Taking Care of Us© (TCU). The TCU© intervention is grounded in the theory of dyadic illness management and was developed to promote collaborative illness management and better physical and mental health of adults with heart failure and their partners.There are more than 1 million hospital admissions and 3 million emergency visits for heart failure in the USA annually. Although spouse/partners make substantial contributions to the management of heart failure and experience poor health and high levels of care strain, they are rarely the focus of heart failure interventions. This protocol describes a pilot randomized controlled trial that tests the feasibility, acceptability, and preliminary change in outcomes of a seven-session couple-based intervention called A two-arm randomized controlled trial will be conducted. Eligible adults with heart failure and their co-residing spouse/partner will be recruited from a clinical site in the USA and community/social media outreach and randomized to either the TCU© intervention or to a control condition (SUPPORT©) that offers education around heart failure management. The target sample is 60 couples (30 per arm). TCU© couples will receive seven sessions over 2 months via Zoom; SUPPORT© couples will receive three sessions over 2 months via Zoom. All participants will complete self-report measures at baseline (T1), post-treatment (T2), and 3 months post-treatment (T3). Acceptability and feasibility of the intervention will be examined using both closed-ended and open-ended questions as well as enrollment, retention, completion, and satisfaction metrics. Preliminary exploration of change in outcomes of TCU© on dyadic health, dyadic appraisal, and collaborative management will also be conducted.Theoretically driven, evidence-based dyadic interventions are needed to optimize the health of both members of the couple living with heart failure. Results from this study will provide important information about recruitment and retention and benefits and drawbacks of the TCU© program to directly inform any needed refinements of the program and decision to move to a main trial.ClinicalTrials.gov (NCT04737759) registered on 27 January 2021. Heart failure is the fastest growing cardiovascular disorder in the USA and the most common reason for both hospitalization and rehospitalization among older adults , 2. AdulHeart failure is a clinical diagnosis based on a history of symptoms and physical examination . Adults Most non-pharmacologic heart failure interventions involve patient education and behavioral counseling, with limited success , 23. PotTaking Care of Us© (TCU) program, the theory of dyadic illness management [collaborate, communicate and feel confident around management of the illness. Greater shared appraisal and engagement in dyadic management behaviors lead to better physical and mental health of both members of the couple. Thus, TCU© focuses on the concepts of dyadic symptom appraisal, dyadic management behaviors and dyadic health.Across illness contexts, there is strong evidence of the interdependent nature of the experience within couples and the important roles of support and a sense of “we-ness” –36. Builnagement , focusesShared dyadic appraisal is vital to the effective management of heart failure within couples . StudiesTaking Care of Us© . We will stratify by gender to maximize equal distribution between the two conditions. Both programs span 2 months in length and are delivered by trained interventionists to the couple via Zoom. All participants will be assessed at baseline (T1), post-treatment (T2), and 3 months post-treatment (T3) using separate self-report web-based measures. The study design is guided by the Consolidated Standards of Reporting Trials (CONSORT) extension criteria for pilot and feasibility trials  and the Adults with heart failure are eligible to participate if they self-report a diagnosis of heart failure as an adult; currently experience heart failure symptoms or have been told they are NYHA Class II or III or AHA/ACC Stage C; are at least 18 years of age; have a spouse or partner they have lived with for at least 6 months that is willing and eligible to participate in the study; and have access to a device with a camera  to participate in Zoom sessions, or a phone to participate in phone sessions. Partners (the term partner is used throughout the study to refer to both spouses and intimate partners) are eligible to participate in the study if they are also at least 18 years of age and have lived with the adult with heart failure for at least 6 months.Couples are excluded if either member has major uncorrected hearing impairment, has significant cognitive impairment, is enrolled in another intervention trial that would prevent them from completing the requirements of this study, and has active psychosis or severe substance abuse that would impair their ability to complete the study. Couples will also be excluded if the adult with heart failure has had a heart transplantation, is in receipt of a mechanical circulatory support device, or has another terminal illness that would prevent them from participating in a five-month study. Couples are not required to be married and no couples will be excluded based on sexuality or gender identity.Couples are recruited through the Tufts Medical Center Heart Failure clinic, Boston, Massachusetts, and also through community outreach locally  and nationally via clinical partners in cardiology clinics, websites  and social media . Study investigators at Tufts Medical Center will communicate with eligible patients in their heart failure clinic about the study and provide them with the study recruitment materials that include the study phone number at Boston College and QR code managed by the study research team at Boston College. Interested participants contact the Boston College study team either by phone or the QR code and are screened for eligibility by phone. Similarly, our community outreach recruitment involves distributing information through media, social media, and presentations, and interested participants are provided information to call, email, or use the QR code to contact the Boston College study team for more information and/or to schedule a time for a phone eligibility screening. Eligible and interested couples are e-mailed separate links to provide consent using a web-based survey, though participants are provided the option to complete paper versions of the consent form by mail. Couples are considered to be formally enrolled and consented when electronic or written consent forms are completed by both members of the couple.Participants complete three surveys over the course of the study at baseline, month 2 (post-treatment), and month 5 (3 months post-treatment). Adults with heart failure and their partners complete separate surveys. Participants can complete the surveys either by Research Electronic Data Capture (REDCap)—a HIPAA-compliant, secure, web-based application—or by mail survey. This allows participants to have greater choice for their preferred mode, which increases both recruitment and retention across the adult lifespan. In rare circumstances, we will also provide a phone interview to complete the survey. All participating couples will be assigned a code number and all identifying information will be removed from all data sources (electronic and hard copy). All study data will be stored in a secure, password-protected network folder on the Boston College server. Data from mail surveys will be entered and verified by trained research staff before merging with data obtained via REDCap. Due to minimal risk of the study, MPIs are responsible for data monitoring.Upon completing the baseline survey, couples are randomized by the project coordinator to either the TCU© arm or the SUPPORT© arm and receive a phone call from their assigned interventionist to inform them of their assigned program and to schedule the first session. Upon completion of the study, couples receive a $100 gift card. In cases where one or both members of the couple cannot or does not want to continue participating in their assigned program (TCU© or SUPPORT©), either member of the couple may still choose to complete follow-up data assessments, at approximately 2 and 5 months post-baseline. However, participants cannot continue in their assigned program as individuals (they must complete the program together).Taking Care of Us© is a theoretically and empirically informed intervention that is communication-based and relationship-focused, building on the strengths of the couple while fostering new skills. Drawing upon our theory of dyadic illness management [nagement , previouContent builds throughout the program and is tailored to the area couples agree to work on together, reflecting a respect for each couple’s readiness to change. Early on the importance of respectful and supportive communication is introduced with specific skills the couple can practice. Strong emphasis is placed on speaker-listener techniques so that members of the couple can share and hear in a facilitated context. The program also places emphasis on the social aspect of confidence and role of supporting one another in increasing confidence as a team. Because the program is strengths-based, it provides couples with skills, confidence, and knowledge to collaborate and support one another, and communicate with each other to balance their respective health needs and take a team approach to living with heart failure. Couples will practice skills and try out simple strategies between sessions and then reflect on how things went with the interventionist and each other to brainstorm when changes would help. The goal of such exercises is to encourage the couple to practice skills learned in sessions and demonstrate the manageable way goals can be broken down into small and simple strategies. Successful strategies will be noted and combined with a shared collaborative plan the couple creates during the sessions that will be sent to the couple on completion of the program. The seven sessions and their content and format are presented in Table Taking Care of Us© binder with materials to accompany each session . The binder also includes local and national resources that may be helpful .Each couple will receive a The SUPPORT© program is an attention-control condition and comprises of three sessions that occur approximately 1, 4, and 8 weeks after the baseline survey is completed . Each session is 45–60 min in length and takes place via Zoom or phone. The program is an educational counseling program similar to heart failure educational interventions currently available and is, therefore, a more realistic comparison condition than “usual care.” Although it is a class I guideline recommendation that all patients with heart failure should receive education and support to facilitate self-care , there aSession 1 overlaps with the first session of TCU© by focusing on heart failure symptoms and self-care of heart failure. Session 2 focuses on healthy eating, and session 3 focuses on physical activity. All sessions are designed to facilitate reflection and preliminary action planning and focus primarily on the person with heart failure . Materials represent current clinical practice guidelines and publicly available educational information developed by the Heart Failure