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Among women of color in the United States, infection with the human immunodeficiency virus (HIV) is rising. Most of the research on this topic, however, has focused on individual-level risk factors, which do not fully explain racial or ethnic differences in infection rates. This article uses structural violence as a conceptual framework to examine ecological-level risk factors leading to disparate rates of heterosexually transmitted HIV among women of color in Syracuse, New York. Three ecological pathways to disproportionate infection are discussed: community rates of infection, concurrent partnerships, and increased vulnerability. The discussion of the pathways considers the following macro-level risk factors: disproportionate incarceration rates of African American men, residential segregation, gang turf, constraints on access to sexually transmitted disease services, an African American sex ratio in which women outnumber men, social norms stigmatizing homosexuality, and commercial sales of douching products. The authors argue that health care providers and policy analysts must address ecological-level risk factors for HIV transmission in underserved communities. [ABSTRACT FROM AUTHOR]

This article presents the multifaceted efforts of Syracuse Healthy Start, a federally funded initiative of the Onondaga County Health Department and over 20 partnering agencies to reduce racial and ethnic disparities in infant mortality. The analyses presented in this article demonstrate that many women—Caucasian, African American, and Hispanic—have serious risks for low birth weight and infant death. In many cases, multiple, simultaneous risks complicate a pregnant woman's situation and in other cases the longitudinal cumulative risks impact health across generations. Infant mortality decreased overall, and for both Caucasian and African American infants during the first 3 years of the project. [ABSTRACT FROM AUTHOR]

This article examines the economics of abortion safety in Egypt. Under Egyptian law induced abortion is restricted to cases in which two physicians certify that the pregnancy presents a danger to the health or life of the mother. Despite this legal restriction, the available data indicate that abortion is quite widely practiced. Multifaceted strands of legal, religious, economic, and health care policy influence both discourse about and access to abortion in Egypt. Interviews with 18 Egyptian women who sought to terminate their pregnancies revealed a wide range of abortion methods that varied in both safety and cost. Three levels of safety were identified: (1) indigenous (wasfa baladi) methods were potentially the least safe; (2) biomedical abortions at clandestine clinics appeared safer than indigenous methods, but were not without risk: and (3) biomedical abortions administered by private gynecologists, were the most safe. Safety is expensive. Wealthy women can literally buy safety, while poor women's lack of financial resources put their lives at great risk. [ABSTRACT FROM AUTHOR]

People who use substances commonly experience sleep disruptions, affecting the regulation of physical and mental health, and presenting a significant barrier to treatment success. Sleep impairments are noted in all phases of substance use; however, differences between subjective versus objective methods used to measure sleep quality have been reported. While polysomnography is the gold-standard for sleep measurement, recent advances in actigraphy may help address the discordance between subjective and objective sleep reports. This systematic review examined emerging evidence (2016-present) for sleep impairment in people who use substances, with the twofold goal of: (1) identifying whether sleep outcomes vary across substance type (alcohol, nicotine, cannabis, cocaine, methamphetamine and opioids); and (2) contrasting results from subjective and objective measures. While some differences between subjective and objective sleep were noted, there was overwhelming evidence of clinically relevant sleep impairment in people who use alcohol, nicotine, cocaine, methamphetamine and opioids, with less consistent results for cannabis. Gaps in the literature are identified and future recommendations are presented, including utilization of common methodological frameworks, identification of mechanisms, and closer examination of sleep across stages of substance use and the interconnection between sleep and return to use., (© 2024 European Sleep Research Society.)

Background: Fatigue is a multidimensional condition that may overlap with depression. Initial studies found that fatigue responds in only a limited way to standard monoaminergic antidepressants and mood stabilizers but does respond positively to intravenous (IV) racemic (R,S)-ketamine (ketamine). However, IV ketamine's use is limited by cost and access barriers. To date, no study has evaluated intranasal (IN) ketamine in individuals with fatigue. This study sought to evaluate the anti-fatigue effects of a single 50 mg dose of IN ketamine in individuals with major depressive disorder (MDD) or bipolar depression (BDep), both with and without comorbid alcohol use disorder (AUD)., Methods: Twenty-eight individuals with primary diagnoses of MDD or BDep I/II currently experiencing a depressive episode with active suicidality were enrolled; approximately 60 % had comorbid AUD. Changes in the NIH-Brief Fatigue Inventory (NIH-BFI) were assessed at baseline and at 4, 24, and 48 h post-treatment., Results: The group x time interaction for NIH-BFI score was significant (F = 3.44, p = 0.022), favoring IN ketamine over placebo. IN ketamine was well-tolerated with minimal adverse effects., Limitations: Limitations include the limited sample size, short duration, and single, fixed dose., Conclusions: IN ketamine appears to induce rapid anti-fatigue effects in individuals with severe MDD and BDep both with and without comorbid AUD. This suggests that IN ketamine holds potential as an alternative, rapid-acting, anti-fatigue option for different medical conditions., Competing Interests: Declaration of competing interest Dr. Machado-Vieira has received consulting fees from Eurofarma Pharmaceuticals, Abbott, and BioStrategies group; has research contracts with Boerhinger Ingelheim and Janssen Pharmaceuticals; has received speaker fees from Otsuka, EMS, and Cristalia; and is a member of the scientific boards of Symbinas Pharmaceuticals and Allergan. Dr. Machado-Vieira is also the PI for the following grants: NIH (R21HD106779 and R21MH129888), Milken Institute (BD-0000000081), Dr Machado-Vieira was PI for the Janssen 54135419TRD4005 study. Dr. Soares has served on the Advisory Board of Alkermes; as a Consultant for Boehringer, Johnson and Johnson, Livanova, and Sunovian; and received research grants from Compass Pathways, Mind Med, and Relmada. Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorder. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise., (Copyright © 2024. Published by Elsevier B.V.)

