Impact of Therapist Training on Parent Attendance in Mental Health Services for Children with ASD.

OBJECTIVE: The current study explored the impact of training therapists in a mental health intervention for children with autism spectrum disorder (ASD) on parent attendance in their children's therapy sessions. We also examined family, therapist, and program factors as potential moderators. METHOD: Data were drawn from a cluster-randomized community effectiveness trial of "An Individualized Mental Health Intervention for ASD (AIM HI)". Participants included 168 therapists yoked with 189 children recruited from publicly-funded mental health services. Data included family (caregiver strain, parent sense of competence, race/ethnicity), therapist (background, experience), and program (service setting) characteristics, and parent session attendance. Multilevel models were used to evaluate the effectiveness of AIM HI therapist training on caregiver attendance and identify moderators of training effects on parent attendance. RESULTS: Parents attended a higher percentage of sessions in the AIM HI training condition compared to the Usual Care condition. Program service setting moderated the effect of AIM HI training, with higher parent attendance in non-school (mostly outpatient) settings compared to school settings and a significantly smaller difference between the settings in the AIM HI condition. CONCLUSIONS: Effective strategies to promote parent engagement, especially in service settings such as schools, are warranted. Findings support the effectiveness of AIM HI training in promoting parent attendance across multiple publicly-funded mental health service settings. The larger effect in school-based programs supports the utility of training in evidence-based interventions such as AIM HI to increase the feasibility of parent attendance in such services.

Caregiver Participation Engagement in Child Mental Health Prevention Programs: a Systematic Review.

Prevention programs are a key method to reduce the prevalence and impact of mental health disorders in childhood and adolescence. Caregiver participation engagement (CPE), which includes caregiver participation in sessions as well as follow-through with homework plans, is theorized to be an important component in the effectiveness of these programs. This systematic review aims to (1) describe the terms used to operationalize CPE and the measurement of CPE in prevention programs, (2) identify factors associated with CPE, (3) examine associations between CPE and outcomes, and (4) explore the effects of strategies used to enhance CPE. Thirty-nine articles representing 27 unique projects were reviewed. Articles were included if they examined CPE in a program that focused to some extent on preventing child mental health disorders. There was heterogeneity in both the terms used to describe CPE and the measurement of CPE. The majority of projects focused on assessment of caregiver home practice. There were no clear findings regarding determinants of CPE. With regard to the impact of CPE on program outcomes, higher levels of CPE predicted greater improvements in child and caregiver outcomes, as well as caregiver-child relationship quality. Finally, a small number of studies found that motivational and behavioral strategies (e.g., reinforcement, appointment reminders) were successful in promoting CPE. This review highlights the importance of considering CPE when developing, testing, and implementing prevention programs for child mental health disorders. Increased uniformity is needed in the measurement of CPE to facilitate a better understanding of determinants of CPE. In addition, the field would benefit from further evaluating strategies to increase CPE as a method of increasing the potency of prevention programs.

Adapting parent engagement strategies for an evidence-based parent-mediated intervention for young children at risk for autism spectrum disorder.

AIMS: Aims included (a) characterizing provider feedback on parent engagement strategies integrated into a parent-mediated intervention for toddlers at risk for autism spectrum disorder (ASD) and (b) identifying provider characteristics that predict attitudes about parent engagement strategies. METHODS: A mixed method approach was utilized, including gathering quantitative data via survey (breadth) and collecting qualitative data via interview (depth). Acceptability, utility, appropriateness, sustainment, generalizability, and perceived effectiveness were examined. Fourteen agency leaders and 24 therapists provided input. RESULTS: Providers perceived the integration of parent engagement strategies as having a positive impact on implementation. Providers considered the strategies to be acceptable, appropriate, and effective, though barriers of time and complexity were noted. Provider characteristics did not consistently predict attitudes about the engagement strategies. CONCLUSIONS: Incorporating parent engagement strategies into parent-mediated interventions for ASD is well-received by providers and may improve quality of service delivery for families served in early intervention for ASD.

Parent Mental Health Problems and Motivation as Predictors of Their Engagement in Community-Based Child Mental Health Services.

