Cardiovascular toxicities with pediatric tyrosine kinase inhibitor therapy: An analysis of adverse events reported to the Food and Drug Administration.

We sought to examine cardiovascular toxicities associated with tyrosine kinase inhibitors in pediatrics. We examined 1624 pediatric adverse events with imatinib, dasatinib, sorafenib, pazopanib, crizotinib, and ruxolitinib reported to the Food and Drug Administration between January 1, 2015, and August 14, 2020. There were 102 cardiovascular event reports. Hypertension was the most commonly reported cardiovascular event and was most frequently associated with sorafenib and pazopanib. The presence of infection increased the reporting odds of cardiovascular events overall and specifically cardiac arrest, heart failure, and hypertension. These data provide early insight into cardiovascular toxicities with tyrosine kinase inhibitor use in pediatrics.

Improving vitamin D testing and supplementation in children with newly diagnosed cancer: A quality improvement initiative at Rady Children's Hospital San Diego.

BACKGROUND: Vitamin D deficiency and insufficiency have been associated with poorer health outcomes. Children with cancer are at high risk for vitamin D deficiency and insufficiency. At our institution, we identified high variability in vitamin D testing and supplementation in this population. Of those tested, 65% were vitamin D deficient/insufficient. We conducted a quality improvement (QI) initiative with aim to improve vitamin D testing and supplementation among children aged 2-18 years with newly diagnosed cancer to ≥80% over 6 months. METHODS: An inter-professional team reviewed baseline data, then developed and implemented interventions using Plan-Do-Study-Act (PDSA) cycles. Barriers were identified using QI tools, including lack of automated triggers for testing and inconsistent supplementation criteria and follow-up testing post supplementation. Interventions included an institutional vitamin D guideline, clinical decision-making tree for vitamin D deficiency, insufficiency and sufficiency, electronic medical record triggers, and automated testing options. RESULTS: Baseline: N = 26 patients, four (15%) had baseline vitamin D testing; two (8%) received appropriate supplementation. Postintervention: N = 33 patients; 32 (97%) had baseline vitamin D testing; 33 (100%) received appropriate supplementation and completed follow-up testing timely (6-8 weeks post supplementation). Change was sustained over 24 months. CONCLUSIONS: We achieved and sustained our aim for vitamin D testing and supplementation in children with newly diagnosed cancer through inter-professional collaboration of hematology/oncology, endocrinology, hospital medicine, pharmacy, nursing, and information technology. Future PDSA cycles will address patient compliance with vitamin D supplementation and impact on patients' vitamin D levels.

The Application of Next-generation Sequencing Tumor Molecular Profiling in the Diagnosis and Management of a Case of Acute Myelogenous Leukemia With MLL-PTD in a Pediatric Heart Transplant Recipient.

A 6-year-old girl with a history of heart transplantation was diagnosed with myelodysplastic syndrome, which progressed to acute myelogenous leukemia. Comprehensive genomic profiling of her tumor discovered an MLL-PTD (partial tandem duplication) and she received chemotherapy and a hematopoietic stem cell transplant (HSCT). She subsequently relapsed and tumor molecular profiling was repeated, revealing 2 new potentially targetable mutations (FLT3 and IDH2). A novel treatment regimen targeting these mutations with sorafenib and azacitidine without using cytotoxic chemotherapy produced remission and she subsequently pursued a second HSCT. She remains disease-free 17 months after HSCT. This case report demonstrates how repeated tumor molecular profiling provided novel actionable information for the diagnosis and management at 2 timepoints.

Yoga as a Complementary and Alternative Therapy in Children with Hematologic and Oncologic Disease.

A diagnosis of a hematologic or oncologic disease in a child can be stressful for the patient and the family. Yoga as an intervention has been reported to decrease stress in adults diagnosed with chronic disorders but few studies have been reported with children and their families. A convenience sample of patients diagnosed with cancer or a blood disorder (ages 7-17 years) and their caregivers was selected to participate in a single bedside yoga class. Participants were surveyed pre and post yoga with the Spielberger State Trait Anxiety Scale. Children were also surveyed pre and post yoga with the Wong-Baker Faces Pain Scale. Children had a significant decrease in pain post yoga but no change in anxiety. Adolescents and parents had a significant decrease in anxiety post yoga intervention.

