Multiple Perspectives on Motivating Parents in Pediatric Primary Care to Initiate Participation in Parenting Programs.

OBJECTIVE: To use multiple perspectives to identify the key components of pediatric primary care conversations for motivating parents to utilize parenting programs. We aim to develop an actionable framework that primary care clinicians (PCCs) can follow for effective conversations with parents. METHODS: We conducted focus groups and interviews with researchers (n = 6) who have experience delivering parenting interventions through primary care, clinical personnel in federally qualified health centers (FQHCs) (n = 9), parents of 3-5-year olds who receive services at a FQHC pediatric clinic (n = 6), and parent educators (n = 5). Groups and interviews were informed by nominal group technique, and researchers triangulated consolidated strategies across the groups. RESULTS: Key strategies for PCCs to motivate parents to utilize parenting programs followed three steps: 1) learning about a parent's questions and concerns, 2) sharing resources, and 3) following up. PCCs can learn about parents' needs by empathizing, listening and responding, and asking questions that acknowledge parents' expertise. When sharing resources, PCCs can motivate participation in parenting programs by explaining each resource and its benefits, providing options that support parents' autonomy, and framing resources as strengthening rather than correcting parents' existing strategies or skills. Finally, PCCs can continue to engage parents by scheduling follow-up conversations or designating a staff member to check-in with parents. We provide examples for each strategy. CONCLUSIONS: Findings provide guidance from multiple perspectives on strategies to motivate parents in pediatric primary care setting for utilizing parenting programs.

Reduction of Mental Health-Related Emergency Department Admissions for Youth and Young Adults Following a Remote Intensive Outpatient Program: Quality Improvement Analysis.

BACKGROUND: Pediatric mental health emergency department (ED) visits are increasing at 6% to 10% per year, at substantial cost, while 13% of youth with psychiatric hospitalizations are readmitted in the following weeks. Hospitals do not have the resources to meet escalating youth's mental health needs. Intensive outpatient (IOP) programs, which provide multiple hours of care each week, have the power to reduce the number of patients in need of hospitalized care and provide a step-down option for patients discharging from ED's in order to prevent readmissions. OBJECTIVE: The purpose of this program evaluation was to assess (1) whether youth and young adult ED admission rates decreased following participation in a remote IOP program and (2) whether there were differences in readmission rates between youth and young adults by gender identity, sexual orientation, race, or ethnicity. METHODS: Data were collected from intake and 3-month postdischarge surveys for 735 clients who attended at least 6 sessions of a remote IOP program for youth and young adults. Patients reported if they had been admitted to an ED within the previous 30 days and the admission reason. Over half (407/707, 57.6%) of clients were adolescents and the rest were young adults (300/707, 42.4%; mean age 18.25, SD 4.94 years). The sample was diverse in gender identity (329/687, 47.9% female; 196/687, 28.5% male; and 65/669, 9.7% nonbinary) and sexual orientation (248/635, 39.1% heterosexual; 137/635, 21.6% bisexual; 80/635, 10.9% pansexual; and 170/635, 26.8% other sexual orientation) and represented several racial (9/481, 1.9% Asian; 48/481, 10% Black; 9/481, 1.9% Indigenous; 380/481, 79% White; and 35/481, 7.2% other) and ethnic identities (112/455, 24.6% Hispanic and 28/455, 6.2% other ethnic identity). RESULTS: Mental health-related ED admissions significantly decreased between intake and 3 months after discharge, such that 94% (65/69) of clients with a recent history of mental health-related ED admissions at IOP intake reported no mental health-related ED admissions at 3 months after discharge from treatment (χ21=38.8, P<.001). There were no differences in ED admissions at intake or in improvement at 3 months after discharge by age, gender, sexuality, race, or ethnicity. CONCLUSIONS: This study documents a decrease in ED admissions between intake and 3 months after discharge among both youth and young adults who engage in IOP care following ED visits. The similar outcomes across demographic groups indicate that youth and young adults experience similar decreases after the current tracks of programming. Future research could conduct a full return-on-investment analysis for intensive mental health services for youth and young adults.

