as more studies accrue in the literature. [ABSTRACT FROM AUTHOR]

Background: Monoamine oxidase inhibitors (MAOIs) were the first class of modern antidepressants; however, they are under-utilized as compared to the newer antidepressants.Methods: In this systematic review, network meta-analysis was used to investigate the comparative efficacy and acceptability of MAOIs for depressive disorders. Overall, the network meta-analysis included 52 double-blind, randomized controlled trials (RCTs) that compared 14 antidepressants or placebo. Across studies, the mean arm size was n = 58 participants from a total N = 6462 (5309 active drug; 1153 placebo).Results: Except fluvoxamine, all antidepressants demonstrated superior efficacy to placebo, and none demonstrated substantially better or worse all-cause dropout rates. Phenelzine demonstrated superior evidence for efficacy compared to all other treatments, and clomipramine demonstrated superior evidence for acceptability compared to all other treatments.Limitations: The study is primarily limited by low estimate precision due to a relative paucity of studies for some of the included treatment conditions. Further evidence is required to study the relative efficacy of MAOIs against newer antidepressants.Conclusions: The results of this analysis largely support the re-evaluation of the use of MAOIs as antidepressant agents in the treatment algorithm of depression. [ABSTRACT FROM AUTHOR]

Objective The present study examined the effects of home-based remotely supervised transcranial direct current stimulation on quantitative sensory testing measurements in older adults with knee osteoarthritis. Participants were hypothesized to experience improved pain measurements over time. Design Open-label, single-arm trial. Setting Southeast Texas between March and November 2018 at a nursing school and participant homes. Subjects Older adults (aged 50–85 years) with self-reported unilateral or bilateral knee osteoarthritis pain who met eligibility criteria set by the American College of Rheumatology. Methods The intervention was applied with a constant current intensity for 20 minutes every weekday for two weeks (10 total sessions). Quantitative measures of pain were collected three times over 10 days (days 1, 5, and 10) and included heat threshold and tolerance, pressure pain threshold, punctate mechanical pain, pain, and conditioned pain modulation. Analyses used nonparametric tests to evaluate differences between day 1 and day 10. Generalized linear mixed models were then used to evaluate change across all three time points for each measure. Bayesian inference was used to provide the posterior probability of longitudinal effects. Results Nonparametric tests found improvements in seven measures, and longitudinal models supported improvements in 10 measures, with some nonlinear effects. Conclusions The home-based, remotely supervised intervention improved quantitative measurements of pain in older adults with knee osteoarthritis. This study contributes to the growing body of literature supporting home-based noninvasive stimulation interventions. [ABSTRACT FROM AUTHOR]

Senior financial exploitation (FE) is prevalent and harmful. Its often insidious nature and co-occurrence with other forms of mistreatment make detection and substantiation challenging. A secondary data analysis of N = 8,800 Adult Protective Services substantiated senior mistreatment cases, using machine learning algorithms, was conducted to determine when pure FE versus hybrid FE was occurring. FE represented N = 2514 (29%) of the cases with 78% being pure FE. Victim suicidal ideation and threatening behaviors, injuries, drug paraphernalia, contentious relationships, caregiver stress, and burnout and victims needing assistance were most important for differentiating FE vs non-FE-related mistreatment. The inability to afford housing, medications, food, and medical care as well as victims suffering from intellectual disability disorder(s) predicted hybrid FE. This study distinguishes socioecological factors strongly associated with the presence of FE during protective service investigations. These findings support existing and new indicators of FE and could inform protective service investigation practices. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) has demonstrated effectiveness in reducing clinical and experimental measures of pain in patients with chronic pain; however, research examining the mechanisms of action for the effects of tDCS has been lacking. The present study investigated the effect of active tDCS on measures of inflammation and stress. Older adults (aged 50–70 years) with knee osteoarthritis (OA) were randomly assigned to receive daily 20-min sessions of either tDCS (n = 20) or sham tDCS (n = 20) for 5 consecutive days. Participants provided blood samples at baseline and the end of treatment. The following measures of immune function and stress were collected: interleukin (IL)-6 and 10, tumor necrosis factor-α (TNF-α), C-reactive protein, cortisol, and β-endorphin. Generalized linear modeling evaluated each posttreatment measure as a function of tDCS group, controlling for baseline (measuring residual change, analogous to analysis of covariance). Bayesian statistical inference was used to directly quantify the probability of the effect of active tDCS. IL-6, IL-10, TNF-α, and β-endorphin demonstrated lower levels of stress and inflammation in the active tDCS group. These findings provide preliminary evidence that active (relative to sham) tDCS is associated with reduced levels of inflammation. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) in the U.S. has tripled in the prior five years, and injecting drug use is the primary risk for HCV, with up to 90% of older and former people who inject drugs (PWIDs) testing positive. Laboratory testing of HCV for any PWIDs is the gold standard, however many PWIDs lack access to health treatment or services. Identifying risks of HCV via a data science approach would aid community health workers (CHW) to rapidly link those most at risk of infection with treatment. This study employed a data-science approach to determine the strongest risk factors of HCV in a sample of Mexican-Americans WIDs n = 221 (96 negative/125 positive). Data included 238 demographic and psychosocial predictors. A Random Forest machine learning algorithm demonstrated significant prediction improvement over baseline no information rate comparison. Strongest risks for positive HCV included sharing drug-use equipment and younger age at first heroin use; receiving drug-education during incarceration was protective. A ROC curve fit to the prediction yielded an area under the curve of 0.77. Predictive variables of HCV in the present analysis can be obtained via screening by CHW. Identification of patients most at risk of HCV within community settings can maximize treatment utilization. [ABSTRACT FROM AUTHOR]

