Early Childhood Education and Care (ECEC) settings are important environments to support children’s physical activity (PA). In 2021, COVID-19 regulations recommended the provision of indoor–outdoor free-play programs in ECEC settings to reduce the transmission of COVID-19, resulting in an increased uptake of this practice. As the context has since changed, research suggests that ECEC services could cease the implementation of these practices. Therefore, this pilot randomised controlled trial (RCT) aims to examine the feasibility, acceptability, and impact of a sustainment strategy to ensure the ongoing implementation (sustainment) of ECEC-delivered indoor–outdoor free-play programs. Twenty ECEC services located in New South Wales, Australia that have implemented indoor–outdoor free-play programs since the release of COVID-19 guidelines will be recruited. The services will be randomly allocated either the sustainment strategy or usual care. The “Sustaining Play, Sustaining Health” program consists of eight strategies, developed to address key barriers against and facilitators of sustainment informed by the Integrated Sustainability Framework. The outcomes will be assessed via internal project records, staff surveys, and a self-reported measure of free play. This study will provide important data to support the performance of a fully powered trial within Australian ECEC settings and to inform the development of future sustainment strategies. Globally, physical inactivity is the fourth leading risk factor for mortality, contributing to approximately 3.2 million deaths each year and accounting for 198.4 disability-adjusted life years (DALYs) per 100,000 people ,6,7, redEarly Childhood Education and Care (ECEC) settings are important settings to reach young children with PA-promotion efforts ,14,15. AIn 2021, in response to the Coronavirus (COVID-19) pandemic, state education authorities in Australia released guidance for ECEC services that included recommendations to services to “consider operating an indoor–outdoor program for the full day/session” and to “encourage appropriate outdoor programs to support social distancing” ,23,24. SEnsuring indoor–outdoor free-play programs are sustained is crucial to guaranteeing that the ongoing health benefits for children can continue to be achieved . There i(i)Acceptability, feasibility, and impact of the SPSH program for the sustainment of indoor–outdoor free-play programs  in ECEC services;(ii)Feasibility of trial methods to inform the performance of a fully powered RCT;(iii)Barriers and facilitators to the sustainment of indoor–outdoor free-play programs in ECEC services.Specifically, the aims of this research are to assess the:The study will employ a 6-month pilot, parallel group RCT design, using guidance on undertaking pilot implementation trials outlined by Pearson et al.  and repoThe research team undertook a telephone survey with a randomly selected sample of 231 Long Day Care (LDC) services and preschools in NSW from October 2021 to June 2022, of which 99 services met the eligibility criteria for the current study and form the current sampling frame. These LDC services usually operate from 7 a.m. to 6 p.m. Monday through Friday and cater for children from birth to school age, while preschools cater for children aged 3–5 years and operate from 9 a.m. to 3:30 p.m. .To be eligible to participate, ECEC services needed to report the implementation of indoor–outdoor free-play programs for most of the day  on a typical day since the introduction of the COVID-19 guidance for ECEC services (July 2021) . A typicAll services in the sampling frame will receive an invitation email consisting of a recruitment package including an information statement and a link to an online consent form outlining study requirements and requesting participation. Once the consent form has been completed by the nominated supervisor, the online survey will automatically generate the recruitment survey to assess eligibility. A member of the research team will telephone services that have not responded after two weeks of receiving the email to discuss study details, confirm eligibility and request consent for study participation. Recruitment will continue until 20 ECEC services have consented ,31. AddiFollowing baseline data collection, services will be randomly allocated to either receive the SPSH program or usual care. A statistician will set up block randomisation using a computerised random number generator. Block randomisation will be used to ensure group allocation is approximately equal. This will be uploaded onto the online data-capturing platform (REDCap) ,33, wherThe development of the 6-month sustainment strategy to increase sustainment of indoor–outdoor free-play programs was overseen by an advisory group consisting of implementation and behavioural scientists, health-promotion staff and health policymakers; it was informed by the Integrated Sustainability Framework developed by Shelton et al. . The IntFrom this data, we identified 20 barriers associated to the sustainment of PA programs in the ECEC and school settings, which mapped to all five domains of the Integrated Sustainability Framework. This resulted in the development of eight strategies see  that souAs this is a pilot study, a formal sample-size calculation on efficacy was not performed, in line with best-practice guidance . HoweverFollowing baseline-data collection and randomisation, services allocated to the intervention group will receive the sustainment strategy. Specifically, services will be supported to continue to implement indoor–outdoor free-play programs.The delivery of the SPSH program will include a minimum of four remotely delivered scheduled contacts, including two meetings via video calls and two support emails see . The use(a)Identify opinion leaders at the service:Engage with local opinion leaders ERIC Strategy: Lack of administrative buy-in and support/leadership/management and lack of program leaders/facilitators/champions.Barriers Targeted: Engaging with opinion leaders is an important strategy to understand the existing internal support for the EBP within the service and is a key driver of implementation in ECEC settings ,59,60,61(b)Affirm intent of continuity:Affirm formal commitmentsERIC Strategy: Lack of motivation/interest, limited cost-effectiveness/feasibility of program, time required to implement and record uptake of the program and competing resources, responsibilities and curriculum demands.Barriers targeted: This strategy aims to assess whether commitments are being upheld and whether new commitments are required to help sustain the intervention . Service(c)Provide local technical assistance to support integrating strategies:Provide local technical assistanceERIC Strategy: Lack of training/professional development opportunities to upskill and lack of clear data on effectiveness of program.Barriers targeted: This strategy was previously found to support the implementation of ECEC-based interventions and to be effective in improving implementation, staff motivation and problem solving within these interventions ,63,64. T(d)Develop a formal sustainment blueprint:Develop a formal implementation blueprintERIC Strategy: Lack of centralised coordination and absence of plans with defined measures.Barriers targeted: Similar strategies haves been used in previous implementation interventions to facilitate improvement in implementation within ECEC services . Service(e)Distribute educational materials to support ongoing implementation:Distribute educational materialsERIC Strategy: Lack of future external/financial support, lack of state requirements, lack of evidence-based treatments, government perceptions, lack of training/professional development opportunities to upskill and lack of clear data on effectiveness of program.Barriers targeted: Distributing educational materials to services has been found to be highly acceptable among ECEC service staff and is commonly used as part of multicomponent implementation interventions ,66,67. S(f)Engaging with family members:Involve patients/consumers and family membersERIC Strategy: Lack of collaboration with community groups, communicating information to stakeholders, lack of parental buy-in/support and staff turnover.Barriers targeted: Engaging with family members and communities is critical to support initial adoption and implementation of programs ,68. This(g)Reviewing and embedding change into policy:Mandate changeERIC Strategy: Absence of plan with defined measures, lack of centralised coordination and lack of training/professional development opportunities to upskill.Barriers targeted: Implementing a written policy around PA has been associated with higher levels of PA ,70,71. T(h)Develop an ongoing monitoring strategy:Develop and implement tools for quality monitoringERIC Strategy: Accuracy in assessing impact of program, lack of clear data on effectiveness of program and absence of plan with defined measures.Barriers targeted: Ongoing monitoring is important to allow services to continue to determine whether they are implementing the program as intended . ServiceThe delivery of intervention components will be under the control of the research team and will not be provided to the control-group services during the intervention period. The ECEC services in the control group will receive ‘usual care’. This includes the provision of a generic email with a link to the benefits of outdoor free play provided by a HPO . Baseline data were collected in September–December 2022, while follow-up data collection will occur at approximately 6 months  and 12 months post-baseline. The following data will be collected using either a telephone or online survey undertaken by a member of the research team. The nominated supervisor/service manager (or the opinion leader responsible for implementation of the SPSH program) will be asked to report on the feasibility and acceptability of the SPSH program, as well as the factors that influence the ongoing delivery of indoor–outdoor free-play programs in their service setting . In addi(i) Acceptability, feasibility, and potential impact of the SPSH program on the sustainment of indoor–outdoor free-play program (defined as ongoing implementation of the EBP) in ECEC services;(1) Acceptability of the SPSH program:This is defined as ECEC service-staff perceptions of the extent to which the SPSH program is agreeable, palatable, or satisfactory .During the 6-month post-baseline follow-up telephone or online survey, the service manager at the intervention services will be asked to report on 8 items capturing information related to the acceptability  of the SPSH program. These items are underpinned by the Theoretical Framework of Acceptability (TFA), a validated framework used to assess the acceptability of healthcare interventions from the perspectives of intervention deliverers and recipients .This survey consists of 7 items measured on a Likert scale with response options ranging from 1 to 5. The domains include their affective attitude towards SPSH (“Did you like or dislike SPSH?”), the effort involved, or “Burden” (“How much effort to engage in SPSH?”), the perceived effectiveness of SPSH (“SPSH has helped to continue the sustainment of indoor–outdoor free-play programs?”), intervention coherence (“is it clear how SPSH has helped to continue the sustainment of indoor-outdoor free play programs”), self-efficacy (“How confident did you feel about participating in SPSH?”), opportunity costs (“Participating in SPSH interfered with other priorities”) and general acceptability (“How acceptable was SPSH?”). Generally, 1 is a negative response/disagreement with the statement, while 5 is a