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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.

Background 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 HADS-A 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. This article is protected by copyright. All rights reserved.

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.

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.

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 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.

To evaluate marijuana use by adolescents and young adults with inflammatory bowel disease (IBD).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.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%).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.

Purpose We sought to describe the prevalence of the nonmedical use of prescription opioids (NMUPO) and its association with co-occurring substance use disorders in a sample of adolescents in substance treatment. Methods Adolescents in two substance treatment programs were recruited for participation between 2009 and 2013. The Composite International Diagnostic Interview—Substance Abuse Module (CIDI-SAM) was administered to assess substance use patterns and lifetime abuse or dependence. Results A total of 378 adolescents completed the CIDI-SAM (mean age 16.1 [standard deviation = 1.1], 78% male, 50% white, non-Hispanic). Of the 378 adolescents, 62 (16.4%) reported NMUPO and 59 (15.6%) were diagnosed with opioid/heroin abuse or dependence. The mean age at first NMUPO was 14.3 (standard deviation = 1.4). NMUPO was associated with a 3.31-fold (95% confidence interval: 2.83–3.79) increase in having three or more co-occurring substance use diagnoses. Conclusions NMUPO is quite prevalent among adolescents in substance use treatment. Intervention to interrupt NMUPO from progressing to heroin use or developing into a disorder is critical.

Purpose: The opioid epidemic in the United States is an ongoing public health concern. Health care institutions use standardized patient satisfaction surveys to assess the patient experience and some offer incentives to their providers based on the results. We hypothesized that providers who report being incentivized based on patient satisfaction surveys are more likely to report an impact of such surveys on their opioid prescribing practices. Methods: We developed a 23-item survey instrument to assess the self-perceived impact of patient satisfaction surveys on opioid prescribing practices in primary care and the potential impact of institutional incentives. The survey was emailed to all 1404 members of the Colorado Academy of Family Physicians. Results: The response rate to the online survey was 10.4% (n = 146). Clinical indications for which responders prescribe opioids included acute pain (93%), cancer pain (85%), and chronic nonmalignant pain (72%). Among physicians using patient satisfaction surveys, incentivized physicians reported at least a slight impact on opioid prescribing 3 times more often than physicians who were not incentivized (36% vs 12%, P = .004). Conclusions: Efforts to improve patient satisfaction may have potentially untoward effects on providers9 opioid prescribing behaviors. Our results suggest a need to further study the impact of provider incentive plans that are based on patient satisfaction scores.

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

Objectives The aim of the study was to describe use of oral or sublingual cannabis oil (CO) by adolescent and young adult patients with inflammatory bowel disease (IBD). Methods A descriptive study of IBD patients 13 to 23 years of age seen between January 2015 through December 2017 at Children's Hospital Colorado. Information obtained included chart abstraction, electronic and interview self-report, and serum cannabinoid levels. We compared CO users and cannabis non-users for clinical characteristics and perceptions of risk. Users of CO provided information on routes, patterns, motivations, and perceived benefits and problems with use. Results The 15 users and 67 non-users were similar for clinical characteristics and pain and appetite scores. 9 of 15 (60%) CO users had used in the past 30 days, an average of 22 ± 9 times; and 4 used daily. A variety of strengths and CBD:THC ratios were reported. Most common perceived effect of use was on sleep quality, nausea, and increase in appetite. Of the 15 users, 6 used only CO and no additional forms of cannabis. Of these 6 CO only users, 5 reported a medical reason for use, most commonly to relieve pain. Conclusions Adolescent and young adults with IBD used oral CO and many used other cannabis products as well. Users perceived some medical benefit. Care teams should strive for open communication about use until further information on safety and efficacy becomes available.

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

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=6,003) 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%(-3M), 24%(-2M), and 27%(-1M); after surgery, opioid fill rates were 62%(1M), 28%(2M), 24%(3), 24%(4M), 23%(5M), and 22%(6M). 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

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.

