Using the matrixed multiple case study methodology to understand site differences in the outcomes of a Hybrid Type 1 trial of a peer-led healthy lifestyle intervention for people with serious mental illness.

Site differences in implementation trial outcomes are common but often not examined. In a Hybrid Type 1 trial examining the effectiveness-implementation of a peer-led group life-style balance (PGLB) intervention for people with serious mental illness (SMI) in three supportive housing agencies, we found that PGLB recipients' physical health outcomes differed by study sites. The matrixed multiple case study methodology was used to explore how implementation outcomes and changes in context of usual care (UC) services contributed to these site differences. Two implementation outcomes (i.e. PGLB fidelity ratings and intervention recipients' acceptability of PGLB and UC) and changes in healthcare services integration at the study sites were examined. ANOVAs were used to examine site differences in fidelity ratings and client satisfaction. Directed content analysis was used to analyze leadership interviews to identify changes in the context of UC services. Site 3 showed a trend approaching significance (P = .05) towards higher fidelity ratings. High levels of satisfaction with PGLB were reported at all sites. Significant differences in PGLB recipients' satisfaction with UC were found, with Site 3 reporting the lowest levels of satisfaction. Agency leaders reported an increase in prioritizing client's health throughout the trial with sites differing in how these priorities were put into action. Differences in PGLB recipients' satisfaction with UC, and changes in healthcare service integration seemed to have contributed to the site differences in our trial. The matrixed multiple case study methodology is a useful approach to identify implementation outcomes contributing to the heterogeneity of multisite implementation trial results.

A healthy lifestyle intervention delivered by people with lived experience of serious mental illness (SMI) led to improved health outcomes among participants living with SMI in three supportive housing agencies, but these outcomes differed by study sites. This study aimed to identify which factors influenced these site differences in study outcomes by examining if the intervention was delivered as intended, intervention recipients' satisfaction with the intervention and the pre-existing health care services delivered at each study site, and what changes occurred in health care services offered at each of the supportive housing agencies throughout the study. The intervention was found to have high levels of satisfaction across all three agencies but the agency which had the best outcomes also had the highest levels of intervention delivery adherence and the lowest levels of intervention recipients' satisfaction with existing health care services. Additionally, during the study period, the same agency described minimal changes in their existing health care services while the other two agencies were found to have made more significant changes integrating health care services to their day-to-day operations. As a result, findings from this study emphasize the importance of understanding the context in which interventions are delivered in routine practice settings to ensure their overall success.

Learning, doing and sticking with it: A qualitative study on achieving clinically significant reduction in cardiovascular disease risk in a healthy lifestyle intervention for people with serious mental illness.

People with serious mental illness (SMI; e.g. schizophrenia) have mortality rates two to three times higher than the general population, largely due to a higher prevalence of cardiovascular disease (CVD). Healthy lifestyle interventions can improve the health of people with SMI, but information about why these interventions work for some and not others is scarce. Our study aims to qualitatively explore differences in these two groups' overall experiences and application of the intervention. Data were drawn from a randomised effectiveness trial of a peer-led healthy lifestyle intervention. Qualitative data from interviews and focus groups with 21 participants were linked to their 12-month outcome data. Grounded theory was used to compare the experiences of participants who achieved clinically significant CVD risk reduction (i.e. clinically significant weight loss or clinically significant improvements in cardiorespiratory fitness) versus those who did not. Three qualitative themes: learning, change, sticking with it - differentiated participants who achieved CVD risk reduction and those that did not. Participants achieving CVD risk reduction described learning and applying specific knowledge and skills related to a healthy lifestyle when making health decisions, made healthy concrete changes to diet and physical activity, and stuck with those changes. Participants not achieving clinically significant CVD risk reduction reported surface-level learning about healthy lifestyle practices, difficulty sticking with healthy changes, and were more likely to report ambiguous or no changes. Our findings suggest that healthy lifestyle interventions for people with SMI should provide experiential in-vivo learning experiences while periodically assessing participants' understanding and then tailoring the intervention to their needs. It is important to build self-efficacy for health behaviour changes by creating early perceptions of success, which was found to enhance motivation and sustain behaviour change. Helping people with SMI develop and strengthen their support systems will also be an important factor for building and sustaining health behaviour changes.

Correlates of Attendance in a Peer-Led Healthy Lifestyle Intervention for People with Serious Mental Illness Living in Supportive Housing.

Healthy lifestyle interventions can improve the physical health of people with serious mental illness (SMI; e.g., schizophrenia). Yet, people with SMI report challenges participating in these interventions, thus limiting their potential benefits. This study examined attendance of participants (N = 155), largely comprised of racial and ethnic minorities, in a peer-led healthy lifestyle intervention living in supportive housing. A logistic regression model was used to identify correlates associated with attendance. Results indicated that females, those with at least a high school education, and a diagnosis of schizophrenia were more likely to attend. In contrast, the odds of attending at least one session were significantly lower for those who reported any drug use and for those who rated their health as good or excellent. Our findings indicate certain subgroups of people with SMI could benefit from tailored motivational strategies and supports to improve their participation in healthy lifestyle interventions. clinicaltrials.gov (NCT02175641).

Impact of Moderating Demographic Variables on a Health Intervention for People with Serious Mental Illness.

