Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression.

BACKGROUND: To investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075). METHODS: We used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin. RESULTS: Patients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm. CONCLUSIONS: Overall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment.

Using brief reflections to capture and evaluate end-user engagement: a case example using the COMPASS study.

BACKGROUND: Use of participatory research methods is increasing in research trials. Once partnerships are established with end-users, there is less guidance about processes research teams can use to successfully incorporate end-user feedback. The current study describes the use of a brief reflections process to systematically examine and evaluate the impact of end-user feedback on study conduct. METHODS: The Comparative Effectiveness of Trauma-Focused and Non-Trauma- Focused Treatment Strategies for PTSD among those with Co-Occurring SUD (COMPASS) study was a randomized controlled trial to determine the effectiveness of trauma-focused psychotherapy versus non-trauma-focused psychotherapy for Veterans with co-occurring posttraumatic stress disorder and substance use disorder who were entering substance use treatment within the Department of Veterans Affairs. We developed and paired a process of "brief reflections" with our end-user engagement methods as part of a supplemental evaluation of the COMPASS study engagement plan. Brief reflections were 30-minute semi-structured discussions with the COMPASS Team following meetings with three study engagement panels about feedback received regarding study issues. To evaluate the impact of panel feedback, 16 reflections were audio-recorded, transcribed, rapidly analyzed, and integrated with other study data sources. RESULTS: Brief reflections revealed that the engagement panels made recommended changes in eight areas: enhancing recruitment; study assessment completion; creating uniformity across Study Coordinators; building Study Coordinator connection to Veteran participants; mismatch between study procedures and clinical practice; therapist skill with patients with active substance use; therapist burnout; and dissemination of study findings. Some recommendations positively impact study conduct while others had mixed impact. Reflections were iterative and led to emergent processes that included revisiting previously discussed topics, cross-pollination of ideas across panels, and sparking solutions amongst the Team when the panels did not make any recommendations or recommendations were not feasible. CONCLUSIONS: When paired with end-user engagement methods, brief reflections can facilitate systematic examination of end-user input, particularly when the engagement strategy is robust. Reflections offer a forum of accountability for researchers to give careful thought to end-user recommendations and make timely improvements to the study conduct. Reflections can also facilitate evaluation of these recommendations and reveal end-user-driven strategies that can effectively improve study conduct. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04581434) on October 9, 2020; https://clinicaltrials.gov/ct2/show/study/NCT04581434?term=NCT04581434&draw=2&rank=1 .

Implementation of statistical features of a Bayesian two-armed responsive adaptive randomization trial with post hoc analysis of time trend drift.

Bayesian adaptive designs with response adaptive randomization (RAR) have the potential to benefit more participants in a clinical trial. While there are many papers that describe RAR designs and results, there is a scarcity of works reporting the details of RAR implementation from a statistical point exclusively. In this paper, we introduce the statistical methodology and implementation of the trial Changing the Default (CTD). CTD is a single-center prospective RAR comparative effectiveness trial to compare opt-in to opt-out tobacco treatment approaches for hospitalized patients. The design assumed an uninformative prior, conservative initial allocation ratio, and a higher threshold for stopping for success to protect results from statistical bias. A particular emerging concern of RAR designs is the possibility that time trends will occur during the implementation of a trial. If there is a time trend and the analytic plan does not prespecify an appropriate model, this could lead to a biased trial. Adjustment for time trend was not pre-specified in CTD, but post hoc time-adjusted analysis showed no presence of influential drift. This trial was an example of a successful two-armed confirmatory trial with a Bayesian adaptive design using response adaptive randomization.

Rural libraries implementing walking groups or walking groups plus civic engagement for walkability in rural communities: a comparative effectiveness trial study protocol.

