Persons with schizophrenia frequently discontinue or avoid medications. Under a national community-based mental health program many places in China have started to provide free medications to people with severe mental health disorders in their communities. In the free medication program (FMP) in Liuyang, China, peripatetic psychiatrists prescribed and dispensed antipsychotic medications free of charge at regular intervals and places convenient for all patients through the primary health care system since 2006. Our study aims to test whether adherence to this FMP improves the functioning of people with schizophrenia.The research was conducted in Liuyang, a rural county in central China. Data were obtained from three sources: an ad-hoc survey and the program’s management system in 2013 and in-home interviews in 2014 in Liuyang. We conducted a cross-sectional propensity-score based analysis of the “dose” effect of FMP participation on their level of functioning, using medication refill adherence as a proxy for the participatory intensity in the program.Only 50.9% of 2,332 participants came for all refills in 2012. Higher refill adherence was associated with slightly worse functional outcomes. The main reasons for refill non-adherence were “unwilling to take medication or only took medication when unwell” (23.6%), “forgot or missed the appointment” (20.6%) and “hospitalized” (20.1%).The FMP program in Liuyang seemed to have successfully removed barriers in cost and access. However, better refill adherence was not associated with better functional outcomes in this study, which might have been the result of reverse causation. To improve the effectiveness of the FMP, patient-centered measures should be considered. With a worldwide prevalence of 1%, schizophrenia challenges families, communities and health systems and exemplifies the complexities posed by complex non-communicable diseases . MaintaiLiuyang is a rural county of Hunan province in China and has been one of the first 30 counties participants in the“686 Program”. Free Medication Program (FMP) has operated there since June 2006. Currently, the FMP support includes several streams of funds: “686 Program” from the central government supports program administration and training; regional funds are used to pay for medications and the Liuyang City civil affairs department pays for the travel expenses of medical teams that work through the county. The government of Liuyang has for long prioritized mental health work and has allocated substantial human, financial and organizational resources to this program. The experience in this area may well be useful for other places.We surveyed all patients with schizophrenia registered in Liuyang FMP. The aim was to examine the reasons that FMP participants did not refill their medications and to explore relationships between FMP and patient functioning. We hypothesized that a “dose-response” may exist in that the participants with higher program participatory intensity had better functional outcomes than those with lower program participatory intensity.Eighty-nine percent of Liuyang County’s 1.4 million residents live in 28 rural townships. The net income per capita was approximately USD 2,500 in 2012. In 2006, Liuyang integrated mental health service funding from central, provincial and municipal governments to launch FMP . The LiuThree sources of data were used. First, we retrieved the social-demographic information and collected information regarding their illnesses and treatments in 2012 including the medicine refill record, date of onset of the condition, date of diagnosis, relationship with the informant, hospitalization and outpatient attendance in 2011, medication adherence, duration of participation in the FMP, the frequencies of relapse requiring hospitalization from the FMP management system. The refill times were used as a proxy for the level of intensity of participating in FMP: out of the six required refills in 2011, attending at least five was regarded as “refill-adherent”. Second, the MHAs administered a brief survey to the key informants  of all FMP enrollees regarding their adherence and functional information in early 2013. The survey covered functional evaluation in three domains: employment, daily living and interpersonal relationships. The functional disability in each domain was rated on a 5-point scale ((1) Broadly similar to healthy individuals. (2) Slightly less functional than healthy individuals. (3) Half as functional as healthy individuals. (4) Less than half as functional as healthy individuals. (5) Basically not functional at all). The sum of the score of each domain (the least disabled score of 3 to the most disabled of 15) was used as an indicator of the overall functional capacity. Adherence to medication in the past 6 months and past 1 month was assessed as follows: (1) Complete adherence daily. (2) Adherence on most days. (3) Adherence half of the time approximately. (4) Less than half of the time. (5) Take almost no medication. Finally, we conducted household interviews in four randomly selected townships to assess medication refill history from 2011 to 2013 and reasons for missing refills in July 2013. We collected 199 responses out of 226 FMP participants. Informed consent for participating in the surveys was obtained from all participants.The four townships were randomly selected with the simple random sampling method. Once the townships were randomly selected, we found a total of 315 program enrollees. From 2011 to 2013, only 89 out of those 315 patients came for each of the scheduled refills for their medications. We made a home visit to each of the 226 people who missed some of their refills and succeeded in obtaining the reasons for their missing the refills from 199 people—27 of the 226 were not at home or declined our interview. All the instruments used in the study were self-development and implemented by our trained master degree public health students. Although those instruments were not validated, we consulted widely with various stakeholders and experts and piloted them in several sites before official fielding. The final form of the instruments was revised in accordance with the feedback we have received. The household interviews were conducted by the first author of this article and one trained master degree public health student.We first performed descriptive analyses. Then we compared the functional levels of FMP enrollees between the refill-adherent and non-adherent groups, using propensity score analysis: we first calculate a “propensity score” for each participant; and then conduct a regression analysis to examine the relationship between functioning and refill-adherence, with those propensity scores included as covariates to control for known confounders . The proAfter patients were assigned a propensity score, their functional outcomes were compared between the two groups of patients of different FMP participatory intensity but otherwise in the same quintile of propensity scores. Though unobserved characteristics were not captured by the propensity score, including the propensity scores in the analysis allowed us to make a fairer comparison of functions between the two sets to examine the hypothesis that with other things being equal, participants with higher program participatory intensity had better functional outcomes than those with lower program participatory intensity. STATA 12 was used for the analysis.n = 2,126), female mean of 8.12 ± 4.16  and male mean of 8.25 ± 4.16 (n = 877).The FMP covered 2,332 participants in 2012: the mean age was 42; 1,364 were women (of whom 78.0% were married) and 968 men (35.5% married). The level of education was generally low, with 54% of participants only having primary school education or below. 2,052 (87.9%) were farmers and 2,187 (93.8%) were receiving family care. Functional disability scores ranged from 3 to 15 , with anp = 0.015), after using propensity score to control for a range of potential confounders including socioeconomic and demographic variables, severity of disease and family support and engagement in care, the functioning score in the adherent group is 8.6 (95% CI [8.16–9.04]) (p < 0.001) and in the non-adherent group it is 7.7 (95% CI [7.26–8.22]) (p < 0.001).The group with higher refill-medication adherence had a small but statistically significant degree of poorer functioning as compared to its less adherent peer group in 2011  and better than many other places, including Beijing (46%) . The selSome practices in Liuyang may explain the relative strengths of the Liuyang program. First of all, the antipsychotics were offered for free to all program participants in Liuyang while only the people meeting certain conditions such as the poverty line received free medication in most other places. Second, Liuyang has been one of the earliest participants in the 686 Program and is likely to have accumulated more program experiences than other places. Lastly, the government of Liuyang has for long prioritized mental health work and has allocated more human, financial and organizational resources to the mental health program.We found that greater refill-adherence was not associated with better functioning in our sample. There are several plausible explanations: firstly, a higher refill adherence in those whose condition was more severe was not as unexpected as patients or their families may have been more keen to seek better control with medication. In other words, our observation was the result of reverse causation. As we do not collect information on baseline followed by follow up, this potential explanation cannot be confirmed or refuted. Also, getting a refill did not equate to taking the medication. While the FMP addressed barriers associated with cost and access, it did not overcome those “patient-centered” matters such as side effects that matter to the patient, the stigma associated with taking the medication and cognitive deficiency that leads to forgetfulness of taking medications.In the survey we conducted in the four counties, we found that the main reasons for refill non-adherence were “unwilling to take medication or only took medication when unwell” (23.6%), “forgot or missed the appointment” (20.6%) and “hospitalized” (20.1%). To improve the effectiveness of the FMP, efforts to modify the negative attitudes among some patients towards antipsychotic medications and to explain the benefits of medications would be useful. There is also good evidence that reminders may improve compliance . This maDespite its imperfection, this relatively low-cost community-based free medicine solution in Liuyang may provide an example in mental health for other low and middle-income countries. The program with free medication as its core has several features that may have significant implications for the countries with limited resources. First, the model of free medications provided by touring psychologists, nurses and the medication van on fixed dates and fixed locations near where people live may reduce access to care and medication. Second, the program is kept at low cost, with mostly inexpensive medications and the use of existing health system structures. Third, it is collaborative care among psychiatrists, MHAs, village doctors and the family members and patients with cascading tasks of care appropriate for each level. Finally, the way of program management and financing enables multi-agency  approaches to deal with severe mental disorders. Elements of the program can potentially be implemented in many other low and middle-income countries where human resources for mental health is scarce and medications are not easily accessible.Our study has several limitations. First, we use “dose-response” as a proxy for program effect, but the linkage between this proxy and the actual effect may not be definitively established. Second, even though we have used a propensity score to try to control for as many as possible potential and available confounders, we cannot control for unobservable and unavailable confounders. Third, as we surveyed a large sample, we used a simple question to assess patient function as complicated functional assessment was infeasible. Finally, due to limitations in our data, it is hard to examine the true association between the free medicine program and functioning in patients with schizophrenia in Liuyang.Free antipsychotic medications, routinely and conveniently delivered through the public health service to persons suffering schizophrenia, removed barriers related to cost and access. Medication refill was higher and hospitalization was lower compared to many other regions in China. However, better refill adherence alone was not associated with better functional outcomes in this study. Comprehensive approaches may be needed to address patient preferences, unwanted side effects, suboptimal treatments and other rehabilitative needs , 2019. L10.7717/peerj.8929/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.8929/supp-2Supplemental Information 2Click here for additional data file.


