Introduction to Helping to End Addiction Long-Term Prevention Cooperative: Overview and Strategies.

This supplemental issue describes the individual studies and collaborative efforts of the Helping to End Addiction Long-term Prevention Cooperative's (HPC's) innovative approaches to rapidly develop evidence-based prevention programs for widespread dissemination. This introduction succinctly reviews (1) the context that demands the rapid development of efficacious prevention programs and their scale-ups, (2) the unique objectives of the individual HPC research projects, and (3) collective efforts to harmonize research across studies to advance the prevention of opioid misuse and gain insight into opioid misuse etiology to inform improvements in preventive interventions. At the conclusion of HPC studies, we anticipate the availability of multiple evidence-based programs to prevent opioid misuse and use disorder for persons who experience particular sources of risk and for delivery in settings where prevention has traditionally been lacking. By harmonizing and coordinating efforts across 10 distinct outcomes studies of prevention programs and making data available for analysis by non-HPC researchers, the HPC's efficacy and etiology evidence will far surpass the additive contributions of 10 individual research projects.

Multidisciplinary Strategies for Preventing Opioid Misuse and Escalation by Targeting Mental Health Symptoms and Conditions.

We aim to review the association between childhood-onset mental health conditions and increased risk for early substance use including opioid misuse and opioid use disorders (OUD). The association between mental health conditions and opioid misuse suggests youth with mental health conditions may benefit from opioid prevention efforts that concurrently address mental health. To aid in the identification of youth with mental health conditions who could benefit from interventions, we will review opportunities and challenges associated with screening for mental health symptoms or substance use in settings where youth at high risk for mental health conditions present. We will also review how research projects within the National Institutes of Health's Helping to End Addiction Long-term (HEAL) Prevention Cooperative are addressing mental health within opioid misuse and OUD prevention interventions for youth.

Methodological Strategies for Prospective Harmonization of Studies: Application to 10 Distinct Outcomes Studies of Preventive Interventions Targeting Opioid Misuse.

The Helping to End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is rapidly developing 10 distinct evidence-based interventions for implementation in a variety of settings to prevent opioid misuse and opioid use disorder. One HPC objective is to compare intervention impacts on opioid misuse initiation, escalation, severity, and disorder and identify whether any HPC interventions are more effective than others for types of individuals. It provides a rare opportunity to prospectively harmonize measures across distinct outcomes studies. This paper describes the needs, opportunities, strategies, and processes that were used to harmonize HPC data. They are illustrated with a strategy to measure opioid use that spans the spectrum of opioid use experiences (termed involvement) and is composed of common "anchor items" ranging from initiation to symptoms of opioid use disorder. The limitations and opportunities anticipated from this approach to data harmonization are reviewed. Lastly, implications for future research cooperatives and the broader HEAL data ecosystem are discussed.

Power analysis for idiographic (within-subject) clinical trials: Implications for treatments of rare conditions and precision medicine.

Power analysis informs a priori planning of behavioral and medical research, including for randomized clinical trials that are nomothetic (i.e., studies designed to infer results to the general population based on interindividual variabilities). Far fewer investigations and resources are available for power analysis of clinical trials that follow an idiographic approach, which emphasizes intraindividual variabilities between baseline (control) phase versus one or more treatment phases. We tested the impact on statistical power to detect treatment outcomes of four idiographic trial design factors that are under researchers' control, assuming a multiple baseline design: sample size, number of observations per participant, proportion of observations in the baseline phase, and competing statistical models (i.e., hierarchical modeling versus piecewise regression). We also tested the impact of four factors that are largely outside of researchers' control: population size, proportion of intraindividual variability due to residual error, treatment effect size, and form of outcomes during the treatment phase (phase jump versus gradual change). Monte Carlo simulations using all combinations of the factors were sampled with replacement from finite populations of 200, 1750, and 3500 participants. Analyses characterized the unique relative impact of each factor individually and all two-factor combinations, holding all others constant. Each factor impacted power, with the greatest impact being from larger treatment effect sizes, followed respectively by more observations per participant, larger samples, less residual variance, and the unexpected improvement in power associated with assigning closer to 50% of observations to the baseline phase. This study's techniques and R package better enable a priori rigorous design of idiographic clinical trials for rare diseases, precision medicine, and other small-sample studies.

