Missing the mark? Exploratory analysis of the 10-year-old cutoff as an independent marker of high-risk disease in pediatric B-ALL.

This single-center, retrospective study evaluated age as a risk factor for relapsed/refractory disease and/or death in 153 children with B-cell acute lymphoblastic leukemia. The study sample included children near the 10-year age cutoff for high-risk disease (6.0-13.9 years at diagnosis) and without other high-risk features (high white cell count, unfavorable cytogenetics). Children 10.0-13.9 years treated per high-risk protocols did not have inferior outcomes compared with children aged 6.0-9.9 years initiating treatment per standard-risk protocols. The study indicates that, in the era of cytogenetics, an age threshold of 10 years might not be an independent prognostic marker. Multicenter analyses are needed.

High burden of clinically significant adverse events associated with contemporary therapy for pediatric T-cell acute lymphoblastic leukemia/lymphoma.

BACKGROUND: Despite improvements in survival for children with T-cell acute lymphoblastic leukemia and lymphoma (T-ALL/LLy), morbidity remains high. However, data are lacking regarding comprehensive descriptions of clinically relevant adverse events (AEs) experienced during early intensive chemotherapy. PROCEDURE: This single-institution retrospective study evaluated children aged 1-21 years with T-ALL/T-LLy diagnosed from 2010 to 2020. Physician chart abstraction identified and graded 20 clinically relevant AEs. AE rates were analyzed by T-ALL or LLy, minimal residual disease status, induction steroid, and use of antimicrobial prophylaxis. Statistical comparisons used the Kruskal-Wallis test (continuous variables) and Chi-square or Fisher's exact test (categorical variables). RESULTS: The cohort included 120 patients (T-ALL: 88; T-LLy: 32). Most patients experienced AEs during induction (85 out of 120; 70.8%) and consolidation (89 out of 111; 80.2%). Nonsepsis infection was common in induction (26 out of 120; 21.7%) and consolidation (35 out of 111; 31.5%). Patients treated with dexamethasone during induction had significantly higher rates of nonsepsis infection and/or sepsis during consolidation than those who received prednisone (p < .01). CONCLUSIONS: Clinically significant AEs are extremely common during induction and consolidation therapy for patients with T-ALL/LLy. Infectious AEs are particularly prevalent. These results can inform conversations with patients and families and aid in the development of toxicity-related aims in the next generation of, prospective clinical trials in T-ALL/LLy.

Differences in palliative opportunities across diagnosis groups in children with cancer.

BACKGROUND: Childhood cancer causes significant physical and emotional stress. Patients and families benefit from palliative care (PC) to reduce symptom burden, improve quality of life, and enhance family-centered care. We evaluated palliative opportunities across leukemia/lymphoma (LL), solid tumors (ST), and central nervous system (CNS) tumor groups. PROCEDURE: A priori, nine palliative opportunities were defined: disease progression/relapse, hematopoietic stem cell transplant, phase 1 trial enrollment, admission for severe symptoms, social concerns or end-of-life (EOL) care, intensive care admission, do-not-resuscitate (DNR) status, and hospice enrollment. A single-center retrospective review was completed on 0-18-year olds with cancer who died from January 1, 2012 to November 30, 2017. Demographic, disease, and treatment data were collected. Descriptive statistics were performed. Opportunities were evaluated from diagnosis to death and across disease groups. RESULTS: Included patients (n = 296) had LL (n = 87), ST (n = 114), or CNS tumors (n = 95). Palliative opportunities were more frequent in patients with ST (median 8) and CNS tumors (median 7) versus LL (median 5, p = .0005). While patients with ST had more progression/relapse opportunities (p < .0001), patients with CNS tumors had more EOL opportunities (p < .0001), earlier PC consultation, DNR status, and hospice enrollment. Palliative opportunities increased toward the EOL in all diseases (p < .0001). PC was consulted in 108 (36%) patients: LL (48%), ST (30%), and CNS (34%, p = .02). CONCLUSIONS: All children with cancer incur many events warranting PC support. Patients with ST and CNS tumors had more palliative opportunities than LL, yet received less subspecialty PC. Understanding palliative opportunities within each disease group can guide PC utilization to ease patient and family stress.