Parent or caregiver engagement in child mental health treatment is an important element of treatment effectiveness, particularly for children with disruptive behavior problems. Parent or caregiver characteristics, such as their mental health and/or motivation to participate in treatment, may impact engagement and subsequent treatment outcomes. However, a lack of empirical research exists examining these potential links, particularly in community-based treatment settings. The current pilot study: 1) examines whether parent mental health problems and/or early parent motivation to participate in treatment predict three indicators of parent engagement in child treatment, controlling for the other predictor; and 2) examines and compares the differential influence of parent mental health and parent motivation on each parent engagement indicator. Participants in this study include 19 dyads from 18 therapists who were recruited from community mental health clinics. Results indicated a significant association between parent mental health and session attendance, and a marginally significant association between parent mental health and therapist-rated parent engagement. Parent mental health predicted outcomes above and beyond parent motivation. These findings preliminarily suggest that parent mental health problems early in child mental health treatment may be important to consider as an impactful target to promote parent treatment engagement, in addition to focusing on parent motivation to participate in treatment.

Randomized Trial of the Parent And Caregiver Active Participation Toolkit for Child Mental Health Treatment.

The purpose of this pilot study was to examine preliminary feasibility, acceptability, and effectiveness of a toolkit (Parent And Caregiver Active Participation Toolkit) to increase parent participation in community-based child mental health services. Study participants included 29 therapists (93% female; M age = 34.1 years; 38% Latino) and 20 parent/child dyads (children 80% female; M age = 8.6 years; parents 40% Latino) in 6 diverse community mental health clinics. Therapists were randomly assigned to standard care or the toolkit with standard care. Therapist and parent survey data and observational coding of treatment sessions were utilized. Mean comparisons and repeated measures analyses were used to test differences between study conditions over 4 months. Results supported preliminary feasibility and acceptability of the toolkit, with therapists assigned to the toolkit participating in ongoing training, adhering to toolkit use, and perceiving the toolkit as feasible and acceptable within their setting. Results preliminarily demonstrated improvement in therapists' job attitudes, as well as actual use of parent engagement strategies. Results also preliminarily demonstrated increases in parent participation in child therapy sessions and more regular attendance, as well as some indication of support for perceived treatment effectiveness. Overall, results suggest the feasibility, acceptability, and potential effectiveness of the toolkit to enhance therapist job attitudes; practices that support parent engagement, parent engagement itself, and consumer perspectives on treatment outcomes; and the potential promise of future research in the area of parent participation interventions in child mental health services.

Integrating a Parent-Implemented Blend of Developmental and Behavioral Intervention Strategies into Speech-Language Treatment for Toddlers at Risk for Autism Spectrum Disorder.

Naturalistic developmental behavioral interventions include an explicit focus on coaching parents to use therapy techniques in daily routines and are considered best practice for young children with autism. Unfortunately, these approaches are not widely used in community settings, possibly due to the clinical expertise and training required. This article presents the work of the Bond, Regulate, Interact, Develop, Guide, Engage (BRIDGE Collaborative), a multidisciplinary group of service providers (including speech-language pathologists), parents, funding agency representatives, and researchers dedicated to improving the lives of young children with autism spectrum disorder and their families. The group selected and adapted a parent coaching naturalistic developmental behavioral intervention specifically for use with toddlers and their families for community implementation. Lessons learned from the implementation process include the importance of therapist background knowledge, the complexity of working with parents of young children, and needed supports for those working closely with parents, including specific engagement strategies and the incorporation of reflective practice.

The Parent Participation Engagement Measure (PPEM): Reliability and Validity in Child and Adolescent Community Mental Health Services.

Parent participation in community-based child mental health services is an important yet understudied process associated with treatment effectiveness. This paper describes the development and psychometrics of the Parent Participation Engagement Measure in a sample of 1374 parents and 563 youth receiving publicly-funded mental health services. Analyses indicated excellent internal consistency, and model fit indices/factor loadings supported a one-factor model. Convergent and discriminant validity were supported, although some coefficients were modest in magnitude. Psychometric results were consistent for Caucasian versus Hispanic, parent versus youth, and English versus Spanish-language respondents. The clinical and research utility of this measure are discussed.

Factors contributing to reduced caregiver strain in a publicly-funded child mental health system.

