Objectives: Measuring implementation outcomes for digital mental health interventions is essential for examining the effective delivery of these interventions. The “Implementation Outcome Scale of Digital Mental Health” (iOSDMH) has been validated and used in several trials. This study aimed to compare the iOSDMH for participants in six randomized controlled trials (RCTs) involving web-based interventions and to discuss the implications of the iOSDMH for improving the interventions. Additionally, this study examined the associations between iOSDMH scores and program completion rate (adherence). Methods: Variations in total scores and subscales of the iOSDMH were compared in six RCTs of digital mental health interventions conducted in Japan. The web-based intervention programs were based on cognitive behavioral therapy (2 programs), behavioral activation (1 program), acceptance and commitment (1 program), a combination of mindfulness, behavioral activation, and physical activity (1 program), and government guidelines for suicide prevention (1 program). Participants were full-time employees (2 programs), perinatal women (2 programs), working mothers with children (1 program), and students (1 program). The total score and subscale scores were tested using analysis of variance for between-group differences. Results: Total score and subscale scores of the iOSDMH among six trials showed a significant group difference, reflecting users’ perceptions of how each program was implemented, including aspects such as acceptability, appropriateness, feasibility, overall satisfaction, and harm. Subscale scores showed positive associations with completion rate, especially in terms of acceptability and satisfaction . Conclusions: The iOSDMH may be a useful tool for evaluating participants’ perceptions of features implemented in web-based interventions, which could contribute to improvements and further development of the intervention. Digital mental health interventions have rapidly become available worldwide, with recent studies ,2,3,4 fiWe previously developed and validated the implementation Outcome Scales of Digital Mental Health (iOSDMH) for users  to evaluate implementation aspects of mental health interventions delivered via digital and telecommunication technologies such as internet websites, movies, apps, and e-mails . AlthougThe iOSDMH for users includes 19 implementation items, including acceptability, appropriateness, feasibility, satisfaction, and harm. However, it remains unclear which implementation items are more predictive of completion rate or participant attitude compared with other items. A previous literature review indicated a positive association between treatment satisfaction and adherence, compliance, or persistence . This asWe compared variations of implementation outcomes in six RCTs of digital mental health interventions . Study 1 was an app-based self-help Cognitive Behavioral Therapy (CBT) intervention for pregnant women . Study 2The iOSDMH has several distinct versions for users, providers, and managers. This study utilized the users’ version, which comprises two parts: (1) evaluations (14 items) and (2) adverse events of using digital mental health programs 5 items). Each item’s response was scored on a 4-point Likert-type scale ranging from 1 (disagree) to 4 (agree). The subscales interpreted “relatively agree” and “agree” as being implemented (preferable). Evaluations with their number of items and possible score ranges were as follows: acceptability , appropriateness , feasibility , harm , and satisfaction . The total score has 14 items . Scores were calculated by summing the items’ scores. The original development paper  items. E.The study characteristics were collected as descriptive data: research design , intervention details , facilitations and functions , and findings and presentations .We determined whether iOSDMH scores can differentiate implementation outcomes among the studies by testing group differences with a chi-square test for the proportion implemented in each item. We tested total score and subscale scores using analysis of variance for group differences. The association between implementation subscales and completion rate was assessed by calculating the R-squared value using Microsoft Excel . The statistical significance for all analyses in this study was set at 0.05 (two-tailed), and 95% confidence intervals were calculated. All statistical analyses were performed using the Japanese version of SPSS 28.0 .p = 0.029; others, p < 0.001).advantages outweigh the disadvantages for keeping my mental health) and item 3 (acceptable for me); and (2) low evaluation rates  for item 3 . Study 4 was an e-learning program for full-time workers that encouraged participants to read webpages of interest. This study presented intermediate scores  for items 1  and 3 (acceptable for me) and a low evaluation score  for item 2 .For acceptability, Study 5 demonstrated the highest score for all items among the six trials. Study 5 was an online student peer gatekeeper program that provided basic knowledge about suicide prevention via YouTube video for students willing to become peer supporters of suicide prevention. Study 3 showed the second highest scores for all items in acceptability. Studies 1, 2, and 6 were e-learning programs targeting a specific population. These studies presented similar profile patterns for three items in acceptability: (1) positive evaluation rates fell between 68.9% and 79.7% for item 1 , item 6 , and item 7 (fits my living condition). The studies on prenatal (Study 1) and postnatal (Study 6) experiences demonstrated a positive evaluation rate above 80% in appropriateness-related items, especially for item 5 . Study 2 presented high user evaluations (77.6%) for item 4  and moderate user evaluations for other items. Study 3 also presented high evaluations (84.6%) for item 4  and moderate evaluations for other items. Study 4 demonstrated a low evaluation for item 5  and item 7 (fits my living condition), with a positive evaluation rate of 50.2% and 48.9%, respectively.For appropriateness, Study 5 demonstrated the highest evaluation scores for three of four items among all the programs: item 4 . Study 4 showed moderate user evaluations . Study 6, which required the longest time per session and the longest total time to complete the whole program, reported low scores for item 8 (easy to use), item 9 , item 10 , item 11 (length of one content is implementable), and item 13 (easy to understand), with positive evaluation rates of 58.6%, 34.5%, 41.3%, 48.3%, and 41.4%, respectively.For feasibility, Study 1, Study 3, and Study 5 demonstrated higher user evaluations for all items compared with other programs. Study 2 reported moderate to high feasibility  except for item 9 , while Studies 2 and 6 reported that users regularly perceived excessive learning-related stress .R-squared value = 0.93, R2 = 0.89; respectively). Harm showed a weak inverse association. iOSDMH total scores also showed a high association with completion rate .This study evaluated implementation and dissemination aspects of six RCTs of digital mental health programs using iOSDMH scales as developed in a published study. The iOSDMH was shown to be an effective tool for understanding program characteristics on acceptability, appropriateness, feasibility, overall satisfaction, and harm as well as user evaluations of these points. Moreover, the iOSDMH was found to effectively measure prediction of program completion rates with moderate to high associations. Compared with appropriateness and feasibility, acceptability and satisfaction were more strongly associated with completion rate. These findings might indicate that subjective positive feelings about a program are important for adherence. Examination of iOSDMH total scores or subscales made it possible to clarify future assignments to promote further program implementation.Acceptability considers whether a program’s users feel that the program benefits their mental health and they have a positive impression of the program.Acceptability relates to various factors, including a program’s topics, theory, and participation style. Study 5 (targeting students interested in suicide prevention) seemed to attract users’ interest and utilized effective delivery methods such as peer role play and YouTube, resulting in high acceptability scores. YouTube videos and peer role play might have contributed to these high evaluations of acceptability, a finding that is consistent with a previous study . Study 3Our study showed high associations between acceptability and completion rate, which is consistent with previous studies showing that meeting client needs and preferences, sharing decision-making, and tailoring care are important for improving implementation and effectiveness ,24. Our We found that matching program content with a user’s physical or medical needs is an important factor for appropriateness. In Study 5, students willing to be gatekeepers for suicide prevention might have needed communication skills for suicide prevention and thus felt that the program content was appropriate and suited their social condition. They might have perceived that communication skills useful for listening to peers and connecting to professionals were relevant or correct. The programs on perinatal-specific issues (Studies 1 and 6) also received high scores for content appropriateness and fitting users’ health status. Our finding was consistent with a previous finding that the perceived relevance of program content and personal circumstances were important for treatment engagement and adherence . HoweverFor feasibility, we assessed the difficulty of using the program, time requirements for program participation, and