Treatment and prevention guidelines highlight the key role of health information and evidence-based psychosocial interventions for adolescent depression. Digital health technologies and psychoeducational interventions have been recommended to help engage young people and to provide accurate health information, enhance self-management skills, and promote social support. However, few digital psychoeducational interventions for adolescent depression have been robustly developed and evaluated in line with research guidance.We aimed to evaluate the feasibility, acceptability, and potential impact of a theory-informed, co-designed digital intervention program, MoodHwb.We used a mixed methods  approach to evaluate the program and the assessment process. Adolescents with or at elevated risk of depression and their parents and carers were recruited from mental health services, school counselors and nurses, and participants from a previous study. They completed a range of questionnaires before and after the program , and their Web usage was monitored. A subsample was also interviewed. A focus group was conducted with professionals from health, education, social, and youth services and charities. Interview and focus group transcripts were analyzed using thematic analysis with NVivo 10 .P<.001 for young people; 1.3, 95% CI 0.4 to 2.2; P=.006 for parents and carers).A total of 44 young people and 31 parents or carers were recruited, of which 36 (82%) young people and 21 (68%) parents or carers completed follow-up questionnaires. In all, 19 young people and 12 parents or carers were interviewed. Overall, 13 professionals from a range of disciplines participated in the focus group. The key themes from the interviews and groups related to the design features, sections and content, and integration and context of the program in the young person’s life. Overall, the participants found the intervention engaging, clear, user-friendly, and comprehensive, and stated that it could be integrated into existing services. Young people found the “Self help” section and “Mood monitor” particularly helpful. The findings provided initial support for the intervention program theory, for example, depression literacy improved after using the intervention (difference in mean literacy score: 1.7, 95% CI 0.8 to 2.6; Findings from this early stage evaluation suggest that MoodHwb and the assessment process were feasible and acceptable, and that the intervention has the potential to be helpful for young people, families and carers as an early intervention program in health, education, social, and youth services and charities. A randomized controlled trial is needed to further evaluate the digital program. Adolescent depression is common and is associated with social and educational impairments, deliberate self-harm, and suicide. It can also mark the beginning of long-term mental health difficulties . Early tGuidelines for the prevention and management of depression in young people ,6 stressFindings from a systematic review concluded that psychoeducational interventions were effective in improving the clinical course, treatment adherence, and psychosocial functioning of adults with depression . HoweverDigital health or electronic health  has been identified as a key area of future clinical practice and research in adolescent depression, especially to improve reach and access to therapies at relatively low cost ,12. TherHere, we describe an early stage evaluation of MoodHwb, a digital psychosocial intervention co-designed with, and for young people with, or at elevated risk of depression, and their families and carers ,22. The MoodHwb was designed to engage young people (and families and carers) by using developmentally appropriate language, illustrations, animations, and interactive components. It also aims to promote self help, help-seeking where appropriate, and social support. Although it was founded primarily on psychoeducation, it also includes elements of cognitive behavioral therapy, positive psychology, and interpersonal, family systems and behavioral change theories. It is multi-platform and is available as an app, which includes the interactive components and a mobile-friendly version of the main site.The program was co-designed using a series of interviews and focus groups with potential users: young people (with depressive symptoms or at high risk), parents, carers, and professionals from health, education, social, and youth services and charities. It was also informed by the systematic review noted earlier ; person-The program includes sections on mood and depression, possible reasons for low mood and depression, self-management , finding help, and other issues commonly experienced alongside depression  and for the parent, carer or another person concerned about a young person . The program and the design and development process are described further by Bevan Jones et al [MoodHwb is available in English and Welsh  approach was taken to assess the feasibility, acceptability, and potential effectiveness of the program. Data were collected from the following: (1) semistructured interviews with young people, parents and carers who used the intervention, (2) a focus group with professionals, (3) Web usage data, and (4) pre intervention and post intervention questionnaires.The Dyfed-Powys  and Cardiff University School of Medicine Research Ethics Committees gave a favorable opinion for the research project. Research and development approval was granted by Cwm Taf, Cardiff and Vale, Abertawe Bro Morgannwg, Aneurin Bevan, Hywel Dda, and Powys University Health Boards (UHBs), 6 of the 7 UHBs in Wales. The authors of the questionnaires were contacted where approval was required.We planned to approach around 40 young people, as this sample size was considered sufficient to allow assessment of acceptability and feasibility in a relatively broad sample of the target group. Young people were recruited from specialist Child and Adolescent Mental Health Services (CAMHS), primary mental health teams, school counselors and nurses, and from the Cardiff Early Prediction of Adolescent Depression (EPAD) study . IndividYoung people had to be at least 13 years of age, and to have either (1) a current or past history of depression or (2) be at elevated risk of depression due to a family history of recurrent depression in a parent. The parents and carers of these young people were also invited to take part. Participants were not eligible if they were unable to understand the intervention or questions/discussions .Professionals from health, education, social, and youth services and charities were approached if they worked with young people with mental health difficulties.Eligible young people were identified by their CAMHS and primary mental health practitioners and school counselors and nurses, and provided with letters and information sheets. Individuals from the EPAD study (who had consented to being contacted about other research) were sent a letter and information sheet inviting them to participate. Interested young people and their parents or carers sent a completed reply card to the study team, who then telephoned the young person and parent or carer to discuss the project further. Participants were given the choice of meeting the study team to discuss the project and complete the consent forms in person, or to do this via post. Signed consent was obtained from young people above the age of 16 years, and signed parent and guardian consent and child assent from those under 16 years. Professionals from the appropriate services were identified and sent a letter and information sheet, inviting them to participate, with a reply card as above.Consenting participants were provided a link to the program via email, and they created their own passwords. Parents and carers could create separate accounts to their children. Participants were informed that they could use the program as they wished (MoodHwb includes a section and animation to introduce the program to the user). Young people continued to attend sessions with their practitioner or counselor, if they were seeing someone. They were given access for a minimum of 2 months to allow them sufficient time to work through the program. Professionals were provided with a link to the program 2 weeks before their focus group.Young people were asked whether they would like to be interviewed alone or with a parent or carer. The parent or carer was also asked whether they would like to be interviewed separately. Interviews were held either at Cardiff University or a location convenient for the participant  and lasted up to 90 min. All interviews were completed by RBJ. The interviews were informal, and interviewees had access to MoodHwb on a mobile device.Adolescents were selected for interview based on their usage of MoodHwb , age, gender, service or charity involvement, and primary language . The range of characteristics and number of interviews completed ensured a broad spread of viewpoints.The group session was held at Cardiff University and was facilitated by RBJ and a colleague. The session lasted approximately 120 min. The program was projected on a screen during the group session. We aimed for a balance of professionals in terms of services and charities, gender, and primary language .The interviews and focus group were all audio recorded digitally and transcribed; participants could also write or draw their thoughts.Individual user interactions with the website were captured from bespoke analytics developed by the digital media company.Adolescent participants and their parents or carers were asked to complete questionnaires before and after having access to MoodHwb (after approximately 2 months). As with the consent forms, participants were given the choice of completing the questionnaires in person or via post (with phone or email support if required). Parents and carers completed questions about their child and about themselves.The main outcomes of the evaluation related to the feasibility and acceptability of the digital program and of the evaluation process. Secondary outcomes included the potential effect on mood, knowledge, attitudes, and behavior after using the program.The feasibility of the program was assessed in part through information on usage. This consisted of (1) Web data, including the number of visits to each section, language used on each visit (English/Welsh), and user pathway (for self or another person); and (2) self-reported questionnaire data, including the frequency of use, sections looked at the most often, language option chosen , average time spent on the site each time, and use with others . Participants were also asked about technical issues they experienced in the interviews and focus group.The acceptability of the program was assessed in the interviews, focus group, and feedback questionnaire. The interview topic guide covered (1) general views of the program, (2) specific strengths, (3) areas to develop further regarding the design and content of each section, and (4) integration into services and charities. The interviewing was iterative; where new themes emerged, they were incorporated into the subsequent interviews. The focus group discussion outline evolved from this guide.Assessment of the feasibility of the evaluation process included information related to the recruitment (number and range of participants) and retention of participants, as well as the completeness of data. Participants were also asked about the acceptability of the process in the interviews and via the pre intervention and post intervention questionnaires .Standardized questionnaires were used to explore changes in depression literacy and stigma, help-seeking behavior, self-efficacy, behavioral activation, depression and anxiety symptoms, and general behavior . Findings from the Shapiro-Wilk test did not show statistical evidence to suggest a deviation from normality for any of the reported outcomes. Mean differences and confidence intervals were presented for these analyses. When generating sum scores for the individual pre questionnaires and post questionnaires, missing values were replaced with the mean value for that individual, provided there was less than 10% of missing data. All analyses were conducted using Stata statistical software .Quantitative data from the questionnaires and Web usage were analyzed and presented descriptively with summary statistics . Paired sample The characteristics of participating young people are presented in Descriptive information about interview and focus group participants is provided in Analytics from the digital company revealed that the most common section accessed by young people, parents and carers was “What are mood and depression?” . The other sections were accessed approximately half as often (range 12%-17%). Overall, 16% of usage was in Welsh and 84% was in English. Most participants used the program for themselves (78% of use) and 22% for another person.The questionnaire findings on usage are presented