Allogeneic stem cell transplantation is a common form of treatment for many types of blood cancers and requires active caregiver involvement for 100 days or longer [1]. The stress of caregiving starts before transplantation when families are preparing for the adversities of the transplant process. Caregivers are often involved in patients’ treatment prior to transplantation since most caregivers are patients’ immediate family members. As the start of transplant nears, the realities of the decision to proceed to transplant and associated risks for morbidity and mortality become increasingly concrete to the patient and caregiver. Although there is potential for significant improvement in the patients’ disease status following transplant, there remains a high level of risk with the transplant procedure. Understanding caregiver adjustment to these peri-transplant stressors is important to identify support needs and develop interventions to help caregivers meet the caregiving challenge. Caregivers of cancer patients face considerable risk regarding their own well-being. The burden of caregiving can have a significant impact on emotional, physical and social functioning [2-7], as well as immune and neuroendocrine processes [8, 9]. The patient and caregiver are closely connected in their experiences of dealing with the cancer; patient physical and psychological well-being is related to caregiver emotional and psychological well-being [10, 11]. From a systems perspective, this relationship would be bidirectional. Thus, caring for the caregiver is important for the health of the caregiver as well as the health of the patient. Despite the critical role of caregivers, only limited research has focused on the caregiver experience and even fewer studies have focused on the caregiver during the allogeneic peri-transplant period. When allogeneic transplant patients and caregivers (n=40 and n=39, respectively) were compared on their pre-transplant psychosocial and psychological functioning, patients and caregivers reported significant distress prior to transplant [12]. Relatives of autologous and allogeneic transplant recipients reported stress significantly above the norm on the General Health Questionnaire, with stress greatest before and immediately following transplant [10]. Caregivers experienced greater anxiety and depression prior to transplant than five and 20 days post-transplant [13]. In a large study of autologous transplant caregivers (n=102), caregivers reported low levels of fatigue yet moderate levels of anxiety prior to transplant compared to population norms [14]. These studies suggest distress experienced by transplant caregivers is especially acute in the period preceding and immediately following transplantation of stem cells, i.e., the peri-transplant period. However, studies are limited by small sample sizes, restrictions in outcomes assessed, and heterogeneous patient groups consisting of both autologous and allogeneic transplant recipients or only autologous patient groups who present different caregiver challenges than allogeneic caregivers. The purpose of this study was to describe the peri-transplant psychological status in a sample of caregivers of allogeneic transplant patients using measures of mood, perceived stress, sleep, and caregiving burden while determining if demographic or patient illness characteristics prior to transplant predicted levels of caregiver distress. We predicted that caregiver sex, age and patient status would contribute to overall peri-transplant caregiver distress. We hypothesized that female caregivers and younger caregivers would experience more distress than male or older caregivers.

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.

Some youths develop multiple substance use disorders early in adolescence and have severe, persistent courses. Such youths often exhibit impulsivity, risk-taking, and problems of inhibition. However, relatively little is known about the possible brain bases of these behavioral traits, especially among females. 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.

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.

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

This study examined factors associated with methadone maintenance retention, defined as remaining in treatment for a minimum of 90 days, among street recruited injection drug users (IDUs). Targeted sampling methods were used to establish recruitment quotas in Denver census tracks. A total of 577 IDUs were randomly assigned to either a risk reduction intervention, focusing on safer injection and sex behaviors, or motivational interviewing, addressing more sweeping lifestyle changes including drug treatment. All subjects who wanted treatment were provided transportation, rapid intake and a waiver of the intake fee. In addition, 50% were randomly assigned a coupon for 90 days of free treatment. Overall, 33% entered treatment and of these, 60% remained for at least 90 days. Factors associated with retention included higher methadone dose, free treatment, greater contacts with the clinic and counselor rating of patient cooperation. Although desire for treatment, or motivation, was associated in univariate analyses with greater retention, there were no differences observed between the motivational interviewing and risk reduction interventions.

Substance use disorder is characterized by impaired decision making, impulsivity, and risk taking. Pathological gambling shares many of these characteristics, and having both diagnoses may be associated with greater problems than either diagnosis alone. We investigated whether among substance-dependent individuals, comorbid pathological gambling would be associated with worse decision making, greater impulsivity, risk taking, and drug severity.Ninety-six substance-dependent individuals were recruited from a residential treatment program and divided into 1 of the 2 groups depending on whether they met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for pathological gambling (SDPG, n = 26) or not (SD, n = 70). Ninety-two controls were recruited from the community. Participants completed a decision-making task (modified Iowa Gambling Task), measures of impulsivity (Barratt Impulsivity Scale and Delay Discounting), and risk taking (Balloon Analog Risk Task). Decision making was analyzed using a computational model. We tested for group differences using analysis of covariance or Kruskal-Wallis and appropriate post-hoc tests.The groups differed in decision-making parameters (P0.001) and self-reported impulsivity (P0.001). All post-hoc comparisons were significant on these measures, and indicated stepwise changes in controls, followed by SD, followed by SDPG, with SDPG performing worse on decision making and being more impulsive. Compared with SD, SDPG had greater drug severity (P0.001). No group differences were observed in delay discounting or risk taking.Compared with individuals with substance dependence without pathological gambling, those with both disorders demonstrated worse decision making and significantly more drug-related symptoms. When evaluating patients with substance dependence, clinicians should consider diagnostic assessments for gambling, as the co-occurrence of both disorders may impact clinical characteristics.