Neuropsychiatric features of Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypotonia and poor feeding in infancy which progresses to hyperphagia in early-mid childhood, as well as developmental delays, a spectrum of behavioral and psychiatric concerns, endocrinopathies, orthopedic issues, and less commonly, seizures, sleep apnea, and narcolepsy with or without cataplexy. This study used data in the Global PWS Registry (N = 893) to explore the onset and severity over time of the neuropsychiatric features reported in individuals with PWS and explored its associations with sleep disorders, seizures, and psychiatric symptoms. Results demonstrate that seizures are more common in the deletion subtype and that narcolepsy and cataplexy are more common in individuals who have sleep-related seizures. Finally, this work shows that anxiety and compulsive behaviors are persistent features of PWS that may arise early in childhood, and that anxiety is associated with higher frequency of other comorbid psychiatric diagnoses. In conclusion, this study is one of the largest to date characterizing sleep disorders and neuropsychiatric characteristics of individuals with PWS and reports on the novel association between sleep disorders and seizures. This study is also one of the first to offer details on the nature of the progression of these features in individuals with PWS.

Addressing Barriers to Primary Care Screening and Referral to Prevention for Youth Risky Health Behaviors: Evidence Regarding Potential Cost-Savings and Provider Concerns.

Despite growing evidence and support for co-locating behavioral services in primary care to prevent risky health behaviors, implementation of these services has been limited due to a lack of reimbursement for services and negative perceptions among providers. We investigated potential to overcome these barriers based on new developments in healthcare funding and screening and referral to prevention (SRP) in primary care based on the Consolidated Framework for Implementation Research (CFIR), which could guide future SRP implementation strategies. To investigate the economic need for healthcare-based SRP, we quantified hospital charges to healthcare payors for services arising from adolescent risky behaviors (e.g., substance use, risky sex). Annual North Carolina (NC) hospital charges for these services exceeded $327 M (2019 dollars), suggesting high potential for cost savings if SRP can curb hospital services associated with risky behaviors. To investigate provider barriers and facilitators, we surveyed 151 NC pediatricians and 230 NC family therapists about their attitudes regarding a recently developed well-child visit SRP with family-based prevention. Both sets of professionals reported widespread need for and interest in the SRP but cited barriers of lack of reimbursement, training, and referrals to/from each other. Physicians, but not family therapists, reported concerns with poor patient or parent compliance. Many barriers could be resolved by co-locating family therapists in pediatric clinics to conduct well-child SRP. Our results support further research to develop business models for payor-funded SRP and CFIR-guided research to develop implementation strategies for primary care SRP to prevent adolescent risky health behaviors.

Association With Deviant Peers Across Adolescence: Subtypes, Developmental Patterns, and Long-Term Outcomes.

Indices of deviant peer group involvement are inconsistent and confound type, frequency, and severity of deviant peer behaviors. These measurement approaches thus obfuscate potential meaningful differences in deviant peer involvement in terms of subtypes, developmental patterns, and long-term outcomes. The current study employed latent class analysis to derive subtypes of deviant peer involvement and examined relations to substance use disorder in adulthood, a common outcome of deviant peer involvement. Youth (76% Caucasian) completed assessments across four time points: ages 10-12 years (Time 1; N = 775, 71% male), 12-14 years (Time 2; n = 649, 72% male), 16 years (Time 3; n = 613, 73% male), and 22 years (Time 4; n = 425, 71% male). At Times 1 to 3, participants completed an interview assessing deviant peer involvement. At Time 4, participants completed a structured interview assessing substance use disorder. Classes of youth with different profiles of deviant peer associations were derived at Times 1, 2, and 3. Classes varied by type (conduct problems vs. substance use) and severity of deviant peer behavior. Youth reported higher levels of involvement with deviant peers across adolescence, suggesting that some of these deviant peer behaviors may be normative. Earlier involvement with deviant peers and involvement with groups defined by severe conduct problems and substance use were related to the greatest risk for substance use disorder at Time 4. Type and severity of peer deviant behavior differentially relate to long-term risk for substance use disorder and should be included in screening and assessment for risk across adolescence.

Residential Transience Among Adults: Prevalence, Characteristics, and Association with Mental Illness and Mental Health Service Use.

