Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents.

BACKGROUND: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant's emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. OBJECTIVE: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. DESIGN: Comparative effectiveness research accounting for underreported vaccination in 3 study cohorts: adolescents (12 to 20 years) during the Delta phase and children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. SETTING: A national collaboration of pediatric health systems (PEDSnet). PARTICIPANTS: 77 392 adolescents (45 007 vaccinated) during the Delta phase and 111 539 children (50 398 vaccinated) and 56 080 adolescents (21 180 vaccinated) during the Omicron phase. INTERVENTION: First dose of the BNT162b2 vaccine versus no receipt of COVID-19 vaccine. MEASUREMENTS: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100, with confounders balanced via propensity score stratification. RESULTS: During the Delta period, the estimated effectiveness of the BNT162b2 vaccine was 98.4% (95% CI, 98.1% to 98.7%) against documented infection among adolescents, with no statistically significant waning after receipt of the first dose. An analysis of cardiac complications did not suggest a statistically significant difference between vaccinated and unvaccinated groups. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (CI, 72.2% to 76.2%). Higher levels of effectiveness were seen against moderate or severe COVID-19 (75.5% [CI, 69.0% to 81.0%]) and ICU admission with COVID-19 (84.9% [CI, 64.8% to 93.5%]). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (CI, 83.8% to 87.1%), with 84.8% (CI, 77.3% to 89.9%) against moderate or severe COVID-19, and 91.5% (CI, 69.5% to 97.6%) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined 4 months after the first dose and then stabilized. The analysis showed a lower risk for cardiac complications in the vaccinated group during the Omicron variant period. LIMITATION: Observational study design and potentially undocumented infection. CONCLUSION: This study suggests that BNT162b2 was effective for various COVID-19-related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time. PRIMARY FUNDING SOURCE: National Institutes of Health.

Leveraging Serologic Testing to Identify Children at Risk For Post-Acute Sequelae of SARS-CoV-2 Infection: An Electronic Health Record-Based Cohort Study from the RECOVER Program.

Using an electronic health record-based algorithm, we identified children with Coronavirus disease 2019 (COVID-19) based exclusively on serologic testing between March 2020 and April 2022. Compared with the 131 537 polymerase chain reaction-positive children, the 2714 serology-positive children were more likely to be inpatients (24% vs 2%), to have a chronic condition (37% vs 24%), and to have a diagnosis of multisystem inflammatory syndrome in children (23% vs <1%). Identification of children who could have been asymptomatic or paucisymptomatic and not tested is critical to define the burden of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection in children.

Venous Access: National Guideline and Registry Development (VANGUARD): Advancing Patient-Centered Venous Access Care Through the Development of a National Coordinated Registry Network.

There are over 8 million central venous access devices inserted each year, many in patients with chronic conditions who rely on central access for life-preserving therapies. Central venous access device-related complications can be life-threatening and add tens of billions of dollars to health care costs, while their incidence is most likely grossly mis- or underreported by medical institutions. In this communication, we review the challenges that impair retention, exchange, and analysis of data necessary for a meaningful understanding of critical events and outcomes in this clinical domain. The difficulty is not only with data extraction and harmonization from electronic health records, national surveillance systems, or other health information repositories where data might be stored. The problem is that reliable and appropriate data are not recorded, or falsely recorded, at least in part because policy, payment, penalties, proprietary concerns, and workflow burdens discourage completeness and accuracy. We provide a roadmap for the development of health care information systems and infrastructure that address these challenges, framed within the context of research studies that build a framework of standardized terminology, decision support, data capture, and information exchange necessary for the task. This roadmap is embedded in a broader Coordinated Registry Network Learning Community, and facilitated by the Medical Device Epidemiology Network, a Public-Private Partnership sponsored by the US Food and Drug Administration, with the scope of advancing methods, national and international infrastructure, and partnerships needed for the evaluation of medical devices throughout their total life cycle.

Skeletal Outcomes in Children and Young Adults with Glomerular Disease.

