Pediatric Health Information System Data Research Articles

Trends in analgesia-sedation of pediatric patients receiving I-131 MIBG in the pediatric intensive care unit: A report from the Pediatric Health Information System database.

Children with neuroblastoma receiving I-131 metaiodobenzylguanidine (MIBG) therapy require sedation-analgesia for strict radiation safety precautions during MIBG infusion and clearance. We evaluated the sedation-analgesia trends of patients undergoing MIBG therapy using the Pediatric Health Information System (PHIS) database. Retrospective data from 476 patient encounters from the PHIS from 2010 to 2019. Total 240/476 (50.45%) children evaluated were under 6years of age. Compared to 2010, in 2018 there was a decrease in benzodiazepine infusion use (60% vs. 40%, p<.04), as well as a decrease in use of opiate infusion (35% vs. 25%, p<.001). Compared to 2010, in 2018 we report an increase in the use of ketamine (from 5% to 10%, p<.002), as well as an increase in dexmedetomidine use (0% vs. 30%, p<.001). Dexmedetomidine was the most used medication in the 0-3years age group compared to children older than 3years of age (14.19% vs. 5.80%, p<.001). Opiate was the most used medication in children greater than 3years compared to the 0-3-year age group (36.23 vs. 23.87, p<.05). Using PHIS data, we discovered considerable variability in the medications used for sedation in patients undergoing MIBG therapy. Although benzodiazepines and opioids were the most used agents, there was a trend toward decreasing use of benzodiazepines and opioids in these patients. Furthermore, there has been an increasing trend in the use of dexmedetomidine and ketamine.

241 Disparities in Access to Epilepsy Surgery Care in Children With Drug Resistant Epilepsy: Implications For Long-Term Survival Outcomes

INTRODUCTION: Our recent publication in Lancet Child and Adolescent Health examined long-term survival rates for pediatric patients with drug-resistant epilepsy (DRE) treated with antiseizure medications (ASMs) only, ASMs plus vagus nerve stimulation (VNS), and ASMs plus cranial epilepsy surgery in a large United States (US) administrative database. The difference in survival probabilities was statistically significant (p &lt; .001). Adjusted probabilities of survival beyond 10 years were 89.27% for the ASMs only cohort (95%CI, 87.71%-90.85%), 92.65% for VNS cohort (95%CI, 90.62%-94.72%), and 98.45% for cranial surgery cohort (95%CI, 97.53%-99.38%). METHODS: Patients aged 0-17 years with DRE between 01/01/2004-31/12/2020 were identified from the Pediatric Health Information System data set across 49 US pediatric hospitals. Patients treated with ASMs only or ASMs plus VNS or ASMs plus cranial epilepsy surgery were included. Chi-square tests determined associations between treatment time and preoperative factors such as treatment type, age, sex, race/ethnicity, insurance type, geographic region, epilepsy type, and medical complexity (presence of pediatric complex chronic conditions [PCCCs]). RESULTS: 18,292 total patients were included: 10,240 patients treated with ASMs only, 5,019 patients with ASMs plus VNS, 3,033 patients with ASMs plus cranial epilepsy surgery. There were significant differences in age, geographic region, race/ethnicity, presence of PCCCs, diagnosis, and insurance type (p &lt; 0.001). Those treated surgically, either with VNS implantation or cranial epilepsy surgery, were 2 years older than ASMs only. ASMs only patients were less ikely to be reported as non-Hispanic white (51.78%), less likely have a focal/partial epilepsy diagnosis (8.74%), and less likely carry private medical insurance (35.82%). CONCLUSIONS: We show a link of disparities in pediatric epilepsy surgery care and survival outcomes. Focused strategies are needed to expand access to comprehensive epilepsy care with neurosurgical evaluation and offerings when appropriate.

73 Use of Probabilistic Linkage to Create a Novel Database to Study the Care of Bronchiolitis in Pediatric Intensive Care Units (PICU)

