Elevate Self Growth program aimed to help participants perform various well-being behaviors, including screen time reduction, quality leisure activities, physical activity, physical relaxation, meditation and improved sleep habits. A multi-method evaluation was undertaken to assess Elevate Self Growth for the 19 program participants who paid to participate in the proof-of-concept program. Social Cognitive Theory was used in the program design and guided the evaluation. A descriptive assessment was performed to examine the proof-of-concept program. Considerations were given to participants’ levels of program progress, performance of well-being behaviors, improvements in well-being, and program user experience. Participants who had made progress in the proof-of-concept program indicated improved knowledge, skills, environmental support and well-being in line with intended program outcomes. Program participants recommended improvements to achieve additional progress in the program, which is strongly correlated with outcome changes observed. These improvements are recommended for the proof-of-concept well-being program prior to moving to a full randomized control trial. This paper presents the initial data arising from the first market offerings of a theoretically mapped proof-of-concept and reports insights that suggest promise for approaches that apply Social Cognitive Theory in well-being program design and implementation.Approximately 1 in 5 Australians experience a mental disorder every year, costing the Australian economy $56.7 billion per year; therefore, prevention and early intervention are urgently needed. This study reports the evaluation results of a social marketing pilot program that aimed to improve the well-being of young adults. The  For decades, mental disorders have been leading causes of the health-related burden world-wide ,2. ApproScholars and experts are asking for new health interventions to support individuals’ mental well-being . Existincompetition is given by examining how other programs deliver intended outcomes. Ideas gathered are considered by potential program users during participatory design. This intervention was theoretically informed, and formative research was undertaken prior to developing a program featuring marketing mix elements that was sold (exchange). The only social marketing element initially described by Andreasen that is missing is segmentation.Social marketing is distinct from other behavior-change approaches which tell rather than sell. In 2002, Andreasen  outlinedElevate Self Growth. First, participants preferred to have a focus on positive language  and increasing positive outcomes rather than decreasing negative outcomes . Second, participants made it clear that they wanted to have opportunities for active learning . Third, people expressed a need for social interaction and connection through social gatherings, group workshops or online communities. During the PD sessions, intervention components were designed, evaluated and improved and, ultimately, a final proof-of-concept organized into five core program modules emerged.Co-creation is the first phase in first-time application of social marketing . A partiThe five-step BUILD process was applied to map theory onto the proof-of-concept well-being program . The proAs a part of the five-step BUILD process, a theory selection process identified SCT as the most suitable theory to underpin the intervention. The pilot program was developed using a novel theory-mapping process that mapped behavior-change methods and intervention components to SCT constructs . The theElevate Self Growth program, which aimed to engage people who were interested in improving their well-being. The Elevate Self Growth program offers videos, assessments, tools and a community to build healthier habits. This study examines data derived from delivery of the proof-of-concept Elevate Self Growth program, which occurred over a 12-month period. The primary objective of this study is to evaluate the utility of using SCT in a social marketing program that aims to improve well-being. This article describes the lessons learned from delivery of the proof-of-concept, theory-driven social marketing intervention.The proof-of-concept program was designed at the end of 2019 and was intended to be delivered in person. However, the COVID-19 pandemic restricted in-person gatherings; therefore, the proof-of-concept was built and trialed online. During the trial, 24 people received free access to the program, and they provided feedback to improve material and delivery format. The free trial was followed by the initial market offering for the proof-of-concept Elevate Self Growth. Several areas of well-being were measured pre- and post-program implementation using a repeated measures design. Baseline data was collected prior to participation in the Elevate Self Growth program (n = 15). After participation in Elevate Self Growth program, a follow-up survey was conducted (n = 11).A multi-method evaluation was conducted using self-report surveys from two waves of data collected before and after participation in Elevate Self Growth program, participants were assessed on several well-being areas , participants’ knowledge, skill and environmental support related to well-being behaviors and performance of the specific well-being behaviors that underpinned the intervention . Due to the small sample size, analysis was limited to descriptive statistics only. Comprehensive statistical tests were not performed due to the limited sample size and insufficient power. Online surveys were included in the first lesson of Elevate Self Growth.After enrolment in the The Brief Resilience Scale (BRS) was used to measure resilience . While WElevate Self Growth program, 15 completed the baseline survey, representing a response rate of 71%.Knowledge, skill and environmental support were measured through direct statements related to each factor. For example, knowledge was measured through the statement “I know the benefits of (well-being behavior)”, skills were measured through the statement “I have the skills to (perform well-being behavior)”, and environment was measured through the statement “My environment enables me to (well-being behavior)”. Finally, the extent to which respondents were performing the well-being behaviors was measured by asking how many minutes they currently spent performing each behavior. A full list of questions can be found in Elevate Self Growth program. Eleven people completed the follow-up survey, representing a response rate of 57% of all Elevate Self Growth participants.The follow-up survey was sent to participants who completed at least 25% of the proof-of-concept Elevate Self Growth program. People who completed the follow-up survey were invited to participate in a phone call to discuss their experiences and provide feedback to improve Elevate Self Growth. Interviewees were asked to share their opinions about what they liked, what they didn’t like and how they thought the program could be improved. The questions were asked according to a feedback grid  is distracting me. And I know how to alter it, so it serves me rather than I serve it.”—30-year-old, Dutch female, unemployed“I was able to spend less time online, and more time in the real world.”—29-year-old, Australian male, self-employed.The fourth most frequently mentioned aspect that people liked was the use of practical tools, including the mobile application, the digital declutter, the full body relaxation audio track and the habit tracker.“I can study whenever, wherever I want”—31-year-old, Spanish female, working full time [about the mobile app].“The lessons helped me to manage my time and control my habits. I engaged in a digital declutter and already started to regain my focus.”—28-year-old, Dutch male, working full time [about the digital declutter].Additional proof-of-concept program components that people liked included lessons related to meditation, sleep and building habits. Some believed the techniques were versatile and applicable to multiple facets of their life. Some participants mentioned the usefulness of having ‘lifetime’ access to the program, so they could return whenever they wanted. Finally, some people noticed a positive transformation in their life as a result of the program.“I could really see a transformation. I’ve become more compassionate and kinder towards others, and I try to be more nurturing and caring toward other people.”—29-year-old, Finnish female, Student.“Now I have a morning routine, which has helped me be regular in my meditation practice, which is one of the things I value most. This transformation has affected not just my morning but my whole day. I feel I have more energy than before. I get more done in my day and I feel more fulfilled in my life.”—23-year-old, British female, working part time.Dislikes. When participants were asked what they disliked about the proof-of-concept program, 3 items emerged. First, two people mentioned that having lifetime access reduced the urgency to complete the program.“It would’ve been better if access to the program would be revoked after a while, so I’m more pushed to engage with the material.”—33-year-old, Australian female, working part time.The proof-of-concept was self-paced to enable flexibility in the learning process. However, two people mentioned that the lack of a set timeframe may have prevented them from making regular progress.“Nobody chased me to complete the course and that’s why I probably didn’t feel the urge to continue at some point.”—31-year-old, Spanish female, working full time.Third, one person wanted to be able to consume the content by listening (an audio program), so they could study while running or driving.Ideas and improvements. When participants were asked what could be improved in the well-being program, 4 distinct topics emerged. First, some participants suggested a clear timeline to complete the course should be set, to prevent participants from dropping out. Second, participants recommended a ratio of online and offline, and pre-recorded and live sessions and resources. Due to COVID-19 restrictions, the pilot delivery was entirely online, and participants felt it would not have been as engaging as in-person events, which is consistent with preferences indicated in the co-creation phase. Therefore, participants recommend hosting sessions in-person where possible. One participant even recommended hosting a live event to bring all participants together to foster a sense of community among participants. Furthermore, most of the online resources were pre-recorded and did not allow instant two-way communication and interaction. One participant mentioned that having the ability to engage and communicate in real time could encourage people to ‘show up’ more frequently. Third, several participants suggested having regular one-on-one check-ins with the program facilitator to keep them more accoun and increase their completion rates. Fourth, one person would have liked to hear other participants’ stories to learn about their experiences, which is now possible following delivery of the proof-of-concept program.Elevate Self Growth may change well-being behavior. Further, participants provided feedback, delivering important insights that can be