Children's National Health System Research Articles

Diet Quality and Cardiometabolic Risk Factors in Adolescents with Down Syndrome.

Youth with Down syndrome (DS) have a high prevalence of obesity and dyslipidemia. Diet quality may influence cardiometabolic risk (CMR) in youth. The aim of this secondary analysis was to investigate the relationship between diet quality (Healthy Eating Index [HEI-2015]) with CMR factors in youth with DS compared with age, sex, race, ethnicity, and body mass index percentile matched, typically developing controls. Adolescents (aged 10 to 20 years) with DS and controls of comparable age, sex, race, ethnicity, and body mass index percentile were recruited from 2012 to 2017 for a cross-sectional study from two large children's hospitals (Children's Hospital of Philadelphia and the Children's National Health System in Washington, DC). CMRs in 143 adolescents with DS were compared with 100 controls. Exclusion criteria consisted of major organ-system illnesses. The average of three 24-hour dietary recalls was used to calculate the HEI-2015. Anthropometrics, blood pressure, and fasting labs were collected. Group differences were tested using Wilcoxon rank-sum tests. Relationships of CMR factors with HEI-2015 score within DS and controls were tested using linear regression models adjusted for sex, age, race, and body mass index z score. Compared with controls (n= 100, median age= 14.8 years [interquartile range= 12.2 to 17.3 years]; 41% male; 24% African American; 65% with body mass index ≥85th percentile), adolescents with DS (n= 143, median age= 14.7 years [interquartile range= 11.4 to 17.4 years]; 44% male; 18% African American; 62% with body mass index ≥85th percentile) had higher scores (more aligned with dietary recommendations) for total HEI-2015 (DS: 52.7 [interquartile range= 46.8 to 58.6] vs controls: 45.1 [interquartile range= 39.5 to 55.0]; P < 0.0001). Youth with DS also had higher HEI-2015 component scores for fruits, greens/beans, dairy, refined grains, and saturated fats, but lower whole grains and sodium scores. Within the group with DS, total HEI-2015 was not significantly associated with CMR measures. Whereas HEI-2015 in the DS group was negatively associated with fasting glucose levels, the difference did not meet the set level of statistical significance (-0.14, 95% CI -0.29 to 0.00; P= 0.053). Adolescents in both the control and DS groups reported low-quality diets, although the DS group had HEI-2015 scores more closely aligned with recommendations. In the DS group, diet quality was not significantly associated with CMR factors. Although further research is needed, these results suggest that dyslipidemia in youth with DS may not be related to dietary intake.

Health Equity in Sickle Cell Research and Access to Therapy

Health Equity in Sickle Cell Research and Access to Therapy

Implications of Perioperative Polypharmacy in Adolescents Undergoing Bariatric Surgery: a Single-Center Experience.

Adolescents seeking bariatric surgery may present with pre-existing psychiatric diagnoses for which they use chronic medications. To heighten awareness concerning perioperative polypharmacy in adolescents with extreme obesity, we conducted a retrospective review of patients undergoing laparoscopic sleeve gastrectomy between February 2010 and May 2017 at Children's National Health System (CNHS). A total of 167 adolescent patients had pre-existing psychiatric diagnoses which included depression (50%), anxiety (23%), ADHD (23%), and binge eating disorder (11%). Medications prescribed to treat these diagnoses included selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Additionally, all patients were given fentanyl, ondansetron, morphine, and acetaminophen perioperatively. Although no life threatening symptoms of drug-drug interactions (DDIs) were appreciated, the combined use of many different potent drugs in these patients warrants attention.

Assessment of the Need for Immediate Trauma Team Presence for Infants Presenting in Cardiac Arrest

Out-of-hospital cardiac arrest (OHCA) is rare in infants, with the cause of arrest often unknown upon presentation. Nonaccidental trauma is a potential etiology of OHCA among infants, but its occult presentation makes this etiology challenging to diagnose. In the absence of apparent injuries, identifying the need for trauma team activation is difficult during the initial resuscitation of infants with OHCA. We performed a retrospective chart review of infants younger than 1 year old who presented to Children's National Health System from 2012 to 2016 with cardiopulmonary resuscitation in progress. Medical records and the trauma registry were reviewed for relevant resuscitation information. Autopsy records provided the cause and manner of death, contributing factors to death, and evidence of injury. Among 592 infants undergoing resuscitation during the study period, 34 infants (5.7%) presented in cardiac arrest. The average age on presentation was 101.2 days (standard deviation 78.7). Most of the patients (n = 32, 94.1%) died in the emergency department, with none surviving to discharge. Among the 32 infants for whom autopsy records were available, the cause of death was nonaccidental trauma in one patient (3.1%). Infant OHCA had poor outcomes, with trauma as a rare etiology. In the absence of external signs of injury or known injury mechanism, immediate trauma team presence was not beneficial for these infants during the initial resuscitation phase.