in Both groups reported looking the most at the “Self help,” “What are mood and depression?,” and “Possible reasons” sections. Young people also reported they looked at the “Mood monitor,” and parents and carers looked at the “Families, carers, friends, professionals” section.There were some difficulties related to the compatibility of the program with certain devices and operating systems, especially NHS computers. Some experienced difficulties with internet access at home or on mobile devices.The overarching themes in the interviews and later in the focus group were as follows: (1) design features, (2) sections and content, and (3) integration and context. These themes were influenced by the primary issues the research team wished to explore, to help refine the content and design of MoodHwb. The overall feedback from participants is presented later, with verbatim examples listed in In general, all interview and focus group participants made favorable comments about MoodHwb and stated that it seemed helpful for young people, families and carers. Some noted they were surprised by the high quality, and that they had reservations about it previously because it might be “academic,” “dry,” or “overwhelming.” Most found the overall design attractive, and more interesting and appropriate than designs for existing resources (quote 1).Overall, participants felt that the program was clearly and consistently structured, easily navigated and user-friendly. They noted that the design and layout made it easy to identify what was relevant. Participants found the color coding, progress bar see , and quiNearly all praised the mix of rating scales (and corresponding face icons) and multiple-choice questions at the start of the program , particularly for their functionality, ease of use, and “fun” element. Some noted that this was their favorite aspect (quote 3). Several professionals approved the message for the user to seek help, if they indicated they had thoughts of self-harm.Some young people had used this to add songs and images, and felt that it helped to personalize the program. However, others had not done so, because they already bookmarked sites they found interesting.Most found “My goals” to be helpful and motivating. They liked how it was possible to add the number of activities, and to note when they were completed (quote 4).A few noted that their use of these interactive elements phased out over time, and that reminders and rewards might increase engagement. They also noted these components could be explained and personalized further.“My profile” was described as helpful, particularly to group together strengths and difficulties and save links to resources. Professionals noted that this section helped users to reflect on and add perspective to their situation (quote 5).Young people, parents and carers described the illustrations and animations as “friendly” and “sophisticated” without being “patronizing.” The characters were designed to appeal to a diverse audience, with abstract minimal features. All young people stated they preferred the illustrative approach to a more photographic one (quote 6).In summary, participants, in particular young people, gave favorable feedback on the design features, including the overall presentation, structure, and interactive and graphic elements. They also suggested the areas to develop further, including the navigation, personalized components, interactive and audiovisual elements, reminders, and rewards, and “native app.”On the whole, participants agreed that the language used was accessible, simple, and jargon-free, but “not too dumbed down.” Many approved of the general tone, stating it was “sensitive” and “affirming” (quote 7).In general, participants were pleased with the content, and found it comprehensive. They liked the flow of information, and how text was broken up , “bite size,” and “short and snappy.”Professionals praised the “extensive,” “authoritative,” and “reliable” information. There were mixed views regarding the amount of text—some felt there was too much, others that it was appropriate (quote 8).All participants made favorable comments about the personal stories, and how they were from a range of perspectives (quote 9). Young people, parents, carers, and a small number of the professionals suggested adding stories from “celebrities,” and including photos, animations, videos, or comic strips.Participants approved of the information on the difference between sadness and depression, how to identify difficulties and associated metaphors (quote 10). Some noted that those with depression might be reluctant to engage with the subject matter (quote 11).Professionals were particularly pleased with this “exploratory” section , and some asked for more self help approaches in specific situations. Professionals approved of the description of services and professionals , and of Most noted that the information was important and comprehensive, particularly on anxiety, eating and weight issues, and physical health. However, a few asked for more specific information , while others were concerned that some users might worry unnecessarily (quote 14).Parents, carers, and professionals praised the “holistic” and “systemic” approach and highlighted the parental mental health subsection (quote 15). Some suggested adding more information on how to talk to a family member or friend (quote 16).Generally, participants approved of most aspects of the content, including the language, tone, personal stories, and the individual sections of the program. Areas to improve upon related to the specific information and amount of text in general.Most participants  thought that MoodHwb would be engaging and helpful for anyone who was interested in learning more about mood and depression (quote 17). Some of those who had not experienced depressive difficulties (from the EPAD study) did not think the program was as relevant to them, while some of those who had completed CAMHS therapy sessions already knew much of the information included in the program. On the whole, participants concluded that MoodHwb was especially appropriate for those starting to experience difficulties. Some stated that the program could help counteract stigma and making it freely available would help with this.Most young people had separate user accounts to their parents and carers; some suggested adding the option to monitor someone else’s mood and share information. Participants felt that the program could help with communication between young people and their family, carers and friends (quote 18).Many felt that MoodHwb could be used in schools, particularly personal, social and health education lessons – and suggested including a “teacher area” within the program. The school-based professionals stated that it could address the “big gap” in resources and training for teachers. However, some young people noted that associating it with schools might make it less appealing.Some noted that the use of MoodHwb could complement existing services, for example, by allowing young people to reflect on their entries with counselors, General Practitioners, and primary mental health and specialist CAMHS practitioners (quote 19).All health care professionals felt that the intervention could be used at their workplace—especially at the school and primary care level. Some noted that it could be helpful for those no longer in services, waiting for an appointment or who did not meet the criteria for mental health services. An educational psychologist noted that the digital program would be relevant for children in care, especially as “they’re moving around a lot” (quote 20).Many professionals highlighted the challenge of keeping the program up to date. One psychiatrist advised that many professionals were not IT-literate and might be reluctant to recommend it.In summary, most participants felt that all young people, families and carers should have access to MoodHwb, and it would be especially helpful as an early intervention in a range of settings for those who were starting to experience difficulties.Overall, young people reported that the program was helpful, especially with finding ways to help themselves . When asFindings were similar for parents and carers; they felt that the young person found it helpful overall and selected “Self help”  and the “Mood monitor”  as the most useful for the young person. Overall parents and carers found the program helpful for themselves . The secOverall, young people, parents, and carers felt that the amount of information included in each section was adequate . Both grDuring the interviews, young people stated they were able to discuss the program openly and appreciated that they could choose the location, and whether they were seen with their parents or carers. They found it helpful to be able to navigate through the program as it was discussed.Data on acceptability of questionnaires were available for 43 young people and 30 parents or carers at baseline, and 34 young people and 19 parents or carers at follow-up. Most felt the number of questions was “about right.” Young people at follow-up were more likely to rate the questionnaires as having a “few too many questions” than at baseline, possibly due to the additional burden of the feedback questions.Levels of depression literacy were higher after using the program . Although the differences were small, several other scores also improved, particularly regarding self-efficacy and depressive symptoms.Parents’ and carers’ own depression literacy improved after using the program . Parent-rated scores of their children’s mood and behavior were similar or slightly worse after using the intervention. Overall, parent-rated scores of their child’s depression, anxiety, and behavior were lower than children’s self-rated scores.We aimed to conduct an early-stage evaluation of a novel digital psychosocial intervention for adolescent depression and to assess the feasibility and acceptability of the assessment process that will be used in a future trial.Most participants noted that the program was engaging, clear, easy to navigate, and well structured, and praised the graphic and animated approach. The content was described as comprehensive, motivational, holistic, and accessible to young people—and also relevant to families, carers and professionals in a range of services. Young people found it easier to use overall and were better able to understand the design elements, although parents, carers and professionals found it acceptable.Nearly all who completed the follow-up used the program, with most young people using it alone and for at least half an hour at a time over the course of the study (minimum of 2 months), which is favorable in terms of adherence in eHealth . ParticiThere were reports of improved depression literacy, self-efficacy , and depressive symptoms—giving preliminary support for the intervention program theory . There wThese results were consistent with a recent systematic review of psychoeducational interventions in adolescent depression , which fMoodHwb might be particularly helpful when a young person starts to experience difficulties and first presents to services—for example to school counseling or nursing, primary care/mental health, youth, or social services. However, given that the majority of young people with depression do not access services , digitalThis evaluation will be used to inform the refinement of MoodHwb, with the aim of improving the user engagement with it. The suggestions for improvement made by participants were discussed with the digital media company and research team. The issues were prioritized according to the level of importance given to them by the participants, and whether they would improve the acceptability, feasibility, and ease of use of the program. Other considerations were the program aims, underlying theory and evidence, technical difficulty, and time, resources, and funds required to make the changes.The main revisions considered included improving the navigation and audiovisual/interactive elements, making it more personalized, developing the app version of the program, and expanding the self help and anxiety sections . Ahead oOne of the main strengths of the project relates to the rigorous mixed methodology, which followed guidance for complex interventions  for bothAnother strength was the diverse range of participants from recruitment centers in urban and rural areas, including in areas with several ethnicities and areas of deprivation. Efforts were made to engage young people, families, and carers by offering to see them where convenient. There was also contact afterwards to promote retention and adherence . The recruitment target of 40 young people was met, and there was a good retention rate (82% of young people). The digital media team was available to address technical issues during the study.The research and digital media teams were involved throughout the project, and it is possible that their personal views could have influenced the development and evaluation process. Considering the number of centers visited, only a small number of potential participants were referred, which may have led to a biased sample. Several of those who initially showed interest did not go on to participate, and often no reason was given. This might reflect the difficulty in engaging young people in mental health research, or that the program might be more useful for certain subgroups or contexts. More females than males participated, although this might reflect in part that depression is more common in females in adolescence .Participants might have reported more favorable responses because they were seen by, or in regular contact with, the researchers. Some had participated in the development phase, which may have influenced their opinion of the program . Outcomes were assessed via self-report and response bias could be an issue, for example, where participants provide socially desirable answers. Young people might have been less likely to give candid responses in the presence of parents or carers, although they were given the option of being seen alone.The results of the questionnaires must be interpreted with caution given the small sample size and limited power. It would have been interesting to explore how factors  might have influenced the results; however, the exploration of subgroups was not feasible given the sample size. It is also possible that some of those whose symptoms or behavior improved may have done so in any case over time, or due to other interventions or factors.This early mixed methods evaluation found that the co-designed prototype of MoodHwb and assessment process were feasible and acceptable. The findings will be used to refine the intervention and inform the design of a randomized controlled trial . If prov