Cocaine use disorder (CUD) is a major public health issue, and greater cocaine use severity has been associated with worse treatment retention and outcomes. Therefore, greater understanding of processes that influence cocaine use is needed. Both anhedonia (i.e., undervaluation of nondrug rewards) and cocaine demand (i.e., cocaine valuation) are related to cocaine use severity and thematically related to each other at face value, but no studies have directly compared these outcomes to our knowledge. The present study represents a secondary analysis from a two-phase sequential, multiple assignment, randomized trial aimed at developing adaptive interventions for CUD. We examined the relationship between anhedonia and cocaine demand and how these measures were related to cocaine use severity. Participants ( N = 116) were treatment-seeking adults with CUD. All measures were taken at baseline before treatment initiation. Analyses revealed (a) moderate and very strong evidence of relationships between cocaine demand factors (i.e., persistence, amplitude) and anhedonia (PP values ≥ 77.8%); (b) positive association between cocaine demand (both persistence and amplitude) and measures of cocaine use severity, with the exception of one relationship, which was in the opposite direction; and (c) demand amplitude continued to be positively related to cocaine use severity, even when considering anhedonia. Overall, findings from this study indicate cocaine demand relates to cocaine use severity more strongly than anhedonia. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Behavioral therapies are considered best practices in the treatment of substance use disorders (SUD) and used as first-line approaches for SUDs without FDA-approved pharmacotherapies. Decades of research on the neuroscience of drug reward and addiction have informed the development of current leading behavioral therapies that, while differing in focus and technique, have in common the overarching goal of shifting reward responding away from drug and toward natural non-drug rewards. This review begins by describing key neurobiological processes of reward in addiction, followed by a description of how various behavioral therapies address specific reward processes. Based on this review, a conceptual 'map' is crafted to pinpoint gaps and areas of overlap, serving as a guide for selecting and integrating behavioral therapies., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

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., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024 Society for Psychophysiological Research.)

Objective: Although individuals with a family history of alcohol use disorder (AUD) have a superior antidepressant response to ketamine, outcomes in patients with current AUD remain unclear. This study sought to investigate whether intranasal (IN) racemic ( R,S )-ketamine had antisuicidal and antidepressant effects in unipolar and bipolar depression and whether comorbid AUD conferred superior antisuicidal outcomes for patients., Methods: This was a double-blind, randomized, placebo-controlled trial (May 2018 to January 2022) of single administration, fixed-dose (50 mg) IN ( R,S )-ketamine (or saline comparator) in unmedicated inpatients meeting Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition, Text Revision, criteria for a current major depressive episode (bipolar or unipolar), with current suicidal ideation (SI) and past attempt. Patients with and without comorbid AUD were enrolled. Change in Scale for Suicide Ideation score was the primary outcome measure, and change in Montgomery-Åsberg Depression Rating Scale score was the secondary outcome measure., Results: No significant group × time effect was noted for SI ( F = 1.1, P = .36). A statistical trend toward superior improvement in suicidality was observed in participants with comorbid AUD. The group × time interaction was significant for improvements in depression ( F = 3.06, P = .03) and largely unaffected by comorbid AUD or primary mood disorder type. Within the ketamine group, a significant correlation was observed between improvement in depressive symptoms and SI for patients without comorbid AUD ( r =0.927, P = .023) that was absent in patients with AUD ( r = 0.39, P = .44)., Conclusion: IN ketamine induced rapid antidepressant effects compared to placebo but did not significantly alter SI scores. The treatment was well tolerated. Continued investigation with IN ketamine as a practical alternative to current formulations is warranted., Trial Registration: ClinicalTrials.gov identifier: NCT03539887., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Background: 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., Method: 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., Results: 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., Discussion: 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., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Background: Widescale evidence points to the involvement of glia and immune pathways in the progression of Alzheimer's disease (AD). AD-associated iPSC-derived glial cells show a diverse range of AD-related phenotypic states encompassing cytokine/chemokine release, phagocytosis and morphological profiles, but to date studies are limited to cells derived from PSEN1, APOE and APP mutations or sporadic patients. The aim of the current study was to successfully differentiate iPSC-derived microglia and astrocytes from patients harbouring an AD-causative PSEN2 (N141I) mutation and characterise the inflammatory and morphological profile of these cells., Methods: iPSCs from three healthy control individuals and three familial AD patients harbouring a heterozygous PSEN2 (N141I) mutation were used to derive astrocytes and microglia-like cells and cell identity and morphology were characterised through immunofluorescent microscopy. Cellular characterisation involved the stimulation of these cells by LPS and Aβ 42 and analysis of cytokine/chemokine release was conducted through ELISAs and multi-cytokine arrays. The phagocytic capacity of these cells was then indexed by the uptake of fluorescently-labelled fibrillar Aβ 42 ., Results: AD-derived astrocytes and microglia-like cells exhibited an atrophied and less complex morphological appearance than healthy controls. AD-derived astrocytes showed increased basal expression of GFAP, S100β and increased secretion and phagocytosis of Aβ 42 while AD-derived microglia-like cells showed decreased IL-8 secretion compared to healthy controls. Upon immunological challenge AD-derived astrocytes and microglia-like cells showed exaggerated secretion of the pro-inflammatory IL-6, CXCL1, ICAM-1 and IL-8 from astrocytes and IL-18 and MIF from microglia., Conclusion: Our study showed, for the first time, the differentiation and characterisation of iPSC-derived astrocytes and microglia-like cells harbouring a PSEN2 (N141I) mutation. PSEN2 (N141I)-mutant astrocytes and microglia-like cells presented with a 'primed' phenotype characterised by reduced morphological complexity, exaggerated pro-inflammatory cytokine secretion and altered Aβ 42 production and phagocytosis., (© 2023. The Author(s).)