positive response/agreement with the statement, except for Burden (domain 2) and Opportunity costs (domain 6), where 1 is a positive response, while 5 is a negative response. The 8th item is an open-ended question to capture any further comments on the acceptability of the SPSH program. (2) Feasibility of the SPSH program:This is defined as ECEC services’ perceptions of the extent to which the SPSH program can be successfully used or carried out at scale within different organisations or settings .At the 6-month post-baseline follow-up time point, the intervention services will be assessed via a survey using 4 items  adapted from the Feasibility of Intervention measure . This qu(3) Sustainment of indoor–outdoor free-play programs :Sustainment as an outcome is defined as: “The extent the innovation is in place or being delivered over the long-term” . The delp < 0.3651). The FPR will be provided to the nominated supervisor/service manager or educators at each ECEC service electronically, via email, by the research team, at baseline and during the follow-up period. The educators/nominated supervisor(s) will be asked to complete the FPR for each session of free play throughout the day across the selected week (5 consecutive days) and return the completed FPR to the research team. If not returned, a follow-up email or phone call will then be made to the appropriate delegate to follow up on the progress of FPR completion. When the research team receive the completed FPR, a phone call will be made to the ECEC service to obtain any missing data, clarify non-legible responses, if required and assess any specific challenges to completing the FPR. The research team have successfully undertaken this with 90 services as part of previous trials [Data on the number of minutes that children are provided with indoor-only, indoor–outdoor, and outdoor-only free play from a randomly selected week will be collected via the FPR. The FPR is adapted from existing ECEC measures of outdoor play: Environment and Policy Assessment and Observation—Self-Report (EPAO—SR) and Nutritional and Physical Activity Self-Assessment for Child Care (NAPSACC) ,78. The s trials .(4) Adoption of SPSH-program recommendations:Adoption is defined as the intention, initial decision, or action undertaken to employ an innovation or evidence-based practice . This wi(ii) Feasibility of use of trial methods to inform the conduct of a fully powered RCT(1) Feasibility of the trial methods:In order to inform a fully powered RCT and to assess whether the trial methods are feasible and replicable, project records will be used to report consent rate, percentage of missing data from completion of the FPR , comparison of consenter/non-consenter characteristics, attrition rate, withdrawal and reasons and contamination ,27. (2) Fidelity to delivering the SPSH program:Fidelity is defined as the degree to which the SPSH program was implemented as described or intended in the original protocol . Fidelit(iii) Barriers to and facilitators of the sustainment of indoor–outdoor free-play programs in ECEC services(1) Barriers to and facilitators of indoor–outdoor free play:During the baseline and 6-month follow-up telephone/online surveys with the nominated supervisor/service manager, barriers, and facilitators to sustaining the EBP will be assessed. This will be conducted using an adapted measure of the 29-item scale, which measures sustainability determinants across the constructs of the Integrated Sustainability Framework  developed by the team. This adapted 9-item scale measures the outer contextual factors and processes that are perceived to be influential in intervention sustainment in ECEC settings. The nominated supervisor/service manager will be asked to rate their level of agreement with a number of items on a scale from 1 (completely disagree) to 5 (completely agree). (2) ECEC service characteristicsData regarding ECEC service characteristics, including service type, age group of children at the service, operating hours, number of children enrolled aged three to six years and number of educators at the service, will be collected via a baseline survey of ECEC nominated supervisors/service managers and educators. Service locations’ postcodes will be used to determine socioeconomic status (SES) and rurality. Services with postcodes ranked in the top 50% of state postcodes based on the 2016 Socio-Economic Indexes for Areas (SEIFA)  will be (3) CostSimilar to a previous analysis , the dirManagement of trial data will be in accordance with a data-management protocol, developed and approved by the nominated advisory group. Data will be stored in accordance with the requirements of the Hunter New England (HNE), University of Newcastle, and Swinburne University of Technology Human Research Ethics Committees (HRECs). All questionnaires and notes will be deidentified and recordings will be stored in a locked HNE Microsoft Teams folder to maintain confidentiality. All statistical analyses will be undertaken using SAS v9.2 statistical software. The main data-collection point will be at 6 months post-baseline, as this will be approximately 2 years from the initial introduction of the COVID-19 guidelines. The 12-month timepoint will be used for assessing whether indoor–outdoor free-play programs continue to be delivered following cessation of active sustainment strategy (the SPSH program). For all outcomes, we will assess for normality and use non-parametric test where non-normality is observed.Descriptive statistics (mean and standard deviation (SD) or median and range when non-normal) will be generated for both acceptability and feasibility at 6 months post-baseline. For acceptability, individual scores from each domain will be summed (reverse scored where necessary) and used to provide a score for each service. For example, ≤2 will be a negative response, indicating the SPSH program is considered unacceptable, while ≥4 will be a positive response, indicating the SPSH program is considered acceptable. In cases of missing values, we will impute the average scores. Answers to the open-ended question will be analysed qualitatively, using thematic analysis to identify key themes. For feasibility, the individual scores of each of the three items  will be summed to provide an overall score for each service, in which ≥4 (higher scores) will indicate greater feasibility, while ≤2 (lower scores) will indicate lower feasibility, consistent the recommendations of Weiner et al. (2017) in the Feasibility of Intervention Measure. For the open-ended question, the responses will be analysed qualitatively, using thematic analysis to identify key themes. Separate analyses will be performed at each follow-up time point (6 and 12 months post-baseline) for each primary outcome, total minutes of indoor-only free play and total minutes of indoor-outdoor free play. Linear regression models will be used to compare intervention and control group differences, controlling for the baseline outcome data. Alternatively, equivalent non-parametric tests will be performed if linear regression assumptions are not met.. Analyses will follow the intention-to-treat principle and include all data analysed according to the group to which each service was originally randomly assigned. Imputation techniques will be applied where appropriate.Adoption will be assessed by counting how many strategies were “complete” out of the minimum of 4 strategies in the Sustainability Action Plan during the 6-month program for each service. The minimum requirement for services is to complete at least one goal from the “Notify families and community members of indoor–outdoor free play” strategy, “Notify staff of indoor–outdoor free play” strategy, “Update policy” strategy and “Conduct indoor–outdoor free play as part of daily routine” strategy. The number of completed strategies will be summed to determine how many strategies were completed by each service. A minimum of 4 strategies set as “complete” will be required for the service to have adopted the SPSH program recommendations. After all intervention services have had their action plan counted, a mean will be calculated, showing the average number of services adopting the SPSH program recommendations. Feasibility of the trial methods will be analysed at baseline and 6 months post-baseline. Consent rate, percentage of missing data from completion of the FPR, comparison of consenter/non-consenter characteristics, attrition rate, withdrawal and reasons and contamination will all be analysed using descriptive statistics. Fidelity will be assessed using an internal spreadsheet tracking recruitment and intervention delivery. Each step records time spent, staff involved and whether it has been completed. Analysis will include summing the number of completed steps according to the protocol for each service to determine the degree of implementation according to the original protocol. Barriers and facilitators of sustainment will be analysed at 6 months post-baseline. The outer contextual factors and processes will be scored individually. The total scores  of each of the two domains will be calculated. The total scores will be calculated by summing all scores for all items within the subdomain and dividing by the total number of responses within the domain. The higher domain scores (≥4) will be considered facilitators of sustainment, while the lower domain scores (<4) will be considered barriers to sustainment.An advisory group will assess suitability for progression to a fully powered trial using data collected around feasibility of trial methods and outcomes related to potential sustainment, fidelity, and acceptability. These decisions will be made via majority, by core members of the research team, including a representative from a health service that intends to adopt the sustainment strategy if it is found to be beneficial. Specifically, the team must deem the intervention and sustainment strategy to be sufficiently acceptable and feasible for it to be likely to be adopted by approximately 25% of ECEC services to which it is offered  . AlternaThe trial is currently in the intervention-delivery stage. It is not anticipated that any events will occur that would warrant discontinuing the trial as the SPSH program will be delivered completely online. Any unforeseen adverse events would be reported to the HNE HREC , and appropriate action would be taken to address the event. The trial’s registration record will be updated with any protocol modifications and any deviations from the original protocol will be reported when publishing trial outcomes.This protocol outlines the development and evaluation of a theory-informed sustainment strategy to increase the sustainment (ongoing implementation) of an evidence-based PA practice (indoor–outdoor programs in ECEC settings). While the sustainment of PA practices in ECEC is needed for continued health improvements in the population and are likely to provide considerable cost savings, there is an absence of empirical evidence on how this can be achieved. This pilot trial seeks to describe, for the first time, the feasibility, acceptability and impact of a program (SPSH) on the sustainment of EBP, providing an insight into how to support the sustainment of health-promotion programs delivered in the ECEC context.This protocol outlines the methods and development of a strategy to improve the sustainment of outdoor-free-play opportunities through ECEC services. The application of the strategy will provide important proof-of-concept data to support the conduct of a fully powered trial, the first of its kind, as well as informing the development of future sustainment strategies in ECEC settings more broadly.