Infectious events in pediatric patients with acute lymphoblastic leukemia/lymphoma undergoing evaluation for fever without severe neutropenia.

BACKGROUND: Infections cause significant treatment-related morbidity during pediatric acute lymphoblastic leukemia/lymphoma (ALL/LLy) therapy. Fevers during periods without severe neutropenia are common, but etiologies are not well-described. This study sought to describe the bloodstream infection (BSI) and non-BSI risk in children undergoing therapy for ALL/LLy. METHODS: Demographic and clinical data were abstracted for febrile episodes without severe neutropenia at two children's hospitals. Treatment courses were stratified by intensity. Multivariate logistic regression evaluated characteristics associated with infection. RESULTS: There were 1591 febrile episodes experienced by 524 patients. Of these, 536 (34%) episodes had ≥1 infection; BSI occurred in 30 (1.9%) episodes. No BSIs occurred in episodes with a recent procedural sedation or cytarabine exposure. Presence of hypotension, chills/rigors, higher temperature, and infant phenotype were independently associated with BSI (p < .05). Of the 572 non-BSIs, the most common was upper respiratory infection (URI) (n = 381, 67%). Compared to episodes without infection, URI symptoms, higher temperature, absolute neutrophil count 500-999/µl, and evaluation during a low-intensity treatment course were more likely to be associated with a non-BSI (p < .05) and inpatient status was less likely to be associated with a non-BSI (p < .05). CONCLUSIONS: The BSI rate in pediatric patients with ALL/LLy and fever without severe neutropenia is low, but one-third of the time, patients have a non-BSI. Future research should test if the need for empiric antibiotics can be tailored based on the associations identified in this study.

Relationship of race and ethnicity on access, timing, and disparities in pediatric palliative care for children with cancer.

PURPOSE: Pediatric palliative care (PPC) improves quality of life for children and adolescents with cancer. Little is known about disparities between different racial and ethnic groups in the frequency and timing of PPC referrals. We evaluated the impact of race and ethnicity on the frequency and timing of PPC referral after initiation of an embedded PPO clinic where no formal consultation triggers exist. METHODS: Patients with cancer between 0 and 25 years at diagnosis who experienced a high-risk event between July 2015 and June 2018 were eligible. Demographic, disease, and PPC information were obtained. Descriptive statistics and logistic regression were used to assess likelihood of receiving PPC services by race/ethnicity. RESULTS: Of 426 patients who experienced a high-risk event, 48% were non-Hispanic White, 31% were non-Hispanic Black, 15% were Hispanic of any race, and 4% were non-Hispanic Asian. No significant differences were found between race/ethnicity and age at diagnosis/death, sex, and diagnosis. PPC consultation (p = 0.03) differed by race. Non-Hispanic Black patients were 1.7 times more likely than non-Hispanic White patients to receive PPC after adjustment (p = 0.01). White patients spent less days in the hospital in the last 90 days of life (3.0 days) compared with Black (8.0), Asian (12.5), or Hispanic patients (14.0, p = 0.009) CONCLUSION: Disparities exist in patients receiving pediatric oncology and PPC services. Cultural tendencies as well as unconscious and cultural biases may affect PPC referral by race and ethnicity. Better understanding of cultural tendencies and biases may improve end-of-life outcomes for children and young adults with cancer.

Association of a pediatric palliative oncology clinic on palliative care access, timing and location of care for children with cancer.