Background: Screening to identify patients at risk for opioid misuse after trauma is recommended but not commonly used to guide perioperative opioid management interventions. The Multimodal Analgesic Strategies for Trauma trial demonstrated that an opioid-minimizing multimodal pain regimen reduced opioid exposure in a heterogeneous trauma patient population. Here, we assess the efficacy of the Multimodal Analgesic Strategies for Trauma multimodal pain regimen in a critical patient subgroup who screened at high risk for opioid misuse., Methods: The Multimodal Analgesic Strategies for Trauma trial compared an opioid-minimizing multimodal pain regimen (oral acetaminophen, naproxen, gabapentin, lidocaine patch, as-needed opioid) against an original multimodal pain regimen (intravenous followed by oral acetaminophen, 48-hour celecoxib and pregabalin, followed by naproxen and gabapentin, scheduled tramadol, as-needed opioid), in a randomized trial conducted from April 2018 to March 2019. A total of 631 enrolled patients were classified either as low- or high-risk via the Opioid Risk Tool. Bayesian analyses evaluated the moderating influence of Opioid Risk Tool risk (high/low) on the effect of Multimodal Analgesic Strategies for Trauma multimodal pain regimen (versus original) on opioid exposure (morphine milligram equivalents/day), opioids prescribed at discharge, and pain scores., Results: Multimodal Analgesic Strategies for Trauma multimodal pain regimen effectively reduced morphine milligram equivalents/day in low- and high-Opioid Risk Tool risk groups. Moderation was observed for opioids at discharge and pain scores; Multimodal Analgesic Strategies for Trauma multimodal pain regimen was effective in the high-risk group only (opioids at discharge: 63% vs 77%, relative risk = 0.86, 95% Bayesian credible interval [0.66-1.08], posterior probability (relative risk <1) = 90%; pain scores: b = 3.8, 95% Bayesian credible interval [3.2-4.4] vs b = 4.0, 95% Bayesian credible interval [3.4-4.6], posterior probability (b <0) = 87%)., Conclusion: This study is the first to show the moderating influence of opioid misuse risk on the effectiveness of an opioid-minimizing multimodal pain regimen. The Opioid Risk Tool was useful in identifying high-risk patients for whom the Multimodal Analgesic Strategies for Trauma multimodal pain regimen is recommended for perioperative pain management., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: In Syracuse, NY among 5998 births in a 3-year period (2017-2019), 24% were to foreign-born women, among whom nearly 5% were refugees from the Democratic Republic of the Congo and Somalia. The impetus for the study was to identify potential risk factors and birth outcomes of refugee women, other foreign-born women, and US born women to inform care., Methods: This study reviewed 3 years of births (2017-2019) in a secondary database of births in Syracuse, New York. Data reviewed included maternal demographics, natality, behavioral risk factors (e.g., drug use, tobacco use), employment, health insurance, and education., Results: In a logistic regression model controlling for race, education, insurance status, employment status, tobacco use and illicit drug use, compared to US born mothers, refugees (OR 0.45, 95% CI 0.24-0.83) and other foreign born (OR 0.63, 95% CI 0.47-0.85) had significantly fewer low birth weight births., Conclusion: The results of this study supported the "healthy migrant effect," a concept that refugees have fewer low birth weight (LBW) births, premature births, and cesarean section deliveries than US born women. This study adds to the literature on refugee births and the healthy migrant effect., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The behavioral economic measure drug demand and the neural measure late positive potential (LPP) are two measures of motivational value that have been associated with drug relapse risk and treatment outcomes. Despite having overlapping themes, no studies have directly compared drug demand and LPP. Participants ( N = 59) included treatment-seeking individuals with cocaine use disorder that had completed both a baseline cocaine demand task and an electroencephalogram (EEG) picture-viewing task of drug-related and pleasant picture cues. Associations between the LPP difference score amplitude (drug-pleasant) and five demand indices ( Q ₀, essential value [EV], O max , P max , and breakpoint [BP]) were evaluated via Bayesian generalized linear modeling. Positive associations (posterior probabilities ≥ 75%) were found between LPP amplitude and four demand indices ( Q ₀, EV, O max , BP). These results suggest that individuals who attach greater relevance to cocaine cues also exhibit greater valuation of cocaine reward. Implications for incorporating methodology from behavioral science and brain imaging are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background and Aims: Identifying modifiable neuropsychological factors associated with more severe CUD could improve CUD treatment. Impairments in processing of non-drug rewards may be one such factor. This study assessed the relationship between reward functioning and cocaine use severity using multi-modal measures of three distinct reward functions: consummatory reward (pleasure or "liking"); motivational reward ("wanting") and reward learning., Methods: Fifty-three adults with at least moderate CUD completed self-report and behavioral measures of consummatory reward, motivational reward and reward learning, and a composite cocaine use severity measure including quantity, frequency and life impacts of cocaine use. We conducted parallel Frequentist and Bayesian multiple regressions with measures of reward functioning as predictors of cocaine use severity., Results: Less self-reported ability to experience pleasure, a hypothesized measure of consummatory reward, significantly predicted greater severity after adjustment for covariates and multiple hypothesis testing, β = 0.39, t(38) = 2.86, p = 0.007. Bayesian analyses confirmed a highly likely association between severity and ability to experience pleasure, and provided moderate evidence for associations with willingness to exert effort and reward learning., Conclusions: Our results suggest that less experience of subjective pleasure is related to greater cocaine use severity. This cross-sectional study cannot establish whether differences in consummatory reward are pre-existing, a result of CUD, or both. However, these results suggest interventions focused on increasing subjective pleasure, such as mindful "savoring", should be investigated for CUD., Competing Interests: Declaration of Competing Interest No conflicts declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: The detection of seasonal patterns in suicidality should be of interest to clinicians and US public health officials, as intervention efforts can benefit by targeting periods of heightened risk., Objectives: To examine recent trends in suicidality rates, quantify the seasonality in suicidality, and demonstrate the disrupted seasonality patterns during the spring 2020 COVID-19-related school closures among US children and adolescents., Design, Setting, and Participants: This population-based, descriptive cross-sectional study used administrative claims data from Optum's deidentifed Clinformatics Data Mart Database. Participants included children aged 10 to 12 years and adolescents aged 13 to 18 years who were commercially insured from January 1, 2016, to December 31, 2021. Statistical analysis was conducted between April and November 2022., Exposures: Month of the year and COVID-19 pandemic., Main Outcomes and Measures: Rates and seasonal patterns of emergency department (ED) visits and hospitalizations for suicidality., Results: The analysis included 73 123 ED visits and hospitalizations for suicidality reported between 2016 and 2021. Among these events, 66.1% were reported for females, and the mean (SD) age at the time of the event was 15.4 (2.0) years. The mean annual incidence of ED visits and hospitalizations for suicidality was 964 per 100 000 children and adolescents (95% CI, 956-972 per 100 000), which increased from 760 per 100 000 (95% CI, 745-775 per 100 000) in 2016 to 1006 per 100 000 (95% CI, 988-10 024 per 100 000) in 2019, with a temporary decrease to 942 per 100 000 (95% CI, 924-960 per 100 000) in 2020 and a subsequent increase to 1160 per 100 000 (95% CI, 1140-1181 per 100 000) in 2021. Compared with January, seasonal patterns showed peaks in April (incidence rate ratio [IRR], 1.15 [95% CI, 1.11-1.19]) and October (IRR, 1.24 [95% CI, 1.19-1.29]) and a nadir in July (IRR, 0.63 [95% CI, 0.61-0.66]) during pre-COVID-19 years and 2021. However, during the spring of 2020, which coincided with school closures, seasonal patterns were disrupted and April and May exhibited the lowest rates., Conclusions and Relevance: The findings of this study indicated the presence of seasonal patterns and an observed unexpected decrease in suicidality among children and adolescents after COVID-19-related school closures in March 2020, which suggest a potential association between suicidality and the school calendar.