Multimodal Treatment of Rhinocerebral Mucormycosis in a Pediatric Patient With Relapsed Pre-B Acute Lymphoblastic Leukemia.

A 17-year-old girl developed invasive rhinocerebral mucormycosis during intensive re-induction chemotherapy for relapsed pre-B acute lymphoblastic leukemia. Due to the high case fatality rate for invasive mucormycosis in profoundly immunosuppressed patients, an aggressive treatment regimen was pursued. In addition to the standard of care treatments with intravenous amphotericin and aggressive surgical debridements, she received intraventricular amphotericin to the brain via an Ommaya reservoir, hyperbaric oxygen treatments, filgrastim, intravenous immunoglobulin and antifungal in vitro synergy testing to allow for more targeted antifungal therapy with the addition of micafungin. After a 3-month treatment course, it was determined that her mucormycosis was under appropriate control, allowing her to continue treatment for her leukemia with hematopoietic stem cell transplant with a plan for continued intravenous antifungal therapy through engraftment.

Effect of Vitamin D Supplementation on Delayed Hyperphosphatemia in Pediatric Acute Lymphoblastic Leukemia Patients During Induction Chemotherapy.

OBJECTIVES: Vitamin D plays a role in maintaining bone health and calcium metabolism, but recent studies cast doubt on vitamin D supplementation's benefits in survivors of acute lymphoblastic leukemia (ALL). Vitamin D supplementation could increase serum phosphate through increased intestinal absorption of phosphate and suppression of parathyroid hormone, which would lead to decreased renal phosphate excretion. Because of the potential for renal injury during induction chemotherapy for ALL, Vitamin D supplementation's potential for increasing hyperphosphatemia could outweigh its suggested but unproven benefits. METHODS: To measure the interaction between vitamin D supplementation and phosphate during chemotherapy induction, a retrospective study was done. Demographic data; clinical information about the diagnosis; laboratory data regarding calcium, phosphate, and vitamin D concentrations; and medication histories were reviewed. RESULTS: A retrospective study of 41 children with ALL showed no statistically significant difference in the final phosphate concentrations that were obtained (4.41 mg/dL vs. 4.53 mg/dL, p = 0.635) with regard to their vitamin D supplementation status. Longitudinal effects with vitamin D and phosphate showed a trend toward increasing phosphate concentrations in patients who received supplemental vitamin D (0.035 vs. 0.010 mg/dL per day; p = 0.102). CONCLUSIONS: Vitamin D potentially poses a risk of hyperphosphatemia in children undergoing induction chemotherapy for ALL.

Inadvertently boarding a pirate ship: disease progression in a paediatric patient with relapsed metastatic Ewing sarcoma receiving treatment at a centre for alternative therapy in Mexico.

Complementary and alternative medicine (CAM) therapies are commonly incorporated into the care of patients with paediatric cancer. Many modalities are safe and effective during cancer treatment and have proved beneficial for symptom relief and quality of life. However, situations where alternative therapy is provided without allopathic medical care supportive care resources can pose a safety risk to patients. This report describes the case of a 16-year-old Chinese girl with metastatic Ewing sarcoma who sought treatment with alternative treatment in Mexico. When her disease progressed with an ensuing significant loss of function, the centre personnel were unable to respond to her acute deterioration or provide necessary medical care. This resulted in her being stranded in a foreign country paralysed, isolated, and with large unanticipated financial expenditures.

Parent-reported outcomes of comprehensive care for children with medical complexity.