Improving antibiotic prescribing in the emergency department for uncomplicated community-acquired pneumonia.

The Pediatric Infectious Disease Society (PIDS) and Infectious Disease Society of America (IDSA) published an evidence-based guideline for the treatment of uncomplicated community-acquired pneumonia (CAP) in children, recommending aminopenicillins as the first-line therapy. Poor guideline compliance with 10%-50% of patients admitted to the hospital receiving narrow-spectrum antibiotics has been reported. A new clinical practice guideline (CPG) was implemented in our emergency department (ED) for uncomplicated CAP. The aim of this study was to examine baseline knowledge and ED provider prescribing patterns pre- and post-CPG implementation. Prior to CPG-implementation, an anonymous case-based survey was distributed to evaluate knowledge of the current PIDS/IDSA guideline. A retrospective chart review of patients treated in the ED for CAP from January 2015 to February 2017 was performed to assess prescribing patterns for intravenous (IV) antibiotics in the ED at Children's National Health System pre- and post-CPG implementation. ED providers were aware of the PIDS/IDSA guideline recommendations, with 86.4% of survey responders selecting ampicillin as the initial antibiotic of choice. However, only 41.2% of patients admitted to the hospital with uncomplicated CAP pre-CPG received ampicillin (P<0.01). There was no statistically significant increase in ampicillin prescribing post-CPG (P=0.40). Providers in the ED are aware of the PIDS/IDSA guideline regarding the first-line therapy for uncomplicated CAP; however, this knowledge does not translate into clinical practice. Implementation of a CPG in isolation did not significantly change prescribing patterns for uncomplicated CAP.

Real-World Use of Emicizumab in Patients with Hemophilia with and without Inhibitors

Introduction Emicizumab is a recombinant humanized monoclonal antibody that bridges factor IXa and Factor Xa and is administered via subcutaneous injection. After initial FDA approval for patients with hemophilia A (HA) and inhibitors, it was approved in October 2018 for prophylaxis in patients with HA without inhibitors of all ages. In clinical trials of subjects without inhibitors, emicizumab was studied only in those &gt;12 years of age. The primary objective of this study was to report our "real-world", post-licensure experience with emicizumab across a more heterogenous patient population, comparing annualized bleeding rates prior to and after initiating emicizumab. Secondary objectives included evaluating for serious adverse events including death, thrombosis or drug discontinuation. Methods We conducted a multi-center observational study at 3 federally funded Hemophilia Treatment Centers: Children's Hospital of Philadelphia, Virginia Commonwealth University and Children's National Health System. Inclusion criteria included patients with HA initiated on emicizumab prior to May 15th 2019. Data extraction included: demographics, diagnosis, prior HA history (inhibitor, prophylaxis treatment regimen), emicizumab dosing data, bleeding events (all bleeds, treated bleeds, joint bleeds, traumatic bleeds) and thrombotic events from the 6 months prior to emicizumab until July 15th 2019. Annualized bleeding rates (ABR) were calculated to account for variable follow up. Wilcoxon Sign-Rank Difference Test was used to test the difference in number of bleeds and McNemar's test was used to test the difference in proportions of patients with ABR=0. Results Ninety-two patients met inclusion criteria: 89 male and 89 with severe HA (3 moderate HA) (Table 1). Age at initiation of emicizumab ranged from 5 weeks to 55 years; median 8.6 yrs (IQR 4.8-13.5 yrs). Nineteen patients had an active inhibitor at the time of starting emicizumab; the remaining 73 did not have an inhibitor, and most (86%) were on prophylaxis prior to emicizumab. Sixty-two patients were &lt; 12 years of age (13 with inhibitors). Median duration of emicizumab therapy was 48 weeks (inhibitors) and 22 weeks (non-inhibitors), with a total follow up of 53.3 patient years. In patients with inhibitors, the ABR (treated bleeds) prior to emicizumab was 6.2 events (95% CI, 0.98 to 11.4) compared to 0.3 events (95% CI, 0 to 0.73) on emicizumab, p=0.002. In subjects without inhibitors, the ABR prior to emicizumab was 1.8 events (95% CI, 0.66 to 2.96) compared to 0.22 events (95% CI, 0.05 to 0.39) on emicizumab, p&lt;0.001. Additional data on bleeding events is provided in Table 1. The proportion of patients with ABR=0 increased in both inhibitor (from 46% to 74%, p=0.06) and non-inhibitor subjects (from 60 to 78%, p=0.015). All patients received 1.5 mg/kg weekly x 4 loading doses, followed by either weekly (27%), every other week (70%), or monthly (3%) dosing; patients with inhibitors were more likely to receive weekly dosing. No patients who initiated emicizumab discontinued the drug or developed a neutralizing antibody to FVIII or emicizumab, although patients have not been consistently screened for these antibodies. No thrombotic or thrombotic microangiopathy events or death have occurred. Conclusions Our favorable clinical experience with emicizumab post-licensure in patients with HA is similar to that reported in the clinical trials. Although excluded from the clinical trials, patients with HA without inhibitors &lt; 12 years accounted for the majority (67%) of our cohort. As anticipated, these younger patients appear to experience the same benefit as patients &gt; 12. No serious drug-related adverse events were reported, although the overall study period is relatively short. Ongoing follow up of these patients, and others, will be important to assess the ongoing safety and efficacy profile of this novel therapy. Updated data on this cohort will be presented at the ASH meeting Disclosures Guelcher: NovoNordisk: Other: Advisory Board; Octapharma: Other: Advisory Board; Takeda: Other: Advisory Board; Genetech: Other: Advisory Board. Butler:pfizer: Other: Advisory board; Hema-Biologics: Consultancy; genetech: Other: Advisory board. Guerrera:Genetech: Other: Advisory Board; Kendrion: Other: Advisory Board; Shire: Other: Advisory Board; Bayer: Other: Advisory Board; Bioverativ: Consultancy; Pfizer: Other: Advisory Board; Novo Nordisk: Consultancy. Raffini:Roche: Other: Advisory Board; Bayer: Other: Advisory Board; CSL Behring: Other: Advisory Board.