Predicting Youth and Young Adult Treatment Engagement in a Transdiagnostic Remote Intensive Outpatient Program: Latent Profile Analysis.

BACKGROUND: The youth mental health crisis in the United States continues to worsen, and research has shown poor mental health treatment engagement. Despite the need for personalized engagement strategies, there is a lack of research involving youth. Due to complex youth developmental milestones, there is a need to better understand clinical presentation and factors associated with treatment engagement to effectively identify and tailor beneficial treatments. OBJECTIVE: This quality improvement investigation sought to identify subgroups of clients attending a remote intensive outpatient program (IOP) based on clinical acuity data at intake, to determine the factors associated with engagement outcomes for clients who present in complex developmental periods and with cooccurring conditions. The identification of these subgroups was used to inform programmatic decisions within this remote IOP system. METHODS: Data were collected as part of ongoing quality improvement initiatives at a remote IOP for youth and young adults. Participants included clients (N=2924) discharged between July 2021 and February 2023. A latent profile analysis was conducted using 5 indicators of clinical acuity at treatment entry, and the resulting profiles were assessed for associations with demographic factors and treatment engagement outcomes. RESULTS: Among the 2924 participants, 4 profiles of clinical acuity were identified: a low-acuity profile (n=943, 32.25%), characterized by minimal anxiety, depression, and self-harm, and 3 high-acuity profiles defined by moderately severe depression and anxiety but differentiated by rates of self-harm (high acuity+low self-harm: n=1452, 49.66%; high acuity+moderate self-harm: n=203, 6.94%; high acuity+high self-harm: n=326, 11.15%). Age, gender, transgender identity, and sexual orientation were significantly associated with profile membership. Clients identified as sexually and gender-marginalized populations were more likely to be classified into high-acuity profiles than into the low-acuity profile (eg, for clients who identified as transgender, high acuity+low self-harm: odds ratio [OR] 2.07, 95% CI 1.35-3.18; P<.001; high acuity+moderate self-harm: OR 2.85, 95% CI 1.66-4.90; P<.001; high acuity+high self-harm: OR 3.67, 95% CI 2.45-5.51; P<.001). Race was unrelated to the profile membership. Profile membership was significantly associated with treatment engagement: youth and young adults in the low-acuity and high-acuity+low-self-harm profiles attended an average of 4 fewer treatment sessions compared with youth in the high-acuity+moderate-self-harm and high-acuity+high-self-harm profiles (ꭓ23=27.6, P<.001). Individuals in the high-acuity+low-self-harm profile completed treatment at a significantly lower rate relative to the other 2 high-acuity profiles (ꭓ23=13.4, P=.004). Finally, those in the high-acuity+high-self-harm profile were significantly less likely to disengage early relative to youth in all other profiles (ꭓ23=71.12, P<.001). CONCLUSIONS: This investigation represents a novel application for identifying subgroups of adolescents and young adults based on clinical acuity data at intake to identify patterns in treatment engagement outcomes. Identifying subgroups that differentially engage in treatment is a critical first step toward targeting engagement strategies for complex populations.

The Impact of Family Therapy Participation on Youths and Young Adult Engagement and Retention in a Telehealth Intensive Outpatient Program: Quality Improvement Analysis.

