Association of the social disorganization index with time to first septic shock event in children with acute myeloid leukemia.

BACKGROUND: Pediatric acute myeloid leukemia (AML) chemotherapy increases the risk of life-threatening complications, including septic shock (SS). An area-based measure of social determinants of health, the social disorganization index (SDI), was hypothesized to be associated with SS and SS-associated death (SS-death). METHODS: Children treated for de novo AML on two Children's Oncology Group trials at institutions contributing to the Pediatric Health Information System (PHIS) database were included. The SDI was calculated via residential zip code data from the US Census Bureau. SS was identified via PHIS resource utilization codes. SS-death was defined as death within 2 weeks of an antecedent SS event. Patients were followed from 7 days after the start of chemotherapy until the first of end of front-line therapy, death, relapse, or removal from study. Multivariable-adjusted Cox regressions estimated hazard ratios (HRs) comparing time to first SS by SDI group. RESULTS: The assembled cohort included 700 patients, with 207 (29.6%) sustaining at least one SS event. There were 233 (33%) in the SDI-5 group (highest disorganization). Adjusted time to incident SS did not statistically significantly differ by SDI (reference, SDI-1; SDI-2: HR, 0.84 [95% confidence interval (CI), 0.51-1.41]; SDI-3: HR, 0.70 [95% CI, 0.42-1.16]; SDI-4: HR, 0.97 [95% CI, 0.61-1.53]; SDI-5: HR, 0.72 [95% CI, 0.45-1.14]). Nine patients (4.4%) with SS experienced SS-death; seven of these patients (78%) were in SDI-4 or SDI-5. CONCLUSIONS: In a large, nationally representative cohort of trial-enrolled pediatric patients with AML, there was no significant association between the SDI and time to SS.

Absolute neutrophil count clinical trial eligibility criteria for pediatric oncology phase I and phase I/II trials by sponsorship.

Normal absolute neutrophil count (ANC) variations, as seen with Duffy-null associated neutrophil count (DANC), are not accounted for in trial eligibility, which may contribute to racial enrollment disparities. We describe ANC eligibility for pediatric oncology phase I/II clinical trials according to primary sponsorship from 2010 to 2023 using ClinicalTrials.gov. Out of 438 trials, 20% were industry-sponsored. Total 17% of trials required ANC ≥1500 cells/µL for enrollment; however, industry-sponsored trials were significantly more likely to require ANC ≥1500 cells/µL than non-industry-sponsored trials (odds ratio 2.53, 95% confidence interval: 1.39-4.62; p < .001). These data suggest laboratory exclusion criteria are one possible mechanism for pediatric clinical trial enrollment disparities.

Applying machine learning to identify pediatric patients with newly diagnosed acute lymphoblastic leukemia using administrative data.

Case identification in administrative databases is challenging as diagnosis codes alone are not adequate for case ascertainment. We utilized machine learning (ML) to efficiently identify pediatric patients with newly diagnosed acute lymphoblastic leukemia. We tested nine ML models and validated the best model internally and externally. The optimal model had 97% positive predictive value (PPV) and 99% sensitivity in internal validation; 94% PPV and 82% sensitivity in external validation. Our ML model identified a large cohort of 21,044 patients, demonstrating an efficient approach for cohort assembly and enhancing the usability of administrative data.

Leveraging machine learning to identify acute myeloid leukemia patients and their chemotherapy regimens in an administrative database.

BACKGROUND: Administrative datasets are useful for identifying rare disease cohorts such as pediatric acute myeloid leukemia (AML). Previously, cohorts were assembled using labor-intensive, manual reviews of patients' longitudinal chemotherapy data. METHODS: We utilized a two-step machine learning (ML) method to (i) identify pediatric patients with newly diagnosed AML, and (ii) among the identified AML patients, their chemotherapy courses, in an administrative/billing database. Using 2558 patients previously manually reviewed, multiple ML algorithms were derived from 75% of the study sample, and the selected model was tested in the remaining hold-out sample. The selected model was also applied to assemble a new pediatric AML cohort and further assessed in an external validation, using a standalone cohort established by manual chart abstraction. RESULTS: For patient identification, the selected Support Vector Machine model yielded a sensitivity of 0.97 and a positive predictive value (PPV) of 0.97 in the hold-out test sample. For course-specific chemotherapy regimen and start date identification, the selected Random Forest model yielded overall PPV greater than or equal to 0.88 and sensitivity greater than or equal to 0.86 across all courses in the test sample. When applied to new cohort assembly, ML identified 3016 AML patients with 10,588 treatment courses. In the external validation subset, PPV was greater than or equal to 0.75 and sensitivity was greater than or equal to 0.82 for patient identification, and PPV was greater than or equal to 0.93 and sensitivity was greater than or equal to 0.94 for regimen identifications. CONCLUSION: A carefully designed ML model can accurately identify pediatric AML patients and their chemotherapy courses from administrative databases. This approach may be generalizable to other diseases and databases.

