Testing an implementation package in a housing skills training pilot for homeless-experienced persons with serious mental illness.

Background: Evidence-based practices (EBPs) improve housing and health for persons who have experienced homelessness with serious mental illness (PEH-SMI) but are challenging to implement. We tested a strategy to support pilot implementation of a 12-session housing skills training intervention for PEH-SMI, tailored from effective social skills training interventions. We aimed to optimize the implementation strategy and intervention prior to an implementation trial. Method: We provided training and technical assistance to nine providers to support pilot implementation of this intervention to six groups of PEH-SMI (n = 35) engaged in VA Greater Los Angeles' homeless services. We used scales and semi-structured interviews with 14 PEH-SMI and all interventionists to inform implementation strategy adaptations, identify factors that impacted implementation, and assess perceptions of the intervention. Attendance was tracked and we observed a random sample of each interventionist's groups to assess treatment fidelity. Results: Interventionists perceived the implementation strategy and the intervention favorably. However, interventionists often lacked physical space, staff, and resources (e.g., computers) to conduct the intervention. Interventionists found the content valuable for participants and a few suggested that group engagement should be a prerequisite for obtaining housing services. PEH-SMI were interested in the intervention's content and receptive to the group-based format. Participants attended a mean of 4 ± 3/12 groups; all groups observed had acceptable fidelity. Problems with intervention retention were described, suggesting challenges maintaining group participation when participants transitioned between VA homeless services. Conclusions: To support the implementation of an EBP for PEH-SMI in homeless programs, these data suggest the value of training/technical assistance and strategies that enhance program-level buy-in to address resource concerns. Intervention adaptations, e.g., using a drop-in, open group format, in community-based settings that are easily accessible to PEH-SMI, may also increase adoption. This project was registered as "Improving Housing Outcomes for Homeless Veterans" Trial registration NCT03646149, registered 8/24/2018.

There are effective social skills programs for people with serious psychiatric disorders; we adapted these programs into a 12-session housing skills program for people who had experienced homelessness. We then tested a training and technical assistance package to support the program's delivery by nine providers (e.g., social workers) to six groups of homeless people with serious psychiatric disorders (n = 35). We used surveys and interviews with some participants (n = 14) and all involved providers (n = 9) to understand their perspectives on our training and technical assistance, as well as the program itself; and to assess their views on factors that affected the program's use in real-world settings. We tracked participants' attendance at the groups and observed a random selection of groups to see if providers adhered to key program elements. We found that participants attended an average of one-third of the program's groups (4/12) but that providers were able to deliver the program to include all key elements. Some providers lacked important resources (e.g., classroom space or computers) to deliver the program as it was intended; they liked the training and technical assistance offered. Participants liked the program's content and format. Difficulties with participant retention may relate to drop-out from homeless services in which the program was delivered. This pilot project suggests that getting buy-in from leaders across levels and structuring the program as a drop-in group, in the community, or in places where attendance is easy for participants may increase its likelihood of being used as part of routine homeless services.

Clinician and Patient Perspectives on the Use of Passive Mobile Monitoring and Self-Tracking for Patients With Serious Mental Illness: User-Centered Approach.

BACKGROUND: Early intervention in mental health crises can prevent negative outcomes. A promising new direction is remote mental health monitoring using smartphone technology to passively collect data from individuals to rapidly detect the worsening of serious mental illness (SMI). This technology may benefit patients with SMI, but little is known about health IT acceptability among this population or their mental health clinicians. OBJECTIVE: We used the Health Information Technology Acceptability Model to analyze the acceptability and usability of passive mobile monitoring and self-tracking among patients with serious mental illness and their mental health clinicians. METHODS: Data collection took place between December 2020 and June 2021 in 1 Veterans Administration health care system. Interviews with mental health clinicians (n=16) assessed the acceptability of mobile sensing, its usefulness as a tool to improve clinical assessment and care, and recommendations for program refinements. Focus groups with patients with SMI (n=3 groups) and individual usability tests (n=8) elucidated patient attitudes about engaging in health IT and perceptions of its usefulness as a tool for self-tracking and improving mental health assessments. RESULTS: Clinicians discussed the utility of web-based data dashboards to monitor patients with SMI health behaviors and receiving alerts about their worsening health. Potential benefits included improving clinical care, capturing behaviors patients do not self-report, watching trends, and receiving alerts. Clinicians' concerns included increased workloads tied to dashboard data review, lack of experience using health IT in clinical care, and how SMI patients' associated paranoia and financial instability would impact patient uptake. Despite concerns, all mental health clinicians stated that they would recommend it. Almost all patients with SMI were receptive to using smartphone dashboards for self-monitoring and having behavioral change alerts sent to their mental health clinicians. They found the mobile app easy to navigate and dashboards easy to find and understand. Patient concerns centered on privacy and "government tracking," and their phone's battery life and data plans. Despite concerns, most reported that they would use it. CONCLUSIONS: Many people with SMI would like to have mobile informatics tools that can support their illness and recovery. Similar to other populations (eg, older adults, people experiencing homelessness) this population presents challenges to adoption and implementation. Health care organizations will need to provide resources to address these and support successful illness management. Clinicians are supportive of technological approaches, with adapting informatics data into their workflow as the primary challenge. Despite clear challenges, technological developments are increasingly designed to be acceptable to patients. The research development-clinical deployment gap must be addressed by health care systems, similar to computerized cognitive training. It will ensure clinicians operate at the top of their skill set and are not overwhelmed by administrative tasks, data summarization, or reviewing data that do not indicate a need for intervention. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/39010.