content difficulty. Time seemed to be a key factor among programs with high feasibility evaluations. Programs that required less than 15 min to complete a session, with six sessions overall, received high evaluations. Study 5 received high feasibility evaluations because its movie sharing media (YouTube) took little time per session, which also shortened the duration of the whole course. Media sharing sites such as YouTube are potential resources for knowledge translation as they are easy to use and free of cost . FurtherOur study included satisfaction evaluations. Programs with high evaluations in other subcategories also showed high satisfaction scores. In implementation science, users’ perceived satisfaction with a program is important and future studies should explore the details. Regarding completion rate, satisfaction showed a high association with completion rate. Previous research suggests that high treatment satisfaction achieves high adherence . Note thThe iOSDMH total scores reflected overall subscale evaluations, with Study 5 receiving the highest scores of all. Study 5 successfully reached the population in need, had appropriate programs utilizing a feasible method, and thus provided a sense of satisfaction. The iOSDMH total scores showed a positive correlation with program completion rate, suggesting that perceived evaluation of implementation aspects has some influence on completion rate. Although completion rate might be influenced more by reminder frequency, internal learning needs, and informal pressures for contextual use, implementation outcomes measured by the iOSDMH partially predict adherence. Revising the program to improve its total score might contribute to program effectiveness and efficacy through increased adherence. Because the programs were based on different psychological models and have different primary outcomes, total scores among different trials should be interpreted with caution. Due to differences among the trials, cutoff points for total scores were not reported in this study. The iOSDMH total scores might be beneficial especially when compared with studies having similar research designs and primary outcomes or to reevaluate implementation aspects of the program after modifying program contents or intervention delivery methods.We found that iOSDMH subscales provided rich information on users’ evaluation of a program in terms of acceptability, appropriateness, feasibility, and overall satisfaction, and these measures seemed to be associated with program completion rate. Researchers can review each subscale score to fulfill unmet needs of the program contents or intervention design as perceived by users. Because this study discussed important factors for each item of implementation, researchers can benefit from our findings to find clues for improvement. After refining a program or study design, researchers can then readminister iOSDMH scales for reevaluation. Moreover, even when an intervention program fails to show a significant effect for primary endpoint outcomes, implementation outcomes would provide researchers essential information to explore the reasons an intervention program did not perform as expected, leading to future improvement of the program. In the clinical practice, using this scale provide the indicator of improvement progress. Comprehensive assessment of iOSDMH may enlighten the target area which needs to be improved and lead further refinement for contents or delivery-related strategies of digital mental health program in clinical settings.This study had several limitations. First, a cut-off point was not reported for each iOSDMH subscale or total score because each study had different study settings and objectives. Second, iOSDMH scales relied on users’ reported outcomes. Therefore, we attempted to compare iOSDMH scores with the program completion rate. Third, as the trials examined in this study consisted of a convenience sample of RCTs, our findings must be validated in other trials. Forth, the iOSDMH was not validated compared to other scales for measuring implementation outcomes of digital interventions. There is still room to examine further priority of the scale compared to other existing scales.This study showed the effectiveness of the iOSDMH scale to evaluate essential aspects of digital mental health programs and serve as a significant indicator of program completion. Evaluation of implementation outcomes might also be important for maximizing effectiveness, which can be highly affected by completion rate. The iOSDMH scale can direct researchers toward future program goals to achieve social implementation and maximum effectiveness.


ARID1a (BAF250), a component of human SWI/SNF chromatin remodeling complexes, is frequently mutated across numerous cancers, and its loss of function has been putatively linked to glucocorticoid resistance. Here, we interrogate the impact of siRNA knockdown of ARID1a compared to a functional interference approach in the HeLa human cervical cancer cell line. We report that ARID1a knockdown resulted in a significant global decrease in chromatin accessibility in ATAC-Seq analysis, as well as affecting a subset of genome-wide GR binding sites determined by analyzing GR ChIP-Seq data. Interestingly, the specific effects on gene expression were limited to a relatively small subset of glucocorticoid-regulated genes, notably those involved in cell cycle regulation and DNA repair. The vast majority of glucocorticoid-regulated genes were largely unaffected by ARID1a knockdown or functional interference, consistent with a more specific role for ARID1a in glucocorticoid function than previously speculated. Using liquid chromatography-mass spectrometry, we have identified a chromatin-associated protein complex comprising GR, ARID1a, and several DNA damage repair proteins including P53 binding protein 1 (P53BP1), Poly(ADP-Ribose) Polymerase 1 (PARP1), DNA damage-binding protein 1 (DDB1), DNA mismatch repair protein MSH6 and splicing factor proline and glutamine-rich protein (SFPQ), as well as the histone acetyltransferase KAT7, an epigenetic regulator of steroid-dependent transcription, DNA damage repair and cell cycle regulation. Not only was this protein complex ablated with both ARID1a knockdown and functional interference, but spontaneously arising DNA damage was also found to accumulate in a manner consistent with impaired DNA damage repair mechanisms. Recovery from dexamethasone-dependent cell cycle arrest was also significantly impaired. Taken together, our data demonstrate that although glucocorticoids can still promote cell cycle arrest in the absence of ARID1a, the purpose of this arrest to allow time for DNA damage repair is hindered. Glucocorticoids are widely used in the clinic due to their potent anti-inflammatory properties and are extensively used as a cancer treatment due to their ability to induce apoptosis and promote cell cycle arrest –3. HowevChromatin remodeling by the BAF (hSWI/SNF) complex is important for genomic GR signaling, with chromatin accessibility being dynamically altered at GR binding sites in target genes to regulate transcription . The MouRecently we found that the SKOV3 ovarian cancer cell line, which harbors a truncating ARID1a mutation, exhibited a highly restricted glucocorticoid transcriptional response . We therTo assess the impact of ARID1a knockdown on dexamethasone (Dex)-induced GR binding, chromatin samples (nine samples each comprising 100 μg chromatin) were immunoprecipitated with GR antibody, and the resulting immunoprecipitates were combined for library preparation and sequencing. Two separate ChIP-Seq experiments were performed independently to allow for concordant peak calling analysis as previously described ; the GR The data are visualized in the hierarchical clustering heatmap Fig. . ClusterAs GR binding influences subsequent chromatin accessibility, we hypothesized that the observed ARID1a-dependent global changes in GR binding would also impact upon global chromatin accessibility. We therefore performed ATAC-Seq, with two independent replicates for each of the four conditions (-Dex baseline and +Dex GR induction for each of ARID1a knockdown and control siRNA conditions), which revealed genome-wide changes in chromatin accessibility upon knockdown of ARID1a Fig. .Fig. 2EfK-means clustering of differentially open regions (DORs) identified 8 discrete cluster groups, each of which describes specific combinations of pre-accessibility and Dex-inducibility for each of the four conditions  and GR binding site locations from the GR ChIP-Seq analysis. The PER1 gene locus Fig.  containsTo better understand the extent of loss or functional interference of ARID1a on gene expression, we performed RNA sequencing (RNA-Seq) following a 6 h Dex timecourse in cells with ARID1a knockdown  in In contrast, cells transfected with ARID1a-CTD-GFP exhibited the highest levels of γH2AX  in the absence of Dex, when compared to matched GFP+ control cells  was used to identify GR-interacting proteins in control cells compared to when ARID1a was knocked down, in order to identify an ARID1a-dependent GR protein complex at the DNA template. These data confirmed an interaction between GR and ARID1a in control cells and further identified ARID1a-dependent GR interactions with key P53-related and DNA repair proteins Fig.  includinOther ARID1a-dependent GR interactions included PARP1, a protein required for DNA repair and linked to regulation of P53 mediated cell cycle arrest , and DNAIn the functional interference study, ARID1a-CTD-GFP was found to interact with GR resulting in the loss of endogenous ARID1a binding  is linked to glucocorticoid resistance  and is w0 is linkATAC-Seq data revealed that chromatin pre-accessibility