Peri-Procedural Management and Outcomes of Patients with Hemophilia on Emicizumab Prophylaxis

Introduction Emicizumab is a recombinant humanized monoclonal antibody that bridges factor IXa and Factor X and is administered via subcutaneous injection. It provides protection against bleeding in patients with hemophilia A (HA) with and without inhibitors of all ages. Since licensure, the use of emicizumab has increased across hemophilia treatment centers (HTCs). Management of patients on this drug who require procedures has not been well established. The objective of this study was to report peri-procedural hemostasis management as well as bleeding and thrombotic outcomes in a heterogenous group of patients with HA on emicizumab requiring interventional procedures. Methods We conducted a multi-center observational study at 3 federally funded Hemophilia Treatment Centers: Children's Hospital of Philadelphia, Virginia Commonwealth University and Children's National Health System. Inclusion criteria included patients with HA initiated on emicizumab prior to May 15th 2019 that underwent a surgical, dental or interventional procedure prior to July 15, 2019. Data extraction included: demographics, diagnosis, inhibitor, emicizumab dosing data, surgery type, factor used during surgery, and bleeding or thrombotic complications during or after surgery. Results There were a total of 19 procedures in 19 subjects during the study period. 18 were male and all had severe HA. Age at initiation of emicizumab in this cohort ranged from 5 weeks to 27 years; median 5.7 (IQR) yrs. There were 6 patients with an active inhibitor at the time of emicizumab initiation. All patients received emicizumab 3.0 mg/kg weekly x 4 loading doses, followed by either weekly (8), every other week (10), or monthly (1) dosing. There were 18 minor procedures during the study period (14 port removals and one of each of the following: PE tube removal, laparoscopic inguinal hernia repair, arthroscopy, and dental extraction) and one major procedure (intracranial ventricular shunt revision )(Table 1). Of the 14 port removals, 5 patients (1 with inhibitor) did not receive pre-procedure factor replacement; the other 7 received rVIIa or factor VIII pre-procedure and 2 of these patients received a subsequent dose as part of their plan. Three of the 14 patients that underwent port removal (one with inhibitor) were noted to have swelling and hematoma at the surgical site 1-2 days post-op and received 1-2 doses of subsequent factor to treat these bleeding events; only one of these patients did not receive pre-procedure factor. The patient who underwent major surgery received multiple doses of FVIII (to keep FVIII levels &gt;50% x 1 week) and did not have bleeding complications. There were no thrombotic complications. Conclusions In general, the 19 patients with HA who required procedures while on emicizumab did well. Port removal was the most common procedure, which was not surprising given the transition from intravenous to subcutaneous prophylaxis. There was variation in practice, particularly in regard to the need for clotting factor prior to port removal. Most patients did well with 0-1 treatments prior to minor procedures, and no additional replacement. Although 3 of the 14 patients required 1-2 unplanned infusions of clotting factor post port removal, there was no clear relationship between pre-procedure factor replacement and post-procedure port hematoma. This observational study provides useful information for providers who manage patients with HA on emicizumab, although larger studies are clearly needed to help determine best practice. Disclosures Guelcher: Takeda: Other: Advisory Board; Octapharma: Other: Advisory Board; Genetech: Other: Advisory Board; NovoNordisk: Other: Advisory Board. Butler:Hema-Biologics: Consultancy; pfizer: Other: Advisory board; genetech: Other: Advisory board. Guerrera:Bioverativ: Consultancy; Novo Nordisk: Consultancy; Pfizer: Other: Advisory Board; Bayer: Other: Advisory Board; Shire: Other: Advisory Board; Kendrion: Other: Advisory Board; Genetech: Other: Advisory Board. Raffini:Roche: Other: Advisory Board; CSL Behring: Other: Advisory Board; Bayer: Other: Advisory Board.

