e18513 Background: Acute kidney injury (AKI) is common in pediatric acute lymphoblastic leukemia (ALL) and can increase the risk of developing chronic kidney disease (CKD). However, AKI phenotypes vary widely in severity, duration, and number of episodes that may be characterized as patterns in estimated glomerular filtration rate (eGFR) trajectories. Distinct eGFR trajectories during therapy for ALL may indicate long-term CKD risk in pediatric ALL survivors. To our knowledge, eGFR trajectories have not been described in the pediatric ALL population. Objective: To identify groups based on eGFR trajectory during ALL therapy and to evaluate characteristics associated with declining eGFR groups. Methods: Electronic health record data were retrospectively collected from pediatric patients treated for de novo B- and T-ALL at Children’s Hospital of Philadelphia (2011-2015), Children’s Healthcare of Atlanta (2010-2018), and Texas Children’s Hospital (2011-2014), three large cancer centers in the Leukemia Electronic Abstraction of Records Network (LEARN). Patients with infant ALL were excluded. Patients were followed from the time of first chemotherapy course in LEARN through upfront chemotherapy completion, death, relapse, conditioning for stem cell transplant, or transfer of care, whichever came first. Latent class mixed models were used to determine course-level eGFR trajectory groups. Bivariate tests and multinomial logistic regressions were used to explore the association of covariates with specific trajectory groups. Results: Cohort characteristics (n=884) included: median (interquartile range) age 5.7 years (3.4-11.4), 56% male, median baseline eGFR 107.6 mL/min/1.73m 2 (89.8-126.8), 2% with Trisomy 21 (T21), and 54% with National Cancer Institute standard risk leukemia. Between 3-4 eGFR trajectory groups were identified in each course. All courses had stable eGFR trajectory groups distinguished by their course-specific baseline eGFR. Induction and Interim Maintenance-1 had additional groups with initial eGFR decline and recovery. Consolidation and Delayed Intensification courses had groups with eGFR decline. Bivariate analyses indicated that declining eGFR trajectory groups were significantly associated with lower course-specific baseline eGFR, AKI during the course, and T21; median number of eGFR values were not consistently associated with specific trajectory groups across courses. Multinomial logistic regression showed that those with higher baseline eGFR had increased odds of being in stable eGFR trajectory groups across all courses. Prior AKI was associated with increased odds of being in a lower eGFR trajectory group in Interim Maintenance-2. Conclusions: Pediatric patients with ALL have distinct eGFR trajectories during therapy. Patients with lower baseline eGFR, AKI, and a diagnosis of T21 may be at highest risk of eGFR decline during therapy and may benefit from increased screening for CKD.

INTRODUCTION:We sought to identify racial/ethnic and neighborhood disparities in acute kidney injury (AKI) in children with acute lymphoblastic or myeloid leukemia (ALL, AML). METHODS:Electronic health record data were retrospectively collected from patients treated for de novo pediatric ALL or AML in the multicenter Leukemia Electronic Abstraction of Records Network. AKI was defined by modified Kidney Disease Improving Global Outcomes criteria. Neighborhood-level resources were defined by the Child Opportunity Level (COL). Prevalence ratios (PRs) for AKI at diagnosis by race/ethnicity and COL were calculated using modified Poisson regression. Cox regression was used to calculate hazard ratios (HRs) of first AKI after initiation of chemotherapy (i.e., "during therapy"). RESULTS:Of 952 ALL patients, Non-Hispanic Black (NHB) ALL patients had significantly increased prevalence of AKI at leukemia diagnosis compared to Non-Hispanic White (NHW) patients in the adjusted model (PR 1.50); there were no significant differences by COL. During ALL therapy overall, NHB patients did not have any significant differences in hazard of AKI by race/ethnicity or COL in adjusted models. Among 168 AML patients, there were no significant differences in AKI at diagnosis by race/ethnicity or COL in AML. During AML therapy overall, NHB patients had significantly higher risk of AKI in both unadjusted (HR 1.95) and adjusted (HR 2.68) models, but no differences by COL. CONCLUSION:NHB patients with ALL had increased risk of AKI at the time of leukemia diagnosis, and NHB patients with AML had significantly increased risk of AKI during therapy. Further studies to identify drivers and interventions that mitigate AKI risk are warranted.