OBJECTIVES/GOALS: Bronchiolitis is a major cause of PICU admission, yet identifying best practices is limited by the lack of existing databases containing the needed demographic and clinical variables. We used probabilistic linkage to join the Virtual Pediatric System (VPS) and Pediatric Health Information Systems (PHIS) databases to overcome this data barrier. METHODS/STUDY POPULATION: We performed a single site study joining VPS and PHIS data. These national databases contain clinical (VPS) and billing and resource use (PHIS) data. Limits on the use of patient identifiers (PI) for multi-center research, makes direct linkage techniques impossible. To demonstrate that probabilistic linkage can accurately link VPS and PHIS records, we obtained our single site VPS and PHIS records and linked them using probabilistic linkage without PI and compared this to a gold standard linkage created with PI. We also compared demographic features of linked and unlinked records to assess the ability of probabilistic linkage to create a representative sample. RESULTS/ANTICIPATED RESULTS: We obtained 920 VPS records of patients with bronchiolitis and linked 91% (839/920) to a PHIS record with 4 (0.5%) false-positive matches. Characteristics of linked and unlinked records are compared in Table 1. Comparison of probabilistically linked and unlinked records showed no difference in median age in years (0.7 [Interquartile range (IQR) 0.3-1.5] v 0.7 [IQR 0.2-1.5], p = 0.76), median number of complex chronic conditions (0 [IQR 0-1] v 0 [IQR 0-1], p = 0.16), median Pediatric Index of Mortality 3 severity of illness scores (-4.6 [IQR -4.7 – 4.4] v -4.6 [IQR -4.7 – 4.4], p = 0.44), median days of PICU stay (4 [IQR 3-6] v 4 [IQR 2-6], p = 0.36), proportion female ( 44% v 46%, p = 0.82), or proportion of patients intubated (28% v 24%, p = 0.41). DISCUSSION/SIGNIFICANCE: Probabilistic linkage creates an accurate combined VPS-PHIS database. Extending our methodology to join data from all 38 hospitals contributing to VPS and PHIS will allow creation of a large database containing the demographic, treatment, and outcome data needed to enable Comparative Effectiveness Research of bronchiolitis care.

The impact of undergoing elective pediatric lung resection during respiratory syncytial virus peak season on patient outcomes: A nationwide retrospective analysis.

Observational data to support delaying elective pediatric thoracic surgery during peak respiratory viral illness season is lacking. This study evaluated whether lung surgery during peak viral season is associated with differences in postoperative outcomes and resource utilization. A retrospective observational cohort study was performed using the Pediatric Health Information System (PHIS). Patients with a congenital lung malformation (CLM) who underwent elective lung resection between 1 January 2016 and 29 February 2020 were included. Respiratory syncytial virus (RSV) incidence was used as a proxy for respiratory viral illness circulation. Monthly hospital-specific RSV incidence was calculated from PHIS data, and peak RSV season was defined by Centers for Disease Control data. Multivariable regression models were built to identify predictors of postoperative mechanical ventilation, which was the main outcome measure, as well as secondary outcomes including 30-day readmission after lung resection, postoperative length of stay (LOS) and hospital billing charges. Of 1542 CLM patients identified, 344 (22.3%) underwent lung resection during peak RSV season. 38% fewer operations were performed per month during peak RSV season than during off-peak months (p < .001). Children who underwent surgery during peak RSV season did not differ from the off-peak group in terms of age at operation, race, or comorbid conditions (i.e., congenital heart disease, newborn respiratory distress, and preoperative pneumonia). There was no association between hospital-specific RSV incidence at the time of surgery and postoperative mechanical ventilation, postoperative LOS, 30-day readmission rate or hospital billing charges. Performing elective lung surgery in children with CLMs during peak viral season is not associated with adverse surgical outcomes or increased utilization of healthcare resources.

Pediatric transplant–associated thrombotic microangiopathy health care utilization and implications of eculizumab therapy

AbstractThe health care use (HCU) burden of transplant-associated thrombotic microangiopathy (TA-TMA) and its treatments are unknown. The objective of this study was to investigate inpatient costs associated with meeting criteria for TA-TMA in the first year after hematopoietic cell transplant (HCT). This institutional review board–approved retrospective multicenter study included serial children who underwent HCT from 1 January 2015 to 1 July 2019. A standardized unit cost (adjusted for geographic location, differences in cost of living, and inflation) for inpatient hospitalization was extracted from the Pediatric Health Information System data and linked to clinical data. Both total cost and cost per day from 15 days before stem cell infusion to 1-year after HCT were calculated. Among allogeneic (allo) transplant recipients, after adjusting for severe grade 3/4 acute graft-versus-host disease (GVHD), infections, and HLA mismatch, costs were not different in TA-TMA (n = 137) vs no TA-TMA (n = 238). Severe GVHD was significantly associated with increased costs. Among allo high-risk (HR) TMA-TMA, unadjusted costs were significantly higher in the eculizumab-treated cohort (n = 19) than in the supportive care group (n = 36). However, after adjusting for gastrointestinal bleeding that occurred disproportionately in the eculizumab (n = 6) vs supportive care (n = 0) cohort, eculizumab treatment was not associated with increased total costs. More studies are needed to determine the etiology of increased HCU costs in those with HR-TA-TMA and predict those more likely to benefit from eculizumab, reducing HCU and improving outcomes.

Incidence of Hospital-Acquired Conditions During Pediatric Clinical Research Inpatient Hospitalizations: A Matched Cohort Study.