BACKGROUND: Rural residents generally lack adequate physical activity to benefit health and reduce disparities in chronic diseases, such as cardiovascular disease and certain cancers. The Socioecological Model describes physical activity as involving a dynamic and reciprocal interaction between individual, social, and community factors. Community group-based walking programs and civic engagement interventions aimed at enhancing physical activity have been successful in rural communities but have not targeted all three socioecological levels. Public libraries can act as innovative public health partners in rural communities. However, challenges remain because rural libraries often lack the capacity to implement evidence-based health promotion programming. The goals of this study are (1) build the capacity for rural libraries to implement evidence-based health promotion programs, (2) compare changes in physical activity between a group-based walking program and a combined group-based walking and civic engagement program with rural residents, and (3) conduct an implementation evaluation. METHODS: We will conduct a comparative effectiveness study of a group-based walking (standard approach) versus a group-based walking plus civic engagement program (combined approach) aimed at enhancing walkability to increase physical activity among rural adults. Key mediators between the program effects and change in outcomes will also be identified. Finally, we will evaluate program implementation, conduct a cost effectiveness evaluation, and use a positive deviance analysis to understand experiences of high and low changers on key outcomes. Twenty towns will be matched and randomized to one of the two conditions and our aim is to enroll a total of 350-400 rural residents (15-20 per town). Study outcomes will be assessed at baseline, and 6, 12, and 24 months. DISCUSSION: This study will build the capacity of rural libraries to implement evidence-based walking programs as well as other health promotion programs in their communities. The study results will answer questions regarding the relative effectiveness and cost effectiveness of two multilevel physical activity interventions targeting rural communities. We will learn what works and how these multilevel interventions can be implemented in rural populations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05677906.

Preventive interventions for children of parents with depression, anxiety, or bipolar disorder: A quasi-experimental clinical trial.

AIM: To investigate the effectiveness of preventive interventions for 8-17-year-old children of patients diagnosed with depression, anxiety, or bipolar disorder. METHODS: Sixty-two families including 89 children received either the more extensive Family Talk Intervention (FTI; n = 35), the brief Let's Talk about Children (LTC; n = 16), or Interventions as Usual (IAU; n = 38) in routine care in adult psychiatry. Parent-rated questionnaire data were collected at baseline, after 6 and 12 months. We used growth curve models to investigate the effect of intervention on child mental health problems (SDQ-P Total Difficulties) and perceived parental control of child behaviour (PLOC-PPC). RESULTS: Parents in the FTI and LTC groups, versus the IAU group, reported more favourable development in terms of preventing increase in child mental health problems with standardised intervention effects of d = -0.86 and -0.88 respectively, by study end, and reported improved perceived parental control, d = 1.08 and 0.71, respectively, by study end. No significant differences in effect were found when FTI and LTC were compared. CONCLUSIONS: The results support continued use of FTI and LTC in adult psychiatry, and since LTC is a brief intervention, it might be useful as a minimum-level preventive intervention.

Happy Talk: A pilot effectiveness study of a targeted-selective speech-language and communication intervention for children from areas of social disadvantage.

