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BackgroundShort-course tuberculosis (TB) prevention regimens, including 12 weeks of isoniazid and rifapentine (3HP), are increasingly used in high-TB-burden countries. Despite established safety and tolerability in efficacy trials, 3HP-related adverse events (AEs) could differ in routine settings. Real-world data on AE type, frequency, and timing are crucial for health systems considering 3HP programmatic scale-up.MethodsWe reviewed AEs among people with human immunodeficiency virus (HIV) participating in a pragmatic implementation trial of facilitated 3HP taken by directly observed therapy (DOT) or self-administered therapy (SAT) in Kampala, Uganda, and classified them using the Common Terminology Criteria for Adverse Events. We assessed AE timing and summarized related clinical actions including laboratory tests, diagnoses made, medications prescribed, and treatment interruptions.ResultsAmong 1655 people with HIV treated between July 2020 and September 2022, 270 (16.3%) reported 451 events; main issues included general (7%), nervous system (6%), musculoskeletal (5%), gastrointestinal (5%), and dermatologic (3%) disorders. Most (61%) occurred within 6 weeks of initiating 3HP. Among those with events, 211 (78%) required further clinician evaluation, 202 (75%) required laboratory testing, 102 (38%) had medications prescribed, 40 (15%) had treatment paused, and 14 (5%) discontinued 3HP. Women, those multidimensionally impoverished, and DOT recipients were more likely to report an AE. SAT users and later enrollees were more likely to have 3HP interrupted or stopped due to an AE.ConclusionsIn a routine setting, 3HP was safe, with 16% of people with HIV reporting AEs and only 3% requiring temporary or permanent treatment interruption. These findings support 3HP expansion in routine HIV/AIDS care settings for TB prevention. Clinical Trials Registration. NCT03934931.

BACKGROUND: Economic incentives can improve clinical outcomes among in-care people living with HIV (PLHIV), but evidence is limited for their effectiveness among out-of-care PLHIV or those at risk of disengagement. We propose a type 1 hybrid effectiveness-implementation study to advance global knowledge about the use of economic incentives to strengthen the continuity of HIV care and accelerate global goals for HIV epidemic control. METHODS: The Rudi Kundini, Pamoja Kundini study will evaluate two implementation models of an economic incentive strategy for supporting two groups of PLHIV in Tanzania. Phase 1 of the study consists of a two-arm, cluster randomized trial across 32 health facilities to assess the effectiveness of a home visit plus one-time economic incentive on the proportion of out-of-care PLHIV with viral load suppression (

BackgroundExpanding access to shorter regimens for tuberculosis (TB) prevention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for reducing global TB burden among people living with HIV (PLHIV). Our coprimary hypotheses were that high levels of acceptance and completion of 3HP could be achieved with delivery strategies optimized to overcome well-contextualized barriers and that 3HP acceptance and completion would be highest when PLHIV were provided an informed choice between delivery strategies.Methods and findingsIn a pragmatic, single-center, 3-arm, parallel-group randomized trial, PLHIV receiving care at a large urban HIV clinic in Kampala, Uganda, were randomly assigned (1:1:1) to receive 3HP by facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between facilitated DOT and facilitated SAT using a shared decision-making aid. We assessed the primary outcome of acceptance and completion (≥11 of 12 doses of 3HP) within 16 weeks of treatment initiation using proportions with exact binomial confidence intervals (CIs). We compared proportions between arms using Fisher's exact test (two-sided α = 0.025). Trial investigators were blinded to primary and secondary outcomes by study arm. Between July 13, 2020, and July 8, 2022, 1,656 PLHIV underwent randomization, with equal numbers allocated to each study arm. One participant was erroneously enrolled a second time and was excluded in the primary intention-to-treat analysis. Among the remaining 1,655 participants, the proportion who accepted and completed 3HP exceeded the prespecified 80% target in the DOT (0.94; 97.5% CI [0.91, 0.96] p < 0.001), SAT (0.92; 97.5% CI [0.89, 0.94] p < 0.001), and Choice (0.93; 97.5% CI [0.91, 0.96] p < 0.001) arms. There was no difference in acceptance and completion between any 2 arms overall or in prespecified subgroup analyses based on sex, age, time on antiretroviral therapy, and history of prior treatment for TB or TB infection. Only 14 (0.8%) participants experienced an adverse event prompting discontinuation of 3HP. The main limitation of the study is that it was conducted in a single center. Multicenter studies are now needed to confirm the feasibility and generalizability of the facilitated 3HP delivery strategies in other settings.ConclusionsShort-course TB preventive treatment was widely accepted by PLHIV in Uganda, and very high levels of treatment completion were achieved in a programmatic setting with delivery strategies tailored to address known barriers.Trial registrationClinicalTrials.gov NCT03934931.