Currently, there is limited knowledge on the impact of father-only sessions or parenting programs supporting impending fatherhood. This research explored an antenatal dads program aimed at fathers to assess the benefits of such interventions.Literature regarding parenting programs and early childhood education initiatives, especially those aimed at children and families in disadvantaged circumstance, have been demonstrated to act as a buffer to poorer health and lifestyle outcomes in later life.A qualitative research approach was used to explore the experiences of 16 fathers and 6 staff of a community-based parenting program with sessions focusing on fatherhood.Four main themes were identified from the data regarding the experiences of groups engaged with the Antenatal Dads and First Year Families program. The first theme ‘Knowledge and Capacity Building’ stated that the information provided in the program helped fathers to be better informed and prepared for their impending fatherhood. The second theme was ‘Mental Health Awareness’ and identified the importance of raising awareness of depression and suicide in fathers, including where and how to get help. The third theme was ‘Soft-Entry’ and highlighted how the attendance at one service helped participants to learn about additional services through word of mouth and targeted promotion. The final theme was ‘Feeling Connected’, which helped fathers to feel more connected with the process of childbirth and development including playing and engaging with their children. Overall, the fathers found that the male-only sessions assisted them by supporting frank discussions on fatherhood. Additionally, the study helped identify the advantages of fathers meeting other fathers through attendance in the program, or even other couples in similar situations that helped fathers to feel less lonely regarding their situation. The SDH acknowledge that the social, socio-economic and political conditions in which a person lives, works, learns and grows can impact a person’s health , despite fathers reporting that they wanted to be more involved , and improves longer term childhood outcomes  initiative in 2004 (Muir ‘Bringing Up Great Kids’ (BUGK) which focuses on the subjects of attachment narratives and mindfulness training. Hunter and Meredith  review oet al., ‘Hey Dad!’ an Indigenous specific program designed to build confidence in parenting and communication skills between Indigenous men and their children , birthing, cognitive and linguistic development of infants and communication with spouse/partners. The First Year Families program acts as a follow-up program to explore the needs and concerns of fathers in their first year of fatherhood.et al., et al., et al., et al., The program also aids fathers to access other services through the identification of individual needs and referrals to relevant agencies within the broader community service sector. However, as acknowledged, significant barriers have existed previously that impact on a father’s ability to participate in services, meaning literature regarding the impact, success or value of such programs is limited  experienced in the design, delivery and evaluation of health in the areas that include acute care, community setting, community parenting and child intervention programs. Fathers then self-selected to participate by contacting the research team to express their interest. This approach reduced coercion and helped ensure that program staff were unaware of those fathers who agreed to participate, which improved anonymity for participating fathers. Of the potential 29 fathers contacted, 16 volunteered to participate. Program facilitators  were contacted via email with a letter of recruitment and a request to participate in the research. Program facilitators self-selected to participate by contacting the research team. The inclusion of program facilitators drew on a purposeful sampling approach as they were able to provide a different perspective of the same shared phenomena (the dad’s experience of the program) that helped give depth to the data Patton, .the type of program;the usefulness of the program;the impact of the program on other aspects of the participants lives ;implications for changes;impact on health .Data were collected through two means including interviews and focus groups with providers, staff and parents. Interviews and focus groups drew on the same open question guide for continuity of results. The open question guide was devised from the reviewed literature and with consideration of the Antenatal Dads program framework that draws from the evidence-based programs outlined in the introduction. Additionally, a reference group consisting of members who delivered CfC programs assessed and offered advice on the open question guide, which included discussion on:The initial data collection took place in the Murraylands region of rural South Australia in 2016. In total, 16 fathers and 6 service provider staff took part in the research. Table et al., Fathers were asked if they preferred to participate in a one-on-one interview or focus group. Written consent was gained before each interview and focus group from each participant. Two members of the research team collected the interview and focus group data (R1 and R2), two members conducted data analysis and coding together (R1 and R3), R2 conducted analysis and coding separately. The interviews ranged from 45 to 120 min in length, and the focus groups lasted up to 240 min in length. The recordings were transcribed verbatim by a third-party transcription service that has a confidentiality agreement with Flinders University, and pseudonyms were assigned to participants during the transcription phase to help maintain confidentiality. All participants were offered the opportunity to review their transcript, except those participants in the focus group, which was explained to the focus group participants via the letter of recruitment and prior to their involvement ; the first step involved reading the transcripts in full and noting participants’ responses of interest in text. This process was repeated and similar ideas were grouped together. This method of analysis is described by Patton  as inducEthical approval was provided by Flinders University’s Social and Behavioural Research Ethics Committee, project number 6719. Additional endorsements for the project were provided by the facilitating partner ac.care Communities for Children Murraylands.Four main themes were identified from the data regarding the experiences of groups engaged with the Antenatal Dads and First Year Families program. The first theme was ‘Knowledge and Capacity Building’ and explored the father’s positive response to the information and services provided. The second theme was ‘Mental Health Awareness’, which identified the importance of raising awareness and early intervention regarding mental health as well as addressing how and where to get help. The third theme was ‘Soft-Entry’, which discussed how attendance at one service helped participants to learn about additional services through ‘word of mouth’ and targeted promotion. The final theme was ‘Feeling Connected’, which discussed how the program helped fathers to feel more connected with the process of child birth and with people sharing a similar situation to their own.In many instances, there were positive comments about the comprehensive nature of the information provided during the program, and how this information helped to raise awareness within the fathers. This increased awareness in turn was identified by staff as helping otherwise ‘at risk’ fathers to build their capacity regarding  their impending fatherhood. This raised awareness also indirectly helps build capacity for both the mother and the child by having the support of the engaged father to draw on.The antenatal program we talk about attachment theory, the importance of fathering, and the bonding that occurs. I hand around a model of an infant’s brain, 400 grams and then a 3 year old at 1200 grams. The dads are shocked at the growth. We give them [dads] an understanding of the importance of talking to by even in utero. They go on to talk about how they were fathered and their relationship with their fathers and how it needs to be different now. (D7)Educating fathers on topics such as infants, parenting and having them reflect on their own childhood and the need to address deficits experienced when fathered by their fathers, helped fathers to better ‘understand’ and ‘attach to’ their infants/children. Participant D2 noted the sections of the education that stood out for them and of the impact this knowledge had:We talked about all sorts of things…skin to skin contact for dad and baby, looking into baby’s eyes, breast feeding. It’s very good for us dads so we know, we can help. So much information it was really good. I felt comfortable asking questions. I feel I know a lot more now…you know what to expect. (D2)Staff member C1 noted that the ‘program is unique, it focuses on the Dads and really gets them engaged into being a father’ and provided an example for why this was important as ‘The dads are often “at risk”, so they’re young, Indigenous, or poor, or CALD backgrounds and frankly without this program their kids would be at risk of removal’.One staff member provided an example of the programs content:This comment highlights how the program indirectly helps to build capacity around the child by helping dads to engage with their child. Capacity building was also noted by fathers who discussed being connected to additional services if required (discussed in theme 3) or being made aware of other services that may help. This capacity raising is important as most fathers discussed their isolation from other families and services and how their participation in the program provided a means for them to connect back to the community.You don’t think about it much in dads. You think about it in the mums all the hormones and everything. It really opened my eyes and gave me lots to think about, you know how I could get help and stuff. They talk about that too all the help that’s out there. (D1)We went through male depression…I was surprised that men get it too…extra information about where to go and to help us cope. All the information on depression, suicide in fathers all helps and the information on baby and mum helps me worry less. It was good to talk about these things [depression and suicide] without the women being present. (D4)Participant D2 also picked up on D1 and D4 points regarding the importance of the program’s education on how and where to gain help, but also noted the importance of early intervention:We need to know where to go to get help [for mental health issues] the Antenatal Dads stuff lets you know what to do and where to get help. You can bring stuff out in the open…get help early. Yes, the early warning signs…who to contact and that. (D2)Also, of note in the above comments was D4’s remark on the importance (to him) of being able to discuss the sensitive subject of mental health and suicide without women present, which suggests in a mixed or partnered format, D4 may have remained quiet.The topics of mental health and