ABSTRACT Importance Leukodystrophies are a diverse group of rare disorders that disrupt central myelination. These disorders present with a broad spectrum of neurological severity and are associated with a range of potential secondary complications, such as scoliosis and failure of independent feeding. Objective We explore real‐world data of leukodystrophy complications to inform future evidence‐based care guidelines across these rare diseases. Design In a cross‐sectional observational study, we use a leukodystrophy‐specific research consortium and the availability of electronic health records (EHR) to capture a cross‐section of real‐world data. Setting Study participants were identified using EHR data from five hospital systems with established expertise in leukodystrophies. Participants Principal investigators or genetic counselors confirmed leukodystrophy diagnoses in all participants. Exposures Time‐to‐event measures were collected, including orthopedic complications (scoliosis, hip subluxation/dislocation), loss of ambulation, artificial ventilation, gastrostomy tube placement, and urinary tract infections (UTIs). Maximum motor milestones, including gain of ambulation by 2 years of age, were captured to stratify cohorts by neurological severity. Main Outcome and Measure A primary outcome was not prespecified, as this was an observational study. Results In total, 1203 participants were identified across 42 leukodystrophies (age range of 9 days to 89 years at last encounter). The most common event was feeding tube placement, and the median time to any first complication varied between disorders (Fleming–Harrington weighted log‐rank test). The specific diagnosis correlated with maximum gross motor milestone attainment (chi‐square test of independence). When all disorders were stratified by maximum motor milestone attainment (not specific diagnosis), the median time to adverse events was significantly associated with function (Fleming–Harrington weighted log‐rank test). Conclusions This cross‐sectional, retrospective observational study demonstrated that key medical events could be identified across institutions using EHR capture. Rates of health events and attainment of maximum motor milestones varied by specific leukodystrophy type. However, when the overall cohort was stratified by severity of motor impairment rather than individual diagnoses, the frequency of health events was associated with motor function. Our findings suggest utility for development of comprehensive care models for leukodystrophies as stratified by motor function and demonstrate the utility of integrated EHR review for real‐world data analyses.

To delineate disease trajectories and longitudinal treatment landscapes in genetic epilepsies through Real-World Data captured from routine clinical care.

Children with acute leukemia are at increased risk of kidney injury. Using electronic health record data from three centers between 2010 and 2018, this study retrospectively described acute kidney injury (AKI) and chronic kidney disease (CKD) prevalence in children with acute lymphoblastic or myeloid leukemia (ALL, AML) using Common Terminology Criteria for Adverse Events (CTCAE) and Kidney Disease Improving Global Outcomes (KDIGO) definitions. AKI during therapy was 25% (ALL) and 32% (AML) using CTCAE, versus 84% (ALL) and 74% (AML) using KDIGO. CKD prevalence was low and Grade 1/Stage 2. Further investigation is needed to optimally define kidney injury in acute leukemia.

IntroductionFebrile infection-related epilepsy syndrome (FIRES) is a severe childhood epilepsy with refractory status epilepticus after a typically mild febrile infection. The etiology of FIRES is largely unknown, and outcomes in most individuals with FIRES are poor.MethodsHere, we reviewed the current state-of-the art genetic testing strategies in individuals with FIRES. We performed a systematic computational analysis to identify individuals with FIRES and characterize the clinical landscape using the Electronic Medical Records (EMR). Among 25 individuals with a confirmed FIRES diagnosis over the last decade, we performed a comprehensive review of genetic testing and other diagnostic testing.ResultsManagement included use of steroids and intravenous immunoglobulin (IVIG) in most individuals, with an increased use of immunomodulatory agents, including IVIG, plasma exchange (PLEX) and immunosuppressants such as cytokine inhibitors, and the ketogenic diet after 2014. Genetic testing was performed on a clinical basis in almost all individuals and was non-diagnostic in all patients. We compared FIRES with both status epilepticus (SE) and refractory status epilepticus (RSE) as a broader comparison cohort and identified genetic causes in 36% of patients with RSE. The difference in genetic signatures between FIRES and RSE suggest distinct underlying etiologies. In summary, despite the absence of any identifiable etiologies in FIRES, we performed an unbiased analysis of the clinical landscape, identifying a heterogeneous range of treatment strategies and characterized real-world clinical practice.DiscussionFIRES remains one of the most enigmatic conditions in child neurology without any known etiologies to date despite significant efforts in the field, suggesting a clear need for further studies and novel diagnostic and treatment approaches.