BackgroundFor people with advanced-stage Kaposi's sarcoma (KS), a common HIV-associated malignancy in sub-Saharan Africa, mortality is estimated to be 45% within 2 years after KS diagnosis, despite increasingly wide-spread availability of antiretroviral therapy and chemotherapy. For advanced-stage KS, chemotherapy in addition to antiretroviral therapy improves outcomes and saves lives, but currently, only ~50% of people with KS in western Kenya who have an indication for chemotherapy actually receive it. This protocol describes the evaluation of a multicomponent patient navigation strategy that addresses common barriers to service penetration of and fidelity to evidence-based chemotherapy among people with advanced-stage KS in Kenya.MethodsThis is a hybrid type III effectiveness-implementation study using a non-randomized, pre- post-design nested within a longitudinal cohort. We will compare the delivery of evidence-based chemotherapy for advanced-stage KS during the period before (2016-2020) to the period after (2021-2024), the rollout of a multicomponent patient navigation strategy. The multicomponent patient navigation strategy was developed in a systematic process to address key determinants of service penetration of and fidelity to chemotherapy in western Kenya and includes (1) physical navigation and care coordination, (2) video-based education, (3) travel stipend, (4) health insurance enrollment assistance, (5) health insurance stipend, and (6) peer mentorship. We will compare the pre-navigation period to the post-navigation period to assess the impact of this multicomponent patient navigation strategy on (1) implementation outcomes: service penetration (chemotherapy initiation) and fidelity (chemotherapy completion) and (2) service and client outcomes: timeliness of cancer care, mortality, quality of life, stigma, and social support. We will also describe the implementation process and the determinants of implementation success for the multicomponent patient navigation strategy.DiscussionThis study addresses an urgent need for effective implementation strategies to improve the initiation and completion of evidence-based chemotherapy in advanced-stage KS. By using a clearly specified, theory-based implementation strategy and validated frameworks, this study will contribute to a more comprehensive understanding of how to improve cancer treatment in advanced-stage KS.

Abstract Background Economic incentives can improve clinical outcomes among in-care people living with HIV (PLHIV), but evidence is limited for their effectiveness among out-of-care PLHIV or those at risk of disengagement. We propose a type 1 hybrid effectiveness-implementation study to advance global knowledge about the use of economic incentives to strengthen the continuity of HIV care and accelerate global goals for HIV epidemic control. Methods The Rudi Kundini, Pamoja Kundini study will evaluate two implementation models of an economic incentive strategy for supporting two groups of PLHIV in Tanzania. Phase 1 of the study consists of a two-arm, cluster randomized trial across 32 health facilities to assess the effectiveness of a home visit plus one-time economic incentive on the proportion of out-of-care PLHIV with viral load suppression (