Society of America and the American College of Sport Medicine. Thus, the program is considered reproducible. Each couple will receive a SUPPORT© binder with materials to accompany each session . The binder also includes the same local and national resources provided to the TCU© group .Both programs are delivered by interventionists with a bachelor’s or master’s degree in mental health. Interventionists were trained by the study MPIs through a series of in-depth sessions guided primarily by the TCU© intervention manual and SUPPORT© manual, which both contain overviews of the respective program, guiding principles, scripts for each session, session materials , protocol for conducting the sessions and completing the session summary sheets and fidelity checklists, tips for dealing with challenging scenarios, and reporting adverse events or safety concerns. The TCU© and SUPPORT© manuals were both reviewed by two experts  that were not involved in the development of the manuals. Suggested revisions to the materials were made before the start of the pilot study.Additionally, interventionists were provided with key background readings on heart failure, caregiving, and a dyadic approach to illness including the theoretical framework underpinning the intervention. Training sessions focused on the elements of the training manual mentioned above, the goals of each session, role-playing, dealing with challenging scenarios , and confidentiality and safety. Over time, interventionists continue to be supervised with sessions reviewed and debriefed regularly. Interventionists are trained to deliver both programs to avoid unnecessary interventionist effects.The current pilot study has been deemed minimal risk and involves a communication-based, relationship-focused intervention compared to an educational program. All members of the team receive training on identifying and reporting adverse events  or safety concerns  to the MPIs promptly. Each member of the research team also receives a research training manual outlining all elements of the research protocol and requesting that adverse events and safety concerns identified during interactions with participants  be reported to the MPIs immediately for determination of action. Interventionists are also required to document adverse events and safety concerns brought up by participants during sessions on the session summary sheet and also reported to the MPIs immediately. Given the minimal risk of the study, a safety monitoring committee consisting of both MPIs and two leading researchers in the fields of heart failure and caregiving research was formed to oversee and monitor any safety concerns or adverse events that might arise during the study. All adverse events will be promptly reported to the Boston College IRB and funding agency.Treatment fidelity in the current study is maximized through the use of clear protocols and manuals that are scripted, ongoing training and supervision throughout the study, and fidelity checks. Fidelity checks include the use of fidelity checklists that are completed at the end of every session by the interventionists to document whether key components of the session were delivered. Session summary sheets are also completed at the end of each session, by the interventionists, to document the engagement of the couple, any challenges encountered in delivering the content, and their role as facilitator. These checklists and summary sheets provide a basis for ongoing training and supervision and are reviewed by MPIs within 24 h of each session. Finally, approximately 5% of sessions will be recorded at random throughout the study. Both MPIs view each recording independently within three days of the session and independently rate the session using the fidelity checklist. Each MPI also prepares a report on what went well during the session and any places where room for improvement or feedback is warranted. MPIs then meet together to discuss any inconsistencies in their observations before meeting with the interventionist to discuss the session. Couples will have the option of opting out of the possibility of being selected to have a session recorded for fidelity purposes. When a session is selected and the couple agrees to the recording, the session is viewed by the principal investigators within 3 days and then destroyed.The aims of the current study will examine the feasibility and acceptability of the program and explore change in the outcomes of dyadic and individual health of the couple, dyadic symptom appraisal, and dyadic management.There will be several indicators of feasibility  and acceptability . We will also assess benefits and drawbacks in both closed-ended  and open-ended questions. Items and measures were drawn from prior studies by members of this team (CJW) , 69. AddThe psychometrically sound 10-item PROMIS Global Health short form  will be The couple’s appraisal of heart failure symptoms  will be assessed at all waves using well-established, reliable, and valid measures. Dyspnea will be measured with the 6-item dyspnea subscale of the Heart Failure Somatic Perception Scale . The scaDyadic management is a broad concept that captures the verbal and non-verbal strategies that help dyads manage and cope with illness , 84. In Communication within the dyad will be examined using the dyadic coping measure, which consists of two subscales (active engagement and protective buffering) , 86. ActCollaboration will be examined through both individual and shared engagement in managing heart failure and engagement in dyadic coping behaviors. Couple engagement in heart failure management will be measured using the management scores of the Self-Care of HF Index v6.2 (SCHFI) . The SCHFinally, confidence to manage heart failure will be assessed using the Stanford Chronic Disease Self-Management measure . CouplesSurveys will also ask couples for key background and socio-demographic data, including, age, gender, length of relationship, educational status, employment status, race/ethnicity, time since diagnosis, stage of heart failure, HFpEF vs. HFrEF status, current heart failure medications, other chronic illnesses, and impact of the coronavirus.We will examine the feasibility and acceptability of the TCU© intervention in several ways. First, adherence to the program will be examined in proportion of couples who completed 5 of the 7 TCU© sessions. Feasibility will be achieved if ≥ 30% of eligible couples enroll in the study, ≥ 70% of assigned couples complete the TCU© program, and ≥ 80% complete the follow-up assessment. Acceptability of the TCU© program will be achieved if ≥ 80% of adults with heart failure and their partners report being satisfied/very satisfied with “the program overall” and “the usefulness of the information provided in sessions” and agree/strongly agree “they would recommend the program to other couples” and “looked forward to the sessions”. Results that fall short of these benchmarks will prompt refinement of the program before proceeding to a main trial. Additionally, quantitative items regarding the strengths and limitations of the program  as well as two open-ended questions about the benefits and drawbacks of the program will be examined to determine needed refinements.p < 0.05 without correction for multiple tests.Multilevel modeling (MLM) will be used to explore changes in outcomes between the two programs. MLM controls for interdependencies of the dyadic data and autocorrelations among repeated assessments. We will run a series of longitudinal models to explore the role of an indicator variable (GROUP) on adult with heart failure and partner changes in dyadic health, dyadic management, and dyadic appraisal variables over time. A significant coefficient for GROUP on the slope parameter will indicate the rate of change across time is statistically dependent on treatment condition. For individual level health variables  individual MLM will be used to examine the role of GROUP. We will also have the option, particularly if we under-recruit, to conduct analysis of covariance to explore change in outcomes between both programs for adults with heart failure and partners separately. Due to the pilot nature of the study and primary focus on feasibility and acceptability, we will conduct two-sided statistical tests with Although there is consensus that pilot studies should have primary focus on feasibility and acceptability, there is less clarity regarding the sample size needed with ranges of 10–75 per group . Recent This program is the first known heart failure dyadic intervention that will target specific, modifiable aspects of the dyadic relationship  to foster skills to enhance the way couples appraise and manage heart failure together. The program is tailored to the strengths and challenges for each couple and facilitates the creation of shared goals for each couple and the strategies to obtain them as a team. Our program is dyad-based  and dyad-focused  . We will


We found few statistically significant differences between metro and non-metro respondents. To answer the second and third research questions, we conducted linear regressions predicting our dependent variables. In terms of satisfaction with services, our model explained very little of the variance, other than finding that being partnered or married was significantly, positively related to satisfaction with services. In predicting satisfaction with community participation, the model explained about a quarter of the variance, with having fewer disabilities and higher health status predicting more satisfaction. This research indicates that there are few differences between metro and non-metro low-income PAS consumers and that more research is needed to understand what factors are related to satisfaction with services and community participation in this population.Personal assistance services (PAS) are supports provided by workers to assist disabled people with their activities of daily living. Access to in-home PAS allows people who need assistance with these activities to live in their own homes and communities, rather than moving to congregate living facilities. Because metro and non-metro areas differ in many ways, we explored the following research questions: (1) Are there differences between non-metro and metro PAS users?, (2) What factors are associated with satisfaction with services?, and (3) What factors are associated with satisfaction with community participation?. We randomly surveyed PAS consumers in five states about their experiences with PAS. To answer the first question, we compared metro or non-metro consumers using independent samples  For over ten million people with disabilitiesDespite the importance of these services and the fact that work in PAS is one of the fastest growing occupations , little There are a number of factors that have been explored in relation to satisfaction with PAS, but the majority have focused on issues around consumer choice and control in hiring, training, and maintaining their workers. Advocates during the Independent Living Movement in the 1970s and 1980s . The mosHaving the ability to participate in community is a component of functioning related to health  that hasIn short, compared to their urban counterparts, rural people with disabilities are doubly challenged in realizing their community participation goals because