Background Adverse events are often misreported in clinical trials, leading to an incomplete understanding of toxicities. We aimed to test automated laboratory adverse event ascertainment and grading (via the ExtractEHR automated package) to assess its scalability and define adverse event rates for children with acute myeloid leukaemia and acute lymphoblastic leukaemia. Methods For this retrospective cohort study from the Children's Oncology Group (COG), we included patients aged 0-22 years treated for acute myeloid leukaemia or acute lymphoblastic leukaemia at Children's Healthcare of Atlanta (Atlanta, GA, USA) from Jan 1, 2010, to Nov 1, 2018, at the Children's Hospital of Philadelphia (Philadelphia, PA, USA) from Jan 1, 2011, to Dec 31, 2014, and at the Texas Children's Hospital (Houston, TX, USA) from Jan 1, 2011, to Dec 31, 2014. The ExtractEHR automated package acquired, cleaned, and graded laboratory data as per Common Terminology Criteria for Adverse Events (CTCAE) version 5 for 22 commonly evaluated grade 3-4 adverse events (fatal events were not evaluated) with numerically based CTCAE definitions. Descriptive statistics tabulated adverse event frequencies. Adverse events ascertained by ExtractEHR were compared to manually reported adverse events for patients enrolled in two COG trials (AAML1031, NCT01371981; AALL0932, NCT02883049). Analyses were restricted to protocol-defined chemotherapy courses (induction I, induction II, intensification I, intensification II, and intensification III for acute myeloid leukaemia; induction, consolidation, interim maintenance, delayed intensification, and maintenance for acute lymphoblastic leukaemia). Findings Laboratory adverse event data from 1077 patients (583 from Children's Healthcare of Atlanta, 200 from the Children's Hospital of Philadelphia, and 294 from the Texas Children's Hospital) who underwent 4611 courses (549 for acute myeloid leukaemia and 4062 for acute lymphoblastic leukaemia) were extracted, processed, and graded. Of the 166 patients with acute myeloid leukaemia, 86 (52%) were female, 80 (48%) were male, 96 (58%) were White, and 132 (80%) were non-Hispanic. Of the 911 patients with acute lymphoblastic leukaemia, 406 (45%) were female, 505 (55%) were male, 596 (65%) were White, and 641 (70%) were non-Hispanic. Patients with acute myeloid leukaemia had the most adverse events during induction I and intensification II. Hypokalaemia (one [17%] of six to 75 [48%] of 156 courses) and alanine aminotransferase (ALT) increased (13 [10%] of 134 to 27 [17%] of 156 courses) were the most prevalent non-haematological adverse events in patients with acute myeloid leukaemia, as identified by ExtractEHR. Patients with acute lymphoblastic leukaemia had the greatest number of adverse events during induction and maintenance (eight adverse events with prevalence >= 10%; induction and maintenance: anaemia, platelet count decreased, white blood cell count decreased, neutrophil count decreased, lymphocyte count decreased, ALT increased, and hypocalcaemia; induction: hypokalaemia; maintenance: aspartate aminotransferase [AST] increased and blood bilirubin increased), as identified by ExtractEHR. 187 (85%) of 220 total comparisons in 22 adverse events in four AAML1031 and six AALL0923 courses were substantially higher with ExtractEHR than COG-reported adverse event rates for adverse events with a prevalence of at least 2%. Interpretation ExtractEHR is scalable and accurately defines laboratory adverse event rates for paediatric acute leukaemia; moreover, ExtractEHR seems to detect higher rates of laboratory adverse events than those reported in COG trials. These rates can be used for comparisons between therapies and to counsel patients treated on or off trials about the risks of chemotherapy. ExtractEHR-based adverse event ascertainment can improve reporting of laboratory adverse events in clinical trials. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

BACKGROUND:An adequate absolute lymphocyte count (ALC) is an essential first step in autologous chimeric antigen receptor (CAR) T-cell manufacturing. For patients with acute myelogenous leukemia (AML), the intensity of chemotherapy received may affect adequate ALC recovery required for CAR T-cell production. We sought to analyze ALC following each course of upfront therapy as one metric for CAR T-cell manufacturing feasibility in children and young adults with AML. PROCEDURE:ALC data were collected from an observational study of patients with newly diagnosed AML between the ages of 1 month and 21 years who received treatment between the years of 2006 and 2018 at one of three hospitals in the Leukemia Electronic Abstraction of Records Network (LEARN) consortium. RESULTS:Among 193 patients with sufficient ALC data for analysis, the median ALC following induction 1 was 1715 cells/μl (interquartile range: 1166-2388), with successive decreases in ALC with each subsequent course. Similarly, the proportion of patients achieving an ALC >400 cells/μl decreased following each course, ranging from 98.4% (190/193) after course 1 to 66.7% (22/33) for patients who received a fifth course of therapy. CONCLUSIONS:There is a successive decline of ALC recovery with subsequent courses of chemotherapy. Despite this decline, ALC values are likely sufficient to consider apheresis prior to the initiation of each course of upfront therapy for the majority of newly diagnosed pediatric AML patients, thereby providing a window of opportunity for T-cell collection for those patients identified at high risk of relapse or with refractory disease.