Lower academic performance and dropout rates among University students with children: a prospective cohort study of nursing students in Bogotá, Colombia.

OBJECTIVES: To determine the association between parenthood and academic performance and dropout among professional Nursing degree program students. METHODS: A prospective cohort was conducted. 310 students were included, 26 parents (exposed) and 284 nonparents (unexposed), who were followed up during 16 weeks. At the end of this follow-up, student records were reviewed. RESULTS: Academic performance in the exposed and unexposed groups was 3.51/5.0 and 3.64/5.0 respectively. Although it was higher in the latter group, i.e., with a difference of 0.13, the values were not statistically significant (p=0.058). After adjusting for confounding variables, a difference of -0.165 point was seen (p=0.037). The risk of students dropping out of college is 34 % less for exposed compared to those who are unexposed (RR: 0.66; CI: 0.075-5.78; p=0.708). CONCLUSION: The results suggest that parenthood has a modest impact on the academic performance, and has no impact on the risk of dropping out.

What Is Childhood Leukemia?

This JAMA Patient Page outlines the symptoms, diagnosis, and treatment of childhood leukemia.

Overcoming challenges to meaningful informed consent for whole genome sequencing in pediatric cancer research.

BACKGROUND: Introducing whole genome sequencing (WGS) into pediatric cancer research at diagnosis poses unique challenges related to informed consent. WGS requires tissue obtained prior to initiating treatment, when families may be overwhelmed with uncertainty and fear. Motivation to participate may be high without fully understanding the range of possible results, including secondary findings. Little is known about parental knowledge, attitudes, and beliefs about this type of research. PROCEDURE: A qualitative study was conducted to investigate parental knowledge about genetic concepts and WGS, thoughts about the informed consent process, and preferences for secondary findings. Focus groups were conducted with parents/guardians of children with cancer and semi-structured interviews were conducted in a control group without cancer. All transcripts were analyzed using content analysis. RESULTS: Four focus groups included 15 participants; eight semi-structured interviews included 10 participants. Basic knowledge about genetics was limited to heredity. Some knowledge of genomic analysis was present in 3/15 focus group participants. Major factors related to participation in WGS research were: (i) hope for their child and future children; (ii) no additional procedures; (iii) and protection of privacy. All favored a two-step consent process, first to store extra tissue from a diagnostic biopsy/resection, followed by consenting to WGS research, one-to-two months later. The desire to receive secondary findings was high among both groups, but there were individuals who did not want these results, fearing increased anxiety. CONCLUSIONS: Parents/guardians of children with cancer have limited knowledge about WGS. A two-step consent process may improve their ability to provide meaningful informed consent.

Relationship between psychoactive substance, alcohol and cigarette use in nursing students. A cross-sectional study.

BACKGROUND: The increase in the use of psychoactive substances, alcohol and cigarettes in young people has become a public health problem. The identification of factors that increase or reduce the risk of exposure to these substances and the possible relationship between them is essential for planning strategies with a risk approach; hence the reason for this study. The objective was to establish the profile of use of psychoactive substances, alcohol and cigarettes and the factors associated with such use in nursing students of a higher education institution. METHODS: Quantitative, observational, analytical cross-sectional study. RESULTS: We included 310 students from 1 st to 9th semester of a Nursing programme from a private higher education institution in Bogotá. The prevalence of psychoactive substance use in the last year was 2.96% (95%CI, 1.36-5.54), with marijuana being the substance most used (55.55%). The prevalence of alcohol and cigarette use during the last 12 months was estimated at 86.64% (95%CI, 83.24-91.0) and 12.16% (95%CI, 8.43-15.88) respectively. A statistically significant association was found between the use of these substances: alcohol use was associated with cigarette use (OR = 3.22; P = 0.006) and smoking was associated with psychoactive substance use (OR = 15.4; P < 0.001). CONCLUSIONS: Alcohol use increases the likelihood of smoking cigarettes, and this in turn increases the likelihood of psychoactive substance use, in this university population.