Background: Economic incentives can improve clinical outcomes among in-care people living with HIV (PLHIV), but evidence is limited for their effectiveness among out-of-care PLHIV or those at risk of disengagement. We propose a type 1 hybrid effectiveness-implementation study to advance global knowledge about the use of economic incentives to strengthen the continuity of HIV care and accelerate global goals for HIV epidemic control. Methods: The Rudi Kundini, Pamoja Kundini study will evaluate two implementation models of an economic incentive strategy for supporting two groups of PLHIV in Tanzania. Phase 1 of the study consists of a two-arm, cluster randomized trial across 32 health facilities to assess the effectiveness of a home visit plus one-time economic incentive on the proportion of out-of-care PLHIV with viral load suppression (< 1000 copies/ml) 6 months after enrollment (n = 640). Phase 2 is an individual 1:1 randomized controlled trial designed to determine the effectiveness of a short-term counseling and economic incentive program offered to in-care PLHIV who are predicted through machine learning to be at risk of disengaging from care on the outcome of viral load suppression at 12 months (n = 692). The program includes up to three incentives conditional upon visit attendance coupled with adapted counselling sessions for this population of PLHIV. Consistent with a hybrid effectiveness-implementation study design, phase 3 is a mixed methods evaluation to explore barriers and facilitators to strategy implementation in phases 1 and 2. Results will be used to guide optimization and scale-up of the incentive strategies, if effective, to the larger population of Tanzanian PLHIV who struggle with continuity of HIV care. Discussion: Innovative strategies that recognize the dynamic process of lifelong retention in HIV care are urgently needed. Strategies such as conditional economic incentives are a simple and effective method for improving many health outcomes, including those on the HIV continuum. If coupled with other supportive services such as home visits (phase 1) or with tailored counselling (phase 2), economic incentives have the potential to strengthen engagement among the subpopulation of PLHIV who struggle with retention in care and could help to close the gap towards reaching global "95–95-95" goals for ending the AIDS epidemic. Trial registration: Phase 1: ClinicalTrials.gov, NCT05248100, registered 2/21/2022. Phase 2: ClinicalTrials.gov, NCT05373095, registered 5/13/2022. [ABSTRACT FROM AUTHOR]

BackgroundRecently, a 3-month (12-dose) regimen of weekly isoniazid and rifapentine (3HP) was recommended by the World Health Organization for the prevention of tuberculosis (TB) among people living with HIV (PLHIV) on common antiretroviral therapy regimens. The best approach to delivering 3HP to PLHIV remains uncertain.MethodsWe developed a three-armed randomized trial assessing optimized strategies for delivering 3HP to PLHIV. The trial will be conducted at the Mulago Immune Suppression Syndrome (i.e., HIV/AIDS) clinic in Kampala, Uganda. We plan to recruit 1656 PLHIV, randomized 1:1 to each of the three arms (552 per arm). Using a hybrid type 3 effectiveness-implementation design, this pragmatic trial aims to (1) compare the acceptance and completion of 3HP among PLHIV under three delivery strategies: directly observed therapy (DOT), self-administered therapy (SAT), and informed patient choice of either DOT or SAT (with the assistance of a decision aid); (2) to identify processes and contextual factors that influence the acceptance and completion of 3HP under each delivery strategy; and (3) to estimate the costs and compare the cost-effectiveness of three strategies for delivering 3HP. The three delivery strategies were each optimized to address key barriers to 3HP completion using a theory-informed approach. We hypothesize that high levels of treatment acceptance and completion can be achieved among PLHIV in sub-Saharan Africa and that offering PLHIV an informed choice between the optimized DOT and SAT delivery strategies will result in greater acceptance and completion of 3HP. The design and planned evaluation of the delivery strategies were guided by the use of implementation science conceptual frameworks.Discussion3HP-one of the most promising interventions for TB prevention-will not be scaled up unless it can be delivered in a patient-centered fashion. We highlight shared decision-making as a key element of our trial design and theorize that offering PLHIV an informed choice between optimized delivery strategies will facilitate the highest levels of treatment acceptance and completion.Trial registrationClinicalTrials.gov: NCT03934931 ; Registered 2 May 2019.

