Future Directions in Clinical Trials and Intention-To-Treat Analysis: Fulfilling Admirable Intentions Through the Right Questions.

We call for clinical trials researchers to carefully consider questions about use of intention-to-treat (ITT) analysis and per protocol analysis. We discuss how questions about efficacy and mechanisms of efficacy are appropriately answered through the application of per protocol analysis. ITT analysis is well-suited and appropriate for addressing questions related to treatment effectiveness, typically adherence to the treatment with respect to an outcome. While guided by admirable intentions, ITT analysis is often not guided by the right questions, leading to ITT misapplication. We address additional misconceptions that often lead to ITT misapplication, including issues relating to treatment noncompletion and violation of random assignment. We further highlight future directions and implications, particularly that future clinical child and adolescent research trial designs will be increasingly characterized by hybrid trials that combine elements of efficacy, effectiveness, and implementation research, where ITT and per protocol analysis will be appropriately applied to answer the right questions.

Perceived Racial and Ethnic Discrimination, Depression, and Alcohol Use Intentions Among Inner-City Latinx Youth: Cross-Generational Effects.

Among the many social determinants linked to adolescent alcohol use and depression, racial and ethnic discrimination is a prevalent determinant among Latinx adolescents and adults that is largely overlooked in preventive interventions. This study explored the influence of perceived racial and ethnic discrimination on depressive symptoms and alcohol use intentions among Latinx adolescents. Additionally, the study explored the cross-generational effects of how mothers' perceived discrimination impacts the depressive symptoms and alcohol use of the adolescent. The study used a sample of 800 inner-city Dominican and Puerto Rican adolescent-mother dyads (adolescent mean age = 12.42 years, SD = 0.81; mother mean age = 40.55 years, SD = 8.70). Employing a five-wave panel design that followed adolescents from 8th grade to 10th grade, the study found statistically significant mediation pathways which showed that adolescents' self-reported racial and ethnic discrimination experiences were associated with increases in their immediate and long-term depressive symptoms, which in turn were associated with stronger intentions to use alcohol in the future. Further, perceived racial and ethnic discrimination experienced by Latinx mothers was associated with increases in adolescents' intentions to drink alcohol in the future, mediated by the mothers' depressive symptoms and subsequently the adolescents' depressive symptoms. As discussed, these findings have wide-ranging implications for alcohol use prevention programs targeting inner-city Latinx adolescents.

Early and recent military and nonmilitary stressors associated with posttraumatic stress symptoms among military service members and their spouses.

Disparities in posttraumatic stress symptoms (PTSS) have been observed among military service members (SMs) and spouses (SPs) compared to their civilian peers, but exposure to military stressors does not adequately explain observed differences. Using a stress process framework, this study considered the associations between early and recent military and nonmilitary stressors and PTSS among SMs and SPs. We analyzed data from 3,314 SM-SP dyads in the Millennium Cohort and Millennium Cohort Family Studies. Accounting for covariates, multiple linear regression and dominance analyses were employed to consider the effects of SM and SP childhood maltreatment, recent nonmilitary stressors (e.g., financial difficulties), and recent military stressors (e.g., deployment) on their own and their partner's self-reported PTSS. For both SMs and SPs, childhood maltreatment was the strongest predictor of their own PTSS, followed by nonmilitary stressors. Couple crossover dynamics were evident as SP maltreatment and nonmilitary stressors significantly predicted SM PTSS, and SM maltreatment predicted SP PTSS. Maltreatment also multiplied the effects of SM, product term B = 0.92, p = .031, and SP, product term B = 0.75, p = .004, nonmilitary stressors. The findings emphasize the essential role of exposure to early adversity in understanding PTSS among SMs and SPs, as childhood maltreatment strongly predicted PTSS and exacerbated the effects of other stressors on PTSS. Providers should assess for early adversity among both SMs and SPs and consider the provision of services at the couple level given the potential for the transmission of stress within couples.

The Effect of Dads Matter-HV on Father Engagement in Home Visiting Services.

