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This study was designed to assess factors associated with change in needle-related risk behaviors as well as predictors of continued high-risk behavior following intervention efforts among injection drug users (IDUs) in Ukraine. In each of three locations--Kiev, Odessa, and Makeevka/Donesk--100 IDUs were recruited using modified targeted sampling methods. Following a baseline interview, participants were offered free HIV testing and, over the course of the next 5 months, individualized interventions focusing on reducing HIV-related risk behaviors. Former IDUs conducted interventions through street outreach. The intervention model was based on the Indigenous Leader Outreach Model (ILOM) and stressed assessing an individual's unique risks and developing strategies by which to minimize those risks. Follow-up assessments showed significant reductions in every risk behavior measured. Following the intervention, however, approximately one of four participants reported front- or backloading, using drugs obtained from a common container or injecting with a used needle/syringe. Although the sample as a whole averaged only 28 years of age, those who were younger were significantly more likely to engage in each of these behaviors than those who were older. In light of the overall young age of the Ukrainian IDUs observed in this study, the consistent finding that younger IDUs were at highest risk foreshadows a worsening HIV epidemic in Ukraine. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of atomoxetine hydrochloride versus placebo on attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) in adolescents receiving motivational interviewing/cognitive behavioral therapy (MI/CBT) for SUD.Method: This single-site, randomized, controlled trial was conducted between December 2005 and February 2008. Seventy adolescents (13 through 19 years of age) with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) ADHD, a DSM-IV ADHD checklist score greater than or equal to 22, and at least one nontobacco SUD were recruited from the community. All subjects received 12 weeks of atomoxetine hydrochloride + MI/CBT versus placebo + MI/CBT. The main outcome measure for ADHD was self-report DSM-IV ADHD checklist score. For SUD, the main outcome was self-report number of days used nontobacco substances in the past 28 days using the Timeline Followback interview.Results: Change in ADHD scores did not differ between atomoxetine + MI/CBT and placebo + MI/CBT (F4,191 = 1.23, p = .2975). Change in days used nonnicotine substances in the last 28 days did not differ between groups (F3,100 = 2.06, p = .1103).Conclusions: There was no significant difference between the atomoxetine + MI/CBT and placebo + MI/CBT groups in ADHD or substance use change. The MI/CBT and/or a placebo effect may have contributed to a large treatment response in the placebo group. Clinical Trials Registry Information-A Randomized, Placebo-Controlled Trial of Atomoxetine for Attention-Deficit/Hyperactivity Disorder in Adolescents with Substance Use Disorder. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00399763. [ABSTRACT FROM AUTHOR]

Objective: The authors examined trends of individual career development awards from the National Institutes of Health (NIH) to psychiatry faculty, especially physicians, in comparison to other departments., Methods: Data were obtained on 33,392 career development awards from 2013 to 2022. We examined the number of awards each year averaged for 46 non-psychiatry departments, and for departments of psychiatry, the number of awards to all faculty, physicians, and physicians without a PhD. Linear regressions determined whether number of career development awards increased with time and if estimated slopes differed between faculty in non-psychiatry departments and other groups., Results: In departments of psychiatry, 534 faculty received an NIH individual career development award during the 10-year period (534/33,392 or 1.6%), with 118 (22%) to physicians. The number of awards increased significantly over time for other departments and departments of psychiatry (estimated slopes of 3.05 and 2.38, respectively) and did not differ from one another. However, the number of awards to physicians and physicians without a PhD in departments of psychiatry (estimated slopes of 0.51 and - 0.07, respectively) have not increased. This lack of growth in awards for physicians and physicians without a PhD in departments of psychiatry differed significantly in comparison with the increase shown in awards to other departments over time (both p < 0.001)., Conclusions: The number of NIH career development awards has increased NIH-wide, and for non-physician faculty but not for physicians in departments of psychiatry. These trends raise concerns for the future of psychiatrists in academic research., (© 2024. The Author(s), under exclusive licence to Academic Psychiatry, LLC.)

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder commonly associated with behavioral challenges. There are few evidence based pharmacological interventions available for the treatment of behavioral symptoms associated with ASD. Cannabidiol (CBD), the non-psychoactive component of cannabis, has potential neuroprotective, antiepileptic, anxiolytic, and antipsychotic effects and may be useful in treating the behavioral symptoms of ASD., Methods: We describe the research methods of a 27-week double-blind placebo-controlled cross-over trial of cannabidiol for the treatment of irritability and aggression associated with ASD, utilizing the irritability subscale of the Aberrant Behavior Checklist-2nd edition (ABC-2) as the primary outcome measure. Adverse effects and safety monitoring protocols are included. Several secondary and exploratory outcomes measures also include anxiety, communication, repetitive behaviors, attention, hyperactivity, autism family experience, and telehealth functional behavior assessment., Conclusion: There is a significant need for clinical research exploring alternative medications for the treatment of behavioral symptoms of ASD. Cannabidiol (CBD) is being studied for the management of irritability, aggression, and other problem behaviors associated with ASD.

Substance use disorders are prevalent, causing extensive morbidity and mortality worldwide. Evidence-based treatments are of low to moderate effect size. Growth in the neurobiological understanding of addiction (e.g., craving) along with technological advancements in neuromodulation have enabled an evaluation of neurosurgical treatments for substance use disorders. Deep brain stimulation (DBS) involves surgical implantation of leads into brain targets and subcutaneous tunneling to connect the leads to a programmable implanted pulse generator (IPG) under the skin of the chest. DBS allows direct testing of neurobiologically-guided hypotheses regarding the etiology of substance use disorders in service of developing more effective treatments. Early studies, although with multiple limitations, have been promising. Still the authors express caution regarding implementation of DBS studies in this population and emphasize the importance of safeguards to ensure patient safety and meaningful study results. In this perspectives article, we review lessons learned through the years of planning an ongoing trial of DBS for methamphetamine use disorder., Competing Interests: DK has served as an advisor for Colorado Clinical and Translational Sciences Institute CCTSI Data Safety Monitoring Board, and Medical Boards for Boston Scientific, Medtronic, and AbbVie Pharmaceutics; received honorarium from AbbVie Pharmaceutics, Abbott, and Boston Scientific, received grants from the Boston Scientific, Medtronic, University of Colorado Department of Neurology, and the Parkinson’s Foundation. AA receives investigator-initiated research funding and received implantable research devices from, and serves on a post approval clinical events committee (epilepsy therapy) for Medtronic. JT has received consulting fees from Icometrix. JAT received grants and honorarium from Medtronic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sakai, Tanabe, Battula, Zipperly, Mikulich-Gilbertson, Kern, Thompson, Raymond, Gerecht, Foster and Abosch.)

