Childrens Hospital of PhiladelphiaPA

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Grover S.A.,University of Toronto | Aubert-Broche B.,Montreal Neurological Institute | Fetco D.,Montreal Neurological Institute | Collins D.L.,Montreal Neurological Institute | And 5 more authors.
Neurology | Year: 2015

Objective: To evaluate the association between physical activity (PA) and multiple sclerosis (MS) disease activity, depression, and fatigue in a cohort of children with MS and monophasic acquired demyelinating syndrome (mono-ADS). Methods: In this cross-sectional study of consecutive patients attending a specialized pediatric MS clinic, we administered the PedsQL Multidimensional Fatigue Scale, Center for Epidemiological Studies Depression Scale, and Godin Leisure-Time Exercise Questionnaire. Quantitative MRI analysis was performed to obtain whole brain and T2 lesion volume in a subset of participants (n 60). Results: A total of 110 patients (79 mono-ADS; 31 MS; 5-18 years; M:F 1:1.2) were included. Patients with MS reported less strenuous (33.21 ± 31.88 metabolic equivalents [METs] vs 15.97 ± 22.73 METs, p 0.002) and total (44.48 ± 39.35 METs vs 67.28 ± 59.65 METs; p 0.0291) PA than those with mono-ADS. Patients with MS who reported greater amounts of moderate PA METs had fewer sleep/rest fatigue symptoms (r -0.4). Participation in strenuous PA was associated with smaller T2 lesion volumes (r -0.66) and lower annualized relapse rate (r -0.66). No associations were found between total brain volume and participation in PA. Conclusions: Children with MS are less physically active than children with mono-ADS. Reasons for this are unclear, but may be related to ongoing disease activity, perceived limitations, or symptoms such as depression or fatigue. Children with MS reporting higher levels of strenuous PA had lower T2 lesion volumes and lower relapse rates, suggesting a potential protective effect of strenuous PA in this population. Further longitudinal studies are needed to establish the relationship of PA to MS symptoms and disease activity in this population. © 2015 American Academy of Neurology.

Donoghue A.J.,Childrens Hospital of PhiladelphiaPA | Abella B.S.,University of Pennsylvania | Merchant R.,University of Pennsylvania | Praestgaard A.,University of Pennsylvania | And 3 more authors.
Resuscitation | Year: 2015

Objectives: To compare outcomes from in-hospital cardiopulmonary resuscitation (CPR) in the emergency department (ED) for pediatric and adult patients and to identify factors associated with differences in outcomes between children and adults. Methods: Retrospective analysis of the Get With The Guidelines - Resuscitation database from January 1, 2000 to September 30, 2010. All patients with CPR initiated in the ED requiring chest compressions for ≥2. min were eligible; trauma patients were excluded. Patients were divided into children (<18. yo) and adults (≥18. yo). Patient, event, treatment, and hospital factors were analyzed for association with outcomes. Univariate analysis was performed comparing children and adults. Multivariate analysis was used to determine factors associated with outcomes. Results: 16,834 events occurred in 608 centers (16,245 adult, 537 pediatric). Adults had more frequent return of spontaneous circulation (53% vs 47%, p=. 0.02), 24. h survival (35% vs 30%, p=. 0.02), and survival to discharge (23% vs 20%, p=. NS) than children. Children were less frequently monitored (62% vs 82%) or witnessed (79% vs 88%), had longer duration (24. m vs 17. m), more epinephrine doses (3 vs 2), and more frequent intubation attempts (64% vs 55%) than adults. There were no differences in time to compressions, vasopressor administration, or defibrillation between children and adults. On multivariate analysis, age had no association with outcomes. Conclusions: Survival following CPR in the ED is similar for adults and children. While univariate differences exist between children and adults, neither age nor specific processes of care are independently associated with outcomes. © 2015 Elsevier Ireland Ltd.

Ng C.M.,Childrens Hospital of PhiladelphiaPA | Ng C.M.,University of Pennsylvania
Biopharmaceutics and Drug Disposition | Year: 2016

Purpose. The two-compartment linear model used to describe the population pharmacokinetics (PK) of many therapeutic monoclonal antibodies (TMAbs) offered little biological insight to antibody disposition in humans. The purpose of this study is to develop a semi-mechanistic FcRn-mediated IgG disposition model to describe the population PK of TMAbs in clinical patients. Methods. A standard two-compartment linear PK model from a previously published population PK model of pertuzumab was used to simulate intensive PK data of 100 subjects for model development. Two different semi-mechanistic FcRn-mediated IgG disposition models were developed and First Order Conditional Estimation (FOCE) with the interaction method in NONMEM was used to obtain the final model estimates. The performances of these models were then compared with the two-compartment linear PK model used to simulate the data for model development. Results. A semi-mechanistic FcRn-mediated IgG disposition model consisting of a peripheral tissue compartment and FcRn-containing endosomes in the central compartment best describes the simulated pertuzumab population PK data. This developed semi-mechanistic population PK model had the same number of model parameters, produced very similar concentration-time profiles but provided additional biological insight to the FcRn-mediated IgG disposition in human subjects compared with the standard linear two-compartment linear PK model. Conclusion. This first reported semi-mechanistic model may serve as an important model framework for developing future population PK models of TMAbs in clinical patients. Copyright © 2015 John Wiley & Sons, Ltd.