BACKGROUND: Most pediatric palliative care (PPC) services are inpatient consultation services and do not reach patients and families in the outpatient and home settings, where a vast majority of oncology care occurs. We explored whether an embedded pediatric palliative oncology (PPO) clinic is associated with receipt and timing of PPC and hospital days in the last 90 days of life. METHODS: Oncology patients (ages 0-25) with a high-risk event (death, relapse/progression, and/or phase I/II clinical trial enrollment) between 07/01/2015 and 06/30/2018 were included. PPO clinic started July 2017. Two cohorts were defined: pre-PPO (high-risk event(s) occurring 07/01/2015-06/30/2017) and post-PPO (high-risk event(s) occurring 07/01/2017-06/30/2018). Descriptive statistics were performed; demographic, disease course, and outcomes variables across cohorts were compared. RESULTS: A total of 426 patients were included (pre-PPO n = 235; post-PPO n = 191). Forty-seven patients with events in both pre- and post-PPO cohorts were included in the post-PPO cohort. Mean age at diagnosis was 8 years. Diagnoses were evenly distributed among solid tumors, brain tumors, and leukemia/lymphoma. Post-PPO cohort patients received PPC more often (45.6% vs. 21.3%, p < 0.0001), for a longer time before death than the pre-PPO cohort (median 88 vs. 32 days, p = 0.027), and spent fewer days hospitalized in the last 90 days of life (median 3 vs. 8 days, p = 0.0084). CONCLUSION: A limited-day, embedded PPO clinic was associated with receipt of PPC and spending more time at home in patients with cancer who had high-risk events. Continued improvements to these outcomes would be expected with additional oncology provider education and PPO personnel.

Impact of respiratory viral panel testing on length of stay in pediatric cancer patients admitted with fever and neutropenia.

BACKGROUND: Polymerase chain reaction (PCR) respiratory viral panel (RVP) testing is often used in evaluation of pediatric cancer patients with febrile neutropenia (FN), but correlation with adverse outcomes has not been well characterized. PROCEDURE: A retrospective cohort of all children ages 0-21 years with cancer admitted to Children's Healthcare of Atlanta for FN from January 2013 to June 2016 was identified. Patient demographic and clinical variables such as age, RVP results, length of stay (LOS), and deaths were abstracted. Relationship between RVP testing and positivity and LOS, highest temperature (Tmax), hypotension and intensive care unit (ICU) admission were compared using Wilcoxon rank sums, chi-square, or Fisher's exact tests adjusting for age, sex, bacteremia, and diagnosis. RESULTS: The 404 patients identified had 787 total FN admissions. RVPs were sent in 38% of admissions and were positive in 59%. Patients with RVPs sent were younger (median 5.5 vs 8.0 years, P < .0001) with higher Tmax (39.2° vs 39.1°, P = .016). The most common virus identified was rhinovirus/Enterovirus (61%). There were no significant differences in highest temperature or lowest blood pressure based on RVP positivity. Patients admitted to the ICU were more likely to have RVPs sent (odds ratio [OR] = 3.19, P < .002); however, neither having RVP testing nor RVP positivity were significantly associated with increased LOS or death. Coinfection with bacteremia and a respiratory virus was identified in 9.1% of patients. CONCLUSIONS: These data raise the question of the utility of sending potentially costly RVP testing as RVP positivity during febrile neutropenia does not impact LOS, degree of hypotension, or ICU admission.

Trends in the Laboratory Detection of Rotavirus Before and After Implementation of Routine Rotavirus Vaccination - United States, 2000-2018.