suicide were actively discussed in the Antenatal Dads and First Year Families program. Fathers noted being impressed by the manner in which ‘sensitive topics such as depression and suicide were addressed’. The prevalence of mental health issues for young fathers in a rural community surprised some participants as D1 and D4 state:We’ve had four suicides here recently…all within six months and I knew them all so I already feel down in the dumps…we talked about going to the doctor and stuff or talk to someone. I’ve seen it with them they all hold it in…it has a roll on effect…having more knowledge and knowing what to expect helps you deal with it [depression]. (D5)All fathers interviewed appeared to know the fathers who had committed suicide and the impact it had on their surviving spouses and children, which also seemed to re-enforce the importance of knowledge on the topic, and of how to get help. This point was well summed up by participant D3 who stated:It was a bit confronting when they [the fatherhood worker] started talking about it [depression and suicide]. Oh shit you know- but it’s for the best. It might be confronting to start off with but it is for the best. I know what to look for and how to get help now. (D3)Staff were also aware of the recent suicides in the area as C1 noted:We have had some suicides lately in the community, it’s tough in a rural community and it is stressful having a child. The Antenatal Dads has really helped with all the mental health stuff. The dads and families are much happier and more confident afterwards. You can see the difference. (C1)This change in outlook for those attending the antenatal dads program was also noted in participant data, for example, D5 notes:I feel supported here. Its ok to talk about all sorts of stuff and the other men feel the same. You can talk about anything. We have made friends with other couples who are having the baby at the same time. I didn’t realise how I was worried, like really worried about what was going to happen. I don’t feel so alone you know worried. (D5)This opportunity to openly discuss sensitive topics was expressed as a relief for the fathers interviewed who, as noted above, may not have otherwise talked in depth on the topic.Critical incidents, such as suicide and depression, can have powerful impacts on small rural communities. The pertinences of a discussion about suicide within a young rural male cohort who were also socially disadvantaged were made sadly clear when participant D5 noted:At the Antenatal Dads and First Year Families program I tell the dads about all the other programs they can access in the community. How they can go along…they don’t need a referral. They can attend. We are here to help each other…it’s a way of getting them connected to other services as well. (S1)A lot of the dads have had no experience with infants and children…they don’t know what to do…some are young parents too and their infants can be neglected so it’s a good way to connect early and let them talk to the other dads and support each other. Antenatal Dads and First Year Families program lets them hear about other services they [fathers] can use…gives them confidence to use other services…helps them connect to other fathers and families. (S2)The soft entry approach helps increase supports around the father by increasing their knowledge of the aid that is available to them, as explained by S1:We use the Antenatal Dads and First Year Families program as a way of connecting clients with other services …providing those wrap around services. So the family support worker would provide case management, therapeutic support but also offer referrals to other agencies. (S1)Interview data from the fathers helped understand the importance of this approach as fathers were either unaware of the service within the local area that were available to them, or of the ease with which those services could be accessed. As D3 relates:You know, I came here and I didn’t realise just how many services we have in Murray Bridge. I never knew we could get so much help. You don’t need to go anyway to get a referral you can attend here it much easier…the other services you can go to don’t need referrals either. Referrals are such a hassle when you’ve got work, home and everything. (D3)The concept of ‘soft entry’ initiatives is important as it helps connect services to disadvantaged and isolated families, and helps integrate these families and their children into the health, education and social systems provided by, or linked to these services.The staff and fathers attending the program highlighted the importance of the ‘soft entry’ approach where attendance at one service helps people identify other services through word of mouth or through direct promotion by program staff. An example of the soft entry approach, and its importance to disadvantaged families, is explained by S1 and S2 as:I know to talk to baby, you know, while it’s in my wife’s tummy…I didn’t know that was important…it has helped me feel connected. I didn’t feel that before…I didn’t know about what was happening inside my wife and how the baby can hear. I know what to do now. You can read to baby right from the beginning you don’t need to wait. (D5)Throughout the results are the examples of fathers discussing how the knowledge gained from the program had helped them to feel less worried. For example, D2 noted how his stress had been reduced due to participation in the program:I stress a bit and if I don’t know then it’s hard, now I know what to expect, [attendance was] most definitely worthwhile. (D2)Participants also spoke of making connections with other fathers (and even other couples who were expecting) that, without attendance at the program, would not have occurred. For example, D3 states:[the program staff member] puts you in the middle [of the group] and talks about what’s around…how you connect and talk to others…other dads. You feel connected…I talk to other dads there and that wouldn’t happen without this program. (D3)As D5 notes in theme 2, the connection that developed with other fathers through attendance at the Antenatal Dads and First Year Families’ program helped participants feel more connected and hence, less alone.The program provides fathers with age appropriate information about child development. This helped fathers to understand notions like why talking to their children while in utero was important to the child development, as the child was able to hear them and develop a bond with their voice. It also had the unintended side effect of having fathers feel more connected to their children, as explained by D5:et al.’s  re-engage with parenthood, is there a universal message that can be applied across programs? Or is it better to tailor material to the intended group? This also includes a consideration of the referrals to on-services that are recommended to fathers.Demographic information about the fathers who took part in the research was restricted due to ethical concerns regarding their vulnerable status  as well as confidentiality concerns as all participants lived in the same rural area. Moreover, there was a general reluctance in participants to share demographic data; hence, additional information regarding the cohort cannot be given. While acting to protect those who took part in the research, it is an acknowledged limitation as it inhibits the generalisability of the study. Furthermore, being a qualitative study with a small sample, limited to participants sourced from one geographical location means that the results cannot be confidently generalised to larger populations. However, the study does provide useful insight into father’s experiences of parenting classes, in disadvantaged cohorts, which is limited within the current literature. Finally, the data collection was conducted by female members of the research team only, and this does indicate a gender bias in the analysis. However, the fathers did state that they were happy to participate with data collected by an all-female team.The success of the Antenatal Dads and First Year Families program is reflected in the positive attitudes of fathers involved as discussed within the themes section presented above. This should hopefully provide motivation to service provider to consider male-only antenatal and/parenting classes. However, the best format for these classes, their implementation, and how to engage more men from disadvantaged groups still needs further investigation. It is encouraging to note that fathers, through engagement with the program, developed further social and support networks that positively assist their development as fathers. This, as well as linking fathers  to other community services, will further help these families to combat the SDH going forward.


Additionally, focal mechanism solutions of the main Mw 6.5 and its biggest triggered aftershock Mw 5.2 events were acquired. Such datasets could provide a basis for further seismology analysis, including seismic tomography, source mechanism analysis, and further seismic hazard analysis in the Ambon and Seram islands. This paper and its dataset are a companion for a published article in the Tectonophysics under the title “Source Mechanism and Triggered Large Aftershocks of the Mw 6.5 Ambon, Indonesia Earthquake” This article presents earthquake catalogs of the 2019 Ambon aftershocks compiled from regional the Agency for Meteorology, Climatology, and Geophysics of Indonesia (BMKG) and local seismic networks deployed in  The second sheet includes the velocity model used in locating the aftershocks in The first dataset contains station coordinates and velocity model for determining the hypocenter location of 2019 Ambon aftershocks. This is a Microsoft Excel worksheet consisting of two sheets. The first sheet contains the coordinates of the eleven local seismographic stations used for monitoring the 2019 Ambon aftershocks A: YEAR; B: MONTH; C: DAY: date type variables indicating the date for each earthquake.D: HOUR; E: MINUTE; F: SECOND: date type variables indicating the time for each earthquake.G: LONGITUDE; H: LATITUDE: double type variables  indicating the location (longitude and latitude) for each event.I: DEPTH: double type variable  indicating the depth of each individual earthquake.J: MAGNITUDE: double type variables indicating the reported magnitudes  for the included earthquakes. The type of the magnitude is ML  for regional BMKG catalog K,L,M: UNCERTAINTY: double type variables indicating the calculated uncertainty  for each event. This information is only available for aftershock catalog determined using local seismic network The second Microsoft Excel file in the Mendeley Data repository includes earthquake catalogs of 2019 Ambon aftershocks. The files contain a total of 1009 and 1764 earthquakes taken from BMKG catalog A–I: similar with the format of the aftershock catalog mentioned earlier.J: MAGNITUDE: double type variable  indicating the final considered moment magnitude for each earthquake included.K: Strike 1; L: Dip 1; M: Rake 1; N: Strike 2; O: Dip 2; P: Rake 2: these columns represent the two nodal planes for the focal mechanism solution for each earthquake; each column contains a number for each mentioned individual parameter .Q: SOURCE: string variables indicating the source of the focal solutions.The third file in the repository is the focal mechanism of the 2019 Ambon aftershock main event and its biggest M 5.2 triggered event. The focal solutions of the main M 6.5 event were taken from Global CMT http://ds.iris.edu/ds/nodes/dmc) under the network codes II, IU, G, IC, dan RM. This file consists of two tables, i.e. represent each focal solution plane. Each table consists of four columns: X and Y location, seismic moments, and rake of each node. The header describes the reference point (X=0 km and Y=0 km) used in the inversion scheme.The fourth Microsoft Excel file is the slip model of the main 2019 Ambon earthquake derived using teleseismic data. The teleseismic dataset of the M 6.5 event was gathered from the Incorporated Research Institutions for Seismology (IRIS) Data Management Center (DMC) (2o and 128.60o and latitudes between −3.70o and −3.30o and occurred between October 18th to December 15th, 2019 were considered during the dataset compilation. During this monitoring period, 1009 and 1764 events were compiled from the BMKG 2019 Ambon aftershocks located in the spatial region spanning longitudes between 128.15Focal mechanism solutions of the 2019 Ambon main event and its largest M 5.2 triggered event were obtained from gCMT The related article has been submitted to the Tectonophysics under the title “Source Mechanism and Triggered Large Aftershocks of the Mw 6.5 Ambon, Indonesia Earthquake”.DPS, ADN, AM, AAR and SR: Conceptualization, Methodology, Software; ZZ, SW, NTP and AP: Writing-Original draft preparation; AL, DK, AA, YH and AWB: Visualization, Software and Validation; HAS: Software, Slip Model.The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article.