Prevalence of unsuspected abnormal echocardiograms in adolescents with down syndrome.

The purpose of this article is to describe the prevalence of cardiac disease previously undiagnosed in healthy asymptomatic children and adolescents with Down syndrome (DS). Subjects with DS ages 10-20 years were recruited from two sites, the Children's Hospital of Philadelphia (Philadelphia, PA) and Children's National Health System (Washington, DC) for a cross-sectional study of body composition and cardiometabolic risk. Echocardiographic and clinical data were collected from patients enrolled in the parent study of cardiometabolic risk. Nine (6%) new cardiac diagnoses were identified out of 149 eligible patients. All new findings resulted in outpatient referrals to pediatric cardiology. Current guidelines recommend screening all newborns with DS for congenital heart disease. Older patients with DS may benefit from rescreening.

Coordination of the Fetal Medicine Institute and the Cleft and Craniofacial Center: Application to Early Management of Infants With Cleft Lip and Palate.

The primary objective of this study is to describe the authors' experience at the Children's National Health System with the coordination of the Fetal Medicine Institute and the Cleft and Craniofacial Center. This collaboration highlights the accuracy and completeness of prenatal diagnosis of cleft abnormalities with expedient postnatal management. With Institutional Review Board approval, the authors retrospectively reviewed 74 patients referred for potential orofacial cleft and 44 met the inclusion criteria. Follow-up fetal ultrasonography is typically performed and three-dimensional imaging was performed when feasible. If questionable anomalies or facial findings are present on these studies, the authors proceed with fetal magnetic resonance imaging. A thorough consultation is held with the cleft team, resulting in a comprehensive plan of care. Postnatal examination confirmed the correct prenatal diagnosis in nearly all patients. Sensitivity and specificity for isolated unilateral cleft lip were 89% and 100%, respectively; for unilateral cleft lip and palate, sensitivity and specificity were 82% and 90%, respectively; for bilateral cleft lip and palate, sensitivity and specificity were 97% and 90%, respectively. Initial postnatal evaluation by the cleft surgeon occurred at an average age of 21 days after birth. All patients who were candidates for presurgical orthodontia were treated at an appropriate young age (mean: 66.5 days). Coordinated prenatal evaluation of patients with cleft lip/palate by multidisciplinary centers plays an important role in the care of these complex patients. The results of the authors' study demonstrated high sensitivity and specificity for the prenatal diagnosis of cleft lip/palate, leading to timely postnatal evaluation and treatment.

Fever of unknown origin: a retrospective review of pediatric patients from an urban, tertiary care center in Washington, DC.

Fever of unknown origin (FUO) continues to challenge clinicians to determine an etiology and the need for treatment. This study explored the most common etiologies, characteristics, and average cost of hospitalization for FUO in a pediatric population at an urban, tertiary care hospital in Washington, DC. Records from patients admitted to Children's National Health System between September 2008 and April 2014 with an admission ICD-9 code for fever (780.6) were reviewed. The charts of patients 2-18years of age with no underlying diagnosis and a temperature greater than 38.3 ºC for 7days or more at time of hospitalization were included. Final diagnoses, features of admission, and total hospital charges were abstracted. 110 patients qualified for this study. The majority of patients (n = 42, 38.2%) were discharged without a diagnosis. This was followed closely by infection, accounting for 37.2% (n = 41) of patients. Rheumatologic disease was next (n = 16, 14.5%), followed by miscellaneous (n = 6, 5.4%) and oncologic diagnoses (n = 5, 4.5%). The average cost of hospitalization was 40,295 US dollars. This study aligns with some of the most recent publications which report undiagnosed cases as the most common outcome in patients hospitalized with FUO. Understanding that, often no diagnosis is found may reassure patients, families, and clinicians. The cost associated with hospitalization for FUO may cause clinicians to reconsider inpatient admission for diagnostic work-up of fever, particularly given the evidence demonstrating that many patients are discharged without a diagnosis.