Engaging fathers early in child and family services has the potential to promote positive father contributions towards positive child development, improve family well-being, and enhance service outcomes over time. However, low father engagement in child and family services remains a persistent problem, and few interventions designed to improve father engagement in these services have been rigorously tested. The current study assesses the effect of a service enhancement intervention called Dads Matter-Home Visiting (Dads Matter-HV) on biological father engagement in home visiting services when compared to home visiting services delivered as usual. To assess the efficacy of the Dads Matter-HV intervention, the research team used a stratified cluster randomized clinical trial design with five agencies delivering early home visiting service programs. Seventeen teams across the five agencies were randomly assigned to either the control group condition (i.e., standard home visiting services as usual) or the intervention condition (i.e., Dads Matter-HV). Data were collected from a total of 204 families at baseline, 4 months postbaseline (92% retention rate), and 12 months postbaseline (84% retention rate). The results suggest that Dads Matter-HV increases biological father engagement for fathers who begin services in the postnatal period, but reduces engagement when services are initiated prenatally. Findings suggest some pathways through which the intervention effects engagement.

How Does Being under the Influence Affect Willingness to Experience Overlapping Effects of Alcohol and Marijuana?

OBJECTIVE: This study tested how individuals anticipate they will respond to opportunities to engage in simultaneous alcohol and marijuana (SAM) use. METHODS: Two studies utilizing a within-subjects design were conducted. Study 1 was conducted in Spring 2021 and a replication (Study 2) was conducted in Fall 2021. Participants were presented with pairs of scenarios. One scenario pair compared how willing participants expected to be to get drunk if they were sober vs. high. Another pair compared how willing participants would be to take a hit of marijuana if they were sober vs. drunk. College attending young adults (Study 1: N = 173; female = 81%; Study 2: N = 212; female = 49.1%) with varying degrees of substance use experience were recruited. RESULTS: In Study 1 participants reported greater willingness to get drunk when sober than when high. This was qualified by a statistically significant interaction whereby differences were greater among those who had more experience with past 30-day heavy drinking. Similar findings emerged for willingness to use marijuana. Participants anticipated greater willingness to use marijuana when sober than when drunk. This was also qualified by a statistically significant interaction whereby differences were greater among experimental or established users of marijuana than among abstainers. Study 2 findings replicated those from Study 1. CONCLUSIONS: College attending young adults state greater willingness to remain under the influence of one substance than to engage in SAM use when opportunities arise. Simultaneous use of alcohol and marijuana among college students is likely an exception, not the rule. Implications for prevention are discussed.

Feasibility, Acceptability and Preliminary Implementation of the Cornerstone Program for Transition-Age Youth with Mental Health Conditions: A Mixed Methods Study.

Transition-age youth with mental health conditions from low socio-economic backgrounds often drop out of mental health services and, as such, do not receive therapeutic doses of treatment. Cornerstone is an innovative team-based, multi-component intervention designed to address the clinical needs of this understudied population through coordination and extensive provision of services in vivo (in the community). The present study used a convergent parallel mixed-methods design. Researchers collected quantitative and qualitative data during a small developmental trial, analyzing the two data types independently and then exploring them side-by-side to evaluate feasibility, acceptability, and preliminary implementation. Semi-structured interviews and quantitative surveys were conducted with transition-age youth, clinic staff, and policy makers. Qualitative interview guides were developed using the Consolidated Framework for Implementation Research to build understanding on implementation determinants alongside feasibility and acceptability. A two-group preliminary randomized trial was conducted to assess feasibility outcomes, such as recruitment, randomization, measurement performance, and trends in pre- to post- outcomes. Using grounded theory coding techniques, transcripts were coded by multiple coders, and themes were identified on acceptability and implementation. The team recruited fifty-six transition-age youth. Randomization was used in the study and the intervention was provided without incident. Results suggest individual components with both the social worker and mentor were more acceptable to participants than group-based approaches. Thematic analyses revealed themes associated with the inner, outer, and policy contexts describing a range of critical implementation determinants. Findings suggest that Cornerstone is feasible, acceptable, and promising for transition-age youth. It represents an innovative multi-component intervention worth exploring for transition-age youth with mental health conditions in a larger efficacy trial.Trial registration: The trial was registered at ClinicalTrials.gov (NCT02696109) on 22 April 16, Protocol Record R34-MH102525-01A1, New York University, Cornerstone program for transition-age youth with serious mental illness: study protocol for a randomized controlled trial.

State-Level Policy Stigma and Non-Prescribed Hormones Use among Trans Populations in the United States: A Mediational Analysis of Insurance and Anticipated Stigma.