Before the introduction of rotavirus vaccine in the United States in 2006, rotavirus infection was the leading cause of severe gastroenteritis among U.S. children (1). To evaluate the long-term impact of rotavirus vaccination on disease prevalence and seasonality in the United States, CDC analyzed national laboratory testing data for rotavirus from laboratories participating in CDC's National Respiratory and Enteric Viruses Surveillance System (NREVSS) during the prevaccine (2000-2006) and postvaccine (2007-2018) periods. Nationally, the median annual percentage of tests positive for rotavirus declined from 25.6% (range = 25.2-29.4) in the prevaccine period to 6.1% (range = 2.6-11.1) in the postvaccine period. When compared with the prevaccine period, the postvaccine period saw declines in the annual peak in rotavirus positivity from a median of 43.1% (range = 43.8-56.3) to a median of 14.0% (range = 4.8-27.3) and in the season duration from a median of 26 weeks (range = 23-27) to a median of 9 weeks (range = 0-18). In the postvaccine period, a biennial pattern emerged, with alternating years of low and high rotavirus activity. Implementation of the rotavirus vaccination program has substantially reduced prevalence of the disease and altered seasonal patterns of rotavirus in the United States; these changes have been sustained over 11 seasons after vaccine introduction. Ongoing efforts to improve coverage and on-time vaccination (2) can help maximize the public health impact of rotavirus vaccination.

Prevalence of Rectal Chlamydial and Gonococcal Infections: A Systematic Review.

We undertook a systematic review to examine rectal Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng) infections in women and men who have sex with men (MSM). English-language publications measuring rectal Ct or Ng prevalence using nucleic acid amplification tests were eligible. Searching multiple electronic databases, we identified 115 eligible reports published between January 2000 and November 2016. Overall, the prevalence of rectal Ct (9%) was higher than that of rectal Ng (4.7%). Rectal Ct prevalence was similar in MSM (9%) and women (9.2%), whereas rectal Ng prevalence was higher in MSM (6.1%) than in women (1.7%). Generally, rectal Ct prevalence was similar in sexually transmitted disease clinics (9.1%) and nonsexual health clinics (8.6%), whereas rectal Ng prevalence was somewhat lower in sexually transmitted disease clinics (4.5%) than in nonsexual health clinics (6%). These infections seem to be relatively common across a range of populations and clinical settings, highlighting the need for additional research on these preventable, treatable conditions.

Unmet Needs for Ancillary Services Among Hispanics/Latinos Receiving HIV Medical Care - United States, 2013-2014.

The prevalence of diagnosed human immunodeficiency virus (HIV) infection in Hispanics/Latinos in the United States is more than twice as high as the prevalence among non-Hispanic whites (1). Services that support retention in HIV medical care and assist with day-to-day living, referred to here as ancillary services, help persons living with HIV access HIV medical care, adhere to HIV treatment, and attain HIV viral suppression. The needs for these ancillary services among Hispanics/Latinos are not well described (2). To obtain nationally representative estimates of and reasons for unmet needs for such services among Hispanic/Latino adults receiving outpatient HIV medical care during 2013-2014, CDC analyzed data from the Medical Monitoring Project (MMP). The analysis found that Hispanics/Latinos in all age and sexual orientation/behavior subgroups reported substantial unmet needs, including 24% needing dental care, 21% needing eye or vision care, 15% needing food and nutrition services, and 9% needing transportation assistance. Addressing unmet needs for ancillary services among Hispanics/Latinos living with HIV might help increase access to HIV care, improve health outcomes, and reduce health disparities.

Unmet Needs for Ancillary Services Among Men Who Have Sex with Men and Who Are Receiving HIV Medical Care - United States, 2013-2014.

Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV) in the United States (1). Ancillary services, defined as services that support retention in HIV medical care and assist with day-to-day living, can improve the health of HIV-infected MSM and help them achieve viral suppression (2). To assess the unmet needs for ancillary services among MSM receiving outpatient HIV medical care during 2013-2014, CDC used data from the Medical Monitoring Project (MMP), a surveillance system designed to assess clinical and behavioral characteristics of adults receiving HIV care, to obtain nationally representative estimates of, and identify reasons for, unmet needs (3). Based on self-reported needs of persons responding to the MMP survey, the most prevalent unmet needs were for non-HIV medical care services: approximately 23% had an unmet need for dental care, and 19% had an unmet need for eye or vision care. Unmet needs were most prevalent among young, non-Hispanic black, and Hispanic/Latino MSM. State and local health departments, community-based organizations, and health care providers might improve the health of MSM living with HIV by promoting access to ancillary services using strategies that increase patient awareness of how to obtain these services, especially among young, non-Hispanic black, and Hispanic/Latino MSM.