BACKGROUND: Despite the public health implications of language difficulties associated with social disadvantage, there is a dearth of effectiveness studies investigating the effects of targeted speech and language programmes in this area. AIMS: To determine the effects of a targeted selective community-based child language intervention programme (Happy Talk), which simultaneously engaged with parents and early childhood educators, in the Republic of Ireland. METHODS & PROCEDURES: A mixed methods methodology was applied with quantitative outcome and qualitative process data collected. Effectiveness was examined using a quasi-experimental single blind study design comparing Happy Talk with 'usual care' across four preschools. Qualitative process data were also gathered to examine the acceptability and feasibility of the Happy Talk approach in practice, and to identify factors to improve the probability of successful wider implementation. Child language (PLS-5) and quality-of-life measures were administered pre- and immediately post- the 11-week intervention. Responsiveness was assessed as the parental outcome, and the oral language environment of preschools was measured using the Communication Supporting Classroom Observation Tool (CSCOT). Retrospective acceptability was analysed with reference to the theoretical framework of acceptability (v 2). OUTCOMES & RESULTS: Pre-/post-expressive and composite language scores were collected for 58 children, and receptive scores for 54 children. Multiple linear regression revealed significant intervention effects for comprehension and total language with large and moderate effect sizes, respectively (0.60 and 0.46 SD). No significant effect was shown for parental responsiveness. No effects were found for the preschool environment or children's quality of life. Preschool staff deemed the programme to be an acceptable method of enhancing children's speech and language skills and rated the intervention positively. CONCLUSIONS & IMPLICATIONS: The Happy Talk pilot effectiveness trial shows that comprehension can be improved (with a large effect) in preschool children from areas of social disadvantage, following an 11-week intervention, in which parents and preschool staff are simultaneously engaged. The ecological validity of the programme, as well as feasibility and acceptability to staff, make it a suitable programme to be delivered at scale. WHAT THIS PAPER ADDS: What is already known on the subject Up to 50% of children from socially disadvantaged areas enter preschool with speech and language difficulties. The majority of intervention studies are (1) researcher led; (2) efficacy trials carried out in ideal conditions; and (3) focus on working with parents or early childhood educators rather than engaging with both groups simultaneously. Many studies omit child language outcomes, and those that include them tend to show relatively modest effects for expressive language and negligible effects for receptive language. What this paper adds to existing knowledge This pilot study shows that the Happy Talk programme, which is embedded in the community and which simultaneously engages with parents and early childhood educators, is highly effective in improving children's receptive language skills. These findings are particularly important in the context of (1) the study taking place in real world conditions; and (2) the programme being designed and refined by speech and language therapy services, rather than one which is researcher led. What are the potential or actual clinical implications of this work? Implementing an 11-week targeted selective community-based language intervention can result in a large positive effect on receptive language for children from areas of social disadvantage. The study findings highlight the importance of embedding intervention programmes in the community and of simultaneously engaging with parents and preschool staff.

Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC).

BACKGROUND: For loco-regionally advanced, but transorally resectable oropharyngeal cancer (OPSCC), the current standard of care includes surgical resection and risk-adapted adjuvant (chemo) radiotherapy, or definite chemoradiation with or without salvage surgery. While transoral surgery for OPSCC has increased over the last decade for example in the United States due to transoral robotic surgery, this treatment approach has a long history in Germany. In contrast to Anglo-Saxon countries, transoral surgical approaches have been used frequently in Germany to treat patients with oro-, hypopharyngeal and laryngeal cancer. Transoral laser microsurgery (TLM) has had a long tradition since its introduction in the early 70s. To date, the different therapeutic approaches to transorally resectable OPSCC have not been directly compared to each other in a randomized trial concerning disease control and survival. The goal of this study is to compare initial transoral surgery to definitive chemoradiation for resectable OPSCC, especially with regards to local and regional control. METHODS: TopROC is a prospective, two-arm, open label, multicenter, randomized, and controlled comparative effectiveness study. Eligible patients are ≥18 years old with treatment-naïve, histologically proven OPSCC (T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0 UICC vers. 7) which are amenable to transoral resection. Two hundred eighty patients will be randomly assigned (1:1) to surgical treatment (arm A) or chemoradiation (arm B). Standard of care treatment will be performed according to daily routine practice. Arm A consists of transoral surgical resection with neck dissection followed by risk-adapted adjuvant therapy. Patients treated in arm B receive standard chemoradiation, residual tumor may be subject to salvage surgery. Follow-up visits for 3 years are planned. Primary endpoint is time to local or locoregional failure (LRF). Secondary endpoints include overall and disease free survival, toxicity, and patient reported outcomes. Approximately 20 centers will be involved in Germany. This trial is supported by the German Cancer Aid and accompanied by a scientific support program. DISCUSSION: This study will shed light on an urgently-needed randomized comparison of the strategy of primary chemoradiation vs. primary surgical approach. As a comparative effectiveness trial, it is designed to provide data based on two established regimens in daily clinical routine. TRIAL REGISTRATION: NCT03691441 Registered 1 October 2018 - Retrospectively registered.

Fit and Strong! Plus: Twelve and eighteen month follow-up results for a comparative effectiveness trial among overweight/obese older adults with osteoarthritis.