BACKGROUND: Children with glomerular disease have unique risk factors for compromised bone health. Studies addressing skeletal complications in this population are lacking. METHODS: This retrospective cohort study utilized data from PEDSnet, a national network of pediatric health systems with standardized electronic health record data for more than 6.5 million patients from 2009 to 2021. Incidence rates (per 10,000 person-years) of fracture, slipped capital femoral epiphysis (SCFE), and avascular necrosis/osteonecrosis (AVN) in 4598 children and young adults with glomerular disease were compared with those among 553,624 general pediatric patients using Poisson regression analysis. The glomerular disease cohort was identified using a published computable phenotype. Inclusion criteria for the general pediatric cohort were two or more primary care visits 1 year or more apart between 1 and 21 years of age, one visit or more every 18 months if followed >3 years, and no chronic progressive conditions defined by the Pediatric Medical Complexity Algorithm. Fracture, SCFE, and AVN were identified using SNOMED-CT diagnosis codes; fracture required an associated x-ray or splinting/casting procedure within 48 hours. RESULTS: We found a higher risk of fracture for the glomerular disease cohort compared with the general pediatric cohort in girls only (incidence rate ratio [IRR], 1.6; 95% CI, 1.3 to 1.9). Hip/femur and vertebral fracture risk were increased in the glomerular disease cohort: adjusted IRR was 2.2 (95% CI, 1.3 to 3.7) and 5 (95% CI, 3.2 to 7.6), respectively. For SCFE, the adjusted IRR was 3.4 (95% CI, 1.9 to 5.9). For AVN, the adjusted IRR was 56.2 (95% CI, 40.7 to 77.5). CONCLUSIONS: Children and young adults with glomerular disease have significantly higher burden of skeletal complications than the general pediatric population.

Antibiotics prior to age 2 years have limited association with preschool growth trajectory.

BACKGROUND: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years. METHODS: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections. RESULTS: 430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain. CONCLUSION: Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2-5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.

Implementation science in pediatric oncology: A narrative review and future directions.

Implementation science (IS) has garnered attention within oncology, and most prior IS work has focused on adult, not pediatric, oncology. This narrative review broadly characterizes IS for pediatric oncology. It includes studies through 2020 using the following search terms in PubMed, Ovid Medline, and Cochrane: "implementation science," "pediatric," "childhood," "cancer," and "oncology." Systematic review was not performed due to the limited number of heterogeneous studies. Of 216 articles initially reviewed, nine were selected as specific to IS and pediatric oncology. All nine examined oncologic supportive care, cancer prevention, or cancer control. The supportive care focus is potentially due to the presence of cooperative study groups such as the Children's Oncology Group, which efficiently drive cancer-directed therapy changes through clinical trials. Future IS within pediatric oncology should embrace this ecosystem and focus on cancer control interventions that benefit patients across multiple cancer types and patients treated outside cooperative group studies.

Privacy-protecting multivariable-adjusted distributed regression analysis for multi-center pediatric study.

BACKGROUND: Privacy-protecting analytic approaches without centralized pooling of individual-level data, such as distributed regression, are particularly important for vulnerable populations, such as children, but these methods have not yet been tested in multi-center pediatric studies. METHODS: Using the electronic health data from 34 healthcare institutions in the National Patient-Centered Clinical Research Network (PCORnet), we fit 12 multivariable-adjusted linear regression models to assess the associations of antibiotic use <24 months of age with body mass index z-score at 48 to <72 months of age. We ran these models using pooled individual-level data and conventional multivariable-adjusted regression (reference method), as well as using the more privacy-protecting pooled summary-level intermediate statistics and distributed regression technique. We compared the results from these two methods. RESULTS: Pooled individual-level and distributed linear regression analyses produced virtually identical parameter estimates and standard errors. Across all 12 models, the maximum difference in any of the parameter estimates or standard errors was 4.4833 × 10-10. CONCLUSIONS: We demonstrated empirically the feasibility and validity of distributed linear regression analysis using only summary-level information within a large multi-center study of children. This approach could enable expanded opportunities for multi-center pediatric research, especially when sharing of granular individual-level data is challenging.

Joining Datasets Without Identifiers: Probabilistic Linkage of Virtual Pediatric Systems and PEDSnet.