Introduction: Obesity and smoking are the two leading causes of preventable death in the USA. Unfortunately, most smokers gain weight after quitting. Postcessation weight gain (PCWG) is frequently cited as one of the primary barriers to a quit attempt and a common cause of relapse. Further, excessive PCWG may contribute to the onset or progression of metabolic conditions, such as hyperglycaemia and obesity. The efficacy of the current treatments for smoking cessation is modest, and these treatments have no clinically meaningful impact on mitigating PCWG. Here, we outline a novel approach using glucagon-like peptide 1 receptor agonists (GLP-1RA), which have demonstrated efficacy in reducing both food and nicotine intake. This report describes the design of a double-blind, placebo-controlled, randomised clinical trial that evaluates the effects of the GLP-1RA exenatide as an adjunct to nicotine patches on smoking abstinence and PCWG., Methods and Analysis: The study will be conducted at two university-affiliated research sites in Houston, Texas, the UTHealth Center for Neurobehavioral Research on Addiction and Baylor College of Medicine Michael E. DeBakey VA Medical Centre. The sample will consist of 216 treatment-seeking smokers with pre-diabetes (haemoglobin A1c of 5.7%-6.4%) and/or overweight (body mass index of 25 kg/m 2 or above). Participants will be randomised (1:1) to receive subcutaneous injections of placebo or 2 mg exenatide, once weekly for 14 weeks. All participants will receive transdermal nicotine replacement therapy and brief smoking cessation counselling for 14 weeks. The primary outcomes are 4-week continuous abstinence and changes in body weight at the end of treatment. The secondary outcomes are (1) abstinence and changes in body weight at 12 weeks post end of treatment and (2) changes in neuroaffective responses to cigarette-related and food-related cues as measured by electroencephalogram., Ethics and Dissemination: The study has been approved by the UTHealth Committee for the Protection of Human Subjects (HSC-MS-21-0639) and Baylor College of Medicine Institutional Review Board (H-50543). All participants will sign informed consent. The study results will be disseminated via peer-reviewed publications and conference presentations., Trial Registration Number: NCT05610800., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Globally, structural racism has been well documented as an important social determinant of health (SODH) resulting in racial inequality related to health. Although studies on structural racism have increased over the years, the selection of appropriate designs, measures, and indexes of measurement that respond to SODH has not been comprehensively documented. Therefore, the lack of evidence seems to exist. This scoping review was conducted to map and summarize global evidence on the use of various designs, measures, and indexes of measurement when studying structural racism as a social determinant of health., Methods: We performed a scoping review of global evidence from 2000 to 2022 published in 5 databases: PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo, Web of Science, ProQuest, and relevant grey literature on structural racism. We conducted a systematic search using keywords and subject headings around 3 concepts. We included peer reviewed original research/review articles which conceived the framework of social determinants of health (SODH) and studied structural racism., Results: Our review identified 1793 bibliographic citations for screening and 54 articles for final review. Articles reported 19 types of study design, 87 measures of exposure and 58 measures of health outcomes related to structural racism. 73 indexes or scales of measurement were used to assess health impacts of structural racism. Majority of articles were primary research (n = 43/54 articles; 79.6%), used quantitative research method (n = 32/54 articles; 59.3%) and predominantly conducted in the United States (n = 46/54 articles; 85.2.6%). Cross-sectional study design was the most used design (n = 17/54 articles; 31.5%) followed by systematic review (n = 7/54 articles; 13.0%) and narrative review (n = 6/54 articles; 11.1%). Housing and residential segregation was the largest cluster of exposure with the highest impact in infant health outcome., Conclusions: Our review found several key gaps and research priorities on structural racism such as lack of longitudinal studies and availability of structural or ecological data, lack of consensus on the use of consolidated appropriate measures, indexes of measurement and appropriate study designs that can capture complex interactions of exposure and outcomes related to structural racism holistically., (© 2022. The Author(s).)

The objective of the current meta-analysis was to assess the effect size of the Late Positive Potential (LPP) to drug and emotional cues in substance users compared to controls. The secondary objective was to test for moderation by: age, gender, years of use, use status, and substance type. Search was performed in August 2021 using PubMed. Inclusion criteria were: substance use disorder/dependence or validated self-report, LPP means, healthy control comparison, non-acute drug study, data available, peer-reviewed journal, English, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. Results (k = 11) indicated LPP to drug cues was larger in substance use compared to control group, with a large effect size (Hedges' g=1.66, 95%CI [0.64,2.67], p = 0.005). There were no overall differences for emotional cues. Though threats of selection bias were not severe, inclusion of more studies with larger sample sizes in future meta-analyses will allow more robust tests of publication bias and more accurate measures of effect size., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Smokers with stronger neuroaffective responses to drug-related cues compared to nondrug-related pleasant images (C > P) are more vulnerable to compulsive smoking than individuals with the opposite brain reactivity profile (P > C). However, it is unknown if these neurobehavioral profiles exist in individuals abusing other drugs. We tested whether individuals with cocaine use disorder (CUD) show similar neuroaffective profiles to smokers. We also monitored eye movements to assess attentional bias toward cues and we further performed exploratory analyses on demographics, personality, and drug use between profiles. Participants with CUD ( n = 43) viewed pleasant, unpleasant, cocaine, and neutral images while we recorded electroencephalogram. For each picture category, we computed the amplitude of the late positive potential (LPP), an event-related potential component that reflects motivational relevance. k-means clustering classified participants based on their LPP responses. In line with what has been observed in smokers, clustering participants using LPP responses revealed the presence of two groups: one with larger LPPs to pleasant images compared to cocaine images (P > C) and one group with larger LPPs to cocaine images compared to pleasant images (C > P). Individuals with the C > P reactivity profile also had higher attentional bias toward drug cues. The two groups did not differ on demographic and drug use characteristics, however individuals with the C > P profile reported lower distress tolerance, higher anhedonia, and higher posttraumatic stress symptoms compared to the P > C group. This is the first study to report the presence of these neuroaffective profiles in individuals with CUD, indicating that this pattern may cut across addiction populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Importance: The Coronavirus Disease (COVID-19) pandemic has significantly impacted mental health outcomes. While the frequency of anxiety and depressive symptoms has increased in the whole population, the relationship between COVID-19 and new psychiatric diagnoses remains unclear., Objective: To compare the population incidence rate of emergence of de novo psychiatric disorders in 2020 compared to the previous years, and to compare the incidence rate of new psychiatric disorder diagnoses between people with vs without COVID-19., Design, Setting, and Participants: This study utilized administrative claims data from the Clinformatics® Data Mart database, licensed from Optum®. The study is a cross-sectional analysis that compared the incidence rate of new psychiatric disorders in 2020 vs. 2018 and 2019 in the entire insured population database. Subsequently, the incidence of new psychiatric disorders in people with vs. without COVID-19 during 2020 was analyzed., Exposure: The exposures included diagnosis and severity of COVID-19 infection., Main Outcomes Measures: The dependent variables of interest were the incidence rates of new psychiatric disorders, specifically schizophrenia spectrum disorders, mood disorders, anxiety disorders, and obsessive-compulsive disorder., Results: The population studied included 10,463,672 US adults (mean age 52.83, 52% female) who were unique people for the year of 2020. Incidence of newly diagnosed psychiatric disorders per 1,000 individuals in the 2020 whole population were 28.81 (CI: 28.71, 28.92) for anxiety disorders, 1.04 (CI: 1.02, 1.06) for schizophrenia disorders, 0.42 (CI: 0.41, 0.43) for OCD and 28.85 (CI: 28.75, 28.95) for mood disorders. These rates were not significantly higher than 2018 or 2019. When comparing incidence rates between COVID-19 vs. non-COVID-19 populations in 2020, the rates were significantly higher in the COVID-19 population: 46.89 (CI: 46.24, 47.53) for anxiety, 49.31 (CI: 48.66, 49.97) for mood disorders, 0.57 (CI: 0.50, 0.65) for OCD, and 3.52 (CI: 3.34, 3.70) for schizophrenia. COVID-19 severity was significantly associated with new diagnoses of schizophrenia, anxiety and mood disorders in multivariate analyses., Conclusions: Compared to 2018 and 2019, in 2020 there was no increased incidence of new psychiatric disorders in the general population based on insurance claims data. Importantly, people with COVID-19 were more likely to be diagnosed with a new psychiatric disorder, most notably disorders with psychosis, indicating a potential association between COVID-19 and mental/brain health., Competing Interests: The authors have declared that no competing interests exist. Dr Soares reported receiving grants from Compass Pathways and Relmada; and personal fees from Boehringer Ingelheim, Merck, and Johnson & Johnson outside the submitted work.