This comparative effectiveness trial compared the longer-term effectiveness (12 and 18 months) of the standard Fit & Strong! physical activity program to Fit & Strong! Plus, which combined physical activity and dietary weight loss. Outcomes were weight, diet quality, physical activity, osteoarthritis symptoms, performance measures, and anxiety/depression. In this study, 413 overweight/obese participants with OA, ≥60 years old and primarily African American, were randomly assigned to Fit & Strong! (F&S!) or Fit & Strong! Plus (F&S! Plus), with outcomes assessed at 2, 6, 12, and 18 months. 356 (86%) participants completed the 18-month visit. Compared with participants randomized to standard F&S!, F&S! Plus participants maintained longer-term benefits at 12 months in weight (mean change ± SE: -1.7 ± 0.3 kg for F&S! Plus vs -0.9 ± 0.3 kg for F&S!, p = 0.049), BMI (-0.6 ± 0.1 vs -0.3 ± 0.1 kg/m2, p = 0.04), waist circumference (-2.7 ± 0.6 vs -0.4 ± 0.6 cm, p = 0.004), and lower extremity strength (1.6 ± 0.2 vs 1.0 ± 0.2 chair stands, p = 0.046). At 18 months, F&S! Plus participants showed improved lower extremity strength (1.4 ± 0.2 vs. 0.7 ± 0.2 chair stands, p = 0.045. African American older adults in the F&S! Plus arm showed sustained modest improvements in weight, waist circumference, and lower extremity strength at 12 months and in lower extremity strength at 18 months compared to F&S!. Implications for the translation of evidence-based programs into community settings to support healthy behaviors in older adults are discussed.

Paris MEM: a study protocol for an effectiveness and efficiency trial on the treatment of traumatic stress in France after the 2015-16 terrorist attacks.

BACKGROUND: The Paris and Nice terrorist attacks affected a thousand of trauma victims and first-line responders. Because there were concerns that this might represent the first of several attacks, there was a need to quickly enhance the local capacities to treat a large number of individuals suffering from trauma-related disorders. Since Reconsolidation Therapy (RT) is brief, relatively easy to learn, well tolerated and effective, it appeared as the ideal first-line treatment to teach to clinicians in this context. METHODS: This study protocol is a two-arm non-randomized, multicenter controlled trial, comparing RT to treatment as usual for the treatment of trauma-related disorders. RT consists of actively recalling one's traumatic event under the influence of the ß-blocker propranolol, once a week, for 10-25 min with a therapist, over 6 consecutive weeks. This protocol evaluates the feasibility, effectiveness, and cost-utility of implementing RT as part of a large multi-center (N = 400) pragmatic trial with a one-year follow-up. DISCUSSION: Paris MEM is the largest trial to date assessing the efficiency of RT in the aftermath of a large-scale man-made disaster. RT could possibly reinforce the therapeutic arsenal for the treatment of patients suffering from trauma-related disorders, not only for communities in western countries but also worldwide for terror- or disaster-stricken communities. TRIAL REGISTRATION: Clinical Trials (ClinicalTrials.gov). June 3, 2016. NCT02789982.

Prenatal Lipid-Based Nutrient Supplements Affect Maternal Anthropometric Indicators Only in Certain Subgroups of Rural Bangladeshi Women.

