Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life.

The broadly neutralizing antibody (bNAb) CAP256-VRC26.25 has exceptional potency against HIV-1 and has been considered for clinical use. During the characterization and production of this bNAb, we observed several unusual features. First, the antibody appeared to adhere to pipette tips, requiring tips to be changed during serial dilution to accurately measure potency. Second, during production scale-up, proteolytic cleavage was discovered to target an extended heavy chain loop, which was attributed to a protease in spent medium from 2-week culture. To enable large scale production, we altered the site of cleavage via a single amino acid change, K100mA. The resultant antibody retained potency and breadth while avoiding protease cleavage. We also added the half-life extending mutation LS, which improved the in vivo persistence in animal models, but did not impact neutralization activity; we observed the same preservation of neutralization for bNAbs VRC01, N6, and PGDM1400 with LS on a 208-virus panel. The final engineered antibody, CAP256V2LS, retained the extraordinary neutralization potency of the parental antibody, had a favorable pharmacokinetic profile in animal models, and was negative in in vitro assessment of autoreactivity. CAP256V2LS has the requisite potency, developability and suitability for scale-up, allowing its advancement as a clinical candidate.

Safety, tolerability, and immunogenicity of the respiratory syncytial virus prefusion F subunit vaccine DS-Cav1: a phase 1, randomised, open-label, dose-escalation clinical trial.

BACKGROUND: Multiple active vaccination approaches have proven ineffective in reducing the substantial morbidity and mortality caused by respiratory syncytial virus (RSV) in infants and older adults (aged ≥65 years). A vaccine conferring a substantial and sustainable boost in neutralising activity is required to protect against severe RSV disease. To that end, we evaluated the safety and immunogenicity of DS-Cav1, a prefusion F subunit vaccine. METHODS: In this randomised, open-label, phase 1 clinical trial, the stabilised prefusion F vaccine DS-Cav1 was evaluated for dose, safety, tolerability, and immunogenicity in healthy adults aged 18-50 years at a single US site. Participants were assigned to receive escalating doses of either 50 µg, 150 µg, or 500 µg DS-Cav1 at weeks 0 and 12, and were randomly allocated in a 1:1 ratio within each dose group to receive the vaccine with or without aluminium hydroxide (AlOH) adjuvant. After 71 participants had been randomised, the protocol was amended to allow some participants to receive a single vaccination at week 0. The primary objectives evaluated the safety and tolerability at every dose within 28 days following each injection. Neutralising activity and RSV F-binding antibodies were evaluated from week 0 to week 44 as secondary and exploratory objectives. Safety was assessed in all participants who received at least one vaccine dose; secondary and exploratory immunogenicity analysis included all participants with available data at a given visit. The trial is registered with ClinicalTrials.gov, NCT03049488, and is complete and no longer recruiting. FINDINGS: Between Feb 21, 2017, and Nov 29, 2018, 244 participants were screened for eligibility and 95 were enrolled to receive DS-Cav1 at the 50 µg (n=30, of which n=15 with AlOH), 150 µg (n=35, of which n=15 with AlOH), or 500 µg (n=30, of which n=15 with AlOH) doses. DS-Cav1 was safe and well tolerated and no serious vaccine-associated adverse events deemed related to the vaccine were identified. DS-Cav1 vaccination elicited robust neutralising activity and binding antibodies by 4 weeks after a single vaccination (p<0·0001 for F-binding and neutralising antibodies). In analyses of exploratory endpoints at week 44, pre-F-binding IgG and neutralising activity were significantly increased compared with baseline in all groups. At week 44, RSV A neutralising activity was 3·1 fold above baseline in the 50 µg group, 3·8 fold in the 150 µg group, and 4·5 fold in the 500 µg group (p<0·0001). RSV B neutralising activity was 2·8 fold above baseline in the 50 µg group, 3·4 fold in the 150 µg group, and 3·7 fold in the 500 µg group (p<0·0001). Pre-F-binding IgG remained significantly 3·2 fold above baseline in the 50 µg group, 3·4 fold in the 150 µg group, and 4·0 fold in the 500 µg group (p<0·0001). Pre-F-binding serum IgA remained 4·1 fold above baseline in the 50 µg group, 4·3 fold in the 150 µg group, and 4·8 fold in the 500 µg group (p<0·0001). Although a higher vaccine dose or second immunisation elicited a transient advantage compared with lower doses or a single immunisation, neither significantly impacted long-term neutralisation. There was no long-term effect of dose, number of vaccinations, or adjuvant on neutralising activity. INTERPRETATION: In this phase 1 study, DS-Cav1 vaccination was safe and well tolerated. DS-Cav1 vaccination elicited a robust boost in RSV F-specific antibodies and neutralising activity that was sustained above baseline for at least 44 weeks. A single low-dose of pre-F immunisation of antigen-experienced individuals might confer protection that extends throughout an entire RSV season. FUNDING: The National Institutes of Allergy and Infectious Diseases.