OBJECTIVES: To 1) probabilistically link two important pediatric data sources, Virtual Pediatric Systems and PEDSnet, 2) evaluate linkage accuracy overall and in patients with severe sepsis or septic shock, and 3) identify variables important to linkage accuracy. DESIGN: Retrospective linkage of prospectively collected datasets from Virtual Pediatrics Systems, Inc (Los Angeles, CA) and the PEDSnet consortium. SETTING: Single-center academic PICU. PATIENTS: All PICU encounters between January 1, 2012, and December 31, 2017, that were deterministically matched between the two datasets. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We abstracted records from Virtual Pediatric Systems and PEDSnet corresponding to PICU encounters and probabilistically linked using 44 features shared by the two datasets. We generated a gold standard deterministic linkage using protected health information elements, which were then removed from datasets. We then calculated candidate pair log-likelihood ratios for all pairs of subjects and selected optimal pairs in a two-stage algorithm. A total of 22,051 gold standard PICU encounter pairs were identified over the study period. The optimal linkage model demonstrated excellent discrimination (area under the receiver operating characteristic curve > 0.99); 19,801 cases (89.9%) were matched with 13 false positives. The addition of two protected health information dates (admission month, birth day-of-year) increased to 20,189 (91.6%) the cases matched, with three false positives. Restricting to patients with Virtual Pediatric Systems diagnosis of severe sepsis or septic shock (n = 1,340 [6.1%]) matched 1,250 cases (93.2%) with zero false positives. Increased number of laboratory values present in the first 12 hours of admission significantly increased log-likelihood ratios, suggesting stronger candidate pair matching. CONCLUSIONS: We demonstrated the use of probabilistic linkage to accurately join two complementary pediatric critical care datasets at a single academic PICU in the absence of protected health information. Combining datasets with curated diagnoses and granular measurements can validate patient acuity metrics and facilitate multicenter machine learning algorithms. We anticipate these methods will generalize to other common PICU diagnoses.

Using Electronic Health Record Data to Rapidly Identify Children with Glomerular Disease for Clinical Research.

BACKGROUND: The rarity of pediatric glomerular disease makes it difficult to identify sufficient numbers of participants for clinical trials. This leaves limited data to guide improvements in care for these patients. METHODS: The authors developed and tested an electronic health record (EHR) algorithm to identify children with glomerular disease. We used EHR data from 231 patients with glomerular disorders at a single center to develop a computerized algorithm comprising diagnosis, kidney biopsy, and transplant procedure codes. The algorithm was tested using PEDSnet, a national network of eight children's hospitals with data on >6.5 million children. Patients with three or more nephrologist encounters (n=55,560) not meeting the computable phenotype definition of glomerular disease were defined as nonglomerular cases. A reviewer blinded to case status used a standardized form to review random samples of cases (n=800) and nonglomerular cases (n=798). RESULTS: The final algorithm consisted of two or more diagnosis codes from a qualifying list or one diagnosis code and a pretransplant biopsy. Performance characteristics among the population with three or more nephrology encounters were sensitivity, 96% (95% CI, 94% to 97%); specificity, 93% (95% CI, 91% to 94%); positive predictive value (PPV), 89% (95% CI, 86% to 91%); negative predictive value, 97% (95% CI, 96% to 98%); and area under the receiver operating characteristics curve, 94% (95% CI, 93% to 95%). Requiring that the sum of nephrotic syndrome diagnosis codes exceed that of glomerulonephritis codes identified children with nephrotic syndrome or biopsy-based minimal change nephropathy, FSGS, or membranous nephropathy, with 94% sensitivity and 92% PPV. The algorithm identified 6657 children with glomerular disease across PEDSnet, ≥50% of whom were seen within 18 months. CONCLUSIONS: The authors developed an EHR-based algorithm and demonstrated that it had excellent classification accuracy across PEDSnet. This tool may enable faster identification of cohorts of pediatric patients with glomerular disease for observational or prospective studies.

Maternal antibiotic use during pregnancy and childhood obesity at age 5 years.