Abstract Background For people with advanced-stage Kaposi’s sarcoma (KS), a common HIV-associated malignancy in sub-Saharan Africa, mortality is estimated to be 45% within 2 years after KS diagnosis, despite increasingly wide-spread availability of antiretroviral therapy and chemotherapy. For advanced-stage KS, chemotherapy in addition to antiretroviral therapy improves outcomes and saves lives, but currently, only ~50% of people with KS in western Kenya who have an indication for chemotherapy actually receive it. This protocol describes the evaluation of a multicomponent patient navigation strategy that addresses common barriers to service penetration of and fidelity to evidence-based chemotherapy among people with advanced-stage KS in Kenya. Methods This is a hybrid type III effectiveness-implementation study using a non-randomized, pre- post-design nested within a longitudinal cohort. We will compare the delivery of evidence-based chemotherapy for advanced-stage KS during the period before (2016–2020) to the period after (2021–2024), the rollout of a multicomponent patient navigation strategy. The multicomponent patient navigation strategy was developed in a systematic process to address key determinants of service penetration of and fidelity to chemotherapy in western Kenya and includes (1) physical navigation and care coordination, (2) video-based education, (3) travel stipend, (4) health insurance enrollment assistance, (5) health insurance stipend, and (6) peer mentorship. We will compare the pre-navigation period to the post-navigation period to assess the impact of this multicomponent patient navigation strategy on (1) implementation outcomes: service penetration (chemotherapy initiation) and fidelity (chemotherapy completion) and (2) service and client outcomes: timeliness of cancer care, mortality, quality of life, stigma, and social support. We will also describe the implementation process and the determinants of implementation success for the multicomponent patient navigation strategy. Discussion This study addresses an urgent need for effective implementation strategies to improve the initiation and completion of evidence-based chemotherapy in advanced-stage KS. By using a clearly specified, theory-based implementation strategy and validated frameworks, this study will contribute to a more comprehensive understanding of how to improve cancer treatment in advanced-stage KS.

Abstract Background Theory-based implementation strategies, such as audit and feedback (A&F), can improve the adoption of evidence-based practices. However, few strategies have been developed and tested to meet the needs of specialty clinics. In particular, frontline staff can execute cardiovascular disease (CVD) risk reduction protocols, but A&F strategies to support them are not well examined. Our objective was to develop and evaluate a theory-based approach to A&F, Interactive and Participatory A&F (IPAF). Methods We developed IPAF informed by two complementary theories, self-regulation theory (SRT) and self-determination theory (SDT). IPAF applies concepts from these theories to inform (1) what to address with staff to improve rates of best practices (SRT) and (2) how to interact with staff to improve behaviors aligned with best practices (SDT). We promoted IPAF fidelity by developing a semi-structured guide to facilitate staff discussion of target behaviors, perceived barriers, goals, and action plans. We evaluated IPAF in the context of eight quasi-experimental implementations in specialty clinics across two health systems. Following a hybrid type 2 effectiveness-implementation design, we reported intervention outcomes for CVD risk reduction elsewhere. This paper reports implementation outcomes associated with IPAF, focusing on feasibility, appropriateness, acceptability, fidelity, and adoption. We evaluated implementation outcomes using mixed-methods data including electronic health record (EHR) data, team records, and staff questionnaire responses. Results Eighteen staff participated in 99 monthly, individual, synchronous (face-to-face or phone) IPAF sessions during the first 6 months of implementation. Subsequently, we provided over 375 monthly feedback emails. Feasibility data revealed high staff attendance (90–93%) and engagement in IPAF sessions. Staff highly rated questionnaire items about IPAF acceptability. Team records and staff responses demonstrated fidelity of IPAF delivery and receipt. Adoption of target behaviors increased significantly (all P values < 0.05), and adoption or behaviors were maintained for over 24 months. Conclusions We developed and evaluated a theory-based approach to A&F with frontline staff in specialty clinics to improve the implementation of evidence-based interventions. The findings support feasibility, appropriateness, acceptability, and fidelity of IPAF, and staff adoption and maintenance of target behaviors. By evaluating multi-site implementation outcomes, we extended prior research on clinic protocols and A&F beyond primary care settings and providers.

