Outcomes based on induction regimens in pediatric kidney transplantation: a NAPRTCS and PHIS collaborative study.

BACKGROUND: Induction agent used at the time of kidney transplant is often based upon center practice and recipient characteristics. We evaluated outcomes across induction therapies among children enrolled in the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) transplant registry with data in the Pediatric Health Information System (PHIS). METHODS: This is a retrospective study of merged data from NAPRTCS and PHIS. Participants were grouped by induction agent: interleukin-2 receptor blocker (IL-2 RB), anti-thymocyte/anti-lymphocyte globulin (ATG/ALG), and alemtuzumab. Outcomes assessed included 1-, 3-, and 5-year allograft function and survival, rejection, viral infections, malignancy, and death. RESULTS: A total of 830 children transplanted between 2010 and 2019. At 1 year post-transplant, the alemtuzumab group had higher median eGFR (86 ml/min/1.73 m2) compared to IL-2 RB and ATG/ALG (79 and 75 ml/min/1.73 m2, respectively; P < 0.001); at 3 and 5 years, there was no difference. Adjusted eGFR over time was similar across all induction agents. Rejection rates were lower among the alemtuzumab group vs. IL-2RB and ATG (13.9% vs. 27.3% and 24.6%, respectively; P = 0.006). Adjusted ATG/ALG and alemtuzumab had higher hazard ratio for time to graft failure compared to IL-2 RB (HR 2.48 and HR 2.11, respectively; P < 0.05). Incidence of malignancy, mortality, and time to first viral infection was similar. CONCLUSION: Although rejection and allograft loss rates were distinct, the incidences of viral infection and malignancy were comparable across induction agents. By 3 years post-transplant, there was no difference in eGFR. A higher resolution version of the Graphical abstract is available as Supplementary information.

Risk Factors for Readmission Following Febrile Neutropenia in Pediatric Oncology Patients.

Febrile neutropenia is the most common reason for admission from the emergency department for pediatric oncology patients. We identified pediatric inpatients age 1 to 21 years with an International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code of malignancy and either fever with neutropenia or fever alone over a 6-year period (2007-2012) using the PHIS+ database. We evaluated factors associated with readmission within 7 days after index hospitalization. There were 4029 index hospitalizations among 2349 patients in 6 hospitals, 294 encounters (7.3%) were followed by readmission within 7 days. Factors associated with increased odds of readmission included being in the lowest quartile for median household income (odds ratio [OR]=1.64, P =0.009), diagnosis of acute lymphoblastic leukemia (OR=1.37, P =0.016), lack of anerobic coverage during index hospitalization (OR=1.48, P =0.026), and absolute neutrophil count <200 cells/µL at discharge from index hospitalizations (OR=1.55, P =0.008). Patients who required readmission had a longer median length of stay and greater hospitalization costs during the index hospitalization. There was a trend towards increasing hospitalization rates for febrile neutropenia over time. While absolute neutrophil count is incorporated into many risk stratification strategies for fever management, further work should focus on addressing socioeconomic factors which may impact readmission rates.

Pulmonary Hypertension in Preterm Infants Treated With Laser vs Anti-Vascular Endothelial Growth Factor Therapy for Retinopathy of Prematurity.