A proof of concept for structure-based vaccine design targeting RSV in humans.

Technologies that define the atomic-level structure of neutralization-sensitive epitopes on viral surface proteins are transforming vaccinology and guiding new vaccine development approaches. Previously, iterative rounds of protein engineering were performed to preserve the prefusion conformation of the respiratory syncytial virus (RSV) fusion (F) glycoprotein, resulting in a stabilized subunit vaccine candidate (DS-Cav1), which showed promising results in mice and macaques. Here, phase I human immunogenicity data reveal a more than 10-fold boost in neutralizing activity in serum from antibodies targeting prefusion-specific surfaces of RSV F. These findings represent a clinical proof of concept for structure-based vaccine design, suggest that development of a successful RSV vaccine will be feasible, and portend an era of precision vaccinology.

Trauma, Family Factors and the Mental Health of Homeless Adolescents.

Family factors, such as poor family functioning and trauma, have been associated with negative outcomes for homeless adolescents. Further study is needed to better understand how family factors and trauma jointly relate to mental health problems and externalizing behaviors among homeless adolescents. Structural equation modeling was used to examine the influence of trauma (encompassing traumatic events experienced prior to, and after, becoming homeless) and family factors (poor family functioning and family conflict) on mental health problems and externalizing behaviors (substance use, delinquent behaviors, and sexual risk) among 201 homeless adolescents, ages 12 to 17 years. Trauma, poor family functioning, and family conflict significantly predicted greater mental health problems, delinquent behaviors, high-risk sexual behaviors and substance use. Overall, the findings suggest that family factors appear to be key to understanding mental health problems and externalizing behaviors among homeless adolescents. Implications, limitations and future directions are addressed.

Developing Valid Measures of Emergency Management Capabilities within US Department of Veterans Affairs Hospitals.

UNLABELLED: Introduction Hospitals play a critical role in providing health care in the aftermath of disasters and emergencies. Nonetheless, while multiple tools exist to assess hospital disaster preparedness, existing instruments have not been tested adequately for validity. Hypothesis/Problem This study reports on the development of a preparedness assessment tool for hospitals that are part of the US Department of Veterans Affairs (VA; Washington, DC USA). METHODS: The authors evaluated hospital preparedness in six "Mission Areas" (MAs: Program Management; Incident Management; Safety and Security; Resiliency and Continuity; Medical Surge; and Support to External Requirements), each composed of various observable hospital preparedness capabilities, among 140 VA Medical Centers (VAMCs). This paper reports on two successive assessments (Phase I and Phase II) to assess the MAs' construct validity, or the degree to which component capabilities relate to one another to represent the associated domain successfully. This report describes a two-stage confirmatory factor analysis (CFA) of candidate items for a comprehensive survey implemented to assess emergency preparedness in a hospital setting. RESULTS: The individual CFAs by MA received acceptable fit statistics with some exceptions. Some individual items did not have adequate factor loadings within their hypothesized factor (or MA) and were dropped from the analyses in order to obtain acceptable fit statistics. The Phase II modified tool was better able to assess the pre-determined MAs. For each MA, except for Resiliency and Continuity (MA 4), the CFA confirmed one latent variable. In Phase I, two sub-scales (seven and nine items in each respective sub-scale) and in Phase II, three sub-scales (eight, four, and eight items in each respective sub-scale) were confirmed for MA 4. The MA 4 capabilities comprise multiple sub-domains, and future assessment protocols should consider re-classifying MA 4 into three distinct MAs. CONCLUSION: The assessments provide a comprehensive and consistent, but flexible, approach for ascertaining health system preparedness. This approach can provide an organization with a clear understanding of areas for improvement and could be adapted into a standard for hospital readiness. Dobalian A , Stein JA , Radcliff TA , Riopelle D , Brewster P , Hagigi F , Der-Martirosian C . Developing valid measures of emergency management capabilities within US Department of Veterans Affairs hospitals. Prehosp Disaster Med. 2016;31(5):475-484.