Interventions are needed to improve well-being and promote community reintegration among Veterans with housing insecurity. The objective was to conduct a developmental formative evaluation of a participatory music program.This single-site, pilot study implemented a participatory music program at a U.S. Department of Veterans Affairs (VA) Homeless Domiciliary that included one-hour sessions (group music instruction and ensemble playing), 3 times per week for 3 months. Intervention development was guided by the Model of Human Occupation (MOHO). Evaluation was guided by the MOHO and the Consolidated Framework for Implementation Evaluation (CFIR). Qualitative data were collected via semi-structured interviews from participants and non-participants, and were analyzed using an interdisciplinary, constant comparison qualitative analysis technique.N = 12) included five participants and seven non-participants. Semi-structured interview responses produced three salient themes illuminating Veterans’ perspectives: (1) key characteristics of the intervention ; (2) the therapeutic power of the program ; and (3) the context and culture (which included Veterans supporting each other and the Domiciliary setting).Sixteen program participants and 8 non-participants were enrolled, age range 26–59  years; 75% were White. The sample for this study (Veterans described the benefits of a participatory music intervention compared to problem-based groups, which included enjoyment, skill acquisition facilitating pride, escape, reconnecting with their identity prior to current problems, and experiencing positive aspects of Veteran culture such as mutual support and discipline. These data support ongoing research about participatory music programs to support Veterans with housing insecurity.The online version contains supplementary material available at 10.1186/s12889-023-16427-8. On any given day, nearly 50,000 Veterans are homeless in the United States . The DepPrograms for persons with housing insecurity often include sports-based or arts-based interventions which serve as pleasurable leisure activities and which may enhance participation and community engagement , 7. PartThis manuscript describes a developmental formative evaluation of a participatory music intervention to plan a future larger-scale study that would examine the potential effectiveness and implementation of a music-based intervention on community reintegration for Veterans with housing insecurity . Our lonThis single-site, non-randomized pilot project was conducted as a developmental formative evaluation with the goal of developing and iteratively refining the intervention program for a future, larger effectiveness and implementation study . DevelopWe sought the perspective of participants about barriers and facilitators of program engagement, their experience with the intervention sessions, and suggestions for program improvement. We also sought the perspectives of non-participants to improve our approach to recruitment and intervention design . This pilot study was not designed to identify potential effects of the intervention on outcomes .The participatory music education program was designed to provide a meaningful activity which had the potential to influence a person’s motivation, identity, and well-being . The intThe Richard L. Roudebush VA Homeless Domiciliary was a 50-bed residence for Veterans with housing insecurity. Veterans are adults who served in any of the branches of the US military . Veterans include individuals who served in wartime  and during peacetime . As of September 2020, there were 19.4 million living US Veterans .Veterans residing at the Domiciliary received interdisciplinary care that included medical, psychiatric, vocational, educational, recreational, and social services to address mental illness and substance abuse, co-occurring medical problems, and psychosocial needs. The Domiciliary interdisciplinary team did not include an occupational therapist but did include recreational therapists who offered both creative arts opportunities  and recreational activities . Although the US active military and Veteran communities have a long-standing history of using music for therapeutic and recreational purposes,  the DomiProgram participants and non-participants were recruited from residents of the Domiciliary who were eligible for elective activities. Veterans were eligible for elective activities if they had been a resident for at least two weeks and had not committed any infractions. Generally, Veterans resided at the Domiciliary for six to nine months. Veterans with visual impairment, profound hearing impairment, cognitive impairment, or other conditions that might interfere with their ability to play an instrument were excluded.Project staff attended the community meetings at the Domiciliary to inform the Veterans about the program, invite them to attend intervention sessions, and reiterate that participation was entirely voluntary; the music educator played short songs on the various instruments during these sessions. Posters about the program were placed in high-traffic areas within the Domiciliary. Participants were invited for interviews at the time of the music-making intervention sessions. Veterans who decided not to participate were invited for interviews at the community meetings. The latter were recruited from Veterans residing at the Domiciliary who were willing to be study participants but who chose not to participate in the music group.The intervention was a participatory music program where participants engaged in music-making as members of a string orchestra. Participants received an instrument of their choice . One-hour lessons with a music educator experienced in adult music education occurred three times per week. Sessions included thirty minutes of group music instruction by followed by thirty minutes of ensemble participation , 18.The repertoire was chosen by the music educator in consultation with participants. Participants were given sheet music for use during their own practice and group sessions. The music educator created instructional videos demonstrating how to play the instruments and providing practice suggestions. Participants were encouraged to practice during their free time.The participatory music program focused on the use of stringed instruments for several reasons. Stringed instruments are appropriate in both solo and group settings. Many Domiciliary programs used a group format, which was familiar and comfortable to potential participants. Playing a stringed instrument within an orchestra setting may promote a sense of accountability, provide opportunities for social participation, and foster the development of a new role (“I am the orchestra’s cellist”). Stringed instruments are melodic , allowing participants to play music that is familiar, facilitating both enjoyment and skill acquisition. In addition, stringed instruments (in contrast to keyboards) facilitate learning and playing because the music is written in one line in a single clef. Finally, although cellos are larger, stringed instruments can be conveniently transported, even if using public transportation.The music educator developed and facilitated the lessons because, based on the MOHO conceptualization, a key objective of the program was to provide participants with new skills. An occupational therapist and music therapist served as consultants on the implementation program team.The evaluation was guided principally by the MOHO framework, –13 supplWe evaluated participants’ experiences of the program by collecting qualitative data from semi-structured interviews conducted one month after enrollment. Veterans who participated in the program were asked about past music education, barriers and facilitators of program participation, experience in intervention sessions, perceptions of their membership in the orchestra, and suggestions for program improvement , anthropology , social work , music education , and medicine . The interviews were conducted by NAR, JM, AJC, and DMB; none of whom had prior relationships with the interviewees but all of whom had experience with qualitative methods. During the interviews only the Veteran and the interviewer were present. Participant interviews took approximately 30 min, non-participant interviews took approximately 15–20 min.The interviews were audio-recorded, transcribed, and reviewed by study team members  to ensure accuracy. Transcripts were imported into NVivo11 for analysis using the constant comparison technique . This meN = 16 participants enrolled in the program. Participants ages ranged from 26 to 59 years: mean age 41  years. The majority of participants were White . Comorbidity was common among participants: 94% had substance use disorder, 69% had depression, 56% had anxiety, 44% had post-traumatic stress disorder (PTSD), 44% had a history of suicidality, and 44% had chronic pain  intervention, (2) therapeutic power, and 3) context. These themes are described and expanded below with exemplary quotes organized under subthemes  influenced the likelihood of participating in and/or enjoying this intervention. For example, one participant noted “The second major theme – therapeutic power – included data describing how participation in the intervention impacted participants’ lived experiences. Veterans described two major ways that the intervention fostered well-being: by providing opportunities for enjoyment and escape.I got joy out of it,” “It’s enjoyable…it’s fun,” and “I have loved participating! I hope it continues for a long time.” Enjoyment was described in relation to reclaiming identity and connecting with others – the enjoyment experienced in the group was also motivating: “It reminded me of my past a little bit. Going to New York and seeing shows on Broadway and listening to the orchestra music. I had forgotten about those good times because of my situation. It reminded me that I need to get back to a place where I can enjoy going to shows and listening…It helped my self-esteem…I got in touch with who I used to be before I had all these issues.” One Veteran, in response to the probe “What were your most favorite parts of the group?” expressed joy in accomplishing the skill of “Learning to read music!”As noted above, Veterans found this intervention to be helpful in that it provided a source of enjoyment, which contrasted with other opportunities at the Domiciliary that were more problem-based. Participants noted: “When I feel stressed…a bit overwhelmed…I practice. Everything else goes away… concentrating on the music, practicing. When I’m done practicing, things don’t seem as bad or important as they were before. In a good way… It helps me.” It provided a way for participants to distance themselves from pressing problems. “It just allows you to escape whatever you’re going through during the day.” Another noted, “I think that it’s relaxing. It helps with stress and anxiety.” Further illustrating this, another explained, it “Let’s you just kinda get out of yourself for a while and just focus on music.” These data suggested the intervention could provide relief from problems, even if it did not directly aim to remediate specific problems. The intervention offered an alternative to problem-based approaches by engaging participants in something meaningful, relaxing, and enjoyable that distracted Veterans from their problems for a time.In addition to enjoyment, participants noted that the intervention provided some relief from stress or negative emotions. “Orchestra is for suburban white people” and “‘Orchestra’ is a bad name…’Music Program’ is better.” Several participants expressed positive sentiments toward playing “the fiddle” and chose the violin because of it.The third main theme categorized data describing cultural and contextual factors that further influenced how Veterans experienced or perceived the intervention. For example, Veterans listed several cultural factors influencing how the program was perceived, providing suggestions to make it more appealing: one noted ““…other guys even though they didn’t participate, they were pretty supportive. I think that’s just the Veteran mentality when they see