The Scope of Practice of an Embedded Pediatric Palliative Oncology Clinic.

CONTEXT: Pediatric palliative care (PPC) improves end-of-life (EOL) outcomes for children with cancer. Though PPC visits are the 'intervention' in studies focused on EOL care, the content of PPC visits within pediatric oncology is poorly understood. OBJECTIVES: This study aimed to understand the scope of PPC practice during visits for children with cancer and their families. METHODS: This was a retrospective cohort study of patients 0-27 years with cancer seen in PPC clinic within an academic pediatric oncology center between 2017 and 2022. During each PPC visit, documenting providers chose the domains discussed or managed (goals of care, symptom management, and care coordination with respective subdomains). Data was abstracted from the electronic health record, PPC clinic database, and Cancer Registry. The differences in frequency and addressed domains were analyzed by demographics, visit type, diagnosis group, and proximity to EOL. RESULTS: Across 351 patients, 1919 outpatient PPC visits occurred. Median domains were higher in visits <90 days vs. 91+ days from EOL (12.0 vs. 10.0; p < 0.0001); pain and hospice collaboration were particularly discussed closer to EOL. Psychological symptoms like anxiety (30.7% vs. 21.1%; p < 0.001) were addressed more in follow-ups than initial visits. Compared to brain tumor or leukemia/lymphoma visits, solid tumor visits addressed more symptom management subdomains, especially pain (79.9%; p < 0.0001). CONCLUSION: The scope of PPC practice is broad and varied. Each visit encompasses many subdomains, the most common being care coordination with oncology teams and helping patients/families cope with the disease. More domains were addressed in solid tumor visits and near EOL.

An Interpretable Machine Learning Framework for Rare Disease: A Case Study to Stratify Infection Risk in Pediatric Leukemia.

Background: Datasets on rare diseases, like pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), have small sample sizes that hinder machine learning (ML). The objective was to develop an interpretable ML framework to elucidate actionable insights from small tabular rare disease datasets. Methods: The comprehensive framework employed optimized data imputation and sampling, supervised and unsupervised learning, and literature-based discovery (LBD). The framework was deployed to assess treatment-related infection in pediatric AML and ALL. Results: An interpretable decision tree classified the risk of infection as either "high risk" or "low risk" in pediatric ALL (n = 580) and AML (n = 132) with accuracy of ∼79%. Interpretable regression models predicted the discrete number of developed infections with a mean absolute error (MAE) of 2.26 for bacterial infections and an MAE of 1.29 for viral infections. Features that best explained the development of infection were the chemotherapy regimen, cancer cells in the central nervous system at initial diagnosis, chemotherapy course, leukemia type, Down syndrome, race, and National Cancer Institute risk classification. Finally, SemNet 2.0, an open-source LBD software that links relationships from 33+ million PubMed articles, identified additional features for the prediction of infection, like glucose, iron, neutropenia-reducing growth factors, and systemic lupus erythematosus (SLE). Conclusions: The developed ML framework enabled state-of-the-art, interpretable predictions using rare disease tabular datasets. ML model performance baselines were successfully produced to predict infection in pediatric AML and ALL.

A Pilot of a Telehealth-Hospice Transition Intervention for Children and Young Adults with Cancer.