AMP!: A Cross-site Analysis of the Effects of a Theater-based Intervention on Adolescent Awareness, Attitudes, and Knowledge about HIV.

AMP! (Arts-based, Multiple component, Peer-education) is an HIV intervention developed for high school adolescents. AMP! uses interactive theater-based scenarios developed by trained college undergraduates to deliver messages addressing HIV/STI prevention strategies, healthy relationships, and stigma reduction towards people living with HIV/AIDS. We used a pre-test/post-test, control group study design to simultaneously assess intervention effect on ninth grade students in an urban county in California (N = 159) and a suburban county in North Carolina (N = 317). In each location, the control group received standard health education curricula delivered by teachers; the intervention group received AMP! in addition to standard health education curricula. Structural equation modeling was used to determine intervention effects. The post-test sample was 46 % male, 90 % self-identified as heterosexual, 32 % reported receiving free or reduced lunch, and 49 % White. Structural models indicated that participation in AMP! predicted higher scores on HIV knowledge (p = 0.05), HIV awareness (p = 0.01), and HIV attitudes (p = 0.05) at the post-test. Latent means comparison analyses revealed post-test scores were significantly higher than pre-test scores on HIV knowledge (p = 0.001), HIV awareness (p = 0.001), and HIV attitudes (p = 0.001). Further analyses indicated that scores rose for both groups, but the post-test scores of intervention participants were significantly higher than controls (HIV knowledge (p = 0.01), HIV awareness (p = 0.01), and HIV attitudes (p = 0.05)). Thus, AMP!'s theater-based approach shows promise for addressing multiple adolescent risk factors and attitudes concerning HIV in school settings.

Depression, Abuse, Relationship Power and Condom Use by Pregnant and Postpartum Women with Substance Abuse History.

Substance-abusing pregnant and postpartum women are less likely to maintain consistent condom use and drug and alcohol abstinence, which is particularly concerning in high HIV-prevalence areas. Data from 224 pregnant and postpartum women in substance abuse treatment were analyzed to examine effects of history of substance use, child abuse, and mental health problems on current substance use and condom-use barriers. Mediators were depression, relationship power and social support. Most participants (72.9 %) evidenced current depression. Less social support (-0.17, p < 0.05) and relationship power (-0.48, p < 0.001), and greater depression (-0.16, p < 0.05) predicted more condom-use barriers. History of mental health problems predicted condom-use barriers, mediated by recent depression and relationship power (0.15, p < 0.001). These findings suggest depression and diminished relationship power limit highest-risk women's ability to negotiate condom use and abstain from substance use, increasing their risk of acute HIV infection and vertical transmission.

Alcohol Use, Partner Violence, and Depression: A Cluster Randomized Controlled Trial Among Urban South African Mothers Over 3 Years.