was significantly affected by ARID1a knockdown, with a significant decrease in pre-accessibility at a large number of sites, and a significant increase at a smaller number of sites. Interestingly, a small but notable subset of sites were Dex-inducible in both ARID1a knockdown and control cells, and many of these were within loci containing genes found to be similarly Dex-regulated in control siRNA and ARID1a knockdown cells in the RNA-Seq analysis. Examples of genes that were in loci found to undergo Dex-inducible chromatin remodeling and Dex-dependent mRNA induction, in both ARID1a knockdown and control cells, included KLF9 , 55, DDISTEAP3 is one of the selectively affected genes identified in our analyses. The lack of chromatin pre-accessibility at sites in this gene may explain the subsequent impairment in its Dex-induced transcriptional regulation in the ARID1a knockdown cells. As an ARID1a-dependent glucocorticoid target, impaired Dex-dependent transcriptional regulation of STEAP3 has considerable functional significance for loss or mutation of ARID1a, as it has been speculated to play a role downstream of P53 to control cell cycle progression. Interestingly, in addition to STEAP3, only a small number of other genes were identified by RNA-Seq analysis as dysregulated by ARID1a knockdown or functional interference, yet according to functional pathway analysis, these were also enriched in the P53, DNA repair, and cell cycle regulatory pathways. Despite the large numbers of ‘so-called’ P53-related genes that were found to be differentially regulated in our study, HeLa cells lack a stable P53 protein . TherefoGlucocorticoids are known to mediate cell cycle arrest , 63, 64,As DNA damage repair (DDR) and cell cycle regulation are intrinsically linked, the prolonged cell cycle arrest observed in ARID1a knockdown cells may be related to the increased DNA damage we have characterized in the ARID1a knockdown cells. ARID1a has previously been shown to be important for DNA damage repair and checkpoint regulation, with ARID1a interacting with AT Rich sequences in DNA and being recruited to DNA strand breaks . No genoIncreased DNA damage was also observed in ARID1a-CTD-GFP cells compared to GFP control cells. However, in contrast to the ARID1a knockdown cells, the highest levels of γH2AX in the ARID1a-CTD-GFP overexpressing cells were detected in the absence of Dex. Consistent with this finding, there was also an effect of ARID1a-CTD-GFP overexpression on cell cycle that was most pronounced in the absence of Dex. Levels of γH2AX then reduced significantly with Dex treatment, indicating that other DNA repair proteins may play a role. Accordingly, the DNA repair proteins PARP9, PARP12 and PARP14 had increased basal expression in the ARID1a-CTD-GFP cells but not in the ARID1a knockdown cells, representing a major point of difference between the two experimental models.Our RNA-Seq data found some striking similarities between the effects of ARID1a knockdown and functional interference experiments, with significantly decreased expression in several DNA repair genes in response to Dex when ARID1a is knocked down or functionally interfered with. Additionally, the data revealed further indications of DNA damage with dysregulation of several interferon genes. Our proteomics data provided new insights into GR’s role in this mechanism, with the identification of a macromolecular complex comprising GR, ARID1a and several proteins involved in DNA repair. The P53 binding protein, P53BP1, detected in the ARID1a-dependent complex with GR, is well known for its multiple roles in the DNA damage response, including promoting checkpoint signaling and acting as a scaffold for recruitment of DNA damage response proteins to damaged chromatin –78. AlsoFurthermore, identification of PARP1, which is important for DNA repair, as well as the regulation of chromatin structure and specific gene expression , 80, celThe presence of the histone acetyltransferase KAT7/Myst2/HBO1 in the ARID1a-dependent GR protein complex revealed further mechanistic insight. In addition to KAT7’s established role in steroid-dependent transcription, demonstrated for the androgen receptor (AR) , the proTaken together, the GR-ARID1a complex we have identified is well placed and adequately prepared to act as a sensor of cellular stress and/or damage to maintain the balance between genome integrity and cell cycle progression. The components of the complex are also druggable targets; PARP inhibitors are already being used as a treatment for women with ovarian or fallopian tube cancers , 51, 86 Finally, in light of our findings, the importance of assessing DNA damage status and cell cycle arrest when deciding on treatment of different cancers becomes more pertinent. For example, in the case of the ARID1a knockdown cells, increased DNA damage was sufficient to initiate and prolong G1 arrest. However, many cell types including the HeLa cells used in our study, and the non-small cell lung cancers used in the study by Prekovic et al. , do not Four siRNAs targeting ARID1a and a non-targeting scrambled oligo control were obtained from Dharmacon . ARID1a-CTD was constructed from 2052 bp of the 3′ portion (4899–6855 bp) from pcDNA6-ARID1a .2.HeLa cells obtained from the European Collection of Cell Cultures  were maintained in Dulbecco’s Modified Eagle Medium (DMEM) with L-glutamine and glucose, 10% fetal calf serum, in a humidified incubator  at 37 °C and 5% COFor ARID1a knockdown, cells were transfected with ARID1a siRNA. The control comparison cells (siRNA control) were transfected with non-targeting oligonucleotides /180 μg chromatin, then immunoprecipitated with H300 GR antibody , RNA Polymerase II (phosphoserine-5) antibody  or rabbit non-immune serum . For sequencing, libraries were prepared from two replicates/condition. RT-qPCR was performed using SYBR reagents (Applied Biosystems) and primers described in  supplemented with DTT, protease, and phosphatase inhibitors, for co-immunoprecipitation with a GR antibody  or rabbit IgG control . Nuclear fractions were incubated with antibody overnight at 4 °C. Protein A magnetic beads were added for 3 h and then the beads were washed, and complexes eluted in 1× Laemmli buffer supplemented with 100 mM DTT. For LC–MS, size selection was performed so that only proteins of 80 kDa or larger were detected using LC–MS. Replicate co-immunoprecipitation experiments were performed for validation by western blot.Cells were washed and collected in ice-cold PBS with phosphatase inhibitors. Cell suspension was centrifuged for 5 min at 500 × Antibodies used for western blotting were: ARID1a/BAF250 A301-040A , ARID1a/BAF250 A301-041A , GR E20 , GR D6H2L , γH2AX , PARP1 46D11 , 53BP1 4937  and SFPQ ab38148 (Abcam), Anti Beta Tubulin T4026 (Sigma) or Anti Lamin A/C 2032 . Secondary antibodies used were, ECL anti-rabbit, NA934V , or ECL anti-mouse, NA931V .https://genome.ucsc.edu/). Enrichment of GR ChIP-Seq to 1% input control, were identified using findPeaks (HOMER v4.9.1) at relaxed settings (-F1 -L1 -P.1 -LP.01 -poisson .1 -style factor). Of these, only concordant replicate enrichments that passed an estimated irreproducible discovery rate threshold were kept for downstream analysis (IDR v2.0.3 – set to 0.01). Any concordant enrichments that overlapped were merged into a single region using mergePeaks (HOMER v4.9.1) and raw input ChIP-Seq tag counts were subtracted from corresponding GR tag counts using annotatePeaks.pl. Differential fold change between all conditions was assessed using getDiffExpression.pl (HOMER v4.9.1) and DESeq2 [p value <0.05 adjusted for multiple comparisons. All other comparisons were given the value 0. All enrichment regions were annotated with annotatePeaks.pl (HOMER v4.9.1) to closest transcriptional start site (TSS) (UCSC RefSeq GCD_000001405.25_GCCh37.p13 (2017-04-19)). Fold change (Log2) between treatments was visualized using heatmap.2 . RStudio: Integrated Development for R. RStudio, Inc., Boston, MA URL http://www.rstudio.com/), GraphPad Prism v6.07 for Windows  and Venny v2.1 (http://bioinfogp.cnb.csic.es/tools/venny/index.html).Quality of sequencing was assessed using FastQC  and sequences were trimmed to 36 bases. Single end reads were uniquely aligned to the human genome assembly (hg19) using Bowtie2 and PCR duplicates removed (SAMtools v1.3.1). Counts were normalized to 10 million tags to allow for cross-sample comparisons and visualized using the UCSC genome browser  values; summed fragments of each transcript with same gene ID. After Benjamini–Hochberg false discovery correction, genes with adjusted p values less than 0.05 were considered as differentially expressed genes . The supGraphpad Prism Version 6  was used to analyze RT-qPCR data by Two-way ANOVAs with a Dunnett’s or Bonferroni post hoc test. For each result, the statistical test used is stated. The mean and standard error of the mean (SEM) values were always calculated.Supplementary figures