In this matched cohort study using data from pediatric hospitals, we compared the incidence of hospital-acquired conditions (HACs) during clinical research hospitalizations to nonresearch hospitalizations. Using Pediatric Health Information System data for inpatient discharges January 2017-June 2022, we matched research hospitalizations (identified by International Classification of Diseases, Tenth Revision, diagnosis code) to nonresearch hospitalizations within hospital on age (±3 y), sex, discharge year (±2), and All Patients Refined Diagnosis Related Groups classification, severity of illness (±1), and risk of mortality (±1). We calculated the incidence (per 1000 discharges) and incidence rate (per 10,000 patient days) of HAC identified by International Classification of Diseases, Tenth Revision, codes and compare research versus nonresearch using logistic and Poisson regression, accounting for matching using generalized estimating equations and adjusting for sociodemographic factors and hospital utilization. We matched 7000 research hospitalizations to 26,447 nonresearch from 28 hospitals. Median age was 6.0 years (interquartile range, 10.6 y). Median length of stay was 4.0 days (interquartile range, 11.0 days) with longer stays among research hospitalizations ( P < 0.001). Incidence of HAC among research hospitalizations was 13.1 versus 7.2 per 1000 for nonresearch ( P < 0.001) and incidence rate 6.7 versus 4.5 per 10,000 patient days. Adjusting for sociodemographic and clinical factors, research stays had 1.65 times the odds of any HAC (95% confidence interval, 1.27-2.16; P < 0.001) and 1.38 times the incidence rate (95% confidence interval, 1.09-1.75; P = 0.009). Our findings indicate that pediatric research hospitalizations are more likely to experience HACs compared with nonresearch hospitalizations. These findings have important safety implications for pediatric inpatient clinical research that warrant further study.

Lack of Medicaid Coverage of Routine Newborn Circumcision Leads to Increased Operative Circumcisions, Chordee Procedures, and Balanitis

To compare proportions of newborn circumcisions, operative circumcisions, chordee procedures, and cases of balanitis in states where Medicaid covers newborn circumcision (covered states) versus states that do not (noncovered states) using the pediatric health information system database. A retrospective review of pediatric health information system data was conducted from 2011 to 2020. The proportions and median ages of newborn circumcision current procedural terminology (CPT 54,150, 54,160), operative circumcision (CPT 54,161), chordee (CPT 54,360), and balanitis (ICD-9 607.1, ICD-10 N48.1, N47.6) were compared in covered versus noncovered states. A total of 118,530 circumcisions were reviewed. Covered states had significantly higher proportions of circumcision overall (9.7% vs 7.1%, P < 0.0001). Noncovered states had significantly higher proportions of Medicaid-covered operative circumcisions (54.9% vs 47.7%, P < 0.0001). Compared to covered states, noncovered states had significantly higher median ages of all types of circumcisions. Noncovered states also had higher numbers of balanitis cases and double the incidence of balanitis compared with covered states. The median age of chordee (1.07 vs 0.79 years, P < 0.0001) and proportion of chordee repairs (15.2% vs 12.9%, P < 0.0001) were also significantly higher in noncovered states. The lack of Medicaid coverage of circumcision increases the number of foreskin procedures done in the operating room. In addition, in states without Medicaid coverage of circumcision, there is an increased burden of disease related to the foreskin. These findings represent a need to further investigate the costs of healthcare associated with Medicaid coverage of circumcision or the lack thereof.

Juvenile Nasopharyngeal Angiofibroma: Outcomes Analysis Based Upon Hospital Volume.

To evaluate the management of juvenile nasopharyngeal angiofibroma (JNA) from a national perspective with outcomes comparison based on hospital volume. Ten-year Pediatric Health Information Systems (PHIS) data analysis. The PHIS database was queried for the diagnosis of JNA. Data regarding demographics, surgical approach, embolization, length of stay, charges, readmission, and revision surgery was collected and analyzed. Hospitals were classified as low volume if fewer than 10 cases and high volume if greater than or equal to 10 cases during the study period. A random effects model compared outcomes based on hospital volume. A total of 287 JNA patients were identified with a mean age of 13.8 (± 2.7) years. Nine hospitals were classified as high volume, accounting for a total of 121 patients. The mean length of hospitalization, blood transfusion rate, and 30-day readmissions did not differ significantly by hospital volume. Patients cared for at high-volume institutions were less likely to require postoperative mechanical ventilation (8.3% vs. 25.0%; adjusted RR=0.32; 95% CI 0.14-0.73; p < 0.01) or return to the operating room for residual disease than patients admitted to low-volume hospitals (7.4% vs. 20.5%; adjusted RR=0.38; 95% CI 0.18-0.79; p=0.01). The management of JNA is complex from both an operative and perioperative management standpoint. Over the past decade, nearly half (42.2%) of JNA patients have been managed at nine institutions in the United States. These centers have significantly lower rates of postoperative mechanical ventilation and the need for revision surgery. 3 Laryngoscope, 133:3216-3220, 2023.