BACKGROUND AND PURPOSE: Frontolimbic circuits are involved in learning and decision-making processes thought to be affected in substance-dependent individuals. We investigated frontolimbic cortical morphometry in substance-dependent men and women and determined whether morphometric measurements correlated with decision-making performance. MATERIALS AND METHODS: Twenty-eight abstinent SDI (17 men/11 women) were compared with 28 controls (13 men/15 women). Cortical thicknesses and volumes were computed by using FreeSurfer. After controlling for age and intracranial volume, group and sex effects were analyzed in 3 a priori regions of interest: the insula, orbitofrontal cortex, and anterior cingulate cortex by using analysis of covariance. A secondary whole-brain analysis was conducted to verify region-of-interest results and to explore potential differences in other brain regions. RESULTS: Region-of-interest analyses revealed a main effect of group on the left insula cortex, which was thinner in SDI compared with controls (P .02). There was a group by sex interaction on bilateral insula volume (left, P .02; right, P .001) and right insula cortical thickness (P .007). Compared with same-sex controls, female SDI had smaller insulae, whereas male SDI had larger insulae. Neither ACC nor OFC significantly differed across group. Performance on a decision-making task was better in controls than SDI and correlated with OFC measurements in the controls. CONCLUSIONS: SDI and controls differed in insula morphology, and those differences were modulated by sex. No group differences in OFC were observed, but OFC measurements correlated with negative-reinforcement learning in controls. These preliminary results are consistent with a hypothesis that frontolimbic pathways may be involved in behaviors related to substance dependence. ABBREVIATIONS: ACC anterior cingulate cortex; DSM-IV Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition; OFC orbitofrontal cortex; SDI substance-dependent individuals; VBM voxel-based morphometry

Major depressive disorder (MDD) frequently co-occurs in adolescents with substance use disorders (SUDs) and attention deficit hyperactivity disorder (ADHD), but the impact of MDD on substance treatment and ADHD outcomes and implications for clinical practice are unclear.Adolescents (n=303; ages 13-18) meeting DSM-IV criteria for ADHD and SUD were randomized to osmotic release methylphenidate (OROS-MPH) or placebo and 16 weeks of cognitive behavioral therapy (CBT). Adolescents with (n=38) and without (n=265) MDD were compared on baseline demographic and clinical characteristics as well as non-nicotine substance use and ADHD treatment outcomes.Adolescents with MDD reported more non-nicotine substance use days at baseline and continued using more throughout treatment compared to those without MDD (p0.0001 based on timeline followback; p0.001 based on urine drug screens). There was no difference between adolescents with and without MDD in retention or CBT sessions attended. ADHD symptom severity (based on DSM-IV ADHD rating scale) followed a slightly different course of improvement although with no difference between groups in baseline or 16-week symptom severity or 16-week symptom reduction. There was no difference in days of substance use or ADHD symptom outcomes over time in adolescents with MDD or those without MDD treated with OROS-MPH or placebo. Depressed adolescents were more often female, older, and not court ordered.These preliminary findings suggest that compared to non-depressed adolescents with ADHD and SUD, those with co-occurring MDD have more severe substance use at baseline and throughout treatment. Such youth may require interventions targeting depression.

This study of 632 drug injectors enrolled in eight residential detoxification centers within the National Drug Abuse Treatment Clinical Trials Network tested three interventions to reduce drug and sex risk behaviors. Participants were randomized to: (a) a two-session, HIV/HCV counseling and education (C&E) model added to treatment as usual (TAU), (b) a one-session, therapeutic alliance (TA) intervention conducted by outpatient counselors to facilitate treatment entry plus TAU, or (c) TAU. Significant reductions in drug and sex risk behaviors occurred for all three conditions over a 6-month follow-up period. C&E participants reported significantly greater rates of attending an HIV testing appointment, but this was not associated with better risk reduction outcomes. Reporting treatment participation within 2 months after detoxification and self-efficacy to practice safer injection behavior predicted reductions in injection risk behaviors. Findings indicate that participation in detoxification was followed by significant decreases in drug injection and risk behaviors for up to 6-months; interventions added to standard treatment offered no improvement in risk behavior outcomes.