Background and Aims: Cognitive impairments are primary hallmarks symptoms of bipolar disorder (BD). Whether these deficits are markers of vulnerability or symptoms of the disease is still unclear. This study used a component-wise gradient (CGB) machine learning algorithm to identify cognitive measures that could accurately differentiate pediatric BD, unaffected offspring of BD parents, and healthy controls. Methods: 59 healthy controls (HC; 11.19 ± 3.15 yo; 30 girls), 119 children and adolescents with BD (13.31 ± 3.02 yo, 52 girls) and 49 unaffected offspring of BD parents (UO; 9.36 ± 3.18 yo; 22 girls) completed the CANTAB cognitive battery. Results: CGB achieved accuracy of 73.2% and an AUROC of 0.785 in classifying individuals as either BD or non-BD on a dataset held out for validation for testing. The strongest cognitive predictors of BD were measures of processing speed and affective processing. Measures of cognition did not differentiate between UO and HC. Conclusions: Alterations in processing speed and affective processing are markers of BD in pediatric populations. Longitudinal studies should determine whether UO with a cognitive profile similar to that of HC are at less or equal risk for mood disorders. Future studies should include relevant measures for BD such as verbal memory and genetic risk scores. [ABSTRACT FROM AUTHOR]

Introduction: Machine learning algorithms such as elastic net regression and backward selection provide a unique and powerful approach to model building given a set of psychosocial predictors of smoking lapse measured repeatedly via ecological momentary assessment (EMA). Understanding these predictors may aid in developing interventions for smoking lapse prevention.Methods: In a randomized-controlled smoking cessation trial, smartphone-based EMAs were collected from 92 participants following a scheduled quit date. This secondary analysis utilized elastic net-penalized cox proportional hazards regression and model approximation via backward elimination to (1) optimize a predictive model of time to first lapse and (2) simplify that model to its core constituent predictors to maximize parsimony and generalizability.Results: Elastic net proportional hazards regression selected 17 of 26 possible predictors from 2065 EMAs to model time to first lapse. The predictors with the highest magnitude regression coefficients were having consumed alcohol in the past hour, being around and interacting with a smoker, and having cigarettes easily available. This model was reduced using backward elimination, retaining five predictors and approximating to 93.9% of model fit. The retained predictors included those mentioned above as well as feeling irritable and being in areas where smoking is either discouraged or allowed (as opposed to not permitted).Conclusions: The strongest predictors of smoking lapse were environmental in nature (e.g., being in smoking-permitted areas) as opposed to internal factors such as psychological affect. Interventions may be improved by a renewed focus of interventions on these predictors.Implications: The present study demonstrated the utility of machine learning algorithms to optimize the prediction of time to smoking lapse using EMA data. The two models generated by the present analysis found that environmental factors were most strongly related to smoking lapse. The results support the use of machine learning algorithms to investigate intensive longitudinal data, and provide a foundation for the development of highly tailored, just-in-time interventions that can target on multiple antecedents of smoking lapse. [ABSTRACT FROM AUTHOR]

Background: Depressive symptoms may contribute to cocaine use. However, tests of the relationship between depression and severity of cocaine use have produced mixed results, possibly due to heterogeneity in individual symptoms of depression. Our goal was to establish which symptoms of depression are most strongly related to frequency of cocaine use (one aspect of severity) in a large sample of current cocaine users. We utilized generalized additive modeling to provide data-driven exploration of the relationships between depressive symptoms and cocaine use, including examination of non-linearity. We hypothesized that symptoms related to anhedonia would demonstrate the strongest relationship to cocaine use.Method: 772 individuals screened for cocaine use disorder treatment studies. To measure depressive symptoms, we used the items of the Beck Depression Inventory, 2nd Edition. Cocaine use frequency was measured as proportion of self-reported days of cocaine use over the last 30 days using the Addiction Severity Index.Results: Models identified 18 significant predictors of past-30-day cocaine use. The strongest predictors were Crying, Pessimism, Changes in Appetite, Indecisiveness, and Loss of Interest. Noteworthy effect sizes were found for specific response options on Suicidal Thoughts, Worthlessness, Agitation, Concentration Difficulty, Tiredness, and Self Dislike items.Conclusions: The strongest predictors did not conform to previously hypothesized "subtypes" of depression. Non-linear relationships between items and use were typical, suggesting BDI-II items may not be monotonically increasing ordinal measures with respect to predicting cocaine use. Qualitative analysis of strongly predictive response options suggested emotional volatility and disregard for the future as important predictors of use. [ABSTRACT FROM AUTHOR]

Highlights • Machine learning was used to optimize modeling of patient aggressive events in a large set of electronic health records in a safety net psychiatric facility. • The best-performing algorithm (penalized generalized linear modeling) achieved an area under the curve = 0.7801. • The strongest predictors of patient aggressive events were homelessness, having witnessed abuse, and prior assault conviction. • A cost-optimized probability threshold of an aggressive event was generated to assist with allocation of hospital resources. Abstract Recent advances in data science were used capitalize on the extensive quantity of data available in electronic health records to predict patient aggressive events. This retrospective study utilized electronic health records (N = 29,841) collected between January 2010 and December 2015 at Harris County Psychiatric Center, a 274-bed safety net community psychiatric facility. The primary outcome of interest was the presence (1.4%) versus absence (98.6%) of an aggressive event toward staff or patients. The best-performing algorithm, penalized generalized linear modeling, achieved an area under the curve = 0.7801. The strongest predictors of patient aggressive events included homelessness (b = 0.52), having been convicted of assault (b = 0.31), and having witnessed abuse (b = −0.28). The algorithm was also used to generate a cost-optimized probability threshold (6%) for an aggressive event, theoretically affording individualized hospital-staff coverage on the 2.8% of inpatients at highest risk for aggression, based on available hospital operating costs. The present research demonstrated the utility of a data science approach to better understand a high-priority event in psychiatric inpatient settings. [ABSTRACT FROM AUTHOR]