used to further refine the program. Finally, the proof-of-concept indicates the value of dynamic evaluation. Each of these contributions is discussed in turn.Improving the mental well-being of individuals—especially now and in the future—requires new, co-designed, theory-based health interventions. This paper detailed the initial implementation and an additional explanation of how a theoretically informed evaluation can be applied to consider if a proof-of-concept is achieving intended outcomes. The paper advances understanding of the potential utility of a theory-driven intervention implementation in three ways. First, this paper details how an evaluation can be performed following delivery of a proof-of-concept program to consider if intended outcomes may be achieved. This paper provides a brief overview to explain how SCT was applied within the proof-of-concept program and details how SCT core constructs can be applied in a repeated measures design to gain insights to inform project planning. Second, this study provides insights into the potential for SCT constructs to be used to change well-being behaviors. This study reports that progress in This study reflects on the learnings following delivery of a proof-of-concept, theory-driven social marketing intervention that aims to improve young peoples’ well-being. The program was underpinned by SCT and sought to improve well-being by changing three theory-based constructs: knowledge, skills and environment. An ongoing debate on the role of theory ,43,44 iswhat behaviors are conducive to better physical and mental health, yet they may not know how to integrate those behaviors into their lifestyle. For example, most participants seemed to know that excessive screen time was not conducive to their well-being, yet their skills to reduce screen time and their ability to influence their environment to reduce screen time were significantly lower prior to program participation. Ample evidence of this knowledge–behavior gap in intervention science exists [This study reports the evaluation of a proof-of-concept that aimed to identify if a program designed to deliver components in accordance with three SCT constructs across 10 behaviors associated with well-being offers potential to improve well-being. This study demonstrates that when a participant’s knowledge about well-being behavior is already high, significant changes in knowledge may not be expected. Data insights indicate that when participants’ skills and environmental support related to a well-being behavior were lower at baseline, their scores did notably improve in those constructs following engagement with the program. It seems that many people already know e exists ,46, demoMany program evaluations happen after interventions are completed ,48,49. TThis study is not without limitations. It only presents a descriptive analysis of 11 participants who engaged in a proof-of-concept well-being program. Few participants completed the full program, and some enrolled participants had not started the program. A longitudinal, controlled research design is needed with sufficient participants to deliver a sufficient sample size to permit statistical testing and determination of effect sizes. Descriptive assessment indicates the potential for this proof-of-concept program, and funding is needed to deliver a scaled test of the iterated program. Additional work is recommended to assess other behaviors that this intervention targeted. Specifically, we recommend undertaking a three-arm randomized controlled trial to compare the current program with other well-being programs that are not theory-driven, as well as a control condition. Then, analytical methods, including hidden Markov modelling, can be applied to identify factors driving change.A series of recommendations were indicated in this study. Program participants who failed to complete the program sought supportive mechanisms through online or in-person contact. An iterated program that includes one or more recommended components can be tested in a field trial delivering a similar sample size to permit a cost–benefit assessment. If higher completion rates and potentially enhanced outcomes had been observed, the relative costs of delivering a form of in-person support could be warranted. Finally, this paper describes a theoretically informed program’s potential to enhance well-being. Future research testing the application of alternate theories in well-being is recommended, along with research that tests interventions informed by SCT in other health and environmental contexts.This study presented an evaluation of a co-created, well-being proof-of-concept based on theory. This study has contributed to understanding success and failures in applying SCT to improve well-being. This research considered whether changes in knowledge, skills and environmental support occurred, and it considered if observed changes may offer potential to contribute to improvements in well-being for program participants. Program improvements were identified. This study delivered further evidence that theory may indeed offer potential to contribute to positive program outcomes. Social marketers are advised to link intervention components to theoretical constructs and include theoretical measures in their evaluation to clearly determine the effectiveness of theory-based intervention design.


Exercise interventions may assist smoking cessation attempts. One such publicly available 10-week program, Walk or Run to Quit (WRTQ), demonstrated success in smoking cessation and physical activity (PA) outcomes. However, initial WRTQ participants (2016-2017) were fairly homogenous in their demographic profile. To increase diversity, subsidies for participation were offered in 2018. This study assessed how the subsidies affected participant demographics, running frequency, smoking cessation, intention to quit, and program attendance and completion.  The $70 registration fee was subsidized for 41% of participants in 2018. A pre-postdesign was used, with participants completing surveys on their demographics and smoking and physical activity behaviours. Descriptive statistics compared the year subsidies were available (2018) and unsubsidized years (2016-2017) and subsidized and unsubsidized participants' data from 2018.  The 2018 participants had lower average attendance and program completion rates compared to 2016-2017 and no statistically significant differences in demographics or smoking cessation and PA outcomes. There were no differences in smoking cessation, run frequency, or demographic variables between the subsidized and unsubsidized participants in 2018.  Offering subsidies did not diversify the participant profile. Subsidies did not have a negative impact on attendance nor primary outcomes. Subsidies may not have addressed barriers that prevented a more diverse sample from participating in WRTQ, such as program location, timing, and design. Equitable access to smoking cessation programs remains essential. As subsidies may play a role in reducing financial barriers disproportionately faced by marginalized groups, the implementation of, and recruitment for, such subsidized programs requires further investigation. Tobacco use is the most preventable cause of death and disease . Most peAmong other existing strategies, exercise may serve as a promising smoking cessation approach given its broad and beneficial proposed effects including substantial evidence that acute bouts of exercise decrease nicotine withdrawal symptoms and alleviate mood disturbance . There iOne such program is the Walk or Run to Quit (WRTQ) physical activity-based smoking cessation program. WRTQ is a Canadian program formed through a multisectoral partnership between an industry (Running Room), nonprofit (Canadian Cancer Society), and academic (UBC) partnership combining other smoking cessation strategies with an overarching exercise intervention in an effort to decrease smoking prevalence and increase overall physical activity and running frequency of participants . OverallAfter the first year of the program, 90.8% of the participants who completed the in-person clinics reported reducing their smoking because of the program. Over 50% of the program completers did not smoke a cigarette within the last week of the program as confirmed by carbon monoxide testing. Despite these benefits, there was some concern about the homogeneity of the participants in recruiting white, college educated individuals from higher socioeconomic backgrounds . The majOne barrier to broader representation may have been the cost of participation (a $70 registration fee). In 2018, some participants had their registration fee subsidized so that they did not have to pay to join the program. This subsidy implementation is of interest as price-based policies, including the use of subsidies, can directly address financial cost as a barrier. In Canada, subsidization policies were associated with modest increases in the use of nicotine replacement therapy (NRT) use and quit success . PreviouN = 745) registered for WRTQ clinics at Running Room stores across Canada (see [Participants were Canadian adults (ada (see  for furthttps://quitnow.ca).WRTQ in-person clinics were held at various Running Room stores across Canada, with a registration fee of $70 CAD per person. This registration fee covered access to the program which included a 10-week smoking cessation and running curriculum led by a coach. Nicotine replacement therapy was available outside programs but was accessible and free/included for all participants as were provincial quitline supports , there was a $70 CAD registration fee. In the third year , 58.9% paid the $70 fee while the remaining (41.1%) received a subsidy. For these analyses, participants were excluded if they were a nonsmoking buddy (n = 30) since this would artificially decrease the 7-day PPA scores.During the first two years . Device-measured carbon monoxide (CO) was collected using a coVita piCO+ Smokerlyzer® device at weeks 1 and 10. Coaches completed a log each week that tracked participants' attendance.Attendance. Program attendance was collected (1-10 sessions).Completion status. Completion of the program was defined as both attending and completing postprogram measures at week 10.Smoking status. Smoking status was represented by 7-day point prevalence abstinence (PPA), which assesses whether participants smoked in the past week. A survey question  and CO scores were used to determine 7-day PPA. Meeting 7-day PPA was defined as not having a puff in the last 7 days and having a CO level of <10 ppm at the week 10 assessment.Run frequency. Physical activity at week 10 was assessed with the item “How many times/week do you currently run (for at least 10 minutes at a time), if at all?”Intention to quit smoking. Intention to quit in the next 30 days was measured at week 1 using a single item with dichotomous yes/no response options. “Are you seriously considering quitting within the next 30 days?”Participant demographics. Demographics reported at baseline included sex , race/ethnicity , age, highest level of education completed ), home ownership (own/rent), and employment status ). Socioeconomic status “(or sometimes socioeconomic position) refers to standing in the stratification system