OBJECTIVE: The benefits of antibiotic treatment during pregnancy are immediate, but there may be long-term risks to the developing child. Prior studies show an association between early life antibiotics and obesity, but few have examined this risk during pregnancy. SUBJECTS: To evaluate the association of maternal antibiotic exposure during pregnancy on childhood BMI-z at 5 years, we conducted a retrospective cohort analysis. Using electronic health record data from seven health systems in PCORnet, a national distributed clinical research network, we included children with same-day height and weight measures who could be linked to mothers with vital measurements during pregnancy. The primary independent variable was maternal outpatient antibiotic prescriptions during pregnancy (any versus none). We examined dose response (number of antibiotic episodes), spectrum and class of antibiotics, and antibiotic episodes by trimester. The primary outcome was child age- and sex-specific BMI-z at age 5 years. RESULTS: The final sample was 53,320 mother-child pairs. During pregnancy, 29.9% of mothers received antibiotics. In adjusted models, maternal outpatient antibiotic prescriptions during pregnancy were not associated with child BMI-z at age 5 years (ß = 0.00, 95% CI -0.03, 0.02). When evaluating timing during pregnancy, dose-response, spectrum and class of antibiotics, there were no associations of maternal antibiotics with child BMI-z at age 5 years. CONCLUSION: In this large observational cohort, provision of antibiotics during pregnancy was not associated with childhood BMI-z at 5 years.

A Bayesian latent class approach for EHR-based phenotyping.

Phenotyping, ie, identification of patients possessing a characteristic of interest, is a fundamental task for research conducted using electronic health records. However, challenges to this task include imperfect sensitivity and specificity of clinical codes and inconsistent availability of more detailed data such as laboratory test results. Despite these challenges, most existing electronic health records-derived phenotypes are rule-based, consisting of a series of Boolean arguments informed by expert knowledge of the disease of interest and its coding. The objective of this paper is to introduce a Bayesian latent phenotyping approach that accounts for imperfect data elements and missing not at random missingness patterns that can be used when no gold-standard data are available. We conducted simulation studies to compare alternative phenotyping methods under different patterns of missingness and applied these approaches to a cohort of 68 265 children at elevated risk for type 2 diabetes mellitus (T2DM). In simulation studies, the latent class approach had similar sensitivity to a rule-based approach (95.9% vs 91.9%) while substantially improving specificity (99.7% vs 90.8%). In the PEDSnet cohort, we found that biomarkers and clinical codes were strongly associated with latent T2DM status. The latent T2DM class was also strongly predictive of missingness in biomarkers. Glucose was missing in 83.4% of patients (odds ratio for latent T2DM status = 0.52) while hemoglobin A1c was missing in 91.2% (odds ratio for latent T2DM status = 0.03 ), suggesting missing not at random missingness. The latent phenotype approach may substantially improve on rule-based phenotyping.

Significance of CNS 2 cerebrospinal fluid status post-induction in pediatric and adolescent patients with acute lymphoblastic leukemia.

BACKGROUND: At diagnosis, there are prognostic implications of low-level leukemic blasts (CNS 2) in the cerebrospinal fluid (CSF) of patients with acute lymphoblastic leukemia (ALL). However, the significance of post-induction CNS 2 results and the impact of equipment on CNS 2 prevalence have not been well studied. PROCEDURE: A single-institution retrospective cohort study was conducted to analyze the outcome of patients with ≥1 post-induction CNS 2. A subanalysis compared the proportion of CNS 2 CSF results using 2 different cytocentrifuges; the Shandon Cytospin used from 2005 to 2008 and the Wescor Cytopro used from 2010 to 2014. RESULTS: Over 4500 post-induction CSF samples were analyzed, of which 59 were CNS 2. In covariate-adjusted analyses, post-induction CNS 2 did not significantly increase relapse risk. The proportion of CNS 2 results increased 4.3-fold in noninfants and 6.3-fold in infants using the Wescor Cytopro. Cytocentrifuge machine did not affect CNS 3 prevalence. CONCLUSIONS: These findings support our current practice of not changing management based on a post-induction CNS 2 CSF and highlight how equipment changes can significantly influence testing results. More data are needed to analyze relapse by subpopulations, such as those with repeated CNS 2 findings.

Health-related Google searches performed by parents of pediatric oncology patients.