somebody trying to do something, whether they do it or not, they will support.” Expanding on Veteran culture, another noted: “most of us are Veterans, and well, and we already have a lot of discipline, but it kind of shows you that you are able to do anything if you really set your mind to it.”Also, regarding culture, participants noted both Veteran culture and the culture of the domiciliary as facilitating and/or supporting participation in the program. For example, one described how at the domiciliary A lot of fear” or being concerned that “I probably won’t have no patience for it.” Regarding programmatic context, participants noted that the fact that “it counts as a class” in terms of domiciliary programming was motivating and helpful. However, they also noted several competing programs – “Just a lot of other activities going on” – and difficulty with participating as they moved to higher levels within the Domiciliary when they were expected to be out working or job seeking.Regarding context, Veterans noted both personal and programmatic contextual factors. The personal context subtheme included concepts related to Veterans’ medical or mental health status , fears, homeless status, and/or status in the domiciliary program. Some expressed having “Our pilot data suggest that the participation-based nature of this music program contributed to wellness. A key finding was that Veterans described the benefits of the program that was participatory rather than problem-based, offering opportunities for enjoyment and escape. Veterans distinguished the music group from other programs that asked them to reflect and focus on negative life situations. As part of the core therapeutic activities that residents of the Domiciliary were required to attend, Veterans were asked to identify key decisions, life-events, and behaviors that led them to their current situation; this process often required the Veterans to acknowledge that their actions negatively influenced relationships, employment, and housing. By contrast, the music group was fun allowed them to recall a time before they had their current problems. This reconnection with their former selves was described as a motivating push to get back to enjoying life and remembering who they were. Social participation and leisure activities have been reported to be more supportive of recovery than problem-based approaches . These pAchieving new skills such as the ability to read music, alongside the supportive encouragement of other Veterans, highlighted existing, positive qualities of Veteran culture: discipline and mutual support . ParticiVeterans described several aspects of the intervention that may facilitate wellness, such as agency, personal choice, and the therapeutic power of music. The music program provided a coping strategy—it was a relief from negative preoccupations. In addition, the music instructor was perceived as non-judgmental, facilitating trust and participation despite Veterans’ anxiety or fear they would not succeed. Kopacz et al.  found thOur findings highlighted several contextual factors to consider in a future clinical trial. Veterans noted the importance of language in describing the program . These data underscored the need for the program design and delivery to be informed by diverse perspectives. The changing contexts of domiciliary residents illustrated how engaging in something beneficial such as the music program became more challenging as Veterans progressed in the domiciliary program and they were expected to hold jobs or be looking for work full-time. These observations are supported by other studies that have described the early recovery period as one of occupational deficit, but that as recovery progresses, occupations and their concomitant demands return, potentially making participation in wellness activities more challenging both in terms of time management and motivation .The MOHO conceptual framework was useful in making sense of the Veterans’ diverse perspectives about the program and why they choice to participate or not participate. We provide three examples of how considering the MOHO domains influenced our understanding of the qualitative results. First, when designing the program, we had conceptualized the habituation domain of the MOHO in terms of providing encouragement and opportunities for practice playing the instruments. We anticipated that program engagement and independent practice would lead to skill acquisition  which would in turn promote positive self-image. In addition, one of the explicit goals of the therapists at the Domiciliary is to provide residents with opportunities to form new meaningful habits as part of their healing journey—which aligned with the MOHO construct of habituation. However, the results revealed that practice was helpful, not via enhanced musical proficiency as we had expected, but rather through relaxation, enjoyment, and distraction. Second, the MOHO volition domain makes explicit motivations for participation. By interviewing both participants and eligible persons who chose not to participate, we learned about program characteristics that either promoted or hindered participation—key knowledge as we seek to improve the program. Third, Veterans with housing insecurity who resided at the Domiciliary had both physical limitations and mental health related barriers to engaging in the music education program. Regarding the performance capacity MOHO domain, we had expected that Veterans with the greatest performance capacity would be the ones most likely to engage in and benefit from the program. However, the results indicated that patients with limitations that potentially inhibited performance capacity  were the ones who reported genuine relief from participation. Practitioners and investigators are encouraged to consider the MOHO in future projects that seek to engage participants in a new activity.Several limitations merit description. First, this pilot project was implemented within a VA Domiciliary and therefore may not be generalizable to other populations  or to other settings. Second, the music instructor was universally regarding positively by program participants, highlighting the importance of selecting instructors with similar appeal in future trials, and the need to carefully evaluate program fidelity and participants’ impressions of the instructor given the variability among potential interventionists and their approaches to music instruction. Third, these pilot data cannot be used to describe the potential role that a music-based program might play in promoting community reintegration because we did not have data from Veterans who transitioned out of the Domiciliary and into community housing. A future study is needed to obtain these key data. Fourth, the qualitative data were obtained from self-report. We sought to minimize possible recall bias in the self-reported data by conducting interviews either immediately after intervention sessions (for participants) or immediately following the community meetings (for non-participants). We sought to minimize potential social desirability bias in the self-reported data by using interviewers who were not part of the intervention program and by explicitly soliciting both positive and negative feedback. Finally, the participants of this study were mostly white men and thus findings reported in this study do not adequately capture the diversity of experiences and contexts within which the participatory music program may be perceived and experienced. Future trials will need to devote significant attention to the recruitment of Black, Indigenous, and other people of color as well as women and gender diverse individuals to fully represent the impact of this program on diverse populations of Veterans.Qualitative evaluation of a participatory music program to support Veterans with housing insecurity reflected several important elements to consider in a future clinical trial. Veterans enjoyed the program and valued the participation-focused rather than problem-focused groups. The universal positive regard for the music instructor illustrated the importance of ensuring that interventionists are supportive and non-judgmental. Future studies seeking to implement programs within the VA Domiciliary setting will have to consider how best to integrate the program in ways that complement rather than conflict with existing offerings. These data support ongoing research into the effectiveness of participatory music programs to support Veterans with housing insecurity.Additional file 1.Additional file 2.


In this mixed-methods study, we explore themes that emerged from a survey assessing the programmatic experiences of mentors and administrators at institutions in low- and middle-income countries (LMICs) hosting trainees supported by the Fogarty International Center’s Global Health Program for Fellows and Scholars. A total of 89 of 170 potential respondents representing 31 countries completed the survey . There was agreement among respondents that their institutions received sufficient funds to support trainees and had the capacity to manage operational and financial aspects of the program. A majority also agreed that both LMIC and U.S. trainees were beneficial to the host institutions, and that trainee projects were relevant to the needs of the host country. Respondents felt that program benefits to LMIC trainees could be improved by increasing the research consumables budget, increasing the flexibility of program timelines, and increasing engagement between LMIC and U.S. trainees and institutions. Respondents indicated that both U.S. and LMIC trainees behaved professionally  and took appropriate initiative to conduct their research projects. Findings from this study will help inform innovations to similar training initiatives that will enhance sustainability and improve program performance, and will be responsive to local needs. When such partnerships are optimized, they create a robust system of collaboration, shared knowledge of local perspectives, and vision anchored on common objectives and outcome benchmarks.Between 2012 and 2021, the FGHFS program supported 892 trainees across 40 countries. At the time of the study, 22 LMIC sites were actively accepting trainees for participation in the program. Low- and middle-income country sites that had hosted at least one trainee for a full training period (1 year) between 2012 and 2021 were eligible for participation. To ensure adequate feedback from both the administrative and mentor perspectives, at least one scientific mentor and one administrator were identified from each site. In some cases, the same person filled both roles, so only one survey response was received from these sites.The purpose of this study was 1) to capture the perspectives of mentors and administrators at the LMIC host institutions and project sites on the burdens and benefits of participating in these training programs from 2012 through 2021, 2) to determine ways in which the partnerships between LMIC and U.S. lead sites could be improved, and 3) to assess trainee preparedness and conduct.