BACKGROUND AND AIMS: Telehealth can improve care for patients with progressive cancer enrolling in hospice. Coordinated telehealth visits (patient/family-hospital-hospice) may improve communication, satisfaction with and interdisciplinary hospice collaboration. This pilot examines the impact of three coordinated telehealth visits on these outcomes. METHODS: This is a prospective pilot study of 0-29-year-old patients with cancer initiating hospice care between 2021-2023. Adult patients, caregivers, oncology and palliative care clinicians, hospice nurses and administrators were surveyed about feasibility and acceptability with telehealth (Technology Acceptance Model 2) after first and third telehealth visits. Hospice satisfaction (Consumer Assessment of Healthcare Providers and Systems) was completed by caregivers after visit 3 and during bereavement. Healthcare professionals completed the Assessment of Interprofessional Team Collaboration Scale II (AITCS-II). Survey responses were summarized and differences in scores were analyzed. RESULTS: Of 40 eligible patients, 24 enrolled, 19 completed visit 1, and 13 completed visit 3. Fourteen caregivers and two adult patients completed visit 1 surveys; nine caregivers and two adult patients completed visit 3 surveys. Participants highly rated telehealth acceptability after visit 1 (Median: 4.5, IQR: 4.0-4.7) and 3 (Median: 4.4, IQR: 4.0-4.7). Hospice services were rated as highly satisfactory at visit 3 (Median: 4.0, IQR: 3.7-4.0) and during bereavement (Median: 3.7, IQR: 3.5-4.0). Healthcare professionals (n = 85 surveys) reported excellent interprofessional collaboration (Hospital clinicians median: 99/115 and hospice teams 111/115). CONCLUSIONS: Participants found coordinated telehealth visits to be feasible, acceptable, and satisfactory. Telehealth may be utilized as an acceptable alternative to clinic visits and fosters hospital-hospice collaboration.

Early Versus Late Outpatient Pediatric Palliative Care Consultation and Its Association With End-of-Life Outcomes in Children With Cancer.

Background: There is no consensus on what constitutes "early" pediatric palliative care (PPC) referral within pediatric oncology. Few studies report outcomes based on PPC timing. Objectives: Investigate associations between early (<12 weeks) or late (≥12 weeks from diagnosis) outpatient PPC consultation with demographics, advance care planning (ACP), and end-of-life (EOL) outcomes. Design: Retrospective chart and database review of demographic, disease, visit data, and PPC/EOL outcomes. Setting/Subjects: Deceased pediatric patients with cancer 0-27 years of age seen at an embedded consultative PPC clinic. Measurements: Patient demographics, disease characteristics, PPC/EOL outcomes: timing/receipt of ACP, hospice enrollment, do-not-resuscitate (DNR) documentation, hospital days in last 90 days of life, concordance between actual and preferred location of death, receipt of cardiopulmonary resuscitation (CPR) at EOL, and death in the intensive care unit. Results: Thirty-two patients received early and 118 received late PPC. Early outpatient PPC was associated with cancer type (p < 0.01). Early PPC (p = 0.04) and ACP documentation (p = 0.04) were associated with documentation of preferred location of death. Early PPC was associated with a preference for home death (p = 0.02). Timing of outpatient PPC was not associated with ACP documentation or other EOL outcomes. In the entire cohort, 73% of PPC patients received hospice, 74% had a DNR order, 87% did not receive CPR at EOL, and 90% died in their preferred location. Conclusions: When using a cutoff of 12 weeks from diagnosis, outpatient PPC timing was only associated with location of death metrics, likely due to high-quality PPC and EOL care among all patients.

Characteristics and outcomes of pediatric oncology patients at risk for guardians declining transfusion of blood components.