INTRODUCTION: Pregnant South African women with histories of drinking alcohol, abuse by violent partners, depression, and living with HIV are likely to have their post-birth trajectories over 36 months significantly influenced by these risks. DESIGN: All pregnant women in 24 Cape Town neighborhoods were recruited into a cluster RCT by neighborhood to either: (1) a standard care condition (n=12 neighborhoods, n=594 mothers); or (2) a home-visiting intervention condition (n=12 neighborhoods, n=644 mothers). SETTING/PARTICIPANTS: Pregnant women residing in urban, low-income neighborhoods in Cape Town, South Africa. INTERVENTION: Home visiting included prenatal and postnatal visits by community health workers (Mentor Mothers) focusing on general maternal and child health, HIV/tuberculosis, alcohol use, and nutrition. MAIN OUTCOME MEASURES: Mothers were assessed in pregnancy and at 18 and 36 months post birth: 80.6% of mothers completed all assessments between 2009 and 2014 and were included in these analyses performed in 2014. Longitudinal structural equation modeling examined alcohol use, partner violence, and depression at the baseline and 18-month interviews as predictors of maternal outcomes at 36 months post birth. RESULTS: Relative to standard care, intervention mothers were significantly less likely to report depressive symptoms and more positive quality of life at 36 months. Alcohol use was significantly related to use over time, but was also related to depression and HIV status at each assessment and partner violence at 36 months. CONCLUSIONS: Alcohol, partner violence, and depression are significantly related over time. A home-visiting intervention improved the emotional health of low-income mothers even when depression was not initially targeted.

Factors influencing readiness to deploy in disaster response: findings from a cross-sectional survey of the Department of Veterans Affairs Disaster Emergency Medical Personnel System.

BACKGROUND: The Disaster Emergency Medical Personnel System (DEMPS) program provides a system of volunteers whereby active or retired Department of Veterans Affairs (VA) personnel can register to be deployed to support other VA facilities or the nation during national emergencies or disasters. Both early and ongoing volunteer training is required to participate. METHODS: This study aims to identify factors that impact willingness to deploy in the event of an emergency. This analysis was based on responses from 2,385 survey respondents (response rate, 29%). Latent variable path models were developed and tested using the EQS structural equations modeling program. Background demographic variables of education, age, minority ethnicity, and female gender were used as predictors of intervening latent variables of DEMPS Volunteer Experience, Positive Attitude about Training, and Stress. The model had acceptable fit statistics, and all three intermediate latent variables significantly predicted the outcome latent variable Readiness to Deploy. RESULTS: DEMPS Volunteer Experience and a Positive Attitude about Training were associated with Readiness to Deploy. Stress was associated with decreased Readiness to Deploy. Female gender was negatively correlated with Readiness to Deploy; however, there was an indirect relationship between female gender and Readiness to Deploy through Positive Attitude about Training. CONCLUSIONS: These findings suggest that volunteer emergency management response programs such as DEMPS should consider how best to address the factors that may make women less ready to deploy than men in order to ensure adequate gender representation among emergency responders. The findings underscore the importance of training opportunities to ensure that gender-sensitive support is a strong component of emergency response, and may apply to other emergency response programs such as the Medical Reserve Corps and the American Red Cross.

Intervening on conflict, parental bonds, and sexual risk acts among adolescent children of mothers living with HIV.

OBJECTIVE: In 1993-1994, a psychosocial intervention conducted in New York City significantly improved outcomes for parents living with HIV and their adolescent children over six years. We examine if the intervention benefits are similar for adolescents of mothers living with HIV (MLH) in 2004-2005 in Los Angeles when MLH's survival had increased substantially. METHODS: Adolescents of MLH in Los Angeles (N = 256) aged 12-20 years old were randomized with their MLH to either: 1) a standard care condition (n = 120 adolescent-MLH dyads); or 2) an intervention condition consisting of small group activities to build coping skills (n = 136 adolescent-MLH dyads, 78% attended the intervention). At 18 months, 94.7% of adolescents were reassessed. Longitudinal structural equation modeling examined if intervention participation impacted adolescents' relationships with parents and their sexual risk behaviors. RESULTS: Compared to the standard care, adolescents in the intervention condition reported significantly more positive family bonds 18 months later. Greater participation by MLH predicted fewer family conflicts, and was indirectly associated with less adolescent sexual risk behavior at the 18 month follow-up assessment. Anticipated developmental patterns were observed--sexual risk acts increased with age. Reports were also consistent with anticipated gender roles; girls reported better bonds with their mothers at 18 months, compared to boys. CONCLUSIONS: Adolescents of MLH have better bonds with their mothers as a function of participating in a coping skills intervention and reduced sexual risk-taking as a function of MLH intervention involvement.