–We reviewed published literature examining the benefits and burdens on institutions and preceptors in LMIC settings that hosted international clinical or research-focused trainees. This review revealed six important themes: 1) administrative responsibilities and site capacity; 2) site engagement in the selection of trainees; 3) general impact on the host institution; 4) trainee attitudes, behavior, and professionalism; 5) trainee preparation and knowledge; and 6) feedback mechanisms.Program managers from the six active FGHFS consortia (as of 2020) provided lists of administrative and scientific mentor contacts for each of their LMIC sites. The survey was disseminated via e-mail, with reminders for nonresponders, and responses were collected in REDCap, a secure, Web-based data collection and database platform.One respondent  took the survey twice, corresponding to roles with two distinct FGHFS consortia. The first response of this respondent was excluded from all analyses. All available data from the 88 surveys (each from a unique respondent) were included for analysis, although five surveys were less than 75% complete. The overall data, or data for a group , were summarized using descriptive statistics such as means ± SD for continuous variables, and frequencies and percentages for categorical variables. All analyses and graphs were completed using software R.4.1.3 , and R packages such as ‘Hmisc’Supplemental Table 1 for results of this subgroup comparison). For both quantitative and qualitative data, we anonymized responses to protect respondent confidentiality.All free-text responses were extracted, deidentified, compiled into a spreadsheet, and organized according to the corresponding survey question. Data abstraction and interpretation were completed using a qualitative content analysis approach.n = 38) were female , Zambia , Peru , South Africa , Tanzania , and Uganda  collectively. The majority of respondents  described their roles in relation to the program as including oversight, supervision, or teaching . Respondents reported an average of 7.7 ± 5.5 years (SD) of experience with the program. More than half the respondents reported hosting both U.S. and LMIC trainees . Two thirds of respondents with a mentor role reported spending between 5 and 20 contact hours per month with each trainee . Most respondent institutions had hosted fewer than five trainees at their sites  and indicated being at below capacity .A total of 89 of 170 potential respondents representing 31 countries took the survey . Forty-three percent of respondents  agreed or strongly agreed that their institution received enough funds to support the trainees . A similar proportion of administrators rated the amount of communication between the host institution and the consortia/program as “appropriate.” However, only 22% of respondents (n = 5) with administrative roles reported being involved in application review and trainee selection (data not shown).Of the 23 administrators who responded to the survey, more than half  reported providing direct feedback to the trainees at the end of the training period , mentors indicated that trainees were required to disseminate information about their project findings to key local stakeholders. Only 32 LMIC mentors (47%) reported being asked to provide feedback about the trainees to the U.S.-based program contacts at the end of the training period. Responses regarding keeping contact with U.S. trainees after the training period were obtained from 66 respondents. More than half of these respondents agreed or strongly agreed that most U.S. trainees remained in contact with the host institution after the end of the fellowship year . The majority of respondents indicated collaboration on projects, papers, or grants  as the most common way to remain in contact .Responses regarding feedback at the end of the training period were obtained from respondents with a mentor role, a majority of whom , have cultural awareness/sensitivity , and understand the realities of working in low-resource settings   . Only fiIn terms of professionalism , most reReflecting on observed cultural competencies of U.S. trainees, 73% of respondents agreed that most U.S. trainees have cultural and religious awareness and sensitivity, and most appreciated their roles as guests (91.1%) . Only 12Respondents provided additional comments to support or clarify their responses on 20 of the survey items. Three main themes emerged from these data: 1) enhancing local program ownership and LMIC trainee experiences, 2) prioritizing preparation for host sites and U.S. trainees, and 3) proposing future directions. Detailed descriptions of these themes are provided next, with themes mapped to key quantitative outcomes in Program mentors and administrators from LMIC host institutions expressed a desire to have a more prominent role in the management of the FGHFS program at their respective sites. Drawing from previous experiences as participating sites, several respondents cautioned that lack of host site involvement in the trainee selection process could result in trainees whose projects are not aligned with existing projects or priorities within their institution. The provision of additional funding support, institutional capacity-building mechanisms, and a more active role in programmatic decision-making processes were perceived as ways of increasing the ability of sites to facilitate the program effectively.Respondents provided numerous ways through which the FGHFS program could be improved to enhance LMIC trainee experiences, including increasing available research funds, offering program extensions, facilitating bidirectional exchanges, and offering additional ways for U.S. and LMIC trainees to engage in research collaborations. The annual orientation all trainees receive at the NIH campus at the beginning of their fellowships was identified as a critical period for expectation setting for both trainees and their mentors. A few individuals stated expressly that the orientation should be offered in person again  to communicate program requirements more effectively and allow networking opportunities for LMIC trainees.Respondents identified aspects of programmatic support in the program preparation phase that could be provided or strengthened to support effectively those trainees hosted at their institutions, including obtaining support for the program from institutional leaders. Individuals also requested guidance on how to select and prepare mentors, reiterating that early involvement of and communication with the host sites help reduce problems after trainees arrive.Respondents also described how prioritizing prearrival U.S. trainee engagement is important for overall program success. All but one respondent, who provided a comment regarding prearrival competencies for U.S. trainees, stated that language training, if necessary, and advanced research skills or content knowledge can be learned in-country via the mentored research experience and local trainings. As such, individuals felt the program should instead prioritize efforts to make U.S. trainees aware of the research setting realities at their host sites. This can be facilitated by early communication between trainees and LMIC mentors prior to deployment to the LMIC sites, and by encouraging additional capacity-building activities if trainees have time outside of their proposed projects.Safety of trainees was mentioned across responses to several different question prompts, each time emphasizing that trainees need to have an awareness of cultural norms and local laws. Most respondents shared the sentiment that U.S. trainees are respectful and “they are [culturally] sensitive, but not very [culturally] aware” (no. 53). Individuals felt host institutions were well-positioned to offer virtual pretravel sessions to provide U.S. trainees with general knowledge on the health-care system, institutional policies, and research ethics requirements, and to increase their awareness of relevant, local sociocultural issues.Respondents identified several ways in which the program could grow to support long-term goals of increasing their institution’s reputation for research eminence. Several respondents suggested adding a local research dissemination requirement. Dissemination outputs were described as ways to ensure trainees meet their research objectives, “inspire other trainees and build capacity” (no. 69), make knowledge accessible that could “benefit other LMICs” (no. 19), and strengthen collaborations with other institutions. However, to support trainee research dissemination efforts, these individuals also recognized that sites would need to provide training and ongoing mentorship on manuscript development, and that the program would need to allow budgeting for dissemination costs, such as publication fees and postfellowship conference attendance.To advance trainee and institutional visibility, respondents identified program support structure gaps that need to be addressed in future program iterations. One individual requested that FGHFS consortium leaders provide the sites with feedback; another highlighted the need to receive trainee feedback on program quality. Some individuals felt trainees should have to provide regular progress updates to ensure project deliverables are produced and can be used to demonstrate visibly the presence of the program at their institutions. As summarized by one respondent, there was a stated desire across responses to “create more opportunities for networking among fellows [and] engage more actively with administrators of the host institution to create more visibility for the program and more recognition for the trainee as well as to attract bigger talent” (no. 79).Supplemental Table 1). There was mixed consensus regarding how to support protected time for trainees and limit burdens to host institutions, with sites that have hosted fewer than 11 fellows advocating for mechanisms to allow fellows to focus on their research project, including salary coverage. However, individuals from sites who hosted 11 or more fellows felt salary coverage and program expectations were clear. Suggested methods for limiting burdens to the host institutions, unique to each level of program experience, included covering the cost of research equipment (< 5 fellows), having paid administrative staff (≥ 11 fellows), and focusing on advanced preparation (5–10 fellows). Most felt salaries for mentors should be included and sites should have access to additional resources from the U.S. institutions. Regardless of the host institution’s experience with the program, all had positive impressions of the program and felt trainee advancement would be best supported by increased opportunities to network and partner with U.S. fellows .Comparisons of individual responses by the number of trainees an institution hosted (threshold of 11 fellows) identified differences in perceptions of how the program benefits host institutions, with a stronger emphasis on capacity building for staff  Research Training Program.Last, effective global health capacity development requires a framework of mutual respect, transparent communication, and intentional engagement of all parties at the decision-making level. We need equitable partnerships that create prospects to equalize access and opportunities of educational experiences.Supplemental materials


Patients with atopic dermatitis can experience chronic eczema with pruritus, skin pain, sleep problems, anxiety, and other problems that reduce their quality of life (QoL). Current treatments aim to improve these symptoms and reduce inflammation, but poor treatment adherence and disease understanding are key concerns in the long-term management of atopic dermatitis. Digital therapeutics can help with these and support patients toward a healthier lifestyle to improve their overall QoL.The aim of the study is to test the feasibility of a digital health program tailored for atopic dermatitis through program engagement, retention, and acceptability.Adults with atopic dermatitis were recruited in Iceland for a 6-week digital health program delivered through a smartphone app. Key components of the digital program were disease and trigger education; medication reminders; patient-reported outcomes (PROs) on energy levels, stress levels, and quality of sleep (referred to as QoL PROs); atopic dermatitis symptom PROs; guided meditation; and healthy lifestyle coaching. The primary outcome was program feasibility, as assessed by in-app retention and engagement. User satisfaction was assessed by the mHealth  App Usability Questionnaire (MAUQ).A total of 21 patients were recruited , 20 (95%) completed the program. On average, users were active in the app 6.5 days per week and completed 8.2 missions per day. The education content, medication reminders, and PROs had high user engagement and retention; all users who were exposed to the QoL PROs (n=17) interacted with these, and 20/21 (95%) users were continuously engaged with the education missions, medication missions, and symptom PROs. Continued engagement with the step counter and mind missions among exposed users was lower . Medication reminder and education task completion remained high over time , but weekly