BACKGROUND: Medical gender affirmation (i.e., hormone use) is one-way transgender (trans) people affirm their gender and has been associated with health benefits. However, trans people face stigmatization when accessing gender-affirming healthcare, which leads some to use non-prescribed hormones (NPHs) that increase their risk for poor health. PURPOSE: We examined whether healthcare policy stigma, as measured by state-level trans-specific policies, was associated with NPHs use and tested mediational paths that might explain these associations. Because stigmatizing healthcare policies prevent trans people from participation in healthcare systems and allow for discrimination by healthcare providers, we hypothesized that healthcare policy stigma would be associated with NPHs use by operating through three main pathways: skipping care due to anticipated stigma in healthcare settings, skipping care due to cost, and being uninsured. METHODS: We conducted analyses using data from the 2015 U.S. Transgender Survey. The analytic sample included trans adults using hormones (N = 11,994). We fit a multinomial structural equation model to examine associations. RESULTS: Among trans adults using hormones, we found that healthcare policy stigma was positively associated with NPHs use and operated through insurance coverage and anticipating stigma in healthcare settings. The effect sizes on key predictor variables varied significantly between those who use supplemental NPHs and those who only use NPHs suggesting the need to treat NPHs use as distinct from those who use supplemental NPHs. CONCLUSIONS: Our work highlights the importance of healthcare policy stigma in understanding health inequities among trans people in the USA, specifically NPHs use.

Minimal-Contact Versus Standard Cognitive Behavioral Therapy for Irritable Bowel Syndrome: Cost-Effectiveness Results of a Multisite Trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a common, often disabling gastrointestinal (GI) disorder for which there is no satisfactory medical treatment but is responsive to cognitive behavior therapy (CBT). PURPOSE: To evaluate the costs and cost-effectiveness of a minimal contact version of CBT (MC-CBT) condition for N = 145 for IBS relative to a standard, clinic-based CBT (S-CBT; N = 146) and a nonspecific comparator emphasizing education/support (EDU; N = 145). METHOD: We estimated the per-patient cost of each treatment condition using an activity-based costing approach that allowed us to identify and estimate costs for specific components of each intervention as well as the overall total costs. Using simple means analysis and multiple regression models, we estimated the incremental effectiveness of MC-CBT relative to S-CBT and EDU. We then evaluated the cost-effectiveness of MC-CBT relative to these alternatives for selected outcomes at immediate posttreatment and 6 months posttreatment, using both an intent-to-treatment and per-protocol methodology. Key outcomes included scores on the Clinical Global Impressions-Improvement Scale and the percentage of patients who positively responded to treatment. RESULTS: The average per-patient cost of delivering MC-CBT was $348, which was significantly less than the cost of S-CBT ($644) and EDU ($457) (p < .01). Furthermore, MC-CBT produced better average patient outcomes at immediate and 6 months posttreatment relative to S-CBT and EDU (p < .01). The current findings indicated that MC-CBT is a cost-effective option relative to S-CBT and EDU. CONCLUSION: As predicted, MC-CBT was delivered at a lower cost per patient than S-CBT and performed better over time on the primary outcome of global IBS symptom improvement.

Directional effects of parent and child anxiety 1 year following treatment of child anxiety, and the mediational role of parent psychological control.

BACKGROUND: We leveraged a recent efficacy trial to investigate directionality between parent anxiety and child anxiety at posttreatment and 12-month follow-up, and the potential role of parent psychological control as a mediator. We also explored child age and sex as moderators. METHOD: Two-hundred and fifty-four children were randomized to individual cognitive behavioral therapy (CBT) or to one of two CBT arms with parent involvement. Parent anxiety was not a treatment target in any of the three arms. RESULTS: Child anxiety at posttreatment was associated with parent anxiety and psychological control at 12-month follow-up, providing evidence of child-to-parent directionality. Parent anxiety at posttreatment was associated indirectly with child anxiety at 12-month follow-up through associations with parent psychological control, providing evidence of parent-to-child directionality. At posttreatment, parent psychological control contemporaneously mediated the relation between parent and child anxiety. Neither child age nor sex moderated any association. CONCLUSIONS: Findings highlight the directional effects between child anxiety, parent anxiety, and psychological control from posttreatment to 12-month follow-up, even when parent anxiety is not a treatment target. Research and clinical implications are discussed, with an emphasis on enhancing durability following treatment effects.