Sodium valproate (VPA) has well-established neuroprotective effects and is recommended as treatment in bipolar disorder patients. The neural effects of VPA in pediatric bipolar disorder (PBD) have yet to be established. This preliminary study explored the effects of VPA on brain structure in PBD. Fourteen PBD patients (10 males; mean = 13.43 ± 3.05 years old) underwent a structural MRI before and after a 6-week VPA treatment period. Bayesian linear mixed modeling explored seven brain region volumes as a function of dichotomous pre/post time. Results showed a decrease in amygdala volume over time. These findings need to be confirmed by large-scale, longitudinal studies. [ABSTRACT FROM AUTHOR]

The neural mechanisms underlying the therapeutic effects of lamotrigine in bipolar depression are still unexplored. This preliminary study compares the effects of a 12-week treatment with lamotrigine on brain volumes in adults with bipolar disorder (BD).12 BD type II patients (age: 49.33 ± 9.95 years, 3 males, 9 females) and 12 age and gender-matched healthy controls (HC) (HC; age: 41 ± 8.60 years, 3 males, 9 females). BD patients were initially administered 25 mg/day of lamotrigine, which was progressively escalated to 200 mg/d. BD participants underwent brain imaging prior to and following lamotrigine treatment. A 50% reduction in depressive scores indicated “remission”. Bayesian general linear models controlled for age, gender and intracranial volume were used to examine changes in relevant brain region following treatment. A posterior probability > 0.90 indicated evidence that there was an effect of diagnosis or remission on brain volumes. Probability distributions of interaction effects between remission and time indicated that BD responders displayed decreased amygdala, cerebellum and nucleus accumbens volumes following lamotrigine treatment. No serious adverse side effects were reported. The antidepressant effects of lamotrigine may be linked to volumetric changes in brain regions involved in mood and emotional regulation. These findings are preliminary and replication in a larger sample is warranted. [ABSTRACT FROM AUTHOR]

Background and Objectives: Delay discounting is associated with numerous clinically significant aspects of substance use disorders (SUDs). Recent studies have demonstrated that different models for assessing discounting may result in disparate conclusions. The current study compared two discounting tasks: money now versus money later (M-M) and methamphetamine now versus money later (MA-M) among non-treatment seeking individuals (N = 59) with methamphetamine use disorder (MAUD). Results from each task were assessed using three different models for assessing delay discounting.Methods: Discounting data were fit to three models of discounting, log k using Mazur's hyperbolic formula, area under the curve (AUC), and an alternative AUC model in which the delay values have been log transformed (AUClog).Results: For both discounting tasks, the distribution of model-related outcomes were normally distributed when using log k and AUClog, but skewed for AUC. Discounting in the MA-M task was significantly greater compared to the M-M task when using log k and AUClog but not AUC.Conclusion: To our knowledge, the current study is the first to report significantly greater discounting in a MA-M relative to M-M discounting task among individuals with MAUD, an outcome consistent with other psychomotor stimulants and drugs of abuse.Scientific Significance: The differential results observed across the three discounting models reaffirm potential issues with AUC noted in recent studies and highlight that researchers must be cautious when deciding on their final model of discounting. (Am J Addict 2018;XX:1-8). [ABSTRACT FROM AUTHOR]

Background: Immune system abnormalities have been repeatedly observed in several psychiatric disorders, including severe depression and anxiety. However, whether specific immune mediators play an early role in the etiopathogenesis of these disorders remains unknown.Methods: In a longitudinal design, component-wise gradient boosting was used to build models of depression, assessed by the Mood-Feelings Questionnaire-Child (MFQC), and anxiety, assessed by the Screen for Child Anxiety Related Emotional Disorders (SCARED) in 254 adolescents from a large set of candidate predictors, including sex, race, 39 inflammatory proteins, and the interactions between those proteins and time. Each model was reduced via backward elimination to maximize parsimony and generalizability.Results: Component-wise gradient boosting and model reduction found that female sex, growth- regulated oncogene (GRO), and transforming growth factor alpha (TGF-alpha) predicted depression, while female sex predicted anxiety.Limitations: Differential onset of puberty as well as a lack of control for menstrual cycle may also have been responsible for differences between males and females in the present study. In addition, investigation of all possible nonlinear relationships between the predictors and the outcomes was beyond the computational capacity and scope of the present research.Conclusions: This study highlights the need for novel statistical modeling to identify reliable biological predictors of aberrant psychological behavior. [ABSTRACT FROM AUTHOR]

• Gray and white matter volumetric increases can be seen after only six weeks of lithium monotherapy. • Such improvements can be seen in younger, less severe patients and a low serum lithium concentration. • Despite clinical shifts towards second-generation antipsychotics as first line mood stabilizers, expanding the use of lithium into demographics represented in this study may have underappreciated benefits in long-term neuronal preservation. Bipolar disorder (BD) is a highly variable and burdensome disease for patients and caregivers. A BD diagnosis almost triples the likelihood of developing dementia as the disease progresses. Neurocognitive reserve appears to be one of the most important influences on lifelong functional outcomes and quality of life in BD. Though several prior studies have assessed the effects of lithium on regional gray and white matter volumes in this population, representative cohorts are typically middle-aged, have a more severe pathology, and are not as commonly assessed in the depressive phase (which represents the majority of most patients' lifespans outside of remission). Here we have shown that positive adaptations with lithium can be observed throughout the brain after only six weeks of monotherapy at low-therapeutic serum levels. Importantly, these results remove some confounders seen in prior studies (patients were treatment free at time of enrollment and mostly treatment naïve). This cohort also includes underrepresented demographics in the literature (young adult patients, mostly bipolar II, and exclusively in the depressed phase). These findings bolster the extensive body of evidence in support of long-term lithium therapy in BD, furthering the possibility of its expanded use to wider demographics. [ABSTRACT FROM AUTHOR]