of higher levels of environmental barriers such as inaccessible infrastructure and a lack of public transportation . It is uIn this exploratory study, we used data collected in early 2020 (pre-pandemic) in a paper-and-pencil mail survey of PAS consumers. We examined differences in non-metro and metro PAS consumers and what factors are related to satisfaction with services and satisfaction with community participation in order to improve our understanding of this unique and understudied rural population. More specifically, we addressed three exploratory research questions:1) Are there differences between non-metro and metro PAS users?2) What factors are associated with satisfaction with services?3) What factors are associated with satisfaction with community participation?t-tests to explore metro and non-metro differences before constructing linear regression models to predict both satisfaction with services and community participation. To follow is a description of recruitment, measures, procedures, and analysis used.To answer these questions, we mailed a paper-and-pencil mail survey (copy of full survey available upon request) to 1,200 Consumer Direct Care Network PAS consumers in January of 2020. In addition to demographic questions and our variables of interest related to satisfaction with services and community participation, the survey also included questions on worker characteristics, health, electronic visit verification, and other topics relevant to PAS. We then conducted independent sample At the time of this study, our partnering organization (Consumer Direct Care Network) was serving mostly self-directed Medicaid-funded consumers in 17 states. Based on feedback from our Rural PAS Advisory Board , we decided to target consumers in five geographically and programmatically diverse states: Arizona, Alaska, Montana, Texas, and Wisconsin. While the majority of consumers in these states were in self-directed programs that allowed for consumer-based worker recruitment, hiring, and management, some agency-based programming continues to exist. Thus, based on 5-year estimates from Consumer Direct Care Network administrative data, we sampled each state differently to maximize rural and agency-based representation  at the University of Montana, we mailed pencil-and-paper surveys to 600 metro and 600 non-metro addresses across the five states. We used a Dillman multi-contact method , includiOf the 1,200 survey packets mailed out, 196 were returned because they were sent to undeliverable addresses, the person had died, or the person did not currently receive PAS. Surveys were returned by 190 participants, ten of which were omitted as they were completed by or for someone under the age of 18. This resulted in a response rate of 19%. Ninety percent of the respondents completed the entire survey. We received 96 non-metro and 85 metro responses.Relevant to this study, the survey included measures of basic demographics, disability type, general health status, satisfaction with services, satisfaction with community participation, metro/non-metro status, and service type (self-directed or agency). To follow is a description of each of the measures.In open-ended questions, participants were asked to indicate their gender and answers were categorized into women and men. Age was also asked using an open-ended question and dichotomized to be working age [18–65] and non-working age (66 and older). We measured race using a check-all-that-apply option of American Indian/Alaska Native, Asian, Black/African American, Native Hawaiian/Other Pacific Islander, White, and Other (with space for a write-in answer). We also asked participants to indicate if they identified as Hispanic or Latino. Answers were then collapsed into a single dichotomous variable of White, Non-Hispanic and Non-White or Hispanic. Partnered-status was measured by asking if participants were single/never married, single/divorced or separated, widowed, married, or living with a serious partner. Partnered-status was then dichotomized as married/partnered or single. To measure income, respondents were provided seven categories of income ranging from < $10,000 to $100,000 or more. For this analysis, these categories were collapsed into a dichotomous variable of $20,000 or less and $20,001 or more.Disability type was measured using the six-item set of dichotomous questions which are also asked in the American Community Survey . RespondGeneral health status was measured using a single item from the Health Related Quality of Life Scale : “Would We asked respondents to answer the question: “If you have more than one paid caregiver, who provides the MOST assistance?”, to which they could select immediate family member, extended family member, friend or someone they knew before, someone they did not know, or fill in an “other” option. For this study, we dichotomized type of care provider as family (including family or extended family members) and non-family.Community Care for the Elderly (CCE) Client Satisfaction Survey . Overall, the most common disability types were serious difficulties walking or climbing stairs, dressing or bathing, and running errands independently. Metro respondents were significantly more likely to report serious difficulty dressing and bathing compared to non-metro respondents , while non-metro respondents were significantly more likely to report serious difficulty running errands independently . Finally, metro respondents had significantly higher number of disabilities compared to non-metro .Prior to conducting the linear regression analyses, we completed Pearson's correlations for all variables. There were no strong correlations to indicate the existence of interacting variables or multicollinearity. To follow is a brief summary of the linear regression results for both satisfaction with services and satisfaction with community participation.p < 0.05).Overall, the linear regression model see  predictiF = 4.37, adjusted R-squared=0.26, p < 0.001), with the variables included in the model explaining 26% of the variance in satisfaction. In this model, the number of disabilities reported by the respondent was negatively related to satisfaction with services , while health status was positively related to the variable of interest .The linear regression model see  predictiIn answer to our first research question, “Are there differences between non-metro and metro PAS users?”, we found that consumers of PAS in metro and non-metro areas were very similar. The exceptions were that non-metro consumers were more likely to be self-directed and have serious difficulties running errands independently compared to metro respondents, while metro respondents were more likely to have serious difficulties dressing and bathing and reported more disabilities on average than non-metro respondents. Higher rates of self-direction among non-metro consumers makes sense in that agencies, like many organizations and businesses, tend to operate out of and in urban centers.These findings may point to barriers in the geographic or built environments of non-metro communities  . This seTo answer our second research question, “What factors are associated with satisfaction with services?”, we found that our model was not effective in explaining variation in satisfaction. While we included variables indicated by previous research, only being partnered was significantly related to satisfaction with services. For the people in this study who are lower income and are receiving home-based services through Medicaid, rurality does not predict or relate to satisfaction with services, regardless of whether or not the care provider is a family member, or the type of program they are enrolled in.To answer our third research question, “What factors are associated with satisfaction with community participation?”, we found that our model was effective in explaining some of the variance in satisfaction with community participation, but many demographic factors, including rurality, were not significantly related to this type of satisfaction. Instead, the number of disabilities experienced by respondents, as well as health status, seem to be driving the significance of this model. This appears to indicate that degree of functional impairment bears on people's satisfaction with community participation. Existing research highlights there are no differences in actual community participation between metro and non-metro older adults, but closer proximity to certain environmental features such as neighborhood resources and public transportation increased social participation across geography .post-hoc factor analyses of the measure revealed that with more data, different aspects of satisfaction with services could provide a more nuanced understanding of PAS users' beliefs about the services they receive. Additional research is also needed to explore how PAS services might be organized or improved to overcome the unique environmental barriers in rural communities. Furthermore, additional research should seek to understand how to improve satisfaction with community participation for people with different disability types, especially disability related to mobility impairments and health status. Previous work suggests that pain, fatigue, and depression are negatively related to leaving the home  under a grant from the National Institute on Disability, Independent Living, and Rehabilitation Research , which is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The research does not necessarily represent the policy of NIDILRR, ACL, or HHS and one should not assume endorsement by the federalgovernment.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.


In North Dakota, 28% of adults over age 65 report falling each year, resulting in substantial morbidity and mortality. Evidence-based fall prevention programs can benefit quality of life and maintenance of daily living activities, particularly for community-dwelling older adults. The Stepping On fall prevention program, a national evidence-based program, is designed to educate older adults about risk factors for falls, safety strategies, and coping behaviors. The program consists of seven weekly community-based workshops conducted in a small-group setting by two trained facilitators. The Stepping On program was introduced in North Dakota in March 2012. Since that time, 132 workshops have taken place in rural communities across the state, serving 1,502 participants. The number of workshops and participants steadily grew between 2012 and 2019. In the year 2012-13, 127 individuals participated in ten workshops. By 2019, before the program was suspended during the pandemic, 199 individuals participated in 16 workshops; 24 workshops had previously been held in 2018. The current study discusses the implementation process as the program scaled up and expanded to more locations. The feasibility and sustainability of conducting the program in isolated rural areas, challenges encountered, and lessons learned will also be discussed. It is important that residents in rural communities have access to evidence-based programs like Stepping On so they can experience the benefits.