BACKGROUND: Transfusion of blood products is a necessary part of successful delivery of myelosuppressive regimens in pediatric cancer. There is a paucity of literature characterizing outcomes or management of pediatric patients with cancer when transfusion is declined. AIMS: The objective of this paper is to describe the clinical characteristics, care, and outcomes of patients with cancer at risk for declining transfusion. METHODS AND RESULTS: A retrospective cohort of patients aged 0-21 years with cancer managed at Children's Healthcare of Atlanta between 2006 and 2020 and with ICD-9 codes indicating risk of "transfusion refusal" or Jehovah's witness (JW) religion was identified. Demographics, disease, and management were abstracted. Descriptive statistics were performed to examine associations with transfusion receipt. Among 35 eligible patients identified as at risk for declining transfusion, 89% had primary guardians who identified as JW, and 45.7% identified as Black, non-Hispanic. Only 40% of guardians actively declined transfusion. Transfusion recipients had significantly lower hemoglobin (g/dl) and platelet counts (1000/µl) at initial presentation (9.6 vs. 11.9, p < .002 and 116.0 vs. 406.5, p = .001, respectively) and at nadir (5.9 vs. 8.7, p < .001 and ≤ 10 vs. 154, p < .001, respectively) than non-recipients. Legal intervention was required in 36.4% of those who ultimately received a transfusion. CONCLUSION: Among pediatric cancer patients whose medical record initially indicated a preference for no transfusion, 60% of guardians accepted blood products when prescribed for oncology care. Guidelines for systematic management and transfusion sparing approaches are needed to honor guardian's preferences when possible yet while maintaining equitable cancer outcomes in this population.

Clinical covariates that improve the description of high dose methotrexate pharmacokinetics in a diverse population to inform MTXPK.org.

The MTXPK.org webtool was launched in December 2019 and was developed to facilitate model-informed supportive care and optimal use of glucarpidase following the administration of high-dose methotrexate (HDMTX). One limitation identified during the original development of the MTXPK.org tool was the perceived generalizability because the modeled population comprised solely of Nordic pediatric patients receiving 24-h infusions for the treatment of acute lymphoblastic leukemia. The goal of our study is to describe the pharmacokinetics of HDMTX from a diverse patient population (e.g., races, ethnicity, indications for methotrexate, and variable infusion durations) and identify meaningful factors that account for methotrexate variability and improve the model's performance. To do this, retrospectively analyzed pharmacokinetic and toxicity data from pediatric and adolescent young adult patients who were receiving HDMTX (>0.5 g/m2 ) for the treatment of a cancer diagnosis from three pediatric medical centers. We performed population pharmacokinetic modeling referencing the original MTXPK.org NONMEM model (includes body surface area and serum creatinine as covariates) on 1668 patients, 7506 administrations of HDMTX, and 30,250 concentrations. Our results support the parameterizations of short infusion duration (<8 h) and the presence of Down syndrome on methotrexate clearance, the parameterization of severe hypoalbuminemia (<2.5 g/dL) on the intercompartmental clearance (Q2 and Q3), and the parameterization of pleural effusion on the volume of distribution (V1 and V2). These novel parameterizations will increase the generalizability of the MTXPK.org model once they are added to the webtool.

Respiratory Syncytial Virus Infection Among Hospitalized Infants in Four Middle-Income Countries.

BACKGROUND: Understanding respiratory syncytial virus (RSV) global epidemiology is important to inform future prevention strategies. METHODS: Hospitalized infants <1-year-old with acute illness were enrolled prospectively in Albania, Jordan, Nicaragua, and Philippines during respiratory seasons in 2015-2017. Medical chart review, parental interview, and post-discharge follow up were conducted. Respiratory specimens were tested using real-time RT-PCR for RSV. Infant characteristics associated with very severe illness (intensive care unit [ICU] admission or receipt of supplemental oxygen) were assessed using logistic regression to adjust for potential confounders (age, sex, study site, and preterm birth). RESULTS: Of 3634 enrolled hospitalized infants, 1129 (31%) tested positive for RSV. The median age of RSV-positive infants was 2.7 (IQR: 1.4-6.1) months and 665 (59%) were male. Very severe illness in 583 (52%) RSV-positive infants was associated with younger age (aOR 4.1, 95% CI: 2.6-6.5 for 0-2 compared to 9-11-months; P < .01), low weight-for-age z-score (aOR 1.9, 95% CI: 1.2-2.8; P < .01), ICU care after birth (aOR 1.6, 95% CI: 1.0-2.5; P = .048), and cesarean delivery (aOR 1.4, 95% CI: 1.0-1.8; P = .03). RSV subgroups A and B co-circulated at all sites with alternating predominance by year; subgroup was not associated with severity (aOR 1.0, 95% CI: 0.8-1.4). Nine (0.8%) RSV-positive infants died during admission or within ≤30 days of discharge, of which 7 (78%) were <6-months-old. CONCLUSIONS: RSV was associated with nearly a third of infant acute illness hospitalizations in four middle-income countries during the respiratory season, where, in addition to young age, factors including low weight-for-age might be important predictors of severity. RSV prevention strategies targeting young infants could substantially reduce RSV-associated hospitalizations in middle-income countries.

