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Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected. Black patients with myelodysplasia-related AML were younger than white patients suggesting intrinsic and/or extrinsic dysplasia-causing stressors. On multivariable analyses of Black patients, NPM1 and NRAS mutations were associated with inferior disease-free and IDH1 and IDH2 mutations with reduced overall survival. Inflammatory profiles, cell type distributions and transcriptional profiles differed between Black and white patients with NPM1 mutations. Incorporation of ancestry-specific risk markers into the 2022 European LeukemiaNet genetic risk stratification changed risk group assignment for one-third of Black patients and improved their outcome prediction., (© 2024. The Author(s).)

Limited prognostic factors have been associated with overall survival (OS) post-relapse in childhood Acute Lymphoblastic Leukemia (ALL). Patients enrolled on 12 Children's Oncology Group frontline ALL trials (1996-2014) were analyzed to assess for additional prognostic factors associated with OS post-relapse. Among 16,115 patients, 2053 (12.7%) relapsed. Relapse rates were similar for B-ALL (12.5%) and T-ALL (11.2%) while higher for infants (34.2%). Approximately 50% of B-ALL relapses occurred late (≥36 months) and 72.5% involved the marrow. Conversely, 64.8% of T-ALL relapses occurred early (<18 months) and 47.1% involved the central nervous system. The 5-year OS post-relapse for the entire cohort was 48.9 ± 1.2%; B-ALL:52.5 ± 1.3%, T-ALL:35.5 ± 3.3%, and infant ALL:21.5 ± 3.9%. OS varied by early, intermediate and late time-to-relapse; 25.8 ± 2.4%, 49.5 ± 2.2%, and 66.4 ± 1.8% respectively for B-ALL and 29.8 ± 3.9%, 33.3 ± 7.6%, 58 ± 9.8% for T-ALL. Patients with ETV6::RUNX1 or Trisomy 4 + 10 had median time-to-relapse of 43 months and higher OS post-relapse 74.4 ± 3.1% and 70.2 ± 3.6%, respectively. Patients with hypodiploidy, KMT2A-rearrangement, and TCF3::PBX1 had short median time-to-relapse (12.5-18 months) and poor OS post-relapse (14.2 ± 6.1%, 31.9 ± 7.7%, 36.8 ± 6.6%). Site-of-relapse varied by cytogenetic subtype. This large dataset provided the opportunity to identify risk factors for OS post-relapse to inform trial design and highlight populations with dismal outcomes post-relapse., (© 2024. The Author(s).)

Introduction: Long-acting injectable (LAI) antipsychotic medications and clozapine are effective yet underutilized medical therapies in early intervention services. The purpose of this study was to conduct a pre-implementation evaluation of contextual determinants of early intervention programs to implement innovations optimizing LAI antipsychotic and clozapine use within a shared decision-making model., Methods: Semi-structured interviews explored barriers and facilitators to implementing LAI antipsychotics and clozapine in early intervention services. Participants were: prescribers ( n  = 2), non-prescribing clinicians ( n  = 5), administrators ( n  = 3), clients ( n  = 3), and caregivers ( n  = 3). Interviews were structured and analyzed using the Consolidated Framework for Implementation Research (CFIR 2.0)., Results: Participants were supportive of using LAI antipsychotics, despite barriers (e.g., transportation, insurance coverage), while most were unfamiliar with clozapine (Innovation). Critical incidents (e.g., COVID-19) did not interfere with implementation, while barriers included lack of performance measures; stigma affecting willingness to take medication; and clozapine considered to be a "last resort" (Outer Setting). Treatment culture was described as client-centered and collaborative, and most participants indicated LAI antipsychotic use was compatible with clinic workflows, but some were in need of resources (e.g., individuals trained to administer LAI antipsychotics; Inner Setting). Participants on the healthcare team expressed confidence in their roles. Family education and collaborative decision-making were recommended to improve client/family engagement (Individuals). Participants related the importance of tracking medication compliance, addressing client concerns, and providing prescribers with updated guidelines on evidence-based treatment (Implementation Process)., Discussion: Results may guide implementation strategy selection for future programs seeking to optimize the use of LAI antipsychotics and clozapine for early-phase schizophrenia, when appropriate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Carroll, Robinson, Kane, Kordon, Bannon, Walunas and Brown.)

Drug checking is a harm reduction measure that provides people with the opportunity to confirm the identity and purity of substances before consumption. The CanTEST Health and Drug Checking Service is Australia's first fixed-site drug checking service, where clients can learn about the contents of the samples they provide while receiving tailored harm reduction and health advice. Three samples were recently presented to the service with the expectation of 4-fluoromethylphenidate (4F-MPH) 1, methoxetamine (MXE) 2 and 3-methylmethcathinone (3-MMC) 3. The identity of all three samples did not meet these expectations and remained unknown on-site, as no high confidence identifications were obtained. However, further analysis by nuclear magnetic resonance spectroscopy, high resolution gas chromatography-electron ionisation-mass spectrometry and liquid chromatography-electrospray ionisation-mass spectrometry at the nearby Australian National University allowed for the structure elucidation of the three samples as 4-fluoro-α-pyrrolidinoisohexanophenone (4F-α-PiHP) 4, 1-(4-fluorobenzyl)-4-methylpiperazine (4F-MBZP) 5 and N-propyl-1,2-diphenylethylamine (propylphenidine) 6, respectively. Given all three samples were not of the expected identity and have not yet been described as new psychoactive substances in the literature, this study presents a full characterisation of each compound. As exemplified by this rapid identification of three unexpected new psychoactive substances, drug checking can be used as an effective method to monitor the unregulated drug market., (© 2024 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Mutations in protein tyrosine phosphatase non-receptor type 11 ( PTPN11 ) have been considered late acquired mutations in acute myeloid leukemia (AML) development. To interrogate the ontogeny of PTPN11 mutations, we utilized single-cell DNA sequencing and identified that PTPN11 mutations can occur as initiating events in some AML patients when accompanied by strong oncogenic drivers, commonly NPM1 mutations. The co-driver role of PTPN11 mutations was confirmed in a novel murine model that exhibits an AML phenotype with early expansion of a diverse set of variably differentiated myeloid cells that engrafted into immunodeficient and immunocompetent mice. This immune diversity was reconstituted from early precursor cells when engrafted into immunodeficient mice. Moreover, immune diversity was also observed in the blast component of patient samples with NPM1 and PTPN11 mutations, providing novel antigen targets for immune based approaches in this subset of AML that is resistant to multiple targeted therapies.

Background: The Collaborative Care Model (CoCM) is an evidence-based mental health treatment in primary care. A greater understanding of the determinants of successful CoCM implementation, particularly the characteristics of multi-level implementers, is needed., Methods: This study was a process evaluation of the Collaborative Behavioral Health Program (CBHP) study (NCT04321876) in which CoCM was implemented in 11 primary care practices. CBHP implementation included screening for depression and anxiety, referral to CBHP, and treatment with behavioral care managers (BCMs). Interviews were conducted 4- and 15-months post-implementation with BCMs, practice managers, and practice champions (primary care clinicians). We used framework-guided rapid qualitative analysis with the Consolidated Framework for Implementation Research, Version 2.0, focused on the Individuals domain, to analyze response data. These data represented the roles of Mid-Level Leaders (practice managers), Implementation Team Members (clinicians, support staff), Innovation Deliverers (BCMs), and Innovation Recipients (primary care/CBHP patients) and their characteristics (i.e., Need, Capability, Opportunity, Motivation)., Results: Mid-level leaders (practice managers) were enthusiastic about CBHP (Motivation), appreciated integrating mental health services into primary care (Need), and had time to assist clinicians (Opportunity). Although CBHP lessened the burden for implementation team members (clinicians, staff; Need), some were hesitant to reallocate patient care (Motivation). Innovation deliverers (BCMs) were eager to deliver CBHP (Motivation) and confident in assisting patients (Capability); their opportunity to deliver CBHP could be limited by clinician referrals (Opportunity). Although CBHP alleviated barriers for innovation recipients (patients; Need), it was difficult to secure services for those with severe conditions (Capability) and certain insurance types (Opportunity)., Conclusions: Overall, respondents favored sustaining CoCM and highlighted the positive impacts on the practice, health care team, and patients. Participants emphasized the benefits of integrating mental health services into primary care and how CBHP lessened the burden on clinicians while providing patients with comprehensive care. Barriers to CBHP implementation included ensuring appropriate patient referrals, providing treatment for patients with higher-level needs, and incentivizing clinician engagement. Future CoCM implementation should include strategies focused on education and training, encouraging clinician buy-in, and preparing referral paths for patients with more severe conditions or diverse needs., Trial Registration: ClinicalTrials.gov(NCT04321876). Registered: March 25,2020. Retrospectively registered., (© 2024. The Author(s).)