PARP inhibitors (PARPi) have broad applicability as monotherapy in tumors with HR defects. However, their combination with radiotherapy (RT) is less advanced owing to the rather modest radiosensitization typically achieved with most tested PARPi, including olaparib. Tumor resistance to PARPi or RT is a significant bottleneck in the clinic, and strategically designed combinations of PARPi and RT may offer approaches to overcome such resistance. Talazoparib (BMN673), as compared to other PARPi, is a superior radiosensitizer. In this review, we discuss our evolving understanding of the mechanistic underpinnings of BMN673 radiosensitization and outline the potential for combinations of BMN673 with RT to treat various forms of cancer.BMN673 is a relatively new PARP inhibitor (PARPi) that exhibits superior efficacy in vitro compared to olaparib and other clinically relevant PARPi. BMN673, similar to most clinical PARPi, inhibits the catalytic activities of PARP-1 and PARP-2 and shows impressive anticancer potential as monotherapy in several pre-clinical and clinical studies. Tumor resistance to PARPi poses a significant challenge in the clinic. Thus, combining PARPi with other treatment modalities, such as radiotherapy (RT), is being actively pursued to overcome such resistance. However, the modest to intermediate radiosensitization exerted by olaparib, rucaparib, and veliparib, limits the rationale and the scope of such combinations. The recently reported strong radiosensitizing potential of BMN673 forecasts a paradigm shift on this front. Evidence accumulates that BMN673 may radiosensitize via unique mechanisms causing profound shifts in the balance among DNA double-strand break (DSB) repair pathways. According to one of the emerging models, BMN673 strongly inhibits classical non-homologous end-joining (c-NHEJ) and increases reciprocally and profoundly DSB end-resection, enhancing error-prone DSB processing that robustly potentiates cell killing. In this review, we outline and summarize the work that helped to formulate this model of BMN673 action on DSB repair, analyze the causes of radiosensitization and discuss its potential as a radiosensitizer in the clinic. Finally, we highlight strategies for combining BMN673 with other inhibitors of DNA damage response for further improvements. Radiotherapy (RT) and chemotherapy are two main pillars of cancer treatment. As the primary treatment modality, RT contributes to about 40% of curative treatments for cancer ,2. TheraThe PARP family of proteins regulates several biochemical processes in a living cell by mediating a post-translational modification called poly- or mono-ADP-ribosylation (PARylation or MARylation). Where PARP-1, 2, 5a, and 5b are capable of modifying their targets through PARylation, the remaining PARP family members modify their targets through MARylation . Among 1Tumors lacking HR and therefore therapeutically treated with PARPi, frequently acquire resistance when treated for a prolonged period with such inhibitors . The priCombination with RT offers an attractive scenario for enhancing the efficacy of PARPi ,27,28,29Exacerbation occasional deregulation, or suppression of the DNA repair machinery is a promising avenue for improvements in cancer treatment utilizing agents generating damage in the DNA. The genomic integrity of higher eukaryotes is continuously challenged by chemical and physical agents capable of introducing covalent DNA modifications ,42. MammIn genetic studies, PARP-1 was originally identified as a key protein in the base excision repair (BER) pathway ,56,57,58+, causing cell death. PARP-1 can also stimulate the gap-filling step and the final DNA ligation step of SSB repair, by intervening with the availability of ATP [PARP-1 promptly detects single-strand breaks (SSBs) through direct interaction with the damaged DNA ,66,67. Oy of ATP . Recent studies have also suggested a role for PARP-1 in DSB repair pathways: classical non-homologous end joining (c-NHEJ), homologous recombination (HR), alternative end joining , and single-strand annealing (SSA). The PARP-1 requirements for c-NHEJ function are less well characterized. It has been demonstrated that PARP-1 can PARylate the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which is the primary coordinator of c-NHEJ . This stThe role of PARP-1 in HR is somewhat complex, and earlier studies showed that PARP-1 is dispensable for HR. In PARP-depleted cells, HR was normal, and PARylation showed a little direct effect on HR . InhibitPARP-1 has a well-established role in alt-EJ. Abrogation of PARP-1 activity by chemical inhibition or transcriptional inactivation reduces the frequency of alt-EJ-mediated chromosomal translocations, suggesting that PARP-1 is an alt-EJ factor ,77,78,79Although the function of PARP-1 in SSA is scarcely documented, studies indicate a minor, indirect role for PARP-1 in this process. For example, it has been reported that deficiency of ERCC1, a component of the excision nuclease complex (ERCC1-XPF), activated during SSA, results in synthetic lethality after olaparib treatment . Moreove®, developed by AstraZeneca, Cambridge, UK) was the first PARPi approved in 2014 by the European Medicines Agency (EMA) and by the Food and Drug Administration (FDA) in the United States for use as a single agent in the clinic. It showed a favorable response in patients with germline BRCA1/2-mutated advanced, recurrent ovarian cancer, and for maintenance treatment of adult patients with recurrent gynecologic cancers [®, developed by Clovis Oncology, Boulder, CO, USA) was approved in 2016 for the treatment of ovarian cancer in patients with somatic and germline BRCA mutations, and in maintenance treatment settings [The discovery of synthetically lethal interactions between BRCA1/BRCA2 loss of function mutations and PARP inhibition paved the way to the development as a monotherapy of clinically relevant PAPRi with strong and specific activity. Olaparib  ,124. To DNA end-resection plays a pivotal role in DSB repair pathway choice. DSB repair pathways can be broadly classified as resection-dependent, or resection-independent. During resection an extended overhang of 3′-ssDNA is generated, which serves HR, alt-EJ, and SSA, while strongly antagonizing c-NHEJ ,128. ResAnother study also reported increase in RPA foci numbers in irradiated cells treated with BMN673 . Notably2-phases of the cell cycle. We recently reported that the contribution of HR rapidly increases to over 50% at doses between 0.1 and 2.0 Gy, while it becomes undetectable above 10 Gy [HR is the only DSB repair pathway that restores the genome with high fidelity, becoming operational in the S -and Gve 10 Gy . For HR ve 10 Gy ,133,134.Our results showed that BMN673 treatment caused a marked increase in Rad51 foci, suggesting elevated engagement of HR–as may be expected from the increased resection observed . SimilarAnother approach to functionally measure effects of various treatments on HR utilizes reporter cell lines with integrated constructs  reporting processing by HR of an I-SceI-induced DSB . Using sWhen comparing results obtained by scoring RAD51 foci in irradiated cells with those obtained with reporter cell lines, it must be kept in mind that the latter assay measures effects on repair of an I-SceI-induced “clean” DSB . It is lTaken together, these results allow the tentative conclusion that BMN673 leaves HR unchanged at “clean” DSBs, but increases its engagement in IR-induced DSBs. It remains, however possible that in irradiated, BMN673-treated cells, a fraction of HR engagements is unproductive. Either way, the anticipated residual HR activity in BMN673 treated cells predicts benefits in cancer management from a combination of BMN673 with agents inhibiting HR, e.g., ATR inhibitors. In mammals, c-NHEJ is the main repair pathway for DSB processing and operates with fast kinetics and efficiency, throughout the cell cycle ,140,141.BMN673 was found to inhibit c-NHEJ at high IR doses with efficiency similar to that achieved by DNA-PK inhibitors . It is aStrikingly, in line with this conclusion, the “end-protector” 53BP1, an antagonist of BRCA1-CtIP-mediated end-resection, is suppressed by BMN673 at low IR doses . This isC-NHEJ is mechanistically suppressed at resected DNA ends owing to the low binding efficiency of Ku heterodimer on processed ends . Thus, dIt is worth mentioning here that in contrast to combinations with IR, BMN673 treatment applied as a monotherapy resulted in elevated levels of 53BP1 foci ,149,150,Alt-EJ is a collective term used to describe DSB processing that cannot be attributed to HR or c-NHEJ, and which engages as a backup when DSB ends are released owing to failures of these repair pathways . AlthougCompared to c-NHEJ, alt-EJ operates with slower kinetics and lower efficiency, and with much greater error-proneness. Consequently, when DSBs are processed by alt-EJ, joining of “wrong”, unrelated DSB ends can occur, drastically increasing thus the probability of chromosomal translocation formation . Indeed,Since PARP-1 plays a vital role in the DSB sensing step of alt-EJ, inhibition of PARP-1 using PARPi generally reduces the frequency of chromosomal translocations. Thus, PARPi such as PJ34, AG14361 and the clinically relevant olaparib, have shown to decrease translocations in irradiated cells ,158,159.Translocations are one of the critical drivers of oncogenesis and the culprits of cell death after exposure of cells to IR . Our stuA previous study tested alt-EJ using reporter cell lines and concluded that suppressing PARP-1-dependent alt-EJ by olaparib correlates positively to its radiosensitizing effect . This obRetention of inhibited PARP on DNA lesions  has been proposed as a key parameter of PAPRi-induced cytotoxicity underpinning the effects of monotherapy applications. PARPi-mediated inhibition of Parp1 auto-PARylation prevents its removal from DNA lesions and leads to replication fork collapse in S-phase cells, or to the suppression of other aspects of the DNA metabolism . BMN63 hWhen analyzing the effects of PAPRi, it is important to address separately effects on cytotoxicity that is enhanced in HR deficient cells, and effects on radiosensitivity and DSB processing reviewed here, as they may be caused by different mechanisms. Thus, while it is possible that the enhanced trapping ability of BMN673 explains its toxicity in HR deficient cancers ,11, it mCan Parp1 trapping explain the above observed effects of BMN673 on DSB processing? The shift of DSB repair from c-NHEJ to HR and alt-EJ that requires extensive processing of DNA ends rules out general Parp1 trapping stopping all processing at the DSB end as a mechanism. Indeed, BMN673 mediated excessive resection and accretion of RPA70 and Rad51 after IR  is plausIt has been shown recently that p97 ATPase/segregase extracts BMN673-induced trapped PARP-1 from chromatin, a process that requires post-translational modification of PARP-1 by PIAS4-mediated SUMOylation and RNF4-mediated ubiquitination . The chrThe above evidence in aggregate shows that BMN673 indeed traps Parp1 at the DSBs and provides clues on possible mechanisms to undo this trapping. It leaves however open the mechanism of how BMN673 specifically inhibits c-NHEJ and enhances in a directly compensating manner, resection-dependent DSB processing. The elucidation of the mechanisms underpinning these effects should be given high priority. 2-phase cells to include effects on HR. At low IR doses, c-NHEJ and HR repair similar fractions of DSBs, with alt-EJ having a small contribution ,145,146.In the current review, we discussed the mechanisms underpinning the superior radiosensitizing potential of BMN673, as compared to other clinically relevant PARPi. In addition, we discussed the critical properties of BMN673 that pave the way for testing it in clinical settings as an adjuvant to RT. BMN673 inhibits c-NHEJ activity at low and high IR doses by promoting DSB end resection. As a result, resection-dependent pathways  show increased activity . This isThe potential of combining BMN673 with RT is evident from several ongoing pre-clinical studies, but the clinical evidence supporting this approach is scarce. The combination has the potential to generate a paradigm shift and to establish BMN673 as a promising radiosensitizer. Our in vitro results, as well as results from other pre-clinical studies (described in