and is usually measured by education, occupation, employment, income, and wealth.” χ2) tests, depicted participant demographic information as well as completion and smoking status. Independent samples t-tests assessed the differences in attendance and run frequency. These tests were used to compare unsubsidized and subsidized participants in 2018 and whether there were any differences between participants who took part pre- (2016-2017) and postsubsidization (2018). An intent-to-treat (ITT) approach was used for 7-day PPA and run frequency. If participants did not have data for both survey and CO criteria , it was assumed that they were still smoking and did not meet 7-day PPA. Participants missing week 10 running frequency data were assumed to have the same running frequency as baseline before starting the program.Descriptive statistics, including chi-square  = 7.2, p < .01). There were also statistically significant differences for attendance, with participants in the presubsidization years attending more sessions  than those in the postsubsidization year  = −2.8, p < .01). There were no statistically significant differences (p′s > .05) for smoking status, sex, identifying as white, education, age, home ownership, employment status, run frequency, or intention to quit smoking.Pre- and postsubsidization results were compared to explore whether the partially subsidized year had a comparable demographic profile and program outcomes to years without subsidies. There were statistically significant differences for program completion status  for any demographic or outcome variables when comparing participants who were subsidized and unsubsidized in 2018.There were no statistically significant differences  is a limitation of the analysis. Current research regarding the effects of subsidies on physical activity participation remains limited, and future research is warranted regarding how subsidies are effectively delivered to alleviate financial barriers.Another consideration is that the nature of the WRTQ program was potentially not attractive to a more diverse group of participants for two reasons. First, as a multisectoral health partnership between a health charity, Canadian Cancer Society and an industry organization, Running Room, the programs were provided at the organization's Running Room stores. These stores are located in high-density, urban settings. Such settings may not have been accessible to many individuals who could have benefited from the program. Future iterations of the WRTQ program should implement broader outreach and move “clinics to the communities.”Second, the connotations associated with leisure time physical activity  may also be a barrier to participation for a broader demographic of participants. Adults with lower SES may be more physically active at work and less active during their leisure time , 20. ThiThere are a number of strengths and limitations associated with this particular program evaluation. The study is limited in that it could not account for extraneous variables that may have influenced subsidy uptake. Income was not directly measured nor was subsidy distribution adequately assessed. Strengths of this study include its national scale and reach, the use of objective measures for smoking cessation, and the ability to compare program demographics both over different program years with and without subsidies and across a single program with some participants receiving the subsidy intervention.Integrating physical activity into smoking cessation interventions may have synergistic health benefits through multiple health behaviour change. Irrespective of cessation outcomes, increasing physical activity may confer some harm reduction benefits . The imp


Predicting the course of depression is necessary for personalized treatment. Impaired glucose metabolism (IGM) was introduced as a promising depression biomarker, but no consensus was made. This study aimed to predict IGM at the time of depression diagnosis and examine the relationship between long-term prognosis and predicted results.Clinical data were extracted from four electronic health records in South Korea. The study population included patients with depression, and the outcome was IGM within 1 year. One database was used to develop the model using three algorithms. External validation was performed using the best algorithm across the three databases. The area under the curve (AUC) was calculated to determine the model’s performance. Kaplan–Meier and Cox survival analyses of the risk of hospitalization for depression as the long-term outcome were performed. A meta-analysis of the long-term outcome was performed across the four databases.p = 0.027) at a 3-year follow-up.A prediction model was developed using the data of 3,668 people, with an AUC of 0.781 with least absolute shrinkage and selection operator (LASSO) logistic regression. In the external validation, the AUCs were 0.643, 0.610, and 0.515. Through the predicted results, survival analysis and meta-analysis were performed; the hazard ratios of risk of hospitalization for depression in patients predicted to have IGM was 1.20 (95% confidence interval [CI] 1.02–1.41, We developed prediction models for IGM occurrence within a year. The predicted results were related to the long-term prognosis of depression, presenting as a promising IGM biomarker related to the prognosis of depression. Depression severely restricts individual psychosocial functions and lowers the quality of life. It leads to national problems such as increased suicide rates and medical expenses because of its chronicity. The World Health Organization cited major depressive disorder as the third cause of the global burden of disease in 2008 and predicted that depression would rank first by 2030 . NumerouPrevious studies have suggested that measuring metabolic markers may be a promising way of predicting long-term clinical outcomes in depression . Recent Machine-learning (ML)-based predictive models are becoming increasingly popular by combining huge data into one model. For depression, conventional regression methods have limitations in prediction; not only well-known demographic factors or factors related to typical treatment but also various comorbidity with physical disease and generally polypharmacy are common , 21. By This study aimed to investigate whether IGM could be utilized as a biomarker that reflects the clinical severity and prognosis of depression. Initially, we attempted to develop a model that predicts IGM occurrence at the time of the first diagnosis of depression through an ML algorithm. Subsequently, using multicenter and longitudinal data, we intended to analyze and validate whether the IGM occurrence predicted by the model is related to the short-term and long-term prognosis of depression.Supplementary Material S1). The clinical data included diagnoses, observations, provider visits, procedures performed, and medications filled. The databases were formatted according to the Observational Medical Outcomes Partnership–Common Data Model version 5.3.1, maintained by the Observational Health Data Sciences and Informatics (OHDSI), and de-identified [This study used data from approximately 6 million patients across the four electronic health record databases in South Korea: Ajou University School of Medicine (AUSOM), Daegu Catholic Medical Center (DCMC), Wonkwang University Hospital (WKUH), and Kyung Hee University Hospital at Gangdong (KHNMC) . Informed consent was not required owing to the use of de-identified data. Access to DCMC, WKUH, and KHNMC databases during the external validation process was allowed under the IRB mutual recognition agreement (research-free zone agreement).The study population included patients with a new depressive episode. The index date was defined as the patient’s first diagnosis of depressive disorder. To verify their first diagnosis of depressive disorder, at least 1 year of observation before the index date was required. Within the 1-year observation period before the index date, relevant covariates on each patient were collected to predict their future diagnosis of IGM. Patients who were treated for depression, those who had antidepressant prescriptions, and had undergone psychiatric procedures after the index date were included. Also, patients who had at least 1 year of follow-up after the index date were included. For the IGM prediction, patients who had at least one measure of HbA1c or fasting glucose within 1 year after the index date were included. As exclusion criteria, patients with diagnosis of bipolar disorder, schizophrenia, and psychosis on or before the index date were excluded. Regarding DM, a previous history of DM, DM complications, and exposures to antidiabetic drugs were excluded.Supplementary Materials S2–S3.The primary outcome for the predictive models was IGM within 1 year after the index date. IGM was defined as pre-DM or T2DM and measured by HbA1c or fasting glucose. For IGM, HbA1c levels were defined as ≥5.6%, and fasting plasma glucose as ≥100 mg/dL . All patWe used the patient-level prediction framework of the OHDSI to develop and validate the predictive models. This framework consisted of standardized model development and validation processes that require defining predictable problems and selecting the study population, outcomes, population settings, predictors, and statistical algorithms . The preExternal validation was conducted to confirm the validity of the model’s performance using the databases of DCMC, WKUH, and KHNMC. Specifically, we evaluated the performance of the final model to other databases in the same setting as in the model development.The patients were followed up 3 years after the index date. During the follow-up, risk of hospitalization for depression in patients who were predicted to have IGM compared with patients who were predicted not to have IGM. Risk of hospitalization for depression was defined as hospitalization caused by the exacerbation of depressive episodes. In addition, rehospitalization after discharge for the first diagnosis was considered . To distDescriptive statistical analyses were appropriately performed. Baseline characteristics are presented as counts with proportions for categorical variables and as median with interquartile range for continuous variables. The chi-square test was used to compare categorical variables between populations. Accuracy, AUROC, and area under the precision and recall curve (AUPRC) were calculated to evaluate the performance of the prediction models. We used the maximal Youden index to select the optimal cutoff value in the prediction model .Moreover, we verified whether the group predicted by the final model was related to the actual IGM occurrence. The final model was used to estimate their predicted IGM at the internal validation dataset, and patients with a relatively high probability of IGM were then labeled as predicted to have IGM. If the patients in the internal validation dataset were predicted to have IGM, they were classified as “predicted to have IGM,” and others were classified as “predicted not to have IGM.” The Kaplan–Meier survival analysis and log-rank test were used to analyze the difference in the occurrence of IGM within 1 year after the index date in the group predicted to have IGM