Infants less than 1 year old diagnosed with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL) are at high risk of remission failure, relapse, and death due to leukemia, despite intensive therapies. Infant KMT2A-r ALL blasts are characterized by DNA hypermethylation. Epigenetic priming with DNA methyltransferase inhibitors increases the cytotoxicity of chemotherapy in preclinical studies. The Children's Oncology Group trial AALL15P1 tested the safety and tolerability of five days of azacitidine immediately prior to the start of chemotherapy on day six, in four post-induction chemotherapy courses for infants with newly diagnosed KMT2A-r ALL. The treatment was welltolerated, with only two of 31 evaluable patients (6.5%) experiencing dose-limiting toxicity. Whole genome bisulfite sequencing of peripheral blood mononuclear cells (PBMCs) demonstrated decreased DNA methylation in 87% of samples tested following five days of azacitidine. Event-free survival was similar to prior studies of newly diagnosed infant ALL. Azacitidine is safe and results in decreased DNA methylation of PBMCs in infants with KMT2A-r ALL, but the incorporation of azacitidine to enhance cytotoxicity did not impact survival. Clinicaltrials.gov identifier: NCT02828358.

It is well established that the integration of behavioral healthcare into the medical home model improves patient outcomes, reduces costs, and increases resident learning. As academic health centers increasingly integrate behavioral healthcare, targeted training for interprofessional collaboration around behavioral healthcare is needed. Simulation educational approaches potentially can provide this training. Health service psychologists are well-poised to support this because of their specialized training in integrated healthcare. The present exploratory study aimed to evaluate existing simulation programs and develop recommendations for integrated behavioral health training and evaluation. Directors of ACGME accredited residency programs that are high utilizers of the medical home model (Pediatrics, Internal Medicine, Medicine/Pediatrics, Family Medicine) as well as Psychiatry residencies and medical schools with membership in the Society for Simulation in Healthcare were recruited to complete a 26-item survey to assess program usage of psychologists as part of simulation training for integrated behavioral healthcare services. Of 79 participants who completed initial items describing their training program, only 32 programs completed the entire survey. While many academic health centers offered integrated team and behavioral health simulations, few utilized psychology faculty in design, implementation, and evaluation. Other behavioral health providers (psychiatrists, social workers) were often involved in medical school and pediatric residency simulations. Few institutions use standardized evaluation. Qualitative feedback and faculty-written questionnaires were often used to evaluate efficacy. Survey responses suggest that psychologists play limited roles in integrated behavioral healthcare simulation despite their expertise in interdisciplinary training, integrated behavioral healthcare, and program evaluation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Hypertension affects 1 in 3 adults in the United States and disproportionately affects African Americans. Kaiser Permanente demonstrated that a "bundle" of evidence-based interventions significantly increased blood pressure control rates. This paper describes a multiyear process of developing the protocol for a trial of the Kaiser bundle for implementation in under-resourced urban communities experiencing cardiovascular health disparities during the planning phase of this biphasic award (UG3/UH3)., Methods: The protocol was developed by a collaboration of faith-based community members, representatives from community health center practice-based research networks, and academic scientists with expertise in health disparities, implementation science, community-engaged research, social care interventions, and health informatics. Scientists from the National Institutes of Health and the other grantees of the Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) Alliance also contributed to developing our protocol., Results: The protocol is a hybrid type 3 effectiveness-implementation study using a parallel cluster randomized trial to test the impact of practice facilitation on implementation of the Kaiser bundle in community health centers compared with implementation without facilitation. A central strategy to the Kaiser bundle is to coordinate implementation via faith-based and other community organizations for recruitment and navigation of resources for health-related social risks., Conclusions: The proposed research has the potential to improve identification, diagnosis, and control of blood pressure among under-resourced communities by connecting community entities and healthcare organizations in new ways. Faith-based organizations are a trusted voice in African American communities that could be instrumental for eliminating disparities., Competing Interests: Conflict of Interest: S.T.L. discloses that she is founder and co-owner of NowPow LLC, a company acquired in 2021 by Unite Us LLC, where she is currently an advisor and stockholder. She is president of MAPSCorps, a 501c3 nonprofit organization, and serves on other nonprofit boards. Neither the University of Chicago nor the University of Chicago Medicine endorses or promotes any NowPow, Unite Us, or MAPSCorps product or service. S.T.L. holds debt in Glenbervie Health LLC and owns health care-related investments managed by third parties. S.T.L. is a contributor to UpToDate, Inc. The University of Chicago receives royalties from UpToDate, Inc. In addition to the acknowledged funding for the CIRCL study, S.T.L., E.M.A., and E.A.P. are also supported by R01MD012630, R01AG064949, R01DK127961, R01HL150909, and P30CA014599. T.L.W. receives research funding from Gilead Sciences for work related to coronavirus disease (COVID) in immunosuppressed populations. O.A.S. is supported by an Administrative Supplement to Promote a Diverse Research Community from the Office of the Vice President for Research at the University of Utah, awarded to J.D.S. F.S.A. was supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute (K23HL155970) and the American Heart Association (AHA number 856917).

Background: The translation of evidence-based interventions into practice settings remains challenging. Implementation science aims to bridge the evidence-to-practice gap by understanding multilevel contexts and tailoring evidence-based interventions accordingly. Engaging community partners who possess timely, local knowledge is crucial for this process to be successful. The Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) Alliance aims to address cardiopulmonary health disparities by engaging diverse community partners to improve the implementation of evidence-based interventions. The goal of the Community Engagement Subcommittee is to strengthen community engagement practice across DECIPHeR. This paper presents the subcommittee's "Why We Engage Communities" statement that outlines why community engagement is critical for implementation science. The paper also provides case examples of DECIPHeR community engagement activities., Methods: To develop the "Why We Engage Communities" statement, we conducted a literature review, surveyed subcommittee members to assess the importance of community engagement in their work, and integrated community partner feedback. We synthesize the findings into three key themes and present examples of community engagement activities and their impact across DECIPHeR projects., Results: The statement presents three themes that illustrate why community engagement increases the impact of implementation and health equity research. Community engagement (1) engages local knowledge and expertise, (2) promotes authentic relationships, and (3) builds community and researcher capacity. The statement provides a guiding framework for strengthening DECIPHeR research and enhancing community partnerships., Conclusion: Community engagement can improve the implementation of evidence-based interventions across diverse settings, improving intervention effectiveness in underserved communities and furthering health equity., Competing Interests: Conflict of Interest: All authors have no conflicts of interest to report.

Objectives: Hypertension is associated with high morbidity and mortality. The complications of hypertension disproportionately impact African American residents in Chicago's South Side neighborhood. To inform the implementation of an evidence-based multilevel hypertension management intervention, we sought to identify community member- and clinician-level barriers to diagnosing and treating hypertension, and strategies for addressing those barriers., Methods: We conducted 5 focus groups with members of faith-based organizations (FBOs) (n=40) and 8 focus groups with clinicians and administrators (n=26) employed by community health centers (CHCs) located in Chicago's South Side., Results: Participants across groups identified the physical environment, including lack of access to clinics and healthy food, as a risk factor for hypertension. Participants also identified inconsistent results from home blood pressure monitoring and medication side effects as barriers to seeking diagnosis and treatment. Potential strategies raised by participants to address these barriers included (1) addressing patients' unmet social needs, such as food security and transportation; (2) offering education that meaningfully engages patients in discussions about managing hypertension (eg, medication adherence, diet, follow-up care); (3) coordinating referrals via community-based organizations (including FBOs) to CHCs for hypertension management; and (4) establishing a setting where community members managing hypertension diagnosis can support one another., Conclusions: Clinic-level barriers to the diagnosis and treatment of hypertension, such as competing priorities and resource constraints, are exacerbated by community-level stressors. Community members and clinicians agreed that it is important to select implementation strategies that leverage and enhance both community- and clinic-based resources., Competing Interests: Conflict of Interest: No conflicts of interest reported by authors.