Background: Gaps still exist in reducing new HIV infections among adolescent girls and young women (AGYW) aged 10–24 years. High Internet coverage and mobile phone penetration rates present opportunities for the use of mobile health  to support access to health services. We present results of an FHI 360 and Zimbabwe Health Interventions-implemented mHealth intervention for reproductive health (RH) and HIV testing service (HTS) referral among AGYW aged 10–19 years between October 2019 and September 2020.Methods: Adolescent girls and young women referred for RH and HTS under the Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe (DREAMS) program had automatic reminders sent to their phones to facilitate access to services through short message service (SMS) and also using a paper-based system. These data were captured in a web-based District Health Information System (DHIS) database, which captured the referral completion status of the AGYW. Data for AGYW referred for RH and HTS for the period October 2018 to September 2019 for the paper-based system and October 2018 to September 2020 for the mHealth were extracted from District Health Information System version 2 (DHIS2) database and analyzed using SPSS to generate descriptive statistics. The Chi-square test was used to assess differences in referral completion rates by age-group; marital status, district, and type of service, as well as differences between mHealth and paper-based referral completion rates within each of the groups for the variables above.Results: A total of 8,800 AGYW referred for RH and HTS, where 4,355 and 4,445 were referred through the mHealth and paper-based systems, respectively. About 95.2%  and 87.8%  referred through mHealth and the paper-based system, respectively completed referrals. The median time for referral completion was 1 day (Range = 0–9 days) for mHealth and 11 days (Range = 0–28 days) for the paper-based system. AGYW referred through mHealth were 17.995 timesp <0.001).more likely to complete the referral system than those referred through the paper-based system (OR =17.995; Conclusion: Compared to the paper-based referral system the mHealth solution resulted in a higher, service referral completion rates and shorter turnaround time. We recommend expansion of the mHealth solution to all DREAMS supported districts to increase uptake of RH and HTS among AGYW aged 10–19 years. Despite reductions in HIV infections globally, gaps still exist in addressing the HIV pandemic among adolescent girls and young women (AGYW) . Thus, iFamily Health International (FHI360) and Zimbabwe Health Interventions (ZHI) with funding from the United States Agency for International Development (USAID) have been implementing the Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe (DREAMS) program in Zimbabwe since 2015. The program aims to reduce HIV incidence among 10–19 year-old AGYW. Under the Zimbabwe DREAMS project, referrals for services were done using a paper-based system where out of school club facilitators (OOSCFs) generated referral slips which the AGYW handed over to the service providers upon presenting themselves for services. The referral slips were completed in duplicate where AGYW were given one of the slips which the service providers signed as confirmation for referral completion and services rendered on presentation. Tracking referral completions was done through the collection and reconciliation of the slips between the referral organization and the service provider. This referral system had the following challenges: poor communication between service providers, loss of referral slips, lack of feedback from the service providers, and long turnaround time for completion of the referral cycle to access services . Under tThis analysis used aggregate and routine program data, extracted from the DHIS2 project database. Routine program data of AGYW enrolled in the DREAMS program and referred for RH and HIV prevention services for the period October 2018–September 2020 were extracted by the data capture clerk from DHIS2. We extracted aggregate data on the following data elements: age, marital status, district, referred health facility, date of referral, and referral outcome.Zimbabwe has been implementing the DREAMS program since 2015. The program is aimed at reducing HIV incidence among AGYW aged 10–24 years old. In Zimbabwe, the program is being implemented in six districts, namely Bulawayo, Chipinge, Gweru, Makoni, Mazowe, and Mutare. The DREAMS core package combines evidence-based approaches that go beyond health, but addresses the structural drivers that directly and indirectly increase girls' risk for contracting HIV. These include poverty, gender inequality, sexual violence, and lack of education. Thus, the program offers in-school and community-based service delivery to build social assets for the AGYW. The program also promotes changing harmful community norms that put AGYW at risk of gender-based violence (GBV). Through layering of services, the DREAMS program delivers clinical and post-GBV services. The clinical services that are delivered through the DREAMS program include HIV testing, Sexually Transmitted Infections (STI) screening, Pre-exposure prophylaxis (PrEP), Post-Exposure prophylaxis (PEP), and reproductive health.The OOSCFs, who are community cadres employed under the DREAMS program, identified AGYW aged between 10 and 19 years who are at risk of contracting HIV. Using the enrolment standard operating procedures (SOPs), written consent was sought from AGYW prior to the administration of the DREAMS eligibility screening tool. The DREAMS eligibility screening tool captures demographic details, orphanhood status, indulgence in sex, experience of any GBV, alcohol misuse, and if the AGYW had experienced any of this, then they are eligible for enrollment into the program and hence referred for services. If the AGYW are eligible, a unique identification code is generated, which will be used for enrolment into the program. The DREAMS program enrolment tool was administered, which captured the demographic and social details, exposure to GBV and HIV risk assessment. Provision or referral for appropriate services was conducted based on AGYW vulnerabilities. Data on screening and enrolment of the beneficiaries were captured in the program database (DHIS2) by Monitoring and Evaluation (M&E) staff.Adolescent girls and young women identified from the community who were screened and enrolled into the DREAMS program and deemed at risk of contracting HIV were either offered services onsite or referred to another implementing partner for services. A referral slip was generated and given to the AGYW, with the duplicate copy remained with the OOSCF for tracking purposes. Upon accessing services at the referral site, the referral slips were collected by a health worker who offered HTS or RH services. The issuing partner will then follow up to determine completion of referral with the service providers. Data on referral slips were later captured in DHIS2 where reminders for those who have not accessed services were generated, and notifications sent through SMS.Since October 2019, referrals were made through the mHealth platform where slips generated manually were immediately captured into DHIS2 upon being issued to the AGYW. If services were not accessed, continuous and automated SMS reminders were sent until the AGYW access the service and an update is made in DHIS2. Referrals are made to both the public and private service providers. Among the public service providers are the Ministry of Health and Childcare (MOHCC) and Zimbabwe National Family Planning Council (ZNFPC) run facilities. Private sector service providers are mainly non-governmental organizations who conduct outreach activities.All AGYW who were enrolled and referred for HTS and RH services in the six districts using the paper-based referral system from October 1, 2018 to September 30, 2019, and those referred through mHealth from October 1, 2019 to September 30, 2020 were included in the analysis. Data were extracted from the project's DHIS2 system.Data were extracted from the DHIS2 database, exported to Microsoft Excel spreadsheet, and analyzed using SPSS  for generating descriptive statistics. The Chi-square-test was used to test if there were differences in the completion of referrals within the following variable groups: age-group, marital status, district, service, organization referred to, and location of service within both the mHealth and the paper-based referral systems. We also used the Chi-square to assess for differences in the referral completion rates between mHealth and paper-based referral systems within each sub-group of the variables listed above. Logistics regression was used to estimate the factors associated with service completion. Cox Proportional Hazard analysis was used to test the difference in time to completion of service referral between the two systems .Ethics approval was obtained from the Medical Research Council of Zimbabwe (MRCZ/E/254). Routine monitoring and evaluation program data were analyzed. Personal identification information of beneficiaries was excluded from the analysis.A total of 8,800 AGYW aged 10–19 years were referred for HTS and RH, where 4,355 were referred through mHealth and 4,445 through the paper-based system. Of these, 1,821 (20.7%) were from Bulawayo district while 10.9%  were from Mazowe district . The majp <0.001).From Less than half, 42.8%  of the AGYW were referred to the MOHCC for HTS and RH while the rest were referred to private organizations.p <0.001; About 95.2%  of AGYW was referred through mHealth, which was significantly higher than the 87.8%  of the AGYW referred through the paper-based system (p < 0.001). Though referral completion was higher in the mHealth system among the divorced and those in Bulawayo district, the difference was not statistically significant .Within all age-groups, type of service, and some districts, referral completion was higher within the mHealth referral system compared to the paper-based system  of the AGYW referred through the mHealth platform completed the service referral on the same day, compared to 0.8%  for the paper-based system . This riX2 = 5868.786, p < 0.001). Also, the Cox regression analysis showed a significant difference in the time to completion of the referral network between mHealth and paper-based systems, Exp (B) = 12.157, 95% CI .The median time for referral completion was 1 day, (range = 0–9 days) for mHealth while it was 11 days (range = 0–28 days) for paper-based