This study examined caregiver strain in families who initiated mental health services for their child. Predictors of strain and the bidirectional relation between strain and child symptoms were examined. Participants included 218 children ages 4-13 with disruptive behavior problems and their caregivers, plus 96 psychotherapists, recruited from six publicly-funded clinics. Child disruptive behavior severity and caregiver strain were assessed at baseline, four, and eight months. Multilevel models were used to examine predictors of reduced caregiver strain, and autoregressive cross-lagged models were used to examine the bidirectional relations between change in caregiver strain and behavior problems over time. There were small to medium decreases in caregiver strain over the eight months after the initiation of mental health services, but few factors predicted change other than initial behavior problem severity. While more severe initial child symptoms predicted greater reductions in caregiver strain, greater child symptom severity sustained at four months predicted lesser improvements in caregiver strain. Simultaneously, greater caregiver strain predicted less improvement in child symptom severity, suggesting that child symptom severity and caregiver strain impact each other over time. These results suggest that attending to both child and caregiver factors may be important in maintaining improvements after initiating usual care.

Searching for elements of evidence-based practices in children's usual care and examining their impact.

Most of the knowledge generated to bridge the research-practice gap has been derived from experimental studies implementing specific treatment models. Alternatively, this study uses observational methods to generate knowledge about community-based treatment processes and outcomes. Aims are to (a) describe outcome trajectories for children with disruptive behavior problems (DBPs), and (b) test how observed delivery of a benchmark set of practice elements common in evidence-based treatments may be associated with outcome change while accounting for potential confounding variables. Participants included 190 children ages 4 to 13 with DBPs and their caregivers, plus 85 psychotherapists, recruited from six clinics. All treatment sessions were videotaped and a random sample of 4 sessions in the first 4 months of treatment was reliably coded for intensity on 27 practice elements (benchmark set and others). Three outcomes (child symptom severity, parent discipline, and family functioning) were assessed by parent report at intake, 4, and 8 months. Data were collected on several potential covariates including child, parent, therapist, and service use characteristics. Multilevel modeling was used to assess relationships between observed practice and outcome slopes while accounting for covariates. Children and families demonstrated improvements in all 3 outcomes, but few significant associations between treatment processes and outcome change were identified. Families receiving greater intensity on the benchmark practice elements did demonstrate greater improvement in the parental discipline outcome. Observed changes in outcomes for families in community care were generally not strongly associated with the type or amount of treatment received.

Consistency with evidence-based treatments and perceived effectiveness of children's community-based care.

This study examined whether delivery of psychotherapeutic strategies consistent with common elements of evidence-based (EB) treatments for child disruptive behavior problems was associated with parents' report of treatment effectiveness. The intensity of delivery of practice elements consistent with EB treatments was coded from a random sample of 538 videotaped psychotherapy sessions with 157 children/families and 75 therapists from six community-based clinics. Multilevel regression analyses tested whether intensity of EB practice elements was associated with parents' report of treatment effectiveness after 4 months, controlling for intensity of other practice elements. Results indicate parents reported greater perceived treatment effectiveness when community-based treatment included more intensive delivery of practice elements consistent with EB treatments to children. These findings may reassure providers about the acceptability of EB practice elements and may motivate efforts to integrate EB practice elements more intensively into community-based care.

Improving community-based mental health care for children: translating knowledge into action.

There is urgent need for improvement in community-based mental health care for children and families. Multiple studies have documented serious limitations in the effectiveness of "usual care." Fortunately, many empirically-supported strategies to improve care have been developed, and thus there is now a great deal of knowledge available to address this significant public health problem. The goal of this selective review is to highlight and synthesize that empirically-supported knowledge to stimulate and facilitate the needed translation of knowledge into action. The review provides a sound foundation for constructing improved services by consolidating descriptive data on the status quo in children's mental health care, as well as evidence for an array of promising strategies to improve (a) Service access and engagement; (b) Delivery of evidence-based practices; and (c) Outcome accountability. A multi-level framework is used to highlight recommended care improvement targets.

Setting Families Up for Success: A Pilot Study of a Toolkit to Enhance the Autism Spectrum Disorder Diagnostic Evaluation Process.

Families of children with autism spectrum disorder (ASD) face challenges engaging in services following diagnosis. This study: (1) developed and implemented a toolkit to tailor ASD evaluation feedback to families' needs, and (2) evaluated caregiver and provider perceptions of the toolkit. Focus groups with providers (N = 11) informed toolkit development. Seven providers participated in pilot training and implementation. Provider and caregiver toolkit perceptions were assessed using interviews, surveys, and a fidelity checklist. Toolkit strategies reflect focus group themes. Provider and caregiver ratings suggest the initial feasibility, acceptability, and utility of the toolkit. This toolkit may be feasible to implement in community settings and may increase caregiver satisfaction, though further refinements are needed to support service connection.