Purpose: Healthy lifestyle interventions can improve the health of people with serious mental illness (SMI). Little is known whether demographic variables moderate the effectiveness of these interventions on health outcomes. Method: Data from an effectiveness trial of a peer-led healthy lifestyle intervention (PGLB) for people with SMI examine whether age, racial/ethnic minoritized status, and gender moderated the effectiveness of PGLB compared to usual care (UC) in achieving clinically significant improvements in weight, cardiorespiratory fitness, and cardiovascular disease (CVD) risk reduction. Results: Compared to UC, PGLB was most beneficial for participants age 49 and younger for achieving clinically significant weight loss and from racial/ethnic minoritized communities for achieving clinically significant weight loss and reductions in CVD risk. Conclusions: These findings suggest the impact of healthy lifestyle interventions for people with SMI may not be uniform and adaptations may be needed to make these interventions responsive to the needs of diverse populations.

Systematic Review of Psychosocial Smoking Cessation Interventions for People with Serious Mental Illness.

OBJECTIVE: Tobacco smoking is a major driver of premature mortality in people with serious mental illness (SMI; e.g., schizophrenia, bipolar disorder). This systematic literature review described randomized control trials of psychosocial smoking cessation interventions for people with SMI, rated their methodological rigor, evaluated the inclusion of racial/ethnic and sexual/gender minorities, and examined smoking cessation outcomes. Methods: Eligible studies included peer-reviewed articles published between 2009 and 2020 that examined psychosocial smoking cessation interventions in people with SMI. We used the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines to conduct our review and the Methodological Quality Rating Scale to evaluate methodological rigor. Results: Eighteen studies were included. Ten were categorized as high methodological rigor given their study characteristics (e.g., longer follow-up) and eight as lower methodological rigor based on their characteristics (e.g., not intent-to-treat). Racial/ethnic and sexual/gender minorities were under-represented in these studies. A range of psychosocial interventions were examined including motivational enhancements, smoking cessation education, cognitive behavioral strategies, and contingency management. Most studies also provided smoking cessation medications (e.g., NRT, bupropion), although provision was not always uniform across treatment conditions. Three studies found the intervention condition achieved significantly higher abstinence from smoking compared to the comparison group. Seven studies found the intervention condition achieved significantly higher reductions in smoking compared to the comparison group. Conclusions: Studies finding significant differences between the intervention and comparison groups shared common evidenced-based components, including providing smoking cessation medications (e.g., NRT, bupropion), motivational enhancement techniques, and cessation education and skills training, but differed in intensity (e.g., number and frequency of sessions), duration, and modality (e.g., group, individual, technology). Methodological limitations and a small number of studies finding significant between-group differences prevent the identification of the most effective psychosocial smoking cessation interventions. Clinical trial designs (e.g., SMART, factorial) that control for the provision of psychosocial medications and allow for the identification of optimal psychosocial treatments are needed. Future studies should also ensure greater inclusion of racial/ethnic and sexual/gender minorities and should be culturally/linguistically adapted to improve treatment engagement and study outcomes.

Ideal Cardiovascular Health in Racially and Ethnically Diverse People with Serious Mental Illness.

Cardiovascular disease is a primary contributor to premature death among people with serious mental illness (SMI). This study used baseline data (N=314) from an effectiveness trial testing a healthy lifestyle intervention for racial/ethnically diverse participants with overweight/obesity and SMI living in supportive housing. We examined the prevalence and correlates of a modified version of the American Heart Association (AHA) metric of ideal cardiovascular health (ICVH). Five AHA ICVH metrics (smoking, body mass index, diet, physical activity, and blood pressure) were used to create a composite ICVH score. The mean ICVH score was 3.15 (range 0-8). Multivariate analysis indicated that higher ICVH scores were associated with lifetime cancer diagnosis and better cardiorespiratory fitness. Lower scores were associated with female gender, racial/ethnic minority status, and antipsychotic use, suggesting that these subgroups of people with SMI may benefit from targeted screening and interventions to improve their cardiovascular health.

The toxin biliatresone causes mouse extrahepatic cholangiocyte damage and fibrosis through decreased glutathione and SOX17.

UNLABELLED: Biliary atresia, the most common indication for pediatric liver transplantation, is a fibrotic disease of unknown etiology affecting the extrahepatic bile ducts of newborns. The recently described toxin biliatresone causes lumen obstruction in mouse cholangiocyte spheroids and represents a new model of biliary atresia. The goal of this study was to determine the cellular changes caused by biliatresone in mammalian cells that ultimately lead to biliary atresia and extrahepatic fibrosis. We treated mouse cholangiocytes in three-dimensional (3D) spheroid culture and neonatal extrahepatic duct explants with biliatresone and compounds that regulate glutathione (GSH). We examined the effects of biliatresone on SOX17 levels and determined the effects of Sox17 knockdown on cholangiocytes in 3D culture. We found that biliatresone caused disruption of cholangiocyte apical polarity and loss of monolayer integrity. Spheroids treated with biliatresone had increased permeability as shown by rhodamine efflux within 5 hours compared with untreated spheroids, which retained rhodamine for longer than 12 hours. Neonatal bile duct explants treated with the toxin showed lumen obstruction with increased subepithelial staining for α-smooth muscle actin and collagen, consistent with fibrosis. Biliatresone caused a rapid and transient decrease in GSH, which was both necessary and sufficient to mediate its effects in cholangiocyte spheroid and bile duct explant systems. It also caused a significant decrease in cholangiocyte levels of SOX17, and Sox17 knockdown in cholangiocyte spheroids mimicked the effects of biliatresone. CONCLUSION: Biliatresone decreases GSH and SOX17 in mouse cholangiocytes. In 3D cell systems, this leads to cholangiocyte monolayer damage and increased permeability; in extrahepatic bile duct explants, it leads to disruption of the extrahepatic biliary tree and subepithelial fibrosis. This mechanism may be important in understanding human biliary atresia. (Hepatology 2016;64:880-893).