system. There was a significant difference in the time to completion service referral network for mHealth and the paper-based systems ]. AGYW aged 10–14 years old were 75.2% less likely to complete service referral than those aged 15–19 years . Single AGYW were also less likely to complete SRN than the married and the divorced [OR = 0.137; 95% CI ; Results from this study showed high referral completion rates among AGYW referred using mHealth than those referred using a paper-based system. mHealth services that integrate SMS reminders help to remind AGYW to access services unlike referral slips which can easily be misplaced. The high mobile phone penetration rate among AGYW also assured that enrolled clients will receive SMS reminders. While the use of mHealth was successful within DREAMS in Zimbabwe, this contrasts findings from a study conducted in Uganda, where the use of mHealth had little effect in improving access and completion of services referred due to limited data bundles and support systems for online follow-up and reporting . In ZimbThere were high HTS and RH service referral completion rates regardless of the marital status of the AGYW, which can be attributed to the integration of HTS and RH for AGYW as reported from other Sub-Saharan countries . There wMost of the AGYW referred using the mHealth innovation accessed HTS and RH services within 5 days, compared to less than a quarter among those referred using the paper-based system. Those enrolled into the mHealth platform received constant reminders, which could have prompted service uptake. Moreover, availability of service directories, which are booklets with names and contact details of service providers, and the use of mHealth in tracking and following clients equipped the AGYW with the tools to access services. The study findings are consistent with the findings for other health interventions from South Africa, where mHealth was preferred among AGYW because it is user-friendly, appeals to youth, and has led to short turnaround times for accessing family planning and HIV self-test services in South Africa , 20.This study has limitations. Completion of service referrals is based on data on referrals captured in DHIS, and some referral slips could have been lost before capture. The analysis was limited to AGYW enrolled into the DREAMS project covering only six districts in a country with more than 57 districts, which makes it difficult to generalize findings beyond study districts. In addition, the analysis used routinely collected program data thereby limiting analysis to variables captured in the database.The study highlights the utility of mHealth in increasing the uptake of HTS and RH services among AGYW. The use of mHealth was effective in reducing the turnaround time from the time of referral to completion among AGYW referred for HTS and RH services and should be expanded to other districts and also to other health services targeting especially youth.The original contributions generated for in the study are included in the article/The studies involving human participants were reviewed and approved by Medical Research Council of Zimbabwe. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.DD, BN, and FM development of the manuscript. TT and GN review of manuscript. ET manuscript development and review. MM data analysis and review of manuscript. TN manuscript development. MP development of manuscript and review. FHM development of manuscript, data analysis, and review of manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background and Objectives: Genomic information is increasingly relevant for disease prevention and risk management at the individual and population levels. Screening healthy adults for Tier 1 conditions of hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia using a population-based approach can help identify the 1–2% of the US population at increased risk of developing diseases associated with these conditions and tailor prevention strategies. Our objective is to report findings from an implementation science study that evaluates multi-level facilitators and barriers to implementation of the In Our DNA SC population-wide genomic screening initiative. Methods: We established an IMPACTeam (IMPlementAtion sCience for In Our DNA SC Team) to evaluate the pilot phase using principles of implementation science. We used a parallel convergent mixed methods approach to assess the Reach, Implementation, and Effectiveness outcomes from the RE-AIM implementation science framework during the pilot phase of In Our DNA SC. Quantitative assessment included the examination of frequencies and response rates across demographic categories using chi-square tests. Qualitative data were audio-recorded and transcribed, with codes developed by the study team based on the semi-structured interview guide. Results: The pilot phase  included recruitment from ten clinics throughout South Carolina. Reach indicators included enrollment rate and representativeness. A total of 23,269 potential participants were contacted via Epic’s MyChart patient portal with 1976 (8.49%) enrolled. Black individuals were the least likely to view the program invitation (28.9%) and take study-related action. As a result, there were significantly higher enrollment rates among White (10.5%) participants than Asian (8.71%) and Black (3.46%) individuals (p < 0.0001). Common concerns limiting reach and participation included privacy and security of results and the impact participation would have on health or life insurance. Facilitators included family or personal history of a Tier 1 condition, prior involvement in genetic testing, self-interest, and altruism. Assessment of implementation  included sample collection rate  and proportion of samples needing recollection . There were no significant differences in sample collection based on demographic characteristics. Implementation facilitators included efficient collection processes and enthusiastic clinical staff. Finally, we assessed the effectiveness of the program, finding low dropout rates , the identification of eight individuals with Tier 1 conditions (0.72% positive), and high rates of follow-up genetic counseling (87.5% completion). Conclusion: Overall, Asian and Black individuals were less engaged, with few taking any study-related actions. Strategies to identify barriers and promoters for the engagement of diverse populations are needed to support participation. Once enrolled, individuals had high rates of completing the study and follow-up engagement with genetic counselors. Findings from the pilot phase of In Our DNA SC offer opportunities for improvement as we expand the program and can provide guidance to organizations seeking to begin efforts to integrate population-wide genomic screening. Genetic information is increasingly relevant for disease prevention and risk management at the individual and population levels ,2. RapidDespite the accessibility of genetic information and growth in population-based screening, challenges exist to scaling up these approaches, including engaging large multidisciplinary teams of researchers and clinicians, ensuring public understanding of genetic information, equitable access and participation of diverse populations in genetic screening, and sustainability of population-based genetic screening programs ,7. SynerIn Our DNA SC, is designed to provide genetic testing for up to 100,000 participants for CDC Tier 1 conditions. In Our DNA SC uses a multi-phased implementation approach, including a pilot phase of program implementation at 10 clinical sites, institutional expansion across clinical sites affiliated with MUSC, and community expansion to people not previously affiliated with MUSC. As part of the program, we established an IMPACTeam (IMPlementAtion sCience for In Our DNA SC Team) to create a strategy evaluation of the program using principles of implementation science  I didn’t know a lot of my grandparents […] some of the things that I go through may be because it’s just a genetic thing” . Prior involvement in clinical genetic testing or personal history of cancer was also a motivating factor for participation. For example, one participant indicated, “I am a cancer survivor, so those things kind of were the benchmarks for me” . Finally, participants cited joining the study to support the greater good and future research findings. For example, one stated, “The more they learn, the more accurate they can get. The more you get to know”  and recognition that this approach is the future of medicine, “It seemed to me like that’s kind of the future of where this thing is going, where you can actually use someone’s DNA to maybe give them a chance at knowing what their future could be” .In Our DNA SC over the pilot period. We report on individual level implementation constructs.Implementation of the population screening program was assessed at both the setting level and the individual level. A detailed assessment of setting-level implementation is underway to consider the acceptability and satisfaction of the program among clinical staff who were responsible for sample collection, fidelity to the protocols, and adaptations made to A total of 1104 samples (55.9%) have been collected so far from those enrolled in the pilot phase of the program. The sample collection rate overall for those invited was 4.74%. Those who provided samples were predominantly female (72.83%) and White (86.96%) with a median age of 50.3 years . A totalQualitative findings provide detail about potential barriers and facilitators to sample collection. While there were not significant differences in collection by demographic groups, over half of those enrolled ultimately had their sample collected (58.5%). Barriers to sample