Constructing and identifying predictors of frailty among homeless adults­a latent variable structural equations model approach.

Homeless urbanites are a heterogeneous population with unique health and social service needs. The study examined situational, behavioral, health-related and resource indicators in terms of their direct impact on frailty, hypothesized as a latent variable. Using structural equation modeling (SEM), a model was tested with 150 homeless men and women, ages 40­73, from three homeless day center drop-in sites on Skid Row and one residential drug treatment (RDT) facility that works with homeless parolees and probationers. In bivariate analyses with the latent construct frailty, months homeless (p < 0.01), female gender (p < 0.05), education (p < 0.05), comorbid conditions (p < 0.001), nutrition (p < 0.001), resilience (p < 0.001), health care utilization (p < 0.01), and falls (p < 0.001) were significantly associated with frailty. In the final path model, significant predictors of frailty included educational attainment (p < 0.01), comorbid conditions (p < 0.001), nutrition (p < 0.001), resilience (p < 0.001), and falls (p < 0.01). These findings will serve as a foundation for future nurse-led, community-based initiatives that focus on key predictors of frailty among the homeless and the development of interventions.

Increasing hepatitis C knowledge among homeless adults: results of a community-based, interdisciplinary intervention.

Homeless adults have high rates of hepatitis C virus infection (HCV) and low levels of HCV knowledge. This study reports results of an interdisciplinary, community-based intervention using stakeholder cooperation, case management, risk factor identification, and modification of dysfunctional psychosocial factors to increase HCV knowledge among homeless adults (N = 747). Data are from a randomized quasi-experimental study, with the major goal of evaluating the effectiveness of a Nurse Case Managed Intervention compared to a Standard Intervention, encouraging completion of a three-series hepatitis A/hepatitis B vaccination program. Increased HCV knowledge was measured with an 18-item questionnaire discerning risk factors for HCV and common misconceptions about individuals with HCV. A significant increase in HCV knowledge resulted regardless of intervention format. Receiving the Nurse Case Managed Intervention predicted greatest gain in HCV knowledge (p < 0.000). Successfully engaging key stakeholders, outreach workers, community organizations, and homeless people themselves proved most efficacious in increasing HCV knowledge.

Predictors of substance abuse treatment participation among homeless adults.

The current study focuses on the relationships among a trauma history, a substance use history, chronic homelessness, and the mediating role of recent emotional distress in predicting drug treatment participation among adult homeless people. We explored the predictors of participation in substance abuse treatment because enrolling and retaining clients in substance abuse treatment programs is always a challenge particularly among homeless people. Participants were 853 homeless adults from Los Angeles, California. Using structural equation models, findings indicated that trauma history, substance use history and chronicity of homelessness were associated, and were significant predictors of greater recent emotional distress. The most notable result was that recent emotional distress predicted less participation in current substance abuse treatment (both formal and self-help) whereas a substance use history alone predicted significantly more participation in treatment. Implications concerning treatment engagement and difficulties in obtaining appropriate dual-diagnosis services for homeless mentally distressed individuals are discussed.

Psychological health of military children: longitudinal evaluation of a family-centered prevention program to enhance family resilience.

Family-centered preventive interventions have been proposed as relevant to mitigating psychological health risk and promoting resilience in military families facing wartime deployment and reintegration. This study evaluates the impact of a family-centered prevention program, Families OverComing Under Stress Family Resilience Training (FOCUS), on the psychological adjustment of military children. Two primary goals include (1) understanding the relationships of distress among family members using a longitudinal path model to assess relations at the child and family level and (2) determining pathways of program impact on child adjustment. Multilevel data analysis using structural equation modeling was conducted with deidentified service delivery data from 280 families (505 children aged 3-17) in two follow-up assessments. Standardized measures included service member and civilian parental distress (Brief Symptom Inventory, PTSD Checklist-Military), child adjustment (Strengths and Difficulties Questionnaire), and family functioning (McMaster Family Assessment Device). Distress was significantly related among the service member parent, civilian parent, and children. FOCUS improved family functioning, which in turn significantly reduced child distress at follow-up. Salient components of improved family functioning in reducing child distress mirrored resilience processes targeted by FOCUS. These findings underscore the public health potential of family-centered prevention for military families and suggest areas for future research.