versus the group predicted not to have IGM.After model development and external validation, Kaplan–Meier and Cox survival analyses for the long-term outcomes were performed to assess the risk of hospitalization for depression in patients who have IGM, as determined by the final model. Then, a meta-analysis was performed to calculate the summary hazard ratio (HR) estimates across four databases.p-values <0.05 were considered statistically significant. All analyses were conducted using R software version 3.6 , OHDSI’s Health Analytics Data to Evidence Suite packages, and open-source statistical R packages.All n = 2,129; WKUH, n = 2,717; and KHNMC, n = 870) were used. Supplementary Tables S1–S3. Among the 3,668 patients with depression in the AUSOM database, 481 (13.1%) experienced IGM within 1 year after the diagnosis of depression. No significant differences were found in age, sex, medical history except hypertension, and psychiatric history between the groups. The proportion of hypertension was significantly lower in with IGM group (p < 0.01). Middle-aged (40–59 years) and female patients were the most predominant in the study population. Hypertension and anxiety disorder were frequent diagnoses .A total of 481 outcomes in 3,668 patients from AUSOM were used for model development, and for the external validation, 543 outcomes in a total of 5,716 patients  in DCMC, 12.0%  in WKUH, and 3.2% (28/870) in KHNMC. The external validation performance of the final model regarding AUROC was 0.643 at DCMC, 0.610 at WKUH, and 0.515 at KHNMC.p < 0.001). Furthermore, patients predicted to have IGM showed significantly worse long-term outcomes. In the overall cohort of AUSOM, survival analysis showed that the risk of hospitalization for depression occurred more frequently in patients who were predicted to have IGM during the 3-year follow-up  (= 0.002) .Figure 2p = 0.027) for patients predicted to have IGM.We further assessed long-term outcomes not only in AUSOM but also in external validation databases. The meta-analytic comparative effect estimates for the risk of hospitalization for depression are presented in We constructed a model to predict the occurrence of IGM within 1 year at the time of depression diagnosis using ML algorithms. By analyzing the longitudinal data of multiple institutions using this prediction model, we identified relationships between IGM prediction and the long-term prognosis of depression. Thus, IGM might be a promising biomarker associated with the prognosis of depression.Despite being a common psychiatric disease, depression has a low treatment success rate because of the heterogeneity and difficulty in predicting its course , 29. ThuRecently, a nationwide study revealed that glucose disturbance is associated with increased suicidal ideation and suicidal behavior in patients with depression . In anotData-driven ML algorithms are in the spotlight as a breakthrough in the discovery of hidden predictors and known clinically meaningful predictors selected by researchers . TherefoSince this study developed an IGM prediction model through an ML algorithm rather than deep learning, understandable explanations for prediction were obtained. Initially, at the time of diagnosis of depression, antipsychotics, including haloperidol, are commonly prescribed. Moreover, studies have reported that antipsychotics are related to an increase in blood sugar . In addiFurthermore, in this study, survival analysis was conducted to determine whether the results of the IGM incidence prediction model were related to the 3-year prognoses of depression. Through a meta-analysis using four other hospital data with the Common Data Model (CDM) database, we identified differences in hospitalization caused by exacerbation of depressive episodes between the two groups divided into IGM prediction models using longitudinal data. This result can be interpreted through the report of previous studies that when depression or anxiety is accompanied by DM, disease burden and emotional distress increase because of poor metabolic control, low rates of blood glucose self-monitoring, and DM complications, which can predict inadequate response to depression treatment , 47.This study has several limitations. First, this study used data from Koreans only; thus, the results cannot be generalized. However, this study showed that the CDM developed through a distributed research network enables a more efficient meta-analysis than in the past without exposing private information. This suggests that a global meta-analysis is possible if the same CDM is established in various countries. Second, this study used longitudinal data, but it has the limitations of a retrospective study. To clarify the relationship between depression and IGM, a prospective study is required. Third, this study did not include social and environmental factors that would be related to depression and IGM in the model development. This is also a limitation of the psychiatric CDM. Thus, developing measurable environmental and sociological variables is necessary. Fourth, model performance was reduced in the external validation of the IGM prediction model. Model performance commonly decreases in the external validation because of the varying characteristics of the enrolled participants, and it is difficult to control them all. Specifically, the external validation performance was low in the analysis of KHNMC compared with AUSOM. The result was assumed to be caused by the varying rates of IGM occurrence, i.e., 13.1% in AUSOM and 3.2% in KHNMC. Furthermore, since there is no overall difference between patients with and without IGM in the baseline characteristics, predicting IGM may be difficult. Fifth, indirect indicators such as depression-related hospitalization were used to determine the relationship between the results of the IGM prediction model and the long-term prognosis of depression. However, several recent studies have derived meaningful results using operational definitions such as this study . Sixth, In summary, we developed an IGM prediction model at the time of depression diagnosis using an ML algorithm and found a relationship between the results of the IGM prediction model and the long-term prognosis of depression using longitudinal data. Thus, we suggest that IGM is likely to be a promising biomarker in predicting the prognosis of depression. Treatment strategies should be established to improve metabolic disturbance, including IGM, and the use of IGM as an evaluation index for lifestyle modification and increased treatment success rate may be expected. Therefore, a more customized and multidimensional approach to the evaluation and treatment of depression would be possible.


Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as the preferred method of mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). Selective (targeted) LN sampling is most commonly performed however studies in early stage NSCLC and locally advanced NSCLC confirm systematic EBUS-TBNA evaluation improves accuracy of mediastinal staging. This study aims to establish the rate of detection of positron emission tomography (PET)-occult LN metastases following systematic LN staging by EBUS-TBNA, and to determine the utility of systematic mediastinal staging for accurate delineation of radiation treatment fields in patients with locally advanced NSCLC.Consecutive patients undergoing EBUS-TBNA for diagnosis/staging of locally advanced NSCLC will be enrolled in this international multi-centre single arm study. Systematic mediastinal LN evaluation will be performed, with all LN exceeding 6 mm to be sampled by TBNA. Where feasible, endoscopic ultrasound staging (EUS-B) may also be performed. Results of minimally invasive staging will be compared to FDG-PET. The primary end-point is proportion of patients in whom systematic LN staging identified PET-occult NSCLC metastases. Secondary outcome measures include (i) rate of nodal upstaging, (ii) false positive rate of PET for mediastinal LN assessment, (iii) analysis of clinicoradiologic risk factors for presence of PET-occult LN metastases, (iv) impact of systematic LN staging in patients with discrepant findings on PET and EBUS-TBNA on target coverage and dose to organs at risk (OAR) in patients undergoing radiotherapy.With specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the exact extent of mediastinal LN involvement in NSCLC in patient with Stage III NSCLC is rarely established. Studies examining systematic LN staging in early stage NSCLC report a significant discordance between PET and EBUS-TBNA. In patients with locally advanced disease this has significant implications for radiation field planning, with risk of geographic miss in the event of PET-occult mediastinal LN metastases. The SEISMIC study will examine both diagnostic outcomes following systematic LN staging with EBUS-TBNA, and impact on radiation treatment planning.ACTRN12617000333314, ANZCTR, Registered on 3 March 2017. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a widely accepted technique for minimally invasive sampling of mediastinal lymph nodes (LN). It is the preferred method for staging of patients presenting with suspected locally advanced lung cancer due to its excellent diagnostic accuracy and safety profile . Non-invAccuracy of PET for detection of metastatic LN in NSCLC patients is imperfect  and consSystematic mediastinal LN staging in early stage NSCLC prior to surgical resection is recommended in patients with risk factors for post-operative up-staging . SystemaTo determine the rate of detection of PET-occult LN metastases in patients with locally advanced (Stage III) NSCLCTo identify the proportion of patients with potentially false positive involvement of mediastinal LN on PETTo identify clinical risk predictors for presence of PET-occult LN metastasesversus PET and EBUS-TBNA.In patients with discrepant findings on PET and EBUS-TBNA, to compare target coverage and radiation dose to OARs using target volumes based on PET alone This prospective international multi-centre study will examine the use of systematic mediastinal LN staging in patients with locally advanced (stage III) NSCLC. Aims of the study include:The importance of accurate LN staging in early stage NSCLC is well established. Guidelines recommend systematic LN staging at the time of curative intent surgery , 8, 9, bVariability in adequacy of LN examination/sampling for resected NSCLC has been suggested to explain a large proportion of intercontinental survival differences . ConsequAccuracy of EBUS-TBNA for systematic LN staging in early stage NSCLC is established, though is recognized to be inferior to that observed for patients with radiologically pathologic mediastinal LN  EBUS-TBNIn contrast to early stage NSCLC where intra-operative LN staging is recommended to achieve completion of pathologic staging, current International guidelines recommend radiation target volumes be constructed based on PET-identified extent of disease , 17 In tIncomplete staging of the mediastinum in patients with locally advanced NSCLC is analogous to R(un) staging described above in patients undergoing resection—while many patients will have the entirety of their disease encompassed by radiation fields, an unknown proportion  in mediastinal staging of lung