interactions declined. All assigned users completed atopic dermatitis symptom PROs on weeks 1-5 and only one did not do so on week 6; the reported number and total severity of atopic dermatitis symptoms reduced during the program. Regarding the QoL PROs, 16/17 (94%) and 14/17 (82%) users interacted with these at least 3 times in the first and last week of the program, respectively, and all reported improvements over time. User satisfaction was high with a total score of 6.2/7.We found high overall engagement and retention in a targeted digital health program among patients with atopic dermatitis, as well as high compliance with missions relating to medication reminders, patient education, and PROs. Symptom number and severity were reduced, and QoL PROs improved over time. We conclude that a digital health program is feasible and may provide added benefits for patients with atopic dermatitis, including the tracking and improvement of atopic dermatitis symptoms. Atopic dermatitis is a chronic, multifactorial, inflammatory skin disease characterized by recurrent eczematous lesions and pruritus ,2. The pOne new way to improve treatment adherence and psychological support for chronic diseases is the use of digital therapeutics (DTx) , but theWe developed a holistic digital health program to reduce symptom severity and increase the QoL of patients with atopic dermatitis. The program promotes lifestyle changes that focus on habit reversal, treatment adherence, disease education, stress reduction, and sleep improvement. In this brief, 6-week-long study, we evaluated the engagement, retention, and acceptability of this digital health program; clinical efficacy results were published previously . The resA 6-week, single-arm feasibility study was conducted in Iceland between November 2021 and January 2022. Participants’ demographic data were collected at baseline, and they underwent clinical dermatological assessments, performed by a dermatologist, both at baseline and after the 6-week study. Participants were also instructed to install the Sidekick Health app and enroll in the atopic dermatitis program during the baseline visit, and their activities were tracked in the app during the study.Patients with atopic dermatitis who visited the Hudlaeknastodin Dermatology Clinic in Iceland were invited to participate. Patients were screened for inclusion by a study nurse; criteria were (1) mild to severe atopic dermatitis, (2) ≥18 years of age, (3) understands verbal and written Icelandic, (4) capacity to consent, and (5) owns and knows how to operate a smartphone. Exclusion criteria were (1) recent (within 4 weeks) or current phototherapy or oral treatment for atopic dermatitis; (2) other inflammatory skin diseases ; (3) pregnancy; and (4) any biological treatment for atopic dermatitis. Participants’ demographic and background information were collected at baseline at the clinic.A digital health program for patients with atopic dermatitis was developed by Sidekick Health, a digital therapeutics company ,15. The The program was composed of education about the disease and how lifestyle affects disease progression; patient-reported outcomes (PROs) on symptoms and quality of sleep, stress, and energy levels; medication reminders; and advice and support on healthy lifestyle provided by a coach. To achieve behavioral modification, participants received these contents as missions throughout the program, which were designed to help them adjust their behavior according to the challenges they face when dealing with atopic dermatitis. Missions were defined as all assignments available in the app; participants were assigned on average 5 missions per day from the above categories that they were asked to complete. In addition, users could complete “open missions” such as guided meditation and logging steps (with a step counter), which were not assigned by the program specifically that day.Education was composed of videos and content cards relating to atopic dermatitis, skin care, symptoms, triggers, comorbidities, stress, sleep, and mindset.PROs on atopic dermatitis symptoms were assigned once a week on a specific day . Users were first asked to select which of the listed symptoms they had experienced in the past week; the options were itch, bleeding skin, cracked skin, flaking skin, dry or rough skin, weeping or oozing clear fluid from eczema, disturbed sleep, or none of these. Based on the response from the first question, users were then asked to rate the severity of their symptoms ranging from 1 (mild) to 9 (severe). The total score per participant was calculated by adding up the ratings from all questions. If a participant responded with “none of these,” then the total score for that week was zero.PROs on quality of sleep, stress, and energy levels were collected 3 times per week from week 2 onward, where participants rated themselves on a 10-point sliding visual analog scale.Medication reminders were set up by the participants with customized timings and frequency. Participants then received the reminder as a mission each time, which was completed when the user pressed “done.”exposed: the number of users passively exposed to the feature, no action was required; (2) interacted: those who interacted during the first week of exposure; (3) activated: those who used the feature again after activation; and (4) retained: those who used the feature in the last week.Program engagement was assessed by determining program usage patterns: how often participants engage with the content, how many tasks were performed, and what types of tasks  were performed. Dedicated users were defined as participants who were active for at least 5 days (or more) every week. The engagement and retention for key app features—education, medication, PROs, step count, and mind exercises—are reported as the number of users calculated in the following four stages: (1) Acceptability of the program was assessed through the mHealth App Usability Questionnaire (MAUQ) for standalone apps, which was administered to participants after the study . The MAUt tests (α=.05). R  was used for all analyses.Descriptive statistics were computed as mean and SD or median and IQR for continuous variables and numbers and percentages for categorical ones. The longitudinal changes in QoL and symptom PROs were tested by comparing the first and the last available measures using paired-sample The study protocol was approved by the Icelandic National Bioethics Committee . All participants were given detailed explanation of study procedures and signed informed consent (in Icelandic) prior to enrollment. All study data were anonymized, and the information collected in the app was encrypted and handled in compliance with General Data Protection Regulation.A total of 21 adult patients were recruited in the study, 20 (95%) of whom completed the program. Information about participants and their average app usage is presented in Breakdown of the adoption of key app features  showed that participants used the medication reminders, QoL PROs, and disease education most consistently throughout the program . These fMedication reminders and education content missions both had high weekly compliance rates; all assigned users (n=20) completed these tasks in the first 2 weeks, and completion remained over 90% for all subsequent weeks . HoweverWe analyzed the weekly engagement with atopic dermatitis symptom PRO surveys as well as the reported number and severity of symptoms  and founP=.006), and there was a trend toward overall improved sleep quality  and reduced stress levels  reported these at least 3 times in week 1 and 12 (70%) continued to do so in week 5 , demonstUser satisfaction was high, as measured by the MAUQ. The median total MAUQ score was 6.2 out of 7 , and the median scores for ease of use, interface satisfaction, and usefulness were 5.9 (IQR 5.6-6.4), 6.4 (IQR 5.4-6.9), and 6.3 (IQR 5.3-6.7), respectively.We found high overall program engagement and user retention in this 6-week-long study, suggesting that a holistic digital health program is feasible for patients with atopic dermatitis. We also analyzed user activity flow over time for key app features and created 4 categories: those users who were passively exposed to a specific feature (exposed), those who then actively interacted with it (interacted), those who continued using the feature (activated), and those who used the feature in the last week (retained). This analysis showed that users complied with the missions in most categories when these were assigned. Particularly, PROs, medication reminders, and educational materials had high compliance, suggesting that participants were interested in self-assessment, learning more about their disease, and acquiring help for managing medication schedules. These results were consistent with another similar 3-month long study where participants interacted the most with the education parts about atopic dermatitis and its treatments, in particular . It remaDetailed analysis of engagement with medication reminders and educational materials corroborated the above findings regarding high user compliance. We found that, while medication mission completion remained stable over time, the average weekly interactions with these tasks gradually decreased. This could be interpreted as people setting fewer medication reminders or deleting them over time as their symptoms improved, while they continued completing those that they kept. Indeed, symptom PROs showed that the average reported number and severity of atopic dermatitis symptoms reduced over time.Similar to medication reminders, we also found an initial high interaction with the education content (weeks 1-3) that decreased after week 4. This can be explained by users exhibiting an initial exploratory behavior—while they actively seek out education content—followed by an “as-necessary” phase when users only complete the missions that were assigned to them. Decreased user engagement with DTx programs is expected and is well documented ,18, but—Another important finding was the feasibility of continuous patient monitoring, as demonstrated by the high compliance with both the symptom and QoL PRO missions. However, there was no control over what time of the day participants rated their sleep quality, energy, or stress levels, which may increase the day-to-day variability of these measurements—future studies will need to further validate the clinical accuracy and reliability of in-app PROs.Several previous studies have assessed the efficacy of multidisciplinary interventions among adult patients, or pediatric patients and their parents . These iThis study was limited by a small sample size and the relatively homogeneous sample; larger, multicenter trials would need to assess the generalizability of these results among a more diverse group of patients. The statistical comparison of QoL and symptom PROs from first to last measurements did not include a control group and should hence be interpreted with caution. In addition, while here we report high medication adherence results, it should be noted that completion of a medication reminder does not guarantee treatment completion . Another limitation of the study was that not all mission categories analyzed here were assigned for users ; therefore, it is difficult to compare the engagement and retention with other assigned mission categories.To our knowledge, this is the first study to assess the feasibility of a holistic digital health program for patients with atopic dermatitis. The high continued program engagement and retention, compliance with medication reminders, education content, symptom, and QoL PROs, and the high user satisfaction provide strong evidence for the feasibility of an atopic dermatitis–specific digital solution for patients. In addition, the decrease in symptom frequency and severity, as well as improved ratings of sleep quality, energy, and stress levels recorded in the app agree with previously reported results of clinical assessments of these patients. These results can inform the design of future randomized controlled trials to further validate the efficacy of a targeted DTx program in atopic dermatitis.