This study examined the association between frequent residential mobility (i.e., residential transience) and mental illness, mental health service use, and unmet need for services. Data are from the 2010 to 2014 National Surveys on Drug Use and Health (n = ~ 229,600). Logistic regression models examined the relationship between proximal (past year) and distal (past 2-5 years) residential transience and past year any mental illness (AMI), serious mental illness (SMI), mental health service use among adults with mental illness, and unmet need for services. Adults with transience had greater odds of AMI and SMI than those without transience. Proximal and distal transience were unrelated to past year mental health service use among adults with mental illness, but the odds of unmet need for services were greater among adults with transience compared with those without, suggesting a level of unmet service need among those with transience.

Clinically differentiating life-course-persistent and adolescence-limited conduct problems: Is age-of-onset really enough?

One important subtyping of behavior problems is Moffitt's (1993) "life-course-persistent" (LCP) and "adolescent limited" (AL) categories of antisocial behavior, which she differentiated in terms of high impulsivity, poor academic performance, and aggression. These problems may be exacerbated by the cumulative effects of chronic stress. Copious evidence has documented validity and developmental differences between these subtypes, whereas far fewer data exist regarding their clinical utility, in spite of the Diagnostic and Statistical Manual's nomenclature including corresponding subtypes based on age-of-onset of behavioral symptoms. The present study evaluated how well age-of-onset based subtyping identifies distinct developmental patterns of antisocial behavior corresponding to Moffitt's subtypes in terms of risk factors and gender between LCP and AL in a prospective sample of chronically stressed youth. A computerized assessment tool (ALEXSA©) was used to obtain data from 1,147 youth aged 8-16. Implications for clinical assessment and intervention strategy, particularly with stressed youth, are discussed.

Psychological dysregulation during adolescence mediates the association of parent-child attachment in childhood and substance use disorder in adulthood.

OBJECTIVE: This prospective study tested the hypothesis that psychological dysregulation in mid-adolescence (age 16) mediates the association between parent-child attachment in late childhood (age 10-12) and development of substance use disorder (SUD) in adulthood (age 22). METHOD: The Youth Attachment to Parents Scale (YAPS) was developed in 10-12-year-old boys and girls (N = 694) at baseline residing in western Pennsylvania. Psychological dysregulation was measured by the neurobehavior disinhibition trait. Substance use was assessed at ages 10-12, 12-14, 16 and 19. SUD was diagnosed at age 22 using the Structured Clinical Interview for DSM Disorders. The mediation of parent-child attachment and SUD by neurobehavior disinhibition was tested separately for mothers and fathers while controlling for baseline substance use. RESULTS: Psychological dysregulation mediates the association between attachment to mothers and SUD, and partially mediates the association between attachment to fathers and SUD. Significant mediation effects remains after controlling for baseline substance use. CONCLUSION: Optimal prevention of SUD should include ameliorating both psychological dysregulation predisposing to SUD and quality of the parent-child relationship.

Toward rigorous idiographic research in prevention science: comparison between three analytic strategies for testing preventive intervention in very small samples.

Psychosocial prevention research lacks evidence from intensive within-person lines of research to understand idiographic processes related to development and response to intervention. Such data could be used to fill gaps in the literature and expand the study design options for prevention researchers, including lower-cost yet rigorous studies (e.g., for program evaluations), pilot studies, designs to test programs for low prevalence outcomes, selective/indicated/adaptive intervention research, and understanding of differential response to programs. This study compared three competing analytic strategies designed for this type of research: autoregressive moving average, mixed model trajectory analysis, and P-technique. Illustrative time series data were from a pilot study of an intervention for nursing home residents with diabetes (N = 4) designed to improve control of blood glucose. A within-person, intermittent baseline design was used. Intervention effects were detected using each strategy for the aggregated sample and for individual patients. The P-technique model most closely replicated observed glucose levels. ARIMA and P-technique models were most similar in terms of estimated intervention effects and modeled glucose levels. However, ARIMA and P-technique also were more sensitive to missing data, outliers and number of observations. Statistical testing suggested that results generalize both to other persons as well as to idiographic, longitudinal processes. This study demonstrated the potential contributions of idiographic research in prevention science as well as the need for simulation studies to delineate the research circumstances when each analytic approach is optimal for deriving the correct parameter estimates.