The Supportive Care Clinic: A Novel Model of Embedded Pediatric Palliative Oncology Care.

CONTEXT: Pediatric palliative care (PPC) improves quality of life and end-of-life outcomes for children with cancer, but often occurs late in the disease course. The Supportive Care Clinic (SCC) was launched in 2017 to expand outpatient PPC access. OBJECTIVES: To describe the inaugural four years (2017-2021) of an academic, consultative, embedded SCC within pediatric oncology. METHODS: Descriptive statistics (demographic, disease, treatment, visit, and end-of-life) and change over time were calculated. RESULTS: During the first four years, 248 patients (51.6% male; 58.1% White; 35.5% Black; 13.7% Hispanic/Latino) were seen in SCC, totaling 1,143 clinic visits (median 4, IQR 2,6), including 248 consultations and 895 follow-up visits. Clinic visits grew nearly 300% from year one to four. Primary diagnoses were central nervous system tumor (41.9%), solid tumor (37.5%), and leukemia/lymphoma (17.3%). The first point of PPC contact became SCC (70.6%) for most referred patients. Among the 136 deceased patients (54.8%), 77.9% had a do-not-resuscitate or Physician Orders for Life Sustaining Treatment in place, and 72.8% received hospice care. When known (n = 112), 89.3% died in their preferred location. The time from SCC consultation to death increased from 74 to 226 days over the four years (P < 0.0001). The proportion of SCC consultations that occurred greater than 90 days from death increased from 39.1% in year one to 85.0% in year four. CONCLUSION: Embedded SCC clinics can be successful, achieve steady growth, improve referrals and timing of PPC, and enhance end-of-life care for children with cancer. Large pediatric cancer centers should include SCC outpatient services.

Evaluating Palliative Opportunities Across the Age Spectrum in Children and Adolescent Patients with Cancer.

Purpose: Adolescent patients with cancer experience unique stressors due to their developmental stage, with increased physical, emotional, and social distress. Palliative care (PC) serves an important role in pediatric cancer care. We examined "palliative opportunities," or events during a patient's cancer course where subspecialty PC would be warranted and compared opportunities between adolescents and younger patients. Methods: Patients from a single center, 0-18 years of age at cancer diagnosis, who died from January 1, 2012, to November 30, 2017, were included. In this secondary analysis, patients were divided into cohorts based on age at diagnosis: 0-12 and 13-18 years. Demographic, disease, and treatment data were collected. Descriptive statistics and modeling were performed. Number, type, and timing of palliative opportunities and PC consultation timing and reason were evaluated across cohorts. Results: Of the 296 patients included for analysis, 27.7% were 13-18 years (82/296) at diagnosis. Frequency of palliative opportunities did not differ by age (median 7.0 [interquartile range 4.0 and 10.0] in both cohorts). PC consultation occurred in 36.5% (108/296), with neither rate nor timing differing by age group. PC consultations in adolescents were more often for symptom management (p = 0.0001). Adolescent patients were less likely to have a do-not-resuscitate order placed before death (61.0%, 50/82) compared to younger patients (73.8%, 158/214, p = 0.03). Conclusion: Adolescent patients with cancer did not experience more palliative opportunities than younger patients in this cohort, although they often have challenging psychological, family, and social stressors that were not identified. Incorporating additional palliative opportunities could enhance identification of stress and symptoms in adolescents with cancer such that PC could be timed to meet their needs.