PURPOSEAdverse events (AEs) on Children's Oncology Group (COG) trials are manually ascertained using Common Terminology Criteria for Adverse Events. Despite significant effort, we previously demonstrated that COG typhlitis reporting sensitivity was only 37% when compared with gold standard physician chart abstraction. This study tested an automated typhlitis identification algorithm using electronic health record data.METHODSElectronic health record data from children with leukemia age 0-22 years treated at a single institution from 2006 to 2019 were included. Patients were divided into derivation and validation cohorts. Rigorous chart abstraction of validation cohort patients established a gold standard AE data set. We created an automated algorithm to identify typhlitis matching Common Terminology Criteria for Adverse Events v5 that included antibiotics, neutropenia, and non-negated mention of typhlitis in a note. We iteratively refined the algorithm using the derivation cohort and then applied the algorithm to the validation cohort; performance was compared with the gold standard. For patients on trial AAML1031, COG AE report performance was compared with the gold standard.RESULTSThe derivation cohort included 337 patients. The validation cohort included 270 patients (961 courses). Chart abstraction identified 16 courses with typhlitis. The algorithm identified 37 courses with typhlitis; 13 were true positives (sensitivity 81.3%, positive predictive value 35.1%). For patients on AAML1031, chart abstraction identified nine courses with typhlitis, and COG reporting correctly identified 4 (sensitivity 44.4%, positive predictive value 100.0%).CONCLUSIONThe automated algorithm identified true cases of typhlitis with higher sensitivity than COG reporting. The algorithm identified false positives but reduced the number of courses needing manual review by 96% (961 to 37) by detecting potential typhlitis. This algorithm could provide a useful screening tool to reduce manual effort required for typhlitis AE reporting.

Background Fasting hypoglycemia is a recognized occurrence among pediatric patients with acute lymphoblastic leukemia (ALL) during maintenance therapy. Existing publications describing this finding are limited to small studies and case reports. Our objective was to determine the incidence of hypoglycemia during maintenance chemotherapy and to investigate the association of age, as well as other potential risk factors, with this outcome in pediatric patients with ALL. Procedure This retrospective cohort study included individuals 1 to 21 years of age with ALL treated with antimetabolite-containing maintenance chemotherapy at a large children's hospital between January 2011 and December 2014. The primary endpoint was time to first documented episode of hypoglycemia during maintenance therapy, defined as single measurement of plasma glucose We identified 126 eligible patients, of whom 63% were documented as White, non-Hispanic, 28% as non-White, non-Hispanic, and 9% as Hispanic. Twenty-eight children (22%) had documented hypoglycemia during maintenance therapy. Younger age at the start of maintenance and hepatotoxicity documented during chemotherapy prior to maintenance initiation were associated with hypoglycemia (adjusted HR age = 0.88; 95% CI, 0.78-0.99; adjusted HR prior hepatotoxicity = 3.50; 95% CI, 1.47-8.36). Conclusions Nearly one quarter of children in our cohort had hypoglycemia documented during maintenance chemotherapy. Younger age at maintenance initiation and hepatotoxicity during chemotherapy prior to maintenance initiation emerged as risk factors. These findings highlight the importance of counseling about the risk of, and monitoring for, hypoglycemia, particularly in young children.