Immunotherapy Trials at Children's National Health System Offer Greater Access for Patients of Diverse Backgrounds

Background Cellular therapy offers an innovative, personalized alternative to traditional therapeutics aimed to treat cancer and viral infections. Often offered in experimental clinical trials, in 2016 a New York Times article argued that immunotherapy is reserved primarily for white patients due to barriers to access. Two prominent immunotherapy trials cited in the article reported 92% and 88% enrollment of white patients, while minority patients represented 9% and 10% of enrollment, respectively. Purpose To examine the races, ethnicity, and gender of patients enrolled in clinical cell therapy trials at Children's National, Washington DC to determine if the enrollment is representative of the current US population. Methods Demographic data was analyzed from databases obtained from IRB-approved cell therapy clinical trials initiated at our Institution. Results/Conclusions Of the patients (between ages of 1 and 64) enrolled into cell therapy clinical trials, 56% identified racially as white (n=95), while 20% identified as black (n=33), 9% as Asian (n=9), 19% as other (n=20), and 3% as unknown (n=5). Among the patients who reported race, 18% identified ethnically as Hispanic (n=31). By sex, 50% were male (n=85) and 50% were female (n=84). In the 2015 US census, 77% of participants identified racially as white, 13.3% as black, and 5.6% as Asian. As per the census, 17% of those surveyed identified ethnically as Hispanic. This stands in contrast to 2 published adult centered cell therapy studies mentioned in the New York Times in which 92% and 88% of patients were identified as white and minorities only constituted

Utilization of a Dual Surveillance Program to Reduce Surgical-site Infections.

Background:Surveillance plays a pivotal role in the surgical-site infections (SSIs) prevention through identifying infections, monitoring changes in infection rates, and evaluating the effectiveness of intervention strategies.Methods:This retrospective study reviewed SSI surveillance systems implemented at the Children’s National Health System in 3 phases between 2007 and 2016 including all surgical procedures. The targeted surveillance was conducted in cardiovascular, spinal fusion, and ventricular shunt surgeries and required an infection preventionist (IP) to review all procedures, to identify SSIs that meet the CDC’s National Healthcare Safety Network definition. SSIs in the remaining surgical procedures were identified through the review of positive microbiology reports daily and followed by full chart review if the specimen type and/or patient location were suggestive of a surgical history. Timely feedback of SSI to stakeholders was the primary mode of intervention, with additional interventions implemented for the 3 targeted surveillance procedures. Data collected between 2013 and 2016 were analyzed to account for a definition change in 2013.Results:For the 3 targeted surveillance procedures, IP reviewed 2,255 procedures and identified 43 SSIs. For the remaining procedures, IPs identified 123 SSIs confirmed by one or more pathogens. The overall SSI rate had a 31% decrease. The cardiovascular and spinal fusion SSI rate had a 61% and 84% decrease, respectively. The ventricular shunt SSI rate increased 29% due to 2 episodes of recurrent infections in 2 patients.Conclusions:It is prudent for hospitals to continue monitoring SSI by establishing surveillance programs with optimal approaches.

High Rates of Community and Hospital Acquired Infections in Patients with Cellular Immunodeficiencies.