Background: Medication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the 'best efficacy' dose.Methods: A double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits for 9 weeks. The primary outcome was longest duration of abstinence (LDA), based on continuous cocaine-negative urine drug screens (UDS). The secondary outcome was probability of cocaine-negative UDS during treatment. A planned interim analysis performed at approximately 50% of recruitment dropped the least-effective active medication. Bayesian inference was used for all analyses with a pre-specified posterior probability (PP) threshold PP ≥ 95% considered statistically reliable evidence RESULTS: Citalopram 40 mg satisfied interim efficacy criteria and was retained for the second half of the trial. For LDA, analyses indicated PP = 82% and PP = 65% of benefit for 40 mg and 20 mg, respectively (each relative to placebo). The odds of having cocaine-negative UDS decreased in all groups over 9 weeks but remained higher for 40 mg (PP = 97.4%) CONCLUSIONS: Neither dose met the 95% PP threshold for the primary outcome; however, 40 mg provided moderate-to-strong evidence for positive effects on LDA and cocaine-negative UDS. The 40 mg dose was declared the "winner" in this DTL trial. [ABSTRACT FROM AUTHOR]

Background: Cisgender (cis) Black women in the USA are more likely to become HIV positive during their lifetime than other women. We developed and implemented a behavioral intervention, Increasing PrEP (iPrEP), the first pilot randomized controlled trial (RCT) aimed at motivating cis Black women to be willing to use PrEP for HIV prevention and attend an initial PrEP clinic visit following an emergency department visit. Methods: Eligible participants were Black cisgender women ages 18–55 years who acknowledged recent condomless sex and substance use. Participants were randomized to iPrEP or usual care (UC). iPrEP is a survey-based intervention designed to raise awareness and knowledge about PrEP. Participants completed an assessment of knowledge of and willingness to use PrEP before and after the intervention, then received a warm-hand off with referral to a local PrEP clinic. Enrolled participants were followed for 6 months. Results: Forty enrolled participants were ages 18–54 years. Education levels varied evenly between some high school education and graduate education. Most participants were single (n = 25) or married (n = 7). Twenty-two participants were employed full-time. Pre-test results indicated that 21 of 40 participants had heard of PrEP. All participants identified PrEP as a daily HIV prevention medication. For those randomized to iPrEP, the odds of knowing about PrEP at post-test, when controlling for baseline, were higher relative to UC (OR = 5.22, 95%CrI = 0.50, 94.1]. iPrEP did not have any effect on willingness relative to UC. The estimate for iPrEP on willingness is marginally higher (4.16 vs. 4.04; i.e., 0.12 points higher); however, the posterior probability of 67.9% does not suggest a strong degree of evidence in favor of an effect. During the post-test, those receiving iPrEP were less ready to take PrEP than those receiving UC. Conclusions: Findings suggest that iPrEP increased knowledge about the PrEP medication but had a negative impact on readiness to take PrEP relative to UC. It is imperative that future research among cisgender Black women carefully considers the content provided in interventions designed to increase PrEP use, balancing the benefits of PrEP with the side effects and daily pill burden. Trial registration: clinicaltrial.gov Identifier: NCT03930654, 29/04/2019. [ABSTRACT FROM AUTHOR]

Objective  Tobacco residue, also known as third-hand smoke (THS), contains toxicants and lingers in dust and on surfaces and clothes. THS also remains on hands of individuals who smoke, with potential transfer to infants during visitation while infants are hospitalized in neonatal intensive care units (NICUs), raising concerns (e.g., hindered respiratory development) for vulnerable infants. Previously unexplored, this study tested handwashing (HW) and sanitization efficacy for finger-nicotine removal in a sample of adults who smoked and were visiting infants in an NICU. Study Design  A cross-sectional sample was recruited to complete an interview, carbon monoxide breath samples, and three nicotine wipes of separate fingers (thumb, index, and middle). Eligible participants (n  = 14) reported current smoking (verified with breath samples) and were randomly assigned to 30 seconds of HW (n  = 7) or alcohol-based sanitization (n  = 7), with the order of finger wipes both counterbalanced and randomly assigned. After randomization, the first finger was wiped for nicotine. Participants then washed or sanitized their hands and finger two was wiped 5 minutes later. An interview assessing tobacco/nicotine use and exposure was then administered, followed by a second breath sample and the final finger wipe (40–60 minutes after washing/sanitizing). Results  Generalized linear mixed models found that HW was more effective than sanitizer for nicotine removal but failed to completely remove nicotine. Conclusions  Without proper protections (e.g., wearing gloves and gowns), NICU visitors who smoke may inadvertently expose infants to THS. Research on cleaning protocols are needed to protect vulnerable medical populations from THS and associated risks. Key Points NICU infants may be exposed to THS via visitors. THS is not eliminated by HW or sanitizing. THS removal protections for NICU infants are needed. [ABSTRACT FROM AUTHOR]

A hypothetical cocaine purchasing task (CocPT) was used to assess changes in cocaine demand in the context of contingency management (CM) treatment for cocaine use disorder (CUD). Participants (N = 89) were treatment-seeking individuals with CUD receiving 4 weeks of abstinence-based, high-magnitude CM. Treatment response (vs. non-response) was operationally defined as the submission of 6 consecutive cocaine-negative urine samples across two weeks. The CPT was assessed at baseline, week 2, and week 5. Demand data were well described by the exponentiated demand model, and baseline demand indices (Q0, Pmax, breakpoint, essential value) were significantly associated with self-report measures of cocaine use. The probability of being a zero-responder reporting zero cocaine consumption at all prices significantly increased over the course of treatment, and was greater among treatment responders vs. non-responders. Among non-zero demand data, decreases in Omax, Pmax, breakpoint, and essential value were observed over the course of CM treatment, favoring responders. To our knowledge, this is the first study to assess change in cocaine demand in the context of CM treatment targeting cocaine abstinence. Our results support the utility of cocaine demand as a measure for both identifying individuals with greater treatment need and tracking relapse risk over the course of treatment. [ABSTRACT FROM AUTHOR]