Parenting as an inhibitor of gender disparities in alcohol use: the case of early adolescents in China.

BACKGROUND: Gender differences in alcohol use are more substantial among early adolescents in China than in the United States, presumably because of more permissive drinking norms for boys than girls in Chinese culture. This study tested a theory that gender differences in early experimentation with alcohol can be reduced through general parenting practices. Whereas traditional research has identified mediators of gender differences in alcohol use, the current research isolated moderators of gender differences and developed their implications for prevention programs. METHODS: The study analyzed the data from the China Global School-Based Student Health Survey (n = 8805 middle school students in four cities). Youth completed anonymous surveys in classroom settings. The study examined interaction effects between gender and parenting variables using multiple regression with robust standard errors. RESULTS: Early adolescent boys exhibited higher levels of drinking than girls for all drinking outcomes. The gender differences in drinking were negatively associated with the level of perceived parental monitoring, parental involvement in adolescent school performance, and parental empathy in a nonlinear way. CONCLUSIONS: Results suggested that early adolescents' perceptions of general parenting practice nonlinearly moderated gender disparities in alcohol use.

Young adult trauma symptoms in the context of community violence exposure.

AIMS: The primary purpose of this study is to understand how community violence exposure is associated with both common and unique variance characterizing posttraumatic stress (PTS) symptoms among young adults living in a low-resourced setting. METHODS: Data were collected using a cross-sectional survey design. Participants were recruited from public housing developments in a city in the eastern United States. Participants completed a survey that included questions related to community violence, PTS symptoms, and optimism. Data were analyzed using structural equation modeling. RESULTS: We found a relationship between a generalized PTS response and each of the PTS symptom categories. Experiencing community violence was significantly related to generalized PTS response over and above other traumatic events. CONCLUSION: Young adults who experience community violence have a general distress response to those experiences, and yet, beyond that general response, there are ways in which each symptom is distinct from a generalized distress reaction.

Factors Associated With Efficacy of Cognitive Behavior Therapy vs Education for Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Among patients with irritable bowel syndrome (IBS), it would be helpful to identify those most likely to respond to specific treatments, yet few factors have been identified that reliably predict positive outcome. We sought to identify pretreatment baseline characteristics that associate with gastrointestinal symptom improvement in patients who received empirically validated regimens of cognitive behavior therapy (CBT) or IBS education. METHODS: We analyzed data from the IBS Outcome Study, in which 436 patients with IBS (average age, 41 years; 80%, female) were randomly assigned to groups that received 4 or 10 sessions of cognitive behavior therapy or education over 10 weeks. Baseline data were collected from all participants on sociodemographic and clinical features and comorbidities. Interaction analyses used a modified linear probability model with Huber-White robust estimators to identify baseline factors that moderated as a function of treatment condition GI symptom improvement based on the IBS-version of the Clinical Global Impressions-Improvement Scale. RESULTS: Whether the primary outcome of IBS symptom improvement was rated by patients or physician assessors blind to treatment 2 weeks after it ended, higher percentages of patients had symptom improvement after CBT compared with EDU among those with low levels of trait anxiety (71.3% vs 34.9%; P < .05) or anxiety sensitivity (71.7% vs 38.6%; P < .05) and for those with baseline typical levels of trait anxiety (66.0% vs 47.1%; P < .05) or anxiety sensitivity (66.3% vs 47.1%; P < .05). For patients with high trait anxiety or anxiety sensitivity, the difference in percentage of responders to CBT vs EDU was non-significant for trait anxiety (60.6% vs 59.2%) and anxiety sensitivity (60.9% vs 55.9%). If patients scored at or below 22 on the Trait Anxiety Inventory, CBT had a statistically significant advantage over EDU. If patients scored at or below 29 on the Anxiety Sensitivity Inventory, there was a statistically significant advantage for CBT vs EDU. CONCLUSIONS: In analyses of outcomes of patients with treatment-refractory IBS, baseline levels of trait anxiety and anxiety sensitivity (fear of arousal symptoms) were associated with improved gastrointestinal symptoms following CBT compared to IBS education. These findings and approaches might be used to optimize selection of treatment for patients with IBS.