Graft versus host disease (GVHD) causes significant morbidity and mortality after allogeneic stem cell transplant (SCT). Little is known about genetic determinants of GVHD risk, including human leukocyte antigen (HLA) genotypes outside of HLA-mismatch. HLA-DQ2 and DQ8 genotypes are associated with celiac disease (CD) and are present in ≥90% of patients with CD. Both GVHD and CD are systemic inflammatory conditions that may have T cell-mediated enteropathy. We hypothesized HLA-DQ alleles associated with CD risk would confer increased risks of acute (a) and chronic (c) GVHD in pediatric SCT recipients.We performed a retrospective cohort study of children aged 0-21 years undergoing first allogeneic SCT at the Children's Hospital of Philadelphia from 10/1/12 — 7/1/16. Patients with primary graft failure or missing HLA-DQ genotypes were excluded. We grouped patients by low, moderate or high CD risk (Clin Gastroenterol Hepatol 2009, 7:966). Primary outcomes were 1) 100-day aGVHD incidence; 2) day 100 — 1-year cGVHD incidence; and 3) time to GVHD with relapse, death, secondary graft failure, second SCT, or donor lymphocyte infusion as competing risks. Logistic regressions were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Sub-distribution hazard models were used to estimate crude and adjusted sub-distribution hazard ratios (sHR) in time-to-event analyses. Multivariate models were adjusted for race-ethnicity, malignant/nonmalignant SCT indication, donor/mismatch, and graft source.We identified 167 patients (mean age 9.2 ±6.2 years). Proportions by CD risk were: low-risk n=108 (64.7%), moderate n=33 (19.8%), and high n=26 (15.6%). Day 100 incidence of ≥grade 2 aGVHD was 14.4% (8.4% had ≥grade 3). cGVHD 1-year incidence was 42.7% (14% had extensive). CD risk was protective against GVHD but did not reach statistical significance (Table 1).Risk of clinically significant GVHD (≥grade 2 or any chronic) was reduced in children with CD risk in the adjusted time-to-event model (moderate: sHR 0.42, 95% CI 0.18 — 0.95, p=0.037; high: sHR 0.31, 95% CI 0.12 – 0.8, p=0.016; Figure 1A). The protective effect of high CD risk was more pronounced for severe GVHD (≥grade 3 or chronic extensive) but did not reach statistical significance (adjusted sHR 0.14, 95%CI 0.02-1.09, P = 0.061; Figure 1B).In contrast to our hypothesis, CD risk by HLA-DQ is protective against GVHD in a dose-responsive manner. Reports of HLA-DQ2 and DQ8 protecting against other non-CD autoimmune diseases (rheumatoid arthritis and inflammatory bowel disease) support our observations. These results require confirmation and evaluation in a larger patient sample to define this novel GVHD risk modifier more robustly. Graft versus host disease (GVHD) causes significant morbidity and mortality after allogeneic stem cell transplant (SCT). Little is known about genetic determinants of GVHD risk, including human leukocyte antigen (HLA) genotypes outside of HLA-mismatch. HLA-DQ2 and DQ8 genotypes are associated with celiac disease (CD) and are present in ≥90% of patients with CD. Both GVHD and CD are systemic inflammatory conditions that may have T cell-mediated enteropathy. We hypothesized HLA-DQ alleles associated with CD risk would confer increased risks of acute (a) and chronic (c) GVHD in pediatric SCT recipients. We performed a retrospective cohort study of children aged 0-21 years undergoing first allogeneic SCT at the Children's Hospital of Philadelphia from 10/1/12 — 7/1/16. Patients with primary graft failure or missing HLA-DQ genotypes were excluded. We grouped patients by low, moderate or high CD risk (Clin Gastroenterol Hepatol 2009, 7:966). Primary outcomes were 1) 100-day aGVHD incidence; 2) day 100 — 1-year cGVHD incidence; and 3) time to GVHD with relapse, death, secondary graft failure, second SCT, or donor lymphocyte infusion as competing risks. Logistic regressions were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Sub-distribution hazard models were used to estimate crude and adjusted sub-distribution hazard ratios (sHR) in time-to-event analyses. Multivariate models were adjusted for race-ethnicity, malignant/nonmalignant SCT indication, donor/mismatch, and graft source. We identified 167 patients (mean age 9.2 ±6.2 years). Proportions by CD risk were: low-risk n=108 (64.7%), moderate n=33 (19.8%), and high n=26 (15.6%). Day 100 incidence of ≥grade 2 aGVHD was 14.4% (8.4% had ≥grade 3). cGVHD 1-year incidence was 42.7% (14% had extensive). CD risk was protective against GVHD but did not reach statistical significance (Table 1). Risk of clinically significant GVHD (≥grade 2 or any chronic) was reduced in children with CD risk in the adjusted time-to-event model (moderate: sHR 0.42, 95% CI 0.18 — 0.95, p=0.037; high: sHR 0.31, 95% CI 0.12 – 0.8, p=0.016; Figure 1A). The protective effect of high CD risk was more pronounced for severe GVHD (≥grade 3 or chronic extensive) but did not reach statistical significance (adjusted sHR 0.14, 95%CI 0.02-1.09, P = 0.061; Figure 1B). In contrast to our hypothesis, CD risk by HLA-DQ is protective against GVHD in a dose-responsive manner. Reports of HLA-DQ2 and DQ8 protecting against other non-CD autoimmune diseases (rheumatoid arthritis and inflammatory bowel disease) support our observations. These results require confirmation and evaluation in a larger patient sample to define this novel GVHD risk modifier more robustly. Table 1Adjusted risk of clinically significant GVHD by CD riskOR (95% CI)PaGVHDmoderate0.60 (0.16 — 2.25)0.45high0.13 (0.01 — 1.28)0.08cGVHDmoderate0.44 (0.17 — 1.13)0.09high0.30 (0.09 — 1.00)0.05 Open table in a new tab