Depression, poor sleep duration and low self-efficacy are common in mothers of children with sleep problems. However, research rarely extends beyond the postpartum period. This study investigated the multifaceted relationship between child sleep and maternal depression in early motherhood. A confidential survey assessed child sleep problems, maternal sleep duration, parental self-efficacy and depressive symptoms in 477 Australian mothers of children aged 3 months to 5 years. We found no relationship between child age and maternal depression, supporting our decision to look beyond postpartum depression. Robust bootstrapped mediation modelling tested the hypothesis that both maternal sleep duration and parental self-efficacy would mediate child sleep problems as predictors of maternal depression. After controlling for child age, results showed a significant parallel mediation effect, demonstrating that maternal sleep duration and parental self-efficacy both mediate the relationship between child sleep problems on maternal depression. While the total effect of child sleep problems on maternal depression was statistically significant, after partialling out the effects of other variables, child sleep problems no longer predicted maternal depression. Akaike information criterion analyses supported the full model, with both mediators explaining meaningful variance in maternal depression. This study expands our knowledge beyond the postpartum period, and divulges the disparate effects of sleep deprivation and parental self-efficacy on the relationship between child sleep and depression in early motherhood. Maternal sleep duration and self-efficacy are modifiable risk factors of maternal depression, indicating possible efficacious treatments. Parental self-efficacy stands out as a direction for clinical practice and further psychobiological study., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PI COG ) that maximized discrimination of the predictive model. Patients with higher PI COG have higher predicted relapse risk. The PI COG reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PI COG identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PI COG identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PI COG identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PI COG can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure., (© 2024. The Author(s).)

Background: Up to 20% of youth have impairing mental health problems as early as age 3. Early identification and intervention of mental health risks in pediatric primary care could mitigate this crisis via prevention prior to disease onset. The purpose of this study was to establish the feasibility and acceptability of implementing a brief transdiagnostic screening instrument in pediatric primary care for irritability and corollary impairment., Method: Five pediatric clinicians in a Midwest clinic implemented the Multidimensional Assessment Profiles-Early Assessment Screener of Irritability (MAPS-EASI) for toddlers (24-30 months) and their families. MAPS-EASI (psychometrically derived from the well-validated MAPS-Scales) includes six items (scored 0-5) about symptoms (e.g., tantrums, grumpy mood), context, and frequency and two items (scored 0-3) assessed impairment. Positive screens (MAPS-EASI ≥ 5 plus impairment ≥ 2) were referred to an evidence-based parenting intervention. We assessed reach and outcomes of MAPS-EASI screening. Follow-up interviews with clinicians assessed perspectives on irritability screening and MAPS-EASI implementation., Results: Of 201 eligible families, 100 (49.8%) completed the screener for a 24- or 30-month well-child visit. Mean MAPS-EASI scores were 5.8 (SD = 3.2), mean impairment scores were 0.9 (SD = 0.9), and 24 (24.0%) screened positive. Clinicians indicated that irritability screening for toddlers was aligned with their prevention-oriented, developmentally based practice. MAPS-EASI had face validity and increased clinician decision-making confidence. Finally, clinicians identified barriers and facilitators to large-scale implementation., Conclusions: MAPS-EASI proved to be feasible and acceptable in pediatric primary care. Further tailoring will be needed as the MAPS-EASI processes are scaled out to new contexts and populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Social-emotional risk for subsequent behavioral health problems can be identified at toddler age, a period where prevention has a heightened impact. This study aimed to meaningfully engage pediatric clinicians, given the emphasis on health promotion and broad reach of primary care, to prepare an Implementation Research Logic Model to guide the implementation of a screening and referral process for toddlers with elevated social-emotional risk., Method: Using an adaptation of a previously published community partner engagement method, six pediatricians from community health centers (CHCs) comprised a Clinical Partner Work Group. The group was engaged in identifying determinants (barriers/facilitators), selecting and specifying strategies, strategy-determinant matching, a modified Delphi approach for strategy prioritization, and user-centered design methods. The data gathered from individual interviews, two group sessions, and a follow-up survey resulted in a completed Implementation Research Logic Model., Results: The Clinical Partner Work Group identified 16 determinants, including barriers (e.g., patient access to electronic devices) and facilitators (e.g., clinician buy-in). They then selected and specified 14 strategies, which were prioritized based on ratings of feasibility, effectiveness, and priority. The highest-rated strategies (e.g., integration of the screener into the electronic health record) provided coverage of all identified barriers and comprised the primary implementation strategy "package" to be used and tested., Conclusions: Clinical partners provided important context and insights for implementation strategy selection and specification to support the implementation of social-emotional risk screening and referral in pediatric primary care. The methodology described herein can improve partner engagement in implementation efforts and increase the likelihood of success. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: Screening to promote social-emotional well-being in toddlers has positive effects on long-term health and functioning. Communication about social-emotional well-being can be challenging for primary care clinicians for various reasons including lack of time, training and expertise, resource constraints, and cognitive burden. Therefore, we explored clinicians' perspectives on identifying and communicating with caregivers about social-emotional risk in toddlers., Method: In 2021, semistructured interviews were conducted with pediatric clinicians (N = 20) practicing in Federally Qualified Health Centers in a single metropolitan area. Most participants identified as female (n = 15; 75%), white non-Hispanic/Latino (n = 14; 70%), and were Doctors of Medicine or Osteopathic Medicine (n = 14; 70%). Thematic analysis was conducted on audio-recorded interview transcripts., Results: Clinicians used various approaches to identify social-emotional concerns which were sometimes difficult to distinguish from other developmental concerns. The clinician-caregiver relationship guided identification and communication practices and cut-across themes. Themes include: starting with caregivers' concerns, communicating concerns with data and sensitivity, navigating labels, culture, and stigma, and limiting communication based on family capacity and interest., Discussion: Prioritizing the clinician-caregiver relationship is consistent with best practice and family-centered care. Yet, the dearth of standardized decision support may undermine clinician confidence and impede timely conversations about social-emotional concerns. An evidence-based approach with developmentally based culturally informed quantitative tools and standardized decision supports could help ensure equitable management and decision making about young children's social and emotional well-being and development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: Depression is a risk factor for coronary heart disease and left ventricular hypertrophy (LVH) is a potent predictor of coronary heart disease events. Whether depression is associated with LVH has received limited investigation. This study assessed cross-sectional and 20-year longitudinal associations of depressive symptoms with LVH outcomes after accounting for important known confounders., Methods: From 5115 participants enrolled in 1985-1986 in the Coronary Artery Risk Development in Young Adults Study, 2533 had serial measures of depressive symptoms and subsequent echocardiography to measure normal LV geometry, concentric remodeling, and LVH. The primary exposure variable was trajectories of the Center for Epidemiologic Studies Depression (CES-D) scale score from 1990-1991 to 2010-2011. Multivariable polytomous logistic regression was used to assess associations of trajectories with a composite LV geometry outcome created using echocardiogram data measured in 2010-2011 and 2015-2016. Sex-specific conflicting results led to exploratory models that examined potential importance of testosterone and sex hormone-binding globulin., Results: Overall CES-D and Somatic subscale trajectories had significant associations with LVH for female participants only. Odds ratios for the subthreshold (mean CES-D ≈ 14) and stable (mean CES-D ≈ 19) groups were 1.49 (95% confidence interval = 1.05-2.13) and 1.88 (95% confidence interval = 1.16-3.04), respectively. For female participants, sex hormone-binding globulin was inversely associated with LVH, and for male participants, bioavailable testosterone was positively associated with concentric geometry., Conclusions: Findings from cross-sectional and longitudinal regression models for female participants, but not male ones, and particularly for Somatic subscale trajectories suggested a plausible link among depression, androgens, and LVH. The role of androgens to the depression-LVH relation requires additional investigation in future studies., (Copyright © 2024 by the American Psychosomatic Society.)