Clinical trial recruitment of people who speak languages other than English: a Children's Oncology Group report.

BACKGROUND: Persons who speak languages other than English are underrepresented in clinical trials, likely in part because of inadequate multilevel resources. We conducted a survey of institutions affiliated with the Children's Oncology Group (COG) to characterize current research recruitment practices and resources regarding translation and interpretation services. METHODS: In October 2022, a 20-item survey was distributed electronically to institutions affiliated with COG to assess consent practices and resources for recruiting participants who speak languages other than English to COG trials. Descriptive statistics were used to summarize responses; responses were compared by institution size and type as well as respondent role. RESULTS: The survey was sent to 230 institutions, and the response rate was 60% (n = 139). In total, 60% (n = 83) of those respondents had access to short-form consent forms. Full consent form translation was required at 50% of institutions, and 12% of institutional review boards restricted use of centrally translated consent forms. Forty-six percent (n = 64) of institutions reported insufficient funding to support translation costs; 19% (n = 26) had access to no-cost translation services. Forty-four percent (n = 61) were required to use in-person interpreters for consent discussions; the most frequently cited barrier (56%) to obtaining consent was lack of available in-person interpreters. Forty-seven percent (n = 65) reported that recruiting persons who speak languages other than English to clinical trials was somewhat or very difficult. CONCLUSIONS: Institutions affiliated with COG face resource-specific challenges that impede recruitment of participants who speak languages other than English for clinical trials. These findings indicate an urgent need to identify strategies aimed at reducing recruitment barriers to ensure equitable access to clinical trials.

Household income and health-related quality of life in children receiving treatment for acute myeloid leukemia: Potential impact of selection bias in health equity research.

OBJECTIVE: Examine the influence of household income on health-related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). DESIGN: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. EXPOSURE: Household income was self-reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. OUTCOME: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. RESULT: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2-20.2). Seven percent of enrolled patients presented with high acuity (ICU-level care in the first 72 h), and 16% had high toxicity (any ICU-level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. CONCLUSIONS: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research.

Persistence of chironomids in metal polluted andean high altitude streams: does melanin play a role?

In high altitude Andean streams an intense solar radiation and coinciding metal pollution allow the persistence of only a few specialized taxa, including chironomids. The aim of the present study was therefore to determine the mechanisms underlying the persistence of chironomids under these multiple stress conditions, hypothesizing that melanin counteracts both the adverse effects of solar radiation and of metals. Melanin was determined in chironomids from reference and metal polluted streams at 3000 and 4000 m altitude, being 2-fold higher at 4000 m compared to 3000 m, and 2-fold higher in polluted streams than in reference streams at both altitudes. The field observations were experimentally verified by assessing the combined effects of Cu and UV-B on the survival and melanin concentration in larvae of the model species Chironomus riparius (Chironomidae, Diptera). In laboratory exposures, the highest melanin concentrations were found in larvae surviving toxic Cu concentrations, but not in those exposed to the highest UV-B radiation. Pre-exposure to UV-B decreased the sensitivity of the larvae to UV-B and to Cu+UV-B. It is concluded that in the field, melanin may protect chironomids partially against both elevated metal concentrations and solar radiation, allowing them to persist under the harshest conditions in high altitude streams.

Opportunities to improve diagnosis in emergency transfers to the pediatric intensive care unit.