Objective: To investigate the association of cannabis use with major depression and suicidal behavior in adolescence., Method: Data are from the National Comorbidity Survey-Adolescent Supplement N = 10 , 123 , a nationally representative survey of adolescents aged 13 to 18 years. Weighted logistic regression and ordinal regression analyses of major depression and suicidal behavior outcomes were conducted on cannabis variables, incorporating sociodemographic characteristics., Results: Adolescents with lifetime cannabis use have 2.07 times higher odds of mild/moderate (adjusted odds ratio [aOR]; 95% CI = 1.69 ,   2.53 ) and 3.32 times higher odds of severe major depressive disorder (MDD; aOR; 95% CI = 2.31 ,   4.75 ). Cannabis use (aOR 6.90, 95% CI = 4.67 , 10.19 ), mild/moderate MDD (aOR 4.10, 95% CI = 2.82 ,   5.98 ), and severe MDD (aOR 13.97, 95% CI = 7.59, 25.70) were associated with higher odds of suicide attempt. Past 12-month cannabis use (aOR 3.70, 95% CI = 2.16, 6.32), mild/moderate major depressive episodes (MDE) (aOR 7.85, 95% CI = 3.59 ,   17.17 ), and severe MDE (aOR 36.36, 95% CI = 13.68 , 96.64 ) were associated with higher odds of suicide attempt. The frequency of past 12-month cannabis use was associated with higher odds of suicide attempt and with MDE severity, with higher odds among individuals who use cannabis 3 or more days than among individuals who use cannabis less frequently, suggesting a dose effect. Among cannabis users, older age of onset of cannabis use was associated with lower odds of suicidal behaviors., Conclusion: Cannabis use is associated with higher odds of depression and depression severity in adolescence. Furthermore, depression and cannabis use are independently associated with higher odds of suicide attempt., Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group., Competing Interests: Disclosure: Dr. Hinckley has received research support from AACAP, NIDA, the University of Colorado Department of Psychiatry, and the Doris Duke Foundation. Dr. Mikulich-Gilbertson has received research support from the Colorado Department of Public Health and Environment, the Department of Veterans Affairs, NCI, NIDA, NIDDK, NIMH, and the University of Colorado Department of Psychiatry. Dr. Bhatia has received research support from NIMH. Dr. Ellingson has received research support from NIAAA, the Institute of Cannabis Research at Colorado State University Pueblo, and the University of Colorado Department of Psychiatry. Dr. Merikangas has received research support from NIDA and NIMH. Dr. Sakai has received research support from NIAAA, NIDA, NIMH, the Kane Family Foundation, and the Hewit Family Foundation. He received reimbursement in 2012 for completing a policy review for the WellPoint Office of Medical Policy & Technology Assessment (OMPTA), WellPoint, Inc. Dr. Vu and Ms. He have reported no biomedical financial interests or potential conflicts of interest.

Background: Prosocial behavior is negatively associated with psychopathic traits and paradigms which measure prosocial behavior in the laboratory may be useful in better understanding moderators of this association., Methods: We revised a previously validated game of prosocial behavior by including a new trial type (i.e., trials where the participant will lose money and the charity will gain money). This version of the game was administered online and participants were randomized to group (exposed to a control stimulus video or a video used to elicit moral elevation, i.e. a positive response to witnessing another's act of kindness). We used repeated game administration to test whether a moral elevation stimulus affected game behavior and moderated the negative association between psychopathic traits and prosocial behavior., Results: Prosocial behavior on the new trial types added in this revised game correlated strongly with prosocial behavior on the old trial type (i.e., trials where the participant will gain money and the charity will lose money; r = 0.71; p-value<0.001; n = 485). Graphing trial acceptance rates by trial characteristics demonstrated expected patterns of behavior. Number of prosocial choices on the game correlated with psychopathic trait score (Levenson Factor 1 score; r = -0.52; p-value<0.001). Game repetition with a control stimulus in between runs, supported high immediate test-retest reliability of overall game behavior. Exposure to the moral elevation stimulus in between runs did not affect game behavior nor moderate the association between psychopathic traits and prosocial behavior., Conclusions: Choices on this revised game of prosocial behavior, which can be administered online, are associated with psychopathic traits scores. The game appears to have high immediate test-retest reliability. Exposure to the moral elevation stimulus did not affect prosocial behavior or impact the relationship between psychopathic trait scores and prosocial behavior. Future research should continue to test potential moderators of this relationship. Limitations of the current study are discussed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sakai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although sex differences in food intake have been observed consistently, contributing factors are not well understood. Using a cross-sectional online survey ( n = 306; 151 men, 155 women), this study aimed to assess how sex impacts relationships between food ratings (appeal/desire to eat for high-calorie (HC) and low-calorie (LC) food images) and eating-related attitudes/behaviors, body mass index (BMI), and mood. Across participants, increased state- and trait-based hunger, disinhibition, and cravings were associated with both increased HC appeal and desire ( p < 0.001). Increased state-based hunger and cravings were associated with greater LC desire ( p < 0.001). Greater satiety was associated with decreased desire for both HC and LC ( p < 0.001), while greater anxiety was associated with increased desire for both HC and LC ( p < 0.001). Significant associations between BMI and food ratings were not observed. Women reported greater dietary restraint, trait-based hunger, disinhibition, eating disorder-related behaviors, depression, and stress compared to men, in addition to greater appeal and familiarity with LC foods (all p < 0.05). Significant effects of sex on the associations between food ratings and eating-related attitudes/behaviors, BMI, and mood were not observed, however. Findings support the importance of considering mood and eating-related attitudes/behaviors in investigations of food cue responsivity.

Purpose: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a demanding treatment that requires caregiver support during the first 100 days post-transplant. Little is known about the association between caregivers' employment changes and their well-being during this lengthy and challenging time when caregivers may be balancing work with caregiving responsibilities., Methods: We used data from employed caregivers of Allo-HSCT patients who participated in two randomized clinical trials (N = 187) of an intervention for caregivers. Caregiver depression and anxiety were assessed using the Center for Epidemiologic Studies Depression and the Spielberger State-Trait Anxiety Inventory. ANCOVA was used to measure the associations between reducing work with depression and anxiety. Caregiver's demographics and baseline employment status were controlled in the analysis along with the patient's transplant conditioning intensity., Results: Approximately 45% of caregivers reduced hours worked following the resumption of their caregiving duties. These caregivers, on average, had 3.49 points higher depression scores than caregivers who did not report a reduction in work (p < 0.01). Similarly, these caregivers also reported, on average, 3.56 higher anxiety scores (p < 0.10)., Conclusions: Caregivers who reduced hours worked while caregiving reported greater distress. The underlying cause of this distress deserves further investigation., Implications for Cancer Survivors: Caregivers of patients diagnosed with cancer may experience considerable stress related to work discontinuation and caregiving. Interventions are needed to support caregivers who are trying to balance work and caregiving responsibilities., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Study Objective: In the United States, alcohol use disorder adversely affects 5.6% of all adults. Excessive alcohol consumption adversely affects organ functions critical for adaptation to stress induced by surgery. Colorectal resection is one of the most common major surgeries in patients at risk for alcohol use disorder. The objective of this study was to assess the impact of alcohol use disorder on hospital outcomes after colectomy using a population-based discharge database., Setting: Population-based discharge database., Patients: The Premier Healthcare Database was queried for the 603,730 adult patients who underwent colectomy from 2016 to 2019., Interventions: None., Measurements: Multiple logistic regressions estimated the associations between in-hospital mortality, length of stay, and hospitalization cost with alcohol use disorder as the primary predictor, adjusting for other substance use disorders, psychotic disorders, depression, other Elixhauser comorbidities, age, payor, race, gender, non-elective surgery, and other unbalanced variables., Main Results: A discharge code for alcohol use disorder was identified in 2.9% of colectomy patients and the overall in-hospital mortality rate in all sampled colectomy patients was 1.4%. Alcohol use disorder was associated with a significantly increased risk of in-hospital mortality after adjusting for other factors (AOR 1.36, 95% CI 1.24-1.48, p < 0.0001). Alcohol use disorder was also significantly associated with long length of stay (AOR 1.45, 95% CI 1.39-1.52, p < 0.0001) and high hospitalization costs (AOR 1.63, 95% CI 1.56-1.70, p < 0.0001)., Conclusions: Alcohol use disorder is associated with an increased risk of in-hospital mortality in patients undergoing colectomy, one of the most common major surgeries. Future research should examine if enhanced efforts to identify patients with alcohol use disorder could enable anesthesiologists to provide worthwhile perioperative interventions for this high-risk population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Caregivers of patients with advanced cancer experience significant anxiety, depression, and distress. Caregivers have barriers to accessing in-person treatment to manage stress. Technology allows for the dissemination of evidence-based interventions in a convenient way. This study examined usage rates of Pep-Pal (an evidence-based mobilized intervention to help caregivers of patients with advanced cancer manage distress) and estimates of efficacy on anxiety, depression, stress, and sexual dysfunction., Methods: Fifty-six primary caregivers of patients with advanced cancer were recruited through oncology clinics and randomized to either Pep-Pal (a mobilized psychoeducation and skills-based intervention for caregivers, n = 26) or treatment as usual (TAU; n = 30). All were screened for moderate anxiety on the Hospital Anxiety and Depression Scale-Anxiety screening assessment (A ≥ 8) at baseline., Results: Participants randomized to Pep-Pal experienced greater reductions in perceived stress (PSS; F = 3.91, p = .05), greater increases in ability to learn and use stress management skills (F = 6.16, p = 0.01), and greater increases in sexual function (women only; F = 5.07, p = 0.03) compared to participants in TAU. Of Pep-Pal participants, only 10 (38.5%) watched at least 7/9 full-length sessions. The a priori hypothesis and criterion that participants would watch at least 75% full-length sessions were not met., Conclusions: A brief, easily disseminated mobile intervention showed poor adherence, but had limited estimates of efficacy for secondary outcomes; perceived stress, learning stress management skills, and sexual functioning (women only). Future directions are discussed., (© 2020 John Wiley & Sons Ltd.)