Background CART19-related toxicities may require treatment inpatient or in the ICU. We sought to describe inpatient/ICU resource utilization within 30 days of CART19 infusion and evaluate trends in resource utilization from 2012-2019. Methods We identified patients (pts) with ALL treated with CART19 on a clinical trial (NCT01626495, NCT02906371, and NCT02374333) or with the commercial product, tisagenlecleucel, at Children's Hospital of Philadelphia. Demographic, pharmacy, and inpatient data were extracted from the EHR from day of infusion (d0) to d+30 using a semi-automated EPIC data query tool. The Virtual Pediatric Systems database was queried for resource utilization data and PRISM 3 and PIM 2 severity of illness scores. Log-binomial and linear regression were used to estimate the association of patient characteristics with inpatient/ICU admission and inpatient/ICU length of stay (LOS). Similar models were used to estimate trends over time. Results The analyses included 213 pts. Median age was 12y (range 1-29y); 60% were male. Prior to CART19, 42% had an alloHCT. Pre-infusion, 19% had high tumor burden (HTB), defined as bone marrow blasts ≥40%. From 2012-2019, the proportion of pts with prior alloHCT or HTB decreased (Table 1).CART19 was infused in the outpatient setting in 198 (93%) pts. From d0 to d+30, 149 (70%) had ≥1 inpatient admission, starting at a median of d+2 (IQR +1 to +6). Among admitted pts, median cumulative inpatient LOS was 7d (IQR 4-13). From 2012-2019, there were linear trends toward decreases in proportion of pts admitted (p<.001) and in inpatient LOS (p<.001, Figure 1). These decreases persisted after adjustment for HTB (p=0.03 and p<.001).ICU admission was required for 49 (23%) pts, starting at a median of day +5 (IQR +4 to +7). ICU admission was more frequent for pts with HTB [HTB, 68% (95% CI, 52-81) vs. low burden, 11% (95% CI, 7-17), p<.001]. Among ICU pts, resources utilized included tocilizumab (n=36, 75%), vasoactives (n=36, 75%), invasive mechanical ventilation (n=18, 8%), and dialysis (n=4, 8%). In the 30d follow-up period, median ICU LOS was 7d (IQR 3-12), but 6 (13%) pts remained in the ICU after d+30. Median duration of vasoactive, mechanical ventilation, and dialysis use was 5d, 7d and 2d, respectively. Predicted median risk of mortality was 6% (IQR 5-7) by PIM 2 and 11% (IQR 7-27) by PRISM 3 scores. However, observed 30d mortality was 1% (n=2) across the cohort, or 4% among ICU pts. From 2012-2019, there was a decrease in ICU admissions (p<.01), but no significant change in ICU LOS (Figure 1).Other than HTB, baseline characteristics were not associated with inpatient/ICU admission or LOS. Conclusion In a cohort of 213 pediatric pts, over 90% were safely infused with CART19 in the outpatient setting. Though 70% required at least one admission, the proportion of pts admitted to the hospital or ICU and cumulative inpatient LOS decreased over the past 7 years.

Objectives: A method to identify pediatric sepsis episodes that is not affected by changing diagnosis and claims-based coding practices does not exist. We derived and validated a surveillance algorithm to identify pediatric sepsis using routine clinical data and applied the algorithm to study longitudinal trends in sepsis epidemiology. Design: Retrospective observational study. Setting: Single academic children's hospital. Patients: All emergency and hospital encounters from January 2011 to January 2019, excluding neonatal ICU and cardiac center. Exposure: Sepsis episodes identified by a surveillance algorithm using clinical data to identify infection and concurrent organ dysfunction. Interventions None. Measurements and Main Results: A surveillance algorithm was derived and validated in separate cohorts with suspected sepsis after clinician-adjudication of final sepsis diagnosis. We then applied the surveillance algorithm to determine longitudinal trends in incidence and mortality of pediatric sepsis over 8 years. Among 93,987 hospital encounters and 1,065 episodes of suspected sepsis in the derivation period, the surveillance algorithm yielded sensitivity 78% (95% CI, 72-84%), specificity 76% (95% CI, 74-79%), positive predictive value 41% (95% CI, 36-46%), and negative predictive value 94% (95% CI, 92-96%). In the validation period, the surveillance algorithm yielded sensitivity 84% (95% CI, 77-92%), specificity of 65% (95% CI, 59-70%), positive predictive value 43% (95% CI, 35-50%), and negative predictive value 93% (95% CI, 90-97%). Notably, most "false-positives" were deemed clinically relevant sepsis cases after manual review. The hospital-wide incidence of sepsis was 0.69% (95% CI, 0.67-0.71%), and the inpatient incidence was 2.8% (95% CI, 2.7-2.9%). Risk-adjusted sepsis incidence, without bias from changing diagnosis or coding practices, increased over time (adjusted incidence rate ratio per year 1.07; 95% CI, 1.06-1.08; p < 0.001). Mortality was 6.7% and did not change over time (adjusted odds ratio per year 0.98; 95% CI, 0.93-1.03; p = 0.38). Conclusions: An algorithm using routine clinical data provided an objective, efficient, and reliable method for pediatric sepsis surveillance. An increased sepsis incidence and stable mortality, free from influence of changes in diagnosis or billing practices, were evident.