Caregiving for hematopoietic stem cell transplant patients (HSCTp) is burdensome resulting in inadequate self-care, possibly leading to negative patient outcome. This potential Caregiver–HSCTp relationship was examined through assessment of caregiver objective and subjective sleep measures. We hypothesized that better caregiver sleep would be related to shorter time to patient engraftment (TtoE). Dyads ( N = 109) were HSCTp (M (SD) age = 48.2(12.7)) and caregivers (M (SD) age = 52.7(12.6)). Linear regression controlled for clinically relevant patient variables (age, sex, pre-transplant treatment intensity, clinical status). Better caregiver subjective sleep quality (Pittsburgh Sleep Quality Index) and objective sleep efficiency (SE; actigraphy) collected prior to engraftment significantly predicted TtoE (std beta’s = .20 and −.30 respectively; p ’s p R squared = 24%). Further, the timespan of sleep assessment relative to engraftment (M (SD) days = 18.5(12.1)) was controlled for to address the potential bidirectional relationship (e.g., shorter TtoE led to better caregiver sleep), and significant effects of caregiver SE remained (std beta = −.18; p (Supported by NIH grant CA126971 and PCORI contract CE-1304-6208.)

89 Background: Allogeneic hematopoietic stem cell transplant (Allo-HSCT) is a particularly stressful time for patient and caregivers alike. As such, well-being within patient-caregivers dyads is highly correlated in previous studies. It is less clear how this dyadic relationship changes over the course of treatment and recovery. Methods: In these secondary analyses of a randomized clinical trial of psychoeducational support (5 time points across 12 months), partial correlations, adjusting for group assignment and age, tested the relationship between individual mental and physical summary scores of patients and caregivers. 117 Allo-HSCT patient and caregivers provided baseline data, with available data used at each subsequent timepoint. Quality of life was measured with the Short-Form Health Survey; divided into mental (MCS) and physical summary (PCS) scores. Results: Patients were primarily men (69.6% male; Mage=49.36; SD=13.04); caregivers were primarily female (78%;Mage=53.26;SD=12.34). Patient and caregivers’ MCS were significantly correlated at baseline (r=.23;p

Adolescent inhalant users are significantly more likely than other patients to have conduct disorder, to report abuse and neglect, and to have previously attempted suicide. Yet little has been published regarding treatment outcome for inhalant users.Eighty male adolescents admitted to a residential treatment program underwent baseline assessment during treatment, and follow-up assessment at two-years post admission. Subjects reporting any lifetime inhalant use at baseline (n = 34) were compared to the other patients (n = 46) on 4 outcome variables.Adolescents reporting any lifetime inhalant use at baseline assessment reported twice as many past-year conduct disorder symptoms at two-year follow up (p = 0.03). The relationship between inhalant use and conduct disorder symptoms remained significant (p = 0.03) in analyses that controlled for age, time in jail or restricted environments in the 6-months preceding follow-up, as well as baseline-reported lifetime number of conduct disorder symptoms. Inhalant users were not significantly worse on these other outcome measures: crime in the last month (p = 0.60), days of nontobacco substance use in the last 6 months (p = 0.65), or, commission of selected crimes in the last 6 months (p = 0.06).Inhalant use among adolescent males in treatment for substance and behavior problems may predict more severe conduct disorder symptoms after treatment.

Background: To study the validity of transdermal assessment of alcohol concentration measured by a lightweight, noninvasive device. Methods: Subjects wore a 227-g anklet that sensed transdermal alcohol concentrations (TACs) every 15 to 30 minutes, downloading results to a remote computer each day. Twenty-four subjects entered a laboratory and received a dose of 0, 0.28, or 0.56 g/kg of ethanol. Breath alcohol concentrations (BrAC) and TAC were measured every 15 to 30 minutes Twenty others [10 alcohol dependent (AD) and 10 not (NAD)] in the community who wore the anklet for 8 days kept a drinking log and provided a BrAC sample each day. Results: In the laboratory, no zero-dose subject, and every subject receiving alcohol, had alcohol-positive TACs. The device distinguished low- and high-alcohol–dosing groups using peak (t14=3.37; p

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.