Background: Pulmonary complications related to residual neuromuscular blockade lead to morbidity and mortality. Using an interrupted time series design, we tested whether proportions of reintubation for respiratory failure or new noninvasive ventilation were changed after a system-wide transition of the standard reversal agent from neostigmine to sugammadex., Methods: Adult patients undergoing a procedure with general anesthesia that included pharmacologic reversal of neuromuscular blockade and admission ≥1 night were eligible. Groups were determined by date of surgery: August 15, 2015 to May 10, 2016 (presugammadex), and August 15, 2016 to May 11, 2017 (postsugammadex). The period from May 11, 2016 to August 14, 2016 marked the institutional transition (washout/wash-in) from neostigmine to sugammadex. The primary outcome was defined as a composite of reintubation for respiratory failure or new noninvasive ventilation. Event proportions were parsed into 10-day intervals in each cohort, and trend lines were fitted. Segmented logistic regression models appropriate for an interrupted time series design and adjusting for potential confounders were utilized to evaluate the immediate effect of the implementation of sugammadex and on the difference between preintervention and postintervention slopes of the outcomes. Models containing all parameters (full) and only significant parameters (parsimonious) were fitted and are reported., Results: Of 13,031 screened patients, 7316 patients were included. The composite respiratory outcome occurred in 6.1% of the presugammadex group and 4.2% of the postsugammadex group. Adjusted odds ratio (OR) and 95% confidence intervals (CIs) for the composite respiratory outcome were 0.795 (95% CI, 0.523-1.208) for the immediate effect of intervention, 0.986 (95% CI, 0.959-1.013) for the difference between preintervention and postintervention slopes in the full model, and 0.667 (95% CI, 0.536-0.830) for the immediate effect of the intervention in the parsimonious model., Conclusions: The system-wide transition of the standard pharmacologic reversal agent from neostigmine to sugammadex was associated with a reduction in the odds of the composite respiratory outcome. This observation is supported by nonsignificant within-group time trends and a significant reduction in intercept/level from presugammadex to postsugammadex in a parsimonious logistic regression model adjusting for covariates.

Aims: Population pharmacokinetic models of Δ9-tetrahydrocannabinol (THC) have been developed for THC plasma and blood concentration data. Often, only the metabolites of THC are measurable when blood samples are obtained. Therefore, we performed a population pharmacokinetic analysis of THC, 11-OH-THC and THCCOOH plasma concentration data from a Phase I clinical trial of THC smoking., Methods: Frequently obtained plasma THC, 11-OH-THC and THCCOOH concentration data were obtained over 168 h from 6 subjects who smoked low (15.8 mg) and high dose (33.8 mg) THC cigarettes on 2 occasions. Bayesian estimates of the THC pharmacokinetic model from each individual for each dose were fixed prior to the sequential pharmacokinetic analysis of the metabolites., Results: A 3-compartment model of THC was developed that has a steady-state volume of distribution (Vd SS ) of 3401 ± 788 L and a clearance of 0.72 ± 0.10 L/min. 11-OH-THC was characterized by 50 ± 6% of the THC being directly cleared to a 3-compartment model with a Vd SS of 415.2 ± 4.3 L and clearance of 0.78 ± 0.05 L/min. The THCCOOH model shared the central compartment of the 11-OH-THC model with a Vd SS of 29.1 ± 0.05 L and a clearance of 0.12 ± 0.02 L/min. First order kinetics were observed for THC and THCCOOH between the low and high doses, but a nonlinear pattern was observed for 11-OH-THC., Conclusion: We describe the pharmacokinetics of THC, 11-OH-THC and THCCOOH including inter- and intraindividual variability of the parameter estimates of the model., (© 2019 The British Pharmacological Society.)

Purpose: Although cesarean delivery is the most common surgical procedure in the United States, postoperative opioid prescribing varies greatly. We hypothesized that patient characteristics, procedural characteristics, or both would be associated with high vs low opioid use after discharge. This information could help individualize prescriptions., Methods: In this prospective cohort study, we quantified opioid use for 4 weeks following hospital discharge after cesarean delivery. Predischarge characteristics were obtained from health records, and patients self-reported total opioid use postdischarge on weekly questionnaires. Opioid use was quantified in milligram morphine equivalents (MMEs). Binomial and Poisson regression analyses were performed to assess predictors of opioid use after discharge., Results: Of the 233 patients starting the study, 203 (87.1%) completed at least 1 questionnaire and were included in analyses (86.3% completed all 4 questionnaires). A total of 113 patients were high users (>75 MMEs) and 90 patients were low users (≤75 MMEs) of opioids postdischarge. The group reporting low opioid use received on average 44% fewer opioids in the 24 hours before discharge compared with the group reporting high opioid use (mean = 33.0 vs 59.3 MMEs, P <.001). Only a minority of patients (11.4% to 15.8%) stored leftover opioids in a locked location, and just 31 patients disposed of leftover opioids., Conclusions: Knowledge of predischarge opioid use can be useful as a tool to inform individualized opioid prescriptions, help optimize nonopioid analgesia, and reduce opioid use. Additional studies are needed to evaluate the impact of implementing such measures on prescribing practices, pain, and functional outcomes., (© 2020 Annals of Family Medicine, Inc.)

