Provider Perceptions for Withdrawing Life Sustaining Therapies at a Large Pediatric Hospital.

CONTEXT: More than 74% of pediatric deaths occur in an intensive care unit (ICU), with 40% occurring after withdrawal of life-sustaining therapies (WOLST). No needs assessment has described provider needs or suggestions for improving the WOLST process in pediatrics. OBJECTIVES: This study aims to describe interdisciplinary provider self-reported confidence, needs, and suggestions for improving the WOLST process. METHODS: A convergent parallel mixed-methods design was used. An online survey was distributed to providers involved in WOLSTs in a quaternary children's hospital between January and December 2018. The survey assessed providers' self-reported confidence in their role, in providing guidance to families about the WOLST, experiences with the WOLST process, areas for improvement, and symptom management. Kruskal-Wallis testing was used for quantitative data analysis with P values <0.05 considered significant. Analysis was performed with SPSS v27. Qualitative data were thematically analyzed using Atlas.ti.8 and NVivo. RESULTS: A total of 297 surveys were received (48% survey completion) that consisted of multiple choice, Likert-type, and yes/no questions with options for open-ended responses. Mean provider self-rated confidence was high and varied significantly between disciplines. Qualitative analysis identified four areas for refining communication: 1) between the primary team and family, 2) within the primary team, 3) between the primary team and consulting providers, and 4) logistical challenges. CONCLUSIONS: While participants' self-rated confidence was high, it varied between disciplines. Participants identified opportunities for improved communication and planning before a WOLST. Future work includes development and implementation of a best practice guideline to address gaps and standardize care delivery.

Mutation-specific signaling profiles and kinase inhibitor sensitivities of juvenile myelomonocytic leukemia revealed by induced pluripotent stem cells.

Juvenile myelomonocytic leukemia (JMML) is an uncommon myeloproliferative neoplasm driven by Ras pathway mutations and hyperactive Ras/MAPK signaling. Outcomes for many children with JMML remain dismal with current standard-of-care cytoreductive chemotherapy and hematopoietic stem cell transplantation. We used patient-derived induced pluripotent stem cells (iPSCs) to characterize the signaling profiles and potential therapeutic vulnerabilities of PTPN11-mutant and CBL-mutant JMML. We assessed whether MEK, JAK, and PI3K/mTOR kinase inhibitors (i) could inhibit myeloproliferation and aberrant signaling in iPSC-derived hematopoietic progenitors with PTPN11 E76K or CBL Y371H mutations. We detected constitutive Ras/MAPK and PI3K/mTOR signaling in PTPN11 and CBL iPSC-derived myeloid cells. Activated signaling and growth of PTPN11 iPSCs were preferentially inhibited in vitro by the MEKi PD0325901 and trametinib. Conversely, JAK/STAT signaling was selectively activated in CBL iPSCs and abrogated by the JAKi momelotinib and ruxolitinib. The PI3Kδi idelalisib and mTORi rapamycin inhibited signaling and myeloproliferation in both PTPN11 and CBL iPSCs. These findings demonstrate differential sensitivity of PTPN11 iPSCs to MEKi and of CBL iPSCs to JAKi, but similar sensitivity to PI3Ki and mTORi. Clinical investigation of mutation-specific kinase inhibitor therapies in children with JMML may be warranted.

The codesign of an interdisciplinary team-based intervention regarding initiating palliative care in pediatric oncology.

PURPOSE: Children with advanced cancer are often not referred to palliative or hospice care before they die or are only referred close to the child's death. The goals of the current project were to learn about pediatric oncology team members' perspectives on palliative care, to collaborate with team members to modify and tailor three separate interdisciplinary team-based interventions regarding initiating palliative care, and to assess the feasibility of this collaborative approach. METHODS: We used a modified version of experience-based codesign (EBCD) involving members of the pediatric palliative care team and three interdisciplinary pediatric oncology teams (Bone Marrow Transplant, Neuro-Oncology, and Solid Tumor) to review and tailor materials for three team-based interventions. Eleven pediatric oncology team members participated in four codesign sessions to discuss their experiences with initiating palliative care and to review the proposed intervention including patient case studies, techniques for managing uncertainty and negative emotions, role ambiguity, system-level barriers, and team communication and collaboration. RESULTS: The codesign process showed that the participants were strong supporters of palliative care, members of different teams had preferences for different materials that would be appropriate for their teams, and that while participants reported frustration with timing of palliative care, they had difficulty suggesting how to change current practices. CONCLUSIONS: The current project demonstrated the feasibility of collaborating with pediatric oncology clinicians to develop interventions about introducing palliative care. The procedures and results of this project will be posted online so that other institutions can use them as a model for developing similar interventions appropriate for their needs.