Arpan I.,University of Florida | Willcocks R.J.,University of Florida | Forbes S.C.,University of Florida | Finkel R.S.,Childrens Hospital of PhiladelphiaPA | And 14 more authors.
Neurology | Year: 2014

Objective: To evaluate the effects of corticosteroids on the lower extremity muscles in boys with Duchenne muscular dystrophy (DMD) using MRI and magnetic resonance spectroscopy (MRS). Methods: Transverse relaxation time (T2) and fat fraction were measured by MRI/MRS in lower extremity muscles of 15 boys with DMD (age 5.0-6.9 years) taking corticosteroids and 15 corticosteroid-naive boys. Subsequently, fat fraction was measured in a subset of these boys at 1 year. Finally, MRI/MRS data were collected from 16 corticosteroid-naive boys with DMD (age 5-8.9 years) at baseline, 3 months, and 6 months. Five boys were treated with corticosteroids after baseline and the remaining 11 served as corticosteroid-naive controls. Results: Cross-sectional comparisons demonstrated lower muscle T2 and less intramuscular (IM) fat deposition in boys with DMD on corticosteroids, suggesting reduced inflammation/damage and fat infiltration with treatment. Boys on corticosteroids demonstrated less increase in IM fat infiltration at 1 year. Finally, T2 by MRI/MRS detected effects of corticosteroids on leg muscles as early as 3 months after drug initiation. Conclusions: These results demonstrate the ability of MRI/MRS to detect therapeutic effects of corticosteroids in reducing inflammatory processes in skeletal muscles of boys with DMD. Our work highlights the potential of MRI/MRS as a biomarker in evaluating therapeutic interventions in DMD.

Wingerchuk D.M.,Mayo Medical School | Banwell B.,Childrens Hospital of PhiladelphiaPA | Bennett J.L.,University of Colorado at Denver | Cabre P.,Center Hospitalier University Of Fort Of France | And 15 more authors.
Neurology | Year: 2015

Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS. © 2015 American Academy of Neurology.

Lim S.-W.,Seoul National University | Lee H.-E.,Gachon University | Davis M.,Childrens Hospital of PhiladelphiaPA | Park K.,Seoul National University
Neurourology and Urodynamics | Year: 2016

Aims Integrating regular intermittent catheterization (IC) into daily life is essential for good medical outcomes in patients with neurogenic bladders. The goal is to identify long-term IC-related barriers, or difficulties in Korean patients with spinal dysraphism and their parents. Methods The data were prospectively collected using questionnaires from spinal dysraphism patients from two sources: an online community, and those visiting the outpatient clinic of Seoul National university hospital. The questions included were barriers in general and school life, respectively. Also, an open question was included regarding suggestions for school managers or the government in order to overcome identified IC related difficulties. Results A total of 20 patients and 40 parents answered the questionnaire. Common barriers found in general life were related to lack of places, time, or helpers to perform IC. Substantial numbers of adolescent patients also complained that IC could not be adequately performed due to problems related to privacy or lack of understanding at school. However, the number and nature of barriers varied according to the developmental stage and school environments. Almost all IC barriers seemed to be significant in adolescence. Some parents requested that the government provide space and broaden insurance coverage of catheters in order to facilitate IC. Conclusions Various perceived barriers were identified in those who need IC and differences were demonstrated over time. Both dedicated space and time are issues. In addition, patients may benefit from emotional support and enhanced communication with community agencies and government to resolve the problems related with privacy. © 2014 Wiley Periodicals, Inc.