Importance: Anti-vascular endothelial growth factor (VEGF) therapy for retinopathy of prematurity (ROP) has potential ocular and systemic advantages compared with laser, but we believe the systemic risks of anti-VEGF therapy in preterm infants are poorly quantified. Objective: To determine whether there was an association with increased risk of pulmonary hypertension (PH) in preterm infants with ROP following treatment with anti-VEGF therapy as compared with laser treatment. Design, Setting, and Participants: This multicenter retrospective cohort study took place at neonatal intensive care units of 48 children's hospitals in the US in the Pediatric Health Information System database from 2010 to 2020. Participants included preterm infants with gestational age at birth 22 0/7 to 31 6/7 weeks who had ROP treated with anti-VEGF therapy or laser photocoagulation. Exposures: Anti-VEGF therapy vs laser photocoagulation. Main Outcomes and Measures: New receipt of pulmonary vasodilators at least 7 days after ROP therapy was compared between exposure groups, matched using propensity scores generated from preexposure variables, and adjusted for birth year and hospital. The odds of receiving an echocardiogram after 30 days of age was also included to adjust for secular trends and interhospital variation in PH screening. Results: Among 1577 patients (55.9% male) meeting inclusion criteria, 689 received laser photocoagulation and 888 received anti-VEGF treatment (95% bevacizumab, 5% ranibizumab). Patients were first treated for ROP at median 36.4 weeks' postmenstrual age (IQR, 34.6-38.7). A total of 982 patients (491 in each group) were propensity score matched. Good covariate balance was achieved, as indicated by a model variance ratio of 1.15. More infants who received anti-VEGF therapy were treated for PH, but when adjusted for hospital and year, this was no longer statistically significant (6.7%; 95% CI, 2.6-6.9 vs 4.3% 95% CI, 4.4-10.2; adjusted odds ratio, 1.62; 95% CI, 0.90-2.89; P = .10). Conclusions and Relevance: Anti-VEGF therapy was not associated with greater use of pulmonary vasodilators after adjustment for hospital and year. Our findings suggest exposure to anti-VEGF may be associated with PH, although we cannot exclude the possibility of residual confounding based on systemic comorbidities or hospital variation in practice. Future studies investigating this possible adverse effect seem warranted.

STEPP IN: A Multicenter Quality Improvement Collaborative Standardizing Postoperative Handoffs.

OBJECTIVE: To reduce care failures by 30% through implementation of standardized communication processes for postoperative handoff in NICU patients undergoing surgery over 12 months and sustained over 6 months. METHODS: Nineteen Children's Hospitals Neonatal Consortium centers collaborated in a quality improvement initiative to reduce postoperative care failures in a surgical neonatal setting by decreasing respiratory care failures and all other communication failures. Evidence-based clinical practice recommendations and a collaborative framework supported local teams' implementation of standardized postoperative handoff communication. Process measures included compliance with center-defined handoff staff presence, use of center-defined handoff tool, and the proportion of handoffs with interruptions. Participant handoff satisfaction was the balancing measure. Baseline data were collected for 8 months, followed by a 12-month action phase and 7-month sustain phase. RESULTS: On average, 181 postoperative handoffs per month were monitored across sites, and 320 respondents per month assessed the handoff process. Communication failures specific to respiratory care decreased by 73.2% (8.2% to 4.6% and with a second special cause signal to 2.2%). All other communication care failures decreased by 49.4% (17% to 8.6%). Eighty-four percent of participants reported high satisfaction. Compliance with use of the handoff tool and required staff attendance increased whereas interruptions decreased over the project time line. CONCLUSIONS: Team engagement within a quality improvement framework had a positive impact on the perioperative handoff process for high-risk surgical neonates. We improved care as demonstrated by a decrease in postoperative care failures while maintaining high provider satisfaction.

Metric Development for the Multicenter Improving Pediatric Sepsis Outcomes (IPSO) Collaborative.