BACKGROUND:  Early treatment dropout among youths and young adults (28%-75%) puts them at risk for poorer outcomes. Family engagement in treatment is linked to lower dropout and better attendance in outpatient, in-person treatment. However, this has not been studied in intensive or telehealth settings. OBJECTIVE:  We aimed to examine whether family members' participation in telehealth intensive outpatient (IOP) therapy for mental health disorders in youths and young adults is associated with patient's treatment engagement. A secondary aim was to assess demographic factors associated with family engagement in treatment. METHODS:  Data were collected from intake surveys, discharge outcome surveys, and administrative data for patients who attended a remote IOP for youths and young adults, nationwide. Data included 1487 patients who completed both intake and discharge surveys and either completed or disengaged from treatment between December 2020 and September 2022. Descriptive statistics were used to characterize the sample's baseline differences in demographics, engagement, and participation in family therapy. Mann-Whitney U and chi-square tests were used to explore differences in engagement and treatment completion between patients with and those without family therapy. Binomial regression was used to explore significant demographic predictors of family therapy participation and treatment completion. RESULTS:  Patients with family therapy had significantly better engagement and treatment completion outcomes than clients with no family therapy. Youths and young adults with ≥1 family therapy session were significantly more likely to stay in treatment an average of 2 weeks longer (median 11 weeks vs 9 weeks) and to attend a higher percentage of IOP sessions (median 84.38% vs 75.00%). Patients with family therapy were more likely to complete treatment than clients with no family therapy (608/731, 83.2% vs 445/752, 59.2%; P<.001). Different demographic variables were associated with an increased likelihood of participating in family therapy, including younger age (odds ratio 1.3) and identifying as heterosexual (odds ratio 1.4). After controlling for demographic factors, family therapy remained a significant predictor of treatment completion, such that each family therapy session attended was associated with a 1.4-fold increase in the odds of completing treatment (95% CI 1.3-1.4). CONCLUSIONS:  Youths and young adults whose families participate in any family therapy have lower dropout, greater length of stay, and higher treatment completion than those whose families do not participate in services in a remote IOP program. The findings of this quality improvement analysis are the first to establish a relationship between participation in family therapy and an increased engagement and retention in remote treatment for youths and young patients in IOP programing. Given the established importance of obtaining an adequate dosage of treatment, bolstering family therapy offerings is another tool that could contribute to the provision of care that better meets the needs of youths, young adults, and their families.

Mental Health Outcomes for Youths With Public Versus Private Health Insurance Attending a Telehealth Intensive Outpatient Program: Quality Improvement Analysis.

BACKGROUND: COVID-19 exacerbated a growing mental health crisis among youths and young adults, worsened by a lack of existing in-person options for high-acuity care. The emergence and growth of remote intensive outpatient programs (IOPs) is a solution to overcome geographic limitations to care. However, it remains unclear whether remote IOPs engender equivalent clinical outcomes among youths with public insurance (eg, Medicaid) versus private insurance (eg, commercial) given the disparities found in previous research on place-based treatment in both clinical and engagement outcomes. OBJECTIVE: This analysis sought to establish, as part of ongoing quality improvement efforts, whether engagement and clinical outcomes among adolescents and young adults attending remote IOP treatment differed between youths with public and those with private insurance. The identification of disparities by payer type was used to inform programmatic decisions within the remote IOP system for which this quality improvement analysis was conducted. METHODS: Pearson chi-square analyses and independent 2-tailed t tests were used to establish that the 2 groups defined by insurance type were equivalent on clinical outcomes (depression, suicidal ideation, and nonsuicidal self-injury [NSSI]) at intake and compare changes in clinical outcomes. McNemar chi-square analyses and repeated-measure 2-tailed t tests were used to assess changes in clinical outcomes between intake and discharge in the sample overall. In total, 495 clients who attended the remote IOP for youths and young adults in 14 states participated in ≥7 treatment sessions, and completed intake and discharge surveys between July 2021 and April 2022 were included in the analysis. RESULTS: Overall, the youths and young adults in the remote IOP attended a median of 91% of their scheduled group sessions (mean 85.9%, SD 16.48%) and reported significantly fewer depressive symptoms at discharge (t447=12.51; P<.001). McNemar chi-square tests of change indicated significant reductions from intake to discharge in suicidal ideation (N=470, χ21=104.4; P<.001), with nearly three-quarters of youths who reported active suicidal ideation at intake (200/468, 42.7%) no longer reporting it at discharge (142/200, 71%), and in NSSI (N=430, χ21=40.7; P<.001), with more than half of youths who reported NSSI at intake (205/428, 47.9%) reporting lower self-harm at discharge (119/205, 58%). No significant differences emerged by insurance type in attendance (median public 89%, median private 92%; P=.10), length of stay (t416=-0.35; P=.73), or reductions in clinical outcomes (depressive symptom severity: t444=-0.87 and P=.38; active suicidal ideation: N=200, χ21=0.6 and P=.49; NSSI frequency: t426=-0.98 and P=.33). CONCLUSIONS: Our findings suggest that youths and young adults who participated in remote IOP had significant reductions in depression, suicidal ideation, and NSSI. Given access to the same remote high-acuity care, youths and young adults on both public and private insurance engaged in programming at comparable rates and achieved similar improvements in clinical outcomes.