Objectives: Misuse of opioid medications (ie, using opioids differently than how a doctor prescribed the medication) is common among US adolescents and associated with preventable health consequences (eg, severe respiratory depression, seizures, heart failure, and death). 1 New guidelines and recommendations have made providers more attuned to overprescribing and more vigilant about screening for opioid misuse. 2 We hypothesized that youth who misused prescription opioids were more likely to report engaging in a broad range of other risky behaviors., Methods: We used the Centers for Disease Control and Prevention's 2017 Youth Risk Behavior Surveillance Survey ( n = 14 765), a cross-sectional, nationally representative survey of high school students. Students were sampled by using a 3-stage random cluster design. We conducted weighted logistic regressions to determine the strength of the association between our independent variable, ever misusing prescription opioids, and 22 dependent variables in the following categories: risky driving behaviors (4 variables), violent behaviors (3 variables), risky sexual behaviors (4 variables), substance use (10 variables), and suicide attempt (1 variable)., Results: In 2017, 14% of US adolescents reported ever misusing opioids. Those who misused prescription opioids were significantly more likely to have engaged in all 22 risky behaviors (adjusted odds ratios ranged from 2.0 to 22.3; P < .0001 for all tests) compared with other adolescents., Conclusions: Adolescents reporting ever misusing prescription opioids were more likely to have engaged in a broad range of risky behaviors. Health care providers screening for prescription opioid misuse may be ideally positioned to identify these high-risk youth and initiate early interventions., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Background: Overprescribing of opioid medications for patients to be used at home after surgery is common. We sought to ascertain important patient and procedural characteristics that are associated with low versus high rates of self-reported utilization of opioids at home, 1-4 weeks after discharge following gastrointestinal surgery., Methods: We developed a survey consisting of questions from NIH PROMIS tools for pain intensity/interference and queries on postoperative analgesic use. Adult patients completed the survey weekly during the first month after discharge. Using regression procedures we determined the patient and procedure characteristics that predicted high post-discharge opioid use operationalized as 75 mg oral morphine equivalents/50 mg oxycodone reported taken., Results: The survey response rate was 86% (201/233). High opioid use was reported by 52.7% of patients (106/201). Median reported intake of opioid pain pills was 7 for week #1 and 0 for weeks #2-4. Combinations of acetaminophen and non-steroidal and anti-inflammatory drugs were used by 8.9%-12.5% of patients after discharge. Following adjustment for significant variables of the univariate analysis, last 24-h in-hospital opioid intake remained as a significant co-variate for post-discharge opioid intake., Conclusions: After gastrointestinal surgery, the equivalent of each oxycodone 5 mg tablet taken in the last 24 h before discharge increases the likelihood of taking the equivalent of > 10 oxycodone 5 mg tablets by 5%. Non-opioid analgesia was utilized in less than half of the cases. Maximizing non-opioid analgesic therapy and basing opioid prescriptions on 24-h pre-discharge opioid intake may improve the quality of post-discharge pain management.

Background: Psychological interventions reduce caregiver distress (CG-distress). Less distress in caregivers may contribute to improved patient quality of life (QoL), but empirical evidence is lacking. Will a caregiver stress management intervention improve patient QoL?, Methods: In this replication study, we randomized 155 allogeneic hematopoietic stem cell transplant (Allo-HSCT) patients and caregivers to PsychoEducation, Paced Respiration, and Relaxation (PEPRR) or enhanced treatment as usual (eTAU). We provided PEPRR over 3 months following transplant. Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) evaluated patient QoL, and CG-distress was based on depressive, anxious, and stress symptoms. Hierarchical linear models tested intervention, time, and interactions as fixed effects with participant as random effects., Results: Patients whose caregivers received PEPRR did not differ on FACT-BMT between baseline and 6 months (mean = +3.74; 95% CI, -3.54 to 11.02) compared with patients of caregivers in eTAU (mean = +3.16; 95% CI, -2.88 to 9.20) even though CG-distress was decreased by PEPRR (mean = -0.23; 95% CI, -0.448 to -0.010) compared with those receiving eTAU (mean = +0.27; 95% CI, 0.033-0.504) at 6 months., Conclusions: PEPRR reduced CG-distress without affecting their patient's FACT-BMT score. The FACT-BMT may not have distinguished unique psychological changes associated with their caregiver receiving PEPRR., (© 2019 John Wiley & Sons, Ltd.)

Purpose: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a demanding treatment requiring caregiver support. The pre-transplant period is particularly stressful. How patient and caregiver dyads respond to these stressors can impact post-transplant outcomes. The purpose of this cross-sectional study was to assess pre-transplant patient and caregiver distress, patient quality of life (pQoL), and simultaneously investigate relationship between caregiver distress, patient distress, and patient QoL., Methods: We measured caregiver anxiety, depressive symptoms, perceived stress, sleep quality, caregiver burden, and pQoL in148 dyads compared to clinical thresholds or population norms. To reduce comparisons, we created a composite distress score from affective measures. Associations within dyads were examined via correlation and path analysis., Results: Most dyads scored above norms for psychological measures. Patient distress was positively associated with caregiver distress. Higher caregiver distress significantly predicted poorer pQoL after accounting for the interdependence of patient and caregiver distress. Specifically, patients' physical functioning was the primary driver of this interrelationship., Conclusions: Allo-HSCT patients and their caregivers reported elevated distress pre-transplant. Both patient and caregiver distress contributed to pQoL, with patients' physical functioning accounting significantly for caregiver well-being. Supporting the patient-caregiver dyad before transplantation is a priority for supportive services.

Medical research is often designed to investigate changes in a collection of response variables that are measured repeatedly on the same subjects. The multivariate generalized linear mixed model (MGLMM) can be used to evaluate random coefficient associations (e.g. simple correlations, partial regression coefficients) among outcomes that may be non-normal and differently distributed by specifying a multivariate normal distribution for their random effects and then evaluating the latent relationship between them. Empirical Bayes predictors are readily available for each subject from any mixed model and are observable and hence, plotable. Here, we evaluate whether second-stage association analyses of empirical Bayes predictors from a MGLMM, provide a good approximation and visual representation of these latent association analyses using medical examples and simulations. Additionally, we compare these results with association analyses of empirical Bayes predictors generated from separate mixed models for each outcome, a procedure that could circumvent computational problems that arise when the dimension of the joint covariance matrix of random effects is large and prohibits estimation of latent associations. As has been shown in other analytic contexts, the p-values for all second-stage coefficients that were determined by naively assuming normality of empirical Bayes predictors provide a good approximation to p-values determined via permutation analysis. Analyzing outcomes that are interrelated with separate models in the first stage and then associating the resulting empirical Bayes predictors in a second stage results in different mean and covariance parameter estimates from the maximum likelihood estimates generated by a MGLMM. The potential for erroneous inference from using results from these separate models increases as the magnitude of the association among the outcomes increases. Thus if computable, scatterplots of the conditionally independent empirical Bayes predictors from a MGLMM are always preferable to scatterplots of empirical Bayes predictors generated by separate models, unless the true association between outcomes is zero.

When presented with decisions that require simultaneously weighing self-benefit and other harm, adolescents with callous-unemotional traits compared with controls engage in less Costly Helping (i.e., giving up a benefit to protect a beneficent other). Young adults completed questionnaires, played an online-administered game of Costly Helping, and viewed an Elevation stimulus video (when witnessing another's act of virtue, individuals may experience a positive or elevating response). Subjects were assigned to one of four study arms, which varied the order of presentation. Higher levels of Factor 1 (callousness) psychopathic trait scale scores (assessed using the Levenson Self-Report Psychopathy Scale) were associated with significantly less Costly Helping. Elevation associated positively with Costly Helping behaviors and negatively with psychopathic traits. Introducing Elevation as an independent variable in regression analyses attenuated the relationship between psychopathic traits and Costly Helping, suggesting mediation. Those viewing the Elevation stimulus video prior to playing the game, as opposed to after, trended toward more Costly Helping by taking less money for themselves ($3.28vs. $3.72). Results support that this simple game provides meaningful behavioral data associated with psychopathic traits. Differences in Elevation may, in part, explain the observed differences in prosocial behavior in those with high psychopathic traits., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Reflective capacity is the ability to review and reconstruct the importance, emotional impact, and outcomes of an experience to give it added meaning and context. In medicine, greater reflective capacity is associated with greater empathy and diagnostic accuracy. This project implemented a four-week reflective writing curriculum for third-year medical students during their psychiatric clerkship., Methods: A single class of medical students participated in a pilot reflective writing program during their four-week Psychiatry Care Block. Students were provided with weekly writing prompts, and the reflective capacity of their writing assignments was assessed using the REFLECT rubric., Results: Medical students who participated in the reflective writing course demonstrated a significant increase in Wald Rubric reflective writing scores across the four-week clerkship., Conclusions: These results suggest a short, four-week reflective writing curriculum can enhance reflective capacity in a class of third-year medical students.