Background: Chronic cocaine users show impairments in cognitive processes associated with dopamine (DA) circuitry. Medications aimed at bolstering cognitive functions via DA modulation might enhance treatment outcome.Methods: The trial used a double-blind, double-dummy, parallel-group design with four treatment arms comparing placebo (PLC) to levodopa/carbidopa 800 mg/200 mg alone (LR0), levodopa plus extended release (XR) ropinirole 2 mg (LR2) or XR ropinirole 4 mg (LR4). Adults (n = 110) with cocaine use disorder attended thrice weekly clinic visits for 10 weeks. Potential cognitive mediators assessed at week 5 consisted of measures of decision-making (Iowa Gambling Task, Risky Decision-Making Task), attention/impulsivity (Immediate Memory Task), motivation (Progressive Ratio task), and cognitive control (Cocaine Stoop task). The primary outcome measure was the treatment effectiveness score (TES) calculated as the number of cocaine-negative urines collected from weeks 6-10.Results: Bayesian mediation examined indirect and total effects of the relationships between each active treatment (compared to PLC) and TES. Total (direct) effects were supported for LR0 and LR2, but not for LR4. Indirect effects were tested for each mediator. Notably, 22.3 % and 35.4 % of the total effects of LR0 and LR2 on TES were mediated by changes in attention/impulsivity.Conclusions: The hypothesized mediation effect was strongest for levodopa plus 2 mg ropinirole, indicating that this DA medication combination predicted change (improvement) in attention/impulsivity, which in turn predicted change (reduction) in cocaine use. This finding provides modest support for cognitive enhancement as a target for medications to treat cocaine use disorder. [ABSTRACT FROM AUTHOR]

Prescribed opioids are a mainstay pain treatment after traumatic injury, but a subgroup of patients may be at risk for continued opioid use. We evaluated the predictive utility of a traditional screening tool, the Opioid Risk Tool (ORT), and two other measures: average in-hospital milligram morphine equivalents (MME) per day and an assessment of opioid demand in predicting pain outcomes. Assessments of pain-related outcomes (pain intensity, interference, injury-related stress, and need for additional pain treatment) were administered at 2 weeks and 12 months post-discharge in a sample of 34 patients hospitalized for traumatic injury. Bayesian linear models were used to evaluate changes in responses over time as a function of predictors. High-risk ORT, higher MME per day, and greater opioid demand predicted less change in outcomes over time. This report provides first evidence that malleable factors of opioid and opioid demand have utility in predicting pain outcomes following traumatic injury. [ABSTRACT FROM AUTHOR]

Substance use disorders are characterized by marked changes in reward and error processing. The primary objective of this meta‐analysis was to estimate effect sizes for the reward positivity (RewP) and error‐related negativity (ERN), two event‐related potential indicators of outcome monitoring, in substance users compared to controls. The secondary objective was to test for moderation by demographic, substance type, and EEG experiment parameters. Final PubMed searches were performed in August 2023. Inclusion criteria were substance use disorder/dependence or validated self‐report of substance misuse, RewP/ERN means available, healthy control comparison group, non‐acute drug study, peer‐reviewed journal, English language, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3‐parameter selection model tests. The RewP results (19 studies, 1641 participants) did not support an overall effect (Hedges' g = 0.07, 95% CI [−0.44, 0.58], p =.777) and nor effect of any moderators. The ERN results (20 studies, 1022 participants) indicated no significant overall effect (g = 0.41, 95%CI [−0.05, 0.88]). Subgroup analyses indicated that cocaine users had a blunted ERN compared to controls (g = 1.12, 95%CI [0.77, 1.47]). There was limited evidence for publication/small study bias. Although the results indicate a potential dissociation between substance types, this meta‐analysis revealed the need for additional research on the RewP/ERN in substance using populations and for better designed experiments that adequately address research questions. Biomarkers have proven useful for detecting medical conditions, but remain elusive for psychiatric problems, including substance misuse. This meta‐analysis investigated how biomarkers of reward and punishment processing differ between substance misuse and comparison groups. This work has the potential to enhance the way we identify substance misuse problems and has implications for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Just-in-time adaptive interventions (JITAI) aim to prevent smoking lapse using tailored support delivered via mobile technology in the moments when it is most needed. Effective smoking cessation JITAI rely on the development of accurate decision rules that determine when someone is most likely to lapse. The primary goal of the present study was to identify the strongest predictors of first lapse among smokers undergoing a quit attempt.Methods: Smokers attending a clinic-based smoking cessation program (n = 74) were asked to complete ecological momentary assessments five times daily on study-provided smartphones for 4 weeks post-quit. A three-stage modeling process utilized Cox proportional hazards regression to examine time to lapse a function of 31 predictors. First, univariate models evaluated the relationship between each predictor and time to lapse. Second, the elastic net machine learning algorithm was used to select the best predictors. Third, backwards elimination further reduced the set of predictors to optimize parsimony.Results: Univariate models identified seven predictors significantly related to time to lapse. The elastic net algorithm retained five: perceived odds of smoking today, confidence in ability to avoid smoking, motivation to avoid smoking, urge to smoke, and cigarette availability. The reduced model demonstrated inadequate approximation to the non-penalized baseline model.Conclusions: Accurate estimation of moments of high risk for smoking lapse remains an important goal in the development of JITAI. These results demonstrate the utility of exploratory data-driven approaches to variable selection. The results of this study can inform future JITAI by highlighting targets for intervention. [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]

• 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]