To identify characteristics, including current high-risk drug and sex behaviors, associated with self-reported HIV infection among injection drug users (IDUs) in Ukraine.Targeted sampling of IDUs from Kiev, Odessa, and Makeevka/Donetsk, Ukraine.From June through August 2002, 100 IDUs from each site were recruited through street outreach, including 212 who had previously been tested for HIV and knew their serostatus. Subjects were administered a standardized computer-assisted interview assessing HIV-related drug and sex risk behaviors and history of HIV testing.Twenty six percent of the 212 participants reported they were HIV-positive. Univariate followed by multiple logistic regression analyses were used to identify factors associated with HIV infection. In the 30-day period before their interview, HIV-infected IDUs were significantly more likely to have injected with a needle previously used by another injector without disinfecting, frontloaded and/or backloaded, and shared the drug solution from a common container. In addition, they had higher prevalence rates for hepatitis B virus and hepatitis C virus than those not infected with HIV. On the other hand, they were more likely to have reported no sex partners and, if sexually active, more likely to have used a condom.The high HIV seroprevalence among IDUs in Ukraine, combined with their continued engagement in needle-related risk behaviors, assures the continuance of the epidemic in this region, a region that is the epicenter of HIV in Europe.

Aims: Abused drugs activate dopaminergic (DA) “reward” regions (dorsal and ventral striatum, midbrain), promoting further drug-taking. While adverse effects lead most adolescents to limit risky drug use, some with genetic vulnerabilities to substance use disorders (SUD) and conduct problems, undeterred by risks, press on, developing SUD. We asked: (1) is the enhanced vulnerability of those youths mediated by excess reward-system activity, or by deficient inhibition of risky behaviors; (2) do those mechanisms differ by gender? Methods: Our fMRI analyses of 41 adolescent patients with severe SUD and conduct problems (20 males) and 40 comparison youths (20 males) continue. In each of 90 risky-decision trials youths decided between pressing a cautious button to earn 1 cent, or a risky one that either won 5 or lost 10 cents. Riskypress “win” odds gradually fell from 0.78 to 0.22. We analyzed brain activity during 4-sec pre-response deliberations with voxel-level and cluster-level FWE correction before risky, and separately before cautious, presses. Results: Making cautious responses required inhibiting the more-rewarded risky ones; to do so, bothmale and female comparison youths significantly activated frontopolar, temporal, parietal, or cerebellar regions, or DLPFC, more than patients; the regions differed by gender. No group activated DA regions before cautious responses. Before risky responses all four groups showed reward anticipation, activating DA regions. Comparison boys activatedmanymore, andcomparisongirlsmany fewer,DAvoxels than patients, but those differences were not statistically significant. Conclusions: Patients’ DA regions did not differ significantly from comparison youths’ at the power available here. Before cautious responses comparison youths more than patients activated other regions that may sustain cautious decisions despite temptations (e.g., drug availability, peer pressure). Those control-related regions may underlie patients’ and healthy youths’ differing vulnerabilities to SUD. Financial support: NIDA DA 011015; Kane Family Foundation.

Objective To examine the influence of conduct disorder (CD) on substance use initiation. Method Community adolescents without CD (n = 1,165, mean baseline age = 14.6 years), with CD (n = 194, mean baseline age = 15.3 years), and youth with CD recruited from treatment (n = 268, mean baseline age = 15.7 years) were prospectively followed and re-interviewed during young adulthood (mean ages at follow-up respectively: 20, 20.8, and 24). Young adult retrospective reports of age of substance initiation for 10 substance classes were analyzed using Cox regression analyses. Hazard ratios of initiation for the CD cohorts (community without CD as the reference) at ages 15, 18, and 21 were calculated, adjusting for baseline age, gender, and race/ethnicity. Results Among community subjects, CD was associated with elevated adjusted hazards for initiation of all substances, with comparatively greater hazard ratios of initiating illicit substances at age 15 years. By age 18, the adjusted hazard ratios remained significant except for alcohol. At age 21, the adjusted hazard ratios were significant only for cocaine, amphetamines, inhalants, and club drugs. A substantial portion of community subjects without CD never initiated illicit substance use. Clinical youth with CD demonstrated similar patterns, with comparatively larger adjusted hazard ratios. Conclusions CD confers increased risk for substance use initiation across all substance classes at age 15 years, with greater relative risk for illicit substances compared to licit substances. This effect continues until age 18 years, with the weakest effect for alcohol. It further diminishes for other substances by age 21, However, the likelihood of initiating cocaine, amphetamines, inhalants and club drug use among those who have not initiated yet continues to be highly elevated by age 21.