Provider perspectives and reach of an evidence-based intervention in community services for toddlers.

LAY ABSTRACT: Expert recommendations for toddlers who are likely to develop autism include caregivers being actively involved in the services children receive. However, many services available in the community may not follow these recommendations. Evidence suggests that an intervention named Project ImPACT for Toddlers demonstrates positive parent and child outcomes for families in the community. Project ImPACT for Toddlers was designed specifically for toddlers by a group of parents, clinicians, researchers, and funders. It teaches parents of young children strategies to support their child's development in daily routines. This study reports the perspectives of early intervention providers who learned to use Project ImPACT for Toddlers on whether the intervention was a good fit for their practice and easy to use. The study also examines how many agencies are using Project ImPACT for Toddlers and how many families have received the intervention in the community. The goal of the study is to inform the continued use of Project ImPACT for Toddlers in the community and support offering the intervention in other regions. Participants include 38 community providers who participated in a training study of Project ImPACT for Toddlers and completed a survey and semi-structured interview after approximately 3 months of using Project ImPACT for Toddlers with families. Participants perceived the training model as acceptable and appropriate, and identified the group-based model of training, comprehensive materials, and agency support as strengths of the approach. Survey findings complemented the results from the interviews. Data indicate an increasing number of agencies and families accessing Project ImPACT for Toddlers. Efforts to expand evidence-based intervention in early intervention should continue to build upon the model used for Project ImPACT for Toddlers.

EEG and video-EEG seizure monitoring has limited utility in patients with hypothalamic hamartoma and epilepsy.

PURPOSE: Hypothalamic hamartomas (HHs) are a malformation of the ventral hypothalamus and tuber cinereum, associated with gelastic seizures and epilepsy. We sought to determine the spectrum of electroencephalography (EEG) abnormalities in a large cohort of HH patients. METHODS: Data was collected for HH patients undergoing evaluation between 2003 and 2007. Data included seizure history, prior treatment, and results of diagnostic studies. After informed consent, data were entered into a database. KEY FINDINGS: We reviewed 133 HH patients. Mean age at time of data analysis was 15.7 years (59.4% male). Most patients had gelastic (77%) and/or complex partial seizures (58%). Records for 102 EEG studies on 73 patients were reviewed. Interictal epileptiform abnormalities were seen in 77%, localizing predominately to the temporal and frontal regions. Records for 104 video-EEG (VEEG) studies on 65 patients were reviewed. Of 584 gelastic seizures (GS) captured, no ictal EEG change was noted in 438 (75%). Of GS with localizing features, 89% suggested onset from the temporal and/or frontal regions. There were 160 complex partial seizures (CPS). For those with localizing features, 100% localized to the temporal and/or frontal head regions. EEG and VEEG findings correlated with the side of HH attachment. VEEG did not influence outcome. SIGNIFICANCE: EEG features in HH patients are diverse. The majority of gelastic seizures fail to demonstrate change in the EEG. The lack of EEG changes with many clinical seizures, and the false localization seen in those events with an ictal change suggest the utility of EEG is limited in the evaluation of these patients.

Parent And Caregiver Active Participation Toolkit (PACT): Adaptation for a Home Visitation Program.

OBJECTIVES: Parent engagement poses a persistent challenge to home visitation (HV) programs. Previous work on parent engagement in HV has focused primarily on enrollment, attendance, and retention, with less attention on participation. The purpose of this study was to adapt an engagement toolkit originally developed for child mental health treatment settings, the Parent And Caregiver Active Participation Toolkit (PACT), and test the adapted toolkit in a HV program, SafeCare® (SC), with a focus on parent participation. METHODS: Toolkit adaptation was informed by interviews/focus groups with parents and home visitors. Next, home visitors (n = 6) were trained to use adapted PACT for SC as part of SC delivery to 18 parents. A comparison group included 24 parents who received SC one year prior to this study. Analyses compared PACT for SC participants to the comparison group on parent participation and home visitor fidelity to assignment of homework. Qualitative and quantitative data from parents, home visitors, and supervisors (n = 4) assessed the acceptability, utility, appropriateness, and feasibility of PACT for SC. RESULTS: Parents receiving PACT for SC had higher participation and reported greater home visitor fidelity to homework assignment than comparison parents. Parents found PACT for SC acceptable and useful as part of SC. Home visitors and supervisors identified some limitations in PACT for SC's utility but generally found it to be a positive, feasible addition to HV services. CONCLUSIONS: Results suggest that enhancing HV programs with an engagement toolkit may improve parents' participation in services and providers' assignment of homework between sessions.