Passive Mobile Self-tracking of Mental Health by Veterans With Serious Mental Illness: Protocol for a User-Centered Design and Prospective Cohort Study.

BACKGROUND: Serious mental illnesses (SMI) are common, disabling, and challenging to treat, requiring years of monitoring and treatment adjustments. Stress or reduced medication adherence can lead to rapid worsening of symptoms and behaviors. Illness exacerbations and relapses generally occur with little or no clinician awareness in real time, leaving limited opportunity to modify treatments. Previous research suggests that passive mobile sensing may be beneficial for individuals with SMI by helping them monitor mental health status and behaviors, and quickly detect worsening mental health for prompt assessment and intervention. However, there is too little research on its feasibility and acceptability and the extent to which passive data can predict changes in behaviors or symptoms. OBJECTIVE: The aim of this research is to study the feasibility, acceptability, and safety of passive mobile sensing for tracking behaviors and symptoms of patients in treatment for SMI, as well as developing analytics that use passive data to predict changes in behaviors and symptoms. METHODS: A mobile app monitors and transmits passive mobile sensor and phone utilization data, which is used to track activity, sociability, and sleep in patients with SMI. The study consists of a user-centered design phase and a mobile sensing phase. In the design phase, focus groups, interviews, and usability testing inform further app development. In the mobile sensing phase, passive mobile sensing occurs with participants engaging in weekly assessments for 9 months. Three- and nine-month interviews study the perceptions of passive mobile sensing and ease of app use. Clinician interviews before and after the mobile sensing phase study the usefulness and feasibility of app utilization in clinical care. Predictive analytic models are built, trained, and selected, and make use of machine learning methods. Models use sensor and phone utilization data to predict behavioral changes and symptoms. RESULTS: The study started in October 2020. It has received institutional review board approval. The user-centered design phase, consisting of focus groups, usability testing, and preintervention clinician interviews, was completed in June 2021. Recruitment and enrollment for the mobile sensing phase began in October 2021. CONCLUSIONS: Findings may inform the development of passive sensing apps and self-tracking in patients with SMI, and integration into care to improve assessment, treatment, and patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05023252; https://clinicaltrials.gov/ct2/show/NCT05023252. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39010.

Engaging stakeholders to inform national implementation of critical time intervention in a program serving homeless-experienced Veterans.

The Veterans Affairs (VA) Grant and Per Diem Case Management "Aftercare" program provides 6 months of case management for homeless-experienced Veterans (HEVs) transitioning to permanent housing, with the aim of decreasing returns to homelessness. Implementing Critical Time Intervention (CTI)-an evidence-based case management practice-would standardize care across the 128 community-based agencies that provide Aftercare services. To prepare for national CTI implementation in Aftercare, guided by Replicating Effective Programs (REP), we conducted a four-site pilot in which we adapted a CTI implementation package (training, technical assistance, and external facilitation); characterized stakeholder perspectives regarding the acceptability and appropriateness of this package; and identified contextual factors that affected CTI implementation. We engaged a stakeholder workgroup to tailor existing CTI training and technical assistance materials for Aftercare. To provide tailored support for providers and leaders to adopt and incorporate evidence-based practices (EBPs) into routine care, we also developed external facilitation materials and processes. Over 9 months, we implemented this package at four sites. We conducted semi-structured interviews at pre-implementation, mid-implementation, and 6 months post-implementation, with HEVs (n = 37), case managers (n = 16), supervisors (n = 10), and VA leaders (n = 4); these data were integrated with templated reflection notes from the project facilitator. We used rapid qualitative analysis and targeted coding to assess the acceptability and appropriateness of CTI and our implementation package and identify factors influencing CTI implementation. Stakeholders generally found CTI acceptable and appropriate; there was consensus that components of CTI were useful and compatible for this setting. To adapt our implementation package for scale-up, this pilot highlighted the value of robust and tangible CTI training and technical assistance-grounded in real-world cases-that highlights the congruence of CTI with relevant performance metrics. Variations in agency-level contextual factors may necessitate more intense and tailored supports to implement and sustain complex EBPs like CTI. Processes used in this pilot are relevant for implementing other EBPs in organizations that serve vulnerable populations. EBP scale-up and sustainment can be enhanced by engaging stakeholders to tailor EBPs for specific contexts; pilot testing and refining implementation packages for scale-up; and using qualitative methods to characterize contextual factors that affect EBP implementation.