Improvement in Gastrointestinal Symptoms After Cognitive Behavior Therapy for Refractory Irritable Bowel Syndrome.

BACKGROUND & AIMS: There is an urgent need for safe treatments for irritable bowel syndrome (IBS) that relieve treatment-refractory symptoms and their societal and economic burden. Cognitive behavior therapy (CBT) is an effective treatment that has not been broadly adopted into routine clinical practice. We performed a randomized controlled trial to assess clinical responses to home-based CBT compared with clinic-based CBT and patient education. METHODS: We performed a prospective study of 436 patients with IBS, based on Rome III criteria, at 2 tertiary centers from August 23, 2010, through October 21, 2016. Subjects (41.4 ± 14.8 years old; 80% women) were randomly assigned to groups that received the following: standard-CBT (S-CBT, n = 146, comprising 10 weekly, 60-minute sessions that emphasized the provision of information about brain-gut interactions; self-monitoring of symptoms, their triggers, and consequences; muscle relaxation; worry control; flexible problem solving; and relapse prevention training), or 4 sessions of primarily home-based CBT requiring minimal therapist contact (MC-CBT, n = 145), in which patients received home-study materials covering the same procedures as S-CBT), or 4 sessions of IBS education (EDU, n = 145) that provided support and information about IBS and the role of lifestyle factors such as stress, diet, and exercise. The primary outcome was global improvement of IBS symptoms, based on the IBS-version of the Clinical Global Impressions-Improvement Scale. Ratings were performed by patients and board-certified gastroenterologists blinded to treatment allocation. Efficacy data were collected 2 weeks, 3 months, and 6 months after treatment completion. RESULTS: A higher proportion of patients receiving MC-CBT reported moderate to substantial improvement in gastrointestinal symptoms 2 weeks after treatment (61.0% based on ratings by patients and 55.7% based on ratings by gastroenterologists) than those receiving EDU (43.5% based on ratings patients and 40.4% based on ratings by gastroenterologists) (P < .05). Gastrointestinal symptom improvement, rated by gastroenterologists, 6 months after the end of treatment also differed significantly between the MC-CBT (58.4%) and EDU groups (44.8%) (P = .05). Formal equivalence testing applied across multiple contrasts indicated that MC-CBT is at least as effective as S-CBT in improving IBS symptoms. Patients tended to be more satisfied with CBT vs EDU (P < .05) based on immediate posttreatment responses to the Client Satisfaction Questionnaire. Symptom improvement was not significantly related to concomitant use of medications. CONCLUSIONS: In a randomized controlled trial, we found that a primarily home-based version of CBT produced significant and sustained gastrointestinal symptom improvement for patients with IBS compared with education. Clinicaltrials.gov no.: NCT00738920.

Durability and Decay of Treatment Benefit of Cognitive Behavioral Therapy for Irritable Bowel Syndrome: 12-Month Follow-Up.

BACKGROUND: There is a need for safe and effective IBS treatments that provide immediate and sustained improvement of IBS symptoms, particularly among more severe patients. The aim was to assess long-term clinical response of cognitive behavioral therapy (CBT) with reference to IBS education. METHODS: A total of 436 Rome III-diagnosed IBS patients (80% F, M age = 41 years) were randomized to: 4 session home-based CBT (minimal contact (MC-CBT)), 10 session clinic-based CBT (standard (S-CBT)), or 4 session IBS education (EDU). Follow-up occurred at 2 weeks and 3, 6, 9, and 12 months following treatment completion. Treatment response was based a priori on the Clinical Global Improvement Scale (global IBS symptom improvement) and IBS Symptom Severity Scale (IBS-SSS). RESULTS: Post-treatment CGI gains were generally maintained by MC-CBT patients at quarterly intervals through 12-month follow-up with negligible decay. For MC-CBT and S-CBT, 39 and 33% of respondents maintained treatment response at every follow-up assessment. The corresponding percent for EDU was 19%, which was significantly lower (p < 0.05) than for the CBT groups. On the IBS-SSS, therapeutic gains also showed a pattern of maintenance with trends towards increased efficacy over time in all conditions, with the mean unit reductions between baseline and follows-up being approximately -76 at immediate and approximately -94 at 12 months (-50 = clinically significant). CONCLUSIONS: For treatment-refractory IBS patients, home- and clinic-based CBT resulted in substantial and enduring relief of multiple IBS symptoms that generally extended to 12-month post treatment.