Moderate improvements were also seen in fatigue  and several aspects of work performance . Moderate effect sizes were also seen for positive affect (d = 0.566) and fatigue severity (d = 0.577) among the Program Only arm, whereas no noteworthy effect sizes were observed among the Desk Only arm. Combining an online sedentary behavior modification program with height-adjustable desk provisions appeared to positively affect mental well-being and work performance among remote employees.Sedentary behavior negatively impacts mental health, which can decrease employee productivity. Employee mental well-being and work performance may improve with sedentary reduction interventions, especially strategies that include environmental workplace modifications and behavior-changing strategies. However, such interventions have not been examined among employees working remotely during the COVID-19 pandemic. As part of the Stand Up Kansas program, 95 sedentary university employees working from home were randomized into one of four intervention arms: height-adjustable desk provision (Desk Only), online sedentary behavior modification program (Program Only), Desk + Program, or Control. The outcomes were measured at a baseline (November 2020) and following the 12-week intervention (February 2021). Employees reported mood (positive and negative affect), stress, fatigue  and work performance  were measured using established self-report instruments. The effect sizes, by comparing the Control arm to the Desk + Program arm, revealed large improvements in mood (positive affect,  High levels of sedentary behavior, defined as “any waking behavior characterized by an energy expenditure ≤1.5 metabolic equivalents (METs), while in a sitting, reclining, or lying posture . Mental Stand More AT (SMArT) Work and Stand Up Victoria trials [Given the negative impacts of sedentary behavior on employee health ,3,4, enva trials ,14. Thesa trials ,14. Despa trials .The primary environmental intervention used to reduce sedentary behavior in the workplace has been the provision of height-adjustable desks, which allow employees to alternate between sitting and standing postures while working . This inRecently, the unforeseen workplace challenges that have accompanied the COVID-19 pandemic have prompted additional concerns about workforce sedentary behavior, mental well-being and job performance. Socially distanced employees have reported increased sedentary time, more negative mood, increased stress levels, decreased energy levels, poorer sleep quality, decreased concentration, decreased satisfaction with work and decreased productivity compared to prior to the pandemic ,24,25. Tclinicaltrials.gov (NCT04641689) and has been described by Mailey et al. [The design of this pilot randomized controlled trial was pre-registered at y et al. . The priy et al. . The effy et al. . The cury et al. .Briefly, participants who met the inclusion criteria were sent online questionnaires via a Qualtrics survey that assessed baseline mental well-being and work performance. After obtaining this information and stratifying by sex and BMI, employees were randomized into one of four intervention arms: Desk Only, Program Only, Desk + Program, or Control . All outThe protocols used for the height-adjustable desk and for the behavioral intervention program have been previously described . BrieflyThe participants were university employees who volunteered for the study after recruitment via university announcements . The parDemographic information, including participant age, sex and body mass index  was collected at the baseline . Four seTo assess mood, which is primarily influenced by positive and negative affect , the PANTo assess stress, the four-question PSS was used, which has similar reliability levels but better internal validity for reporting stress levels than the ten-question PSS ,37. AddiThe FSI was used to assess employee fatigue. This scale consists of 13 questions that assess fatigue duration, interference with daily activities and severity level, with possible responses ranging from 0 to 10. Higher FSI scores are associated with more severe degrees of fatigue duration, interference with activities and severity ,39. The To evaluate employee work performance, the HWQ was used . This suQualitative questions developed by the study team provided additional insight into the intervention effects on study participants. Participants responded to the following questions on the post-intervention survey: please describe any positive changes  you have noticed since using the desk (Desk Only and Desk + Program arms); and please describe any positive changes you have made since starting this program (Program Only and Desk + Program arms).d) were calculated to reflect the magnitude of variable changes from pre- to post-intervention between the Desk Only, Program Only and Desk + Program intervention arms versus the Control arm.Frequencies, proportions, means and standard deviations were calculated for categorical and continuous variables. Prior to the main analyses, Shapiro–Wilks tests were conducted to test the normal distribution assumption for the outcome variables. Change scores were calculated for all outcomes by subtracting the baseline value from the post-intervention value. Effect sizes . A second investigator then reviewed the themes, and some were discarded or combined after checking them against the full dataset. The first investigator then coded the full list of responses, with some responses being assigned to more than one theme if appropriate. The second investigator checked all codes, and a small number of codes were revised following discussion. Finally, frequencies were calculated by dividing the number of times each theme was mentioned by the total number of participants who responded to each question.A full CONSORT diagram from the initial pilot study has been previously published  and is ad effect size was large for positive affect (d = 1.106) and moderate for focus (d = 0.702) and work satisfaction (d = 0.751). Although not statistically significant, moderate effect sizes were also noted for improvements in productivity (d = 0.572), non-work satisfaction (d = 0.603), fatigue duration (d = −0.533) and fatigue interference with activities (d = −0.648) in the Desk + Program arm compared to the Control. Among the Program Only arm compared to the Control, fatigue worsened with a moderate effect size . Conversely, positive affect improved, with a moderate effect size between the Program Only and Control arms (d = 0.566). Regarding mood in the Desk Only arm, no effect was noted for positive affect change, whereas negative affect worsened compared to the Control , an increased awareness of healthy habits (36% of responses) and improvements in work performance , and the combination of an environmental and behavioral program appears most effective at reducing sedentary behavior (d = −1.84) [Stand More AT (SMArT) Work and Stand Up Victoria [The primary effects of these environmental and behavioral interventions on sedentary behavior have previously been reported, indicating that both environmental and behavioral programs are effective at reducing the number of minutes that remote employees spend sitting during the day (= −1.84) . The cur= −1.84) ,41,42,43Victoria . These sVictoria .However, the current study differs from previous trials in several ways. Firstly, the prior trials evaluated the combined effects of environmental and behavioral interventions ,14, wherThe current study is also unique from previous trials because this study was conducted in a work-from-home environment during the COVID-19 pandemic, whereas previous trials have been conducted in traditional, office-based settings ,14. BefoThe behavioral program used in the current study relied on multiple behavior-changing techniques, including the provision and promotion of social support to reduce sitting and the promotion of small increases in physical activity . Social Physical activity changes among employees using the behavioral program are an important consideration when analyzing the outcomes of the current study because the implementation of social-distancing protocols in response to the COVID-19 pandemic likely created additional barriers to changing the physical activity levels for the current study population . The behThis is also the first study to evaluate the effects of height-adjustable desk provisions on remote-employee-reported mental well-being and work performance during the COVID-19 pandemic. Employee workstation design, which includes the desk, is important to consider when evaluating remote work outcomes, as having an inadequate home workstation setup has been associated with increased employee stress and decreased productivity . At the Prior to the pandemic, studies indicated that, with proper organizational support, employees working remotely can be equally, if not, more productive than when working in the office ,52. HoweThis study is limited primarily by the number of desks available and thus by its sample size; therefore, the study was not fully powered to detect statistically significant differences in these secondary outcomes. Qualitative data were added to supplement the limited statistical tests, but the sample size still limits the generalizability of this study’s findings. Additionally, because the participants were aware that they could receive a free height-adjustable desk if they volunteered for the study, the study findings may be influenced by a motivated population. Differences in participant engagement in interventions may have also influenced the results, as the previous primary outcomes study indicated that individuals who viewed the online behavioral program content more had a greater reduction in their sedentary time compared to participants who viewed the content less . This stThis pilot study evaluates the benefits of using environmental and behavioral interventions to reduce sedentary behavior and to improve remote employees’ mental well-being and work performance. This study is the first to analyze how each of the three intervention types  impacts employee-reported mood, stress, fatigue and work performance in a COVID-19 work-from-home environment. The results indicate that utilizing a combination of environmental and behavioral program interventions generates moderate to large improvements in mental well-being and work performance, such as in mood, fatigue, focus, work satisfaction, non-work satisfaction and productivity.