collection primarily included modifications made to the appointment at which the sample was going to be collected and the distance required to travel to provide the sample. For example, research coordinator tracking logs included questions about how to provide a sample after a missed appointment or failure to collect, “My provider had to cancel my scheduled appointment tomorrow morning […] is there a way to reschedule when I provide the sample for the research study?” Distance was also a common concern, “I would have to drive to Charleston depending on what day it was […] it just depends on whether it was worth it for me” .Implementation facilitators for in-clinic collection included efficient collection processes and enthusiastic staff. For example, “They did all my normal office visit stuff […] walked into the room and it’s like boom boom boom you know very quick getting all the free stuff done before the doctor came in […] while you are waiting for her go ahead and spit in the tube and here’s a pamphlet if you need more information” .In Our DNA SC was assessed through assessing the proportion of individuals who completed the program  compared to those who dropped out . In total, 8 of those with samples collected (0.72%) were found to be positive for a Tier 1 condition and 7 (87.5%) followed-up with a genetic counselor. One of the participants who declined genetic counseling was already aware of their positive result and the other was unable to be reached. All individuals were able to schedule their genetic counseling appointment within one week of results disclosure.The effectiveness of Our qualitative assessment of participant experience and effectiveness of aspects of the program included a need to simplify and shorten the initial consent form to help ensure people understand what they are committing to as part of the program. Participants recommended the study team modify the consent form to ensure it is “more digestible” and “not as intimidating”  by offering “synopsis of what it was and answer questions that I may have” . Opportunities to promote better understanding of the program included sharing what will be sent to the participants after they enroll  and aligning the next steps with what it means for participants, “So I did all of this and it is helpful research to the state of South Carolina. But what does this mean for me? How do I navigate it and am I going to do anything with it? I mean, that’s a personal choice, but how do I get that information?” .In Our DNA SC include population-level screening for actionable Tier 1 genetic conditions and fostering ongoing translational genomics research. Identifying an individual’s risk can allow for proactive screening for treatable conditions, which can enable precision-based clinical engagement of subpopulations who could benefit most. During the pilot phase of the program, we assessed program reach, implementation, and effectiveness.The goals of We found low overall engagement, or reach, among racial minority individuals throughout the pilot phase of the program. Although Black individuals comprised approximately 30% of those initially invited, they were significantly less likely to open the initial MyChart recruitment message and less likely to take further actions of declining or enrolling in the study. Lower participation of racial and ethnic minority populations has been well-documented in the literature, with most genome-wide association study participants (81%) being of European ancestry ,11. HoweIn Our DNA SC expands, we have incorporated efforts to increase the reach and representativeness of our population. These include the development of a community advisory board with representation from organization across South Carolina, the adoption of a diversity, equity, and inclusion statement for the program, the expansion of recruitment strategies to include community events and at home collection, as well as high-touch outreach through text message follow-ups and phone calls to individuals who express interest. Other opportunities include community capacity building or equipping already established, trusted groups, such as community health workers, to understand and participate as partners in genomic research [Alternative models to facilitate recruitment and retention of diverse participants into population wide genomic screening are needed to avoid perpetuating existing disparities in genetic research and access to genetic services ,21. Notaresearch ,35,36.Our focus on recruiting from and then collecting samples through clinical sites may have also contributed to the observed lower view rate of invitations among men 37.0%) compared to women (42.7%) and overall lower enrollment of males (7.45%) compared to females (8.91%). In addition to sites being skewed toward female populations , 5 sites were family medicine/primary care practices. Female gender is associated with portal-based communication .0% compa,39. ThusIn Our DNA SC. We have also implemented other sample collection opportunities, including through drop-off at events facilitated by research staff and through at-home mail kits.The initial rate of sample collection (55.9%) is on par with collection rates among other population genomic screening programs . NotablyIn Our DNA SC program provided information about how well we achieved the primary public health goal of identifying individuals with Tier 1 conditions of hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia. Among those who provided a sample during the pilot phase of the program, we found 8 individuals (0.72%) who were positive for Tier 1 conditions. This screen positivity rate aligns with screening positivity rate for other programs screening for Tier 1 conditions of approximately 1-2% of the population [Finally, our assessment of the effectiveness of the pulation . Of thosIn Our DNA SC workflow) and individual level  is currently outside of the scope of our early findings but is planned to be included as part of the ongoing evaluation of the program.Our approach is not without limitations. As part of the pilot of the population screening program, we focused only on recruitment in clinical settings, limiting our overall reach to participants. While this was a necessary step to support the technical aspects of implementation, other forms of recruitment and outreach will be critical to ensure representativeness of the South Carolina population. Additionally, the assessment of our program primarily focuses on individual-level barriers and facilitators to reach, implementation, and effectiveness. Factors beyond the individual level were described as part of qualitative interviews  and noted during sample collection ; however, we did not focus on these as part of the present evaluation. Further, our assessment of the program did not explicitly include “adoption” and “maintenance” of the RE-AIM framework. Adoption was not included in this evaluation, given that the program was an institutional priority, all clinical sites were required to adopt the program. The assessment of maintenance at the clinic or site level (e.g., continued use of In Our DNA SC and ensure the sustainability of population-level genetic testing. Ultimately, this approach supports MUSC’s efforts to use learning health system strategies where implementation research questions are evaluated at the point of care. Such approaches will eventually allow us to realize the promise of population genomics screening and maximize the utility of precision-approaches for individuals in our community and multidisciplinary teams of researchers and providers. The model-based components of our evaluation program can help support the generalization of lessons learned from In Our DNA SC and the identification of best practices to streamline the expansion of similar population genomics programs at other institutions.Population screening offers a unique opportunity to integrate precision-based approaches across clinical and public health settings. As access to population-based screening grows, it is critical to identify outcomes and develop strategies to rapidly assess progress toward these goals. The use of implementation science can help better understand how to support the success of


Puppy raisers volunteer their time to take care of, and train, selected puppies until they are mature enough to undertake advanced training to become assistance dogs. Emerging evidence suggests a central role for puppy raisers in bringing out the best in assistant dog puppies. However, most puppy raisers are not professional dog trainers and, to optimise outcomes, they may require various kinds of support from the host organisation that places the puppy in their home, as well as from their personal networks and local communities. From a behaviour change perspective, coordinated efforts at different levels would be expected to better enable puppy raisers to improve training outcomes for the puppies. The aim of this paper is to discuss the potential application of a well-established behaviour change framework to the practice of puppy raising. After discussing relevant findings, we suggest a holistic approach to supporting puppy raisers and propose a behaviour model to help volunteers improve their puppy raising practice.Puppy raising (PR) programs recruit volunteer community members (raisers) to raise assistance dog (AD) candidates from puppyhood until the dogs are ready for advanced training. Once qualified, ADs assist human handlers with a disability to live more independently. Unfortunately, about 50% of all puppies do not meet the behavioural standards required for further training after completing a PR program. This increases costs and lengthens the time taken for a handler to obtain an AD. Research has identified several