BACKGROUND: A 56 US hospital collaborative, Improving Pediatric Sepsis Outcomes, has developed variables, metrics and a data analysis plan to track quality improvement (QI)-based patient outcomes over time. Improving Pediatric Sepsis Outcomes expands on previous pediatric sepsis QI efforts by improving electronic data capture and uniformity across sites. METHODS: An expert panel developed metrics and corresponding variables to assess improvements across the care delivery spectrum, including the emergency department, acute care units, hematology and oncology, and the ICU. Outcome, process, and balancing measures were represented. Variables and statistical process control charts were mapped to each metric, elucidating progress over time and informing plan-do-study-act cycles. Electronic health record (EHR) abstraction feasibility was prioritized. Time 0 was defined as time of earliest sepsis recognition (determined electronically), or as a clinically derived time 0 (manually abstracted), identifying earliest physiologic onset of sepsis. RESULTS: Twenty-four evidence-based metrics reflected timely and appropriate interventions for a uniformly defined sepsis cohort. Metrics mapped to statistical process control charts with 44 final variables; 40 could be abstracted automatically from multiple EHRs. Variables, including high-risk conditions and bedside huddle time, were challenging to abstract (reported in <80% of encounters). Size or type of hospital, method of data abstraction, and previous QI collaboration participation did not influence hospitals' abilities to contribute data. To date, 90% of data have been submitted, representing 200 007 sepsis episodes. CONCLUSIONS: A comprehensive data dictionary was developed for the largest pediatric sepsis QI collaborative, optimizing automation and ensuring sustainable reporting. These approaches can be used in other large-scale sepsis QI projects in which researchers seek to leverage EHR data abstraction.

Poverty and Targeted Immunotherapy: Survival in Children's Oncology Group Clinical Trials for High-Risk Neuroblastoma.

BACKGROUND: Whether social determinants of health are associated with survival in the context of pediatric oncology-targeted immunotherapy trials is not known. We examined the association between poverty and event-free survival (EFS) and overall survival (OS) for children with high-risk neuroblastoma treated in targeted immunotherapy trials. METHODS: We conducted a retrospective cohort study of 371 children with high-risk neuroblastoma treated with GD2-targeted immunotherapy in the Children's Oncology Group trial ANBL0032 or ANBL0931 at a Pediatric Health Information System center from 2005 to 2014. Neighborhood poverty exposure was characterized a priori as living in a zip code with a median household income within the lowest quartile for the cohort. Household poverty exposure was characterized a priori as sole coverage by public insurance. Post hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. All statistical tests were 2-sided. RESULTS: In multivariable Cox regressions adjusted for disease and treatment factors, household poverty-exposed children experienced statistically significantly inferior EFS (hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.28 to 2.82, P = .001) and OS (HR = 2.79, 95% CI = 1.63 to 4.79, P < .001) compared with unexposed children. Neighborhood poverty was not independently associated with EFS or OS. In post hoc analyses exploring the joint effect of neighborhood and household poverty, children with dual-poverty exposure (neighborhood poverty and household poverty) experienced statistically significantly inferior EFS (HR = 2.21, 95% CI = 1.48 to 3.30, P < .001) and OS (HR = 3.70, 95% CI = 2.08 to 6.59, P < .001) compared with the unexposed group. CONCLUSIONS: Poverty is independently associated with increased risk of relapse and death among neuroblastoma patients treated with targeted immunotherapy. Incorporation of social and environmental factors in future trials as health-care delivery intervention targets may increase the benefit of targeted therapies.

Development of a Quality Improvement Learning Collaborative to Improve Pediatric Sepsis Outcomes.

Pediatric sepsis is a major public health problem. Published treatment guidelines and several initiatives have increased adherence with guideline recommendations and have improved patient outcomes, but the gains are modest, and persistent gaps remain. The Children's Hospital Association Improving Pediatric Sepsis Outcomes (IPSO) collaborative seeks to improve sepsis outcomes in pediatric emergency departments, ICUs, general care units, and hematology/oncology units. We developed a multicenter quality improvement learning collaborative of US children's hospitals. We reviewed treatment guidelines and literature through 2 in-person meetings and multiple conference calls. We defined and analyzed baseline sepsis-attributable mortality and hospital-onset sepsis and developed a key driver diagram (KDD) on the basis of treatment guidelines, available evidence, and expert opinion. Fifty-six hospital-based teams are participating in IPSO; 100% of teams are engaged in educational and information-sharing activities. A baseline, sepsis-attributable mortality of 3.1% was determined, and the incidence of hospital-onset sepsis was 1.3 cases per 1000 hospital admissions. A KDD was developed with the aim of reducing both the sepsis-attributable mortality and the incidence of hospital-onset sepsis in children by 25% from baseline by December 2020. To accomplish these aims, the KDD primary drivers focus on improving the following: treatment of infection; recognition, diagnosis, and treatment of sepsis; de-escalation of unnecessary care; engagement of patients and families; and methods to optimize performance. IPSO aims to improve sepsis outcomes through collaborative learning and reliable implementation of evidence-based interventions.