Purpose: Patients with Down syndrome (DS) and B-ALL experience increased rates of relapse, toxicity, and death. We report results for patients with DS B-ALL enrolled on Children's Oncology Group trials between 2003 and 2019., Methods: We analyzed data for DS (n = 743) and non-DS (n = 20,067) patients age 1-30 years on four B-ALL standard-risk (SR) and high-risk trials., Results: Patients with DS exhibited more frequent minimal residual disease (MRD) ≥0.01% at end induction (30.8% v 21.5%; P < .001). This difference persisted at end consolidation only in National Cancer Institute (NCI) high-risk patients (34.0% v 11.7%; P < .0001). Five-year event-free survival (EFS) and overall survival (OS) were significantly poorer for DS versus non-DS patients overall (EFS, 79.2% ± 1.6% v 87.5% ± 0.3%; P < .0001; OS, 86.8% ± 1.4% v 93.6% ± 0.2%; P < .0001), and within NCI SR and high-risk subgroups. Multivariable Cox regression analysis of the DS cohort for risk factors associated with inferior EFS identified age >10 years, white blood count >50 × 10 3 /μL, and end-induction MRD ≥0.01%, but not cytogenetics or CRLF2 overexpression. Patients with DS demonstrated higher 5-year cumulative incidence of relapse (11.5% ± 1.2% v 9.1% ± 0.2%; P = .0008), death in remission (4.9% ± 0.8% v 1.7% ± 0.1%; P < .0001), and induction death (3.4% v 0.8%; P < .0001). Mucositis, infections, and hyperglycemia were significantly more frequent in all patients with DS, while seizures were more frequent in patients with DS on high-risk trials (4.1% v 1.8%; P = .005)., Conclusion: Patients with DS-ALL exhibit an increased rate of relapse and particularly of treatment-related mortality. Novel, less-toxic therapeutic strategies are needed to improve outcomes.

Purpose: Multiple studies suggest an association between DLG2 and neurodevelopmental disorders and indicate the haploinsufficiency of this gene; however, few cases have been thoroughly described. We performed additional studies to confirm this clinical association and DLG2 haploinsufficiency., Methods: Chromosomal microarray analysis was performed on 11,107 patients at the Cytogenetics Laboratory at the University of Alabama at Birmingham. The Database of Genomic Variants-Gold Standard Variants and the Genome Aggregation Database were selected for the association analysis. Fifty-nine patients from the literature and DECIPHER, all having DLG2 intragenic deletions, were included for comprehensive analysis of the distribution of these deletions., Results: A total of 13 patients with DLG2 intragenic deletions, from 10 families in our cohort, were identified. Nine of 10 probands presented with clinical features of neurodevelopmental disorders. Congenital anomalies and dysmorphism were common in our cohort of patients. Association analysis showed that the frequency of DLG2 deletions in our cohort is significantly higher than those in the Database of Genomic Variants-Gold Standard Variants and the Genome Aggregation Database. Most of DLG2 intragenic deletions identified in 69 unrelated patients from our cohort, the literature, and DECIPHER map to the 5' region of the gene, with a hotspot centered around HPin7, exon 8, and HPin8., Conclusion: Our findings reinforce the link between DLG2 intragenic deletions and neurodevelopmental disorders, strongly support the haploinsufficiency of this gene, and indicate that these deletions might also have an association with congenital anomalies and dysmorphism., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Clinical outcome of patients with acute myeloid leukemia (AML) is associated with demographic and genetic features. Although the associations of acquired genetic alterations with patients' sex have been recently analyzed, their impact on outcome of female and male patients has not yet been comprehensively assessed. We performed mutational profiling, cytogenetic and outcome analyses in 1726 adults with AML (749 female and 977 male) treated on frontline Alliance for Clinical Trials in Oncology protocols. A validation cohort comprised 465 women and 489 men treated on frontline protocols of the German AML Cooperative Group. Compared with men, women more often had normal karyotype, FLT3-ITD, DNMT3A, NPM1 and WT1 mutations and less often complex karyotype, ASXL1, SRSF2, U2AF1, RUNX1, or KIT mutations. More women were in the 2022 European LeukemiaNet intermediate-risk group and more men in adverse-risk group. We found sex differences in co-occurring mutation patterns and prognostic impact of select genetic alterations. The mutation-associated splicing events and gene-expression profiles also differed between sexes. In patients aged <60 years, SF3B1 mutations were male-specific adverse outcome prognosticators. We conclude that sex differences in AML-associated genetic alterations and mutation-specific differential splicing events highlight the importance of patients' sex in analyses of AML biology and prognostication., (© 2023. The Author(s).)

Background: We sought to identify depressive symptom subgroups in a community sample of young adults, investigate their stability over time, and determine their association with prevalent and incident cardiovascular disease (CVD) risk factors., Method: Participants were 3377 adults from the Coronary Artery Risk Development in Young Adults study. Using latent class and latent transition analysis, we derived subgroups based on items of the 20-item version of the Center for Epidemiologic Studies Depression Scale in 1990, and examined patterns of change over a 10-year period (1990-2000). Cox regression models were used to examine associations between subgroup membership and prevalent (2000) and incident (2000 to 2016) obesity, hypertension, and diabetes., Results: Three baseline subgroups were identified and labeled: "No Symptoms" (63.5%), "Lack of Positive Affect" (PA, 25.6%), and "Depressed Mood" (10.9%). At 10-year follow-up, individuals in "No Symptoms" subgroup had the highest probability (0.84) of being classified within the same subgroup. Participants classified as "Lack of PA" were likely (0.46) to remain in the same subgroup or be classified as "No Symptoms." Participants in the "Depressed Mood" were most likely to transition to the "Lack of PA" subgroup (0.38). Overall, 30.5% of participants transitioned between subgroups, with 11.4% classified as "Worsening" and 19.1% as "Improving." Relative to the "No Symptoms Stable," other subgroups ("Depressed Stable," "Worsening," and "Improving") were associated with prevalent obesity and hypertension., Conclusion: We identified distinct depressive symptom subgroups that are variably stable over time, and their change patterns were differentially associated with CVD risk factor prevalence., (© 2023. International Society of Behavioral Medicine.)