High and low neurobehavior disinhibition clusters within locales: implications for community efforts to prevent substance use disorder.

BACKGROUND: Knowledge of where substance use and other such behavioral problems frequently occur has aided policing, public health, and urban planning strategies to reduce such behaviors. Identifying locales characterized by high childhood neurobehavioral disinhibition (ND), a strong predictor of substance use and consequent disorder (SUD), may likewise improve prevention efforts. OBJECTIVES: The distribution of ND in 10-12-year olds was mapped to metropolitan Pittsburgh, PA, and tested for clustering within locales. METHODS: The 738 participating families represented the population in terms of economic status, race, and population distribution. ND was measured using indicators of executive cognitive function, emotion regulation, and behavior control. Innovative geospatial analyzes statistically tested clustering of ND within locales while accounting for geographic barriers (large rivers, major highways), parental SUD severity, and neighborhood quality. RESULTS: Clustering of youth with high and low ND occurred in specific locales. Accounting for geographic barriers better delineated where high ND is concentrated, areas which also tended to be characterized by greater parental SUD severity and poorer neighborhood quality. CONCLUSIONS AND SIGNIFICANCE: Offering programs that have been demonstrated to improve inhibitory control in locales where youth have high ND on average may reduce youth risk for SUD and other problem behaviors. As demonstrated by the present results, geospatial analysis of youth risk factors, frequently used in community coalition strategies, may be improved with greater statistical and measurement rigor.

Feasibility of combining biosensor and ecological momentary assessment to measure stress experiences among economically disadvantaged adolescents.

Adolescent stress is complex and impairing. Novel measures are needed to understand stress variability within individuals over time from a physiological as well as a subjective perspective. To test the feasibility of combining ecological momentary assessment (EMA) and wearable biosensors to assess adolescent stress, using an idiographic approach with experience sampling methods. A small sample (n = 23) of predominantly African American, economically disadvantaged adolescents were asked to complete EMA surveys four times per day and wear an armband measuring Heart rate (HR) and skin response for a 2-week period. Descriptive analyses examined number of hours of armband wear, percentage of viable data, and percentage of surveys completed by gender and race. Associations between biosensor data and EMA reports within and across individuals were also examined using hierarchical linear regression. EMA survey completion was good (81%) as was adherence to biosensor protocols, although technological difficulties interfered with collection of HR variability for youth with darker skin tones. Youth reported stressful events in 12.79% of EMA surveys, although 43% reported no negative mood experiences. Convergent validity was supported for detecting between-person (EMA) and within-person (EMA and biosensors) variability in stress across time, although associations across youth were highly variable. Results suggest value for biobehavioral methods in understanding day-to-day stress in adolescents but highlight variability in stress experiences as well as technological limitations, especially for youth of colour.

Substance Use Screening and Prevention for Adolescents in Pediatric Primary Care: A Randomized Clinical Trial using the Family Check-Up.

This study evaluated acceptability, engagement in prevention, and efficacy of a primary care screening-and-referral-to-prevention program to reduce substance use in early adolescence. Screening tools were the Youth Risk Index and Transmissible Liability Index and prevention consisted of the Family Check-Up (FCU). Three hundred sixty-one 10- to 13-year-olds from low resource neighborhoods (85.9% African American; 52.4% female) screened "at risk" during primary care visits and were randomized to the FCU (n = 123) or usual care (n = 238). Screening was acceptable to parents and youths: nearly 95% of each rated it as important, about 90% of each were happy with or did not mind it, and only 2.4% of parents did not want their child to be screened at their next check-up. Of parents who had a chance to receive the FCU (or waitlist-control), 87.5% followed through with researchers while 93.5% who were offered FCU engaged in it. FCU efficacy primarily involved interactions such that youth with greater risk at baseline experienced larger benefits. At 12-month follow-up, FCU was associated with 11% reduced risk of initiating a new substance per substance that had been initiated before baseline; greater reductions in tolerance of deviance among those with higher tolerance of deviance at baseline; and a main effect of reduced anxiety, but no effect for conduct problems. Pediatric well-child check-up screening can identify high-risk youth before, or in the initial stages of, problematic SU; engage families in a preventive intervention; and reduce rates of substance use and related risk factors.