BACKGROUND: Maternal undernutrition and low macro- and micronutrient intake and weight gain during pregnancy have been reported in Bangladesh. OBJECTIVE: We aimed to determine the effects of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on weight gain and midupper arm circumference (MUAC) during pregnancy. METHODS: The Rang-Din Nutrition Study, a cluster-randomized effectiveness trial conducted in Bangladesh, enrolled 4011 pregnant women at ≤20 wk gestation who received either 60 mg Fe + 400 µg folic acid/d or 20 g LNS-PL/d (118 kcal) containing essential fatty acids and vitamins and minerals until delivery. At 36 wk gestation, women were interviewed at home and then attended a follow-up examination at local clinics (n = 2877), where anthropometric measurements were taken. RESULTS: No significant differences between intervention groups in maternal weight gain per week, low weight gain per week, or MUAC at 36 wk gestation were observed in the full sample. However, among multiparous women aged ≥25 y, those in the LNS-PL group gained 34 g/wk more than their counterparts in the iron and folic acid (IFA) group (P = 0.001), whereas no differences were seen in the other parity/age subgroups. Women aged ≥25 y in the LNS-PL group had a 0.4-cm greater MUAC than their counterparts in the IFA group (P = 0.003); no significant differences were observed in the other age groups. Among women whose height at baseline was in the lowest quartile of the distribution, those in the LNS-PL group had a 0.1-0.3-cm greater MUAC at 36 wk gestation than those in the IFA group (P = 0.004-0.014). CONCLUSIONS: Lipid-based nutrient supplements provided during pregnancy did not affect maternal anthropometric indicators in the overall sample but increased MUAC among women aged ≥25 y and those with lower stature and weight gain among multiparous women aged ≥25 y. This trial was registered at clinicaltrials.gov as NCT01715038.

Implementing Family-Centered Prevention in Rural African American Communities: a Randomized Effectiveness Trial of the Strong African American Families Program.

Efforts to disseminate evidence-based prevention programs are hampered by a lack of real-world effectiveness trials undertaken with community providers. The Strong African American Families (SAAF) program is an empirically validated intervention designed to prevent problem behavior among rural African American youth. To evaluate the effectiveness of SAAF and its implementation protocols when delivered by a community provider, we conducted a randomized, wait-list-controlled trial with outcome measurements assessed longitudinally at baseline and 6 months after baseline. A total of 465 African American youth and their parents were recruited randomly from public school lists of fifth- and sixth-grade students in eight rural counties in south Georgia. Youth and parents assessed targeted outcomes in their homes. The main outcome, problem behavior vulnerability, was operationalized as a latent construct comprising three indicators: tolerance for deviance, intentions to engage in risky behavior, and affiliations with risk-taking peers. SAAF was implemented with uniformly high levels of adherence (85.5%; SD = 10.8) and attendance (M = 4.1, SD = 2.9, range = 0-7). Intent-to-treat and complier average causal effect analyses revealed significant program effects on intervention-targeted parenting practices, youth self-regulatory processes, and problem behavior vulnerability. SAAF influenced problem behavior vulnerability indirectly via effects on targeted parenting and youth processes. This study supported the effectiveness of SAAF in a community setting when a systematic implementation model supports participant engagement and intervention adherence.

Maternal mental distress influences child outcomes in brief parent training.

BACKGROUND: Brief Parent Training (BPT) promotes effective parenting in parents of children with conduct problems. As previous research has provided inconsistent results, this study explored the impact of maternal mental distress on outcomes of BPT. METHOD: Participants included 216 families randomized to BPT or a comparison group. RESULTS: Maternal distress negatively predicted five of eight outcomes, regardless of intervention allocation. Low-maternal distress predicted lower conduct problems (parent- and teacher-reported), whereas high distress predicted higher teacher-reported conduct problems in BPT relative to comparisons. CONCLUSIONS: Refinement of interventions to help children with conduct problems and distressed mothers should be prioritized.

Study protocol for a randomized controlled trial of supportive parents - coping kids (SPARCK)-a transdiagnostic and personalized parent training intervention to prevent childhood mental health problems.