Eosinophilic esophagitis (EoE) is a chronic eosinophil-predominant esophageal inflammatory condition, and is now recognized as one of the most common organic causes of dysphagia in pediatrics. While fibrostenotic esophageal strictures are a common complication of adult EoE, characterization of the stricturing phenotype in pediatric EoE remains at an early stage.Describe the Canadian pediatric EoE experience, with focus on the stricturing phenotype.New pediatric EoE diagnoses from 2015-2018 were retrospectively identified in Vancouver (BC), Northern Alberta (AB), Hamilton (ON) and Nova Scotia (NS). Incidence rates were calculated using 2016 Federal census data. Clinical, endoscopic and histologic data were gathered for each patient’s initial clinical encounter and for any esophagogastroduodenoscopies (EGD) until the end of the follow-up period .332 new EoE cases were identified during the study period across all 4 sites. The incidence of EoE in patients less than 15 years old was 9.1 (AB), 6.5 (NS), 3.1 (BC) and 5.4 (combined) per 100,000 person-years. Incidence was not calculated for Hamilton due to risk of ascertainment bias given their catchment area overlaps with multiple other centers. Of identified cases, 40 (12.0%) had endoscopically-identified esophageal strictures at diagnosis or during the follow-up period, with a subset of 11 (3.3%) of these patients undergoing mechanical esophageal dilation. Another 11 (3.3%) patients had more subtle signs of esophageal narrowing , while the majority had no evidence of esophageal narrowing . The median age at diagnosis was higher in the cohort with strictures  than those without  but with wide IQR's. A similar trend was seen for the median duration of symptoms at diagnosis . Patient reported food bolus impaction  and dysphagia  were associated with stricturing disease, with other symptoms less clearly linked. Trachealization was the endoscopic finding most closely associated with esophageal strictures . Esophageal stricture(s) were noted on 72 EGDs, including 27 endoscopic esophageal dilations, but excluding 10 esophageal dilations by interventional radiology. Of the 65 EGDs done in follow-up of a known esophageal stricture (see Table), 4 of 31 had resolution of this finding post mechanical dilation, and 19 of 39 had resolution of the stricture after initiation of new medical or dietary treatments (without dilation).EoE is common in Canadian children, with esophageal strictures within a few years of diagnosis in 12% of cases. Interestingly, a large portion of strictures resolved without mechanical dilation, which seems to point away from fibrosis as the primary driver of esophageal strictures in this patient population.CAG, OtherWomen and Children's Health Research InstituteNone Declared


Research has consistently found that people with mental illness (known as consumers) experience lower levels of participation in meaningful activities, which can limit their opportunities for recovery support. The aim of this study was to describe the outcomes of participation in a group program designed to address all stages of activity participation, known as Pathways to Participation (P2P). A descriptive longitudinal design was utilized, collecting data at three time points. Outcomes were measured by the Camberwell Assessment of Need Short Appraisal (CANSAS), Recovery Assessment Scale—Domains and Stages (RAS-DS), Behavior and Symptom Identification Scale (BASIS-24), Living in the Community Questionnaire (LCQ), and time-use diaries. All data were analyzed using descriptive statistics and Chi-square analyses. A total of 17 consumers completed baseline data, 11 contributed post-program data, and 8 provided follow-up data. Most were female (63.64%) and had been living with mental illness for 11.50 (±7.74) years on average. Reductions in unmet needs and improvements in self-rated recovery scores were reported, but no changes were identified in either time use or psychosocial health. The findings indicate that the P2P program may enable consumers to achieve positive activity and participation outcomes as part of their personal recovery. The link between participation in meaningful activity and health or well-being has been well established through rigorous research studies across age and diagnostic groups . For peoHowever, a considerable body of evidence demonstrates that consumers participate in lower levels of activity than members of the general community. An Australian study of consumers living in the community  found thDecreased participation in meaningful activity has multiple, cumulative effects on consumer health and well-being, increasing the risk of both physical and psychiatric morbidity ,10. PeopGiven the serious consequences of decreased participation, several interventions have been developed to enable consumers to engage in meaningful activities. To date, these interventions have mostly focused on vocational participation. A survey of Australian mental health consumers found that 76% were unemployed , with boInterventions that address the earlier phases of activity participation during recovery have begun to emerge in the past decade. The Action Over Inertia (AOI)  program The Balancing Everyday Life (BEL) intervention  is a 12-The preliminary evidence for both AOI and BEL provides promising data regarding their impact on consumer participation. However, none of the available interventions address a complete continuum of activity participation from initial engagement through to workforce participation as part of personal recovery. Participants in these programs may therefore need access to additional interventions to meet their vocational needs, which may not provide a coherent or well-articulated pathway to their ultimate recovery goals. The aim of this study was to describe the outcomes of a group program designed to address all stages of activity participation during recovery, known as Pathways to Participation (P2P).The study utilized a descriptive pilot longitudinal design to investigate outcomes for consumers participating in a single community mental health service. The study received ethical approval to proceed from the relevant Human Research Ethics Committee (HREC 2017.074).The P2P intervention is a hybridized program that aims to enable consumers to engage in meaningful activities at all stages of recovery. The P2P program combines two evidence-based interventions, the Action Over Inertia (AOI) program and The WORKS program. In addition to the overview of AOI presented above, the program emphasizes gradual momentum towards personal recovery goals and aims to increase engagement, enhance activity balance, promote social interaction and community engagement, and improve overall health and well-being. The WORKS framework  was deveThe developers of both the AOI and WORKS programs encourage modifications for local conditions, and the first author undertook adaptations based on her previous experience of delivering these interventions in community mental health services. The model of co-facilitation by occupational therapists and peer support workers was retained from previous iterations of the WORKS, given the positive feedback provided by stakeholders of that program . ConsultPrior to the commencement of the P2P program at each site, facilitating occupational therapists and peer support workers were provided with intervention training based on the manual content. This training was instituted based on previous findings , which iA single iteration of the P2P program was delivered at each of the four catchment areas of the adult mental health service. Each co-facilitated session lasted for two hours, with the first four weeks based on AOI content and the final six weeks based on The WORKS content. An information session was provided to consumers prior to P2P commencement, ensuring they understood the commitment required before agreeing to attend. Consumers were encouraged to attend the P2P program every week; however, it was not compulsory, and anyone missing a session was provided with extra contact from the facilitators to support them to rejoin and catch up on content. An overview of the content of each session is provided below in A total of five key outcomes were identified for investigation in this study: consumer identified needs, time use, self-rated recovery, psychosocial health, and community participation. Consumer identified needs were measured using the Camberwell Assessment of Need Short Appraisal (CANSAS) , which wTime use was measured via a 24 h time diary, in which consumers listed the activities they participated in, where it was performed and whom it was performed with at hourly intervals for the previous day. This method of gathering time use data is practiced across a range of disciplines, although it can be susceptible to recall bias . Data rePsychosocial health was measured using the Behavior and Symptom Identification Scale (BASIS-24) , which iIn combination, the outcome measures used in this study took approximately 15 min to complete. Outcomes were measured at the beginning of the P2P program (T1), immediately post P2P program (T2), and 3 months post P2P program (T3). Demographic data were also collected for all consumers at recruitment; at subsequent time points, a further question regarding any other vocational interventions was included. Participating consumers were reimbursed for their time completing data collection tasks with shopping vouchers. Initially, presentations about the P2P program were provided to multidisciplinary teams at each local service. Posters and brochures were also distributed to multidisciplinary team members to provide to potential participants and were displayed in the waiting room of each service to enable consumer self-referral. Multidisciplinary team members were not expected to recruit consumers, only to provide them with information and support the consumer to complete a brief registration form if required. Participation in the P2P program was not contingent on participating in this study. All local community services within the catchment of the mental health service were included in this study, comprising Continuing Care Units, Prevention and Recovery Care Services, and Community Mental Health Teams. For inclusion in the study, consumers needed to be aged between 18 and 65 years old and be receiving care from one of the participating services at the time of recruitment. Other inclusion criteria were (1) generally stable health ; (2) formal diagnosis with a serious mental illness or mental disorder with associated significant levels of disturbance and psychosocial disability; (3) spoken English to a level sufficient to participate in the group program without an interpreter; (4) capacity to independently provide informed consent, and (5) considered to present low to moderate risk by their key clinician. As co-morbidity was so prevalent amongst consumer populations , those wOnce registered for the P2P program, the consumer was provided with information regarding this study from the first author at an information session for all group attendees prior to the program commencing. Individual, specific written consent was obtained for every consumer participant in this study. Consumers were provided with a plain language statement prior to consent being sought and were encouraged to ask questions from their supporters prior to confirming their intention to participate. Participating consumers could choose extended P2P session attendance, a separate clinic appointment, or a telephone interview to complete outcome measures at each time point. Descriptive analysis was undertaken for all outcome measures collected in this study. Interval variables were analyzed using means, standard deviations, and ranges, while categorical variables were analyzed using frequencies and proportions. Where descriptive analysis indicated a large change in outcomes, analytical analysis was deployed using the Chi-square test. n = 1), moving away (n = 2), and choosing not to continue (n = 6). Most consumers were female . Mood disorders, anxiety disorders, and schizophrenia were the most prevalent psychiatric diagnoses, which consumers had been living with for 11.50 years (±7.74) on average. They also experienced other health conditions , which were also long-standing . Around half of the sample  had co-morbidities in addition to their mental illness. A total of 17 consumers were recruited for this study; however, 6 were lost to follow-up prior to the end of the P2P program. The following analysis focuses on the 11 consumers for whom repeat measures were available at T2 and the 8 consumers who provided data at T3. Reasons for attrition from this study included gaining employment  were singled or divorced, gained income from welfare, had completed high school education, and did not have children. A similar proportion  were living with family members and undertaking additional vocational interventions to the P2P program during the study. Most consumers  experienced a decrease in unmet needs over the course of this study. There was a significant change in the proportion of identified needs between T1 and T2, with met needs increasing and unmet needs decreasing, χ2  = 4.55, p = 0.033. Further decreases in both met and unmet needs were reported at T3, but these were not statistically significant. Information about conditions or treatment  was the most commonly unmet need at T1, along with self-care . Money was frequently identified at T1  and T2 , while physical health  and daytime activities  were highlighted T2  and T3 . Distress  and psychotic symptoms  were only prevalent at T3. Most consumers (n = 3), productivity activities (n = 2), and leisure activities (n = 4) during this study. Both positive and negative changes in activity participation times were recorded across the study, and there was considerable variability between individual consumers. The amount of time consumers spent in the community remained steady from T1 , to T2 , and T3 . As shown below in While time used for sleep remained stable for most, some consumers increased or maintained participation in activities of daily living  experienced an increase in total recovery scores between T1 and T2, while 5 consumers (62.5%) experienced further increase or maintenance of their total recovery scores between T2 and T3.There were no statistically significant changes in total or subscale BASIS-24 scores over time for any participating consumers. Psychosocial health remained constant for consumers throughout the study, with any changes observed being small fluctuations in scores.The proportion of consumers rating their social participation as ‘about right’ increased by 46% between T1 and T2, with smaller increases reported for caring participation (17%) and work participation (17%). A further 25% of consumers rated their participation in unpaid work as ‘about right’ at T3; however, , having a say in the community (30%), and hopefulness (21%). However, fewer consumers felt positive about having a say within families, having opinions respected, happiness, goal achievement, and belonging after 3 months than at T2. This study has described the outcomes of consumers participating in a group program designed to address all stages of activity participation during recovery, known as Pathways to Participation (P2P). While this pilot study can only provide a limited perspective on effectiveness, the findings presented here indicate the program did achieve some positive outcomes for the consumers who took part. P2P appeared to have the most positive impact on decreasing unmet needs for consumers and on social recovery and participation. The specific mechanisms by which consumers were able to meet their needs more effectively were not part of the data collection for this study but should be qualitatively investigated in future research. However, an Israeli study of the needs of people with serious mental illness  asserts However, some of the improvements reported by consumers between baseline and the end of the program were not sustained over the following three months. The evaluation of the long-term effects of occupational interventions is important to understand whether they have had a meaningful impact on the consumer, particularly as a fading of reported effectiveness over time is reported in many therapeutic studies . Given tThis aspect of the finding also raises questions about whether a program like P2P is most appropriately delivered by occupational therapists employed by state-based statutory mental health services. The complexity of factors that influence the activity and participation of consumers indicates that longer-term psychosocial rehabilitation is needed to enable recovery. In recent years, rehabilitation has had less of a presence in Australian mental health policy, with much of the public discourse focused on the tension between resourcing acute and community-based services . HoweverWhile some positive outcomes were short-lived, no significant changes in other outcomes were identified during this study. Both time use and psychosocial health outcomes remained steady across all time points, which suggests the P2P program made no impact on either of them. However, the proportion of consumers rating their social participation and unpaid work as ‘about right’ increased, as did the number of participants identifying their well-being as good to excellent. The AOI program is a time-use intervention , and so The findings of this study also highlight that recovery is a very individualized and personal process for consumers. Recovery is not a linear process, which is why recovery scales do not have ‘clinically significant’ change thresholds . The traThis study has several limitations that must be considered when interpreting the findings. The small sample size as a pilot study means that effectiveness could not be comprehensively assessed, and the participating consumers were not representative of any larger population. It was also completed within a limited geographical area and did not reflect prevailing changes to practice required since the COVID-19 pandemic. Aside from the methodology, there was also significant attrition from the study and loss of follow-up over time. This issue may be particularly problematic for mental health studies, as participants are experiencing a range of issues that may interfere with their ability to participate . DespiteIn conclusion, this study has described the outcomes experienced by consumers participating in pilot iterations of the Pathways to Participation (P2P) program. Some positive outcomes were identified regarding unmet needs and social participation, but no significant improvements were recorded in time use or psychosocial health. The findings presented here provide a basis for ongoing research into the effectiveness of the P2P program, which should include qualitative and mixed methodologies to better capture consumer experiences of the program.