Background: CD19-targeted chimeric antigen receptor T cell therapy (CART19) has demonstrated remarkable clinical efficacy in treating relapsed/refractory B cell ALL, but associated toxicities may require treatment in inpatient or intensive care units (ICU). We sought to: (1) describe inpatient and ICU resource utilization within 30 days of CART19 infusion; and (2) evaluate trends in resource utilization from 2012-2019. Methods: We identified patients treated with CART19 on a clinical trial (NCT01626495, NCT02906371, and NCT02374333) or with the commercial product, tisagenlecleucel, at Children's Hospital of Philadelphia. Patients who received a prior cell therapy product were excluded. Demographic, pharmacy, and inpatient data were extracted from the electronic medical record from day of infusion (day 0) to day +30, censored at disease progression or death, using a semi-automated EPIC data query tool (ExtractEHR). The Virtual Pediatric Systems (VPS) database was queried for clinical data, resource utilization data, and Pediatric Risk of Mortality (PRISM) 3 and Pediatric Index of Mortality (PIM) 2 severity of illness scores. Log-binomial regression and linear regression were used to estimate the association of patient characteristics with the need for inpatient/ICU admission and inpatient/ICU length of stay (LOS), respectively. Similar models were used to estimate trends in outcomes from 2012-2019. Results: A total of 213 patients were included in the analyses. Median patient age was 12.4 years (range 1.4-29.1) at infusion; 60% were male, 66% were Caucasian, and 80% were non-Hispanic. Prior to CART19, 42% had an allogeneic hematopoietic cell transplant (alloHCT). At time of infusion, 19% had high disease burden, defined as bone marrow blasts ≥40% by flow cytometry. From 2012-2019, the proportion of patients with prior alloHCT or high disease burden decreased (Table 1). CART19 was infused in the outpatient setting in 93% of patients. In the 30 days after infusion, 70% had at least one inpatient admission, starting at a median of day +2 (IQR +1 to +6). Among the 149 patients admitted, median cumulative inpatient LOS was 7 days (IQR 4-13). Cumulative LOS increased with increasing grade of cytokine release syndrome (CRS). Median LOS was 0, 5, and 15 days for patients with no, mild, and severe CRS, respectively. From 2012-2019, there were linear trends toward decreases in proportion of patients admitted (p<.0001) and in cumulative inpatient LOS (p=0.001, Figure 1), which remained significant after adjustment for disease burden (p=0.032 and p<.0001). ICU admission was required for 23% (95% CI, 17-29) of the cohort, starting at a median of day +5 (IQR +4 to +6.5). ICU admission was more frequent for patients with high disease burden than those with low disease burden [68% (95% CI, 52-81) vs. 11% (95% CI, 7-17), p<.0001]. Among the 48 patients admitted to the ICU, resources utilized included vasoactive agents (n=36, 75%), non-invasive or invasive mechanical ventilation (n=24, 50%), and renal replacement therapy (RRT; n=4, 8%). In the 30-day follow-up period, median ICU LOS was 7 days (IQR 3-11.5), but 6 (12.5%) patients remained in the ICU after day +30. Among patients who required vasoactives, invasive mechanical ventilation, or RRT, the median duration of resource utilization was 5, 7.2, and 2 days, respectively. Seventy five percent (n=36) of patients admitted to the ICU received tocilizumab. Predicted median risk of mortality was 6.02% (IQR 5.04-7.32%) by PIM 2 and 10.74% (IQR 6.78-27.08%) by PRISM 3 scores. However, observed 30-day mortality was 1% (n=2) across the cohort, or 4% among ICU patients. From 2012-2019, there was a decrease in proportion of patients requiring ICU admission (p=0.001), but no significant changes in cumulative ICU LOS (Figure 1). Other than high disease burden, baseline patient characteristics were not significantly associated with inpatient/ICU admission or inpatient/ICU LOS. Conclusion: In a cohort of 213 pediatric patients with ALL who received CART19, over 90% were safely infused in the outpatient setting. Though the majority of patients required at least one inpatient admission, the proportion of patients admitted to the hospital or ICU and cumulative inpatient LOS in the 30 days post-infusion decreased over the past 7 years. Mortality was 1%. Additional analyses will investigate the impact of changes in supportive care practices on resource utilization outcomes. Disclosures Grupp: GSK: Consultancy; Cure Genetics: Consultancy; Humanigen: Consultancy; CBMG: Consultancy; Novartis: Research Funding; Kite: Research Funding; Novartis: Consultancy, Research Funding; Roche: Consultancy; Servier: Research Funding; Jazz: Other: study steering committees or scientific advisory boards; Adaptimmune: Other: study steering committees or scientific advisory boards. Maude:Novartis: Consultancy; Kite: Consultancy.