Mental Health Service Use Among Young Adults: A Communication Framework for Program Development.

Research on mental health service engagement has been dominated by attempts to identify determinants of engagement. Such knowledge is important but incomplete. Once identified, program designers need to use evidence-based principles to design programs to bring about changes in the empirically identified determinants. Research is relatively silent on such principles. This article develops a framework to guide program designers' as they address factors that constrain and/or facilitate engagement. The framework is grounded in communication theory and evidence from related behavioral science research. The literature is summarized and used to generate a check-list of questions to consider when structuring engagement programs.

Parental monitoring, adolescent dishonesty and underage drinking: A nationally representative study.

Little research has connected underage drinking with adolescent information management strategies. The present study uses longitudinal analyses to theoretically link adolescent lying with parental "monitoring knowledge," and, in turn, with prospective adolescent drinking, in a large nationally representative sample of U.S. seventh- and eighth-graders (N = 4020). Structural equation modeling evaluated and supported, two key hypotheses: (1) dishonesty promotes future alcohol use by decreasing parental monitoring knowledge, and (2) dishonesty directly predicts alcohol consumption independent of its effects on parental monitoring. Maternal warmth and adolescent satisfaction with maternal relationships, but not parental control, were associated with lessened lying, and predicted parental monitoring and underage drinking. Our data implicate the role of adolescent agency for parental monitoring and highlight advantages of cohesive as opposed to over-restrictive parenting.

The mediating role of cardiovascular risk factors in the relationship between symptoms of apathy and incident cardiovascular disease in community-dwelling older individuals.

BACKGROUND: In old age, both apathy and depression have been associated with an increased cardiovascular disease (CVD) risk. This study evaluated the mediating role of cardiovascular risk factors in the relationship of apathy and mood symptoms with incident CVD. METHODS: Prospective cohort study of 1,790 community-dwelling older individuals (70-78 years) without a history of CVD or stroke. At baseline, apathy and mood symptoms were assessed with the 15-item Geriatric Depression Scale (GDS-15), of which three items represent apathy symptoms. The mediational risk factors included were diabetes mellitus (DM), body mass index (BMI), current smoking, physical inactivity, systolic blood pressure, and total cholesterol. Incident CVD was evaluated after two years of follow-up. Data were analyzed using structural equation modeling (SEM). RESULTS: Incident CVD occurred in 59 (3.3%) participants. Apathy symptoms had a significant estimated total effect on incident CVD, with increases of 2.2% for each unit increase in apathy score. Of this total effect, 22.7% was due to the mediational effects of physical inactivity (13.6%), current smoking (4.5%), and DM (4.5%). The remaining 77.3% was due to direct effects reflecting other mediational dynamics. No significant (in)direct effects of mood symptoms on incident CVD were found. CONCLUSIONS: Physical inactivity, smoking, and DM account for nearly one-fourth of the variation reflecting the link between apathy symptoms and incident CVD. This illustrates the relevance of unfavorable health behaviors and assessment of DM in older individuals with apathy. The majority of the effect of apathy symptoms on incident CVD is caused by other, yet unknown, factors.

Moving to Second-Stage Treatments Faster: Identifying Midtreatment Tailoring Variables for Youth with Anxiety Disorders.

The current study presents an approach for empirically identifying tailoring variables at midtreatment of cognitive behavioral therapy (CBT) protocols for youth with anxiety disorders that can be used to guide moves to second-stage treatments. Using 2 independent data sets (Study 1 N = 240, M age = 9.86 years; Study 2 N = 341; M age = 9.53 years), we examined treatment response patterns after 8 sessions of CBT (i.e., CBT midtreatment). We identified and replicated 3 classes of response patterns at CBT midtreatment: Early Responders, Partial Responders, and Nonresponders. Class membership at CBT midtreatment was predictive of outcome at CBT posttreatment. Receiver operating characteristics curves were used to derive guidelines to optimize accuracy of assignment to classes at CBT midtreatment. These findings support the promise of treatment response at CBT midtreatment to identify tailoring variables for use in abbreviating first-stage treatments and facilitating moves to second-stage treatments.