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, but it has been underutilized by women. Anticipated stigma regarding use of PrEP is a contributing factor in the underutilization of this prevention strategy. The current study explored the relationships among PrEP stigma, sex risk (i.e., inconsistent condom use, condomless sex with persons of unknown serostatus, or sex in exchange for money or drugs), substance use, attitudes toward HIV testing, and medical mistrust. Participants were 106 primarily ethnic-minority women who reported recent substance use and agreed to participate in a study exploring HIV prevention attitudes. Within this sample, the majority of participants had one or more CDC-defined PrEP indications. Findings indicate that medical mistrust was associated with perceived PrEP stereotypes and HIV testing attitudes. These results provide some insight into reasons for low PrEP uptake among women at risk for HIV. Implications for HIV prevention with women are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Thirdhand smoke (THS) is ultrafine particulate matter and residue resulting from tobacco combustion, with implications for health-related harm (eg, impaired wound healing), particularly among hospitalized infants. Project aims were to characterize nicotine (THS proxy) transported on neonatal intensive care unit (NICU) visitors and deposited on bedside furniture, as well as infant exposure.Methods: Cross-sectional data were collected from participants in a metropolitan NICU. Participants completed a survey and carbon monoxide breath sample, and 41.9% (n = 88) of participants (n = 210) were randomly selected for finger-nicotine wipes during a study phase when all bedside visitors were screened for nicotine use and finger-nicotine levels. During an overlapping study phase, 80 mother-infant dyads consented to bedside furniture-nicotine wipes and an infant urine sample (for cotinine analyses).Results: Most nonstaff visitors' fingers had nicotine above the limit of quantification (>LOQ; 61.9%). Almost all bedside furniture surfaces (93.8%) and infant cotinine measures (93.6%) had values >LOQ, regardless of household nicotine use. Participants who reported using (or lived with others who used) nicotine had greater furniture-nicotine contamination (Mdn = 0.6 [interquartile range, IQR = 0.2-1.6] µg/m2) and higher infant cotinine (Mdn = 0.09 [IQR = 0.04-0.25] ng/mL) compared to participants who reported no household-member nicotine use (Mdn = 0.5 [IQR = 0.2-0.7] µg/m2; Mdn = 0.04 [IQR = 0.03-0.07] ng/mL, respectively). Bayesian univariate regressions supported hypotheses that increased nicotine use/exposure correlated with greater nicotine contamination (on fingers/furniture) and infant THS exposure.Conclusions: Potential furniture-contamination pathways and infant-exposure routes (eg, dermal) during NICU hospitalization were identified, despite hospital prohibitions on tobacco/nicotine use. This work highlights the surreptitious spread of nicotine and potential THS-related health risks to vulnerable infants during critical stages of development.Implications: THS contamination is underexplored in medical settings. Infants who were cared for in the NICU are vulnerable to health risks from THS exposure. This study demonstrated that 62% of nonstaff NICU visitors transport nicotine on their fingers to the NICU. Over 90% of NICU (bedside) furniture was contaminated with nicotine, regardless of visitors' reported household-member nicotine use or nonuse. Over 90% of infants had detectable levels of urinary cotinine during NICU hospitalizations. Results justify further research to better protect infants from unintended THS exposure while hospitalized. [ABSTRACT FROM AUTHOR]

Inflammation is implicated in cocaine use and associated problems, including depression and cognitive impairment. We assessed 18 cytokines, cocaine use, cognition, and depression in individuals with Cocaine Use Disorder. Our general hypothesis was that higher pro-inflammatory cytokines would relate to more cocaine use, poorer cognition, and more depression, while higher anti-inflammatory cytokines would relate to less cocaine use, better cognition, and less depression. Data were collected from 85 individuals (76.5% male, 80% African American) aged 18–65. The ASI, Shipley-2, and BDI-II assessed frequency and duration of cocaine use, cognition, and depression. Cytokines were tested using Bio-Plex Pro™ assays. Elastic net regression identified which cytokines related to each measure, controlling for confounds. Lower IL-29 (B = −0.08, bootstrapped 95%CI = [−0.24,0.07]), scD163 (B = −0.11, bootstrapped 95%CI = [−0.27,0.04]), Eotaxin-1 CCL11 (B = −0.11, bootstrapped 95%CI = [−0.30,0.08]), and higher APRIL/TNFSF13 (B = 0.11, bootstrapped 95%CI = [−0.08,0.30]) related to more frequent cocaine use. Lower IL-29 (B = −0.24, bootstrapped 95% CI = [−2.26,1.79]) and IL-20 (B = −1.62, bootstrapped 95%CI = [−3.53,0.29]) related to longer duration of cocaine use. Higher Eotaxin-2 CCL24 (B = 2.79, bootstrapped 95%CI = [−0.59,6.17]) and TWEAK (B = 2.83, bootstrapped 95%CI = [−0.80,6.45]) related to better cognition. Finally, higher IL-20 (B = −1.83, bootstrapped 95%CI = [−3.70,0.04]) and Osteocalcin (B = −1.56, bootstrapped 95%CI = [−3.81,0.70]) related to lower depressive symptoms. However, none of these relationships survived bootstrapped analyses. Pro- and anti-inflammatory cytokines may relate to cocaine use, cognition, and depression, but inconsistent with our hypotheses, higher pro-inflammatory cytokines related to better functioning in several domains. Additionally, cytokines were selected at low frequencies and demonstrated weak relationships with outcomes. These preliminary findings suggest complex relationships between inflammation and cocaine use. [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]