BACKGROUND:The allergic march describes the natural history of allergic conditions as they develop during childhood. Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease that can be triggered by specific foods. Despite its allergic pathophysiology, the epidemiologic relationship between EoE and established members of the allergic march is unknown. OBJECTIVE:We sought to determine whether EoE meets epidemiologic criteria for being considered a member of the allergic march. METHODS:Using a primary care birth cohort of 130,435 children, we determined the natural histories of atopic dermatitis (AD), IgE-mediated food allergy (IgE-FA), asthma, EoE, and allergic rhinitis (AR) in individual patients. We then performed case-control analyses to establish the extent that existing allergic conditions influence the rate of subsequent EoE diagnosis. RESULTS:A total of 139 children developed EoE during the observation period (prevalence of 0.11%). The peak age of EoE diagnosis was 2.6 years, as compared with 0.3 years, 1 year, 1.1 years, and 2.1 years for AD, IgE-FA, asthma, and AR, respectively. The presence of AD (hazard ratio [HR] 3.2, 95% confidence interval [CI] 2.2-4.6), IgE-FA (HR 9.1, 95% CI 6.5-12.6), and asthma (HR 1.9, 95% CI 1.3-2.7) was independently and cumulatively associated with subsequent EoE diagnosis. The presence of AR was associated with subsequent EoE diagnosis (HR 2.8, 95% CI 2.0-3.9), and the presence of EoE was associated with subsequent AR diagnosis (HR 2.5, 95% CI 1.7-3.5). CONCLUSIONS:Allergic comorbidities are positively associated with EoE diagnosis. Together, our findings suggest that EoE is a late manifestation of the allergic march.

Background Surveillance for surgical site infections (SSIs) after ambulatory surgery in children requires a detailed manual chart review to assess criteria defined by the National Health and Safety Network (NHSN). Electronic health records (EHRs) impose an inefficient search process where infection preventionists must manually review every postsurgical encounter (< 30 days). Using text mining and business intelligence software, we developed an information foraging application, the SSI Workbench, to visually present which postsurgical encounters included SSI-related terms and synonyms, antibiotic, and culture orders. Objective This article compares the Workbench and EHR on four dimensions: (1) effectiveness, (2) efficiency, (3) workload, and (4) usability. Methods Comparative usability test of Workbench and EHR. Objective test metrics are time per case, encounters reviewed per case, time per encounter, and retrieval of information meeting NHSN definitions. Subjective measures are cognitive load using the National Aeronautics and Space Administration (NASA) Task Load Index (NASA TLX), and a questionnaire on system usability and utility. Results Eight infection preventionists participated in the test. There was no difference in effectiveness as subjects retrieved information from all cases, using both systems, to meet the NHSN criteria. There was no difference in efficiency in time per case between the Workbench and EHR (8.58 vs. 7.39 minutes, p = 0.36). However, with the Workbench subjects opened fewer encounters per case (3.0 vs. 7.5, p = 0.002), spent more time per encounter (2.23 vs. 0.92 minutes, p = 0.002), rated the Workbench lower in cognitive load (NASA TLX, 24 vs. 33, p = 0.02), and significantly higher in measures of usability. Conclusion Compared with the EHR, the Workbench was more usable, short, and reduced cognitive load. In overall efficiency, the Workbench did not save time, but demonstrated a shift from between-encounter foraging to within-encounter foraging and was rated as significantly more efficient. Our results suggest that infection surveillance can be better supported by systems applying information foraging theory.

Objective The objective was to prospectively derive and validate a prediction rule for detecting cases warranting investigation for surgical site infections (SSI) after ambulatory surgery. Methods We analysed electronic health record (EHR) data for children who underwent ambulatory surgery at one of 4 ambulatory surgical facilities. Using regularized logistic regression and random forests, we derived SSI prediction rules using 30 months of data (derivation set) and evaluated performance with data from the subsequent 10 months (validation set). Models were developed both with and without data extracted from free text. We also evaluated the presence of an antibiotic prescription within 60 days after surgery as an independent indicator of SSI evidence. Our goal was to exceed 80% sensitivity and 10% positive predictive value (PPV). Results We identified 234 surgeries with evidence of SSI among the 7910 surgeries available for analysis. We derived and validated an optimal prediction rule that included free text data using a random forest model (sensitivity = 0.9, PPV = 0.28). Presence of an antibiotic prescription had poor sensitivity (0.65) when applied to the derivation data but performed better when applied to the validation data (sensitivity = 0.84, PPV = 0.28). Conclusions EHR data can facilitate SSI surveillance with adequate sensitivity and PPV.