Patients with primary immunodeficiency diseases (PID) are perceived to be at high risk for acquiring as well as developing complications from infections. There is little data describing the infection type and frequency these patients may acquire in the community or during hospital admissions. Data is critically needed in order to inform best practices on how to protect these vulnerable patients. This is a retrospective study which included PID patients who were discharged from Children's National Health System (CNHS) from January 1, 2011, through August 31, 2017, and were assigned a discharge diagnosis code indicating PID. Hospitalizations that occurred in the study period were reviewed to extract information on the type of infections upon admission and during hospitalization. The rate of hospital acquired infections (HAIs) was calculated by the number of HAIs divided by the total number of days between date of admission and date of discharge or receiving the first bone marrow transplant, whichever the one came first. The rates were then compared to the HAI rate among oncology patients receiving treatment at CNHS during the same study period. During this study period, 33 PID patients were admitted 80 times for a total of 1855 patient days. Of these 80 admissions, 31 were due to an infection. Ten of the 31 admissions with severe combined immunodeficiency disease (SCID) were infection related, 4/4 in ectodermal dysplasia with immunodeficiency due to gain of function mutation (IkappaBalpha) patients, 8/10 in Wiskott-Aldrich patients, 1/2 in STAT3 mutation patients, 1/1 in Hyper IGM patient, 1/5 in severe chronic active EBV (SCAEBV) patients, 1/1 NK defect, 2/21 in primary hemophagocytic lymphohistiocytosis patients, 3/4 chronic granulomatous disease, and 0/1 congenital neutropenia. HAI occurred in 11 out of 80 admissions (13.75%). Patients with SCID had the highest HAI rate of 13.09 per 1000 patient days, followed by SCAEBV (11.10), IkappaBalpha (6.58), and Wiskott-Aldrich (4.91). Comparing to oncology patients in which the HAI rate was 0.92 per 1000 patient days. SCID patients had 11.7 (95% confidence interval 3.7-29; p < 0.001) and T cell defects excluding SCID had 4.8 (95% CI 1.0-14.8; p = 0.03) times greater risk of acquiring an infection during a hospitalization. Patients with severe T cell defects such as SCID are at greater risk for infections in the community and in hospital settings. Additional infection prevention measures are likely needed when caring for these patients in a clinic or as an inpatient. Further studies are urgently needed to determine the most appropriate measures for these patients.

Relationship of Pulmonary Outcomes, Microbiology, and Serum Antibiotic Concentrations in Cystic Fibrosis Patients.

To determine the frequency of subtherapeutic exposure to intravenously administered β-lactam antibiotics in a cohort of cystic fibrosis (CF) patients who were treated for a pulmonary exacerbation, and its impact on pulmonary function. Nineteen CF patients between the ages of 5 and 21 years treated at Children's National Health System for a pulmonary exacerbation were followed between March 2015 and August 2016 in a prospective, longitudinal study. Pharmacokinetic modeling and minimum inhibitory concentrations (MICs) of the involved pathogens were used to determine therapeutic or subtherapeutic β-lactam antibiotic exposure based on the time the antibiotic concentration was above the MIC. Clinical outcomes were measured by spirometry values. The 19 participants were treated with a total of 29 courses of antibiotics. The most common β-lactam antibiotics used in a treatment course were ceftazidime (62%) and meropenem (45%). There was no difference in age, CF genotype, or creatinine clearance between the 9 participants (47%) who reached therapeutic concentrations versus the 10 (53%) who did not. Those who achieved sufficiently high antibiotic exposure had more significant improvement of their pulmonary function tests. We found that sufficient antibiotic exposure during treatment of CF pulmonary exacerbations was associated with improved pulmonary function. Moreover, it was impossible to predict, solely from the dosing regimen used, which patients were going to reach therapeutic β-lactam antibiotic serum concentrations. This suggests that CF patients may benefit from closer monitoring of their β-lactam exposure and bacterial MIC for optimal clinical outcomes.

10,000 Good Catches: Increasing Safety Event Reporting In A Pediatric Health Care System.

Background:In 2014, Children’s National Health System’s executive leadership team challenged the organization to double the number of voluntary safety event reports submitted over a 3-year period; the intent was to increase reliability and promote our safety culture by hardwiring employee event reporting.Methods:Following a Donabedian quality improvement framework of structure, process, and outcomes, a multidisciplinary team was formed and areas for improvement were identified. The multidisciplinary team focused on 3 major areas: the perceived ease of reporting (ie, how difficult is it to report an event?); the perceived safety of reporting (ie, will I get in trouble for reporting?); and the perceived impact of reporting (ie, does my report make a difference?) technology, making it safe to report, and how reporting makes a difference. The team developed a key driver diagram and implemented interventions designed to impact the key drivers and to increase reporting.Results:Children’s National increased the number of safety event reports from 4,668 in fiscal year 2014 to 10,971 safety event reports in fiscal year 2017. Median event report submission time was decreased by nearly 30%, anonymous reporting decreased by 69%, the number of submitting departments increased by 94%, and the number of reports submitted as “other” decreased from a baseline of 6% to 2%.Conclusions:Children’s National Health System’s focus on increasing safety event reporting resulted in increased organizational engagement and attention. This initiative served as a tangible step to improve organizational reliability and the culture of safety and is readily generalizable to other hospitals.