This secondary analysis of a randomized clinical trial investigates the proportion of correct answers on neonatal resuscitation options among parents after seeing a video on these options. In the randomized clinical trial (RCT) of the smartphone Preemie Prep for Parents (P3) program,3 we provided neonatal resuscitation education in early pregnancy and evaluated the association of the program with knowledge at 25 weeks’ gestational age (GA).For infants born during the periviable period of gestation, the decision to provide delivery room resuscitation is based on parental preference.CONSORT reporting guidelines  , most individuals were pregnant and had more than a high school diploma . Among 1P3 is a novel prenatal program that provides neonatal resuscitation education in early pregnancy to parents with preterm birth risk factors. In this secondary analysis of an RCT, most parents watched at least 1 video and video use increased parental knowledge.4 This situation is characterized by crucial information delivered with limited time for family discussion or contemplation. Although this time pressure may influence decisions,5 these limitations are assumed to be unavoidable. However, for pregnancies at risk of preterm birth, P3 videos provide parents with a framework of this decision and available options prior to hospitalization.Published research on improving the periviable decision-making process has focused on informing parents of neonatal resuscitation options at the time of delivery hospitalization.6This study is limited in that findings were based on post hoc analysis. While our single-center trial was not intended to examine effects of knowledge on periviable resuscitation decisions (1 of 120 patients delivered at 22-24 weeks), already having foundational knowledge of options may allow counseling during hospitalization to focus more on personalized information and parental values.Whether to resuscitate an infant who is periviable and preterm is a complex, preference-sensitive decision. These results suggest that the P3 program may offer families with high-risk pregnancies the opportunity to learn about options available and contemplate what they would value for their baby before they may need to make the choice.


BCR::ABL1 fusion has significant prognostic value and is screened for chronic myeloid leukemia (CML) disease monitoring as a part of routine molecular testing. To overcome the limitations of the current standard real-time quantitative polymerase chain reaction (RQ-PCR), we designed and validated a next-generation sequencing (NGS)-based assay to quantify BCR::ABL1 and ABL1 transcript copy numbers.After PCR amplification of the target sequence, deep sequencing was performed using an Illumina Nextseq 550Dx sequencer and in-house–designed bioinformatics pipeline. The Next-generation Quantitative sequencing (NQ-seq) assay was validated for its analytical performance, including precision, linearity, and limit of detection, using serially diluted control materials. A comparison with conventional RQ-PCR was performed with 145 clinical samples from 77 patients.BCR::ABL1 0.00028% international scale (IS)]. The NQ-seq exhibited excellent precision and linear range from MR 2.0 to 5.0. The IS value from the NQ-seq was highly correlated with conventional RQ-PCR.The limit of detection of the NQ-seq was the molecular response (MR) 5.6 [BCR::ABL1 transcripts in CML patients with high sensitivity and reliability. Prospective assessment of the unselected large series is required to validate the clinical impact of this NGS-based monitoring strategy.We conclude that the NQ-seq is an effective tool for monitoring The online version contains supplementary material available at 10.1186/s12935-023-02938-2. BCR::ABL1 fusion gene from the translocation between chromosomes 9 and 22 [t]. The BCR::ABL1 fusion gene has several pathological significance in CML patients. First, BCR::ABL1 is a diagnostic biomarker for CML patients. The BCR:ABL1 fusion produces a chimeric protein with constitutive tyrosine kinase activity, resulting in unregulated cell proliferation and the development of CML[BCR::ABL1 is a predictive biomarker for tyrosine kinase inhibitor (TKI) eligibility. TKIs such as imatinib, nilotinib, and dasatinib selectively inhibit the growth of BCR::ABL1 positive cells by inhibiting tyrosine kinase activity. The use of TKI dramatically improved the survival rate of patients with CML-CP[Chronic myeloid leukemia (CML) is diagnosed in approximately 1.8 per 100,000 individuals per year. About 10–15% of all adult cases of leukemia are CML[th CML-CP. Finallyth CML-CP, 5.BCR::ABL1 are associated with a p210 oncoprotein. Molecular testing for BCR::ABL1 fusion is the most sensitive routine test for monitoring responses to therapy in patients with CML[BCR::ABL1 transcript levels are calculated as the ratio between BCR::ABL1 transcripts and a reference gene according to international scale (IS) values to standardize results between centers. However, RQ-PCR has several limitations, including its limit of detection, its sensitivity to PCR-inhibitors, loss of quantification precision and accuracy at low transcript concentrations, and need of a standard curve constructed from a standard material of known copy number for quantitation[In more than 95% of CML patients, transcripts located within e13a2 (b2a2) or e14a2 (b3a2)  with CML. Currentntitation. TherefoBCR::ABL1 and ABL1 transcripts and validate the analytical performance of the developed assay.In this study, we designed a next-generation sequencing (NGS)-based assay, Next-generation Quantitative sequencing (NQ-seq), to quantify BCR::ABL1 and ABL1. The PCR conditions consisted of an initial denaturation step of 95℃ for 5 min, followed by 26 cycles of 98℃ for 45 s, 60℃ for 1 min, 72℃ for 1 min, and a final elongation step at 72℃ for 5 min. The libraries were cleaned with Agencourt AMPure XP beads . A total of seven sets of primers were designed for detecting the BCR::ABL1 major types and the ABL1 as a reference for normalization. The first target was the BCR::ABL1 major types that covered exon 13–14 of BCR and exon 2 of ABL1 . The cDNA  was amplified with primers targeting BCR::ABL1 fusion junctions were called using STAR 2.7.3a, and final fusion copy numbers were determined through international scale (IS) conversion[ABL1 control reads. The test results used IS values by determining and maintaining conversion factors (CF) and molecular response (MR) to reduce variation and improve accuracy. BCR::ABL1 transcripts types were visualized by the Arriba[Raw demultiplexed NGS data were mapped to the reference genome of GRCh38 using Spliced Transcripts Alignment to a Reference (STAR) aligner tool[onversion with fushe Arriba.BCR::ABL1 b3a2 RNA Dilution Set  to evaluate analytical performance. This standard material consists of RNA that has been extracted from confirmed BCR::ABL1 b3a2 positive and BCR::ABL1 negative cell lines. Also, levels not contained in this reagent (copy numbers 10− 6 and 10− 7) were manually mixed by the serial dilution method from b3a2 RNA (10− 5 copy numbers) positive and negative materials.We used the BCR::ABL1 standard materials. Precision and linearity were assessed using five levels of standard materials . To evaluate assay precision, each material was measured seven times, including two or three replicates per single run on three separate days. Each dilution was measured three times to evaluate linearity. The LOD was estimated based on measurements at seven levels of dilution  at five replicates for each. Additionally, the LOB was assessed by repeating a total of 24 times for four days using two BCR::ABL1 negative RNA specimens consisting of subtypes b2a2 and b3a2.Precision, linearity, limit of detection (LOD), and limit of blank (LOB) were evaluated with varying levels of BCR::ABL1 transcripts at diagnosis or follow-up. We selected samples with evenly distributed BCR::ABL1 quantitative values among residual samples sufficient to perform the NGS test and compared them with the RQ-PCR test. This study was approved by the Institutional Review Board of Severance Hospital, Yonsei University Health System (4-2019-0277). Informed consent was waived for this retrospective study that evaluated anonymized samples and data and involved no potential risk to patients. Total RNA was extracted from bone marrow aspirate or whole blood with a QIAamp RNA Blood Mini Kit  according to the manufacturer’s protocol. RNA quality control and quantification were performed with an Agilent 4200 Tapestation  . The samples were referred to our laboratory to detect and quantify System 4-019-0277.BCR::ABL1 expression was performed using the Ipsogen kit and protocol . This protocol quantifies BCR::ABL1 copy numbers relative to a total ABL1 copy number using a real-time TaqMan method. We used 5 µL of cDNA  as a template in a 25 µL PCR reaction. Any BCR::ABL1 or ABL1 real-time PCR for individual samples was performed in duplicate.RQ-PCR analysis for Uhlig et al.