INTRODUCTION Non-smoking policies are strictly enforced in neonatal intensive care units (NICUs), which may still become contaminated by thirdhand smoke (THS), posing potential health risks to medically fragile infants. Study aims were to explore contamination routes by characterizing nicotine levels (THS proxy) found on the fingers of NICU medical staff and to assess finger-nicotine correlates. METHODS NICU medical staff were surveyed regarding smoking and electronic nicotine devices (ENDS) use/exposure, and household characteristics. Approximately 35% of staff were randomly selected for a finger-nicotine wipe. Three separate quantile regressions modeled percentiles associated with: presence of any finger nicotine, fingernicotine levels above the median field blank level (i.e. 0.377 ng/wipe), and finger-nicotine levels two times the median blank. RESULTS The final sample size was 246 (n=260 approached; n=14 refusals). Over three-quarters (78.5%) reported some exposure to tobacco smoke or ENDS vapor/aerosols. After field-blank adjustments, the median nicotine level (ng/finger wipe) was 0.232 (IQR: 0.021--0.681) and 78.3% of medical staff had measurable finger-nicotine levels. Both being near smoking in friends'/family members' homes and finger-surface area were related to elevated finger-nicotine levels (p<0.05) in the median blank model. CONCLUSIONS Almost four in five NICU staff had measurable finger nicotine, with finger surface area and frequency of reported exposure to tobacco smoke in friends'/family members' homes emerging as important correlates. Future research will determine the impact of THS on NICU infants. Medical personnel working in a NICU should be cognizant of secondhand smoke and THS, particularly inside friends'/family members' homes, to reduce potential NICU contamination and infant exposures. [ABSTRACT FROM AUTHOR]

Background: Apathy is among the most common behavioral symptoms in dementia and is consistently associated with negative outcomes in Alzheimer's disease (AD). Despite its prevalence and clinical relevance, available pharmacological and non-pharmacological strategies to treat apathy in AD have been marked, respectively, by potentially severe side effects and/or limited efficacy. Transcranial direct current stimulation (tDCS) is a relatively novel non-pharmacological method of neuromodulation with promising results. Compared to previous tDCS formats, recent technological advances have increased the portability of tDCS, which creates the potential for caregiver-administered, home use. Our study aims to evaluate the feasibility, safety, and efficacy of home-based tDCS for the treatment of apathy in AD. Methods/design: This is an experimenter- and participant-blinded, randomized, sham-controlled, parallel-group (1:1 for two groups) pilot clinical trial, involving 40 subjects with AD. After a brief training, caregivers will administer tDCS for participants at home under remote televideo supervision by research staff to ensure the use of proper technique. Participants will be assessed at baseline, during treatment (week 2, week 4, and week 6), and 6 weeks post-treatment. Dependent measures will cover cognitive performance, apathy, and other behavioral symptoms. Data about side effects and acceptability will also be collected. Discussion: Our study will address apathy, an overlooked clinical problem in AD. Our findings will advance the field of non-pharmacological strategies for neuropsychiatric symptoms, presenting a great potential for clinical translation. Trial registration: ClinicalTrials.gov, NCT04855643. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoid products have become popular and have led to an increased number of patients presenting to emergency departments and psychiatric hospitals. The purpose of this study was to evaluate the impact of synthetic cannabinoid use at admission on length of stay and doses of antipsychotics at discharge in individuals with bipolar disorder, schizophrenia and other psychotic disorders. We retrospectively examined medical records of 324 inpatients admitted from January 2014 to July 2015. We found that synthetic cannabinoid use predicted length of stay and antipsychotic dose using structural equation modeling. Further, the association of synthetic cannabinoid use with length of stay was partly mediated by antipsychotic dose. These associations were independent of specific diagnosis. In conclusion, patients with bipolar disorder, schizophrenia, or other psychotic disorders who reported synthetic cannabinoid use at admission had shorter length of stay and received lower doses of antipsychotics, irrespective of clinical diagnoses. [ABSTRACT FROM AUTHOR]

Background: Research on risk factors for neuropsychiatric adverse events (NAEs) in smoking cessation with pharmacotherapy is scarce. We aimed to identify predictors and develop a prediction model for risk of NAEs in smoking cessation with medications using Bayesian regularization. Methods: Bayesian regularization was implemented by applying two shrinkage priors, Horseshoe and Laplace, to generalized linear mixed models on data from 1203 patients treated with nicotine patch, varenicline or placebo. Two predictor models were considered to separate summary scores and item scores in the psychosocial instruments. The summary score model had 19 predictors or 26 dummy variables and the item score model 51 predictors or 58 dummy variables. A total of 18 models were investigated. Results: An item score model with Horseshoe prior and 7 degrees of freedom was selected as the final model upon model comparison and assessment. At baseline, smokers reporting more abnormal dreams or nightmares had 16% greater odds of experiencing NAEs during treatment (regularized odds ratio (rOR) = 1.16, 95% credible interval (CrI) = 0.95 – 1.56, posterior probability P(rOR > 1) = 0.90) while those with more severe sleep problems had 9% greater odds (rOR = 1.09, 95% CrI = 0.95 – 1.37, P(rOR > 1) = 0.85). The prouder a person felt one week before baseline resulted in 13% smaller odds of having NAEs (rOR = 0.87, 95% CrI = 0.71 – 1.02, P(rOR < 1) = 0.94). Odds of NAEs were comparable across treatment groups. The final model did not perform well in the test set. Conclusions: Worse sleep-related symptoms reported at baseline resulted in 85%—90% probability of being more likely to experience NAEs during smoking cessation with pharmacotherapy. Treatment for sleep disturbance should be incorporated in smoking cessation program for smokers with sleep disturbance at baseline. Bayesian regularization with Horseshoe prior permits including more predictors in a regression model when there is a low number of events per variable. [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]