BACKGROUND: Each year in the USA, 1.5-2.5 million Americans are so severely injured that they require inpatient hospitalization. Multiple conditions including posttraumatic stress disorder (PTSD), alcohol and drug use problems, depression, and chronic medical conditions are endemic among physical trauma survivors with and without traumatic brain injuries. METHODS/DESIGN: The trauma survivors outcomes and support (TSOS) effectiveness-implementation hybrid trial is designed to test the delivery of high-quality screening and intervention for PTSD and comorbidities across 24 US level I trauma center sites. The pragmatic trial aims to recruit 960 patients. The TSOS investigation employs a stepped wedge cluster randomized design in which sites are randomized sequentially to initiate the intervention. Patients identified by a 10-domain electronic health record screen as high risk for PTSD are formally assessed with the PTSD Checklist for study entry. Patients randomized to the intervention condition will receive stepped collaborative care, while patients randomized to the control condition will receive enhanced usual care. The intervention training begins with a 1-day on-site workshop in the collaborative care intervention core elements that include care management, medication, cognitive behavioral therapy, and motivational-interviewing elements targeting PTSD and comorbidity. The training is followed by site supervision from the study team. The investigation aims to determine if intervention patients demonstrate significant reductions in PTSD and depressive symptoms, suicidal ideation, alcohol consumption, and improvements in physical function when compared to control patients. The study uses implementation science conceptual frameworks to evaluate the uptake of the intervention model. At the completion of the pragmatic trial, results will be presented at an American College of Surgeons policy summit. Twenty-four representative US level I trauma centers have been selected for the study, and the protocol is being rolled out nationally. DISCUSSION: The TSOS pragmatic trial simultaneously aims to establish the effectiveness of the collaborative care intervention targeting PTSD and comorbidity while also addressing sustainable implementation through American College of Surgeons regulatory policy. The TSOS effectiveness-implementation hybrid design highlights the importance of partnerships with professional societies that can provide regulatory mandates targeting enhanced health care system sustainability of pragmatic trial results. TRIAL REGISTRATION: ClinicalTrials.gov NCT02655354 . Registered 27 July 2015.

Abstract Background Knee Osteoarthritis (OA) is a leading cause of global disability. The Collaborative Model of Care between Orthopaedics and Allied Healthcare Professionals (CONNACT) Model of Care (MoC) was developed by optimizing evidence-based non-surgical treatments to deliver value-based care for people with knee OA. The primary aim of this study is to determine the clinical effectiveness of the CONNACT MoC (3 months) compared to usual care. The secondary aims are: a) To determine the cost-effectiveness and b) To develop an evaluation and implementation framework to inform large scale implementation for this MoC. Methodology Type 1 Effectiveness-Implementation Hybrid Trial using an explanatory sequential mixed-method approach. The study consists of 3 components. The first component is the pragmatic, parallel-arm, single-blinded randomized control trial. Inclusion criteria are patients with knee OA based on the National Institute of Health and Care Excellence (NICE) criteria with radiographic severity of greater than Kellgren-Lawrence 1, and Knee Injury and OA Outcome Score (KOOS4) of equal or less than 75. Exclusion criteria include other forms of arthritis, history of previous knee arthroplasty or wheelchair-bound patient. KOOS4 is the primary outcome measure at 3 months, 6 months and 1 year. Secondary outcomes include KOOS individual subscales, quality of life scoring, functional performance, global, diet and psychological related outcomes. The second component is an economic evaluation of the cost-effectiveness of the CONNACT MoC using a societal perspective. The third component is an implementation and evaluation framework using process evaluation under the RE-AIM framework using a mixed-method approach. Sample size of 100 patients has been calculated. Discussion CONNACT MoC is a complex intervention. In line with the MRC guidance for developing and evaluating complex interventions, a pilot feasibility study was completed and a comprehensive approach including an RCT, economic evaluation and process evaluation is described in this study protocol. Results from this study will help clinicians, healthcare administrators and policymakers guide the sustainable and effective implementation of the CONNACT MoC for knee OA and serve as a basis for similar multidisciplinary MoC for chronic degenerative musculoskeletal conditions to be developed. Trial registration Clinicaltrials.gov Identifier: NCT03809975 . Registered January 182,019.