Benzodiazepine withdrawal is a widespread problem with potentially severe and deadly consequences. Currently, the only medications available for treating benzodiazepine withdrawal are short-acting and long-acting benzodiazepines. Identifying other drugs to help in treating benzodiazepine withdrawal is necessary. Gabapentin, an anxiolytic drug that is also used off-label to treat alcohol withdrawal, is a potential candidate for modulating benzodiazepine withdrawal. Using electronic records from a large inpatient psychiatric facility, a retrospective study of 172 patients presenting with benzodiazepine withdrawal was conducted to determine if the coincidental use of gabapentin for other medical conditions was associated with better outcomes of benzodiazepine withdrawal (N=57 gabapentin, N=115 no gabapentin). The primary outcomes were hospital length of stay and total amount of benzodiazepines given (lorazepam milligram equivalent). In this retrospective analysis of electronic medical record data, the patients experiencing benzodiazepine withdrawal who received gabapentin as an adjunct to the use of benzodiazepines were administered a smaller amount of benzodiazepines and had a shorter length of hospital stay relative to the comparison group who did not receive adjunctive gabapentin. These results suggest the potential use of gabapentin as an adjunct to the use of benzodiazepines for treating benzodiazepine withdrawal. The limitations of this study included a small sample size and variability in medication management strategies across the sample., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

74Distress tolerance (DT; perceived or actual ability to tolerate aversive physical or emotional states) is related to both posttraumatic stress disorder (PTSD) symptoms and substance use disorders (SUD). This investigation evaluates self-report and behavioral measures of DT as potential predictors of PTSD and SUD cognitive-behavioral therapy outcomes. Participants included 41 treatment-seeking adults (53.7% women; 73.2% African American; M age  = 44.90, SD  = 9.68) who met at least four symptoms of DSM-5 PTSD and DSM-IV substance dependence, assessed via structured interviews. At baseline (pre-treatment), participants completed the Distress Tolerance Scale (DTS), Mirror-Tracing Persistence Task (MTPT), Breath Holding task, and Paced Auditory Serial Addition Task. The Clinician-Administered PTSD Scale for DSM-5 severity scores and percent days of primary substance use, measured via Timeline Follow-back, were used as indicators of PTSD symptoms and substance use, respectively. Covariates included treatment condition, baseline PTSD symptom severity, and baseline substance use. Lower perceived DT at baseline (DTS total score) was associated with higher PTSD symptom severity at end-of-treatment. Lower behavioral DT at baseline (MTPT duration) was associated with higher substance use at the conclusion of treatment (i.e. proportion of number of use days to total number of days between two final treatment sessions).