BACKGROUND: To meet the scientific and political call for effective prevention of child and youth mental health problems and associated long-term consequences, we have co-created, tested, and optimized a transdiagnostic preventive parent-training intervention, Supportive parents - coping kids (SPARCK), together with and for the municipal preventive frontline services. The target group of SPARCK is parents of children between 4 and 12 years who display symptoms of anxiety, depression, and/or behavioral problems, that is, indicated prevention. The intervention consists of components from various empirically supported interventions representing different theorical models on parent-child interactions and child behavior and psychopathology (i.e., behavioral management interventions, attachment theory, emotion socialization theory, cognitive-behavioral therapy, and family accommodation intervention). The content and target strategies of SPARCK are tailored to the needs of the families and children, and the manual suggests how the target strategies may be personalized and combined throughout the maximum 12 sessions of the intervention. The aim of this project is to investigate the effectiveness of SPARCK on child symptoms, parenting practices, and parent and child stress hormone levels, in addition to later use of specialized services compared with usual care (UC; eg. active comparison group). METHODS: We describe a randomized controlled effectiveness trial in the frontline services of child welfare, health, school health and school psychological counselling services in 24 Norwegian municipalities. It is a two-armed parallel group randomized controlled effectiveness and superiority trial with 252 families randomly allocated to SPARCK or UC. Assessment of key variables will be conducted at pre-, post-, and six-month follow-up. DISCUSSION: The current study will contribute with knowledge on potential effects of a preventive transdiagnostic parent-training intervention when compared with UC. Our primary objective is to innovate frontline services with a usable, flexible, and effective intervention for prevention of childhood mental health problems to promote equity in access to care for families and children across a heterogeneous service landscape characterized by variations in available resources, personnel, and end user symptomatology. TRIAL REGISTRATION: ClinicalTrials.gov ID: NTCT05800522.

A comparative effectiveness trial of functional behavioral assessment methods.

Clinicians report primarily using functional behavioral assessment (FBA) methods that do not include functional analyses. However, studies examining the correspondence between functional analyses and other types of FBAs have produced inconsistent results. In addition, although functional analyses are considered the gold standard, their contribution toward successful treatment compared with other FBA methods remains unclear. This comparative effectiveness study, conducted with 57 young children with autism spectrum disorder, evaluated the results of FBAs that did (n = 26) and did not (n = 31) include a functional analysis. Results of FBAs with and without functional analyses showed modest correspondence. All participants who completed functional communication training achieved successful outcomes regardless of the type of FBA conducted.

HPV Multilevel Intervention Strategies Targeting Immunization in Community Settings (HPV MISTICS): Study protocol for a hybrid 1 stepped-wedge cluster randomized trial.

BACKGROUND: This protocol paper describes the overall design for HPV MISTICS, a multilevel intervention to increase human papillomavirus (HPV) vaccination initiation and completion rates among adolescents aged 11-17. METHODS: We will conduct a hybrid type 1 implementation-effectiveness trial using a stepped-wedge cluster randomized trial in eight federally qualified health centers (FQHCs) in Florida. Intervention components target three levels: system, providers, and parents. Outcomes will be assessed using quantitative (e.g., vaccination data, survey data) and qualitative methods (e.g., staff and parent interviews). We expect to quantify changes in HPV vaccine series initiation and completion rates for adolescents ages 11-17 in the eight FQHCs. We have hypothesized a 20-percentage point increase in HPV vaccine series initiation and a 10-percentage point increase in series completion. We also anticipate being able to explore factors at the system, provider, and patient levels as potential covariates. Implementation outcomes, barriers, and facilitators identified in the study will help characterize the implementation process and inform potential future intervention scale-up. RESULTS: The project is ongoing; effectiveness and implementation outcomes will be determined following project completion. CONCLUSIONS: Findings will provide evidence of an equity-informed research design and implementation procedures that could help improve HPV vaccination rates in similar health systems. CLINICAL TRIALS IDENTIFIER: NCT05677360 (date registered: 2022-12-22); https://clinicaltrials.gov/study/NCT05677360?lead=Moffitt%20Cancer%20Center%20&aggFilters=status:rec&page=2&rank=17.

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.

Hybrid effectiveness-implementation trial of guided relaxation and acupuncture for chronic sickle cell disease pain (GRACE): A protocol.