Abstract Background Recently, a 3-month (12-dose) regimen of weekly isoniazid and rifapentine (3HP) was recommended by the World Health Organization for the prevention of tuberculosis (TB) among people living with HIV (PLHIV) on common antiretroviral therapy regimens. The best approach to delivering 3HP to PLHIV remains uncertain. Methods We developed a three-armed randomized trial assessing optimized strategies for delivering 3HP to PLHIV. The trial will be conducted at the Mulago Immune Suppression Syndrome (i.e., HIV/AIDS) clinic in Kampala, Uganda. We plan to recruit 1656 PLHIV, randomized 1:1 to each of the three arms (552 per arm). Using a hybrid type 3 effectiveness-implementation design, this pragmatic trial aims to (1) compare the acceptance and completion of 3HP among PLHIV under three delivery strategies: directly observed therapy (DOT), self-administered therapy (SAT), and informed patient choice of either DOT or SAT (with the assistance of a decision aid); (2) to identify processes and contextual factors that influence the acceptance and completion of 3HP under each delivery strategy; and (3) to estimate the costs and compare the cost-effectiveness of three strategies for delivering 3HP. The three delivery strategies were each optimized to address key barriers to 3HP completion using a theory-informed approach. We hypothesize that high levels of treatment acceptance and completion can be achieved among PLHIV in sub-Saharan Africa and that offering PLHIV an informed choice between the optimized DOT and SAT delivery strategies will result in greater acceptance and completion of 3HP. The design and planned evaluation of the delivery strategies were guided by the use of implementation science conceptual frameworks. Discussion 3HP—one of the most promising interventions for TB prevention—will not be scaled up unless it can be delivered in a patient-centered fashion. We highlight shared decision-making as a key element of our trial design and theorize that offering PLHIV an informed choice between optimized delivery strategies will facilitate the highest levels of treatment acceptance and completion. Trial registration ClinicalTrials.gov: NCT03934931 ; Registered 2 May 2019.

Despite established knowledge that Low and Middle Income Countries (LMICs) bear the majority of the worlds burden of mental disorders, and more than a decade of efficacy research showing that the most common disorders, such as depression and anxiety, can be treated using readily available local personnel in LMICs to apply evidence-based treatments, there remains a massive mental health treatment gap, such that 75 % of those in LMICs never receive care. Here, we discuss the use of a new type of implementation science study design, the effectiveness-implementation hybrids, to speed the translation and scale up of mental health care in LMICs. We use our current study of Interpersonal Psychotherapy (IPT) delivered by local personnel for depression and trauma-related disorders among HIV+ women in Kenya as an example of effectiveness-implementation hybrid design for mental health services research in LMICs.