factors that influence raisers’ experiences. It has also shown that raisers’ socialisation and training practices affect perceived puppy behaviour. Drawing on the argument that puppy raiser practices are central to improving overall puppy raising program outcomes, this paper interprets recent findings within the framework provided by the behaviour change wheel—an established behaviour change framework—to suggest a coordinated approach to supporting puppy raisers. The recommendations will allow future research to employ more objective measures and more rigorous experimental designs as the field attempts to corroborate existing findings and develop evidence-based models of practice. High demand for assistance dogs (ADs) has emphasised the importance of appropriate selection and training of AD candidates, to increase their chance of meeting high performance and behaviour standards. Many potential ADs are selected as puppies, following which they typically live with volunteer raisers during a puppy raising (PR) program that may last for up to a year. During such programs the puppy learns life skills and basic education, enabling them to proceed to advanced training if suitable ,2. EfforPuppy behaviour is influenced by genetics and environmental factors during all stages of development: prenatal, neonatal, transition, socialisation, juvenile, and pubertal periods . ExperieThese objectives are consistent with a behaviour change approach in which contextual factors such as organisational support can encourage desirable behaviours  and discourage undesirable behaviours . The aim of this paper is to discuss the potential application of this behaviour change framework to PR practices and research in this field. This paper firstly summarises findings from three recent studies. These studies were concerned with raiser practices and their influences on puppies’ behaviours and included a cross-sectional qualitative study , an onliBecause puppy behaviour is a predominant outcome variable in current AD research, two studies, a cross-sectional qualitative study  and an oThe initial study  revealedA limitation of the survey study is that it was not possible to fully characterise what the respondents meant by the words socialisation or training–socialisation, for example, which can be used to refer to age-appropriate exposure to various stimuli under controlled conditions or to uncontrolled overexposure of puppies to new and frightening stimuli which may inadvertently cause anxiety and stress . HoweverThe only significant organisational support predictor in the online survey study  was the Although access to puppy sitters influenced puppies’ perceived excitability, it is instructive that raisers with higher ratings on their socialisation and training practices rated not only their puppy’s excitability more favourably, but also their trainability, general anxiety, adaptability, and distractibility. It was therefore concluded that raisers’ socialisation and training practices may be among the best predictors of puppies’ behaviour and that, consequently, understanding and promoting factors that contribute to puppy raisers’ engagement in optimal training and socialisation practices is an important area for future research and practice in this field. To understand the nature of, and factors that affect, raisers’ practices, a longitudinal qualitative study  was condForemost amongst the identified predictors of raisers’ practices was the provision of support from the AD organisation that supplied the puppies, which provided both informational and emotional benefits to raisers. Support from other sources was also identified as important. Although the survey findings  showed tAn additional finding of note from the longitudinal study was an interaction between puppy characteristics and raiser practices. There were clear benefits associated with having an easy-going puppy and several negative impacts of raising a high-energy puppy. Raisers in the survey study  associatThe influences of contextual and puppy factors on raiser practices can be interpreted using frameworks developed in family-centred research in human development. In a child developmental study, Kelly and Coughlan  intervieThe parents in Kelly and Coughlan’s study  played aWe could not find any studies in the AD training literature that examine those programs from a raiser- or owner-centred approach. Indeed, a focus on the experiences of raisers and on when and how they apply different strategies is absent from the available literature. This is important because most dog training programs are aimed at providing information directly to PR raisers or companion dog owners . This reflects an assumption that efforts to better inform raisers’ practices will benefit their puppies’ behaviour. This assumption may not be warranted, however, because provision of information may not be sufficient to engender behaviour change. Instead, the relationship between puppy and raiser may be bidirectional, whereby puppy behaviour may benefit from and also affect the raiser’s PR practices. Such ‘child effects’ are well established in human family research ,21,22. The transactional family dynamics theory  proposesBehavioural intervention refers to a process by which a set of actions are performed to promote desirable behaviour, or to reduce the likelihood of a specific undesirable behaviour, either by discouraging it or promoting engagement in an incompatible behaviour . AlthougThe behaviour change wheel (BCW) was synthesised from 19 behaviour theories, models, and frameworks  see Fig. At its Definitions of the nine intervention functions are presented in A comprehensive behaviour support program may aim to achieve all nine functions depending on the circumstances of the specific raiser-puppy team, but each support plan should be individualised to suit the raiser’s circumstances and their puppy’s training requirements. For instance, while focusing on providing training to puppy raisers , program providers may also restrict access to local areas with known aggressive dogs . The PR organisation may also collaborate with each raisers’ employer to accommodate their puppy at the workplace  and offer extra assistance from competent dog sitters who could provide supplementary or special socialisation and training sessions for puppies when raisers are not available . For some raisers, restrictions concerning contact with aggressive dogs may not be relevant in their local settings. Instead, they may need restrictions around approaching small animals to avoid developing undesirable behaviours such as pulling on the leash, barking, and/or chasing. As raisers and program providers agree on specific goals for each puppy , they may consider a behavioural intervention program to ensure raisers can achieve these goals. The outermost layer of the BCW model lists seven policy categories—the highest level of influence where peak bodies and governing authorities regulate their member organisations to promote or reduce certain behaviours at the individual level. Since the evidence discussed in this paper is limited to how organisations may help raisers to engage in optimal practices, the seven policy categories are beyond the scope of this commentary. Future research is needed to suggest the relevance of industry-level recommendations.As discussed above, the COM-B model and the nine intervention functions of the BCW framework provide a general approach for promoting an individual’s engagement in target behaviours, which can easily be applied to the PR context. This section extends this framework, proposing a raiser-centred behavioural support framework, called the triple triangle (3T) model see , which wAs the name suggests, the model encompasses three individual triangles representing the capability, opportunity, and motivation conditions in the COM-B system. The three triangles form a larger overarching triangle representing the holistic approach to improving raisers’ practices. The edges of the three triangles refer to the program functions to promote the COM-B condition that the respective triangle represents. For instance, to provide suitable opportunities for raisers to engage in a recommended behaviour, program providers may consider strategies relevant to environmental restructuring, enablement, and/or restriction functions. All nine functions are represented by the three triangles but, in the 3T model, each component triangle also targets one of three raiser practices that we believe are fundamental to effective puppy raising: provision of frequent socialisation and consistent training for the puppy, and effective learning  on the part of the raiser. Although the importance of promoting puppy socialisation and training is self-evident, providing raisers with ongoing training and professional development is equally necessary to ensure they can conduct effective puppy-focused practices . Successfully performing those tasks requires appropriate education, skills training, and extensive skills modelling—the three edges of the capability triangle. This can sometimes be accomplished quite easily. Our longitudinal qualitative study , for exaThe opportunity triangle is concerned with raisers’ puppy socialisation practices. Providing puppies with more socialisation appears to rely mostly on raisers having opportunities to perform relevant tasks. PR programs may consider strategies focusing on environmental restructuring, enablement, and/or restrictions to increase socialisation opportunities—the three edges of the opportunity triangle. As revealed in the longitudinal qualitative study , raisersThe last triangle is motivation, which, in the PR context, primarily refers to raisers’ engagement in consistent puppy training. Assuming that raisers have