Financial outcomes of high-flow nasal cannula use for bronchiolitis on the general pediatric floor.

High-flow nasal cannula (HFNC) is an increasingly common treatment utilized for bronchiolitis on general pediatric hospital floors. This could present a financial burden for hospitals if reimbursement has not accounted for the increased costs associated with increased HFNC use. Pediatric Health Information System and Revenue Management Program data set discharges from 2018 to 2019 were utilized to calculate the ratio of reimbursements to costs as a cost coverage ratio (CCR). The CCR was compared by HFNC use, the severity of illness, and payor type. The CCR was highest at 1.68 for children with high severity and HFNC use but varied greatly by payor. The lowest CCR at 0.77 was seen for children with low severity and public insurance and indicated potential financial losses for these patients. This was lower than low-severity patients on HFNC with private payors (1.68) and high-severity patients on HFNC with public payors (1.18).

Dexamethasone for Pediatric Critical Asthma: A Multicenter Descriptive Study.

Systemic corticosteroids are vital to critical asthma management. While intravenous methylprednisolone is routinely used in the pediatric intensive care unit (PICU) setting, recent data supports dexamethasone as an alternative. Using the Pediatric Health Information System (PHIS) registry, we assessed trends and variation in corticosteroid prescribing among children hospitalized for critical asthma. We performed a multicenter retrospective cohort study using PHIS data among children 3-17 years of age admitted for critical asthma from 2011 through 2019. Primary outcomes were corticosteroid prescribing rates by year and participating sites. Exploratory outcomes were corticosteroid-related adverse effects, rates of adjunctive pharmaceutical and respiratory interventions, mortality and length of stay. Of the 49 children's hospitals assessed, 26 907 encounters were included for study. Mean dexamethasone exposure rates were 18.1 ± 2.4% where 2.4 ± 1.2% represented dexamethasone-alone prescribing. Dexamethasone alone prescribing exhibited a linear trend (annual increase of 0.5 ± 0.1% annually R2 = 0.845) without correlation to cumulative site critical asthma admission rates. Compared to encounters prescribed solely methylprednisolone or a combination of dexamethasone and methylprednisolone, subjects provided dexamethasone alone had reduced asthma severity indices, length of stay, and exposure rates to adjunctive asthma interventions. Adverse events were rare and the dexamethasone-alone group less frequently experienced gastritis and hyperglycemia. In this multicenter retrospective study from 49 children's hospitals, dexamethasone prescribing rates appear increasing for pediatric critical asthma. Observed variability in corticosteroid prescribing implies a continued need for controlled prospective comparative analyses to define ideal corticosteroid regimens for pediatric critical asthma.

Heliox for Pediatric Critical Asthma: A Multicenter, Retrospective, Registry-Based Descriptive Study.

In cases of critical asthma (CA), heliox may be applied as an adjunctive rescue therapy to avoid invasive mechanical ventilation (MV), improve deposition of aerosolized medications, and enhance laminar airflow through obstructed airways. Using the Pediatric Health Information System (PHIS) registry, we evaluate heliox prescribing and explored for differences in MV rates and hospital length of stay (LOS) among children with and without heliox exposure. We performed a retrospective cohort study using PHIS data from 42 pediatric intensive care units among children 5-17 years of age admitted for CA from 2010 through 2019. Primary outcomes were heliox prescribing rates and trends. Secondary outcomes were invasive MV rates and LOS assessed in a subgroup of children receiving ≥ 1 adjunctive intervention(s). Of the 19,780 studied, heliox was prescribed in 12.5% and linearly declined from 16.1% in 2010 to 5.6% in 2019. The overall MV rate was 12.8% and was lower in subjects receiving heliox alone (4.9%) compared to heliox plus alternative adjunctive therapies [31.2%] or children receiving non-heliox adjunctive therapies [22.1%], P < .01). Accounting for MV, no difference in LOS was observed. In exploratory adjusted models, MV free hospitalization was associated with heliox-only exposure (OR: 0.33, 95% CI: 0.17-0.63, P < .01) and exposure to multiple adjunctive therapies was associated with MV (OR: 2.48, 95% CI: 1.56-3.94, P < .01). In this multicenter retrospective study from 42 children's hospitals, heliox prescribing for CA declined over the last decade. Subjects receiving multiple adjunctive therapies more commonly required invasive MV perhaps indicating a greater severity of illness. At this time, prospective trials needed to identify the role of heliox for pediatric CA.