Background: Economic incentives can improve clinical outcomes among in-care people living with HIV (PLHIV), but evidence is limited for their effectiveness among out-of-care PLHIV or those at-risk of disengagement. We propose a type 1 hybrid effectiveness-implementation study to advance global knowledge about the use of economic incentives to strengthen the continuity of HIV care and accelerate global goals for HIV epidemic control., Methods: The Rudi Kundini, Pamoja Kundini study will evaluate two implementation models of an economic incentive strategy for supporting two groups of PLHIV in Tanzania. Phase 1 of the study consists of a two-arm, cluster randomized trial across 32 health facilities to assess the effectiveness of a home visit plus one-time economic incentive on the proportion of out-of-care PLHIV with viral load suppression (<1000 copies/ml) 6 months after enrollment (n = 640). Phase 2 is an individual 1:1 randomized controlled trial designed to determine the effectiveness of a short-term counseling and economic incentive program offered to in-care PLHIV who are predicted through machine learning to be at-risk of disengaging from care on the outcome of viral load suppression at 12 months (n = 692). The program includes up to three incentives conditional upon visit attendance coupled with adapted counselling sessions for this population of PLHIV. Consistent with a hybrid effectiveness-implementation study design, phase 3 is a mixed methods evaluation to explore barriers and facilitators to strategy implementation in phases 1 and 2. Results will be used to guide optimization and scale-up of the incentive strategies, if effective, to the larger population of Tanzanian PLHIV who struggle with continuity of HIV care., Discussion: Innovative strategies that recognize the dynamic process of lifelong retention in HIV care are urgently needed. Strategies such as conditional economic incentives are a simple and effective method for improving many health outcomes, including those on the HIV continuum. If coupled with other supportive services such as home visits (phase 1) or with tailored counselling (phase 2), economic incentives have the potential to strengthen engagement among the subpopulation of PLHIV who struggle with retention in care and could help to close the gap towards reaching global '95-95-95' goals for ending the AIDS epidemic.Phase 1: Clinicaltrials.gov, NCT05248100, registered 2/21/2022 https://clinicaltrials.gov/ct2/show/NCT05248100Phase 2: Clinicaltrials.gov, NCT05373095, registered 5/13/2022 https://clinicaltrials.gov/ct2/show/NCT05373095., Competing Interests: Competing interests: The authors declare that they have no competing interests.

Background: Each year in the USA, 1.5-2.5 million Americans are so severely injured that they require inpatient hospitalization. Multiple conditions including posttraumatic stress disorder (PTSD), alcohol and drug use problems, depression, and chronic medical conditions are endemic among physical trauma survivors with and without traumatic brain injuries.Methods/design: The trauma survivors outcomes and support (TSOS) effectiveness-implementation hybrid trial is designed to test the delivery of high-quality screening and intervention for PTSD and comorbidities across 24 US level I trauma center sites. The pragmatic trial aims to recruit 960 patients. The TSOS investigation employs a stepped wedge cluster randomized design in which sites are randomized sequentially to initiate the intervention. Patients identified by a 10-domain electronic health record screen as high risk for PTSD are formally assessed with the PTSD Checklist for study entry. Patients randomized to the intervention condition will receive stepped collaborative care, while patients randomized to the control condition will receive enhanced usual care. The intervention training begins with a 1-day on-site workshop in the collaborative care intervention core elements that include care management, medication, cognitive behavioral therapy, and motivational-interviewing elements targeting PTSD and comorbidity. The training is followed by site supervision from the study team. The investigation aims to determine if intervention patients demonstrate significant reductions in PTSD and depressive symptoms, suicidal ideation, alcohol consumption, and improvements in physical function when compared to control patients. The study uses implementation science conceptual frameworks to evaluate the uptake of the intervention model. At the completion of the pragmatic trial, results will be presented at an American College of Surgeons' policy summit. Twenty-four representative US level I trauma centers have been selected for the study, and the protocol is being rolled out nationally.Discussion: The TSOS pragmatic trial simultaneously aims to establish the effectiveness of the collaborative care intervention targeting PTSD and comorbidity while also addressing sustainable implementation through American College of Surgeons' regulatory policy. The TSOS effectiveness-implementation hybrid design highlights the importance of partnerships with professional societies that can provide regulatory mandates targeting enhanced health care system sustainability of pragmatic trial results.Trial Registration: ClinicalTrials.gov NCT02655354 . Registered 27 July 2015. [ABSTRACT FROM AUTHOR]