Background: Pregnant Mexican Americans (hereafter called Latinas) and Black/African American women are at increased risk for psychological distress, contributing to preterm birth and low birthweight; acculturative stress combined with perceived stress elevates depressive symptoms in Latinas. Based on our prior research using a psychoneuroimmunology framework, we identified psychological and neuroendocrine risk factors as predictors of preterm birth in Latina women that are also identified as risk factors for Black/African American women. Methods/design: In this prospective, randomized controlled trial with parallel group design we will explore psychosocial, neuroendocrine, and birth outcome effects of the Mastery Lifestyle Intervention (MLI). The MLI is a culturally relevant, manualized, psychosocial, group intervention integrating two cognitive behavioral therapies for both pregnant Latinas and Black/African American women (total n = 221). Study inclusion criteria are: women with current pregnancy at 14–20 weeks gestation, ability to read and speak English or Spanish, self-identify as Latina of Mexican heritage or Black/African American, 18–45 years old, born in the US or Mexico, and currently living in the US. Participants must receive Medicaid or other government-supported insurance, and meet screening criteria for anxiety, depressive symptoms, or stress. Participants are randomly assigned to either the intervention (MLI) or usual care group (UCG) in groups of 6–8 participants that occur over 6 consecutive weeks. Data are collected at 3 time points: enrollment (14–20 weeks gestation), following treatment (20–26 weeks), and 6 weeks after treatment (32–36 weeks gestation). Additional outcome, mediating, and moderating data are collected from the electronic health record during pregnancy and at birth. Analyses will primarily use generalized linear mixed modeling (GLMM) to evaluate the relationships between predictors and outcomes. Discussion: This RCT will test the efficacy of two combined third generation cognitive behavioral therapies (the MLI), given in a group format over 6 sessions, as compared to a usual prenatal care group, for both Latina and African American pregnant women. If efficacious, it may be provided as an adjunct to routine prenatal care and improve mental health, as well as babies being born too small and too soon. Trial registration: The trial was retrospectively registered at ClinicalTrials.gov. Bethesda (MD): National Library of Medicine. Identifier NCT05012072, Reducing Pregnancy Risks: The Mastery Lifestyle Intervention (MLI); August 19, 2021. The trial is currently recruiting participants. [ABSTRACT FROM AUTHOR]

The death of a spouse is associated with maladaptive immune alterations; grief severity may exacerbate this link. We investigated whether high grief symptoms were associated with an amplified inflammatory response to subsequent stress among 111 recently bereaved older adults. Participants completed a standardized psychological stressor and underwent a blood draw before, 45 min after, and 2 hr after the stressor. Those experiencing high grief symptoms (i.e., scoring > 25 on the Inventory of Complicated Grief) experienced a 45% increase in interleukin-6 (IL-6; a proinflammatory cytokine) per hour, whereas those experiencing low grief symptoms demonstrated a 26% increase. In other words, high grief was related to a 19% increase in IL-6 per hour relative to low grief. The grief levels of recently bereaved people were associated with the rate of change in IL-6 following a subsequent stressor, above and beyond depressive symptoms. This is the first study to demonstrate that high grief symptoms promote inflammation following acute stress. [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: Apathy is among the most frequent neuropsychiatric syndromes in Alzheimer's disease (AD).Objective: To determine the prevalence of apathy and the associated clinical and laboratorial parameters (focus on inflammatory biomarkers) in patients with dementia enrolled at the Texas Alzheimer's Research and Care Consortium (TARCC) study.Methods: This is a cross-sectional analysis of TARCC baseline. Participants were evaluated through different clinical tools, including the Mini-Mental State Examination (MMSE) and the Lawton-Brody Instrumental Activities of Daily Life (IADL)/Physical Self-Maintenance Scale (PSMS). Apathy was defined by a positive response to the respective item in the Neuropsychiatric Inventory-Questionnaire applied to caregivers. Serum levels of 16 biomarkers were determined by HumanMap multiplex immunoassay. Comparisons between apathy versus non-apathy groups were carried out with non-parametric tests. Logistic regression and the least absolute shrinkage and selection operator (LASSO) were used to separately model apathy as a function of each biomarker, adjusted for the potential confounders.Results: From 1,319 patients with AD (M/F: 579/740, mean age ± SD: 75.3 ± 8.4), 373 (28.3%) exhibited apathy. When categorized according to the presence of apathy, the groups had significant differences in sex, diabetes diagnosis, and tobacco use. The apathy group also had worse cognitive performance and daily functioning than the non-apathy group as assessed, respectively, by MMSE and IADL/PSMS. Higher levels of interleukin-6, interleukin-10, and leptin were associated with higher odds of apathy.Conclusion: Apathy is associated with cognitive and functional status in AD. The association between apathy and peripheral inflammatory mediators deserves further investigation. [ABSTRACT FROM AUTHOR]

This study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed whether 4 weeks of contingency management (CM) improved response with the addition of Acceptance and Commitment Therapy (ACT). Phase 2 assessed pharmacological augmentation with modafinil (MOD) vs. placebo (PLA) for individuals not achieving abstinence during Phase 1. For Phase 1 of treatment, participants (N =118) were randomly allocated to ACT+CM or Drug Counseling (DC+CM), the comparison condition. At week 4, treatment response was defined as the submission of six consecutive cocaine-negative urine drug screens (UDS). Phase 1 non-responders were re-randomized to MOD or PLA as adjunct to their initial treatment. Phase 1 responders continued receiving their initial treatment. Primary outcomes included response rate and proportion of cocaine-negative UDS for Phase 1 and 2. Analyses used Bayesian inference with 80% pre-specified as the posterior probability (PP) threshold constituting moderate evidence that an effect exists. Phase 1 response was higher in the ACT+CM group (24.5%) compared to the DC+CM group (17.5%; PP = 84.5%). In Phase 2, the proportion of cocaine-negative UDS among Phase 1 responders did not differ by initial treatment (PP = 61.8%) but remained higher overall compared to Phase 1 non-responders (PPs > 99%). No evidence of an effect favoring augmentation with MOD was observed. Adding ACT to CM increased abstinence initiation. Initial responders were more likely to remain abstinent compared to initial non-responders, for whom modafinil was not an effective pharmacotherapy augmentation strategy. • Adaptive designs that tailor treatment based on patient response may be useful for cocaine use disorder. • A Sequential Multiple Assignment Randomized Trial (SMART) design is well suited for developing adaptive interventions. • Response rates for achieving initial abstinence were highest among participants receiving ACT + CM • Pharmacological augmentation with modafinil did not increase the probability of abstinence during Phase 2. • Stronger strategies are needed to achieve optimal outcomes after initial non-response. [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]