Background: The burden of cardiovascular disease (CVD) is particularly high in several US states, which include the state of Michigan. Hypertension and smoking are two major risk factors for mortality due to CVD. Rural Michigan is disproportionally affected by CVD and by primary care shortages. The Healthy Hearts for Michigan (HH4M) study aims to promote hypertension management and smoking cessation through practice facilitation and quality improvement efforts and is part of the multi-state EvidenceNOW: Building State Capacity initiative to provide external support to primary care practices to improve care delivery., Methods: Primary care practices in rural and underserved areas of Michigan were recruited to join HH4M, a pragmatic, single-arm hybrid Type 2 effectiveness-implementation study during which practice facilitation was delivered at the practice level for 12 months, followed by a 3-month maintenance period., Results: Fifty-four practices were enrolled over a 12-month recruitment period. At baseline, the mean proportion (standard deviation) of patients at the practice level meeting the clinical quality measures were: blood pressure, 0.72 (0.12); tobacco screening, 0.80 (0.30); tobacco cessation intervention, 0.57 (0.28); tobacco screening and cessation intervention: 0.78 (0.26)., Conclusion: This three-year research program will evaluate the ability of rural and medically underserved primary care practices to implement the quality improvement model by identifying drivers of and barriers to sustainable implementation, and test whether the model improves (a) blood pressure control and (b) tobacco use screening and cessation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Adolescence is a vulnerable developmental period, characterized by high rates of mental health concerns, yet few adolescents receive treatment. Public libraries support adolescents by providing them with access to teen programming, technological resources, and have recently been providing mental health services. Digital mental health (DMH) services may help libraries provide scalable mental health solutions for their adolescent patrons and could be well positioned to address the mental health needs of historically underrepresented racial and ethnic (HURE) adolescents; however, little research has been conducted on the compatibility of DMH services with adolescent patron mental health needs or resource needs of library workers supporting them., Methods: The research team formed a partnership with a public library, which serves a large HURE adolescent population. We conducted needs assessment and implementation readiness interviews with 17 library workers, including leadership, librarians, and workers with specialized areas of practice. Interview questions focused on library infrastructure, as well as library needs and preferences around the design and implementation of DMH services for adolescents. We used the Consolidated Framework for Implementation Research as guiding implementation determinant framework to code and analyze the interview transcripts., Results: Our findings revealed library workers play an important role in guiding patrons to desired resources and share a goal of implementing adolescent DMH resources into the library and elevating marginalized adolescents' voices. Existing library resources, such as the library's role as a safe space for adolescents in the community, close relationships with external and community organizations, and availability of no-cost technological resources, could help facilitate the implementation of DMH services. Barriers related to community buy-in, mental health stigma, and library worker confidence in supporting adolescent mental health could affect service implementation., Conclusions: Our findings suggest public libraries are highly promising settings to deploy DMH services for adolescents. We identified important determinants that may impact the implementation of DMH services in public library settings. Special considerations are needed to design services to meet the mental health needs of HURE adolescent populations and those adolescents' most experiencing health inequities., Competing Interests: AK has accepted consulting fees from Woebot, Inc. DM has accepted honoraria and consulting fees from Apple, Inc., Otsuka Pharmaceuticals, Pear Therapeutics, and the One Mind Foundation, royalties from Oxford Press, and has an ownership interest in Adaptive Health, Inc. AG, VH, and RS are employed by the Oak Park Public Library. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Knapp, Hersch, Wijaya, Herrera, Kruzan, Carroll, Lee, Baker, Gray, Harris, Simmons, Kour Sodhi, Hannah, Reddy, Karnik, Smith, Brown and Mohr.)

Background: Elevated depressive symptoms and cigarette smoking are independently associated with poorer cardiovascular health (CVH), but it is unknown whether their treatment can synergistically improve CVH. We sought to characterize CVH of adults with comorbid depression and smoking and examine changes in CVH associated with changes in smoking and depression., Methods: Participants (N = 300, 55 % women) were adult smokers (≥ 1 cigarette/day) with lifetime major depressive disorder enrolled in a 12-week intervention trial targeting depression and smoking. Multiple linear regression examined prospective associations between changes in depression (Beck Depression Inventory-II), smoking (past 24-hour cigarettes or smoking abstinence), and modified CVH score (per American Heart Association, excluding smoking: diet, physical activity, body mass index, blood glucose, cholesterol, blood pressure)., Results: Baseline mean CVH score was 5.87/12 points (SD = 2.13). No participants met "ideal" on all CVH components (blood glucose: 48 %, cholesterol: 46 %, physical activity: 38 %, body mass index: 24 %, blood pressure: 22 %, diet: 3 %). CVH scores did not change from baseline to end-of-treatment (M = 0.18 points, SD = 1.36, p = .177), nor did change in depression × smoking predict change in CVH (p = .978). However, greater reductions in depression were significantly associated with greater improvements in CVH (β = -0.04, SE = 0.01, p = .015)., Limitations: This study was limited by a short follow-up period, missing blood glucose and cholesterol data, and treatment-seeking smokers., Conclusions: Adults with comorbid depression and smoking had poor CVH. Although integrated treatment for depression and smoking improved both conditions, only reductions in depression were associated with improvements in CVH. These findings have implications for integrating psychosocial treatment into CVH promotion efforts., Registration: NCT02378714 (clinicaltrials.gov)., Competing Interests: Declaration of competing interest Drs. Schnoll and Hitsman have received varenicline and placebo free from Pfizer. Dr. Schnoll has provided consultation to Pfizer, GlaxoSmithKline, and Palliatech. In the last 3 years, Dr. Huffman has received support from the World Heart Federation through unrestricted education grants from Boehringer Ingelheim, Novartis, and Bupa and from the American Heart Association, Verily, and AstraZeneca for work unrelated to this research. Dr. Huffman has also received salary support from the American Medical Association for his role as an associate editor for JAMA Cardiology. Dr. Huffman has planned patents for combination therapy for the treatment of heart failure. The George Institute for Global Health has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy through its social enterprise business, George Medicines., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Trisomy 21, the genetic cause of Down syndrome (DS), is the most common congenital chromosomal anomaly. It is associated with a 20-fold increased risk of acute lymphoblastic leukemia (ALL) during childhood and results in distinctive leukemia biology. To comprehensively define the genomic landscape of DS-ALL, we performed whole-genome sequencing and whole-transcriptome sequencing (RNA-Seq) on 295 cases. Our integrated genomic analyses identified 15 molecular subtypes of DS-ALL, with marked enrichment of CRLF2-r, IGH::IGF2BP1, and C/EBP altered (C/EBPalt) subtypes compared with 2257 non-DS-ALL cases. We observed abnormal activation of the CEBPD, CEBPA, and CEBPE genes in 10.5% of DS-ALL cases via a variety of genomic mechanisms, including chromosomal rearrangements and noncoding mutations leading to enhancer hijacking. A total of 42.3% of C/EBP-activated DS-ALL also have concomitant FLT3 point mutations or insertions/deletions, compared with 4.1% in other subtypes. CEBPD overexpression enhanced the differentiation of mouse hematopoietic progenitor cells into pro-B cells in vitro, particularly in a DS genetic background. Notably, recombination-activating gene-mediated somatic genomic abnormalities were common in DS-ALL, accounting for a median of 27.5% of structural alterations, compared with 7.7% in non-DS-ALL. Unsupervised hierarchical clustering analyses of CRLF2-rearranged DS-ALL identified substantial heterogeneity within this group, with the BCR::ABL1-like subset linked to an inferior event-free survival, even after adjusting for known clinical risk factors. These results provide important insights into the biology of DS-ALL and point to opportunities for targeted therapy and treatment individualization., (© 2023 by The American Society of Hematology.)