cancer has long been established, with complementary reach of the techniques allowing a greater number of LN stations to be assessed via minimally invasive means. More recently use of the endobronchial video-bronchoscope has allowed “complete” mediastinal staging. EUS using the bronchoscope (EUS-B) can be performed by pulmonologists in the same procedure as EBUS-TBNA , 22 and in NSCLC , 23 ConsStudy design The SEISMIC study  is a prospective international multi-centre single arm interventional study.Setting seven international tertiary lung cancer services.Intervention systematic LN staging with EBUS-TBNA will be performed at the time of staging EBUS as previously described [escribed  At centrescribed  mediastiPatient population patients with known or suspected NSCLC and suspected or known mediastinal metastases (i.e. cN2/3 disease), based upon CT and PET findings. Inclusion and Exclusion criteria are recorded in Box 1.Outcomes the primary study outcome is proportion of patients in who PET-occult mediastinal LN metastases are detected by systematic LN staging with EBUS-TBNA/(EUS-B-FNA).Proportion of patients with endoscopy-demonstrated benign LN at sites of FDG-avidity on PET/CTMulti-regression analysis of clinic- radiologic factors to identify risk factors for endoscopic detection of PET-occult diseaseDifference in planned radiation dose to lymph nodes and adjacent critical organs in treatment plans based on FDG-PET/CT only vs FDG-PET/CT & EBUS-TBNA in patients where EBUS-TBNA staging demonstrates discrepant extent of mediastinal involvement compared with FDG-PET/CT.Radiomics analysis to identify risk factors for EBUS-PET discrepancy regarding extent of mediastinal LN involvement.Incidence of detection of PET-occult disease by EUS-B-FNADevelopment of a radiomics signature to predict nodal status as defined by EBUSOutcomes of surgical staging (where performed) in patients with PET + /EBUS– findingsSecondary outcomes include:All patients’ demographic and clinical data will be collected including gender, age, smoking status, whether symptomatic disease, and histology.vs central position  of primEBUS imaging features; including whether endobronchial tumour was seen  and whicAdditionally, collection of data will include; final N-stage as determined by EBUS-TBNA/EUS-B, highest LN station involved by NSCLC, and any discrepancy between PET and EBUS-TBNA staging.Integrated PET-CT scans will be performed before recruitment into the study and performance of EBUS staging bronchoscopy. Pre-treatment staging established according to the 8th edition of the Lung Cancer Stage Classification, the TNM descriptors for which are reviewed in detail elsewhere Visual examination of the following LN stations is required in all cases – 2R, 2L, 4R, 4L, 7. In centres where EUS-B is utilized, endoscopic examination also requires visualization of stations 4L, 5, 7, 8, 9.Any visible LN exceeding 6 mm in these stations will be sampled via EBUS-TBNA and/or EUS-B-FNA. Rapid on-site cytology examination (ROSE) of TBNA/FNA aspirates will be used where available to confirm adequate specimens/diagnostic tissue is obtained before proceeding to the next LN station.Systematic sampling should commence at the highest echelon mediastinal LN visualized (ie. N3) and proceed more proximally, guided by ROSE results. Where ROSE was unavailable, PET-positive LN should be sampled a minimum of three times by TBNA. Assessment of contralateral hilar LN is not planned due to the impact on procedure time & complexity, given the exceedingly low expected rate of disease at this anatomic site For PET-negative LN (low pre-test probability) where ROSE demonstrates adequate samples, no further sampling from that site will occur. We would plan to perform as few as 1 TBNA per LN stationFor PET-positive LN , Three TBNA needle passes will be performed when ROSE indicates benign tissue, to ensure highest NPV at these high risk sites.Samples per nodal station:At centres where expertise & experience allows, endoscopic staging will comprise both EBUS and EUS-B mediastinal examination & sampling. Remaining centres will undertake systematic sampling of mediastinal LN via EBUS-TBNA.Endoscopic staging will be performed according to the following methodology:This component is an in silico study that will examine dosimetric consequences of PET-EBUS-TBNA discrepancies observed. Clinical treatment plans will be constructed after active involvement in the study has been completed. Dosimetry of radiation treatment plans are routinely performed in all patients using standardised computer-based dosimetric calculations, which include routine dose/volume constraints such as the volume of lung that receives 5 Gray (Gy) (V5Gy), the V20Gy, V30Gy and mean lung dose. Clinical treatment plans are routinely constructed on the basis of PET-identified disease extent. Where Endosonographic findings suggest a different extent of mediastinal involvement, the dosimetric differences in lymph node and critical organ dose between treatment plans based on FDG-PET/CT only vs FDG-PET/CT & EBUS-TBNA staging will be calculated.EBUS-TBNA identifies PET-occult disease (PET-/EBUS +): The clinical treatment plan will be constructed to include in the treatment field both the PET + and EBUS + mediastinal LN sites. The hypothetical plan will be based solely on PET + sites. The difference in radiation dose at PET-/EBUS + sites between the clinical and hypothetical plans will be determined. From this difference the risk of recurrence will be estimated according to published studies relating radiation dose to tumour control probability.EBUS-TBNA demonstrates benign lymph node tissue in PET-positive lymph nodes (PET + /EBUS-): The clinical treatment plan will be constructed to include all PET + sites . The hypothetical plan will be based on the endosonographic-determined disease extent. The difference in radiation dose to critical organs including the lung, heart, oesophagus between the clinical and hypothetical treatment plans will be calculated. Estimates of toxicity probability will be computed based on existing relationships between organ dose and toxicity risk.For study endpoints, two different scenarios will occur where dosimetric consequences of systematic endosonographic staging will be calculated. These will be theoretical in nature, comparing the radiation plan based upon PET based target volumes to a radiation plan based upon PET- and EBUS- based target volumes.Study sample size has been calculated at 190. This is based on the view of investigators regarding the expected primary outcome (proportion of participants with PET-occult disease detected by EBUS-TBNA) of 9–11 percent, based on previously published studies 95% CI for this outcome with n = 190 is 7.3–16.4%.Primary study outcome will be reported using observed prevalence (%) with 95% confidence intervals.Identification of clinicoradiologic risk factors for presence of PET-occult disease will be completed using multinomial or ordinal regression.Application of established risk prediction tools for prediction of nodal disease in patients with NSCLC as determined by EBUS-TBNA  will alsRadiation dosimetry endpoints will be based on in silico radiation plans developed according to staging based on PET findings alone, versus PET + EBUS staging findings.Individual lymph node stations will be manually contoured on the diagnostic contrast enhanced CT and PET scans of all patients by a radiation oncologist and used as the volume of interest (VOI). Radiomic features will be extracted from the VOI using a specialized, validated, open source software (PyRadiomics) available on the python platform. Radiomics features extracted will include first order features, shape features and second order texture features, including grey scale co-occurrence matrix, neighbourhood grey tone difference matrix, grey level run-length matrix, grey level size zone matrix, and level dependence matrix. The association between lymph node status and radiomics features will be modelled using a variety of binary classifiers . Each of the classifiers will be employed within a nested ten-fold cross-validation framework and classifier accuracy will be reported with sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).Non-invasive staging is a critical step in assessment of patients with NSCLC. However the imperfect sensitivity of PET in mediastinal staging of NSCLC means  invasive confirmation of findings is frequently sought. With specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the extent of mediastinal evaluation during staging EBUS-TBNA varies considerably , 30, andSystematic mediastinal LN staging with EBUS-TBNA in patients with early stage NSCLC has demonstrated a significant rate of detection of PET-occult disease  as well We hypothesize that systematic mediastinal LN staging in patients with Stage III NSCLC will provide more accurate information on the extent of mediastinal LN involvement. The SEISMIC study will examine both the outcomes following systematic LN staging, as well as the impact on radiation treatment planning.On the other hand, systematic mediastinal assessment with EBUS-TBNA as compared to selective sampling is a non-trivial extension of current practice. Additional procedural time and potential for complications must be outweighed by the clinical utility of the approach. It may be that the low-intermediate dose wash of current radiotherapy treatments may cover subclinical radiological disease sufficiently to achieve cancer control. The purpose of this study is to evaluate these possibilities in a rigorously conducted prospective trial.Patterns of lymph node metastases, based on primary tumour position have been reported previously in surgical cohorts  as have This study is not intended as an examination of diagnostic accuracy of EBUS-TBNA. Given the previously reported specificity of EBUS-TBNA for detection of NSCLC of 100% , findingWhile EUS-B-FNA may be performed by pulmonologists, this is dependent on local expertise and institutional credentialing practice. Thus we expect only a minority of patients to have undergone “complete” endoscopic mediastinal staging. Furthermore, PET staging will include assessment of all LN stations, while endoscopic staging will be limited only to LN stations accessible by the technique. EBUS is unable to assess Stations 5, 6, 8 and 9.Prediction models estimating the probability of nodal disease have been validated  and may While in silico modeling will examine the dosimetric consequences of PET-EBUS discrepancies, this study will not directly compare survival outcomes. Delivery of radiotherapy will be determined by local tumour control board assessments, incorporating both PET and EBUS-TBNA findings.While the importance of accurate LN staging, both for prognostication and treatment decision-making, for patients with early stage NSCLC is emphasized in the literature as well as international society guidelines, the same importance is not attached to LN staging in patients with stage III disease undergoing curative-intent therapy, despite the evidence supporting the critical impact this may have on treatment planning and outcomes. We intend that this study provide evidence to support increasing use of this simple and established technique of EBUS-TBNA in this patient group.