Trends in Incidence of Nicotine Use Disorder Among Adolescents in the Pediatric Hospital, 2012-2019.

OBJECTIVES: To assess trends in the incidence of nicotine use disorder (NUD) and describe associated factors among adolescents in the pediatric emergency department (ED) and inpatient settings. METHODS: We conducted a retrospective cohort study of all adolescents (11-18 years) with a hospital encounter (inpatient, observation, or ED) in the Pediatric Health Information System between January 1, 2012, and September 30, 2019. After excluding adolescents with a previous International Classification of Diseases, Ninth Revision, and International Classification of Diseases, Tenth Revision, NUD diagnosis in the past 2 years, adolescents with new NUD diagnosis (ie, NUD incidence) were identified. A multivariable generalized liner mixed model was used to assess adjusted NUD incidence and investigate the relationship of NUD with patient characteristics and any interactions between characteristics and time. Spearman's correlation coefficient was used to assess the correlation between NUD incidence and e-cigarette use reported among youth. RESULTS: Of 3 963 754 adolescents, 15 376 (0.4%) had a new diagnosis of NUD. Between 2012 and 2019, NUD incidence increased from 0.3% to 0.4% (P < .001). Findings from the time interaction effect analysis revealed increasing NUD incidence among certain subpopulations, including boys, those with a commercial or other insurance type, adolescents seen in the ED, those from the lowest and highest median household income quartile, and those in the South and West US Census regions. The correlation between NUD incidence and e-cigarette use among high school students was ρ = 0.884 (P = .006). CONCLUSIONS: The incidence of NUD among adolescents is increasing. Efforts to increase the screening and treatment of NUD among adolescents in the hospital, particularly among the at-risk populations identified, are needed.

Variation in tonsillectomy cost and revisit rates: analysis of administrative and billing data from US children's hospitals.

BACKGROUND: Tonsillectomy is one of the most common and cumulatively expensive surgical procedures in children. We determined if substantial variation in resource use, as measured by standardised costs, exists across hospitals for performing tonsillectomy and if higher resource use is associated with better quality of care, as measured by revisits to hospital. METHODS: We conducted a retrospective analysis of children undergoing routine outpatient tonsillectomy between 2011 to 2017 across US children's hospitals using an administrative and billing data source. The primary outcome measures were the hospital tonsillectomy standardised cost and the 30-day revisit rate to hospital. We analysed the interhospital variation in standardised cost by determining the number of outlier hospitals in standardised cost and the intraclass correlation coefficient. RESULTS: 131 814 children (median age 6 years, IQR: 4,9; female sex 52.5%) underwent tonsillectomy for airway obstruction (62.9%) and infection (23.9%) across 28 hospitals. The median adjusted hospital standardised cost for tonsillectomy was $2392 (IQR: $1827, $2793; range: $1166 to $4222). There was substantial interhospital variation in costs as 11 (40%) hospitals were cost outliers, and the intraclass correlation coefficient was 0.62, suggesting that 62% of the variation in cost was attributable to variation between hospitals. The median hospital revisit rate was 9.5% (IQR: 7.8, 12.1) and higher hospital costs did not correlate with lower revisit rates (rs =0.03, 95% CI -0.36 to 0.41; p=0.87). CONCLUSIONS: There is substantial variation in hospital resource use and standardised costs for routine outpatient tonsillectomy across US children's hospitals. Higher resource use is not associated with lower revisit rates. Further study is needed to understand the practices of lower resource use hospitals who deliver high quality of care.

Mucosal barrier injury-associated bloodstream infections in pediatric oncology patients.