The web-based BeUpstanding Champion Toolkit was developed to support work teams in addressing the emergent work health and safety issue of excessive sitting. It provides a step-by-step guide and associated resources that equip a workplace representative—the champion—to adopt and deliver the 8-week intervention program (BeUpstanding) to their work team. The evidence-informed program is designed to raise awareness of the benefits of sitting less and moving more, build a supportive culture for change, and encourage staff to take action to achieve this change. Work teams collectively choose the strategies they want to implement and promote to stand up, sit less, and move more, with this bespoke and participative approach ensuring the strategies are aligned with the team’s needs and existing culture. BeUpstanding has been iteratively developed and optimized through a multiphase process to ensure that it is fit for purpose for wide-scale implementation.The study aimed to describe the current version of BeUpstanding, and the methods and protocol for a national implementation trial.The trial will be conducted in collaboration with five Australian workplace health and safety policy and practice partners. Desk-based work teams from a variety of industries will be recruited from across Australia via partner-led referral pathways. Recruitment will target sectors  that are of priority to the policy and practice partners. A minimum of 50 work teams will be recruited per priority sector with a minimum of 10,000 employees exposed to the program. A single-arm, repeated-measures design will assess the short-term (end of program) and long-term (9 months postprogram) impacts. Data will be collected on the web via surveys and toolkit analytics and by the research team via telephone calls with champions. The Reach, Effectiveness, Adoption, Implementation, and Maintenance Framework will guide the evaluation, with assessment of the adoption/reach of the program (the number and characteristics of work teams and participating staff), program implementation (completion by the champion of core program components), effectiveness , and maintenance (sustainability of changes). There will be an economic evaluation of the costs and outcomes of scaling up to national implementation, including intervention affordability and sustainability.The study received funding in June 2018 and the original protocol was approved by institutional review board on January 9, 2017, with national implementation trial consent and protocol amendment approved March 12, 2019. The trial started on June 12, 2019, with 48 teams recruited as of December 2019.The implementation and multimethod evaluation of BeUpstanding will provide the practice-based evidence needed for informing the potential broader dissemination of the program.Australian New Zealand Clinical Trials Registry ACTRN12617000682347; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372843&isReview=true.DERR1-10.2196/15756 Only vesit less .Sitting time can be strongly contextually driven, dictated by the environmental and social settings in which it occurs . For manWithin this context, the Stand Up Australia collaborative research program was developed . Its aimtrain-the-champion approach was used as workplace champions have been shown to be critical to the success of workplace interventions, acting as role models and drivers for staff participation and work team change [The no-cost, web-based BeUpstanding Champion Toolkit  providesm change -32. ThisThe translation of what has been learned from the Stand Up Australia intervention trials to the BeUpstanding program has involved multiple, iterative phases . These pPlan, Do, and Review). The low cost/no cost requirement also meant that sit-stand workstations, which have been shown to effectively reduce workplace sitting (particularly when part of a multicomponent approach) [Phase 1, described in detail elsewhere , involvepproach) , are notPhase 2 involved a quantitative and qualitative evaluation of a small-scale pilot of the beta (test) version of the toolkit . Seven tThe learnings from phase 2 then informed the optimization of the toolkit (phase 3) to ensure it was fit for purpose for an implementation trial. Phase 3 included the development of a web-based, user-friendly onboarding system (to both promote the toolkit and enable champions to sign up for the toolkit) using human-centered design principles , enhancesoft launch of the program, with over 100 champions enrolling in the program during this period (September 2017 to May 2019). Several key learnings were gained from these early adopters. Firstly, despite the minimal promotion during the soft launch, there was strong uptake of the program, with champions enrolled from throughout Australia and across multiple sectors. This provides strong indication that there is an industry need for a program such as BeUpstanding. Secondly, workplaces were at different stages of readiness, with some champions wanting only to use select program materials  to help raise awareness of the importance of sitting less and moving more, whereas others were ready to run the full program. Thirdly, there was wide variation in how champions engaged with the toolkit, measured by the number of log-ons, with some champions repeatedly logging on throughout the program and others logging on rarely and/or infrequently. Finally, we found that although the toolkit was designed well for delivery by a single champion to their team of workers, it was not sufficiently flexible for larger organizations with large workplaces. It was identified that in a number of instances, there was a combined team formed of several teams led by champions who each adopted more nuanced roles (such as oversight without necessarily directly intervening on staff). Adaptations to the toolkit were made accordingly to suit a range of toolkit user roles.This updated version was tested via a These key learnings, which were complemented by discovery interviews and in-depth case studies with select participants , were used to inform further optimization of the program and toolkit and the protocol development for the national implementation trial of the BeUpstanding program (phase 4). Adaptions were done taking into account considerations from multiple perspectives, including the end users, the partners, the researchers, and the financial constraints ,40. The team. There are three phases to the program  and five steps as part of the BeUpstanding program (training) on the purpose of each step and task and resources to support the implementation of each task. As part of the implementation trial, champions will receive further training via coaching calls. The most critical step of the program is the staff workshop (Step 3.3). This step is designed to get everyone in the work team on board in terms of why and how the team can BeUpstanding together. In line with participatory design principles [The BeUpstanding program is designed to be implemented within a workplace  by a champion to their work team (colocated members of the workplace) of which the champion is also a member. Larger workplaces may run BeUpstanding by having several champions deliver the intervention to their teams concurrently. For the purposes of accrual targets and statistical analyses, these multiple teams are counted as one combined  program . Each stinciples , work teinciples , are proStand Up, Sit Less, Move More. Stand Up is a prompt to break up long periods of sitting, Sit Less is a prompt to reduce overall sitting time throughout the day by swapping some sitting with either standing or moving, and Move More is a prompt to increase physical activity  throughout the day. Increased activity and decreased sitting are primarily targeted through organizational, environmental, and social approaches. Messaging throughout the resources encourages regular postural shifts and reminders to listen to your body in recognition that there are also adverse outcomes associated with prolonged unbroken standing [The program’s behavioral targets are to achieve an even 50:50 split between sitting and nonsitting  activities at work and to alternate posture at least every 30 min between sitting and upright (or vice versa)—consistent with public, occupational, and clinical guidelines -45. To sstanding -48. No sThe BeUpstanding program is delivered via the BeUpstanding Champion Toolkit hosted on the BeUpstanding website . The webadoption/reach of the program (the number and characteristics of work teams and participating staff), program implementation (completion by the champion of core program components), effectiveness , and maintenance (sustainability of changes). The implementation trial is funded by a National Health and Medical Research Council (NHMRC) of Australia Partnership Project Grant (number 1149936), which includes cash and/or in kind support from the five partners (see below). Ethical approval was gained by The University of Queensland Human Research Ethics Committee . The trial was prospectively registered on May 12, 2017 (ACTRN12617000682347), before the soft launch of the program and last updated on the June 11, 2019. All participants will provide informed consent to participate.The aim of this study is to evaluate the BeUpstanding program in the context of a national implementation trial. The research questions to be answered are those important to informing the dissemination (phase 5) : in partA single-arm design will be used to evaluate the BeUpstanding program, with repeated cross-sectional evaluations at preprogram (0 weeks), end of program , and at 9 months postprogram (approximately 12 months post sign up). Repeated cross-sectional evaluations provide a flexible evaluation protocol  that canteam when the intervention is concurrent and within a workplace as per the criteria; otherwise, separate teams will be permitted to participate. Each champion will invite all employees within their work team to participate in the program and its evaluation. All workers invited will be considered eligible unless they indicate within the staff survey that they are unable to currently walk or stand for at least 10 min without an assistive device or requiring assistance from another person. Accrual targets have been set at 50 or more work teams per priority sector and 10,000 or more staff exposed to the program in total (see sample size). Performance against these accrual targets will be reviewed at the quarterly steering committee meetings, with the promotion and marketing plan adapted as required to ensure targets are met.On the basis of data reported by the champion as part of the web-based registration process, eligible Australian-based work teams will be those who had not run the BeUpstanding program previously with a minimum of five staff members, job roles or tasks that predominantly involve desk-based work, and a staff member willing to perform the duties of a workplace champion. Champions must also be planning to run the program within the recruitment window. For large organizations, including those located across numerous sites, multiple work teams from the one organization will be eligible to participate. These will be treated as a single combined push via an awareness raising event, will build on and coordinate with existing communication channels and resources from the partners and participating