BACKGROUND: Little is known about the specific information parents of children with cancer search for online. Understanding the content of parents' searches over time could offer insight into what matters most to parents and identify knowledge gaps that could inform more comprehensive approaches to family education and support. METHODS: We describe parents' health-related Google searches starting six months before cancer diagnosis and extending through the date of study enrollment, which was at least one month after initiating cancer treatment. Searches were obtained retrospectively and grouped into health-related and non-health-related categories. The median time to parent enrollment from date of cancer diagnosis was 264 days. RESULTS: Parents searched for health-related topics more frequently than the general population (13% vs 5%). Health-related searches increased in the months preceding the child's cancer diagnosis and most commonly pertained to symptoms and logistics, "directions to hospital." Health-related search volume peaked about a month after cancer diagnosis when general health-related searches were present in addition to cancer-specific searches. Eighteen percent of health-related searches were cancer specific, and of these cancer-specific searches, 54% pertained to support, for example "cancer quote for son." CONCLUSIONS: Google search content offers insight into what matters to parents of cancer patients. Understanding search content could inform more comprehensive approaches to family education and support initiatives.

Development and evaluation of a computable phenotype to identify pediatric patients with leukemia and lymphoma treated with chemotherapy using electronic health record data.

BACKGROUND: Widespread implementation of electronic health records (EHR) has created new opportunities for pediatric oncology observational research. Little attention has been given to using EHR data to identify patients with pediatric hematologic malignancies. METHODS: This study used EHR-derived data in a pediatric clinical data research network, PEDSnet, to develop and evaluate a computable phenotype algorithm to identify pediatric patients with leukemia and lymphoma who received treatment with chemotherapy. To guide early development, multiple computable phenotype-defined cohorts were compared to one institution's tumor registry. The most promising algorithm was chosen for formal evaluation and consisted of at least two leukemia/lymphoma diagnoses (Systematized Nomenclature of Medicine codes) within a 90-day period, two chemotherapy exposures, and three hematology-oncology provider encounters. During evaluation, the computable phenotype was executed against EHR data from 2011 to 2016 at three large institutions. Classification accuracy was assessed by masked medical record review with phenotype-identified patients compared to a control group with at least three hematology-oncology encounters. RESULTS: The computable phenotype had sensitivity of 100% (confidence interval [CI] 99%, 100%), specificity of 99% (CI 99%, 100%), positive predictive value (PPV) and negative predictive value (NPV) of 100%, and C-statistic of 1 at the development institution. The computable phenotype performance was similar at the two test institutions with sensitivity of 100% (CI 99%, 100%), specificity of 99% (CI 99%, 100%), PPV of 96%, NPV of 100%, and C-statistic of 0.99. CONCLUSION: The EHR-based computable phenotype is an accurate cohort identification tool for pediatric patients with leukemia and lymphoma who have been treated with chemotherapy and is ready for use in clinical studies.

Management of Refractory Pediatric Kaposiform Hemangioendothelioma With Sirolimus and Aspirin.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor characterized by aggressive local invasion and a syndrome of platelet trapping known as Kasabach-Merritt phenomenon that, through deposition of platelet derived growth factors, may perpetuate the growth of the tumor. Although many cases of KHE are successfully treated with local control or low-intensity chemotherapy, some cases are often refractory even to aggressive treatment. Herein, we describe a patient with a refractory, recurrent KHE despite multiple attempts at local control and intensive chemotherapy, that ultimately was successfully treated with rationally designed and low-intensity combination therapy of sirolimus and aspirin.

Relationship Between State-Level Google Online Search Volume and Cancer Incidence in the United States: Retrospective Study.