BACKGROUND: Late recognition of in-hospital deterioration is a source of preventable harm. Emergency transfers (ET), when hospitalized patients require intensive care unit (ICU) interventions within 1 h of ICU transfer, are a proximal measure of late recognition associated with increased mortality and length of stay (LOS). OBJECTIVE: To apply diagnostic process improvement frameworks to identify missed opportunities for improvement in diagnosis (MOID) in ETs and evaluate their association with outcomes. DESIGN, SETTINGS, AND PARTICIPANTS: A single-center retrospective cohort study of ETs, January 2015 to June 2019. ET criteria include intubation, vasopressor initiation, or ≥ $\ge \phantom{\rule{}{0ex}}$ 60 mL/kg fluid resuscitation 1 h before to 1 h after ICU transfer. The primary exposure was the presence of MOID, determined using SaferDx. Cases were screened by an ICU and non-ICU physician. Final determinations were made by an interdisciplinary group. Diagnostic process improvement opportunities were identified. MAIN OUTCOME AND MEASURES: Primary outcomes were in-hospital mortality and posttransfer LOS, analyzed by multivariable regression adjusting for age, service, deterioration category, and pretransfer LOS. RESULTS: MOID was identified in 37 of 129 ETs (29%, 95% confidence interval [CI] 21%-37%). Cases with MOID differed in originating service, but not demographically. Recognizing the urgency of an identified condition was the most common diagnostic process opportunity. ET cases with MOID had higher odds of mortality (odds ratio 5.5; 95% CI 1.5-20.6; p = .01) and longer posttransfer LOS (rate ratio 1.7; 95% CI 1.1-2.6; p = .02). CONCLUSION: MOID are common in ETs and are associated with increased mortality risk and posttransfer LOS. Diagnostic improvement strategies should be leveraged to support earlier recognition of clinical deterioration.

Factors Associated With 30 Day Survival in Adults With Influenza Infection Receiving Extracorporeal Membrane Oxygenation.

Acute respiratory distress syndrome (ARDS) secondary to influenza in adults is associated with a high rate of morbidity and mortality. Extracorporeal membrane oxygenation (ECMO) is a supportive alternative for severe and refractory cases. This study aimed to perform a hospital-based case-control study between February 2018 and February 2020 for determining the factors associated with 30 day survival in adults with severe ARDS caused by influenza infection who are provided ECMO support. A total of 17 adults received ECMO support, mostly veno-venous for hypoxemic respiratory failure, with a 30 day survival rate of 65%. The cohort of patients who did not survive at 30 days compared with the cohort of those who did survive had higher body mass index (34 vs. 31), higher Sequential Organ Failure Assessment score (9.5 vs. 7) and lower Respiratory ECMO Survival Prediction score (2 vs. 4). This study shows the importance of evaluating the severity scores of patients before ECMO support initiation, which offers an acceptable survival in patients with severe ARDS, making it a feasible alternative in critical patients who are refractory to conventional management.

Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma.

CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of "CIC-rearranged" sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases.

Limitations of Applying the Hematopoietic Cell Transplantation Comorbidity Index in Pediatric Patients Receiving Allogeneic Hematopoietic Cell Transplantation.

Identifying which patients are at high risk for transplant-related mortality, prior to allogeneic hematopoietic cell transplantation (alloHCT), is crucial both to guide decision making with patients and families and to inform the alloHCT approach. There is a paucity of data evaluating the utility of the HCT comorbidity index (HCT-CI) in pediatric patients. We performed a retrospective cohort study of 188 patients who underwent alloHCT between January 2008 and October 2016 and assessed pretransplant comorbidities defined and weighted by the HCT-CI. The primary endpoint of our study was overall survival (OS). Kaplan-Meier method was used to assess survival estimates at 1-year post-transplant and did not differ based on HCT-CI scores: 78.7% (SE 6.69%) for HCT-CI = 0, 74.7% (SE 6.33%) for HCT-CI = 1 to 2, and 77.3% (SE 4.17%) for HCT-CI ≥3. Multivariable Cox proportional hazards analysis did not show HCT-CI having an effect on OS: hazard ratio (HR) of 0.633 (95% confidence interval [CI], 0.297 to 1.347) for HCT-CI scores 1 to 2 and HR of 0.935 (95% CI, 0.456 to 1.918) for HCT-CI scores ≥3 compared to scores of 0. The most frequent comorbidities observed were hepatic disease (mild in 29%, severe in 23%) and pulmonary disease (moderate in 15% and severe in 29%). However, only 55% were able to complete pulmonary function testing. Hepatic disease was based on transaminitis in 48% and by bilirubin alone in 26% of patients; 46% of patients with hepatic dysfunction had an underlying hemoglobinopathy and hyperbilirubinemia related to ongoing hemolysis. This study evaluates HCT-CI comorbidities in greater detail than has been performed previously in children undergoing alloHCT. We identify challenges with the HCT-CI in the pediatric population and highlight the comorbidities that may benefit from adjustments to their definition to create an improved risk assessment tool for children.

Current Status of Indications, Timing, Management, Complications, and Outcomes of Tracheostomy in Traumatic Brain Injury Patients.