The purpose of this study is to evaluate the adequacy of the developed protocol by verifying the validity of the expert group for the earthquake and fire response simulation protocol. A protocol development team consisting of one emergency rescue professor, one counseling psychology professor, three paramedics, and one firefighter developed the study’s protocols to promote the core response and capabilities required at an earthquake fire site. We checked the content validity for the appropriateness of the contextual connection for each stage for the protocol. We also created an evaluation checklist to measure the items for each stage. The protocol developed in this study consists of earthquake response, fire response, evacuation, and fire suppression. We set the situation for each stage and composed learner activities and learning performance goals. The earthquake response stage included (1) shout “it’s an earthquake,” (2) protect yourself, (3) turn off electricity and gas, and (4) evacuate to a safe place. In the fire response stage, (1) shout “fire,” (2) press the emergency bell and call 119, (3) close the door of a dangerous place where fire can spread, and (4) evacuate to a safe place. In the evacuation stage, (1) open the emergency exit, (2) cover your nose and mouth, (3) lower your posture, and (4) evacuate quickly in one direction. Lastly, in the firefighting stage, (1) pull out the safety pin, (2) hold the nozzle and face the fire, (3) grab the handle, and (4) spray the powder evenly. The protocol contributes to the development of systematic and elaborate simulation education materials in the future. Furthermore, it provides basic data for future disaster simulation operation and protocol development through continuous training and practical exercises. In recent years, natural disasters have continued worldwide. Among them, earthquakes are unpredictable and unexpected, moving away from certain areas affected by the circum-Pacific orogenic zone ,2. In paIn Korea, awareness of disaster safety is increasing day by day. The Ministry of Public Safety and Security designates mandatory education on disaster safety for employees working at public health centers and fire stations every year. However, there are many limitations in enhancing disaster preparedness capacity. For example, the Ministry only holds one annual ‘Multiple Casualty First Aid Training’ and ‘Comprehensive Emergency Rescue Training for Disaster Preparedness’ . In addiThis study is a methodological study to evaluate the adequacy of the developed protocol by verifying the validity of the contents of the expert group for the earthquake and fire response simulation protocol.The theme of this study is ‘Development and Validation of Earthquake Fire Response Simulation Protocol’. We recruited a protocol development team consisting of one emergency rescue professor, one counseling psychology professor, three paramedics, and one firefighter to evaluate the adequacy of the protocol content structure. The subjects of this study were students majoring in Health Programs. The simulation training in a team unit was composed of a group of five people. In the simulation operation method, this protocol takes about 20 min and consists of four stages: earthquake response, fire response, evacuation, and fire suppression. A protocol was constructed in which the simulation was run for about 20 min until the participant achieved the educational goal of each step. If the participants did not reach the educational goal after 20 min, the simulation protocol was set to end. The simulation process consisted of five students in the practice class suddenly feeling vibration, detecting objects shaking severely, and then recognizing an earthquake and hiding under a desk. At the same time, the protocol includes a fire that occurs due to an electric leak, causing an emergency. At this time, students should quickly evacuate to a safe place while protecting themselves, perform proper fire response, and implement fire suppression. We set out to prepare masks, telephones, and fire extinguishers to facilitate earthquake and fire response in this protocol. The preparation time consisted of 10 min of pre-briefing, 20 min of simulation, and 20 min of debriefing .Four experts verified the protocol developed in this study, including one firefighter, one industrial health manager, one hospital emergency responder, and one first aid instructor. In addition, this protocol included four steps referencing the Crisis Training Guideline  of the MThe content expert evaluation calculated the mean and standard deviation, and the validity of each item was confirmed using the CVR  proposed by Lawshe  to evaluThe purpose and process of the study were explained to 16 field experts, and they agreed to participate in the study voluntarily, and it was explained that they would not be disadvantaged by giving up halfway. In addition, the researcher directly explained that all matters recorded are computerized anonymously, so personal secrets are guaranteed. It was investigated anonymously for confidentiality and collected in sealed envelopes. K University’s IRB committee confirmed that it was not a study that actually applied or harmed the subjects due to the classification of the study, and it was confirmed that it would not require ethical approval. Therefore, it was excluded from IRB deliberation.The 16 experts who evaluated the relevance of the content filled out a questionnaire composed of 21 items on a Likert scale ranging from 0 points of ‘not at all appropriate’ to 4 points of ‘very appropriate’.The relevance of the contents of the expert’s checklist presented in this study ranged from the highest point of 4.00 (±0.00) to the lowest point of 3.25 (±1.29). The CVR values ranged from 0.500 to 1.000 and all exceeded the standard value of 0.49, confirming that there was no abnormality in content validity . After eThe final protocol developed in this study is an earthquake fire response simulation protocol, consisting of seismic response, fire response, evacuation, and fire suppression. Each protocol stage included a situation setting, learner activity, and learning performance goal . The firThis protocol consists of four stages . Within each stage are four steps for appropriate action measures and crisis response.In the earthquake response stage, these protocol settings require you to DROP where you are to your hands and knees before the earthquake knocks you down to keep you safe during an earthquake. Then, you should be able to cover your head, neck, and possibly your entire body under a sturdy desk or table. The context is consistent with the prior study  of perfoWe also highlighted the importance of emphasizing the initial response through simulation to cut off electricity and gas to reduce fire occurrence. Through these considerations, we believe that learners can complete the earthquake response protocol successfully. In this protocol, we set not only earthquake response but also fire response. Since the existing earthquake simulation emphasizes only earthquake response methods, it is a limitation that simulation settings accompanied by fire are rare. In a prior study , researcIn this study’s protocol, there are also four items in the third step. This protocol set is in line with the part mentioned in the previous study , where rThis study developed a protocol for applying the simulation of earthquake and fire response to health-related college students. First, because this protocol is for college students in health-related programs, the study’s limitation is that it did not cover all age groups. Therefore, researchers should develop protocols for the elderly and children. Second, as this study focused on the simulation of an actual earthquake and fire response, it did not deal with the psychological first aid part that helps individuals cope in disasters. As a result, future research will also need to develop education and protocol on psychological first aid that should accompany earthquake fires. Lastly, since disasters are sudden and unpredictable, it is considered to be very important to develop a protocol taking into account the disaster response ability, awareness, weather, and situation of the subject. In the future, it is hoped that the simulation protocol will be developed and applied by subdividing it into beginner, intermediate, and advanced courses in the future in consideration of students’ disaster response ability, awareness, weather, and building situation.This study developed an earthquake fire response simulation protocol and evaluated the protocol content suitability through expert evaluation. Our study had a total of four stages  and four steps in each stage. In this study, the validity of the simulation protocol was verified by 16 experts, and the CVR  value was found to exceed the reference point of 0.49 in all items, confirming that there was no problem in applying the protocol.The four-stage four-step model developed in this study includes simple, clear, and easy-to-follow protocols and contributes to providing basic data for the development of various earthquake disaster simulations.