Objective: To evaluate marijuana use by adolescents and young adults with inflammatory bowel disease (IBD)., Study Design: This descriptive cross-sectional study of patients seen between December 2015 through June 2017 at Children's Hospital Colorado for IBD enrolled patients 13-23 years of age, independent of marijuana use status. Information obtained consisted of chart review, electronic and interview self-report, and serum cannabinoid levels. Marijuana ever-users were compared with never-users for clinical characteristics and perceptions of risk with use; users provided information on routes, patterns, motivations, and perceived benefits and problems with use., Results: Of 99 participants, ever-use was endorsed by 32% (32 of 99) and daily or almost daily use by 9% (9 of 99). Older age was the only characteristic related to endorsing marijuana use. Twenty-nine ever-users completed all questionnaires. After adjusting for age, users were 10.7 times more likely to perceive low risk of harm with regular use (P < .001). At least 1 medical reason for use was endorsed by 57% (17 of 30), most commonly for relief of physical pain (53%, 16 of 30) (2 did not complete all questionnaires). Problems from use were identified by 37% (11 of 30), most commonly craving/strong urge to use. Most common route of use was smoking (83%) followed by edibles (50%), dabbing (40%), and vaping (30%)., Conclusions: Marijuana use by adolescents and young adults with IBD is common and perceived as beneficial. Guidelines for screening, testing, and counseling of marijuana use should be developed for patients with IBD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Limited translational success in critical care medicine is thought to be in part due to inadequate methodology, study design, and reporting in preclinical studies. The purpose of this study was to compare reporting of core features of experimental rigor: blinding, randomization, and power calculations in critical care medicine animal experimental research. We hypothesized that these study design characteristics were more frequently reported in 2015 versus 2005., Methods: We performed an observational bibliometric study to grade manuscripts on blinding, randomization, and power calculations. Chi-square tests and logistic regression were used for analysis. Inter-rater agreement was assessed using kappa and Gwet's AC1., Results: A total of 825 articles from seven journals were included. In 2005, power estimations were reported in 2%, randomization in 35%, and blinding in 20% (n = 482). In 2015, these metrics were included in 9, 47, and 36% of articles (n = 343). The increase in proportion for the metrics tested was statistically significant (p < 0.001, p = 0.002, and p < 0.001)., Conclusions: Only a minority of published manuscripts in critical care medicine journals reported on recommended study design steps to increase rigor. Routine justification for the presence or absence of blinding, randomization, and power calculations should be considered to better enable readers to assess potential sources of bias.

Background: Knowledge of incidence and risk factors for long-term opioid prescribing is critical for surgical patients. In this retrospective cohort study, we linked information available at the time of surgery with prescription data to ascertain characteristics associated with prolonged opioid therapy., Methods: Patients (n = 6003) with claims in the Colorado All Payer Claims Database (APCD) were matched with 20,501 encounters in a clinical database. Rates of prescription filling were defined by at least one monthly opioid claim relative to the date of surgery. Associations of variables with claims during months 2-6 post-operatively ("long-term prescription filling") were evaluated, and significant variables were jointly modeled using binomial regression., Results: Rates of patients filling opioid prescriptions preoperatively [month (M) relative to date of surgery] were 22%(-3 M), 24%(-2 M), and 27%(-1 M); after surgery, opioid fill rates were 62%(1 M), 28%(2 M), 24%(3), 24%(4 M), 23%(5 M), and 22%(6 M). The majority, 71-76%, of patients filling prescriptions in months 2-6 after surgery had also filled before surgery. In the binomial regression model, long-term opioid use was associated with prior opioid use (p < 0.0001), age ≥26 to <65 relative to age ≥ 65 (p < 0.0001), orthopedic surgery (p = 0.001), colorectal surgery (p = 0.003), multiple procedures (p < 0.0001), and worse physical status classification (p < 0.0001)., Conclusions: Patients who had filled opioid prescriptions preoperatively comprised the majority of the group who filled long-term prescriptions. Surgical procedures were associated with discontinuation of previous opioid prescribing in some patients. For others, surgery marked the initiation of prolonged opioid therapy. Surgical encounters should include interventions aimed to reduce long-term opioid use., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Identification of the majority of organisms present in human-associated microbial communities is feasible with the advent of high throughput sequencing technology. As substantial variability in microbiota communities is seen across subjects, the use of longitudinal study designs is important to better understand variation of the microbiome within individual subjects. Complex study designs with longitudinal sample collection require analytic approaches to account for this additional source of variability. A common approach to assessing community changes is to evaluate the change in alpha diversity (the variety and abundance of organisms in a community) over time. However, there are several commonly used alpha diversity measures and the use of different measures can result in different estimates of magnitude of change and different inferences. It has recently been proposed that diversity profile curves are useful for clarifying these differences, and may provide a more complete picture of the community structure. However, it is unclear how to utilize these curves when interest is in evaluating changes in community structure over time. We propose the use of a bi-exponential function in a longitudinal model that accounts for repeated measures on each subject to compare diversity profiles over time. Furthermore, it is possible that no change in alpha diversity (single community/sample) may be observed despite the presence of a highly divergent community composition. Thus, it is also important to use a beta diversity measure (similarity between multiple communities/samples) that captures changes in community composition. Ecological methods developed to evaluate temporal turnover have currently only been applied to investigate changes of a single community over time. We illustrate the extension of this approach to multiple communities of interest (i.e., subjects) by modeling the beta diversity measure over time. With this approach, a rate of change in community composition is estimated. There is a need for the extension and development of analytic methods for longitudinal microbiota studies. In this paper, we discuss different approaches to model alpha and beta diversity indices in longitudinal microbiota studies and provide both a review of current approaches and a proposal for new methods.

Background: Caregiving for allogeneic hematopoietic stem cell transplant (Allo-HSCT) patients can be significantly burdensome. Caregiver well-being often mirrors patients' suffering. However, to our knowledge, this dyadic relationship has not been linked to patient outcome., Objective: Caregiver's objective and subjective sleep and overall distress before transplantation were hypothesized to be related to patient's time to engraftment in secondary analyses., Methods: Dyads (N = 124) were Allo-HSCT patients (mean [SD] age, 49.2 [12.7] years) and their caregivers (mean [SD] age, 52.7 [12.3] years). Caregiver's subjective sleep quality was measured via the Pittsburgh Sleep Quality Index, objective sleep was measured by actigraphy, and distress was measured by combining validated psychological measures., Results: Both caregiver reports of worse sleep (β = .22; P < .05) and objective measurement of caregiver sleep patterns (higher sleep efficiency; less time awake after sleep onset) collected before engraftment significantly predicted shorter time to patient engraftment (β values = -.34 and .29, respectively; P values < .05). Caregiver distress was unrelated to engraftment (β = .14; P = .22)., Conclusions: Despite limitations in available patient data, these findings appear to link caregiver well-being to patient outcome. This underscores the interrelatedness of the patient-caregiver dyad in Allo-HSCT. Future research should examine psychological and biomedical mediators., Implications for Practice: Given that caregiver well-being during the peritransplantation period was associated with patient outcome in this study, such findings highlight the need to address caregiver and patient well-being during Allo-HSCT. There may be potential to improve patient outcome by focusing on the caregiver, which nursing staff is well positioned to monitor.

