Long-read epigenomic diagnosis and prognosis of Acute Myeloid Leukemia.

Acute Myeloid Leukemia (AML) is an aggressive cancer with dismal outcomes, vast subtype heterogeneity, and suboptimal risk stratification. In this study, we harmonized DNA methylation data from 3,314 patients across 11 cohorts to develop the Acute Leukemia Methylome Atlas (ALMA) of diagnostic relevance that predicted 27 WHO 2022 acute leukemia subtypes with an overall accuracy of 96.3% in discovery and 90.

Piloting Home Produce Delivery to Improve Food Security, Budget, and Diet in Families with Children: A Mixed-Methods Study.

Background: Few children in food insecure (FI) households meet dietary recommendations for fruit and vegetables ("produce"). Barriers include affordability, accessibility, and desirability. Home produce delivery may reduce FI, increase produce consumption, and decrease budget tradeoffs.

Insight Into Severe Neonatal COVID-19 Gained Through Whole Exome Sequencing of Twin Neonates.

The genetic basis of neonatal COVID-19 infection, which exhibits a range of severity, has not been investigated. We identified both shared and unique genetic variants involved in antiviral immune responses through whole exome sequencing of an infant who developed severe COVID-19 pneumonia and multisystem inflammatory syndrome and the twin brother also positive for severe acute respiratory syndrome-coronavirus-2, but with only moderate respiratory symptoms.

Disparities in accessing specialty behavioral health services during the COVID-19 pandemic and why we need pediatric integrated primary care.

Objective: Youth unmet behavioral health needs are at public health crisis status and have worsened since the onset of the coronavirus disease 2019 pandemic (Covid-19). Integrating behavioral health services into pediatric primary care has shown efficacy in addressing youth behavioral health needs. However, there is limited guidance on facilitating equitable access to care in this setting, including in triaging access to co-located services (i.

Chromatin Profiles Are Prognostic of Clinical Response to Bortezomib-Containing Chemotherapy in Pediatric Acute Myeloid Leukemia: Results from the COG AAML1031 Trial.

The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children's Oncology Group phase 3 trial AAML1031 (NCT01371981). Proteasome inhibition influences the chromatin landscape and proteostasis, and we hypothesized that baseline proteomic analysis of histone- and chromatin-modifying enzymes (HMEs) would identify AML subgroups that benefitted from bortezomib addition. A proteomic profile of 483 patients treated with AAML1031 chemotherapy was generated using a reverse-phase protein array.

Refractive Error Change and Overminus Lens Therapy for Childhood Intermittent Exotropia.

Importance: Increased myopic shift was found to be associated with 1 year of overminus spectacle treatment for children with intermittent exotropia (IXT). Persistence of myopic shift after discontinuing overminus spectacles is unknown.

Objective: To compare refractive error change over 3 years in children with IXT originally treated with overminus vs nonoverminus spectacles.

Structural variants involving MLLT10 fusion are associated with adverse outcomes in pediatric acute myeloid leukemia.

MLLT10 gene rearrangements with KMT2A occur in pediatric acute myeloid leukemia (AML) and confer poor prognosis, but the prognostic impact of MLLT10 in partnership with other genes is unknown. We conducted a retrospective study with 2080 children and young adults with AML registered on the Children's Oncology Group AAML0531 (NCT00372593) and AAML1031 trials (NCT01371981). Transcriptome profiling and/or karyotyping were performed to identify leukemia-associated fusions associated with prognosis.

Major Drug-Drug Interaction Exposure Among Medicaid-Insured Children in the Outpatient Setting.

Background And Objectives: Drug-drug interactions (DDIs) can cause adverse drug events, but little is known about DDI exposure in children in the outpatient setting. This study aimed to determine the prevalence of major DDI exposure and factors associated with higher DDI exposure rates among children in an outpatient setting.

Methods: We performed a cross-sectional study of children aged 0 to 18 years with ≥1 ambulatory encounter, and ≥2 dispensed outpatient prescriptions study using the 2019 Marketscan Medicaid database.

Barriers to the Diagnosis, Care, and Management of Pediatric Patients With Ehlers-Danlos Syndrome in the United States: A Qualitative Analysis.

Ehlers-Danlos Syndromes (EDS) are a family of heritable connective tissue diseases. Primary practitioners are capable of diagnosing and managing EDS; however, few are knowledgeable and comfortable enough to see patients with EDS, resulting in delays in diagnosis and care. This study explores the barriers physicians experience with diagnosing, managing, and caring for patients with EDS, and potential resolutions to those barriers.

The Design of the Electronic Health Record in Type 1 Diabetes Centers: Implications for Metrics and Data Availability for a Quality Collaborative.

Background: Systematic and comprehensive data acquisition from the electronic health record (EHR) is critical to the quality of data used to improve patient care. We described EHR tools, workflows, and data elements that contribute to core quality metrics in the Type 1 Diabetes Exchange Quality Improvement Collaborative (T1DX-QI).