BACKGROUND: In the United States, cancer is common, with high morbidity and mortality; cancer incidence varies between states. Online searches reflect public awareness, which could be driven by the underlying regional cancer epidemiology. OBJECTIVE: The objective of our study was to characterize the relationship between cancer incidence and online Google search volumes in the United States for 6 common cancers. A secondary objective was to evaluate the association of search activity with cancer-related public events and celebrity news coverage. METHODS: We performed a population-based, retrospective study of state-level cancer incidence from 2004 through 2013 reported by the Centers for Disease Control and Prevention for breast, prostate, colon, lung, and uterine cancers and leukemia compared to Google Trends (GT) relative search volume (RSV), a metric designed by Google to allow interest in search topics to be compared between regions. Participants included persons in the United States who searched for cancer terms on Google. The primary measures were the correlation between annual state-level cancer incidence and RSV as determined by Spearman correlation and linear regression with RSV and year as independent variables and cancer incidence as the dependent variable. Temporal associations between search activity and events raising public awareness such as cancer awareness months and cancer-related celebrity news were described. RESULTS: At the state level, RSV was significantly correlated to incidence for breast (r=.18, P=.001), prostate (r=-.27, P<.001), lung (r=.33, P<.001), and uterine cancers (r=.39, P<.001) and leukemia (r=.13, P=.003) but not colon cancer (r=-.02, P=.66). After adjusting for time, state-level RSV was positively correlated to cancer incidence for all cancers: breast (P<.001, 95% CI 0.06 to 0.19), prostate (P=.38, 95% CI -0.08 to 0.22), lung (P<.001, 95% CI 0.33 to 0.46), colon (P<.001, 95% CI 0.11 to 0.17), and uterine cancers (P<.001, 95% CI 0.07 to 0.12) and leukemia (P<.001, 95% CI 0.01 to 0.03). Temporal associations in GT were noted with breast cancer awareness month but not with other cancer awareness months and celebrity events. CONCLUSIONS: Cancer incidence is correlated with online search volume at the state level. Search patterns were temporally associated with cancer awareness months and celebrity announcements. Online searches reflect public awareness. Advancing understanding of online search patterns could augment traditional epidemiologic surveillance, provide opportunities for targeted patient engagement, and allow public information campaigns to be evaluated in ways previously unable to be measured.

Effect of Levofloxacin Prophylaxis on Bacteremia in Children With Acute Leukemia or Undergoing Hematopoietic Stem Cell Transplantation: A Randomized Clinical Trial.

Importance: Bacteremia causes considerable morbidity among children with acute leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). There are limited data on the effect of antibiotic prophylaxis in children. Objective: To determine the efficacy and risks of levofloxacin prophylaxis in children receiving intensive chemotherapy for acute leukemia or undergoing HSCT. Design, Setting, and Participants: In this multicenter, open-label, randomized trial, patients (6 months-21 years) receiving intensive chemotherapy were enrolled (September 2011-April 2016) in 2 separate groups-acute leukemia, consisting of acute myeloid leukemia or relapsed acute lymphoblastic leukemia, and HSCT recipients-at 76 centers in the United States and Canada, with follow-up completed September 2017. Interventions: Patients with acute leukemia were randomized to receive levofloxacin prophylaxis for 2 consecutive cycles of chemotherapy (n = 100) or no prophylaxis (n = 100). Those undergoing HSCT were randomized to receive levofloxacin prophylaxis during 1 HSCT procedure (n = 210) or no prophylaxis (n = 214). Main Outcomes and Measures: The primary outcome was the occurrence of bacteremia during 2 chemotherapy cycles (acute leukemia) or 1 transplant procedure (HSCT). Secondary outcomes included fever and neutropenia, severe infection, invasive fungal disease, Clostridium difficile-associated diarrhea, and musculoskeletal toxic effects. Results: A total of 624 patients, 200 with acute leukemia (median [interquartile range {IQR}] age, 11 years [6-15 years]; 46% female) and 424 undergoing HSCT (median [IQR] age, 7 years [3-14]; 38% female), were enrolled. Among 195 patients with acute leukemia, the likelihood of bacteremia was significantly lower in the levofloxacin prophylaxis group than in the control group (21.9% vs 43.4%; risk difference, 21.6%; 95% CI, 8.8%-34.4%, P = .001), whereas among 418 patients undergoing HSCT, the risk of bacteremia was not significantly lower in the levofloxacin prophylaxis group (11.0% vs 17.3%; risk difference, 6.3%; 95% CI, 0.3%-13.0%; P = .06). Fever and neutropenia were less common in the levofloxacin group (71.2% vs 82.1%; risk difference, 10.8%; 95% CI, 4.2%-17.5%; P = .002). There were no significant differences in severe infection (3.6% vs 5.9%; risk difference, 2.3%; 95% CI, -1.1% to 5.6%; P = .20), invasive fungal disease (2.9% vs 2.0%; risk difference, -1.0%; 95% CI, -3.4% to 1.5%, P = .41), C difficile-associated diarrhea (2.3% vs 5.2%; risk difference, 2.9%; 95% CI, -0.1% to 5.9%; P = .07), or musculoskeletal toxic effects at 2 months (11.4% vs 16.3%; risk difference, 4.8%; 95% CI, -1.6% to 11.2%; P = .15) or at 12 months (10.1% vs 14.4%; risk difference, 4.3%; 95% CI, -3.4% to 12.0%; P = .28) between the levofloxacin and control groups. Conclusions and Relevance: Among children with acute leukemia receiving intensive chemotherapy, receipt of levofloxacin prophylaxis compared with no prophylaxis resulted in a significant reduction in bacteremia. However, there was no significant reduction in bacteremia for levofloxacin prophylaxis among children undergoing HSCT.