Tracheostomy is the commonest bedside surgical procedure performed on patients needing mechanical ventilation with traumatic brain injury (TBI). The researchers made an effort to organize a narrative review of the indications, timing, management, complications, and outcomes of tracheostomy in relation to neuronal and brain-injured patients following TBI. The study observations were collated from the published literature, namely original articles, book chapters, case series, randomized studies, systematic reviews, and review articles. Information sorting was restricted to tracheostomy and its association with TBI. Care was taken to review the correlation of tracheostomy with clinical correlates including indications, scheduling, interventions, prognosis, and complications of the patients suffering from mild, moderate and severe TBIs using Glasgow Coma Scale, Glasgow Outcome Scale, intraclass correlation coefficient, and other internationally acclaimed outcome scales. Tracheostomy is needed to overcome airway obstruction, prolonged respiratory failure and as indispensable component of mechanical ventilation due to diverse reasons in intensive care unit. Researchers are divided over early tracheostomy or late tracheostomy from days to weeks. The conventional classic surgical technique of tracheostomy has been superseded by percutaneous techniques by being less invasive with lesser complications, classified into early and late complications that may be life threatening. Additional studies have to be conducted to validate and streamline varied observations to frame evidence-based practice for successful weaning and decannulation. Tracheostomy is a safer option in critically ill TBI patients for which a universally accepted protocol for tracheostomy is needed that can help to optimize indications and outcomes.

Financial impact of post-transplant complications among children undergoing allogeneic hematopoietic cell transplantation.

Complications following allogeneic hematopoietic cell transplantation (alloHCT) continue to be a significant challenge that often result in significant morbidity/mortality and increased healthcare utilization and cost. In this study, we analyzed the impact of post-alloHCT complications on healthcare utilization and cost during first year post-transplant. We analyzed data on 240 pediatric patients. Complications analyzed included kidney injury, liver injury, lung injury, viral infections, bacterial infections, fungal infections, and acute graft-versus-host disease (GVHD). Patients were divided into three groups based on the number of complications (0-1, 2-3, and >3). Cost was estimated from charges recorded in the Pediatric Health Information System database and hospital accounting records. Patients with >3 complications had higher healthcare utilization and cost, primarily driven by inpatient hospitalization and intensive care unit admissions. Multivariable analysis of risk factors identified bacteremia ($90,166, SE = 26,636, p < 0.001), lung injury ($108,529, SE = 28,196, p < 0.001), liver injury ($90,805, SE = 28,660, p = 0.002), and grade II-IV aGVHD ($137,866, SE = 28,472, p < 0.001) as associated with significantly increased cost. Our study highlights the significant impact complications have on the overall cost of alloHCT. The identification that complications associated with high morbidity (aGVHD, pulmonary disease) are also associated with the highest financial burden emphasizes the need for future research in these areas to expand management options and improve outcomes for our patients.

Novel biopesticide based on Erinnyis ello betabaculovirus: characterization and preliminary field evaluation to control Erinnyis ello in rubber plantations.

BACKGROUND: The hornworn Erinnyis ello is the major pest of natural rubber crops in Colombia, mainly controlled using toxic chemical insecticides. The use of E. ello Betabaculovirus is an environmentally sustainable alternative for its control. The aim of the present work was to characterize a prototype biopesticide formulation and evaluate its efficacy under different conditions. RESULTS: Quality control evaluations of formulated biopesticide revealed that all the parameters evaluated were under the permissible level. The lethal concentrations LC50 and LC90 of the biopesticide were 4.3 × 103 and 5.5 × 104 occlusion bodies (OBs) mL-1 , respectively. Biopesticide efficacies against second and fourth instar larvae under greenhouse conditions were higher than 80%. Evaluation of two application rates in a clonal garden resulted in 84% and 88% efficacy, comparable to that obtained with the chemical. The biopesticide in a commercial plantation showed efficacies between 74% and 82%. Biopesticide post-application persistence was estimated at least in 1 week under field natural conditions. Results allowed selection of the lowest evaluated dose (1 × 1011 OBs ha-1 ) as the basis for further field evaluations. CONCLUSION: Formulated ErelGV showed high efficacy to control the hornworm in rubber crops and high potential to be included in integrated pest management programs, thus it could be an interesting alternative to replace agrochemicals. © 2018 Society of Chemical Industry.