Improved Outcomes of Infant Lung Transplantation Over 3 Decades

BackgroundLung transplantation is the definitive surgical treatment for end-stage lung disease. However, infants comprise less than 5% of pediatric cases. This study sought to provide an overview of infant lung transplantation outcomes over the past 3 decades by using linked United Network for Organ Sharing (UNOS) and Pediatric Health Information System (PHIS) data. MethodsInfants undergoing lung transplantation from 1989 to 2020 in UNOS were reviewed. UNOS and PHIS records for patients who underwent lung transplantation from 1995 to 2020 were linked using date of birth, sex, and date of surgery ± 3 days. The study assessed underlying diagnoses, pretransplant and posttransplant extracorporeal membrane oxygenation support, retransplant-free survival to discharge, hospital experience (≥1 annual transplant for ≥4 years in a 5-year period), operative decade, bronchiolitis obliterans syndrome, long-term survival, and functional status at latest follow-up. ResultsA total of 112 lung transplants were performed in 109 infants over 31 years. Of these, 21 patients died before discharge, and 2 underwent repeat transplantation during the same admission. The study linked 80.6% (83 of 103) of UNOS and PHIS records. Hospital survival was lower for infants with idiopathic pulmonary hypertension and those who underwent transplant procedures at less experienced centers. All 7 infants requiring postoperative extracorporeal membrane oxygenation support died. Median freedom from bronchiolitis obliterans syndrome was 8.1 years (interquartile range, 4.6 to 11.6 years). After discharge, median survival was 10.3 years (interquartile range, 6.3 to 14.4 years), with improved 10-year survival for those patients who underwent transplantation from 2010 to 2020 (87.3%) vs 2000 to 2009 (52.4%; P = .098) and 1989 to 1999 (34.1%; P = .004). A total of 84.6% (33 of 39) of survivors had minor or no restrictions at latest follow-up. ConclusionsCarefully selected infants experience promising short- and long-term outcomes after lung transplantation.

Influence of Geographic Access on Surgical Center Readmissions After Index Congenital Heart Surgery

To assess the impact of geographic access to surgical center on readmission risk and burden in children after congenital heart surgery. Children <6years old at discharge after congenital heart surgery (Risk Adjustment for Congenital Heart Surgery-1 score 2-6) were identified using Pediatric Health Information System data (46 hospitals, 2004-2015). Residential distance from the surgery center, calculated using ZIP code centroids, was categorized as <15, 15-29, 30-59, 60-119, and ≥120 miles. Rurality was defined using rural-urban commuting area codes. Geographic risk factors for unplanned readmissions to the surgical center and associated burden (total hospital length of stay [LOS], costs, and complications) were analyzed using multivariable regression. Among 59 696 eligible children, 19 355 (32%) had ≥1 unplanned readmission. The median LOS was 9days (IQR 22) across the entire cohort. In those readmitted, median total costs were $31 559 (IQR $90 176). Distance from the center was inversely related but rurality was positively related to readmission risk. Among those readmitted, increased distance was associated with longer LOS, more complications, and greater costs. Compared with urban patients, highly rural patients were more likely to have an unplanned readmission but had fewer average readmission days. Geographic measures of access differentially affect readmission to the surgery center. Increased distance from the center was associated with fewer unplanned readmissions but more complications. Among those readmitted, the most isolated patients had the greatest readmission costs. Understanding the contribution of geographic access will aid in developing strategies to improve care delivery to this population.

Mortality, Risk Factors and Disparities Associated with Esophageal Variceal Bleeding in Children's Hospitals in the US

To use a large administrative database to determine the mortality, risk factors, and comorbidities of esophageal variceal bleeding in children. Retrospective cohort study using Pediatric Health Information System data from 50 tertiary children's hospitals in the US. International Classification of Diseases(ICD) codes (FY 2020 ICD-10 update and revision 10 of ICD-9) from 2004 through 2019 identified children 18years and younger with variceal bleeding and complications. Univariate analyses used the Student t -test for continuous variables (age) and the χ2 test for categorical variables (all others). A mixed-effects linear regression was performed for multiple variables. There were 1902 patients who had 3399 encounters for esophageal variceal bleeding. The mortality rate for variceal bleeding was 7.3%, increasing to 8.8% by 6weeks; any mortality during the study was 20.1%. Transfusion was required in 54.7% of encounters, and 42.6% were admitted to the intensive care unit. Variceal bleeding encounters were complicated by peptic ulcer disease (6.9%), bacteremia (11.4%), acute renal failure (5.1%), mechanical ventilation (18%), ascites (21.3%), and peritonitis (3.3%). Multivariable mixed-effects logistic regression showed that Black race (OR, 2.59; P<.001) or Hispanic ethnicity (OR, 2.31; P=.001), but not sex, household income, or insurance type, were associated with increased mortality. Bacteremia, peritonitis, mechanical ventilation, acute renal failure, and transfusion were associated with higher mortality (ORs of 2.29, 2.18, 1.93, 6.33, and 1.81, respectively; P<.001, .005, .011, <.001, and .005, respectively). The 6-week mortality rate for variceal bleeding in children is 8.8%. Black or Hispanic children are at higher risk of dying. Serious morbidities associated with variceal hemorrhage impact mortality. These data can inform consideration of prophylactic or therapeutic interventions for children at risk.