Immigrant Family Financial and Relationship Stress From the COVID-19 Pandemic.

We tend to overlook immigrant families in policy and program discussions related to the COVID-19 pandemic, yet they are some of the most vulnerable to the effects of this continuing crisis. This study examined the impact of the COVID-19 pandemic on immigrant families in an upper Midwest state. We interviewed 19 human and social service providers from agencies serving Somali, Latinx, and Karen (refugees from Burma/Myanmar) immigrant families between June and August 2020. Results analyzed for this paper focused on responses to questions asked about COVID-19-related financial and familial stress, and coping resources and constraints that providers were observing with their immigrant clients. Guided by the Family Adjustment and Adaptation Response Model (Patterson, 1988), we identified a pile-up of financial and relationship stressors including employment, housing, and family relationship strains, and resource access constraints. We found that job loss in already financially vulnerable immigrant families was particularly impactful. Housing insecurity soon followed. Immigrant families also faced significant constraints to resource access including lack of documentation, fear of making a mistake, language barriers, and lack of technology skills. We identified family and community resources that families used to meet demands, coping strategies, and glimmers of resilience. As we near the end of the pandemic, we urge family researchers to monitor long-term effects of the crisis on immigrant families. Findings can inform the creation of programs and policies that address immigrant family needs for resources and culturally relevant services to support their financial recovery post-COVID.

Missing Data in Research on Youth and Family Programs.

BACKGROUND: Multilevel data can be missing at the individual level or at a nested level, such as family, classroom, or program site. Increased knowledge of higher-level missing data is necessary to develop evaluation design and statistical methods to address it. METHODS: Participants included 9,514 individuals participating in 47 youth and family programs nationwide who completed multiple self-report measures before and after program participation. Data were marked as missing or not missing at the item, scale, and wave levels for both individuals and program sites. RESULTS: Site-level missing data represented a substantial portion of missing data, ranging from 0-46% of missing data at pre-test and 35-71% of missing data at post-test. Youth were the most likely to be missing data, although site-level data did not differ by the age of participants served. In this dataset youth had the most surveys to complete, so their missing data could be due to survey fatigue. CONCLUSIONS: Much of the missing data for individuals can be explained by the site not administering those questions or scales. These results suggest a need for statistical methods that account for site-level missing data, and for research design methods to reduce the prevalence of site-level missing data or reduce its impact. Researchers can generate buy-in with sites during the community collaboration stage, assessing problematic items for revision or removal and need for ongoing site support, particularly at post-test. We recommend that researchers conducting multilevel data report the amount and mechanism of missing data at each level.

Resilience in the system: COVID-19 and immigrant- and refugee-serving health and human service providers.