Background: People with sickle cell disease frequently use complementary and integrative therapies to cope with their pain, yet few studies have evaluated their effectiveness. The 3-arm, 3-site pragmatic Hybrid Effectiveness-implementation Trial of Guided Relaxation and Acupuncture for Chronic Sickle Cell Disease Pain (GRACE) has 3 priorities: (1) evaluate guided relaxation and acupuncture to improve pain control; (2) determine the most appropriate and effective treatment sequence for any given patient based on their unique characteristics; and (3) describe the processes and structures required to implement guided relaxation and acupuncture within health care systems. Methods: Participants (N = 366) are being recruited and randomized 1:1:1 to one of 2 intervention groups or usual care. The acupuncture intervention group receives 10 sessions over approximately 5 weeks. The guided relaxation intervention group receives access to video sessions ranging from 2 to 20 min each viewed daily over 5 weeks. The usual care group receives the standard of clinical care for sickle cell disease. Participants are re-randomized at 6 weeks depending on their pain impact score. Assessments occur at 6 weeks, 12 weeks, and 24 weeks. The primary outcome is the change in pain impact score and secondary measures include opioid use, anxiety, depression, sleep, pain catastrophizing, substance use, global impression of change, constipation, and hospitalizations. The GRACE study uses the Consolidated Framework for Implementation Research to plan, execute, and evaluate the associated implementation processes. Conclusion: The results from GRACE will represent a critical step toward improving management of pain affecting patients with sickle cell disease.ClinicalTrials.gov Identifier: NCT04906447.

Principle-Guided Psychotherapy for Children and Adolescents (FIRST): Study Protocol for a Randomized Controlled Effectiveness Trial in Outpatient Clinics.

Background: Hundreds of youth psychotherapy randomized trials have generated scores of helpful empirically supported treatments (ESTs). However, the standardized structure of many ESTs and their focus on a single disorder or homogeneous cluster of problems may not be ideal for clinically referred youths who have comorbidity and whose treatment needs may shift from week to week. This concern has prompted development of flexible transdiagnostic, modular youth psychotherapies. One of these, designed for efficient training and implementation, is FIRST-a transdiagnostic intervention built on five empirically supported principles of change (i.e., feeling calm, increasing motivation, repairing thoughts, solving problems, and trying the opposite) and targeting common internalizing and externalizing youth mental health disorders and problems. FIRST has shown promise in improving youth mental health in three open trials. Now, in a more rigorous test, we seek to (1) conduct a randomized controlled trial comparing FIRST to usual care in real-world clinical practice settings; (2) examine a promising candidate mediator of change-regulation of negative emotions; and (3) explore variables that may influence clinicians' treatment implementation. Methods: This is an assessor-naïve randomized controlled effectiveness trial in youth outpatient community clinics in New England and Texas. Using double randomization, clinic-employed clinicians and treatment-referred youths (7-15 years old) are independently randomly allocated (1:1) to FIRST or usual care. We aim to recruit 212 youth participants, all referred through normal community pathways, with elevated symptoms of anxiety, depression, conduct problems, or post-traumatic stress. This study will test the effectiveness of FIRST compared to usual care on mental health outcomes, examine whether those outcomes are mediated by regulation of negative emotions, and explore clinician factors that may be associated with FIRST implementation and outcomes. Session recordings are coded to assess treatment fidelity. Discussion: This study will evaluate the effectiveness of FIRST in youth community mental health settings, relative to the care usually provided in those settings. If FIRST is found to be effective, it could offer an efficient and practical method to increase use of empirically supported treatment principles in real-world practice contexts. Trial registration: NIH Clinical Trials Registry, NCT04725721. Registered 27 January 2021, https://clinicaltrials.gov/ct2/show/study/NCT04725721.

Principle-Guided Psychotherapy for Children and Adolescents (FIRST): study protocol for a randomized controlled effectiveness trial in outpatient clinics.