the necessary skills and competency and opportunities to facilitate frequent socialisation and training sessions with their puppy, the remaining condition is that raisers have the motivation to perform consistent and correct dog training techniques during these activities. This motivation can be enhanced if raisers perceive sufficient incentivisation, persuasion, or coercion associated with the tasks at hand. In Chur-Hansen et al.’s  study, rAlthough the coercion function aims primarily to prevent undesirable practices, program providers should be aware of external factors that may prevent raisers from performing instructed tasks. For example, raisers in our study  reportedIn short, the 3T model presents three triangles representing the three COM-B conditions to promote behaviour change, namely, capability, opportunity, and motivation. In general, puppy raising programs should ‘motivate’ raisers to carry out training that they have already been taught how to conduct (capability) and provide the right conditions (opportunity) for these behaviours to occur. Each condition targets a specific practice, namely, effective learning on the part of the puppy raiser, and frequent socialisation and consistent training for the puppy. The three edges of each triangle represent the program functions required to enhance each condition that the triangle represents. The larger triangle refers to the interconnectedness of different PR practices and their underlying behavioural principles. Central to the model are puppy characteristics, with this emphasising the ultimate purpose of the PR program—to produce an adult dog with desirable behaviour and temperament, who is healthy and who can perform the tasks relevant to their future assistance role.PR programs typically involve several stakeholders: raisers and their household members, friends and colleagues; members of the public; mentors and supporters; and staff from the host organisation. The practical implications of this paper correspond to those stakeholders, with clear recommendations emerging from the findings.Prospective raisers should seek clarification of what is required of them and consider the skills and resources they have, and available organisational support, when deciding whether to become a puppy raiser. Interested volunteers may initially perceive many potential benefits. However, raising a successful puppy requires a long-term commitment and efforts that may be beyond what was originally anticipated. It may be instructive for potential raisers to gain experience through undertaking short-term fostering. Once they have joined a PR program, they should be encouraged to actively seek advice and assistance from staff and those with experience at their organisation. Ongoing professional development (learning) equips raisers with appropriate knowledge and skills. It subsequently helps puppies when raisers learn to arrange convenient and enjoyable opportunities for socialisation and when they persevere and are consistent with organisational requirements regarding training practices.All household members should join prospective raisers in the decision-making process to raise a puppy. They should be aware of their influence on both the raiser and the puppy. During the PR program, household members are likely to be in close contact with, and involved in the training of, the puppy. Simply understanding and being respectful of the training process is essential. With skills, knowledge, and active involvement in the program, household members may share raising responsibilities and help raisers fulfil their commitment. Although friends and colleagues may be less involved than household members, it is important that they show understanding for the raiser’s volunteering commitment and perhaps assist when raisers bring a puppy to social events or workplaces. Friends, colleagues, and the raiser should establish boundaries to minimise any negative impacts on themselves, the puppy, and their social and workplace dynamics.Members of the public may influence PR in many ways, ranging from enjoying the presence of AD puppies and appreciating raisers’ volunteer commitment through to expressing inappropriate personal opinions about contested training practices. Although social interactions may often be welcomed by raisers and helpful to puppies’ socialisation, unsolicited encounters may over-excite friendly puppies, frighten timid ones, and take up raiser time when they are busy or in a hurry. Therefore, it is recommended that members of the public always ask permission from raisers prior to any engagement. Furthermore, although public concerns and constructive feedback are essential to the sustainability of working dog industries , membersStaff responsible for raiser training and support should consider several aspects of each raiser’s life, as various factors may counter both the raiser’s and the organisation’s efforts. Administratively, program providers should assess risks and hazards associated with raisers’ fitness, living environments, and local and work settings. For instance, there are many potential risks to raisers, members of the public, and puppies, if physically unsuitable raisers are required to handle physically strong and highly distractible or excitable puppies in highly stimulating settings. Given the support available within raisers’ personal networks , staff should involve and formally acknowledge the contribution of those individuals. In terms of program design, PR providers should focus their support on ensuring raisers’ awareness of the tasks involved during induction, raisers’ engagement in ongoing effective learning, creating convenient opportunities for raisers to offer their puppy sufficient socialisation experiences, and adhering to program-specific instructions.This paper devised a behavioural intervention PR model, the 3T model, targeting three practices, with nine specific program functions to guide program providers when developing strategies for individual raisers and organisation wide. This theory-informed model provides organisations with a framework to explain the interconnectedness of PR factors and suggests program outcome criteria for evaluation of their support programs. At this early stage, the 3T model requires collaboration between program providers and researchers interested in behaviour change to evaluate existing support strategies or to develop and implement new strategies consistent with the model. We appreciate that this is a massive and costly undertaking. Therefore, peak bodies, such as the International Guide Dog Federation  and AssiThough we are very confident in directing research attention towards understanding how raiser-related factors determine outcomes for AD puppies, the specifics of the 3T model were developed based on only three recent studies. Since each AD organisation has its own policies and practices, generalisation of the model remains unclear. For instance, some organisations may lack access to stable raiser homes, resulting in puppies having to shift from one raiser to another due to reasons such as raiser unavailability. Puppies sourced from shelters  or privaCapability triangle) may benefit from a range of raiser-centred support strategies, including skill training , skill modelling  and education . In terms of the operationalisation of outcome measures, to date, apart from the self-reported Raiser Practice Questionnaire [Opportunity triangle) or consistency of training  may be less difficult to implement, as may existing measures of puppy behaviours. There are many standardised measures of puppy behaviour available  so reseIn short, further understanding of raiser factors contributing to the outcomes of PR programs is imperative for the AD industry. Developing this understanding requires empirical designs and objective measures of various PR factors, which must be supported by a strong theoretical framework, such as that provided by the proposed 3T model. Over time this will inform program providers of more effective operating models, ensuring the efficiency of their investments, positive program experiences for raisers, higher puppy success rates, and more ADs to meet the demands of waiting handlers.This paper adopted a systems-level perspective to further understanding of both human and puppy outcomes of assistance dog puppy raising programs. Previous studies reported various factors that influence raiser practices and also demonstrated direct relationships between raiser practices and their ratings of puppy behaviour. Raisers are volunteers who make a long-term commitment to a raising program. Their effectiveness and retention determine the success of the industry, making their subjective program experiences of great interest to AD providers. Integrating a puppy into a raiser’s life and implementing program-specific instructions designed to ensure optimal outcomes may create tension in daily living. Contextual factors such as different sources and types of support influence raiser practices. However, the extent to which raisers benefit from these factors depends on their help-seeking behaviour and the compatibility of available support with their preferred learning modalities. Many factors related to raisers’ daily lives determine their PR practices—which consequently, at least partially, determine whether the puppies they raise are successful. Successful PR may be promoted via a raiser-centred behavioural support approach, but this is dependent on the development of underlying theoretical models and an evidence base. Undertaking this work is imperative because improving raiser practices will benefit puppy behavioural outcomes and, eventually, outcomes for handlers with disabilities who benefit from the important work of assistance dogs.