Caregiving represents a significant stressor affecting both behavioral and physiological regulation including increased inflammatory markers. At what time does caregiving begin to impact physiological and behavioral systems? As part of a randomized intervention for caregiver distress, we compared caregivers of blood or marrow transplant (BMT) recipients around the time of transplantation (baseline) to non-caregiving controls, with regard to plasma inflammatory markers (CRP and IL-6), blood pressure, BMI, natural cytotoxicity, and diurnal salivary cortisol. Female caregivers ( n = 51, age 50.6) were compared to female non-caregivers ( n = 19, age 47.9). Caregivers spent 10.7 h/day caring for the patient at baseline. Patients were diagnosed a median 18 months prior to transplant. Subjects completed the Perceived Stress Scale (PSS), Center for Epidemiological Studies-Depression scale (CESD), and Spielberger State Anxiety Inventory (STAI). Blood samples were assessed for inflammatory markers (CRP, IL6) by EIA. Lysis of K562 tumors indicating natural cytotoxicity was reported as lytic units/NK+ cell. At baseline, caregivers were significantly elevated on the PSS, CESD and STAI compared to controls ( NIH Grant CA126971 .)

Background Youth with conduct problems (CP) often make decisions which value self-interest over the interests of others. Self-benefiting behavior despite loss to others is especially common among youth with CP and callous-unemotional traits (CU). Such behavioral tendencies are generally measured using self- or observer-report. We are unaware of attempts to measure this tendency with a behavioral paradigm. Methods/Principal Findings In our AlAn's (altruism-antisocial) game a computer program presents subjects with a series of offers in which they will receive money but a planned actual charity donation will be reduced; subjects decide to accept or reject each offer. We tested (1) whether adolescent patients with CP (n = 20) compared with adolescent controls (n = 19) differed on AlAn's game outcomes, (2) whether youths with CP and CU differed significantly from controls without CP or CU, and (3) whether AlAn's game outcomes correlated significantly with CP and separately, CU severity. Patients with CP and CU compared with controls without these problems took significantly more money for themselves and left significantly less money in the charity donation; AlAn's game outcomes were significantly correlated with CU, but not CP. Conclusions/Significance In the AlAn's game adolescents with conduct problems and CU traits, compared with controls without CP/CU, are disposed to benefit themselves while costing others even in a novel situation, devoid of peer influences, where anonymity is assured, reciprocity or retribution are impossible, intoxication is absent and when the “other” to be harmed is considered beneficent. AlAn's game outcomes are associated with measures of CU. Results suggest that the AlAn's game provides an objective means of capturing information about CU traits. The AlAn's game, which was designed for future use in the MRI environment, may be used in studies attempting to identify the neural correlates of self-benefiting decision-making.

Objective To evaluate the effect of fluoxetine hydrochloride vs placebo on major depressive disorder, substance use disorder (SUD), and conduct disorder (CD) in adolescents receiving cognitive behavioral therapy (CBT) for SUD. Design Randomized controlled trial. Setting A single-site study conducted between May 2001 and August 2004. Participants One hundred twenty-six adolescents aged 13 to 19 years recruited from the community and meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic criteria for current major depressive disorder, lifetime CD, and at least 1 nontobacco SUD. Interventions Sixteen weeks of fluoxetine hydrochloride, 20 mg/d, or placebo, with CBT. Main Outcome Measures For depression, Childhood Depression Rating Scale–Revised and Clinical Global Impression Improvement; for SUD, self-reported nontobacco substance use and urine substance use screen results in the past 30 days; and for CD, self-reported symptoms in the past 30 days. Results Fluoxetine combined with CBT had greater efficacy than did placebo and CBT according to changes on the Childhood Depression Rating Scale–Revised (effect size, 0.78) but not on the Clinical Global Impression Improvement treatment response (76% and 67%, respectively; relative risk, 1.08). There was an overall decrease in self-reported substance use (4.31 days; 95% confidence interval, 2.12-6.50) and CD symptoms (relative risk, 1.20; 95% confidence interval, 0.82-1.59), but neither difference between groups was statistically significant. The proportion of substance-free weekly urine screen results was higher in the placebo-CBT group than in the fluoxetine-CBT group (mean difference, 2.10; 95% confidence interval, 0.37-4.15). Conclusions Fluoxetine and CBT had greater efficacy than did placebo and CBT on one but not both depression measures and was not associated with greater decline in self-reported substance use or CD symptoms. The CBT may have contributed to higher-than-expected treatment response and mixed efficacy findings, despite its focus on SUD.