Sustained implementation is required for evidence-based parenting programs to promote children and their families’ wellbeing at the societal level. Previous literature has examined the role of a range of different factors in enhancing sustainability. However, the inter-relationship between, and the relative importance of different factors remain largely unknown. The overall aim of this study is to identify predictors of sustained program use, the relative importance of factors, and potential mediation pathways.We surveyed 1202 practitioners who were trained in at least one variant of the Triple P-Positive Parenting Program, at least one and half years before data collection. The present data were linked with data collected during professional training. We first examined the independent effect of each factor on sustained program use, then, developed and evaluated a structural equation model of sustained program use.The structural equation model explained a considerable amount of variance in sustained program use, with seven positive predictors and one negative predictor identified. Organisational support was identified as a key facilitator, which was not only positively linked with other facilitators but also had an independent positive effect. Perceived usefulness of the program was the most important practitioner-level facilitator, which might be contributed by both research-based evidence and practice-based evidence. Practitioners’ self-regulation in program delivery impacted sustained use by influencing other factors such as perceived usefulness of the program.The findings provided insight into factors influencing the sustainability of evidence-based parenting programs which could be used to inform future implementation practice.The online version contains supplementary material available at 10.1007/s10488-022-01226-x. The use of evidence-based parenting programs has the potential to reduce the prevalence of mental health disorders in, promote the resilience for, and foster the healthy development of children Sanders, . At the Despite the benefits evidence-based parenting programs might have on child and parent wellbeing, only a small proportion of parents have participated in them globally  with about half trained for more than five years, and the majority identified as current users of Triple P (81.4%). Due to the impact of Covid-19, where lockdowns and restrictions interrupted regular service delivery, some practitioners who were categorised as a current user did not use the program in the last six months. About 23.3% of practitioners did not deliver any session in the last six months, 31.5% delivered one to five sessions, 24.6% delivered six to 19 sessions, and 20.5% delivered more than 20 sessions. For detailed information, please see Supplementary Material Table 1.To investigate sustained use of Triple P, trained practitioners were only included if they had started using the program within 6 months of being trained and had been trained at least one and a half years from the time of data collection. A total of 1202 practitioners who completed their Triple P training between 1997 and 2019 were included in the current study, with 91.3% identifying as female, 7.4% as male, 0.5% as a not listed gender-identity (0.8% did not provide gender information). Most practitioners were aged between 35 and 64 years (83.9%). Practitioners were mostly trained in the United States (34.9%), Canada (23.7%), Australia (19.3%), or the United Kingdom (16.5%). Mental health workers constituted 43.0% of practitioners, 19.6% were teachers/educators, 4.7% were allied health and correction services, 3.7% were medical personnel, and 28.6% did not fit in one of these listed work disciplines. Most practitioners (70.8%) had completed a bachelor’s degree or higher, with 26.7% of the remaining practitioners having completed some tertiary level study. On average, practitioners were trained for six years .Two aspects of sustained program use were measured, namely user status and frequency of use. User status was defined as a practitioner who had started using the program within the first 6 months post-training and who still considered themselves to be using the program currently. Practitioners who said yes to using Triple P within the first six months after training, were asked whether they had stopped using Triple P or not. User status was coded as a dichotomous variable where a practitioner who had not stopped using was coded as a current user (coded as 1) and a practitioner who had stopped using was coded as a stopped user (coded as 0). Frequency of use was measured with one question, “How confident are you in conducting parent consultations about child behaviour?” and “Do you feel adequately trained to conduct parent consultations about child behaviour?”. Responses to the two items were averaged to create a scale score, with higher score indicating higher self-efficacy. In the current study, the scale displayed good to excellent internal consistency .Practitioners’ current self-efficacy, as well as their self-efficacy pre-, post- and one-month-following training were assessed with the Practitioner Confidence subscale of the Parent Consultation Skills Checklist  to assess a wide range of factors that may potentially impact sustained program use. Items were mainly taken from previous Triple P implementation studies , value propensity , perceived usefulness , perceived interference , satisfaction with program features , and session management ability . The internal consistency of each subscale ranged from acceptable to excellent . All subscales were positively coded except for program interference and subscale totals were an average score of the items.For this study, we developed a 51-item questionnaire called the Facilitators and Barriers Checklist was tested first  to determine the number of latent factors to include in further Structural Equation Modelling (SEM) analysis to test a model of the relationships among study variables. In the preliminary analyses, we first examined the correlation between latent factors and frequency of use, and logistic regressions of each latent factor on user status. The hypothesised model of the latent factors was created based on theoretical considerations. When research gaps remain around certain factor, we occasionally consulted the correlation matrix between latent factors. A regression path was only established if it is theoretically justifiable and the correlation between two factors exceeded medium level (0.30 according to Cohen 2), the comparative fit index (CFI), the root-mean-squared error of approximation (RMSEA), and the Standardized Root Mean Squared Residual (SRMR) were used following guidelines for suggested cut-off values  = 17815.75, p < .001, suggested that the data was not missing completely at random. Separate variance t-tests suggested that the missingness of some variables was influenced by other variables within the study, indicating the data was missing at random  the other practitioner-related variables. Organisational support was expected to predict both current self-regulation and satisfaction with program features because practitioners are more likely to develop skills and be convinced by the program quality in supportive organisations. The direction of the prediction relationship between self-regulation and satisfaction with program features remained unclear. The remaining three factors, namely perceived usefulness, session management ability and value propensity were expected to be predicted by organisational support, self-regulation, and satisfaction with program features but not predicting other factors. This is because these three factors are independent surface-level factors that are influenced by higher level factors such as their self-regulation capacity in delivery. Perceived interference was not predicted by other factors. The direct paths between all factors and two sustained program use variables were examined. A hypothesised regression path would only be formed if the correlation between two factors exceeds 0.30. The hypothesised model is displayed in Supplementary Material.The hypothesised model was created after determining the factor structure of the Lavaan package in R Studio. The initial model did not fit well. After investigating the modification indices and checking the validation processes for the PSRS – Practitioner and the FBC, three covariations between similar items were added, one at a time . The modified model (Model C) fit the data adequately well, χ2(1301) = 6249.41, p < .001, CFI = 0.901, SRMR = 0.054, RMSEA = 0.054 [90%CI: 0.053-0.056]. All factor loadings were significant at p < .001 level and range from 0.35 to 0.91.The measurement model was evaluated first by allowing all latent factors to correlate with each other. We used MLR estimator in the Lavaan package in R Studio, which is the most appropriate estimation method for dichotomous variables  = 4632.31, p < .001, CFI = 0.871, SRMR = 0.054, RMSEA = 0.036 [90%CI: 0.035-0.037]. Given we used a different estimation method (WLSMV) to the measurement model evaluation and the validation process of other measures included, as demonstrated in Table 2(1243) = 2804.67, p < .001, CFI = 0.900, SRMR = 0.046, RMSEA = 0.033 [90%CI: 0.031-0.034]. The final model and all coefficients are displayed in Fig. Given one of the dependent variables (user status) was a dichotomous categorical variable, we used weighted least square mean and variance adjusted estimator (WLSMV) in the s Brown, . All pre, organisational support , and current self-regulation on sustained program use . Session management ability mediated the effects of satisfaction with program features , organisational support , and current self-regulation on user status . The relationship between organisational support and perceived usefulness of the program is mediated by satisfaction with program features , and current self-regulation .The mediation indirect effects were calculated for important pathways. Perceived usefulness partially mediated the effect of satisfaction with program features  on sustained program use  to develop collaborative partnerships with program purveyors to maintain their capacity at an optimal level . Given most previous research used single-site studies with relatively brief measurement periods (Shelton & Lee, Several limitations need to be mentioned. One primary limitation is the dependence on practitioners’ self-report data on all variables including the retrospective estimation of program use. Although using self-report measures is more feasible and practical for large-scale international studies, it is vulnerable to response bias, and has limits in presenting objective information about program use and organisational capacity. Future studies should include more objective measures of program use (e.g. case files, rebate records; for example, see Brookman-Frazee et al., This exploratory study sought to identify factors influencing the sustained program use of Triple P, and to investigate the relative importance of different factors and the relationships between factors. Three key findings were obtained. First, organisational support was found to be central to sustainability. It was not only positively associated with a range of other facilitators such as self-regulation and perceived usefulness but had independent facilitating effects on sustained program use above other factors. Second, practitioners’ perceived usefulness of the program was the most important practitioner level facilitator of sustained program use. Practitioners were more likely to use the program when they were convinced by both research-based and practice-based evidence. Third, self-regulation impacted sustained program use through influencing other factors such as perceived usefulness of the program. The self-regulation measure used in the current study could be considered as an alternative to evaluate training outcomes.Below is the link to the electronic supplementary material.Supplementary Material 1