Background: The outcome of children with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia significantly improved with the combination of imatinib and intensive chemotherapy. We aimed to investigate the efficacy of dasatinib, a second-generation ABL-class inhibitor, with intensive chemotherapy in children with newly diagnosed Ph-positive acute lymphoblastic leukaemia., Methods: CA180-372/COG AALL1122 was a joint Children's Oncology Group (COG) and European intergroup study of post-induction treatment of Ph-positive acute lymphoblastic leukaemia (EsPhALL) open-label, single-arm, phase 2 study. Eligible patients (aged >1 year to <18 years) with newly diagnosed Ph-positive acute lymphoblastic leukaemia and performance status of at least 60% received EsPhALL chemotherapy plus dasatinib 60 mg/m 2 orally once daily from day 15 of induction. Patients with minimal residual disease of at least 0·05% after induction 1B or who were positive for minimal residual disease after the three consolidation blocks were classified as high risk and allocated to receive haematopoietic stem-cell transplantation (HSCT) in first complete remission. The remaining patients were considered standard risk and received chemotherapy plus dasatinib for 2 years. The primary endpoint was the 3-year event-free survival of dasatinib plus chemotherapy compared with external historical controls. The trial was considered positive if one of the following conditions was met: superiority over chemotherapy alone in the AIEOP-BFM 2000 high-risk group; or non-inferiority (with a margin of -5%) or superiority to imatinib plus chemotherapy in the EsPhALL 2010 cohort. All participants who received at least one dose of dasatinib were included in the safety and efficacy analyses. This trial was registered with ClinicalTrials.gov, NCT01460160, and recruitment is closed., Findings: Between March 13, 2012, and May 27, 2014, 109 patients were enrolled at 69 sites (including 51 COG sites in the USA, Canada, and Australia, and 18 EsPhALL sites in Italy and the UK). Three patients were ineligible and did not receive dasatinib. 106 patients were treated and included in analyses (49 [46%] female and 57 [54%] male; 85 [80%] White, 13 [12%] Black or African American, five [5%] Asian, and three [3%] other races; 24 [23%] Hispanic or Latino ethnicity). All 106 treated patients reached complete remission; 87 (82%) were classified as standard risk and 19 (18%) met HSCT criteria and were classified as high risk, but only 15 (14%) received HSCT in first complete remission. The 3-year event-free survival of dasatinib plus chemotherapy was superior to chemotherapy alone (65·5% [90% Clopper-Pearson CI 57·7 to 73·7] vs 49·2% [38·0 to 60·4]; p=0·032), and was non-inferior to imatinib plus chemotherapy (59·1% [51·8 to 66·2], 90% CI of the treatment difference: -3·3 to 17·2), but not superior to imatinib plus chemotherapy (65·5% vs 59·1%; p=0·27). The most frequent grade 3-5 adverse events were febrile neutropenia (n=93) and bacteraemia (n=21). Nine remission deaths occurred, which were due to infections (n=5), transplantation-related (n=2), due to cardiac arrest (n=1), or had an unknown cause (n=1). No dasatinib-related deaths occurred., Interpretation: Dasatinib plus EsPhALL chemotherapy is safe and active in paediatric Ph-positive acute lymphoblastic leukaemia. 3-year event-free survival was similar to that of previous Ph-positive acute lymphoblastic leukaemia trials despite the limited use of HSCT in first complete remission., Funding: Bristol Myers Squibb., Competing Interests: Declaration of interests SPH received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Amgen, Servier, and Jazz; received support for travel from Bristol Myers Squibb (BMS) and owns common stock in Amgen. GCaz received funding from BMS to perform molecular testing for AALL1122 patients. AVM received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Amgen. KRS was on advisory boards for Jazz and Novartis. PM-R owns stock in BMS and is an employee of BMS. GCar received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Novartis and Servier; was on an advisory board for Jazz; and received support for attending meetings from Jazz. EAR was on a data and safety monitoring board for Celgene and BMS. MJB received support for the present manuscript from Amgen; and was on an advisory board for Amgen. JMG-F received support for the present manuscript from the National Cancer Institute and BMS. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Although the cost of implementing evidence-based interventions (EBIs) is a key determinant of adoption, lack of cost information is widespread. We previously evaluated the cost of preparing to implement Family Check-Up 4 Health (FCU4Health), an individually tailored, evidence-based parenting program that takes a whole child approach, with effects on both behavioral health and health behavior outcomes, in primary care settings. This study estimates the cost of implementation, including preparation., Methods: We assessed the cost of FCU4Health across the preparation and implementation phases spanning 32 months and 1 week (October 1, 2016-June 13, 2019) in a type 2 hybrid effectiveness-implementation study. This family-level randomized controlled trial took place in Arizona with n = 113 predominantly low-income, Latino families with children ages > 5.5 to < 13 years. Using electronic cost capture and time-based activity-driven methods, budget impact analysis from the perspective of a future FCU4Health adopting entity-namely, ambulatory pediatric care clinicians-was used to estimate the cost of implementation. Labor costs were based on 2021 Bureau of Labor Statistics Occupational Employment Statistics, NIH-directed salary cap levels or known salaries, plus fringe benefits at a standard rate of 30%. Non-labor costs were based on actual amounts spent from receipts and invoices., Results: The cost of FCU4Health implementation to 113 families was $268,886 ($2380 per family). Actual per family cost varied widely, as individual tailoring resulted in families receiving a range of 1-15 sessions. The estimated cost of replicating implementation for future sites ranged from $37,636-$72,372 ($333-$641 per family). Using our previously reported preparation costs (i.e., $174,489; $1544 per family), with estimated replication costs of $18,524-$21,836 ($164-$193 per family), the total cost of delivering FCU4Health was $443,375 ($3924 per family), with total estimated replication costs of $56,160-$94,208 ($497-$834 per family)., Conclusions: This study provides a baseline for costs associated with implementation of an individually tailored parenting program. Results provide critical information for decision makers and a model for future economic analysis and can be used to inform optimization thresholds for implementation and, when necessary, benchmarks for program adaptation to promote scale-up., Trial Registration: This trial was prospectively registered on January 6, 2017, at ClinicalTrials.gov (NCT03013309)., (© 2023. The Author(s).)

We measured minimal residual disease (MRD) by multiparameter flow cytometry at three time points (TP) in 117 infants with KMT2A (lysine [K]-specific methyltransferase 2A)-rearranged and 58 with KMT2A-germline acute lymphoblastic leukemia (ALL) on Children's Oncology Group AALL0631 study. For KMT2A-rearranged patients, 3-year event-free survival (EFS) by MRD-positive (≥0.01%) versus MRD-negative (<0.01%) was: TP1: 25% (±6%) versus 49% (±7%; p = .0009); TP2: 21% (±8%) versus 47% (±7%; p < .0001); and TP3: 22% (±14%) versus 51% (±6%; p = .0178). For KMT2A-germline patients, 3-year EFS was: TP1: 88% (±12%) versus 87% (±5%; p = .73); TP2: 100% versus 88% (±5%; p = .24); and TP3: 100% versus 87% (±5%; p = .53). MRD was a strong independent outcome predictor in KMT2A-rearranged, but not KMT2A-germline infant ALL., (© 2023 Wiley Periodicals LLC.)

The Medical Library Association (MLA) has defined 7 domain hubs aligning to different areas of information professional practice. To assess the extent to which content in the Journal of the Medical Library Association ( JMLA ) is reflective of these domains, we analyzed the magnitude of JMLA articles aligning to each domain hub over the last 10 years. Bibliographic records for 453 articles published in JMLA from 2010 to 2019 were downloaded from Web of Science and screened using Covidence software. Thirteen articles were excluded during the title and abstract review because they failed to meet the inclusion criteria, resulting in 440 articles included in this review. The title and abstract of each article were screened by two reviewers, each of whom assigned the article up to two tags corresponding to MLA domain hubs (i.e., information services, information management, education, professionalism and leadership, innovation and research practice, clinical support, and health equity & global health). These results inform the MLA community about our strengths in health information professional practice as reflected by articles published in JMLA ., (Copyright © 2023 Holly J. Thompson, Jill T. Boruff, Roy Brown, Alexander J. Carroll, John W. Cyrus, Melanie J. Norton, Katherine G. Akers.)

To determine the prognostic significance of central nervous system (CNS) leukemic involvement in newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL), outcomes on consecutive, phase 3 Children's Oncology Group clinical trials were examined. AALL0434 and AALL1231 tested efficacy of novel agents within augmented-Berlin-Frankfurt-Münster (aBFM) therapy. In addition to testing study-specific chemotherapy through randomization, the AALL0434 regimen delivered cranial radiation therapy (CRT) to most participants (90.8%), whereas AALL1231 intensified chemotherapy to eliminate CRT in 88.2% of participants. In an analysis of 2164 patients with T-ALL (AALL0434, 1550; AALL1231, 614), 1564 had CNS-1 (72.3%), 441 CNS-2 (20.4%), and 159 CNS-3 (7.3%). The 4-year event-free-survival (EFS) was similar for CNS-1 (85.1% ± 1.0%) and CNS-2 (83.2% ± 2.0%), but lower for CNS-3 (71.8% ± 4.0%; P = .0004). Patients with CNS-1 and CNS-2 had similar 4-year overall survival (OS) (90.1% ± 0.8% and 90.5% ± 1.5%, respectively), with OS for CNS-3 being 82.7% ± 3.4% (P = .005). Despite therapeutic differences, outcomes for CNS-1 and CNS-2 were similar regardless of CRT, intensified corticosteroids, or novel agents. Except for significantly superior outcomes with nelarabine on AALL0434 (4-year disease-free survival, 93.1% ± 5.2%), EFS/OS was inferior with CNS-3 status, all of whom received CRT. Combined analyses of >2000 patients with T-ALL identified that CNS-1 and CNS-2 status at diagnosis had similar outcomes. Unlike B-ALL, CNS-2 status in T-ALL does not impact outcome with aBFM therapy, without additional intrathecal therapy, with or without CRT. Although nelarabine improved outcomes for those with CNS-3 status, novel approaches are needed. These trials were registered at www.clinicaltrials.gov as #NCT00408005 (AALL0434) and #NCT02112916 (AALL1231)., (© 2023 by The American Society of Hematology.)