institutes, including social media, web links, email listservers, newsletters, workplace health promotion and occupational health networks, conferences, and workshops.The implementation trial will be conducted in partnership with five Australian workplace health and safety policy and practice organizations: Safe Work Australia, Comcare, Queensland Office of Industrial Relations, The Victorian Health Promotion Foundation , and Healthier Workplace Western Australia. These organizations are responsible for developing, implementing, and/or promoting Australian workplace health and safety policy. Each partner has committed to endorse and promote the toolkit across their relative jurisdictions. Desk-based employees from a wide cross-section of industries will be targeted, inclusive of sectors collectively identified as priorities by the partners . To ensure efforts are coordinated, a detailed action-mobilization plan will be developed with the partners. The plan, which will include an annual promotional The BeUpstanding website  is desigOutcome and process data and the characteristics of the workplaces, champions, and staff taking part in the implementation trial will be collected via the dedicated, stand-alone BeUpstanding website  and by the project manager , as outlined in The promotional activities undertaken by partners will be recorded at the 6-weekly partner meetings, with their impact on registrations tracked through the analytics in the toolkit website. The promotional pathways will be tracked through URL identifiers, through Google Analytics, and via champion self-reporting through the champion profile survey. Factors potentially influencing uptake and engagement with the program  will also be tracked via the registration survey and implementation checks. To ensure minimum data accrual targets are met, the project manager will follow up with champions (via email/phone) where necessary to encourage and support data collection.The project manager will have a minimum of five telephone contacts with the champion across the implementation trial evaluation: (1) recruitment, (2) confirmation of consent and explanation of next steps, (3) as soon as possible following the staff workshop, (4) at the end of the program, and (5) 9 months after the end of the program. Focus groups will be undertaken with a subsample of consenting staff from participating teams (n was approximately 15) at the end of the program to assess their perspectives on the processes and outcomes of the program. A mix of teams who made small/no, midrange, and large improvements and from different sectors will be purposively sampled, with focus groups conducted either in person or on the web via a virtual meeting room.Outcomes and measures are shown in Work team characteristics to be measured include organizational size, workplace location (postcode), industry, and team size. Team size is asked initially on the registration survey and confirmed by the project management team. Team size is visibly displayed on the feedback reports  for champions, and champions have the opportunity to modify their team size within their individual profile page. To assess eligibility and inform accrual targets, information on sector, job roles, and proportion of the team undertaking desk-based work will also be assessed. To understand the health and well-being culture of the work team, champions will be asked if their team is currently participating in any other workplace wellness/health promotion programs, the everyday interest of the team in health and well-being , the team’s motivation to sit less and move more at work , and their team’s level of stress . Workplace readiness for change will be assessed via the context, change efficacy, and change-related effort subscales of the Workplace Readiness Questionnaire [ionnaire . The worionnaire , will beChampion characteristics to be measured include sex; age (years), job classification , and job title (open ended). Champions will also be asked if they have a Health and Safety role in their workplace, whether they have done any training in workplace health programs before, and whether they have delivered and/or evaluated a workplace health program before, with responses of yes, no, and unsure for each item. Champions will be asked what they hope to achieve with the program, an also to describe their current workplace culture in terms of sitting, standing, and moving .The extent of participation of staff in the various BeUpstanding activities will be determined from the champion-reported team size, and champion-reported numbers or percentages participating in BeUpstanding events . Staff characteristics to be collected via the staff survey include age, sex, education, job classification, work hours, and the number of days in the last week where they had done a total of 30 min or more of physical activity, which was enough to raise their breathing rate . Staff wThe primary implementation outcome is program completion. At a minimum, successful completion is considered as completing all the core elements of the program . Secondar=0.74, 95% CI 0.51 to 0.87) and criterion validity  against workplace sitting in bouts of 30 min or more as recorded by the activPAL3 [The primary effectiveness outcome is self-reported workplace sitting time. This will be measured by the Occupational Sitting and Physical Activity Questionnaire (OSPAQ) , which activPAL3 .Participants will be asked “if you were given a choice at work, what percentage of the time would you want to spend: sitting, standing, moving.” Activity preference alignment at work will be calculated as the absolute value of the difference between their preferred behavior and their self-reported behavior. The alignment scores for sitting, standing, and moving each theoretically range from 0 (desired and performed are exactly the same) to 100 (desiring 100% and doing 0% or vice versa) .walks the talk when it comes to modeling standing and moving more at work; and whether their work team has a culture that supports standing and moving. These five items will be used to create an organizational social norms score.In line with the measure used in the pilot study , staff wenablers score.Staff will be asked (yes/no) whether they believe that too much sitting is detrimental to their health and well-being, whether a dynamic work environment is beneficial to their productivity, whether they want to sit less at work, and whether they have access to a height-adjustable desk. These four items will be used to create an weird if I sat less at work, my health prevents me from standing and moving more at work, and I need prompting to remember to sit less at work. Scores from these items will be used to create a barriers score. Participants will also be asked an open-ended question on any other factors that are preventing them from being able to sit, stand, or move at their desired levels at work.Participants will be asked on a 5-point Likert scale (1=strongly disagree to 5=strongly agree) the extent to which they agree or disagree with seven statements regarding perceived barriers to sitting less and moving more at work: I am too busy to sit less at work, I worry that I would be perceived as being unproductive if I sat less at work, I need new equipment  to support me to sit less at work, the tasks I have to do in my job prevent me from being able to sit less at work, I worry that I would be perceived as strategy use score.Participants will be provided with a menu of common strategies that have been used to promote standing up, sitting less, and moving more in the desk-based environment inclusive of those promoted in the BeUpstanding resources ,18,59 anSelf-rated job performance  and job Musculoskeletal symptoms in the last week will be measured using 3-items adapted from the Nordic Musculoskeletal Questionnaire ,64 to asThe experience of any adverse events associated with program participation will be asked of both champions and staff.Feedback on the BeUpstanding program will be sought from both champions and staff using fixed-option questions and qualitatively via open ended questions and qualitative interviews (in a subsample). Questions will cover program awareness, enjoyment, satisfaction, and potential for improvement. At the end of program, the staff survey will gather staff perceptions of the impact of the BeUpstanding program  on five success dimensions: the culture in their work team around sitting, standing, and moving; their knowledge of the benefits of sitting less; their attitudes toward sitting, standing, and moving; their awareness of their sitting behavior; and their activity outside of work. Champions will be asked to report, using a 5-point Likert scale , their perception of the extent to which the program raised awareness of the benefits of sitting less in the team, built a culture in their work team that supports sitting less and moving more, and reduced the amount their team engaged in prolonged unbroken sitting time. Adaptions and modifications to the program or program resources by the champions will be collected and recorded through the scheduled implementation checks.At postprogram assessment (approximately 9 months after the 8-week program completion), champions will be interviewed to understand current workplace policies and practices related to sitting less and moving more and ongoing or new BeUpstanding strategy use. All staff will be sent the maintenance survey (a repeat of the baseline staff survey) to understand the sustainability of any changes.The economic evaluation will address the costs and outcomes of scaling up to national implementation, including intervention affordability and sustainability. The economic analysis will be undertaken from a societal perspective, but with the major focus on a workplace perspective (covering both costs and benefits to employers and employees). The study design lends itself to a cost-outcome description as a full economic evaluation such as cost-effectiveness analysis would require a control arm. The primary economic analysis will comprise the analyses of costs, outcomes, and the relationship between costs and outcomes. Detailed pathway analysis will be used to identify all resource use associated with the intervention delivery. The intervention will be assumed to be operating in steady state , all costs associated with preplanning and development will be excluded. The included costs will relate to workplace recruitment  and intervention delivery . Data on the strategies adopted by individual work teams (including estimated costs) will be collected via the implementation checks. All resources will be valued in Australian dollars for the 2019 reference year. The economic outcomes for the implementation study will be presented as total costs, average costs per work team, and per work team of different size. Analysis of who incurs the associated costs  will be undertaken to assess intervention affordability and sustainability.team clustering. The primary endpoint is the end of program (approximately 8 weeks). The pragmatic aspects of the champion-led collection of anonymous data from staff within a workplace means the staff surveys will be sent out to all staff who are team members at the time in a repeated cross-sectional fashion. Most are likely a core cohort sent all surveys (not known to the research team) who may respond to none