In-Session Caregiver Behaviors during Evidence-Based Intervention Delivery for Children with ASD in Community Mental Health Services.

An Individualized Mental Health Intervention for ASD, ("AIM HI"), is a collaborative, caregiver-mediated and child-directed intervention for reducing challenging behaviors in children with autism spectrum disorder developed for delivery in community mental health programs. Using observational data from AIM HI sessions, the present study characterized the occurrence of two types of in-session caregiver behaviors: expressed concerns (i.e., expressing concerns about treatment strategies; expressing difficulty using skills; expressing difficulty completing homework) and participation engagement (i.e., asking questions; participating in session activities; showing commitment to therapy). Further analyses examined cultural differences in caregiver behaviors and associations between caregiver behaviors and clinician adherence. Participants included 39 caregiver-clinician dyads enrolled in a community effectiveness trial of AIM HI. Video recordings from 107 sessions during the first two months of treatment were coded for in-session caregiver behaviors and clinician adherence. Results indicated that expressed concerns were observed in 47% of sessions. When controlling for household income, Latinx caregivers were rated lower for expressing concerns about treatment strategies and demonstrated lower participation engagement behaviors in session compared with non-Latinx White caregivers, suggesting that cultural factors may impact verbal engagement in sessions. Finally, expressing concerns about treatment strategies, expressing difficulty using skills, and participation engagement were positively associated with clinician adherence. Findings suggest that some expressed concerns and participation engagement behaviors may be indicators of positive caregiver engagement in the context of a collaborative intervention, and lower levels of such caregiver engagement may actually impede clinicians' delivery of intensive evidence-based intervention in routine care.

Observational Assessment of Engagement Strategies to Promote Parent Homework Planning in Community-Based Child Mental Health Treatment: A Pilot Study.

Therapy homework includes tasks given to clients to complete outside of session to facilitate new knowledge/skills or to advance treatment goals. Homework completion, an important element of parent engagement in child mental health (MH) treatment, has been associated with improved child outcomes. The current pilot study assessed the design/assign phase of the therapy homework process to examine a) the extent to which therapists implemented engagement strategies with parents and b) whether therapist deployment of engagement strategies in early treatment predicted subsequent parent participation in homework planning. We included an ethnically-diverse sample of 10 therapists and 11 parent/child dyads receiving community-based MH services who participated in a pilot intervention study. Two observational coding systems were developed to code treatment session recordings for the extent to which a) therapists implemented engagement strategies with parents and b) parents contributed to therapy homework planning. Findings revealed low extensiveness of therapist implementation of engagement strategies with parents. As hypothesized, therapist use of engagement strategies (Collaboration, Empowerment, and Psychoeducation) in early treatment significantly predicted subsequent parent homework planning (sharing perspective on homework planning). However, therapist use of Alliance was unrelated to parent homework planning. These preliminary results suggest that therapist implementation of engagement strategies in early treatment may promote parent participation in homework planning, which is an important precursor to homework completion. This pilot study suggests potential future directions for both research on and training for community-based therapists in implementing successful strategies to promote parent homework planning in child MH treatment.

Stakeholder perspectives on a toolkit to enhance caregiver participation in community-based child mental health services.