2017 Visionary Leader: Maureen Maurano.

The following manuscript is the winning 2017 Richard Hader Visionary Leader Award entry submitted to Nursing Management in recognition of Maureen Maurano, BSN, RN, nurse manager of the neonatal intensive care unit at Children's National Health System in Washington, D.C. Ms. Maurano was formally recognized for her achievements before the Keynote Address at Congress2017, October 4, in Las Vegas, Nev. There, she received the award, sponsored by Hackensack Meridian Health.

Newborn Care Curriculum: The Late Preterm Infant in the Level II Neonatal Intensive Care Unit.

Late preterm births represent the largest category of preterm deliveries. Although these infants are frequently managed in normal newborn nurseries, they have an increased risk of readmissions and mortality. Thus, we designed this PowerPoint-based learning module to provide learners with a computer-based educational resource on late preterm infants in the level II neonatal intensive care unit. This module can be completed using the included pretest and posttest to assess for change in knowledge. The module should take approximately 20 to 30 minutes to complete. Between May and June of 2016, members of the pediatric hospitalist division at Children's National Health System in Washington, DC participated in a study of the module as a self-directed learning tool and completed the pretest, posttest, and postmodule evaluation forms. There was an overall increase in knowledge, with an increase in posttest score from 64% to 94%. Furthermore, this module was well-received by learners, as 55% of learners agreed or strongly agreed that the material presented in the module would change their clinical practice, and 100% agreed or strongly agreed that the module increased their comfort with teaching on this topic. Initial implementation of the module indicates it could be a valuable tool to address a perceived educational need in the area of late preterm infant care in the level II neonatal intensive care unit.

Targeted Education after an Emergency Department Visit Increases Hydroxyurea Initiation in Children with Sickle Cell Anemia

Introduction: Hydroxyurea decreases many complications of sickle cell anemia (SCA) but is underused in treatment-eligible patients. Barriers to hydroxyurea initiation occur on the health care system, provider, and patient level. Novel strategies to increase hydroxyurea use in patients with SCA are needed. To address this challenge at our center, we implemented the Quick Start Hydroxyurea Initiation Project (Q-SHIP).Methods: Patients with SCA were eligible to participate in Q-SHIP if they presented to the Children's National Health System (CNHS) emergency department (ED) for pain or acute chest syndrome and were not taking hydroxyurea. Patients <9 months old, on chronic transfusions, pregnant, or not followed by CNHS hematology were excluded. Eligible patients were referred to a weekly Q-SHIP clinic visit focused on hydroxyurea education and were offered initiating treatment at the visit's conclusion. Participants completed a pre-session questionnaire, discussed hydroxyurea with a hematologist using a handbook developed by CNHS, and watched videos featuring patients and parents of children with SCA sharing their experience with hydroxyurea. Subjects were classified as starting hydroxyurea if they had a clinic visit for hydroxyurea monitoring within 3 months of participation in a Q-SHIP session.Results: Over 13 months (2/1/2016 - 3/31/2017) 65 eligible patients participated in Q-SHIP a median of 5 days (IQR 2, 20 days) after ED or hospital discharge. Although 44% (28/64) of participants reported no previous hydroxyurea offer, provider clinic documentation indicated that 61% (17/28) of these families had declined a previous hydroxyurea offer. After Q-SHIP, 55% (36/65) of participants started hydroxyurea. Subjects who started hydroxyurea after Q-SHIP were similar to those who did not, except subjects who started were more likely have a history of an intensive care unit admission (Table 1). After a median follow-up of 11 months, 81% (29/36) of participants who started hydroxyurea after Q-SHIP continued on therapy. Among Q-SHIP participants continuing treatment, mean corpuscular volume increased by a median of 8.6 fL (IQR +5.4, +17.7, p<0.0001) and hemoglobin F increased by a median of 5.8% (IQR +3.0, +11.3, p<0.001). One year after implementation of Q-SHIP, the proportion of treatment-eligible patients with SCA who presented to the ED with pain or ACS who were receiving hydroxyurea increased; February 2016: 56% (32/57) vs. February 2017: 73% (43/59), p=0.059.Conclusion: Addressing indications for hydroxyurea therapy in a clinic encounter exclusively for this purpose soon after a SCA complication is a meaningful time to meet with families of children with SCA to initiate treatment. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

RON Kinase Inhibition Reduces Renal Endothelial Injury in Sickle Cell Disease Mice