The increased risk of alcohol use disorder (AUD) in individuals with post-traumatic stress disorder (PTSD) is well-documented. Compared to individuals with PTSD or AUD alone, those with co-existing PTSD and AUD exhibit greater symptom severity, poorer quality of life, and poorer treatment outcomes. Although the treatment of comorbid AUD is vital for the effective management of PTSD, there is a lack of evidence on how to best treat comorbid PTSD and AUD, and currently, there are no FDA-approved treatments for the PTSD-AUD comorbidity. The objective of this manuscript is to review the evidence of a promising target for treating the AUD-PTSD comorbidity. First, we summarize the epidemiological evidence and review the completed clinical studies that have tested pharmacotherapeutic approaches for co-existing AUD and PTSD. Next, we summarize the shared pathological factors between AUD and PTSD. We conclude by providing a rationale for selectively inhibiting aldehyde dehydrogenase-2 as a potential target to treat comorbid AUD in persons with PTSD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The present investigation examined the predictive utility of nonjudgmental acceptance, a facet of mindfulness defined as the ability to remain aware and nonevaluative about internal experience, in terms of substance-related cue reactivity among adults with substance use disorders (SUD) and posttraumatic stress (PTS) symptomatology. We hypothesized that higher nonjudgmental acceptance, indexed via self-report, would predict higher levels of self-reported control over oneself and safety 'in the moment', broadly, and lower levels of substance-related craving in response to substance script cues. Effects were expected after subtracting reactivity to neutral script cues from each outcome rating. PTS severity was included as a covariate. The sample was comprised of 53 adults (48.1% women; 75.9% African American; 74.1% with past-month PTSD) with substance dependence per DSM-IV and at least four symptoms of PTSD per DSM-5. Higher baseline nonjudgmental acceptance predicted greater safety and control in response to substance cues; no effects were found for craving. These experimental laboratory results elucidate the potential clinical utility of mindfulness-based interventions in bolstering recovery from addiction among adults with SUD/PTS by fostering safety and control in response to substance cues., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Opioid misuse and opioid-related death are a growing public health concern. One population of interest is recent trauma and/or surgery patients, who are at increased risk of developing an opioid use disorder (OUD). Although a variety of assessments have been developed to screen for risk of opioid misuse, each has limitations and prediction needs improvement. One promising measure is drug demand, a behavioral economic measure assessing drug consumption at different price points. In the current proposal, we assessed the utility of a brief assessment of opioid demand. Demand and various pain-related self-report measures among trauma-surgery patients ( N = 103) were assessed at 4 weeks post-discharge. Opioid demand was significantly associated with self-report measures of pain and amount of morphine milligram equivalents (MME) received during the hospital stay. The current result support the utility of the opioid demand as an adjunctive and complementary measure to assess risk of opioid misuse. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objective: High-acuity publicly funded inpatient psychiatric settings usually feature short lengths of stay and high readmission rates. This study examined the influence of an early intervention program for serious mental illnesses (SMI) on readmissions at 6 and 12 months postdischarge at a high-volume, urban public inpatient psychiatric hospital., Methods: The Early Onset Treatment Program (EOTP) is a cost-free, 90-day inpatient multidisciplinary service intervention program for uninsured patients who are within 5 years of SMI onset, funded as a pilot program by the Texas state legislature. Rehospitalization rates at 6 and 12 months were extracted from electronic medical records for EOTP participants (n=165) and comparison patients matched on demographics and diagnosis (n=155). The comparison group received treatment as usual at the same psychiatric hospital. Group re-admission rates were compared using logistic and Poisson regression analyses., Results: Group membership was a significant predictor of rehospitalization (P<0.0001) at both 6 and 12 months. Expressed as 1/odds ratio (OR), the EOTP group was less likely to readmit once and more than once at 6 months postdischarge (1/OR=3.82 and 4.74, respectively) compared with the non-EOTP group. The EOTP group was also less likely to readmit once and more than once at 12 months postdischarge (1/OR=2.96 and 3.51, respectively)., Conclusions: The results suggest that participation in the EOTP service in this high-acuity setting was significantly related to reduced likelihood of rehospitalization at 6 and 12 months. Several variables may account for this observation, including length of stay, longer medication adherence, environmental stability, and more individualized and extensive psychotherapy treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Prescription opioids are an effective pain treatment strategy but can lead to long-term opioid misuse. Identifying at risk patients during hospitalization can inform the development of prevention interventions post-discharge. Using the Opioid Risk Tool (ORT) as a screening measure, this study predicted factors associated with pain and opioid use at 2 weeks post-discharge in trauma patients., Design: A quality improvement prospective study design was used., Setting: Participant recruitment took place at an inpatient Level 1 trauma center in Houston, Texas., Participants: Participants (n = 103) were patients admitted to the adult trauma service. Patients completed the ORT in the hospital and a survey at 2 weeks post-discharge., Main Outcome Measure: The survey assessed pain intensity and interference, injury-related stress, medication use, and need for additional pain treatment. Wilcoxon-Mann-Whitney U test, the Spearman rank-order correlation, and chisquare test of independence tested the ORT as a predictor of follow-up outcomes. Post hoc analyses relied on logistic and quantile regression., Results: The ORT identified 15.5 percent of patients at high risk for opioid-related aberrant behavior. Survey results indicated high percentages of patients reporting moderate to severe pain (79.6 percent), pain interference (77.9 percent), taking pain pills (59.6 percent), experiencing stress (76.9 percent), and needing pain treatment (52.4 percent). The ORT predicted injury-related stress with the high-risk category having higher stress levels than low risk (Z = 2.518, p = 0.012)., Conclusion: Risk of opioid misuse assessed in hospitalized trauma patients was associated with injury-related stress reported post-discharge. This highlights the importance of including stress assessments in follow-up appointments.

Cocaine use continues to be a significant public health problem with limited treatment options and no approved pharmacotherapies. Cognitive-behavioral therapy (CBT) remains the mainstay treatment for preventing relapse, however, people with chronic cocaine use display cognitive impairments that are associated with poor response to CBT. Emerging evidence in animal and human studies suggests that the peroxisome proliferator-activated receptor-gamma (PPAR- γ) agonist, pioglitazone, improves white matter integrity that is essential for cognitive function. This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from cocaine use disorder. This paper describes the design of a mechanism-focused phase 2 randomized clinical trial that aims first to evaluate the effects of pioglitazone on targeted mechanisms related to white matter integrity, cognitive function, and cocaine craving; and second, to evaluate the extent to which improvements on target mechanisms predict CBT response. Positive results will support pioglitazone as a potential cognitive enhancing agent to advance to later stage medication development research., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Individuals with serious mental illness (SMI) are at increased risk for arrest and incarceration relative to the same-community population without SMI. Publicly-funded inpatient psychiatric hospitals usually feature short lengths of stay and limited opportunities for extended services that might impact criminal justice involvement after discharge. This study examined the influence of an early intervention program for SMI at a high-volume public psychiatric hospital on involvement in the criminal justice system post-discharge. The Early Onset Treatment Program (EOTP) is an extended service intervention program for uninsured patients who are within 5 years of SMI onset. Criminal justice records (number of arrests with conviction, days of incarceration) were obtained for EOTP participants (n = 164) and comparison patients (n = 164) matched on demographics, diagnosis, and discharge date via propensity score matching. Data were zero-inflated and analyzed using hurdle models, controlling for prior arrests. The EOTP group was less likely to be convicted of at least one crime post-discharge (0 arrests vs. > 0, p < .001), and spent fewer days incarcerated (if incarcerated ≥1 day, p < .03). Participation in the EOTP service was linked to reduced likelihood of post-discharge arrest and days incarcerated. Several alternative variables may contribute to this preliminary observation, including length of stay, medication adherence, longer environmental stability, and individual patient characteristics., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Importance: People with major psychiatric disorders are more likely to have comorbidities associated with worse outcomes of COVID-19. This fact alone could determine greater vulnerability of people with major psychiatric disorders to COVID-19., Objective: To assess the odds of testing positive for and mortality from COVID-19 among and between patients with schizophrenia, mood disorders, anxiety disorders and a reference group in a large national database., Design, Setting, and Participants: This cross-sectional study used an electronic health record data set aggregated from many national sources in the United States and licensed from Optum with current and historical data on patients tested for COVID-19 in 2020. Three psychiatric cohorts (patients with schizophrenia, mood disorders, or anxiety disorders) were compared with a reference group with no major psychiatric conditions. Statistical analysis was performed from March to April 2021., Exposure: The exposures observed include lab-confirmed positivity for COVID-19 and mortality., Main Outcomes and Measures: The odds of testing positive for COVID-19 in 2020 and the odds of death from COVID-19 were measured., Results: The population studied included 2 535 098 unique persons, 3350 with schizophrenia, 26 610 with mood disorders, and 18 550 with anxiety disorders. The mean (SD) age was 44 (23) years; 233 519 were non-Hispanic African American, 1 583 440 were non-Hispanic Caucasian; and 1 580 703 (62%) were female. The schizophrenia cohort (positivity rate: 9.86%; adjusted OR, 0.90 [95% CI, 0.84-0.97]) and the mood disorder cohort (positivity rate: 9.86%; adjusted OR, 0.93 [95% CI, 0.87-0.99]) had a significantly lower rate of positivity than the anxiety disorder cohort (positivity rate: 11.17%; adjusted OR, 1.05 [95% CI, 0.98-1.12) which was closer to the reference group (11.91%). After fully adjusting for demographic factors and comorbid conditions, patients with schizophrenia were nearly 4 times more likely to die from the disease than the reference group (OR, 3.74; 95% CI, 2.66-5.24). The mood disorders COVID-19 cohort had a 2.76 times greater odds of mortality than the reference group (OR, 2.76; 95% CI, 2.00-3.81), and the anxiety disorders cohort had a 2.39 times greater odds of mortality than the reference group (OR, 2.39; 95% CI, 1.68-3.27)., Conclusions and Relevance: By examining a large database while controlling for multiple confounding factors such as age, race and ethnicity, and comorbid medical conditions, the present study found that patients with schizophrenia had much increased odds of mortality by COVID-19.