Importance: The 2017 Clinical Practice Guideline (CPG) for the diagnosis and management of pediatric hypertension (PHTN) categorizes a greater proportion of children with elevated blood pressure and PHTN, yet several barriers to CPG adherence have been noted., Objective: To assess adherence to the 2017 CPG for the diagnosis and management of PHTN and use of a clinical decision support (CDS) tool to calculate blood pressure percentiles., Design, Setting, and Participants: This cross-sectional study used electronic health record-extracted data from January 1, 2018, to December 31, 2019, among patients visiting 1 of 74 federally qualified health centers in AllianceChicago, a national Health Center Controlled Network. Children and adolescents (aged 3-17 years; hereinafter referred to as children) who attended at least 1 visit and had at least 1 blood pressure reading at or above the 90th percentile or diagnosis of elevated blood pressure or PHTN were eligible for data to be included in the analysis. Data were analyzed from September 1, 2020, to February 21, 2023., Exposures: Blood pressure at or above the 90th or 95th percentile., Main Outcomes and Measures: Diagnosis of PHTN (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10], code I10) or elevated blood pressure (ICD-10 code R03.0) and CDS tool use; blood pressure management (antihypertensive medication, lifestyle counseling, referral); and follow-up visit attendance. Descriptive statistics described the sample and rates of guideline adherence. Logistic regression analyses identified patient- and clinic-level associations with guideline adherence., Results: The sample consisted of 23 334 children (54.9% boys; 58.6% White race; median age, 8 [IQR, 4-12] years). Guideline-adherent diagnosis was observed in 8810 children (37.8%) with blood pressure at or above the 90th percentile and 146 of 2542 (5.7%) with blood pressure at or above the 95th percentile at 3 or more visits. The CDS tool was used to calculate blood pressure percentiles in 10 524 cases (45.1%) and was associated with significantly greater odds of PHTN diagnosis (odds ratio, 2.14 [95% CI, 1.10-4.15]). Among 15 422 children with blood pressure at or above the 95th percentile, antihypertensive medication was prescribed to 831 (5.4%), lifestyle counseling was provided to 14 841 (96.2%), and blood pressure-related referrals were given to 848 (5.5%). Guideline-adherent follow-up was observed in 8651 of 19 049 children (45.4%) with blood pressure at or above the 90th percentile and 2598 of 15 164 (17.1%) with blood pressure at or above the 95th percentile. Differences in guideline adherence by patient- and clinic-level factors were observed., Conclusions and Relevance: In this study, fewer than 50% of children with elevated blood pressure had a guideline-adherent diagnosis code or attended guideline-adherent follow-up. Using a CDS tool was associated with guideline-adherent diagnosis, but the tool was underused. Further work is needed to understand how to best support implementation of tools promoting PHTN diagnosis, management, and follow-up.

Recently, the European LeukemiaNet (ELN) revised its genetic-risk classification of acute myeloid leukemia (AML). We categorized 1637 adults with AML treated with cytarabine/anthracycline regimens according to the 2022 and 2017 ELN classifications. Compared with the 2017 ELN classification, 2022 favorable group decreased from 40% to 35% and adverse group increased from 37% to 41% of patients. The 2022 genetic-risk groups seemed to accurately reflect treatment outcomes in all patients and patients aged <60 years, but in patients aged ≥60 years, relapse rates, disease-free (DFS) and overall (OS) survival were not significantly different between intermediate and adverse groups. In younger African-American patients, DFS and OS did not differ between intermediate-risk and adverse-risk patients nor did DFS between favorable and intermediate groups. In Hispanic patients, DFS and OS did not differ between favorable and intermediate groups. Outcome prediction abilities of 2022 and 2017 ELN classifications were similar. Among favorable-risk patients, myelodysplasia-related mutations did not affect patients with CEBPA bZIP mutations or core-binding factor AML, but changed risk assignment of NPM1-mutated/FLT3-ITD-negative patients to intermediate. NPM1-mutated patients with adverse-risk cytogenetic abnormalities were closer prognostically to the intermediate than adverse group. Our analyses both confirm and challenge prognostic significance of some of the newly added markers., (© 2023. The Author(s).)

Background: Quality improvement (QI) interventions in primary care are increasingly designed and implemented by multisector partnerships, yet little guidance exists on how to best monitor or evaluate these partnerships. The goal of this project was to describe an approach for evaluating the development and effectiveness of a multisector partnership using data from the first year of the Healthy Hearts for Michigan (HH4M) Cooperative, a multisector partnership of nine organizations tasked with designing and implementing evidence-based QI strategies for hypertension management and tobacco cessation in 50 rural primary care practices., Methods: The researchers developed a 49-item online survey focused on factors that facilitate or hinder multisector partnerships, drawing on implementation science and partnership, engagement, and collaboration research. The team surveyed all 44 members of the HH4M Cooperative (79.5% response rate) and conducted interviews with 14 members. The interviews focused on implementation phase-specific goals, accomplishments, and challenges. Descriptive analysis was used for the survey results, and thematic analysis for the interview data., Results: Respondents reported strong overall performance by the Cooperative during its first year, which facilitated the successful completion of several intervention design tasks. Strengths included having a clear purpose and trust and respect among members. Areas for improvement included a need for common terminology, clarification of roles and functions, and improvement in communication across workgroups. Lack of engagement from physician practices due to capacity constraints, exacerbated by the COVID-19 pandemic, was the Cooperative's biggest challenge., Conclusion: This multimethod approach to evaluating the development and effectiveness of a multisector partnership yielded practical, actionable feedback to program leaders., (Copyright © 2023 The Joint Commission. All rights reserved.)

The purpose of this study was to contextualize the challenges of diagnosing and managing pediatric hypertension (pHTN) in federally qualified health centers. We conducted a survey among primary care clinicians (N = 72) who treat children (3-17 years old) in a national network of health centers. Clinicians reported practices of blood pressure (BP) measurement, barriers to diagnosis and management of pHTN, and use of population health tools. Most clinicians (83%) used electronic devices to measure BP, only 49% used manual BP readings for follow-up measurements, and more than half measured BP at each encounter. The highest-rated barrier to pHTN management was lack of comfort with antihypertensive medications (71% of respondents). Few clinicians (10%) had used population health tools, but most (78%) indicated they would like to use them for pHTN. These results offer clinician-level insights regarding implementation of the pHTN guideline in pediatric primary care settings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We surveyed pediatric primary care clinicians working in Federally Qualified Health Centers about their perceptions of children's social-emotional wellbeing. We identified clinician's current methods for assessing social-emotional wellbeing in practices, perceived implementation barriers to providing behavioral health care, and interest in adopting a validated, low-burden developmentally sensitive parent-report instrument for screening for social-emotional wellbeing in young children. We surveyed 72 PCCs working in FQHCs from 9 US states. Analyses included examining central tendencies, correlations, analysis of variance, and group differences via t-tests. Average PCC perceptions of social-emotional wellbeing importance for overall health were statistically significantly higher than their confidence in providing care for common social-emotional wellbeing concerns (mean difference = 1.31, 95% CI = 1.13-1.49). PCCs expressed low satisfaction with currently available screening measures for identifying concerns in social-emotional wellbeing. Fewer than half of clinicians reported using any standardized parent-reported measure for identifying concerns in social-emotional wellbeing. Assessment methods and decision tools that improve clinician confidence concerning risk indications are needed, particularly at the critical early childhood period. Policymakers and payers ought to facilitate funding mechanisms that support pediatric PCCs in identifying early concerns in social-emotional wellbeing and providing referral guidance to evidence-based interventions to support parents and caregivers.