Longitudinal Trends in Costs for Hospitalizations at Children's Hospitals.

Children's hospitals are increasingly focused on value-based improvement efforts to improve outcomes and lower costs. Such efforts are generally focused on improving outcomes in specific conditions. Examination of cost drivers across all admissions may facilitate strategic prioritization of efforts. Pediatric Health Information System data set discharges from 2010 to 2017 were aggregated into services lines and billing categories. The mean annual growth per discharge as a percentage of 2010 total costs was calculated for aggregated medical and surgical service lines and 6 individual service lines with highest rates of growth. The mean annual growth per discharge for each billing category and changes in length of stay was further assessed. The mean annual growth in total costs was similar for aggregated medical (2.6%) and surgical (2.7%) service lines. Individual medical service lines with highest mean annual growth were oncology (3.5%), reproductive services (2.9%), and nonsurgical orthopedics (2.8%); surgical service lines with highest rate of growth were solid organ transplant (3.7%), ophthalmology (3.3%), and otolaryngology (2.9%). Room costs contributed most consistently to cost increases without concomitant increases in length of stay. Value-based health care initiatives must focus on room cost increases and their impacts on patient outcomes.

The Impact of Donor Type on Outcomes and Cost of Allogeneic Hematopoietic Cell Transplantation for Pediatric Leukemia: A Merged Center for International Blood and Marrow Transplant Research and Pediatric Health Information System Analysis.

Allogeneic hematopoietic stem cell transplantation (alloHCT) may be associated with significant morbidity and mortality, resulting in increased healthcare utilization (HCU). To date, no multicenter comparative cost analyses have specifically evaluated alloHCT in children with acute leukemia. In this retrospective cohort study, we examined the relationship between survival and HCU while investigating the hypothesis that matched sibling donor (MSD) alloHCT has significantly lower inpatient HCU with unrelated donor (URD) alloHCT, and that among URDs, umbilical cord blood (UCB) alloHCT will have higher initial utilization but lower long-term utilization. Clinical and transplantation outcomes data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were merged with inpatient cost data from the Pediatric Health Information System (PHIS) database using a probabilistic merge methodology. The merged dataset comprised US patients age 1 to 21 years who underwent alloHCT for acute leukemia between 2004 and 2011 with comprehensive CIBMTR data at a PHIS hospital. AlloHCT was analyzed by donor type, with specific analysis of utilization and costs using PHIS claims data. The primary outcomes of overall survival (OS), leukemia-free survival (LFS), and inpatient costs were evaluated using Kaplan-Meier curves and Cox and Poisson models. A total of 632 patients were identified in both the CIBMTR and PHIS data. The 5-year LFS was 60% for MSD alloHCT, 47% for well-matched matched unrelated donor bone marrow (MUD) alloHCT, 48% for mismatched unrelated donor alloHCT, and 45% for UCB alloHCT (P=.09). Total adjusted costs were significantly lower for MSD alloHCT versus MUD alloHCT by day 100 (adjusted cost ratio [ACR], .73; 95% confidence interval [CI], .62 to .86; P < .001), and higher for UCB alloHCT versus MUD alloHCT (ACR, 1.27; 95% CI, 1.11 to 1.45; P < .001). By 2 years, total adjusted costs remained significantly lower for MSD alloHCT compared with MUD alloHCT (ACR, .67; 95% CI, .56 to .81; P < .001) and higher for UCB alloHCT compared with MUD alloHCT (ACR, 1.25; 95% CI, 1.02 to 1.52; P=.0280). Our data show that UCB and MUD alloHCT provide similar survival outcomes; however, MUD alloHCT has a significant advantage in cost by day 100 and 2 years. More research is needed to determine whether the cost difference among URD alloHCT approaches remains significant with a larger sample size and/or beyond 2 years post-alloHCT.