Objective: Among young children excessive externalizing behaviors often predict adolescent conduct and substance use disorders. Adolescents with those disorders show aberrant brain function when choosing between risky or cautious options. We therefore asked whether similarly aberrant brain function during risky decision-making accompanies excessive externalizing behaviors among children, hypothesizing an association between externalizing severity and regional intensity of brain activation during risky decision-making., Method: Fifty-eight (58) 9-11 year-old children (both sexes), half community-recruited, half with substance-treated relatives, had parent-rated Child Behavior Checklist Externalizing scores. During fMRI, children repeatedly chose between doing a cautious behavior earning 1 point or a risky behavior that won 5 or lost 10 points. Conservative permutation-based whole-brain regression analyses sought brain regions where, during decision-making, activation significantly associated with externalizing score, with sex, and with their interaction., Results: Before risky responses higher externalizing scores were significantly, negatively associated with neural activation (t's: 2.91-4.76) in regions including medial prefrontal cortex (monitors environmental reward-punishment schedules), insula (monitors internal motivating states, e.g., hunger, anxiety), dopaminergic striatal and midbrain structures (anticipate and mediate reward), and cerebellum (where injuries actually induce externalizing behaviors). Before cautious responses there were no significant externalizing:activation associations (except in post hoc exploratory analyses), no significant sex differences in activation, and no significant sex-by-externalizing interactions., Conclusions: Among children displaying more externalizing behaviors extensive decision-critical brain regions were hypoactive before risky behaviors. Such neural hypoactivity may contribute to the excessive real-life risky decisions that often produce externalizing behaviors. Substance exposure, minimal here, was a very unlikely cause., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Different types of outcomes (e.g. binary, count, continuous) can be simultaneously modeled with multivariate generalized linear mixed models by assuming: (1) same or different link functions, (2) same or different conditional distributions, and (3) conditional independence given random subject effects. Others have used this approach for determining simple associations between subject-specific parameters (e.g. correlations between slopes). We demonstrate how more complex associations (e.g. partial regression coefficients between slopes adjusting for intercepts, time lags of maximum correlation) can be estimated. Reparameterizing the model to directly estimate coefficients allows us to compare standard errors based on the inverse of the Hessian matrix with more usual standard errors approximated by the delta method; a mathematical proof demonstrates their equivalence when the gradient vector approaches zero. Reparameterization also allows us to evaluate significance of coefficients with likelihood ratio tests and to compare this approach with more usual Wald-type t-tests and Fisher's z transformations. Simulations indicate that the delta method and inverse Hessian standard errors are nearly equivalent and consistently overestimate the true standard error. Only the likelihood ratio test based on the reparameterized model has an acceptable type I error rate and is therefore recommended for testing associations between stochastic parameters. Online supplementary materials include our medical data example, annotated code, and simulation details.

We sought to identify brain activation differences in conduct-problem youth with limited prosocial emotions (LPE) compared to conduct-problem youth without LPE and community adolescents, and to test associations between brain activation and severity of callous-unemotional traits. We utilized a novel task, which asks subjects to repeatedly decide whether to accept offers where they will benefit but a beneficent other will be harmed. Behavior on this task has been previously associated with levels of prosocial emotions and severity of callous-unemotional traits, and is related to empathic concern. During fMRI acquisition, 66 male adolescents (21 conduct-problem patients with LPE, 21 without, and 24 typically-developing controls) played this novel game. Within typically-developing controls, we identified a network engaged during decision involving bilateral insula, and inferior parietal and medial frontal cortices, among other regions. Group comparisons using non-parametric (distribution-free) permutation tests demonstrated LPE patients had lower activation estimates than typically-developing adolescents in right anterior insula. Additional significant group differences emerged with our a priori parametric cluster-wise inference threshold. These results suggest measurable functional brain activation differences in conduct-problem adolescents with LPE compared to typically-developing adolescents. Such differences may underscore differential treatment needs for conduct-problem males with and without LPE., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Methods: We recruited right-handed female patients, 14-19 years of age, from a university-based treatment program for youths with substance use disorders and community controls similar for age, race and zip code of residence. We obtained 43 T1-weighted structural brain images (22 patients and 21 controls) to examine group differences in cortical thickness across the entire brain as well as six a priori regions-of-interest: 1) medial orbitofrontal cortex; 2) rostral anterior cingulate cortex; and 3) middle frontal cortex, in each hemisphere. Age and IQ were entered as nuisance factors for all analyses., Results: A priori region-of-interest analyses yielded no significant differences. However, whole-brain group comparisons revealed that the left pregenual rostral anterior cingulate cortex extending into the left medial orbitofrontal region (355.84 mm2 in size), a subset of two of our a priori regions-of-interest, was significantly thinner in patients compared to controls (vertex-level threshold p = 0.005 and cluster-level family wise error corrected threshold p = 0.05). The whole-brain group differences did not survive after adjusting for depression or externalizing scores. Whole-brain within-patient analyses demonstrated a positive association between cortical thickness in the left precuneus and behavioral disinhibition scores (458.23 mm2 in size)., Conclusions: Adolescent females with substance use disorders have significant differences in brain cortical thickness in regions engaged by the default mode network and that have been associated with problems of emotional dysregulation, inhibition, and behavioral control in past studies.

Background: Some conduct-disordered youths have high levels of callous unemotional traits and meet the DSM-5's "with limited prosocial emotions" (LPE) specifier. These youths often do aggressive, self-benefitting acts that cost others. We previously developed a task, the AlAn's game, which asks participants to repeatedly decide whether to accept or reject offers in which they will receive money but a planned charity donation will be reduced. In our prior work, more "costly helping" (i.e., rejecting the offered money and protecting the donation) was associated with lower callous unemotional traits. Here we extend that prior work in a larger sample of adolescent male patients with serious conduct problems and controls, and test whether this association is mediated specifically by a Moral Elevation response (i.e., a positive emotional response to another's act of virtue)., Methods: The adolescent male participants were: 45 patients (23 with LPE) and 26 controls, who underwent an extensive phenotypic assessment including a measure of Moral Elevation. About 1 week later participants played the AlAn's game., Results: All AlAn's game outcomes demonstrated significant group effects: (1) money taken for self (p = 0.02); (2) money left in the charitable donation (p = 0.03); and, (3) costly helping (p = 0.047). Controls took the least money and did the most costly helping, while patients with LPE took the most money and did the least costly helping. Groups also significantly differed in post-stimulus Moral Elevation scores (p = 0.005). Exploratory analyses supported that the relationship between callous unemotional traits and costly helping on the AlAn's game may be mediated in part by differences in Moral Elevation., Conclusions: The AlAn's game provides a standardized behavioral measure associated with callous unemotional traits. Adolescents with high levels of callous unemotional traits engage in fewer costly helping behaviors, and those differences may be related to blunting of positive emotional responses.

Objective: Caregiving for allogeneic hematopoietic stem cell transplant (Allo-HSCT) patients carries a significant psychological burden, yet it remains unclear whether Allo-HSCT caregivers demonstrate disruptions to stress systems, such as the hypothalamic-pituitary-adrenal axis. Greater intraindividual cortisol variability (ICV) has been observed in psychiatric disorders; however, there is a knowledge gap evaluating ICV in caregivers. We predicted that greater ICV would be related to poorer mental health in Allo-HSCT caregivers., Methods: Allo-HSCT caregivers (n = 140) collected saliva for 3 consecutive days at 4 time points/d. Psychological variables included sleep quality and a summary composite score of overall mental health., Results: Regression analyses demonstrated that greater ICV was significantly related to poorer overall mental health (β = 0.25, p = .009), whereas poorer sleep did not reach significance (β = 0.16, p = .069). No significant relationships emerged for the cortisol area under the curve, diurnal decline, or awakening response., Conclusions: Results extend prior work examining ICV as a unique marker that is possibly more sensitive than other widely applied measures of hypothalamic-pituitary-adrenal axis dysregulation to a distressed population of caregivers.