BACKGROUND: Hundreds of youth psychotherapy randomized trials have generated scores of helpful empirically supported treatments (ESTs). However, the standardized structure of many ESTs and their focus on a single disorder or homogeneous cluster of problems may not be ideal for clinically referred youths who have comorbidity and whose treatment needs may shift from week to week. This concern has prompted development of flexible transdiagnostic, modular youth psychotherapies. One of these, designed for efficient training and implementation, is FIRST-a transdiagnostic intervention built on five empirically supported principles of change (i.e., feeling calm, increasing motivation, repairing thoughts, solving problems, and trying the opposite) and targeting common internalizing and externalizing youth mental health disorders and problems. FIRST has shown promise in improving youth mental health in three open trials. Now, in a more rigorous test, we seek to (1) conduct a randomized controlled trial comparing FIRST to usual care in real-world clinical practice settings; (2) examine a promising candidate mediator of change-regulation of negative emotions; and (3) explore variables that may influence clinicians' treatment implementation. METHODS: This is an assessor-naïve randomized controlled effectiveness trial in youth outpatient community clinics in New England and Texas. Using double randomization, clinic-employed clinicians and treatment-referred youths (7-15 years old) are independently randomly allocated (1:1) to FIRST or usual care. We aim to recruit 212 youth participants, all referred through normal community pathways, with elevated symptoms of anxiety, depression, conduct problems, or post-traumatic stress. This study will test the effectiveness of FIRST compared to usual care on mental health outcomes, examine whether those outcomes are mediated by regulation of negative emotions, and explore clinician factors that may be associated with FIRST implementation and outcomes. Session recordings are coded to assess treatment fidelity. DISCUSSION: This study will evaluate the effectiveness of FIRST in youth community mental health settings, relative to the care usually provided in those settings. If FIRST is found to be effective, it could offer an efficient and practical method to increase use of empirically supported treatment principles in real-world practice contexts. TRIAL REGISTRATION: NIH Clinical Trials Registry, NCT04725721. Registered 27 January 2021, https://clinicaltrials.gov/ct2/show/study/NCT04725721.

Testing the effectiveness of a sexual assault resistance programme in 'real-world' implementation.

Background: In a multi-site randomized controlled trial (RCT), the EAAA programme designed for first year university women (17-24 years old) was shown to reduce the likelihood of any (attempted and completed) rape in the next year by 50% (Senn, C. Y., Eliasziw, M., Barata, P. C., Thurston, W. E., Newby-Clark, I. R., Radtke, H. L., & Hobden, K. L. (2015). Efficacy of a sexual assault resistance program for university women. New England Journal of Medicine, 372(24), 2326-2335). Through a non-profit organization, EAAA has been available to universities globally since 2016 using a Train-the-Trainer model. Observations of the 'real world' implementation suggested that universities often altered eligibility criteria (especially year of study and age) in their recruitment.Objective: The current study (2017-2021) evaluated whether EAAA was effective when implemented by universities in Canada outside of the constraints of an RCT.Method: Five universities participated. Women students who signed up to take the EAAA programme on their campuses were recruited for the research. Participants completed surveys at 1-week pre-program and 1-week and 6-months post-programme. Compared to the RCT, participant eligibility was broader, the sample was more diverse in terms of race and sexual identity and had a higher proportion of survivors. Programme fidelity was adequate.Results: Comparisons in this quasi-experimental design, between students who took the programme and students in the control group (i.e. those who signed up but did not attend the programme), confirmed the effectiveness of the EAAA programme. Reduction of any rape exceeded the a priori benchmark of 37.5%. Completed rape was significantly reduced by 57.3% at 6-months. Reduction in attempted rape of 32.9% was lower than in the RCT likely due to the somewhat older (average age 22 vs 18) sample. Positive changes to previously established mediators of the programme effects were all replicated.Conclusions: These findings suggest that the EAAA is highly effective when implemented by universities even when eligibility for students in terms of year of study and age is broadened.

This study evaluates whether the EAAA programme is effective when implemented by university staff at five Canadian universities outside of the constraints of an RCT.Women-identified students who attended the EAAA programme experienced a 57.3% reduction in completed rape and other benefits including increased confidence and reductions in rape myth beliefs when compared to a comparable group of students who signed up but didn't attend the programme.These reductions in sexual victimization in the 'real-world' implementation of the EAAA programme in a sample of diverse undergraduate and graduate students enhances our confidence in its ability to reduce the pervasive public health issue of sexual violence experienced by women in university.