Background: Effective and efficient implementation of the Collaborative Care Model (CoCM) for depression and anxiety is imperative for program success. Studies examining barriers to implementation often omit patient perspectives., Objectives: To explore experiences and attitudes of eligible patients referred to CoCM who declined participation or were unable to be reached, and identify implementation barriers to inform strategies., Design: Convergent mixed-methods study with a survey and interview., Participants: Primary care patients at an academic medical center who were referred to a CoCM program for anxiety and depression by their primary care clinician (PCC) but declined participation or were unable to be reached by the behavioral health care manager to initiate care (n = 80). Interviews were conducted with 45 survey respondents., Main Measures: Survey of patients' referral experiences and behavioral health preferences as they related to failing to enroll in the program. Interview questions were developed using the Consolidated Framework for Implementation Research version 2.0 (CFIR 2.0) to identify implementation barriers to enrollment., Key Results: Survey results found that patients were uncertain about insurance coverage, did not understand the program, and felt services were not necessary. Referred patients who declined participation were concerned about how their mental health information would be used and preferred treatment without medication. Men agreed more that they did not need services. Qualitative results exhibited a variety of implementation determinants (n = 23) across the five CFIR 2.0 domains. Barriers included mental health stigma, perceiving behavioral health as outside of primary care practice guidelines, short or infrequent primary care appointments, prioritizing physical health over mental health, receiving inaccurate program information, low motivation to engage, and a less established relationship with their PCC., Conclusions: Multiple barriers to enrollment led to failing to link patients to care, which can inform implementation strategies to address the patient-reported experiences and concerns., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Not all participants will benefit equally from even well-established, evidence-based prevention programs. For this reason, the field of prevention science is beginning to embrace individual tailoring of interventions. The Family Check-Up was among the first prevention programs to tailor at the family level as opposed to the more prevalent focus on adapting programs for different cultures, genders, and other immutable participant characteristics. Despite tailoring, families with lower levels of stress and parental mental health issues, children with lower baseline conduct problems, and families living in an extremely deprived neighborhood benefitted less from the Family Check-Up. This study examined baseline targeted moderation (BTM) within a trial of the Family Check-Up 4 Health (FCU4Health) program, an adaptation of the Family Check-Up for primary care delivery and explicit targeting of obesogenic behaviors. Ethnically diverse, low-income families (N = 240) with children ages 5.5 to 12 years identified in pediatric primary care with elevated body mass index (BMI) were enrolled and randomized to FCU4Health or usual care. Few BTM effects were found using single-variable-as-moderator and latent-class-as-moderator analytic approaches across the primary (child BMI, body composition) and secondary outcomes (family health routines; child eating behaviors, food choices, emotional problems, problem behaviors, quality of life; caregiver BMI and body composition), as well as hypothesized mediators (child self-regulation, parenting skills). The high-risk nature of the sample and the FCU4Health being individually tailored might have mitigated finding BTM effects. This trial was prospectively registered (NCT03013309 ClinicalTrials.gov)., (© 2021. Society for Prevention Research.)

Background: Previous studies have identified racial and ethnic disparities in childhood acute lymphocytic leukaemia survival. We aimed to establish whether disparities persist in contemporaneous cohorts and, if present, are attributable to differences in leukaemia biology or insurance status., Methods: Patients with newly diagnosed acute lymphocytic leukaemia in inpatient and outpatient centres in the USA, Canada, Australia, and New Zealand, aged 0-30 years, who had race or ethnicity data available, enrolled on eight completed Children's Oncology Group trials (NCT00103285, NCT00075725, NCT00408005, NCT01190930, NCT02883049, NCT02112916, NCT02828358, and NCT00557193) were included in this secondary analysis. Race and ethnicity were categorised as non-Hispanic White, Hispanic, non-Hispanic Black, non-Hispanic Asian, and non-Hispanic other. Event-free survival and overall survival were compared across race and ethnicity groups. The relative contribution of clinical and biological disease prognosticators and insurance status was examined through multivariable regression models, both among the entire cohort and among those with B-cell lineage versus T-cell lineage disease., Findings: Between Jan 1, 2004, and Dec 31, 2019, 24 979 eligible children, adolescents, and young adults with acute lymphocytic leukaemia were enrolled, of which 21 152 had race or ethnicity data available. 11 849 (56·0%) were male and 9303 (44·0%) were female. Non-Hispanic White patients comprised the largest racial or ethnic group (13 872 [65·6%]), followed by Hispanic patients (4354 [20·6%]), non-Hispanic Black patients (1517 [7·2%]), non-Hispanic Asian (n=1071 [5·1%]), and non-Hispanic other (n=338 [1·6%]). 5-year event-free survival was 87·4% (95% CI 86·7-88·0%) among non-Hispanic White patients compared with 82·8% (81·4-84·1%; hazard ratio [HR] 1·37, 95% CI 1·26-1·49; p<0·0001) among Hispanic patients and 81·8% (79·3-84·0; HR 1·45, 1·28-1·65; p<0·0001) among non-Hispanic Black patients. Non-hispanic Asian patients had a 5-year event-free survival of 88·1% (95% CI 85·5-90·3%) and non-Hispanic other patients had a survival of 82·8% (76·4-87·6%). Inferior event-free survival among Hispanic patients was substantially attenuated by disease prognosticators and insurance status (HR decreased from 1·37 [1·26-1·49; p<0·0001] to 1·11 [1·00-1·22; p=0·045]). The increased risk among non-Hispanic Black patients was minimally attenuated (HR 1·45 [1·28-1·65; p<0·0001] to 1·32 [1·14-1·52; p<0·0001]). 5-year overall survival was 93·6% (91·5-95·1%) in non-Hispanic Asian patients, 93·3% (92·8-93·7%) in non-Hispanic White patients, 89·9% (88·7-90·9%) in Hispanic, 89·7% (87·6-91·4%) in non-Hispanic Black patients, 88·9% (83·2-92·7%) in non-Hispanic other patients. Disparities in overall survival were wider than event-free survival (eg, among non-Hispanic other patients, the HR for event-free survival was 1·43 [1·10-1·85] compared with 1·74 [1·27-2·40] for overall survival). Disparities were restricted to patients with B-cell acute lymphocytic leukaemia, no differences in event-free survival or overall survival were seen in the T-cell acute lymphocytic leukaemia group., Interpretation: Substantial disparities in outcome for B-cell acute lymphocytic leukaemia persist by race and ethnicity, but are not observed in T-cell acute lymphocytic leukaemia. Future studies of relapsed patients, access to and quality of care, and other potential aspects of structural racism are warranted to inform interventions aimed at dismantling racial and ethnic disparities., Funding: National Cancer Institute and St Baldrick's Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Survival of patients with acute myeloid leukemia (AML) is inversely associated with age, but the impact of race on outcomes of adolescent and young adult (AYA; range, 18-39 years) patients is unknown. We compared survival of 89 non-Hispanic Black and 566 non-Hispanic White AYA patients with AML treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology protocols. Samples of 327 patients (50 Black and 277 White) were analyzed via targeted sequencing. Integrated genomic profiling was performed on select longitudinal samples. Black patients had worse outcomes, especially those aged 18 to 29 years, who had a higher early death rate (16% vs 3%; P=.002), lower complete remission rate (66% vs 83%; P=.01), and decreased overall survival (OS; 5-year rates: 22% vs 51%; P<.001) compared with White patients. Survival disparities persisted across cytogenetic groups: Black patients aged 18 to 29 years with non-core-binding factor (CBF)-AML had worse OS than White patients (5-year rates: 12% vs 44%; P<.001), including patients with cytogenetically normal AML (13% vs 50%; P<.003). Genetic features differed, including lower frequencies of normal karyotypes and NPM1 and biallelic CEBPA mutations, and higher frequencies of CBF rearrangements and ASXL1, BCOR, and KRAS mutations in Black patients. Integrated genomic analysis identified both known and novel somatic variants, and relative clonal stability at relapse. Reduced response rates to induction chemotherapy and leukemic clone persistence suggest a need for different treatment intensities and/or modalities in Black AYA patients with AML. Higher early death rates suggest a delay in diagnosis and treatment, calling for systematic changes to patient care., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)