Resilience-Informed Community Violence Prevention and Community Organizing Strategies for Implementation: Protocol for a Hybrid Type 1 Implementation-Effectiveness Trial.

BACKGROUND: Community violence is a persistent and challenging public health problem. Community violence not only physically affects individuals, but also its effects reverberate to the well-being of families and entire communities. Being exposed to and experiencing violence are adverse community experiences that affect the well-being and health trajectories of both children and adults. In the United States, community violence has historically been addressed through a lens of law enforcement and policing; the impact of this approach on communities has been detrimental and often ignores the strengths and experiences of community members. As such, community-centered approaches to address violence are needed, yet the process to design, implement, and evaluate these approaches is complex. Alternatives to policing responses are increasingly being implemented. However, evidence and implementation guidance for community-level public health approaches remain limited. This study protocol seeks to address community violence through a resilience framework-Adverse Community Experiences and Resilience (ACE|R)-being implemented in a major US city and leveraging a strategy of community organizing to advance community violence prevention. OBJECTIVE: The objective of this research is to understand the impact of community-level violence prevention interventions. Furthermore, we aim to describe the strategies of implementation and identify barriers to and facilitators of the approach. METHODS: This study uses a hybrid type 1 effectiveness-implementation design. Part 1 of the study will assess the effectiveness of the ACE|R framework plus community organizing by measuring impacts on violence- and health-related outcomes. To do so, we plan to collect quantitative data on homicides, fatal and nonfatal shootings, hospital visits due to nonaccidental injuries, calls for service, and other violence-related data. In Part 2 of the study, to assess the implementation of ACE|R plus community organizing, we will collect process data on community engagement events, deliver community trainings on community leadership and organizing, and conduct focus groups with key partners about violence and violence prevention programs in Milwaukee. RESULTS: This project received funding on September 1, 2020. Prospective study data collection began in the fall of 2021 and will continue through the end of 2023. Data analysis is currently underway, and the first results are expected to be submitted for publication in 2024. CONCLUSIONS: Community violence is a public health problem in need of community-centered solutions. Interventions that center community and leverage community organizing show promise in decreasing violence and increasing the well-being of community members. Methods to identify the impact of community-level interventions continue to evolve. Analysis of outcomes beyond violence-specific outcomes, including norms and community beliefs, may help better inform the short-term and proximal impacts of these community-driven approaches. Furthermore, hybrid implementation-effectiveness trials allow for the inevitable contextualization required to disseminate community interventions where communities drive the adaptations and decision-making. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50444.

Mentoring early-career preventionists: current views from mentors and protégés.

In prevention science, much of the training occurs outside of a formal graduate program and mentorship is invaluable to early-career individuals. A sample of the Society for Prevention Research (SPR) membership (N = 97) from a wide range of career levels completed an online questionnaire in spring 2010. Almost 20% identified as mentors, 32% as protégés, and 49% as both a mentor and a protégé. Most mentoring relationships were established in graduate school, but professional organizations such as SPR facilitated nearly one in five mentoring relationships. Qualitative results suggested that participants value their professional organization's support of mentoring and would support initiatives to increase mentoring relationships specifically among SPR members. Although all mentor functions and protégé responsibilities were rated as important, professional support was the highest ranked mentor function and taking initiative the highest ranked protégé responsibility. Additionally, the qualitative results revealed that interpersonal skills and commitment to the mentoring process were seen as key to positive mentoring relationships. We also found that formal documentation of mentoring agreements was rare and a slight preference for a match on gender or ethnicity was observed for protégés from nondominant groups. The discussion includes implications for individuals and implications for promoting high-quality mentoring within professional organizations.

Co-occurrence of Psychopathology Problems in At-Risk Adolescents.