or any number of the three surveys. In addition, some team members will be added or lost with workforce turnover. Accordingly, the evaluation will consist of assessing both changes within baseline responders who are followed up over time, and as this may be a select motivated subset, also assessing time trends in all evaluable cases (responders to any survey). Time trends will be considered both unadjusted and adjusting for potential compositional differences between responders at each assessment (because of variations in team membership with workforce turnover and who responds to each survey). To evaluate sensitivity of conclusions to missing data handling, multiple imputation analyses will also be performed. Team-level variation in effectiveness will be considered. If applicable, then program engagement, characteristics of the work teams and workplace champions, and the timing (month/year) of the intervention will be explored as reasons for the differential effectiveness.Adoption, reach, and implementation outcomes will be described overall and within each priority sector. Effectiveness outcomes will also be evaluated overall and within each priority sector, with all work teams that are located in multiple sectors  examined as part of every sector to which they belong. Effectiveness outcomes collected at the end of program only from champions and/or staff  will be described. Effectiveness of the intervention on the primary outcome and secondary outcomes (continuous) collected repeatedly in the staff surveys will be assessed using mixed models that account for nonindependence in the form of individuals with repeated observations  and Qualitative data from the focus groups with staff  and semistructured interviews with champions (maintenance—use of policies and practices) will be audio-recorded and transcribed verbatim. Data from focus groups and champion interviews will be analyzed separately. Consistent with the recognized guidelines for qualitative data analyses , two memFor the primary effectiveness outcome (work sitting), the minimum difference of interest will be 20 min per 8 hours at work, which is equivalent to two-thirds of the effect in the pilot (30 min/8 hours)  and whatFunding for the trial was obtained from June 1, 2018, to May 31, 2021. The protocol for the data collection was originally approved by the institutional review board on January 9, 2017, with the national implementation trial consent and protocol amendment approved on March 12, 2019. The start date for the trial was June 12, 2019. As of December 2019, 48 teams have been recruited into the trial.Desk-based workers spend on average an estimated 70% to 80% of their workday sitting , puttingAs an implementation study, there are some inherent limitations. The use of a single-group, pre- to poststudy design is primary among these. A randomized controlled trial (RCT) design was considered, as this design would provide more robust effectiveness outcomes. However, an RCT would not provide better data for the reach, adoption, and implementation outcomes. It was also unclear how to conduct an RCT while preserving the key intervention model being tested of a workplace champion delivering and evaluating the intervention, particularly given the BeUpstanding toolkit is already live and freely available. Experience from the pilot and early adopters phases (phases 2 and 3) led us to expect that we would not be able to recruit champions willing to act as controls and complete all the evaluation but receive none of the intervention (even if they received a delayed intervention). Even the evaluation requires a reasonable amount of effort on the part of the workplace champion: researchers have no contact with the staff. Anyone can sign up to the toolkit  meaning contamination would be very difficult to control in those who sign up and are allocated to the control arm. We would also need to expend significant resources tailoring the toolkit to perform the evaluation but not the delivery intervention functions for those champions whose teams were allocated to a control condition. Therefore, on balance, it was considered that the pre-post design was the most appropriate to evaluate the implementation trial.Providing a menu of options and supporting work teams to collectively choose which intervention strategies will work best for them is a key strength of the program, with findings likely to provide key insights into possible higher order strategies to effectively support workers to sit less and move more , but thi


Tumour recurrence is currently a hot topic in liver transplantation. The basic mechanisms are increasingly discussed, and, for example, recurrence of hepatocellular carcinoma is often described in pre-injured donor livers, which frequently suffer from significant ischemia/reperfusion injury. This review article highlights the underlying mechanisms and describes the specific tissue milieu required to promote tumour recurrence after liver transplantation. We summarise the current literature in this field and show risk factors that contribute to a pro-tumour-recurrent environment. Finally, the potential role of new machine perfusion technology is discussed, including the most recent data, which demonstrate a protective effect of hypothermic oxygenated perfusion before liver transplantation. Liver transplantation (LT) is the gold standard treatment for end-stage liver diseases and early stage nonresectable hepatocellular carcinoma (HCC). It is a valuable tool for HCC treatment because it removes not only the malignant tumour but also the diseased liver parenchyma, which has the potential to develop new malignant lesions. The number of HCC cases listed for LT are continuously increasing worldwide, being already the leading indication for LT in the United States with approximately 24% of registrations in 2015 .p = 0.03; HR = 1.9; p = 0.003; HR = 2.84, respectively). This finding was even more pronounced in liver recipients with aggressive HCC types, including a poor tumour differentiation, micro- and macrovascular invasion, and exceeding Milan criteria, or an alpha-fetoprotein (AFP) of >200 ng/mL .p = 0.001) and recipient WIT  [p < 0.001; ALT, 559.6 vs. 701.4 IU/mL, p < 0.001). Importantly, the PEG-1 group had superior 3- and 5-year recurrence-free survivals (p = 0.003). The multivariate Cox regression analysis found the absence of PEG-1-treatment as the independent risk factor for early HCC recurrence within 12 months  [Such findings were paralleled by another study examining 103 LT patients with HCC . Tumour = 0.001) . Finally= 0.001) . To test= 0.001) . Markers= 0.042) ,54,56. T= 0.042) .Whilst robust evidence is lacking and some results remain controversial, different groups have demonstrated the link between donor livers that are more vulnerable to IRI, including DCD grafts and steatotic livers, or livers from living donors with the need to regenerate, and a higher tumour recurrence with subsequent inferior survival rates after LT ,57,58.The increased utilisation of donor organs with a high risk of IRI and subsequent post-transplant complications (ECD organs)  has unve2)) released from the same site in complex I [The technology of hypothermic machine perfusion (HMP) has evolved throughout recent years and various concepts are currently being tested. To understand the potential impact of any perfusion technique, the underlying mechanisms of protection should be presented. Regarding HMP, several experimental and clinical studies are available in different organs ,61,62. Iomplex I ,70,71,72omplex I ,68,72. Romplex I ,78,79,80omplex I .The technology of HMP and hypothermic oxygenated perfusion (HOPE) of kidneys and livers was developed by different groups over the past 50 years, who repeatedly demonstrated that mitochondria recharge ATP more effectively at hypothermic temperatures and that cold oxygenation triggers succinate metabolization ,75,81. IIn addition to normothermic perfusion techniques, organ viability can be assessed during cold oxygenation, as recently demonstrated . Here, mThe role of mitochondria-derived oxidative injury has gained increasing interest in various processes including aging and cancer growth ,90. As dThe HOPE technique is currently used in extended grafts, including DCD and steatotic livers, or in combinations of other risk factors, such as advanced donor age and cold ischemia time ,84,95,96Nomrothermic perfusion techniques represent a different concept and imitate the physiological conditions, thereby recovering the metabolism of the donor organ and offering nutrients and oxygen at 37 °C. When applied instead of cold storage, NMP abbreviates the hypoxic period, preventing further ATP depletion . AdditioA recent randomized controlled trial has assessed the impact of NMP in DBD and low risk DCD donor livers . NasrallTwo different approaches have been used to apply NMP in clinics. First, an immediate NMP after liver procurement with subsequent device transport and second, an endischemic NMP in the recipient centre with acceptance of a few hours of cold ischemia before starting the normothermic perfusion ,107. TheAlthough the replacement of cold ischemia time by NMP was shown to protect the organ from further ATP depletion and limits the accumulation of metabolic waste products , experimp53 small interfering (si)RNA to silence the p53 tumour suppressor gene in order to prevent apoptosis and mitigate IRI [Therapeutic interventions during NMP, such as the administration of cytoprotective and/or metabolic-modulating agents, may be used to treat IRI, although further studies are still needed to conclusively prove this theory. A recent study, investigating the effect of the pharmacological modulation of the lipid metabolism of discarded donor human livers during NMP, demonstrated the feasibility of the downregulation of markers for oxidative tissue injury , a reduction in the activation of immune cells , and the release of inflammatory cytokines in the perfusate  . An expegate IRI .Goldaracena et al. compared SCS with NMP and an anti-inflammatory cocktail ) in a pig transplant model . The autFuture therapeutic interventions during NMP, tackling specifically the mechanistical links connecting IRI and tumour recurrence after LT, is certainly an interesting area of research. Supplementation of NO precursors, such as L-arginine or chemical destabilisation of HIF-1α using the heat shock protein 90 inhibitor 17-DMAG may improve microvascular function . In addiDespite such promising markers, the most effective strategy to prevent tumour recurrence could be a significant reduction of reperfusion injury prior to organ implantation. Based on the current literature, various hypothermic oxygenated perfusion techniques offer this to the recipients ,118.A combination of sequential HOPE and NMP may offer the further benefit of additional viability assessment during NMP . This meOldani et al. assessed the impact of HOPE or NMP in a rodent model of DCD liver transplantation with 1 h of WIT and subsequent HCC cell injection after reperfusion . CompareCurrent evidence suggests that machine liver perfusion offers superior organ preservation over SCS, which is likely to be associated with the alleviation of the detrimental effects of IRI ,11.Based on the literature, donor factors and severe IRI negatively affect HCC recurrence following LT ,23,24. T