A positive result of VEGF (vascular endothermic growth factor) in blood sample tests implies the need for further research on cognitive changes caused by horticultural activities. This study has limitations due to the small number of participants, but the results suggest that low- to medium-intensity horticultural treatment programs using the upper body and hands could be effective for vocational rehabilitation of the intellectually disabled.For the occupational adaptation and social integration of the intellectually disabled, it is helpful to improve their work performance and interpersonal skills. The purpose of the study was to evaluate the effectiveness of horticultural therapy (HT) programs to improve work performance and interpersonal relationships of persons with intellectual disabilities. Based on observations and analyses of how people with intellectual disabilities work, we have developed a 12-session HT program that includes upper limb movements and physical activities to improve hand function. We recruited, with the consent of their legal guardians, 14  participants who had intellectual disabilities and were working at a sheltered workshop in K-gu, Seoul, South Korea. The program consisted of twelve sixty-minute sessions that were conducted twice a week at a rooftop garden. For pre- and post-evaluation of the program, the survey of functional adaptive behavior (SFAB), interpersonal negotiation strategies, a horticultural job evaluation (self), hand function tests , and blood sample tests for physiological indicators of exercise were conducted. Interpersonal negotiation strategies, functional adaptive behaviors, and physical abilities for job behaviors, including agility and grasping of the hand, improved significantly from before to after the program ( The AAIDD 2021) defines “intellectual disability” as, “a condition characterized by significant limitations in both intellectual functioning and adaptive behavior that originates before the age of 22”. It also defines adaptive behavior as, “the collection of conceptual, social, and practical skills that are learned and performed by people in their everyday lives”. The number of persons in South Korea with intellectual disabilities has increased steadily from 2015 to 2021: 189,752 in 2015; 200,903 in 2017; 212,936 in 2019; and 221,557 in 2021, increasing by 2–3% every year  Czern). Regarding the use of both hands, the participants had to hold a wooden chopstick in their left hand to make a hole and place the seeds with their right hand. Cutting was performed in two sessions (5th and 7th). In the 5th session, succulent plants that fell easily, such as Sedeveria Letizia and Crassula, were used. We asked participants to fill the trays with soil and then insert the succulent leaves in a sequence. In the 7th session, to increase the difficulty, stems of herb plants were cut directly with scissors. We chose plants that could be easily cut with scissors, such as apple mint (Mentha suaveolens) and geranium (Pelargonium inquinans Aiton). The use of hands and arms for trimming the stems and leaves can be linked to the last step of bag making. Since water management was important after planting seeds, we created a “plant care card” to manage water during the 12 sessions and to enable daily physical activity. Participants visited the roof garden daily to conduct activities such as watering, weeding, and talking to plants, and received confirmation from social workers. To manage the sown seeds, seedling sprayers were prepared for them, and they were asked to spray five times with each hand so that both hands could be trained to increase their grip and strength. This task can be linked to the tie-up process using grip power in the third step of bag making. In the 6th and 8th sessions, the sprouted plants were transferred to a garden and harvested. In the 11th session, rooted succulent and herb plants were planted to decorate their pots. In the last session, soap flower baskets were made by inserting soap flowers into baskets at regular intervals to create shapes. Before the activity, the participants practiced placing dots at regular intervals and inserting flowers in the Styrofoam. At first, the process progressed slowly, but after three or more repetitions, accuracy and speed increased. Overall, at the end of the 12-session HT program, persons with intellectual disabilities were able to improve their interpersonal relationships. They learned to be responsible by taking care of their plants and understood how to communicate with other participants. This program was developed by analyzing the steps required for work at sheltered workshops, after considering the characteristics of the persons with intellectual disabilities, and systematically applying the results from this analysis to horticultural activities.In the second stage (4th session), three medium-sized radish seeds were planted in a tray. In the third stage (10th session), a program was developed to improve concentration and hand skills by planting small red mustard seeds  were conducted to analyze the work performance and interpersonal relationships of the intellectually disabled. In addition, the level of brain nerve growth factors related to cognitive functions, such as BDNF, VEGF, and IGF-1 through blood, was analyzed. In order to change the brain nerve growth factor related to the cognitive function of the intellectually disabled, 10 mL of blood was collected before and after the program to analyze the change in the brain renal management factor. A horticultural job evaluation and a self-report questionnaire were conducted before and after the program to evaluate horticultural practice skills, responsibilities, and physical management skills. Subsequently, the participants’ satisfaction with the program was evaluated.The Grooved Pegboard  is used for neuropsychological, visual–motor coordination, and occupational assessments in both adults and children. We asked participants to randomly insert a key peg into 25 holes. The total time used to complete the task was measured only once for each hand . A hand The interpersonal negotiation strategies questionnaire, developed by Beardslee, Schultz, Selman et al. (1986) and modified by Kwon (1989), was used. Suo (1999) reported a Cronbach’s α of 0.76. The relationship with others was expressed at the level of 0 to 3 and evaluated on a 5-point Likert scale. A higher final rating score indicated more positive interpersonal relationships.To assess the SFAB, we partially reconstructed its composition and used the McCarron-Dial System (MDS), an evaluation tool that assesses residential, daily life, learning, and vocational skills. Among all the tests, we only used the vocational skill test. A three-point scale  was used in this test, which consisted of 20 items. In part A, we measured the agility of the fingers and hands, stamina, lift and move skills, upper body coordination, speed, and full-body coordination as physical abilities. In part B, appearance, courtesy, rule compliance, patience, and productivity were evaluated for work performance.Based on the horticultural activity performance assessment (HAPA) tool, developed by Kim  to evaluThe HT program investigated the effects of brain nerve growth factors related to cognitive function in intellectually disabled people. A professional nurse collected 10 mL of blood before and after the activity, and analyzed three types of brain nerve growth factors, including BDNF , VEGF , and IGF-1.Paper bag strapping is a work activity for persons with intellectual disabilities in protective workplaces. To evaluate the improvement of hand functions, 14 persons with intellectual disabilities performed the paper bag strapping activity for 5 min before and after the program. The activity was conducted in the same place under the supervision of the same social worker. The number of completed paper bags per participant was counted.p < 0.05. The Wilcoxon verification of a nonparametric paired t-test was analyzed using SPSS  for the hand function evaluation, SFAB, interpersonal negotiation strategy, and horticultural job evaluation results before and after HT program.The demographic information and satisfaction questionnaire results were analyzed using descriptive statistics in Excel . The level of statistical significance was set at p = 0.05)  .p = 0.04). As a result of the pinch gauge, the score significantly increased from 6.5 to 7.4 after the program (p = 0.02 (A gyrometer and pinch gauge were used to record the highest score among the three results of the dominant hand. The HT program significantly improved grip power from 18.6 to 20.8 (p = 0.02 ).p = 0.00).To evaluate the effects of the HT program, we conducted a paper bag strapping task for 5 min before and after the program . The nump = 0.02), and unilateral (level 1), which changed from 14.1 to 15.7 (p = 0.01). However, there were no significant changes in the means of mutual reciprocity (level 2), which changed from 10.6 to 10.0 (p = 0.33), nor in mutual cooperation (level 3), which changed from 10.2 to 9.1 (p = 0.12).The results of the subcategory-wise analysis of interpersonal negotiation strategies are presented in p = 0.02) and unilateral level . The HT program significantly improved the physical and vocational behaviors of persons with intellectual disabilities from 29.9 to 38.6 and from 25.4 to 25.7, respectively, although there was no statistically significant difference ; practical skills competency by 1.4 points, from 10.1 to 11.5 (p = 0.02); and mental and physical competence by 1.1 points, from 9.7 to 10.8 (p = 0.02).The results of the subcategory-wise analysis of horticultural job evaluations are shown in p = 0.05)  .The participants completed a satisfaction survey at the end of the HT program. Regarding the overall interest in the program, 92.8% (13 participants) were very interested, and 7.1% (1 participant) were interested. Regarding the satisfaction with the duration of the sessions, 71.4% (10 participants) were very satisfied, 21.4% (3 participants) were satisfied, and 7.1% (1 participant) were neutral. Regarding the difficulty of the program, 85.7% (12 participants) answered “easy to understand”, and 14.2% (2) answered “neutral”. In addition, 85.7% (12 participants) answered that they would like the program to continue.In the HT program, planting and decoration (20.5%) was the most common preference, followed by the arrangement of flower baskets (17.9%), sowing (15.4%), planting garden crops (10.3%), and making succulent art (10.3%). This was followed by sprouting (7.7%); hydroponics, ornamental plants, and basket harvesting (5.1%); and leafy vegetable sandwich preparation and herb planting (2.6%).The purpose of this study was to investigate the effects of the 12-session HT on improvements in work performance and interpersonal relationships among persons with intellectual disabilities in the protected workplace.p = 0.05), hand strength and endurance (p = 0.04), and hand agility (p = 0.02). Our results were consistent with those of previous studies since they showed that the HT program, comprising simple to delicate work, improved the grip power of both hands [Prior to conducting the study, researchers observed that persons with intellectual disabilities in a protective workplace mainly used their upper limbs and hands while performing their tasks. Since the HT program consisted of repeated planting and sowing, step by step, to improve hand functions and upper limb movements during horticultural activities, it improved handgrip power   .Although research targets were different, the results of this study were in line with the results of previous studies that found that the elderly who have performed horticultural activities showed significantly higher hand functions  than those who did not , and thap = 0.01). During the horticultural activities, participants were asked to form groups and select their group leaders. Through this process, they were able to communicate with each other and take responsibility for garden management. The cutting activity helped them understand how to control their feelings. This implies that intellectually impaired persons with strong impulses and a lack of understanding of others may be able to alleviate impulses and improve their understanding of others through gardening activities. These results were the same as those in studies that showed decreases in hyperactivity and aggression along with a reduction in antisocial behavior and rebellion in intellectually or mentally impaired students [The present study showed significant increases in the impulse-physical level (level 0) and unilateral level (level 1)  of people with intellectual disabilities working in a sheltered workshop. Furthermore, more research will be needed to verify the effect of changes in brain nerve growth factors related to cognitive function analyzed in this study. Based on the results, it will be possible to find a way to connect the HT program to the vocational rehabilitation program for the intellectually disabled.Occupational rehabilitation is the most important cornerstone for community therapy because it helps the intellectually disabled return to society when applied to their abilities . The resIt was difficult to recruit a control group because of the characteristics of persons with intellectual disabilities. Another limitation was the difficulty in clarifying the effects of previous studies in a short period of six weeks. To complement this study, further studies with larger sample sizes are needed.In conclusion, if the work of the intellectually disabled is analyzed and applied to a scientific horticultural therapy program, social factors such as interpersonal relationships and hand functions could be improved to provide positive possibilities for increasing work efficiency. In addition, this study found changes in the brain nerve growth factor related to cognitive function before and after participating in the program, so that additional research on the effect of horticultural therapy on cognitive changes is needed.


Sickle cell disease (SCD) is characterized by severe acute pain episodes as well as risk for chronic pain. Digital delivery of SCD pain self-management support may enhance pain self-management skills and accessibility for youth. However, little is known about how youth with SCD and their caregivers engage with digital health programs. iCanCope with pain is a digital pain self-management platform adapted for youth with SCD and caregivers through a user-centered design approach. The program was delivered via a website (separate versions for youth and caregiver) and mobile app (youth only).We aimed to characterize patterns of user engagement with the iCanCope with SCD program among youth with SCD and their caregivers.A randomized controlled trial was completed across multiple North American SCD clinics. Eligible youth were aged 12-18 years, diagnosed with SCD, English-speaking, and experiencing moderate-to-severe pain interference. Eligible caregivers were English-speaking with a child enrolled in the study. Dyads were randomized to receive the iCanCope intervention or attention-control education for 8-12 weeks. This report focused on engagement among dyads who received the intervention. User-level analytics were captured. Individual interviews were conducted with 20% of dyads. Descriptive statistics characterized quantitative engagement. Content analysis summarized qualitative interview data. Exploratory analysis tested the hypothesis that caregiver engagement would be positively associated with child engagement.21=6.6; P=.01; ϕ=0.34). Interviews revealed that most dyads would continue to use the program  and recommend it to others . The reasons for app versus website preference among youth were ease of use, acceptable time commitment, and interactivity. Barriers to caregiver engagement included high time burden and limited perceived relevance of content.The cohort included primarily female  and Black (>90% of youth [53/57] and caregivers [50/56]) participants. Among 56 dyads given program access, differential usage patterns were observed: both the youth and caregiver engaged , only the youth engaged , only the caregiver engaged , and neither individual engaged . While most youth engaged with the program , most caregivers did not . Youth were more likely to engage with the app than the website (85% [34/57] versus 68% [23/57]), and the most popular content categories were goal setting, program introduction, and symptom history. Among caregivers, program introduction, behavioral plans, and goal setting were the most popular content areas. As hypothesized, there was a moderate positive association between caregiver and child engagement (χThis is one of the first studies to apply digital health analytics to characterize patterns of engagement with SCD self-management among youth and caregivers. The findings will be used to optimize the iCanCope with SCD program prior to release.ClinicalTrials.gov NCT03201874; https://clinicaltrials.gov/ct2/show/NCT03201874 Sickle cell disease (SCD) is the most common genetic blood condition in North America and primarily affects people of African descent . The halSelf-management has been defined as “the individual’s ability to manage the symptoms, treatment, physical and psychological consequences, and lifestyle changes inherent to living with a chronic illness” . The mosBarriers to implementing cognitive behavioral therapy in SCD populations include the challenge of delivering pain self-management interventions in traditional office-based visits, costly resources required to provide such support, and maintaining patient engagement ,20. UbiqiCanCope with pain is a digital pain self-management platform originally developed for youth with chronic pain -25. The a priori hypothesis that caregiver engagement would be positively associated with child engagement.Little is known about how youth with SCD and their caregivers engage with digital health interventions, and research to date has focused mostly on internet-delivered programs . A scopiA 2-arm randomized trial design was used. Dyads were randomized to 1 of 2 possible study conditions: (1) iCanCope with SCD intervention or (2) attention-control education. Details on the trial methodology are available in an open-access protocol paper , and theThe study was approved by the locally responsible institutional ethics boards .The main recruitment sites were Connecticut Children’s Medical Center, Children’s Healthcare of Atlanta/Emory University, Seattle Children’s Hospital, and The Hospital for Sick Children in Toronto. In addition, study referrals were accepted from University of Mississippi Medical Center, Boston Medical Center, and Northwestern University/Lurie Children’s Hospital. The study was centrally managed at Seattle Children’s Research Institute.Youth were eligible if they (1) were aged between 12 and 18 years, (2) were diagnosed with any SCD genotype, (3) were able to speak and read English, (4) scored at least 4 (indicating moderate-to-severe pain interference over the past month) on the Sickle Cell Pain Burden Interview , and (5)Caregivers were eligible if (1) they were able to speak and read English, (2) they were willing and able to complete online measures, and (3) their child was a study participant. Youth were permitted to enroll in the study even if their caregiver chose not to participate.Dyads assigned to the intervention condition were given user-authenticated access to the iCanCope with SCD program for a period of 8-12 weeks. The program content, based on the principles of cognitive behavioral therapy, was delivered via a modular website and complementary smartphone app as summarized in At baseline, caregivers completed a background questionnaire to capture sociodemographic data , and both caregivers and youth completed information about their technology access and usage. Youth were screened into the study using the Sickle Cell Pain Burden Interview to assess SCD pain burden in the past month. The Sickle Cell Pain Burden Interview yielded a total score ranging from 0 (no pain burden) to 28 (severe pain burden). Dyads additionally completed several other clinical effectiveness outcomes detailed in an open-access protocol paper .User-level analytics were captured for the app and website components of the iCanCope with SCD program. App engagement was characterized using APEEE  , while wTo gather perceptions of the treatment program from youth and caregivers, individual semistructured interviews were conducted with a convenience subset of dyads representing approximately 20% of the intervention group. All dyads were invited to complete an interview following their posttreatment assessment and prior to their 6-month follow-up assessment. Recruitment for the interview continued until 12 caregivers and youth completed the interviews. Separate interviews were conducted with youth and caregivers. The interview guide was designed to capture