Atypical Chronic Myeloid Leukemia in Two Pediatric Patients.

Atypical chronic myeloid leukemia, BCR-ABL1-negative, (aCML) is a rare myeloid neoplasm. Recent adult data suggest the leukemic cells in a subset of patients are dependent on JAK/STAT signaling and harbor CSF3R-activating mutations. We hypothesized that, similar to adult patients, the presence of CSF3R-activating mutations would be clinically relevant in pediatric myeloid neoplasms as patients would be sensitive to the JAK inhibitor, ruxolitinib. We report two cases of morphologically similar pediatric aCML, BCR-ABL1-negative based on WHO 2008 criteria. One patient had CSF3R-activating mutation (T618I) and demonstrated a robust response to ruxolitinib, which was used to bridge to a successful stem cell transplant. The other patient did not have a CSF3R-activating mutation and succumbed to refractory disease <6 months from diagnosis. This report documents CSF3R-T618I in pediatric aCML and demonstrates the efficacy of ruxolitinib in a pediatric malignancy. As the third documented case successfully treating aCML with ruxolitinib, this case highlights the importance of prompt CSF3R sequencing analysis for myeloproliferative and myelodysplastic/myeloproliferative neoplasms.

Feasibility and validity of the pediatric ulcerative colitis activity index in routine clinical practice.

OBJECTIVES: The Pediatric Ulcerative Colitis Activity Index (PUCAI) is a noninvasive disease activity index developed as a clinical trial endpoint. More recently, practice guidelines have recommended the use of PUCAI in routine clinical care. We therefore sought to evaluate the feasibility, validity, and responsiveness of PUCAI in a large, diverse collection of pediatric gastroenterology practices. METHODS: We extracted data from the 2 most recent encounters for patients with ulcerative colitis in the ImproveCareNow registry. Feasibility was determined by the percentage of patients for whom all PUCAI components were recorded, validity by correlation of PUCAI scores across physician global assessment (PGA) categories, and responsiveness to change by the correlation between the change in PUCAI and PGA scores between visits. RESULTS: A total of 2503 patients were included (49.5% boys, age 15.2 ±â€Š4.1 years, disease duration 3.7 ±â€Š3.2 years). All items in the PUCAI were completed for 96% of visits. PUCAI demonstrated excellent discriminatory ability between remission, mild, and moderate disease; discrimination between moderate and severe disease was less robust. There was good correlation with PGA (r = 0.76 [P < 0.001] and weighted kappa κ = 0.73 [P < 0.001]). The PUCAI change scores correlated well with PGA change scores (P < 0.001). Test-retest reliability of the PUCAI was good (intraclass correlation coefficient 0.72 [95% confidence interval 0.70-0.75], P < 0.001). Guyatt responsiveness statistic was 1.18, and the correlation of ΔPUCAI with ΔPGA was 0.69 (P < 0.001). CONCLUSIONS: The PUCAI is feasible to use in routine clinical settings. Evidence of its validity and responsiveness supports its use as a clinical tool for monitoring disease activity for patients with ulcerative colitis.