BACKGROUND: Patients with Sickle Cell Disease (SCD) have an approximately three-fold higher risk of developing chronic kidney disease (CKD) than the general population. Endothelial dysfunction and inflammation which are induced by hemolysis and lead to vasculopathy are major mechanisms in the development of CKD. Red blood cells (RBCs) hemolysis inside the renal tissue stimulates macrophages infiltration. Endocytosis of RBC hemolysis products by infiltrating macrophages activates to MT-SP1 protease which cleaves and activates non-active circulating Macrophage Stimulating Protein 1 (MSP1). MSP1 binds to and activates cell surface receptor tyrosine kinase, recepteur d'origine nantais (RON).OBJECTIVES: To determine the role of RON in the development of renal endothelial injury.METHODS: Human renal glomerular endothelial cells (HGEC) and a mouse model of SCD (Townes) were used. The animal protocol was approved by the Institutional Animal Care and Use Committee at the Children's National Health System. The SCD mice express human Hgb S and Hgb F. Control mice express human Hgb A1. Two-month-old mice were injected with 10 mg/kg of body weight of RONi (BSM-777607, Santa Cruz Scientific), an inhibitor of RON, subcutaneously daily for 14 consecutive days. Kidneys were collected, and paraffin-embedded sections were used for H&E and PAS staining, and immunostaining.RESULTS: Treatment of cultured human renal glomerular endothelial cells (HGEC) with MSP1 activated RON receptor and induced downstream signaling evidenced by increased phosphorylation of ERK and AKT kinases. RONi significantly reduced ERK and AKT phosphorylation. MSP1 treatment also increased motility of HGEC, and expression of F-actin and von Willebrand Factor (vWF). Renal disease in SCD mice was characterized by glomerular hypertrophy, capillary dilation and congestion, and significant endothelial injury demonstrated by H&E and PAS staining, and ICAM, vWF and CD34 immunostaining. We observed accumulation of MSP1 in the glomerular capillaries of SCD mice. Treatment of mice with RONi significantly reduced glomerular hypertrophy, capillary dilation and congestion, and also reduced endothelial injury (Figure 1).CONCLUSIONS: Renal glomerular accumulation of MSP1 and RON kinase activation contribute to the induction of renal endothelial injury in SCD mice. Inhibition of RON kinase activation significantly reduced endothelial injury and development of kidney disease.ACKNOWLEDGMENTS: This work was supported by NIH Research Grants 1P50HL118006, 1R01HL125005 and 5G12MD007597. The content is solely the responsibility of the authors and does not necessarily represent the official view of NHLBI, NIMHD or NIH. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

An initial cost-effectiveness analysis of intraoperative magnetic resonance imaging (iMRI) in pediatric epilepsy surgery.

Previous studies have illustrated the clinical utility of the addition of intraoperative magnetic resonance imaging (iMRI) to conventional microsurgical resection. While iMRI requires initial capital cost investment, long-term reduction in costly follow-up management and reoperation costs may prove economically efficacious. The objective of this study is to investigate the cost-effectiveness of the addition of iMRI utilization versus conventional microsurgical techniques in focal cortical dysplasia (FCD) resection in pediatric patients with medically refractory epilepsy. We retrospectively reviewed the medical records of pediatric subjects who underwent surgical resection of FCD at the Children's National Health System between March 2005 and April 2015. Patients were assigned to one of three cohorts: iMRI-assisted resection, conventional resection with iMRI-assisted reoperation, or conventional resection. Direct costs included preoperative, operative, postoperative, long-term follow-up, and antiepileptic drug (AED) costs. The cost-effectiveness was calculated as the sum total of all direct medical costs over the quality-adjusted life years (QALYs). We also performed sensitivity analysis on numerous variables to assess the validity of our results. Fifty-six consecutive pediatric patients underwent resective surgery for medically intractable FCD. Ten patients underwent iMRI-assisted resection; 7 underwent conventional resection followed by iMRI-assisted reoperation; 39 patients underwent conventional microsurgical resection. Taken over the lifetime of the patient, the cumulative discounted QALY of patients in the iMRI-assisted resection cohort was about 2.91years, versus 2.61years in the conventional resection with iMRI-assisted reoperation cohort, and 1.76years for the conventional resection cohort. Adjusting for inflation, iMRI-assisted surgeries have a cost-effectiveness ratio of $16,179 per QALY, versus $28,514 per QALY for the conventional resection with iMRI-assisted reoperation cohort, and $49,960 per QALY for the conventional resection cohort. Sensitivity analysis demonstrated that no one single variable significantly altered cost-effectiveness across all three cohorts compared to the baseline results. The addition of iMRI to conventional microsurgical techniques for resection of FCD in pediatric patients with intractable epilepsy resulted in increased seizure freedom and reduction in long-term direct medical costs compared to conventional surgeries. Our data suggests that iMRI may be a cost-effective addition to the surgical armamentarium for epilepsy surgery.