BACKGROUND: Single-center reports of central line-associated bloodstream infection (CLABSI) and the subcategory of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) in pediatric hematology oncology transplant (PHO) patients have focused on the inpatient setting. Characterization of MBI-LCBI across PHO centers and management settings (inpatient and ambulatory) is urgently needed to inform surveillance and prevention strategies. METHODS: Prospectively collected data from August 1, 2013, to December 31, 2015, on CLABSI (including MBI-LCBI) from a US PHO multicenter quality improvement network database was analyzed. CDC National Healthcare Safety Network definitions were applied for inpatient events and adapted for ambulatory events. RESULTS: Thirty-five PHO centers reported 401 ambulatory and 416 inpatient MBI-LCBI events. Ambulatory and inpatient MBI-LCBI rates were 0.085 and 1.01 per 1000 line days, respectively. Fifty-three percent of inpatient CLABSIs were MBI-LCBIs versus 32% in the ambulatory setting (P  <  0.01). Neutropenia was the most common criterion defining MBI-LCBI in both settings, being present in ≥90% of events. The most common organisms isolated in MBI-LCBI events were Escherichia coli (in 28% of events), Klebsiella spp. (23%), and viridans streptococci (12%) in the ambulatory setting and viridans streptococci (in 29% of events), E. coli (14%), and Klebsiella spp. (14%) in the inpatient setting. CONCLUSION: In this largest study of PHO MBI-LCBI inpatient events and the first such study in the ambulatory setting, the burden of MBI-LCBI across the continuum of care of PHO patients was substantial. These data should raise awareness of MBI-LCBI among healthcare providers for PHO patients, help benchmarking across centers, and help inform prevention and treatment strategies.

Actively Doing Less: Deimplementation of Unnecessary Interventions in Bronchiolitis Care Across Urgent Care, Emergency Department, and Inpatient Settings.

BACKGROUND AND OBJECTIVES: Quality improvement (QI) initiatives have increased provider adherence to individual components of a bronchiolitis clinical practice guideline (CPG). Few have evaluated complete adherence to a guideline in multiple types of care settings. Our aim with this study was to increase complete adherence to our institutional bronchiolitis CPG in urgent care center, emergency department, and inpatient settings. METHODS: We conducted a QI study at a single pediatric institution with multiple care settings. Encounters for patients with bronchiolitis ages >60 days to <24 months occurring between October 1 and March 31 in 2015-2018 were included. Those in intensive or subspecialty care were excluded. Management of each encounter was considered adherent to the CPG if none of the following were ordered: respiratory pathogen panel, respiratory syncytial virus antigen, complete blood cell count, blood culture, chest radiography, bronchodilator, antibiotic, or systemic corticosteroid. Medical team education, family engagement, order set modifications, and data dissemination were employed to drive deimplementation. We used interrupted time series to assess changes in processes and outcomes both across and within seasons. RESULTS: Analysis included 13 063 patient encounters. Hospital-wide complete adherence to the CPG increased (P < .001) from 40.9% (95% confidence interval 39.3%-42.5%) to 54.6% (95% confidence interval 53.2%-56.0%). Although CPG adherence improved in all 3 clinical settings, the use of individual CPG components varied by setting. Direct cost decreased in the urgent care center (P < .001) and emergency department (P = .001). CONCLUSIONS: We created a strict definition of CPG adherence and used QI methodology to deimplement multiple overused tests and medications across the continuum of patient care.

Changes in opioid prescriptions for Medicaid-enrolled children and young adults, 2012-2016.