SLFN11 is Widely Expressed in Pediatric Sarcoma and Induces Variable Sensitization to Replicative Stress Caused By DNA-Damaging Agents.

Pediatric sarcomas represent a heterogeneous group of malignancies that exhibit variable response to DNA-damaging chemotherapy. Schlafen family member 11 protein (SLFN11) increases sensitivity to replicative stress and has been implicated as a potential biomarker to predict sensitivity to DNA-damaging agents (DDA). SLFN11 expression was quantified in 220 children with solid tumors using IHC. Sensitivity to the PARP inhibitor talazoparib (TAL) and the topoisomerase I inhibitor irinotecan (IRN) was assessed in sarcoma cell lines, including SLFN11 knock-out (KO) and overexpression models, and a patient-derived orthotopic xenograft model (PDOX). SLFN11 was expressed in 69% of pediatric sarcoma sampled, including 90% and 100% of Ewing sarcoma and desmoplastic small round-cell tumors, respectively, although the magnitude of expression varied widely. In sarcoma cell lines, protein expression strongly correlated with response to TAL and IRN, with SLFN11 KO resulting in significant loss of sensitivity in vitro and in vivo Surprisingly, retrospective analysis of children with sarcoma found no association between SLFN11 levels and favorable outcome. Subsequently, high SLFN11 expression was confirmed in a PDOX model derived from a patient with recurrent Ewing sarcoma who failed to respond to treatment with TAL + IRN. Selective inhibition of BCL-xL increased sensitivity to TAL + IRN in SLFN11-positive resistant tumor cells. Although SLFN11 appears to drive sensitivity to replicative stress in pediatric sarcomas, its potential to act as a biomarker may be limited to certain tumor backgrounds or contexts. Impaired apoptotic response may be one mechanism of resistance to DDA-induced replicative stress.

Rhabdoid Tumors Are Sensitive to the Protein-Translation Inhibitor Homoharringtonine.

PURPOSE: Rhabdoid tumors are devastating pediatric cancers in need of improved therapies. We sought to identify small molecules that exhibit in vitro and in vivo efficacy against preclinical models of rhabdoid tumor. EXPERIMENTAL DESIGN: We screened eight rhabdoid tumor cell lines with 481 small molecules and compared their sensitivity with that of 879 other cancer cell lines. Genome-scale CRISPR-Cas9 inactivation screens in rhabdoid tumors were analyzed to confirm target vulnerabilities. Gene expression and CRISPR-Cas9 data were queried across cell lines and primary rhabdoid tumors to discover biomarkers of small-molecule sensitivity. Molecular correlates were validated by manipulating gene expression. Subcutaneous rhabdoid tumor xenografts were treated with the most effective drug to confirm in vitro results. RESULTS: Small-molecule screening identified the protein-translation inhibitor homoharringtonine (HHT), an FDA-approved treatment for chronic myelogenous leukemia (CML), as the sole drug to which all rhabdoid tumor cell lines were selectively sensitive. Validation studies confirmed the sensitivity of rhabdoid tumor to HHT was comparable with that of CML cell lines. Low expression of the antiapoptotic gene BCL2L1, which encodes Bcl-XL, was the strongest predictor of HHT sensitivity, and HHT treatment consistently depleted Mcl-1, the synthetic-lethal antiapoptotic partner of Bcl-XL. Rhabdoid tumor cell lines and primary-tumor samples expressed low BCL2L1, and overexpression of BCL2L1 induced resistance to HHT in rhabdoid tumor cells. Furthermore, HHT treatment inhibited rhabdoid tumor cell line and patient-derived xenograft growth in vivo. CONCLUSIONS: Rhabdoid tumor cell lines and xenografts are highly sensitive to HHT, at least partially due to their low expression of BCL2L1. HHT may have therapeutic potential against rhabdoid tumors.