Capturing, storing, and sharing biological DNA parts data are integral parts of synthetic biology research. Here, we detail updates to the ICE biological parts registry software platform that enable these processes, describe our implementation of the Web of Registries concept using ICE, and establish Bioparts, a search portal for biological parts available in the public domain. The Web of Registries enables standalone ICE installations to securely connect and form a distributed parts database. This distributed database allows users from one registry to query and access plasmid, strain, (DNA) part, plant seed, and protein entry types in other connected registries. Users can also transfer entries from one ICE registry to another or make them publicly accessible. Bioparts, the new search portal, combines the ease and convenience of modern web search engines with the capabilities of bioinformatics search tools such as BLAST. This portal, available at bioparts.org, allows anyone to search for publicly accessible biological part information (e.g., NCBI, iGEM, SynBioHub, Addgene), including parts publicly accessible through ICE Registries. Additionally, the portal offers a REST API that enables third-party applications and tools to access the portal's functionality programmatically.

Background: While studies have investigated the effects of posttraumatic stress disorder (PTSD) symptoms on substance use, information on these associations in the context of drug cue reactivity is lacking, which can provide meaningful information about risk for relapse. The current study assessed the associations between PTSD symptom clusters and reactivity to cues in trauma-exposed adults with cocaine use disorder., Methods: We recorded electroencephalogram on 52 trauma-exposed participants (M age = 51.3; SD = 7.0; 15.4 % women) diagnosed with cocaine use disorder while they viewed pleasant (i.e., erotic, romantic, sweet foods), unpleasant (i.e., mutilations, violence, accidents), neutral, and cocaine-related images. Reactivity was measured with the late positive potential (LPP), an indicator of motivational relevance. It was hypothesized that individuals with greater PTSD avoidance and negative alterations in cognition and mood (NACM) symptoms, as determined by the PTSD Checklist for DSM-5 (PCL-5), would have higher LPPs to cocaine-related images, indicating greater cue reactivity., Results: Linear mixed modeling indicated that higher NACM symptomatology was associated with higher LPPs to cocaine cues and higher arousal/reactivity was associated with lower LPPs to cocaine cues., Conclusions: These results highlight the potential clinical utility of the LPP in assessing drug cue reactivity in trauma-exposed adults with substance use disorder., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rationale: Misuse of dextroamphetamine occurs in work and recreational contexts. While acute drug effects broadly predict abuse liability, few studies have considered the relationship between acute effects and context., Objectives: This study examined how individual differences in acute effects of dextroamphetamine relate to desire to take dextroamphetamine again in different contexts., Methods: This secondary analysis used data from healthy adults with no history of moderate-to-severe substance use disorder, who received oral doses of placebo and dextroamphetamine (10 and 20 mg) over 3 sessions under double-blind, randomized conditions. Subjects rated subjective effects and completed reward-related behavioral tasks. Subjects rated their desire to take dextroamphetamine again in hypothetical work and recreational contexts. Multilevel models examined within-subjects change scores (10 mg-placebo; 20 mg-placebo) to determine how subjective effects and behavioral outcomes predicted desire to take dextroamphetamine again for work versus recreation., Results: Subjects reported more desire to take 20 mg dextroamphetamine again for work than for recreation. At 20 mg, there was an interaction between context and liking/wanting, such that liking/wanting predicted desire to use dextroamphetamine for work only. There was also an interaction at 20 mg between context and psychomotor speed, such that psychomotor speed predicted interest in using dextroamphetamine for recreation only., Conclusions: We found that positive subjective effects predicted desire to use dextroamphetamine again for work, while increased motor effects predicted desire to use dextroamphetamine recreationally. Hedonic effects may be perceived as advantageous when working, while increased physical energy may be preferred during recreation, suggesting that context of intended use is important when examining abuse liability., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Physical assaults perpetrated by patients in psychiatric hospitals against mental health staff (MHS) is a serious concern facing psychiatric hospitals. Assaulted staff reports physical and psychological trauma that affects their personal and professional lives. There is a dearth of literature exploring this phenomenon., Purpose: To explore MHS perspectives of assault by psychiatric patients., Methods: A transcendental phenomenological qualitative design was used to explore and analyze the perspectives of a purposeful sample of 120 MHS perspectives at an acute inpatient psychiatric hospital. Participants' age ranged from 22 to 63 years (mean age = 32.4). Moustakas' theoretical underpinnings guided the study., Results: Two patterns, 8 themes, and 19 subthemes were identified: (a) Psychological impacts revealed four themes-increase of anxiety/fear level, helplessness and hopelessness, flashbacks/burnout, and doubting own competency. (b) Physiosocial impacts revealed four themes-unsupportive superiors, stigmatization of staff victim, failure to report the incident, and environmental safety., Discussion: Participants verbalized that assaults by patients have instilled fear and trauma in them. Most of the assaults occurred when staff were performing their routine job functions and setting limits to patient's behavior., Conclusion: The study allowed MHS opportunities to narrate their lived experiences of being assaulted by patients and provided validation of their perspectives. Findings illuminated the phenomenon and may help to support policy changes in psychiatric hospitals.