Timing of enterostomy closure for neonatal isolated intestinal perforation

PurposeNo consensus guidelines exist for timing of enterostomy closure in neonatal isolated intestinal perforation (IIP). This study evaluated neonates with IIP closed during the initial admission (A1) versus a separate admission (A2) comparing total length of stay and total hospital cost. MethodsUsing 2012 to 2017 Pediatric Health information System (PHIS) data, 359 neonates with IIP were identified who underwent enterostomy creation and enterostomy closure. Two hundred sixty-five neonates (A1) underwent enterostomy creation and enterostomy closure during the same admission. Ninety-four neonates (A2) underwent enterostomy creation at initial admission and enterostomy closure during subsequent admission. For the A2 neonates, total hospital length of stay was calculated as the sum of hospital days for both admissions. A1 neonates were matched to A2 neonates in a 1:1 ratio using propensity score matching. Multivariate models were used to compare the two matched pair groups for length of stay and cost comparisons. ResultsPrior to matching, the basic demographics of our study population included a median birthweight of 960 g, mean gestational age of 29.5 weeks, and average age at admission of 4 days. Eighty-seven pairs of neonates with IIP were identified during the matching process. Neonates in A2 had 91% shorter total hospital length of stay compared to A1 neonates (HR: 1.91; 95% CI for HR: 1.44–2.53; p < .0001). The median length of stay for A1 was 95 days (95% CI: 78–102 days) versus A2 length of stay of 67 days (95% CI: 56–76 days). Adjusting for the same covariates, A2 neonates had a 22% reduction in the average total cost compared A1 neonates (RR: 0.78; 95% CI for RR: 0.64–0.95; p-value = 0.014). The average total costs were $245,742.28 for A2 neonates vs. $315,052.21 for A1 neonates (p < 0.001). ConclusionNeonates with IIP have a 28 day shorter hospital length of stay, $75,000 or 24% lower total hospital costs, and a 22 day shorter post-operative course following enterostomy closure when enterostomy creation and closure is performed on separate admissions. Type of StudyPrognosis Study. Level of EvidenceLevel II.

Reduced Relapse Risk in Children with Acute Myeloid Leukemia (AML) Who Experience Septic Shock (SS)

Background: Relapse remains the major clinical risk in children with AML, and persistent minimal residual disease (MRD) poses a particular therapeutic challenge as a presumably chemoresistant cell population. We previously showed innate immune stimulation can generate durable memory immune responses against leukemia cells in preclinical MRD models (Blood 2009 114:2459; Leukemia 2018 32: 539). These treatments mimic the "danger" signal provided by SS and may offer novel immunotherapeutic approaches for patients who fail or are not eligible for targeted immunotherapies. Demonstrating a protective effect of SS against AML relapse would support clinical development of innate immune stimulants. We hypothesized 1) SS is associated with a decreased risk of AML relapse among children who were able to achieve remission after induction, and 2) this effect is most pronounced in children with persistent MRD, who are more likely to have both SS exposures and relapses. Methods: We used a previously assembled cohort of children with de novo AML using Pediatric Health Information System (PHIS) data merged with patients on two clinical trials from the Children's Oncology Group (COG; PLOS One 2015 10:e0143480). We developed and validated a method to detect SS exposures in PHIS using vasopressor billing codes (PBC 2019 10.1002/pbc.27713 #2024) and used COG data for demographics, treatment, and outcomes. SS exposures were captured starting 7 days from first chemotherapy until last day of the last treatment course or 30 days prior to relapse. Follow-up for relapse and non-relapse mortality (NRM) began after the end of Induction II and continued to last contact, off-study date, or until 5 years from diagnosis. Cumulative incidences of relapse (CIR) and NRM (CIN) were estimated treating each other as competing risks. Sub-distribution hazard regression models were used to estimate crude and adjusted sub-hazard ratios (subHR) and associated 95% confidence intervals (CI) of relapse in relation to SS. SS was treated as a time-varying exposure, so each patient became SS-exposed once the first SS occurred. Demographic and clinical characteristics were evaluated as potential confounders of the associations of interest. Results: We identified 569 COG-PHIS patients with AML who achieved complete remission by the end of Induction II. In this cohort, 188 (33%) experienced SS during therapy. Older age, Black non-Hispanic race-ethnicity, Hispanic ethnicity, and receipt of stem cell transplant (SCT) were associated with SS exposure (Table 1). Median follow-up was 1122 days (IQR 413-1745) from the end of Induction II. Relapse occurred in 220 (38.7%) patients and was associated with male sex and genetic risk (Table 1). Positive end-Induction I MRD approached a significant association with relapse. CIRs were similar among SS-exposed and unexposed patients in the overall cohort and in MRD-negative patients (Figs. 1A-B). Among children with persistent MRD, SS-exposed patients had a lower 5-year CIR than unexposed patients (43% vs. 60.1%; Fig. 1C). Adjusted subHR for relapse for the overall cohort was 0.82 (CI: 0.61-1.11); for the MRD-negative subgroup, adjusted subHR was 0.86 (CI: 0.61-1.21); and for the MRD-positive subgroup, 0.57 (CI: 0.31-1.05). These effects were consistently in the protective direction but did not reach statistical significance. In a sensitivity analysis restricting duration of the exposure effect to 12 months, SS exposure in the overall cohort was associated with a risk reduction (adjusted subHR 0.65; CI: 0.45-0.92). NRM occurred in 28 (4.9%) and was associated with high-risk therapy on AAML1031 and with positive MRD, with a near-significant association with SCT (not shown). SS-exposed patients had a higher 5-year CIN (10.4% v. 2.8%; Fig. 1D). Conclusions: Using merged clinical trial and administrative data, we identified a potentially protective effect of exposure to a strong immune stimulus (SS) that was most pronounced in children with persistent MRD. This suggests immune surveillance for low-level AML can be induced and supports investigation of innate immune stimulant therapy for this very poor prognosis childhood leukemia. While NRM is higher among SS-exposed patients, clinical trials of innate immune stimulants would comprise controlled interventions expected to result in markedly less toxicity than unpredictable SS exposures. Repeated dosing may prolong the effect duration beyond 12 months. Disclosures Fisher: Merck: Research Funding; Pfizer: Research Funding; Astellas: Other: Data Safety Monitoring Board Chair for an antifungal study.