Despite established knowledge that Low and Middle Income Countries (LMICs) bear the majority of the world's burden of mental disorders, and more than a decade of efficacy research showing that the most common disorders, such as depression and anxiety, can be treated using readily available local personnel in LMICs to apply evidence-based treatments, there remains a massive mental health treatment gap, such that 75% of those in LMICs never receive care. Here, we discuss the use of a new type of implementation science study design, the effectiveness-implementation hybrids, to speed the translation and scale up of mental health care in LMICs. We use our current study of Interpersonal Psychotherapy (IPT) delivered by local personnel for depression and trauma-related disorders among HIV+ women in Kenya as an example of effectiveness-implementation hybrid design for mental health services research in LMICs. [ABSTRACT FROM AUTHOR]

This article provides new reflections and recommendations from authors of the initial effectiveness-implementation hybrid study manuscript and additional experts in their conceptualization and application. Given the widespread and continued use of hybrid studies, critical appraisals are necessary. The article offers reflections across five conceptual and methodological areas. It begins with the recommendation to replace the term "design" in favor of "study." The use of the term "design" and the explicit focus on trial methodology in the original paper created confusion. The essence of hybrid studies is combining research questions concerning intervention effectiveness and implementation within the same study, and this can and should be achieved by applying a full range of research designs. Supporting this recommendation, the article then offers guidance on selecting a hybrid study type based on evidentiary and contextual information and stakeholder concerns/preferences. A series of questions are presented that have been designed to help investigators select the most appropriate hybrid type for their study situation. The article also provides a critique on the hybrid 1-2-3 typology and offers reflections on when and how to use the typology moving forward. Further, the article offers recommendations on research designs that align with each hybrid study type. Lastly, the article offers thoughts on how to integrate costs analyses into hybrid studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Curran, Landes, McBain, Pyne, Smith, Fernandez, Chambers and Mittman.)

Background: Knee Osteoarthritis (OA) is a leading cause of global disability. The Collaborative Model of Care between Orthopaedics and Allied Healthcare Professionals (CONNACT) Model of Care (MoC) was developed by optimizing evidence-based non-surgical treatments to deliver value-based care for people with knee OA. The primary aim of this study is to determine the clinical effectiveness of the CONNACT MoC (3 months) compared to usual care. The secondary aims are: a) To determine the cost-effectiveness and b) To develop an evaluation and implementation framework to inform large scale implementation for this MoC.Methodology: Type 1 Effectiveness-Implementation Hybrid Trial using an explanatory sequential mixed-method approach. The study consists of 3 components. The first component is the pragmatic, parallel-arm, single-blinded randomized control trial. Inclusion criteria are patients with knee OA based on the National Institute of Health and Care Excellence (NICE) criteria with radiographic severity of greater than Kellgren-Lawrence 1, and Knee Injury and OA Outcome Score (KOOS4) of equal or less than 75. Exclusion criteria include other forms of arthritis, history of previous knee arthroplasty or wheelchair-bound patient. KOOS4 is the primary outcome measure at 3 months, 6 months and 1 year. Secondary outcomes include KOOS individual subscales, quality of life scoring, functional performance, global, diet and psychological related outcomes. The second component is an economic evaluation of the cost-effectiveness of the CONNACT MoC using a societal perspective. The third component is an implementation and evaluation framework using process evaluation under the RE-AIM framework using a mixed-method approach. Sample size of 100 patients has been calculated.Discussion: CONNACT MoC is a complex intervention. In line with the MRC guidance for developing and evaluating complex interventions, a pilot feasibility study was completed and a comprehensive approach including an RCT, economic evaluation and process evaluation is described in this study protocol. Results from this study will help clinicians, healthcare administrators and policymakers guide the sustainable and effective implementation of the CONNACT MoC for knee OA and serve as a basis for similar multidisciplinary MoC for chronic degenerative musculoskeletal conditions to be developed.Trial Registration: Clinicaltrials.gov Identifier: NCT03809975 . Registered January 182,019. [ABSTRACT FROM AUTHOR]