Objective: This study assessed whether a customized disclosure form increases understanding for adolescents with substance use disorder (SUD) when compared to a standard disclosure for genomic addiction research., Method: We gathered empirical data from adolescents with SUD, family members, former patients followed since adolescence, and community counterparts. The study was conducted in four stages. Stage 1: national experts (n=32) identified current, future, speculative risks of broadly shared biobanks. Stage 2 assessed participants' (n=181) understanding of current risks as a prerequisite for rating saliency of risks via a Visual Analog Scale. Salient risks were incorporated into a customized disclosure form. Stage 3 compared the understanding of customized disclosure by participants (n=165) at baseline; all groups scored comparably. Stage 4 conducted a direct comparison of the standard disclosure to standard disclosure plus customized disclosure (n=195). Independent t-tests compared understanding in those receiving the standard disclosure to standard disclosure plus customized disclosure within 6 groups., Results: The customized disclosure significantly improved understanding in adolescent patients (p=0.002) and parents of patients (p=0.006) to the level of their counterparts. The customized disclosure also significantly improved understanding in siblings of former patients (p=0.034). Understanding of standard disclosure in patients versus controls was significantly different (p=0.005). The groups receiving the customized disclosure scored significantly higher. Understanding of the standard disclosure plus customized disclosure in patients versus controls was not significantly different., Conclusion: Adolescents with addictions understand the risks of participating in genomic addiction research as well as their community counterparts when information provided is salient to them., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

To our knowledge, this is the first study to examine the DSM-5-defined conduct disorder (CD) with limited prosocial emotions (LPE) among adolescents in substance use disorder (SUD) treatment, despite the high rates of CD in this population. We tested previously published methods of LPE categorization in a sample of male conduct-disordered patients in SUD treatment (n=196). CD with LPE patients did not demonstrate a distinct pattern in terms of demographics or co-morbidity regardless of the categorization method utilized. In conclusion, LPE, as operationalized here, does not identify a distinct subgroup of patients based on psychiatric comorbidity, SUD diagnoses, or demographics.

Caregivers of patients receiving allogeneic hematopoietic stem cell transplants (allo-HSCT) serve a pivotal role in patient care but experience high stress, anxiety and depression as a result. We theorized that stress management adapted for allo-HSCT caregivers would reduce distress compared with treatment as usual (TAU). Of 267 consecutive caregivers of allo-HSCT patients approached, 148 (mean=53.5 years, 75.7% female) were randomized to either psychosocial intervention (i=74) or TAU (n=74). Eight one-on-one stress management sessions delivered across the 100-day post-transplant period focused on understanding stress, changing role(s) as caregiver, cognitive behavioral stress management, pacing respiration and identifying social support. Primary outcomes included perceived stress (psychological) and salivary cortisol awakening response (CAR) (physiological). Randomized groups were not statistically different at baseline. Mixed models analysis of covariance (intent-to-treat) showed that intervention was associated with significantly lower caregiver stress 3 months post transplant (mean=20.0, 95% confidence interval (95% CI)=17.9-22.0) compared with TAU (mean=23.0, 95% CI=21.0-25.0) with an effect size (ES) of 0.39 (P=0.039). Secondary psychological outcomes, including depression and anxiety, were significantly reduced with ESs of 0.46 and 0.66, respectively. Caregiver CAR did not differ from non-caregiving controls at baseline and was unchanged by intervention. Despite significant caregiving burden, this psychosocial intervention significantly mitigated distress in allo-HSCT caregivers.

Background: Accidental injury and homicide, relatively common among adolescents, often follow risky behaviors; those are done more by boys and by adolescents with greater behavioral disinhibition (BD)., Hypothesis: Neural processing during adolescents' risky decision-making will differ in youths with greater BD severity, and in males vs. females, both before cautious behaviors and before risky behaviors., Methodology/principal Findings: 81 adolescents (PATIENTS with substance and conduct problems, and comparison youths (Comparisons)), assessed in a 2 x 2 design (, Patients: Comparisons x Male:Female) repeatedly decided between doing a cautious behavior that earned 1 cent, or a risky one that either won 5 or lost 10 cents. Odds of winning after risky responses gradually decreased. Functional magnetic resonance imaging captured brain activity during 4-sec deliberation periods preceding responses. Most neural activation appeared in known decision-making structures. PATIENTS, who had more severe BD scores and clinical problems than Comparisons, also had extensive neural hypoactivity. Comparisons' greater activation before cautious responses included frontal pole, medial prefrontal cortex, striatum, and other regions; and before risky responses, insula, temporal, and parietal regions. Males made more risky and fewer cautious responses than females, but before cautious responses males activated numerous regions more than females. Before risky behaviors female-greater activation was more posterior, and male-greater more anterior., Conclusions/significance: Neural processing differences during risky-cautious decision-making may underlie group differences in adolescents' substance-related and antisocial risk-taking. Patients reported harmful real-life decisions and showed extensive neural hypoactivity during risky-or-cautious decision-making. Males made more risky responses than females; apparently biased toward risky decisions, males (compared with females) utilized many more neural resources to make and maintain cautious decisions, indicating an important risk-related brain sexual dimorphism. The results suggest new possibilities for prevention and management of excessive, dangerous adolescent risk-taking.

This study surveyed all adolescents who were enrolled in behavioral genomic research and provided DNA to a biobank, including 320 patients undergoing treatment for substance and conduct problems (SCPs) and 109 non-SCP controls. Participants selected from three options on the return of individual genomic results (RIR) and rated eight methods of re-contact. Most individuals with SCPs (77.8%) and non-SCP controls (72.5%) wanted RIR involving health or behavioral implications. The majority of individuals with SCPs (67.2%) and non-SCP controls (69.7%) indicated that phone re-contact was 'best', with e-mail (22.5% SCPs, 33.9% non-SCPs) and social networking websites (21.3% SCPs, 20.2% non-SCPs) being viable options. These results suggest a layered approach for RIR: phone calls, followed by e-mails and a secure message to a social networking account. Data from this special and vulnerable population, which includes youth involved in the criminal justice system and substantial minority participation, bring an essential and missing perspective to the discussion of RIR.

Objective: Structural neuroimaging studies have demonstrated lower regional gray matter volume in adolescents with severe substance and conduct problems. These research studies, including ours, have generally focused on male-only or mixed-sex samples of adolescents with conduct and/or substance problems. Here we compare gray matter volume between female adolescents with severe substance and conduct problems and female healthy controls of similar ages., Hypotheses: Female adolescents with severe substance and conduct problems will show significantly less gray matter volume in frontal regions critical to inhibition (i.e. dorsolateral prefrontal cortex and ventrolateral prefrontal cortex), conflict processing (i.e., anterior cingulate), valuation of expected outcomes (i.e., medial orbitofrontal cortex) and the dopamine reward system (i.e. striatum)., Methods: We conducted whole-brain voxel-based morphometric comparison of structural MR images of 22 patients (14-18 years) with severe substance and conduct problems and 21 controls of similar age using statistical parametric mapping (SPM) and voxel-based morphometric (VBM8) toolbox. We tested group differences in regional gray matter volume with analyses of covariance, adjusting for age and IQ at p<0.05, corrected for multiple comparisons at whole-brain cluster-level threshold., Results: Female adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral somatosensory cortex, left supramarginal gyrus, and bilateral angular gyrus. Considering the entire brain, patients had 9.5% less overall gray matter volume compared to controls., Conclusions: Female adolescents with severe substance and conduct problems in comparison to similarly aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior.