[p-value < 0.05 was considered statistically significant.Statistical analysis was carried out using R version 4.02 . The LOD was determined by probit analysis (95% detection rate) using the POD package, which implements the mathematical statistics presented by ig et al. in R sofBCR gene most commonly occurs between exon 13 (e13) and exon 14 (e14) or between e14 and exon 15 (e15) in a region called the major breakpoint cluster or M-BCR[BCR::ABL1 fusion copy quantification: (1) BCR::ABL1 fusion primer and (2) ABL1 control primer  were tested in three batches and triplicated at each level in the final batch. The repeatability of coefficient of variation (CV) was from 3.7 to 47.2%, and the total imprecision was from 5.8 to 44.7%   (Supplementary Table Eight dilutions with known 12) Fig. . Using pr = 0.93, p < 0.001, Fig. We compared NQ-seq with conventional RQ-PCR using 145 clinical samples including before and after treatment. We divided the clinical samples into three batches. The NQ-seq exhibited a good correlation with the RQ-PCR assay  were compared with NQ-seq and RQ-PCR and displayed graphically Fig. B. A totaBCR::ABL1 transcript. For monitoring and assessing molecular responses in CML patients, the current standard assay is RQ-PCR[In the present study, we described the development and validation of an NGS assay to quantify the is RQ-PCR. Our metis RQ-PCR. Above aBCR::ABL1 reads detected by NGS may be actual reads. False-positive reads can be generated due to a PCR or sequencing error. As a result of our evaluation, the LOB of NQ-seq was determined to be three reads, so we only decided on four or more reads as positive in this study.Several studies have concluded that the NGS for the fusion transcript assessment quantitative assay shows higher sensitivity than the conventional methods–16. Our Moreover, this quantitative result of most patients of the analyzed cohort was obtained in concordance with RQ-PCR for quantitative assessments at the MRD level. The MR value of the patients treated with TKI by NQ-seq as log reduction in relation to individual baseline value indicated max 4.9-log reduction, showing reliable detection of deep MRs based on treatment guidelines. A 4.5-log reduction is referred to as DMR, with a higher probability of achieving treatment-free remission (TFR). TFR is achieved in CML patients who have a stable DMR without need for ongoing tyrosine kinase inhibitor treatment. MeanwhiSeveral new effective MRD methods were recently considered, including droplet digital PCR (ddPCR) and NGS. According to previous studies, the ddPCR consequences suggested good performance with a confirmed LOD of MR 4.64 and a maximum CV of 9.3% with less affected primer efficiency than the conventional methods, 19. We BCR::ABL1 transcripts. However, they did not differentiate between e13a2 and e14a2 types. NQ-seq can determine specific transcript types and amounts at once. This can provide additional information on sample identification, which can help improve test accuracy. In addition, a maximum of 42 samples can be performed for ddPCR and 16 samples for RQ-PCR, excluding standard material, but NQ-seq can perform 54 samples based on NextSeq 500/550 Mid Output Kit v2.5 (300 Cycles). Therefore, one can deliver more accurate and faster results to patients using NQ-seq in the clinical setting.NQ-seq has several advantages over existing methods. Real-time quantitative PCR (RQ-PCR) and droplet digital PCR (ddPCR) are used to quantify known fusion transcript types. RQ-PCR and ddPCR can detect major Future improvements to this assay include developing primer and index sets to detect atypical rare transcripts while reducing the sequencing error rate. In addition, evaluation of serial samples from large cohorts for long-term monitoring is required.BCR::ABL1 quantitation that can be used in molecular monitoring in CML patients. The NQ-seq assay can be used as a reliable and promising tool for MRD monitoring in patients with CML.In summary, our study has developed and validated an NGS-based assay for Below is the link to the electronic supplementary material.Supplementary Material 1


Phlebotomus argentipes density reduction ranged from −56% to −83%, and the P. argentipes sand fly mortality ranged from 81% to 99.5% during the 24-month follow-up period. Considering the duration of the efficacy of IWP for controlling VL vectors, Bangladesh National Kala-azar Elimination Program may consider IWP as the best alternative to IRS for the subsequent phases of the program.The success of the visceral leishmaniasis (VL) elimination program largely depends on cost-effective vector control measures. Our goal was to investigate the longevity of the efficacy of insecticidal wall painting (IWP), a new vector control tool, compared with a routine indoor residual spraying (IRS) program for reducing the VL vector density in Bangladesh. This study is the extension of our recent IWP study for VL vector management in Bangladesh, which was undertaken in seven highly VL endemic villages of the Mymensingh district with a 12-month follow-up. In this 24-months follow-up study, we collected sand flies additionally at 15, 18, 21, and 24 months since the interventions from the IWP and control (where the program did routine IRS) clusters to examine the longevity of the efficacy of IWP on sand fly density reduction and mortality. The difference-in-differences regression models were used to estimate the effect of IWP on sand fly reduction against Program IRS. The IWP showed excellent performance in reducing sand fly density and increasing sand fly mortality compared with Program IRS. The effect of IWP for controlling sand flies was statistically significant for up to at least 24 months. The mean female  Leishmania donovani causes VL in Bangladesh and the female Phlebotomus argentipes is its vector which transmits the parasites among community people. First reported VL outbreak in the Bangladesh territory occurred in 1824 when ∼75,000 people died.,,,Visceral leishmaniasis  is a crucial problem for public health worldwide because it is potentially lethal if untreated. The parasite TM with a coverage of 2.43 m2 of the HH wall. Inesfly 5AIGRNG contains alphacypermethrin 0.7%, D-allethrin 1.0%, and pyriproxyfen (0.063%). It is a vinyl paint with an aqueous base formulation with CaCO3 and resin microcapsules as active ingredients, which allow a gradual release of active ingredients. The size of the microcapsules ranges from one to several hundred micrometers. After painting, the concentration of the insecticides per square meter surface area of the wall should be 1.225, 1.75, and 0.11 g/m2 for alphacypermethrin, D-allethrin, and pyriproxyfen, respectively. There were 56 HHs in this experimental arm. The interventions were imposed in November 2015 and followed up until December 2017.Details of the IWP intervention have been described elsewhere.The routine IRS program in NKEP was this study’s reference arm (comparator). The program’s trained team sprayed up to 6 feet (180 cm) of the indoor walls of the HHs of the study villages with deltamethrin 5 WP  before 6- and 18-month follow-ups. The program IRS arm had 54 HHs and presented as reference arm (comparator) in this study.The Trishal upazila (subdistrict) under Mymensingh district was our study area. The study was carried out from November 2015 to December 2017. Trishal is the highest VL endemic upazila of Bangladesh.Detailed study design has been published elsewhere.Trained ento-technicians collected sand flies from the randomly selected 36 HHs from intervention cluster and 36 HHs from Program IRS cluster 2 to 4 weeks before intervention (baseline), and at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months since the intervention. We assessed sand fly mortality through the WHO cone bioassay test in 12 HHs in the intervention cluster at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months since the intervention. Collection of sand fly and density measurement and the WHO cone bioassay test were performed according to the methods described in our recent study.We used two methods to calculate the effect of IWP on sand fly control at HH level using: 1) sand fly density reduction (in percentage) by IWP compared with Program IRS and 2) sand fly mortality rate (in percentage) when exposed to IWP compared with the control.2 test. The mean HH female P. argentipes sand fly values in the cluster defined the female P. argentipes sand fly density (FPAD) of a cluster.Data entry was conducted using the Epi Info software (Version 3.5) for data entry and data management. Before data analysis, data were cleaned with checks for duplication and inconsistency. We dichotomized sociodemographic and economic variables. For calculation of HH asset score, we used principal component analysis. Descriptive analysis was performed. Sociodemographic and economic variables were compared between the two groups using the χThe IWP effect on sand fly density at the HH level against Program IRS was measured by the difference-in-difference (DID) regression model. It accounted for the baseline differences of FPAD and for the variations between IWP and Program IRS regarding their covariates. An interaction term for the intervention cluster at follow-up estimated the intervention effect. The regression follows:First, we fitted the unadjusted regression model by considering only the time and treatment (IWP versus Program IRS) variables in the model to get the unadjusted intervention effect. The model was then extended further by incorporating the variables that differed significantly between IWP and Program IRS clusters to get the adjusted intervention effect. On the basis of the bivariate analysis , in the We considered an intervention effective for killing sand flies if Abbot’s corrected sand fly mortality remained ≥ 80%.P = 0.004) (P = 0.001), ownership of cow in the HH (P < 0.0001), and bed-net use (P = 0.001) significantly differed between IWP and Program IRS at baseline (P = 0.001)  than Program IRS cluster (0.56 [0.17–0.94]) (= 0.004) . We alsobaseline . For exa= 0.001) .P < 0.20 in bivariate analysis .In Bangladesh, the NKEP has reached the elimination target through coordinated interventions and considerable investment, with only 35 VL cases in 2021. Sustainable interventions that are adapted to the low case load must now be set in place in the maintenance phase, or these achievements might be lost, and we will face a resurgence of VL.,IRS is resource-intensive, and its efficacy last only 4 to 6 months.Regarding the efficacy of other vector control tools such as ITNs, one study found that ITNs are effective for up to 18 months.,,DWL is another effective VL vector control tool in the Indian subcontinent.The current price of IWP (30 USD per HH) and DWL (50 USD per HH) for full coverage is comparatively high for communities and national programs. The partial coverage with DWL makes its cost closer to that of IWP but the duration of the efficacy of IWP for controlling VL vector is up to 24 months. Furthermore, DWL is no longer in production.On the other hand, IWP is easy to operate, and intervention can be implemented in the community by the community members themselves. Our recently completed study for IWP feasibility and effectiveness for sand fly control when it is deployed by community members under the supervision of public health workers found encouraging results (unpublished data). Therefore, our present study and the existing body of evidence in the literature clearly indicate that IWP outperforms the existing vector control tools in terms of its feasibility, affordability, and long-term effectiveness.Our study is not without its limitations. First, as reported earlier,In conclusion, all existing vector control tools, including IWP, are effective, but duration of efficacy is different. In this study on the long-term efficacy of IWP, we found that IWP is effective up to at least 24 months for sand fly density reduction and sand fly mortality. We recommend that the NKEP consider IWP as a first choice VL vector control tool against IRS for the subsequent phases of the VL elimination program in Bangladesh.