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 (Q 0 , P max , 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 O max , P max , 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving, and withdrawal symptoms, with post-cessation body weight as a secondary outcome., Methods: Eighty-four prediabetic and/or overweight smokers were randomized (1 : 1) to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received NRT (21 mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal, and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of treatment on the study outcomes., Results: Exenatide increased the risk for smoking abstinence compared to placebo (46.3% and 26.8%, respectively), (risk ratio [RR] = 1.70; 95% credible interval = [0.96, 3.27]; PP = 96.5%). Exenatide reduced end-of-treatment craving in the overall sample and withdrawal among abstainers. Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (PP = 97.4%). Adverse events were reported in 9.5% and 2.3% of participants in the exenatide and placebo groups, respectively., Conclusions: Exenatide, in combination with the NRT improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers. Findings suggest that the GLP-1R agonist strategy is worthy of further research in larger, longer duration studies., Implications: Despite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2021. Published by Elsevier B.V.)

Cocaine demand is a behavioral economic measure assessing drug reward value and motivation to use drug. The purpose of the current study was to develop a brief assessment of cocaine demand (BACD). Results from the BACD were compared with self-report measures of cocaine use. Participants consisted of treatment-seeking individuals with cocaine use disorder (N = 22). Results revealed that indices of brief demand were significantly associated with various self-report measures of cocaine use. Overall, these results support the utility of a BACD for assessing cocaine demand., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Effort-related decision-making and reward learning are both dopamine-dependent, but preclinical research suggests they depend on different dopamine signaling dynamics. Therefore, the same dose of a dopaminergic medication could have differential effects on effort for reward vs. reward learning. However, no study has tested how effort and reward learning respond to the same dopaminergic medication within subjects. The current study aimed to test the effect of therapeutic doses of d-amphetamine on effort for reward and reward learning in the same healthy volunteers. Participants (n = 30) completed the Effort Expenditure for Reward Task (EEfRT) measure of effort-related decision-making, and the Probabilistic Reward Task (PRT) measure of reward learning, under placebo and two doses of d-amphetamine (10 mg, and 20 mg). Secondarily, we examined whether the individual characteristics of baseline working memory and willingness to exert effort for reward moderated the effects of d-amphetamine. d-Amphetamine increased willingness to exert effort, particularly at low to intermediate expected values of reward. Computational modeling analyses suggested this was due to decreased effort discounting rather than probability discounting or decision consistency. Both baseline effort and working memory emerged as moderators of this effect, such that d-amphetamine increased effort more in individuals with lower working memory and lower baseline effort, also primarily at low to intermediate expected values of reward. In contrast, d-amphetamine had no significant effect on reward learning. These results have implications for treatment of neuropsychiatric disorders, which may be characterized by multiple underlying reward dysfunctions.

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.

White matter (WM) abnormalities in patients with cocaine use disorder (CUD) have been studied; however, the reported effects on the human brain are heterogenous and most results have been obtained from male participants. In addition, biological data supporting the imaging findings and revealing possible mechanisms underlying the neurotoxic effects of chronic cocaine use (CU) on WM are largely restricted to animal studies. To evaluate the neurotoxic effects of CU in the WM, we performed an in vivo diffusion tensor imaging assessment of male and female cocaine users (n = 75) and healthy controls (HC) (n = 58). Moreover, we performed an ex vivo large-scale proteomic analysis using liquid chromatography-tandem mass spectrometry in postmortem brains of patients with CUD (n = 8) and HC (n = 12). Compared with the HC, the CUD group showed significant reductions in global fractional anisotropy (FA) (p < 0.001), and an increase in global mean (MD) and radial diffusion (RD) (both p < 0.001). The results revealed that FA, RD, and MD alterations in the CUD group were widespread along the major WM tracts, after analysis using the tract-based special statistics approach. Global FA was negatively associated with years of CU (p = 0.0421) and female sex (p < 0.001), but not with years of alcohol or nicotine use. Concerning the fibers connecting the left to the right prefrontal cortex, Brodmann area 9 (BA9), the CUD group presented lower FA (p = 0.006) and higher RD (p < 0.001) values compared with the HC group. A negative association between the duration of CU in life and FA values in this tract was also observed (p = 0.019). Proteomics analyses in BA9 found 11 proteins differentially expressed between cocaine users and controls. Among these, were proteins related to myelination and neuroinflammation. In summary, we demonstrate convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomics analysis of WM disruption in CUD.

Background: Soil transmitted helminths (STH) are a common infection among pregnant women in areas with poor access to sanitation. Deworming medications are cheap and safe; however, the health benefit of deworming during pregnancy is not clear., Methods / Principal Findings: We created a retrospective cohort of more than 800,000 births from 95 Demographic and Health Survey datasets to estimate the impact of deworming medicine during routine antenatal care (ANC) on neonatal mortality and low birthweight. We first matched births on the probability of receiving deworming during ANC. We then modeled the birth outcomes with the matched group as a random intercept to estimate the effect of deworming during antenatal care after accounting for various risk factors. We also tested for effect modification of soil transmitted helminth prevalence on the impact of deworming during ANC. Receipt of deworming medication during ANC was associated with a 14% reduction in the risk of neonatal mortality (95% confidence interval = 10-17%, n = 797,772 births), with no difference between high and low transmission countries. In low transmission countries, we found an 11% reduction in the odds of low birth weight (95% confidence interval = 8-13%) for women receiving deworming medicine, and in high transmission countries, we found a 2% reduction in the odds of low birthweight (95% confidence interval = 0-5%)., Conclusions / Significance: These results suggest a substantial health benefit for deworming during ANC that may be even greater in countries with low STH transmission., Competing Interests: The authors have declared that no competing interests exist.