Remission from substance dependence: differences between individuals in a general population longitudinal survey who do and do not seek help.

BACKGROUND: Only a minority of individuals who have substance use disorders receives treatment, and those who do typically have more severe disorders. The current study examines the relationship of help-seeking with remission from alcohol and/or drug dependence and other outcomes. METHODS: Data from the Wave 1 (2001-2002) and Wave 2 (2004-2005) National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were used to examine remission at Wave 2 among respondents who had past-year substance dependence disorders at Wave 1 (N=1262). Multi-group structural equation modeling was used to compare individuals with (n=356) and without (n=906) prior help-seeking at Wave 1 on subsequent help-seeking and other factors that influence outcomes. RESULTS: Baseline help-seekers sought help at higher levels over the follow-up period (31% vs. 8%) and had lower rates of remission (50% vs. 68%), as compared with those without prior help-seeking, respectively. Among baseline help-seekers, there were stronger relationships between baseline stress and mental disorders and having sought help since baseline; age and past-year level of stress at follow-up; level of stress and health status at follow-up; and social support and mental disorders at follow-up. Among baseline non-help-seekers, there were stronger relationships between being female and past-year stress at follow-up, and between having sought help since baseline and physical health status at follow-up. CONCLUSIONS: Findings extend our understanding of the factors associated with recovery from substance dependence, including "natural recovery", use of services outside of addiction treatment, and gender differences in help-seeking and remission.

Depression, substance abuse and other contextual predictors of adherence to antiretroviral therapy (ART) among Haitians.

Haiti has the highest number of individuals living with HIV in the Caribbean. Due to Haiti's resource-poor environment and inadequate mental health and substance abuse services, adherence to antiretroviral therapy (ART) may be especially difficult. This study examined associations among demographics, maladaptive coping, partner conflict, alcohol problems, depression, and negative attitudes about medications and their impact on adherence among 194 HIV-positive Haitians. In a mediated directional structural equation model, depression and negative attitudes about ART directly predicted poorer adherence. Greater partner conflict, maladaptive coping and alcohol problems predicted more depression. Maladaptive coping predicted a negative attitude about ART. Alcohol problems predicted partner conflict and maladaptive coping. Significant indirect effects on adherence mediated through both depression and negative attitudes about ART include negative effects of female gender, alcohol problems and maladaptive coping. Results highlight the importance of integrated care for depression, alcohol use and other psychosocial problems to increase ART adherence.

Alcohol problems as a risk factor for postdisaster depressed mood among U.S. veterans.

Alcohol problems may impede adaptive, proactive responses to disaster-related injury and loss, thus prolonging the adverse impact of disasters on mental health. Previous work suggests that veterans of the U.S. armed forces have a relatively high prevalence of alcohol misuse and other psychiatric disorders. This is the first study to estimate the impact of predisaster alcohol problems on postdisaster depressed mood among veterans, using data that were collected before and after the 1994 Northridge, CA, earthquake. The authors assessed the impact of alcohol problems on postdisaster depressed mood in an existing clinical cohort of veterans who experienced the 6.7-magnitude earthquake that struck Northridge in January 1994. One to 3 months after the disaster, interviewers contacted participants by telephone to administer a follow-up questionnaire based on a survey that had been done preearthquake. Postearthquake data were obtained on 1,144 male veterans for whom there were preearthquake data. We tested a predictive path model of the relationships between latent variables for predisaster alcohol problems, functional limitations, and depressed mood on latent variables representing postdisaster "quake impact" and depressive mood. Results showed that veterans who had more alcohol problems before the earthquake experienced more earthquake-related harms and severely depressed mood after the earthquake, compared with those who had fewer alcohol problems. Programs serving veterans with a high prevalence of alcohol problems should consider designing disaster response protocols to locate and assist these patients in the aftermath of disasters.

The mediating roles of stress and maladaptive behaviors on self-harm and suicide attempts among runaway and homeless youth.