INTRODUCTION: Immigrant and refugee families in the U.S. have been particularly hard hit by the COVID-19 pandemic. Health and human service providers who serve these communities have been essential in supporting them during this crisis, yet have also had to adapt the way they provide services. The current study aims to describe the challenges these service providers have faced and the adaptations they have made. METHOD: Our research team conducted semistructured interviews with 19 service providers at 10 organizations identified as serving one or more immigrant and/or refugee communities in the state of Minnesota. We analyzed the interviews for themes and used normalization process theory (May & Finch, 2009) to understand how service providers have shown resilience and where gaps in capacity emerged. RESULTS: Mechanisms of adaptation to the COVID-19 crisis included staff taking on larger workloads, utilizing existing service frameworks in new ways, shifting their services remotely and/or substantively, and utilizing the trust they had built with communities and individuals over time. Challenges that had not been fully overcome included insufficient funding for community need and restrictions on methods of interaction. DISCUSSION: Key implications include allocating funding for immigrant and refugee families, developing and evaluating new service formats in collaboration with clients, providing direct support for staff in times of crisis, and using practice-based evidence to speed implementation science research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Discovery and Characterization of Clinical Candidate LXE408 as a Kinetoplastid-Selective Proteasome Inhibitor for the Treatment of Leishmaniases.

Visceral leishmaniasis is responsible for up to 30,000 deaths every year. Current treatments have shortcomings that include toxicity and variable efficacy across endemic regions. Previously, we reported the discovery of GNF6702, a selective inhibitor of the kinetoplastid proteasome, which cleared parasites in murine models of leishmaniasis, Chagas disease, and human African trypanosomiasis. Here, we describe the discovery and characterization of LXE408, a structurally related kinetoplastid-selective proteasome inhibitor currently in Phase 1 human clinical trials. Furthermore, we present high-resolution cryo-EM structures of the Leishmania tarentolae proteasome in complex with LXE408, which provides a compelling explanation for the noncompetitive mode of binding of this novel class of inhibitors of the kinetoplastid proteasome.

Feasibility of Implementation of a Parenting Intervention with Karen Refugees Resettled from Burma.

Parents and children exposed to war and relocation have high rates of negative relational and mental health outcomes. This study tested the feasibility of implementing an adapted evidence-based parenting intervention for contexts of trauma and relocation stress. Eleven Karen refugee caregivers from Burma participated in the intervention. Participants and a focal child completed ethnographic interviews as well as structured assessments at baseline and follow-up. Caregivers reported changes in their teaching, directions, emotional regulation, discipline, and child compliance. Children reported changes in these areas and in positive parent involvement. Caregivers reported higher mental health distress immediately after the intervention, potentially due to increased awareness. Researchers made personalized referrals for counseling services as needed. Children reported a decrease in mental health symptoms.

Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness.

Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target. However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases.

Ambiguous Loss Experienced by Transnational Mexican Immigrant Families.

In this study, an ambiguous loss framework as described by Boss (1999, Ambiguous loss: Learning to live with unresolved grief, First Harvard University Press, Cambridge, MA) was used to examine and understand the family experiences of Mexican immigrant agricultural workers in Minnesota. Transcripts from interviews with 17 workers in Minnesota and 17 family members in Mexico were analyzed using qualitative methodology to identify experiences of ambiguous loss in the participants' narratives. Key dimensions of ambiguous loss identified in the transcripts include: psychological family, feelings of chronic/recurring loss, finding support, and meaning making. In the category of psychological family, participants in both Mexico and the United States mourned the physical absence of their family members and experienced ambiguity regarding family responsibilities, but worked to maintain their psychological roles within the family. In the category of chronic/recurring loss, participants in both countries experienced chronic worry from not knowing if family members were safe, ambiguity regarding when the immigrant would return, and chronic stressors that compounded these feelings of loss. Participants in both countries coped with both real and ambiguous losses by accessing family support and by using ambiguous communication to minimize worry. Participants in Mexico also accessed work and community-based support. Participants in both countries made meaning of the ambiguous loss by identifying ways their lives were improved and goals were met as a result of the immigration for agricultural work in Minnesota.

Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease.