Method: We conducted interviews with quality improvement (QI) representatives at 13 T1DX-QI centers about their EHR tools, clinic workflows, and data elements.

Reporting and impact of subsequent cycle toxicities in oncology phase I clinical trials.

Background/aims: As oncology treatments evolve, classic assumptions of toxicity associated with cytotoxic agents may be less relevant, requiring new design strategies for trials intended to inform dosing strategies for agents that may be administered beyond a set number of defined cycles. We describe the overall incidence of dose-limiting toxicities during and after cycle 1, frequency of reporting subsequent cycle toxicities, and the impact of post-cycle 1 dose-limiting toxicities on conclusions drawn from oncology phase 1 clinical trials.

Methods: We conducted a systematic review of subsequent cycle toxicities in oncology phase I clinical trials published in the from 2000 to 2020.

Mealtime Insulin BOLUS Score More Strongly Predicts HbA Than the Self-Care Inventory in Youth With Type 1 Diabetes.

Background: To meet their glycated hemoglobin (HbA) goals, youth with type 1 diabetes (T1D) need to engage with their daily T1D treatment. The mealtime insulin Bolus score (BOLUS) is an objective measure of youth's T1D engagement which we have previously shown to be superior to other objective engagement measures in predicting youth's HbA. Here, to further assess the BOLUS score's validity, we compared the strengths of the associations between youth's HbA with their mean insulin BOLUS score and a valid, self-report measure of T1D engagement, the Self-Care Inventory (SCI).

Pediatric Rheumatology Care and Outcomes Improvement Network's Quality Measure Set to Improve Care of Children With Juvenile Idiopathic Arthritis.

Objective: To describe the selection, development, and implementation of quality measures (QMs) for juvenile idiopathic arthritis (JIA) by the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN), a multihospital learning health network using quality improvement methods and leveraging QMs to drive improved outcomes across a JIA population since 2011.

Methods: An American College of Rheumatology-endorsed multistakeholder process previously selected initial process QMs. Clinicians in PR-COIN and parents of children with JIA collaboratively selected outcome QMs.

Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children's Oncology Group.

Purpose: The endoplasmic reticulum (ER) is the major site of protein synthesis and folding in the cell. ER-associated degradation (ERAD) and unfolded protein response (UPR) are the main mechanisms of ER-mediated cell stress adaptation. Targeting the cell stress response is a promising therapeutic approach in acute myeloid leukemia (AML).

Characteristics and prognostic impact of IDH mutations in AML: a COG, SWOG, and ECOG analysis.

Somatic mutations in isocitrate dehydrogenase (IDH) genes occur frequently in adult acute myeloid leukemia (AML) and less commonly in pediatric AML. The objective of this study was to describe the prevalence, mutational profile, and prognostic significance of IDH mutations in AML across age. Our cohort included 3141 patients aged between <1 month and 88 years treated on Children's Cancer Group/Children's Oncology Group (n = 1872), Southwest Oncology Group (n = 359), Eastern Cooperative Oncology Group (n = 397) trials, and in Beat AML (n = 333) and The Cancer Genome Atlas (n = 180) genomic characterization cohorts.

Cost-effectiveness of : an adaptation of the diabetes prevention programme for delivery by community health workers in urban South Africa.

Background: is an adapted version of the Diabetes Prevention Program designed for delivery by community health workers to socioeconomically disadvantaged populations in low- and middle-income countries (LMICs). Results from the trial conducted in an under-resourced community in South Africa indicated that the programme had a significant effect on reducing haemoglobin A1c (HbA1c).

Objective: To estimate the cost of implementation and the cost-effectiveness (in cost per point reduction in HbA1c) of the programme to inform decision-makers of the resources required and the value of this intervention.

Evidence-based practice models and frameworks in the healthcare setting: a scoping review.

Objectives: The aim of this scoping review was to identify and review current evidence-based practice (EBP) models and frameworks. Specifically, how EBP models and frameworks used in healthcare settings align with the original model of (1) asking the question, (2) acquiring the best evidence, (3) appraising the evidence, (4) applying the findings to clinical practice and (5) evaluating the outcomes of change, along with patient values and preferences and clinical skills.

Design: A Scoping review.

The Development and Initial Validation of Items to Assess Parent Fear of Nighttime Hypoglycemia.

Objective: Parents of youth with type 1 diabetes (T1D) are fearful their children will experience nighttime hypoglycemia. Currently, the Hypoglycemia Fear Survey for Parents (HFS-P) lacks items that specifically assess parents' nighttime fear. This study aimed to fill this gap by rigorously identifying new items to specifically assess parent fear of nighttime hypoglycemia and then examine the psychometric properties of the revised Hypoglycemia Fear Survey for Parents including Nighttime Fear (HFS-P-NF).