PROJECT SUMMARY/ABSTRACT Pediatric critical illness exposes children to painful and stressful experiences. High levels of stress and pain increase the risk for adverse acute health outcomes (e.g., delirium) and long-term functional impairment, known as Post-Intensive Care Syndrome in Pediatrics (PICS-p). Respiratory support with intubation and mechanical ventilation (MV) exacerbates a child's stress and pain, for which the standard of care includes narcotics and sedation medication. However, these medications increase the risk of delirium, posttraumatic stress disorder, and impaired cognition. My long-term career goal is to develop mechanistically-based, nonpharmacologic interventions to remediate PICS-p and improve survivorship for children and their families following pediatric critical illness. I am an Assistant Professor in the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh School of Medicine. The training proposed for this K23 award period is crucial for me to successfully launch this program of research as an independent researcher. Listening to music to increase comfort (“music listening”) decreases stress and pain symptoms and related outcomes (e.g., medication use, heart rate) during MV in adults and there is emerging data on feasibility and preliminary efficacy for music listening during MV in pediatrics. However, the mechanisms through which music listening impacts stress and pain is unclear, which limits identifying the `active ingredient' of music listening interventions, resulting in significant variability in intervention components and delivery. These data would result in an optimized music listening intervention for testing in future trials. We hypothesize live music from certified music therapists of child preferred songs may be most efficacious in decreasing stress and pain among children receiving MV compared to recorded music or usual care, due to rhythmic entrainment (active ingredient) and modulated through the autonomic nervous system (primary mechanism). This proposed research uses a mechanistic design, a randomized crossover trial with three conditions to compare their effects on biomarkers of stress and pain across three conditions in children with respiratory failure: Live music listening provided by a music therapist, recorded music listening, and usual care. To fill crucial gaps in my expertise, I propose five training objectives: (1) gain skills in the identification and use of biomarkers in pediatric critical care clinical trials; (2) obtain training in stress and pain physiology; (3) develop expertise in PICS-p outcomes; (4) develop skills in conducting interventional clinical trials; and (5) cultivate practical skills in team science, study implementation, and management. I have assembled a multidisciplinary mentorship team of NIH-funded investigators with expertise in each of my training areas. Completion of the proposed training and research will result in a competitive R21 a...