perspectives on the experience of using the iCanCope with SCD program, including likes, dislikes, value, and areas for improvement. Interviews were 15-20 minutes in duration, conducted over the telephone, and audio recorded for later transcription.Quantitative data were analyzed using STATA version 15.1 . Descriptive statistics were used to summarize background characteristics of the sample and program engagement data. An engagement interaction with the website was defined as a unique content page view. For the app, the following engagement interactions were captured: symptom check-in completed; goal created; library article viewed; and interaction within the community forum. For the youth-specific intervention, program content was distributed across the website and app such that an individual user might access topic-specific information  by viewing a website page or reading an app library article. Given this overlap in program content delivery, engagement data for youth participants were also mapped by content category .To address our exploratory aim regarding the relationship between parent engagement and child engagement, we conducted a chi-square test (significance was set at α<.05) and assessed the strength of the association using the phi correlation. The phi correlation can range from 0 to 1 and was interpreted as follows: no correlation or very weak correlation (0-0.19), weak correlation (0.20-0.29), moderate correlation 0.30-0.49), strong correlation (0.50-0.69), and very strong correlation (0.70-1.00)  a lot of crises, this would be very helpful.Caregiver #537Similarly, a caregiver who characterized the program as a good refresher made the following statement:I like the way it’s laid out in terms of the content being very layman terms. You know, there’s not a lot of – you’re not overwhelmed with a lot of medical things that people are saying ‘oh, well what’s this, and what’s that, and what’s this?’. So, in terms of that content, I think it’s fantastic. So, I would recommend it.Caregiver #119Among the 6 of 12 (50%) caregiver interviewees who did not use the program during the study period, the reasons for low engagement included a perceived lack of relevance to their circumstances.…I found that some of the questions on it, things they would ask me - the exercises the [program] would ask me to do was sort of not relevant to me…I felt like it didn’t really apply to [my child] or to me.Caregiver #127This caregiver also noted that another reason for lack of engagement was the large amount of content.…there’s so many sections within one unit itself. So, when I thought I was almost done, I still had more to do. I’m able to do only one section at a time or not even able to finish the whole unit because of timing.…when I get home, I’m exhausted. I’m a nurse and I work in ICU so we’re very busy at work especially with the COVID…I live really far from work, so I leave home early, I get home really late, and it’s just busy that’s all but nothing else.Among caregivers who did not use the program themselves, some noted that it was helpful for their children.I think it made her more aware and more focused and…process…how she can cope with it and mostly like she’s not alone in this… that there are people out there that care. I think it really helped.Caregiver #126Others noted that the program helped them understand how to better support their children.…it actually shed a lot of light into a couple of things especially when it gets to her mood swings and why she does certain things and also helping her manage her pain.Caregiver #112One youth interviewee who did not engage with the program did not provide a specific reason why but did indicate interest in using it after the study was complete.…because I feel like it’s a good…way to…learn more about it and I could learn and study more myself.Youth #520As shown in I liked the app more because it was easier to use than the website…the app was simple, and it only took a couple of minutes.Youth #537The interactivity of the app feature set was also cited as a reason for use.I like the app more than I like the website because of the daily diaries and connecting to others…and there [is] a library inside the app where you can read and how you can set goals.Youth #126This user continued with the following statement:I think I have some downsides with the website because the website you only have to read, but the app – it’s fun.While technical bugs were rare and minimally disruptive , technical limitations of the website caused frustration among some participants and may have impacted engagement with that program component. For instance, a caregiver who had low program engagement noted the following:…the website can’t save what you write, so every time you come back it does get deleted.Caregiver #537When asked about how they used the program in their day-to-day life, youth interviewees described several concrete ways that the program supported them to engage in SCD self-management, as summarized in Youth who completed the study during the pandemic described that the program helped to mitigate some disruptions to their self-management routines.I found the app very helpful because for me it can be very hard especially because I’m in high school…now that we’re online…I like do my work and…I just stay in my room and I don’t do the stuff that I’m supposed to do to ensure that I’m preventing crises. So, having the app, especially the goal chapter, was very helpful because I was able to put what goals I wanted. For example, if I wanted to drink more water or I wanted to get more sleep that week then I was able to do that. That motivated me to want to achieve the goal.Youth #127This is one of the first studies to characterize patterns of engagement with a web- and app-based pain self-management program among youth with SCD and their caregivers. The data demonstrate that most youth with SCD engaged with the program  while most caregivers did not . The youth program was delivered via a mobile app and a website. Youth were more likely to engage with the app than the website, and the most popular content categories were goal setting, introduction to the program, and symptom history. Among caregivers who engaged with the website, introduction to the program, behavioral plans, and goal setting were the most popular content areas. Exploratory analysis revealed a significant moderate association between caregiver and youth engagement with the intervention. The key insights from qualitative interviews were as follows: (1) nearly all youth intended to continue using the program; (2) caregivers would recommend the program to others living with SCD who were newly diagnosed or who frequently experienced pain crises; (3) caregivers cited the large amount of content and low relevance to their specific circumstance as reasons for low engagement; (4) youth preferred the app over the website because of perceived greater ease of use, acceptable time commitment, and interactivity; and (5) use of the youth program helped to facilitate SCD self-management behaviors such as goal setting, applying strategies for pain management, symptom trend monitoring, and learning through peer support.There are several app- and web-based interventions designed for children and youth with SCD -36 that The iCanCope program has also been assessed in youth with juvenile idiopathic arthritis and chronic pain ,25. UsagSeveral contextual factors may explain the differences in engagement patterns seen across studies in the SCD population, among users of other iterations of the iCanCope program, and generally among the pediatric population. These factors include differences in the intervention scope , distinct definitions of engagement, different study designs and clinical populations, and technology variation  . The litThere is limited research on caregiver engagement with digital health interventions for SCD. Many interventions designed for youth do not have a caregiver component. However, 3 recent digital health studies have reported parent engagement in pediatric SCD, chronic pain, and cancer populations, respectively ,44. The Our study had several strengths. First, a phased evidence-based approach was used to develop the iCanCope with SCD program. A qualitative needs assessment involving youth with SCD, caregivers, and health care providers was completed to determine essential components of the program . Next, dThese findings should be considered in the context of a few limitations. First, caregivers were not heavily included in the design of the iCanCope program, which may partially explain their reduced engagement with the content. As per the user design approach, the creation of iCanCope was focused on meeting the needs of youth, as the primary users were envisioned to be youth, rather than caregivers. However, our study findings indicate that parent engagement with SCD program content is important as it is positively associated with child engagement. Unfortunately, poststudy interviews with caregivers revealed that the program was too content heavy and time-consuming. One strategy to improve caregiver engagement would be to account for the individual need for cognition, which refers to the enjoyment of deep thinking . For thoPrior to public release of the program, there are opportunities for refinement using the elements of persuasive design . Wen et ad hoc sharing of program content with their siblings and the finding that parent and child engagement was positively associated. Furthermore, by partnering with SCD clinics, the program could be introduced to youth and families when the SCD pain becomes more frequent to help cope with the corresponding increase in pain burden.In terms of program dissemination, using strategies to target the family unit, rather than individual members, may increase engagement as SCD typically impacts multiple members of a family. This approach is supported by youth participants who reported This is one of the first studies to apply digital health analytics to characterize patterns of engagement with SCD self-management among youth and caregivers. Differential engagement patterns were found, with more youth engaging in the program than their caregivers; however, youth were more likely to engage with the app than the website. These findings will be used to optimize the iCanCope with SCD program prior to release, with the potential to improve the accessibility and acceptability of pain self-management support for families affected by SCD.