OBJECTIVES: To describe current trends in filled opioid prescriptions for Medicaid-enrolled children, adolescents and young adults (AYAs) from 2012 to 2016, and to identify patient characteristics and clinical settings associated with a higher probability of filled opioid prescriptions. DESIGN: Retrospective cohort study of children and young adults enrolled in Medicaid from 2012 to 2016. SETTING: 10-12 states participating in the Medicaid Marketscan claims database. PARTICIPANTS: Medicaid-enrolled children and young adults (0-21 years old). EXPOSURE: Healthcare encounter(s) that could result in a new opioid prescription. MAIN OUTCOME MEASURE: "Opioid visits," defined as healthcare encounters associated with a new opioid prescription filled within 7 days. Each opioid visit was assigned to the clinical provider most likely to have prescribed an opioid. RESULTS: There were 113,068,027 visits among 4,427,838 Medicaid-enrollees and 1 percent (n = 1,130,006) of these were considered an opioid visit. Adjusted probabilities decreased from 1.2 percent to 0.8 percent from 2012 to 2016. The most frequently prescribed opioids were hydrocodone (48 percent; n = 653,011), codeine (23 percent; n = 305,644), and oxycodone (14 percent; n = 189,700); most of these were in combination with acetaminophen. The high-est adjusted percentages by clinical setting were seen in dental surgery (29 percent), outpatient surgery (21 percent), and inpatient (upon discharge, 10 percent). CONCLUSIONS: Opioid prescriptions filled for Medicaid-enrolled children, adolescents, and young adults are relatively rare and adjusted probabilities decreased from 2012 to 2016. Among opioids filled, combination opioids and those with pedi-atric safety warnings remain commonly prescribed. Further research is critical to better understand drivers of prescribing practices and clinical indications for appropriate opioid use to inform improvements in pain management guidelines in this population.

Sexually Transmitted Infection Testing in Adolescents: Current Practices in the Hospital Setting.

PURPOSE: Adolescents are disproportionately affected by sexually transmitted infections (STIs), and evidence supports expanding sexual health services to the hospital setting. Because STI testing practices in the hospital setting are poorly understood, we sought to describe current STI testing practices among adolescents seen in children's hospitals. METHODS: We performed a retrospective analysis of adolescents (14-18 years old) from 45 children's hospitals in 2015-2016, excluding visits with a billing code for sexual abuse/assault. We calculated rates of STI testing and investigated differences in STI testing by patient and hospital characteristics using generalized linear mixed modeling. RESULTS: Of the 541,714 adolescent encounters, 59,158 (10.9%) underwent STI testing. After adjusting for demographic characteristics, those with an STI test were more likely to be female (adjusted odds ratio [aOR] 1.61; 95% confidence interval [CI] 1.58-1.64), of non-Hispanic black race/ethnicity (aOR 1.20; 95% CI 1.17-1.23), or from the lowest median household income quartile (aOR 1.21; 95% CI 1.17-1.24). There was substantial inter-hospital variation in adjusted rates of STI testing (3%-24%), but strong correlation was observed between STI testing rates in the ED and inpatient settings within individual hospitals (adjusted R2 .99). CONCLUSIONS: Only one in ten adolescents seen in children's hospitals underwent STI testing with wide variation in testing patterns across hospitals. There are critical opportunities to increase adolescent STI testing in this setting. Our findings highlight potential disparities in STI testing rates and patterns that warrant further exploration from the patient, provider, and health system perspective.

Design of the standardizing care to improve outcomes in pediatric end stage renal disease collaborative.

The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative is a North American multi-center quality transformation effort whose primary aim is to minimize exit-site infection and peritonitis rates among pediatric chronic peritoneal dialysis patients. The project, developed by the quality improvement faculty and staff at the Children's Hospital Association's Quality Transformation Network (QTN) and content experts in pediatric nephrology and pediatric infectious diseases, is modeled after the QTN's highly successful Pediatric Intensive Care Unit and Hematology-Oncology central line-associated blood-stream infection (CLABSI) Collaboratives. Like the Association's other QTN efforts, the SCOPE Collaborative is part of a broader effort to assist pediatric nephrology teams in learning about and using quality improvement methods to develop and implement evidence-based practices. In addition, the design of this project allows for targeted research that builds on high-quality, ongoing data collection. Finally, the project, while focused on reducing peritoneal dialysis catheter-associated infections, will also serve as a model for future pediatric nephrology projects that could further improve the quality of care provided to children with end stage renal disease.