Unbiased phenotypic screens enable identification of small molecules that inhibit pathogen growth by unanticipated mechanisms. These small molecules can be used as starting points for drug discovery programs that target such mechanisms. A major challenge of the approach is the identification of the cellular targets. Here we report GNF7686, a small molecule inhibitor of Trypanosoma cruzi, the causative agent of Chagas disease, and identification of cytochrome b as its target. Following discovery of GNF7686 in a parasite growth inhibition high throughput screen, we were able to evolve a GNF7686-resistant culture of T. cruzi epimastigotes. Clones from this culture bore a mutation coding for a substitution of leucine by phenylalanine at amino acid position 197 in cytochrome b. Cytochrome b is a component of complex III (cytochrome bc1) in the mitochondrial electron transport chain and catalyzes the transfer of electrons from ubiquinol to cytochrome c by a mechanism that utilizes two distinct catalytic sites, QN and QP. The L197F mutation is located in the QN site and confers resistance to GNF7686 in both parasite cell growth and biochemical cytochrome b assays. Additionally, the mutant cytochrome b confers resistance to antimycin A, another QN site inhibitor, but not to strobilurin or myxothiazol, which target the QP site. GNF7686 represents a promising starting point for Chagas disease drug discovery as it potently inhibits growth of intracellular T. cruzi amastigotes with a half maximal effective concentration (EC50) of 0.15 µM, and is highly specific for T. cruzi cytochrome b. No effect on the mammalian respiratory chain or mammalian cell proliferation was observed with up to 25 µM of GNF7686. Our approach, which combines T. cruzi chemical genetics with biochemical target validation, can be broadly applied to the discovery of additional novel drug targets and drug leads for Chagas disease.

Eating disorders treatment patterns by age.

This longitudinal, retrospective study examines patterns in eating disorder outpatient mental health treatment by age. Participants (n = 5,445) included patients treated for an eating disorder, with claims for treatment from Cigna, a leading health care insurance provider in the United States. Treatments for individuals 55 and older were less expensive and shorter than for any other age group. Treatments for individuals 44-55 were less expensive than for 15-24. Individual therapy is the most common treatment modality, but younger individuals are likely to receive family therapy. Younger individuals have lower dropout and higher return to care rates.

Including the family in research evaluating integrated care: a call for expanding investigators' scope beyond single-person measures.

As providers across the fields of behavioral- and biomedical- care advance efforts to include patients' families in the care that they provide, we must also include families in the research that we conduct. Additional knowledge about families in treatment could help us screen families at risk for poor outcomes, design more appropriate family based interventions, and more completely assess the impact(s) of interventions on both patients and their families. In this account, we outline assessments that are useful in responding to this call. We consider tools that target general family functioning, that are sensitive to change and progress, and that are adaptable to common time- and administrative- constraints within medical settings. We highlight strengths and weaknesses within the pool of measures that are currently available, and offer suggestions and next-steps in instrument-design and development.

Targeting the ERAD pathway via inhibition of signal peptide peptidase for antiparasitic therapeutic design.

Early secretory and endoplasmic reticulum (ER)-localized proteins that are terminally misfolded or misassembled are degraded by a ubiquitin- and proteasome-mediated process known as ER-associated degradation (ERAD). Protozoan pathogens, including the causative agents of malaria, toxoplasmosis, trypanosomiasis, and leishmaniasis, contain a minimal ERAD network relative to higher eukaryotic cells, and, because of this, we observe that the malaria parasite Plasmodium falciparum is highly sensitive to the inhibition of components of this protein quality control system. Inhibitors that specifically target a putative protease component of ERAD, signal peptide peptidase (SPP), have high selectivity and potency for P. falciparum. By using a variety of methodologies, we validate that SPP inhibitors target P. falciparum SPP in parasites, disrupt the protein's ability to facilitate degradation of unstable proteins, and inhibit its proteolytic activity. These compounds also show low nanomolar activity against liver-stage malaria parasites and are also equipotent against a panel of pathogenic protozoan parasites. Collectively, these data suggest ER quality control as a vulnerability of protozoan parasites, and that SPP inhibition may represent a suitable transmission blocking antimalarial strategy and potential pan-protozoan drug target.