The Medical Home Clinic for Special Needs Children (MHCL) at Arkansas Children's Hospital provides comprehensive care oversight for children with medical complexity (CMC). The objective of this study is to evaluate parent perceptions of health care delivery outcomes after 12 months of enrollment in the MHCL. This is a prospective cohort study of parents of MHCL patients, who completed surveys at initial and 12-month visits. Surveys assessed parent health, child health and function, family stress, and overall satisfaction, using previously validated measures and scales. Paired analyses examined differences in measures between baseline and 12 months. One-hundred and twenty of 174 eligible parents completed the follow-up survey at 12 months. Respondents were 63% White/Caucasian, 90% biological parent, and 48% with an annual family income < $20,000. From baseline to 12 months, a greater number of respondents reported having a care plan (53% vs. 85%, p < .001); fewer respondents needed help with care coordination (78% vs. 31%, p < .001). No changes were seen in reports of having emotional needs met. Parents reported a decline in the physical subscale of the SF-12 Health-Related Quality of Life measure (49.1 vs. 46.4, p < .01), with those parents with ≥ 1 additional child with special needs reporting a marked decline (49.2 vs. 42.5, p < .001). No other changes in family impact were found. We conclude that comprehensive care oversight may improve care coordination for parents of CMC, but no association with improved parent health was found. Future studies should identify the factors that influence parental burden and tailor clinical interventions to address such factors.

Hospital-based comprehensive care programs for children with special health care needs: a systematic review.

OBJECTIVE: To examine the effectiveness of hospital-based comprehensive care programs in improving the quality of care for children with special health care needs. DATA SOURCES: A systematic review was conducted using Ovid MEDLINE, CINAHL, EMBASE, PsycINFO, Sociological Abstracts SocioFile, and Web of Science. STUDY SELECTION: Evaluations of comprehensive care programs for categorical (those with single disease) and noncategorical groups of children with special health care needs were included. Selected articles were reviewed independently by 2 raters. DATA EXTRACTION: Models of care focused on comprehensive care based at least partially in a hospital setting. The main outcome measures were the proportions of studies demonstrating improvement in the Institute of Medicine's quality-of-care domains (effectiveness of care, efficiency of care, patient or family centeredness, patient safety, timeliness of care, and equity of care). DATA SYNTHESIS: Thirty-three unique programs were included, 13 (39%) of which were randomized controlled trials. Improved outcomes most commonly reported were efficiency of care (64% [49 of 76 outcomes]), effectiveness of care (60% [57 of 95 outcomes]), and patient or family centeredness (53% [10 of 19 outcomes). Outcomes less commonly evaluated were patient safety (9% [3 of 33 programs]), timeliness of care (6% [2 of 33 programs]), and equity of care (0%). Randomized controlled trials occurred more frequently in studies evaluating categorical vs noncategorical disease populations (11 of 17 [65%] vs 2 of 16 [17%], P = .008). CONCLUSIONS: Although positive, the evidence supporting comprehensive hospital-based programs for children with special health care needs is restricted primarily to nonexperimental studies of children with categorical diseases and is limited by inadequate outcome measures. Additional high-quality evidence with appropriate comparative groups and broad outcomes is necessary to justify continued development and growth of programs for broad groups of children with special health care needs.

Effect of hospital-based comprehensive care clinic on health costs for Medicaid-insured medically complex children.

OBJECTIVE: To evaluate the effect on all state Medicaid costs of a children's hospital-based multidisciplinary clinic that provides comprehensive and coordinated care for medically complex children. DESIGN: Before-after intervention study. Patients' health care costs for up to 1 year before enrollment in the clinic were compared with patients' health care costs for up to 1 year after enrollment in the clinic. Patients were enrolled in our study from August 2006 to May 2008. SETTING: Tertiary care children's hospital in a rural state. PARTICIPANTS: A total of 225 medically complex children who had at least 2 chronic medical conditions and who were followed up by at least 2 pediatric subspecialists. INTERVENTION: Multidisciplinary teams ensure that each patient receives all the necessary medical, nutritional, and developmental care and that there is improved coordination of care with primary care providers, subspecialists, hospitalists, and community-based services. MAIN OUTCOME MEASURES: Using Arkansas Medicaid claims data, we examined the medical costs for all outpatient, inpatient, emergency department, and prescription drug claims. Costs were calculated on a per month per patient basis and summarized for annual costs. RESULTS: The mean annual cost per patient per month decreased by $1766 for inpatient care (P < .001) and by $6.00 for emergency department care (P < .001). Although the cost per patient per month for outpatient claims (P < .05) and prescriptions (P < .001) increased, the overall cost to Medicaid per patient per month decreased by $1179 (P < .001). CONCLUSIONS: This hospital-based multidisciplinary clinic resulted in a significant decrease in total Medicaid costs for medically complex children.