Client engagement in services is a critical element of effective community-based child and family mental health service delivery. Caregiver engagement is particularly important, as caregivers often serve as gatekeepers to child mental health care and typically must consent for services, facilitate service attendance, and are often the target of intervention themselves. Unfortunately, caregiver engagement has been identified as a significant challenge in community-based child mental health services. To address this gap, the Parent And Caregiver Active Participation Toolkit (PACT), which includes therapist training and participation tools for caregivers and therapists, was developed. Stakeholders' perspectives regarding the delivery of interventions designed to improve the quality and effectiveness of community-based care are essential to understanding the implementation of such interventions in routine service settings. As such, this mixed methods study examined the perspectives of 12 therapists, 8 caregivers, and 6 program managers who participated in a community-based randomized pilot study of PACT. Therapists, caregivers, and program managers agreed that PACT was acceptable, appropriate, and feasible to use in community settings and that both changes in therapist practices and caregiver participation resulted from implementing PACT. Some variable perceptions in the utility of the therapist training components were identified, as well as barriers and facilitators of PACT implementation. Results expand the parent pilot study's findings as well as complement and expand the literature on training community providers in evidence-based practices. (PsycINFO Database Record

Examining ethnic disparities in provider and parent in-session participation engagement.

PURPOSE: Well-documented ethnic disparities exist in the identification and provision of quality services among children receiving community-based mental health services. These disparities extend to parent treatment engagement, an important component of effective mental health services. Currently, little is known about differences in how providers support parents' participation in treatment and the degree to which parents actively participate in it. The purpose of this paper is to examine potential differences in both provider and parent in-session participation behaviours. DESIGN/METHODOLOGY/APPROACH: Participants included 17 providers providing standard community-based mental health treatment for 18 parent-child dyads, with 44 per cent of the dyads self-identifying as Hispanic/Latino. In-session participation was measured with the parent participation engagement in child psychotherapy and therapist alliance, collaboration, and empowerment strategies observational coding systems. FINDINGS: Overall, results indicate significantly lower levels of parent participation behaviours among Hispanic/Latino families compared to their Non-Hispanic/Non-Latino counterparts. No significant differences were seen in providers' in-session behaviours to support parent participation across Hispanic/Latino and Non-Hispanic/Non-Latino families. RESEARCH LIMITATIONS/IMPLICATIONS: These findings contribute to the literature on ethnic differences in parent treatment engagement by utilising measures of in-session provider and parent behaviours and suggest that further investigation is warranted to documenting and understanding ethnic disparities in parents' participation in community-based child mental health treatment. ORIGINALITY/VALUE: This paper contributes to the evaluation of differences in parent treatment engagement through demonstrating the utility of an in-session observational coding system as a measure of treatment engagement.

Improving and sustaining delivery of CPT for PTSD in mental health systems: a cluster randomized trial.

BACKGROUND: Large-scale implementation of evidence-based psychotherapies (EBPs) such as cognitive processing therapy (CPT) for posttraumatic stress disorder can have a tremendous impact on mental and physical health, healthcare utilization, and quality of life. While many mental health systems (MHS) have invested heavily in programs to implement EBPs, few eligible patients receive EBPs in routine care settings, and clinicians do not appear to deliver the full treatment protocol to many of their patients. Emerging evidence suggests that when CPT and other EBPs are delivered at low levels of fidelity, clinical outcomes are negatively impacted. Thus, identifying strategies to improve and sustain the delivery of CPT and other EBPs is critical. Existing literature has suggested two competing strategies to promote sustainability. One emphasizes fidelity to the treatment protocol through ongoing consultation and fidelity monitoring. The other focuses on improving the fit and effectiveness of these treatments through appropriate adaptations to the treatment or the clinical setting through a process of data-driven, continuous quality improvement. Neither has been evaluated in terms of impact on sustained implementation. METHODS: To compare these approaches on the key sustainability outcomes and provide initial guidance on sustainability strategies, we propose a cluster randomized trial with mental health clinics (n = 32) in three diverse MHSs that have implemented CPT. Cohorts of clinicians and clinical managers will participate in 1 year of a fidelity oriented learning collaborative or 1 year of a continuous quality improvement-oriented learning collaborative. Patient-level PTSD symptom change, CPT fidelity and adaptation, penetration, and clinics' capacity to deliver EBP will be examined. Survey and interview data will also be collected to investigate multilevel influences on the success of the two learning collaborative strategies. This research will be conducted by a team of investigators with expertise in CPT implementation, mixed method research strategies, quality improvement, and implementation science, with input from stakeholders in each participating MHS. DISCUSSION: It will have broad implications for supporting ongoing delivery of EBPs in mental health and healthcare systems and settings. The resulting products have the potential to significantly improve efforts to ensure ongoing high quality implementation and consumer access to EBPs. TRIAL REGISTRATION: NCT02449421 . Registered 02/09/2015.