Runaway and homeless youth often have a constellation of background behavioral, emotional, and familial problems that contribute to stress and maladaptive behaviors, which, in turn, can lead to self-harming and suicidal behaviors. The current study examined the roles of stress and maladaptive behaviors as mediators between demographic and psychosocial background characteristics and self-injurious outcomes through the lens of the stress process paradigm. The model was tested in a sample of runaway and homeless youth from Los Angeles County (N = 474, age 12-24, 41 % female, 17 % White, 32.5 % African American, 21.5 % Hispanic/Latino). Background variables (gender, age, sexual minority status, parental drug use history, and emotional distress) predicted hypothesized mediators of maladaptive behaviors and recent stress. In turn, it was hypothesized that the mediators would predict self-harming behaviors and suicide attempts in the last 3 months. Females and LGBT (lesbian, gay, bisexual, transgender) youth were more likely to have self-harmed and attempted suicide; younger participants reported more self-harming. The mediating constructs were associated more highly with self-harming than suicide attempts bivariately, although differences were modest. Maladaptive behaviors and recent stress were significant predictors of self-harm, whereas only recent stress was a significant predictor of suicide attempts. All background factors were significant predictors of recent stress. Older age, a history of parental drug use, and greater emotional distress predicted problem drug use. Males, younger participants, and participants with emotional distress reported more delinquent behaviors. Significant indirect effects on self-harming behaviors were mediated through stress and maladaptive behaviors. The hypothesized paradigm was useful in explaining the associations among background factors and self-injurious outcomes and the influence of mediating factors on these associations.

Neurological function, information-motivation-behavioral skills factors, and risk behaviors among HIV-positive alcohol users.

The purpose of this study was to examine neurological impairment in combination with information-motivation-behavioral skills (IMB) variables. The study tests the role of IMB variables as mediators of antecedent variables of demographics, life stress, social support, and neurological impairment with outcome measures of HIV preventive and risk behaviors in a sample of HIV-positive, alcohol-using adults (n = 250) with a history of alcohol abuse/dependence. Neurological impairment was measured with the Color Trails Test (CTT). Average performance on the CTT by the sample was substantially worse than established norms. In a directional latent variable model, neurological impairment directly predicted lower transmission knowledge scores and poorer performance on an observational condom skills assessment. Greater neurological impairment was significantly associated with greater age. Future interventions geared toward HIV+ adults who use alcohol should take into consideration HIV-related and age-related neurological functioning which may impede the facilitation of safe sex behaviors.

Impact of Abstinence Self-Efficacy and Treatment Services on Physical Health-Related Behaviors and Problems among Dually Diagnosed Patients.

OBJECTIVE: Physical health problems are pervasive among patients with co-occurring substance use and mental disorders. Yet, drug treatment programs often ignore tobacco use and its association with health. Abstinence self-efficacy has been associated with improved outcomes for co-occurring disorders, which in turn may also impact physical health. This study had the goal of assessing whether abstinence self-efficacy for drugs and alcohol, and provision and use of services would influence tobacco use and other health-related outcomes among 351 individuals with co-occurring disorders in residential drug treatment. METHODS: Structural models tested the impact of baseline abstinence self-efficacy and treatment service characteristics on 6-month outcomes of health problems, functional limitations, health perceptions, and cigarette and heavy alcohol use. Demographics and baseline values for outcome variables were included as covariates. RESULTS: Correlations within time for poor health, cigarette use, and heavy alcohol use were substantial. A longer time in drug treatment was associated with less cigarette and heavy alcohol use at a 6-month follow-up. Baseline health problems were associated with more cigarette use and functional limitations at 6-months. Abstinence self-efficacy did not predict less cigarette use, but predicted less heavy alcohol use and fewer functional limitations. Availability of specialized dual-diagnosis groups and more on-site psychological services were not directly associated with outcomes, but had an impact through indirect effects on more psychological service utilization which predicted better subjective health. CONCLUSIONS: Improving overall treatment retention and services utilization among patients with co-occurring disorders may generalize to improved health perceptions, but specific health promotion and smoking-cessation interventions are warranted to improve health outcomes.