Background: Perspectives of adolescent research participants regarding conflicts of interest (COIs) and their impact on trust in researchers have not been studied. This study evaluates views of adolescent patients in treatment for substance and conduct problems compared to controls enrolled in genomic addiction research., Methods: Participants included 273 (190 patients, 83 controls) adolescents. Participants consented or assented (with parental consent) to have their genomic information deposited in a NIH biobank that shares information globally with qualified investigators. As part of that study, participants completed a COI survey. Endorsement of each COI item was analyzed with multiple logistic regressions, evaluating group, age, sex, ethnicity, and highest grade completed., Results: Patients and controls differed in gender, ethnicity and highest grade completed. In response to the survey, 38.4% of patients and 25.3% of controls "want to know" and 35.3% of patients and 37.3% of controls "might want to know" about COIs. Males were less likely to want/might want disclosure about COIs. Older patients were more likely to want disclosure about financial interests; patients were more likely to want disclosure about possible treatments; males were more likely to want information about monetary gains. Both groups requested between 1 paragraph and 1 page of information. Disclosure of COIs did not impact trust for most participants., Conclusion: Adolescent patients and controls in this study want comparable information for disclosure of COIs including monetary gains, salary, publications, grants, and professional awards. Notably, the majority of patients and controls report that disclosure will not undermine trust in researchers., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Adolescents with substance use disorder (SUD) and conduct problems exhibit high levels of impulsivity and poor self-control. Limited work to date tests for brain cortical thickness differences in these youths., Objectives: To investigate differences in cortical thickness between adolescents with substance use and conduct problems and controls., Methods: We recruited 25 male adolescents with SUD, and 19 male adolescent controls, and completed structural 3T magnetic resonance brain imaging. Using the surface-based morphometry software FreeSurfer, we completed region-of-interest (ROI) analyses for group cortical thickness differences in left, and separately right, inferior frontal gyrus (IFG), orbitofrontal cortex (OFC) and insula. Using FreeSurfer, we completed whole-cerebrum analyses of group differences in cortical thickness., Results: Versus controls, the SUD group showed no cortical thickness differences in ROI analyses. Controlling for age and IQ, no regions with cortical thickness differences were found using whole-cerebrum analyses (though secondary analyses co-varying IQ and whole-cerebrum cortical thickness yielded a between-group cortical thickness difference in the left posterior cingulate/precuneus). Secondary findings showed that the SUD group, relative to controls, demonstrated significantly less right > left asymmetry in IFG, had weaker insular-to-whole-cerebrum cortical thickness correlations, and showed a positive association between conduct disorder symptom count and cortical thickness in a superior temporal gyrus cluster., Conclusion: Functional group differences may reflect a more nuanced cortical morphometric difference than ROI cortical thickness. Further investigation of morphometric differences is needed. If replicable findings can be established, they may aid in developing improved diagnostic or more targeted treatment approaches.

Background: Adolescents with conduct disorder (CD) and substance use disorders (SUD) experience difficulty evaluating and regulating their behavior in anticipation of future consequences. Given the role of the brain's default mode network (DMN) in self-reflection and future thought, this study investigates whether DMN is altered in adolescents with CD and SUD, relative to controls., Methods: Twenty adolescent males with CD and SUD and 20 male controls of similar ages underwent functional magnetic resonance imaging as they completed a risk-taking decision task. We used independent component analysis as a data-driven approach to identify the DMN spatial component in individual subjects. DMN activity was then compared between groups., Results: Compared to controls, patients showed reduced activity in superior, medial and middle frontal gyrus (Brodmann area (BA) 10), retrosplenial cortex (BA 30) and lingual gyrus (BA 18), and bilateral middle temporal gryus (BA 21/22) - DMN regions thought to support self-referential evaluation, memory, foresight, and perspective taking. Furthermore, this pattern of reduced activity in patients remained robust after adjusting for the effects of depression and attention-deficit hyperactivity disorder (ADHD). Conversely, when not adjusting for effects of depression and ADHD, patients demonstrated greater DMN activity than controls solely in the cuneus (BA 19)., Conclusions: Collectively, these results suggest that comorbid CD and SUD in adolescents is characterized by atypical activity in brain regions thought to play an important role in introspective processing. These functional imbalances in brain networks may provide further insight into the neural underpinnings of conduct and substance use disorders., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Personality traits such as pathological engagement in approach behaviors, high levels of impulsivity and heightened negative affect are consistently observed in substance dependent individuals (SDI). The clinical course of addiction has been shown to differ between sexes. For example, women increase their rates of consumption of some drugs of abuse more quickly than men. Despite the potential influence of personality and sex on features of addiction, few studies have investigated the interaction of these factors in substance dependence., Methods: Fifty-one SDI (26 males, 25 females) and 66 controls (41 males, 25 females) completed the Behavioral Inhibition/Behavioral Activation System (BIS/BAS) Scales, the Barratt Impulsiveness Scale, and the Positive and Negative Affect Schedule (PANAS-X). Data were analyzed with 2×2 ANCOVAs testing for main effects of group, sex and group by sex interactions, adjusting for education level., Results: Significant group by sex interactions were observed for BAS scores [F(1,116)=7.03, p<.01] and Barratt Motor Impulsiveness [F(1,116)=6.11, p<.02] with female SDI showing the highest approach tendencies and impulsivity followed by male SDI, male controls, and finally female controls. SDI scored higher on negative affect [F(1,116)=25.23, p<.001] than controls. Behavioral Inhibition System scores were higher in women than men [F(1,116)=14.03, p<.001]., Conclusion: Higher BAS and motor impulsivity in SDI women relative to SDI men and control women suggest that personality traits that have been previously associated with drug use may be modulated by sex. These factors may contribute to differences in the disease course observed in male compared to female drug users., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background and Objectives: The longitudinal risk for human immunodeficiency virus (HIV) infection following adolescent substance treatment is not known. Therefore, it is not known if adolescent substance treatment should include HIV prevention interventions. To address this important research gap, this study evaluates the longitudinal prevalence and predictors of injection drug use (IDU) and sex risk behaviors among adolescents in substance treatment., Methods: Participants were 260 adolescents (13-18 years) in substance treatment and 201 community control adolescents (11-19 years). Participants were assessed at baseline and follow-up (mean time between assessments = 6.9 years for the clinical sample and 5.6 years for the community control sample). Outcomes included self-report lifetime history of IDU, number of lifetime sex partners and frequency of unprotected sexual intercourse., Results: At baseline, 7.5% of the clinical sample, compared to 1.0% of the community control sample had a lifetime history of IDU (χ12=10.53, p = .001). At follow-up, 17.4% of the clinical sample compared to 0% of the community control sample had a lifetime history of IDU (χ12=26.61, p = .0005). The number of baseline substance use disorders and onset age of marijuana use significantly predicted the presence of lifetime IDU at follow-up, after adjusting for baseline age, race, and sex. The clinical sample reported more lifetime sex partners and more frequent unprotected sex than the community control sample at baseline and follow-up., Conclusions: Many adolescents in substance treatment develop IDU and report persistent risky sex. Effective risk reduction interventions for adolescents in substance treatment are needed that address both IDU and risky sex., (Copyright © American Academy of Addiction Psychiatry.)