Discrepant Rates of Hypospadias Surgical Complications: A Comparison of U.S. News & World Report and Pediatric Health Information System® Data and Published Literature.

Complication rates of 5% to 10% and 12% to 23% have been observed following distal and proximal hypospadias repair, respectively. However, these rates may be overreported. We hypothesized that data from the Pediatric Health Information System would corroborate the complication rates reported in the literature and refute the rates established by U.S. News & World Report as quality metrics. The Pediatric Health Information System database was interrogated for hypospadias and revision CPT® codes. To evaluate the appropriateness of the U.S. News & World Report code list to identify revisions, 3 CPT groups were defined. Group A included codes sought by U.S. News & World Report, group B included group A plus codes for acquired urethrocutaneous fistula in males and group C included group B plus any revision codes associated with the index procedures. To evaluate the appropriateness of U.S. News & World Report followup interval, we assessed revision rates with ever increasing followup intervals out to 7 years. Yearly revision rates were summarized by median and quantile to correlate whether median revision rates changed significantly depending on whether increased followup or enhanced code lists were used. Average complication rates for group A were 3.32% (range 0.48% to 7.36%) and 12.29% (3.48% to 36.36%) for distal and proximal repairs, respectively. Revision rates increased significantly from group A (median 3.32%) by inclusion of a more expansive list of CPT codes associated with revision procedures (group B, 4.26%, p <0.001 and group C, 6.37%, p <0.001) in distal hypospadias. Among proximal hypospadias cases this difference was not significant when comparing group A (12.29%) to group B (12.53%, p=0.813), but was significant when comparing group A to group C (22.14%, p <0.001). Median revision rates for distal and proximal hypospadias increased with longer followup for all 3 groups, although the upward trend was not statistically significant. Depending on how one defines hypospadias revision, no hospital within the Pediatric Health Information System data set meets the U.S. News & World Report definition of perfection, a finding that is supported by recent reports from some of the largest, most prolific and most highly regarded pediatric urology programs. We posit that the U.S. News & World Report quality metrics do not accurately reflect the nature of hypospadias surgery complication rates.

The use of antimicrobial susceptibility testing in pediatric cystic fibrosis pulmonary exacerbations

BackgroundAlthough antimicrobial susceptibility testing (AST) frequently guides cystic fibrosis (CF) pulmonary exacerbation (PEx) management, its clinical utility is unclear. This study examined associations between AST and antimicrobial switching during PEx treatment and time and occurrence of next PEx as treatment outcomes. MethodsThis retrospective cohort study utilized Pediatric Health Information System data. Children and adolescents aged 1–18 years admitted for a PEx from 2011 to 2016 were studied. Antimicrobial switching was defined as any intra-admission change in intravenous (IV), oral, and/or inhaled antimicrobials. Time to next PEx was defined as the time between index PEx hospital discharge and subsequent hospital admission requiring IV antimicrobials. Odds of antimicrobial switching ≥5 days after treatment initiation were determined by generalized linear mixed models, and associations between AST and time to next PEx were studied using Kaplan-Meier curves and Cox proportional hazards regression. ResultsAST occurred in 2518 (39%) of 6451 PEx at 36 hospitals and was associated with increased odds of antimicrobial switching (OR 1.33, 95% CI 1.16–1.52; p = 0.001) and increased hazard of future PEx (HR 1.32, 95% CI 1.16–1.50; p < 0.001). However, antimicrobial switching was not associated with a longer time to next PEx. ConclusionsAST was associated with both increased probability of antimicrobial regimen change and increased PEx hazard. There was no evidence that antimicrobial regimen change was associated with clinical benefit as assessed by time to next PEx. However, these results indicate residual indication bias remained after adjustment for available disease covariates. Additional studies of the clinical value of AST are warranted.