Factors Associated With Neurobehavioral Complications in Pediatric Abdominal Organ Transplant Recipients Identified Using Computable Composite Definitions*

Abstract

Objectives: Neurologic complications occur in up to 40% of adult abdominal solid organ transplant recipients and are associated with increased mortality. Comparable pediatric data are sparse. This study describes the occurrence of neurologic and behavioral complications (neurobehavioral complications) in pediatric abdominal solid organ transplant recipients. We examine the association of these complications with length of stay, mortality, and tacrolimus levels. Design: The electronic health record was interrogated for inpatient readmissions of pediatric abdominal solid organ transplant recipients from 2009 to 2017. A computable composite definition of neurobehavioral complication, defined using structured electronic data for neurologic and/or behavioral phenotypes, was created. Setting: Quaternary children’s hospital with an active transplant program. Patients: Pediatric abdominal solid organ transplant recipients. Interventions: None. Measurements and Main Results: Computable phenotypes demonstrated a specificity 98.7% and sensitivity of 63.0% for identifying neurobehavioral complications. There were 1,542 readmissions among 318 patients, with 65 (20.4%) having at least one admission with a neurobehavioral complication (total 109 admissions). Median time from transplant to admission with neurobehavioral complication was 1.2 years (interquartile range, 0.52–2.28 yr). Compared to encounters without an identified neurobehavioral complication, encounters with a neurobehavioral complication were more likely to experience ICU admission (odds ratio, 3.9; 2.41–6.64; p < 0.001), have longer ICU length of stay (median 10.3 vs 2.2 d; p < 0.001) and hospital length of stay (8.9 vs 4.3 d; p < 0.001), and demonstrate higher maximum tacrolimus level (12.3 vs 9.8 ng/mL; p = 0.001). Patients with a neurobehavioral complication admission were more likely to die (odds ratio, 5.04; 1.49–17.09; p = 0.009). In a multivariable analysis, type of transplant, ICU admission, and tacrolimus levels were independently associated with the presence of a neurobehavioral complication. Conclusions: Common electronic health record variables can be used to accurately identify neurobehavioral complications in the pediatric abdominal solid organ transplant population. Late neurobehavioral complications are associated with increased hospital resource utilization, mortality, and tacrolimus exposure. Additional studies are required to delineate the relationship between maximum tacrolimus level and neurobehavioral complications to guide therapeutic drug monitoring and dosing.

Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients

“…BBs data can be integrated with patient data and existing diagnostic technologies (brain imaging, neurological assessments, and genotyping) and readily incorporated into current standard-of-care practices. The pathway proposes serial collection of remnant blood samples acutely (admission to 72 h) under resource-limited pandemic conditions, daily (or more frequent) interrogation of BBs in hospitalized patients, and integration of BBs data with EHR-embedded records of neuromorbidity 344 and other structured CDEs. In addition, neurological condition at discharge and long-term follow-up of patients (e.g., 6-12 months) should be integrated with the EHR data.…”

Pediatric intestine and multivisceral transplant

“…Neurological complications such as seizures, encephalopathy, central nervous system (CNS) lymphoproliferative disease or posterior reversible encephalopathy syndrome (PRES), behavioral complications such as altered mental status, depression, posttraumatic stress disorder (PTSD). These complications are associated with more frequent hospitalizations, Intensive care unit (ICU) admissions, longer ICU and hospital length of stay (LOS) and increased mortality [65].…”

Validation of a Computational Phenotype to Identify Acute Brain Dysfunction in Pediatric Sepsis

“…The initial computational phenotype tested was developed to identify ABD in children after solid organ transplantation (10) To target a sensitivity of greater than or equal to 80% for the final computational phenotype to identify ABD with a lower limit of the 95% CI greater than or equal to 65%, we needed a minimum sample of 100 sepsis episodes with ABD. Based on the conservative assumption that 20% of episodes would exhibit ABD, a total of 527 sepsis episodes were randomly selected for the reference cohort (1,2).…”

“…Our aim was to validate a measure of ABD in pediatric sepsis that would include acute neurologic or behavioral concerns for children in the emergency department, general wards, and ICU without reliance on GCS documentation. We iterated upon a computational phenotype previously developed to measure ABD in children after solid organ transplantation using variables extracted from the electronic health record (EHR) indicative of clinician concern for an acute neurologic or behavioral change (10). We hypothesized that an iterated computational phenotype using variables indicative of clinician concern would provide a valid measure of ABD in pediatric sepsis.…”