No known studies have investigated co-occurrence of psychopathology problems in adolescents with biologic and/or environmental susceptibility, including prenatal drug exposure. This study identified comorbidity patterns of psychopathology problems by utilizing data from urban, primarily African American, youth, majority of whom were at heightened risk for exposure to drugs in utero. The roles of Research Domain Criteria (RDoC)-informed behavioral constructs of the Negative Valence (irritability) and Social Process Systems (social disinhibition) as antecedents of the comorbidity patterns were further examined. Lastly, the predictive validity of the identified patterns was evaluated in relation to emerging adulthood outcomes. Participants were 358 urban adolescents, primarily African Americans, drawn from a 21-year prospective birth-cohort study of the effects of prenatal drug exposure. Psychopathology problems were assessed at age 15. Irritability and social disinhibition were self-reported at age 12. Emerging adulthood outcomes were measured at age 21. Latent class modeling indicated four patterns: Normative (57%), substance-use (SU; 24%), mental-health-problems-without-substance-use (MH; 11%), and substance-use-and-other-mental-health-problems (SUMH; 7%). Higher irritability increased the odds of developing the MH pattern, whereas higher social disinhibition increased the odds of developing the SU pattern. The odds of manifesting the SUMH pattern were higher for children with higher irritability. For children with higher social disinhibition, the odds of manifesting the SUMH pattern were higher at a trend level. Adolescent comorbidity patterns were differentially associated with problematic tobacco and marijuana use and clinically relevant mental health problems in emerging adulthood, and completion of high school education. Peri-pubertal identification of individual differences in irritability and social disinhibition may mitigate the emergence of adolescent psychopathology, which could influence emerging adulthood adjustment in this at-risk population.

Racial Discrimination Experienced by Black Parents: Enduring Mental Health Consequences for Adolescent Youth.

OBJECTIVE: Despite evidence linking experiences of racial discrimination by Black parents and problem behaviors in youth, little is known about the mechanisms that explain this link. To elucidate these developmental pathways, a serial mediation model was tested, in which Black parents' experiences of racial discrimination were hypothesized to predict increased parental depression and parent-child conflict in early adolescence, which in turn would be associated with youth depression, anxiety, and conduct problems in early to mid-adolescence. METHOD: Participants were 252 Black parent-child dyads. Youth (56% female) were on average 11.98 years old at study entry (wave 1). Parents and youth completed questionnaires during a home-based assessment at wave 1 and were assessed again 1 and 2 years later (waves 2 and 3). RESULTS: Black parents' experiences of racial discrimination at wave 1 were linked to higher levels of parent-child conflict at wave 2 (0.20; 95% CI [0.05, 0.33]), which in turn predicted greater youth-reported depression at wave 3 (0.30; 95% CI [0.15, 0.47]). There was a significant indirect effect of racial discrimination on youth-reported depression via parent-child conflict (indirect effect: 0.06, 95% CI [0.02, 0.10]). Findings were replicated across multiple outcomes (ie, depression, anxiety, conduct problems) and multiple informants (ie, youth report, parent report). There was no evidence to support a serial mediation model via parental depression and then parent-child conflict. CONCLUSION: This study identified a developmental pathway from Black parents' experiences of racial discrimination to adolescent problem behaviors via parent-child conflict. Findings may inform interventions aimed at promoting resilience in parents and youth faced with pervasive racism. CLINICAL TRIAL REGISTRATION INFORMATION: Substance Use Screening and Prevention for Adolescents in Pediatric Primary Care (SKY); https://clinicaltrials.gov/; NCT03074877.

Directionality Between Tolerance of Deviance and Deviant Behavior is Age-Moderated in Chronically Stressed Youth.

Problem behavior theory posits that tolerance of deviance is an antecedent to antisocial behavior and substance use. In contrast, cognitive dissonance theory implies that acceptability of a behavior may increase after experiencing the behavior. Using structural equation modeling, this investigation tested whether changes in tolerance of deviance precede changes in conduct disorder criteria or substance use or vice versa, or if they change concomitantly. Two-year longitudinal data from 246 8- to 16-year-olds suggested that tolerance of deviance increases after conduct disorder criteria or substance use in 8-to-10- and 11-to-12-year-olds. These results were consistent with cognitive dissonance theory. In 13-to-16- year-olds, no directionality was suggested, consistent with neither theory. These results were replicated in boys and girls and for different types of conduct disorder criteria aggression (covert behavior), deceitfulness and vandalism (overt behavior), and serious rule-breaking (authority conflict). The age-specific directionality between tolerance of deviance and conduct disorder criteria or substance use is consistent with unique etiologies between early onset versus adolescent-onset subtypes of behavior problems.