Walsh C.M.,University of Toronto | Ling S.C.,University of Toronto | Mamula P.,Childrens Hospital of PhiladelphiaPA | Lightdale J.R.,University of Massachusetts Medical School | And 3 more authors.
Journal of Pediatric Gastroenterology and Nutrition | Year: 2015

Objectives: Validated assessment tools are required to support competency-based education. We aimed to assess the reliability and validity of the Gastrointestinal Endoscopy Competency Assessment Tool for Pediatric Colonoscopy (GiECATKIDS), an instrument developed by 41 North American experts using Delphi methodology. Methods: GiECATKIDS consists of a 7-item global rating scale (GRS) and an 18-item checklist (CL). An attending physician assessed 104 colonoscopies performed at 3 North American hospitals by 56 endoscopists, including 25 novices (<50 previous procedures), 21 intermediates (50-250), and 10 advanced endoscopists (>500). Another observer rated procedures to assess interrater reliability using intraclass correlation coefficient (ICC). Test-retest reliability was measured with ICC comparing endoscopists' first and second procedure scores. Discriminative validity was examined by comparing experience level with scores. Concurrent validity was assessed by correlating scores with colonoscopy experience, cecal and terminal ileal intubation rates, and physician global assessment. Results: Interrater reliability of the GiECATKIDS was high (total: ICC=0.88; GRS: ICC=0.79; CL: ICC=0.89). Test-retest reliability was excellent (total: ICC=0.94; GRS: ICC=0.94; CL: ICC=0.84). GiECATKIDS total, GRS, and CL scores differed significantly among novice, intermediate, and advanced endoscopists (P<0.001). There was a significant positive correlation (P<0.001) between scores and number of previous colonoscopies (total: ρ=0.91, GRS: ρ=0.92, CL: ρ=0.84), cecal intubation rate (total: ρ=0.82, GRS: ρ=0.85, CL: ρ=0.77), ileal intubation rate (total: ρ=0.82, GRS: ρ=0.82, CL: ρ=0.80), and physician global assessment (total: ρ=0.95, GRS: ρ=0.94, CL: ρ=0.89). Conclusions: The GiECATKIDS demonstrates strong reliability and validity as a measure of performance of pediatric colonoscopy that can be used to support training and assessment. © Copyright 2015 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.

Donoghue A.,Childrens Hospital of PhiladelphiaPA | Hsieh T.-C.,Childrens Hospital of PhiladelphiaPA | Myers S.,Childrens Hospital of PhiladelphiaPA | Mak A.,Tulane University | And 2 more authors.
Resuscitation | Year: 2015

Objective: To describe the adherence to guidelines for CPR in a tertiary pediatric emergency department (ED) where resuscitations are reviewed by videorecording. Methods: Resuscitations in a tertiary pediatric ED are videorecorded as part of a quality improvement project. Patients receiving CPR under videorecorded conditions were eligible for inclusion. CPR parameters were quantified by retrospective review. Data were described by 30-s epoch (compression rate, ventilation rate, compression:ventilation ratio), by segment (duration of single providers' compressions) and by overall event (compression fraction). Duration of interruptions in compressions was measured; tasks completed during pauses were tabulated. Results: 33 children received CPR under videorecorded conditions. A total of 650. min of CPR were analyzed. Chest compressions were performed at <100/min in 90/714 (13%) of epochs; 100-120/min in 309/714 (43%); >120/min in 315/714 (44%). Ventilations were 6-12 breaths/min in 201/708 (23%) of epochs and >12/min in 489/708 (70%). During CPR without an artificial airway, compression:ventilation coordination (15:2) was done in 93/234 (40%) of epochs. 178 pauses in CPR occurred; 120 (67%) were <10. s in duration. Of 370 segments of compressions by individual providers, 282/370 (76%) were <2. min in duration. Median compression fraction was 91% (range 88-100%). Conclusions: CPR in a tertiary pediatric ED frequently met recommended parameters for compression rate, pause duration, and compression fraction. Hyperventilation and failure of C:V coordination were very common. Future studies should focus on the impact of training methods on CPR performance as documented by videorecording. © 2015 Elsevier Ireland Ltd.

Lasa J.J.,Texas Childrens Hospital | Rogers R.S.,Childrens Hospital of PhiladelphiaPA | Localio R.,Childrens Hospital of PhiladelphiaPA | Shults J.,Childrens Hospital of PhiladelphiaPA | And 8 more authors.
Circulation | Year: 2016

Background - Although extracorporeal cardiopulmonary resuscitation (E-CPR) can result in survival after failed conventional CPR (C-CPR), no large, systematic comparison of pediatric E-CPR and continued C-CPR has been reported. Methods and Results - Consecutive patients <18 years old with CPR events ≥10 minutes in duration reported to the Get With the Guidelines-Resuscitation registry between January 2000 and December 2011 were identified. Hospitals were grouped by teaching status and location. Primary outcome was survival to discharge. Regression modeling was performed, conditioning on hospital groups. A secondary analysis was performed with the use of propensity score matching. Of 3756 evaluable patients, 591 (16%) received E-CPR and 3165 (84%) received C-CPR only. Survival to hospital discharge and survival with favorable neurological outcome (Pediatric Cerebral Performance Category score of 1-3 or unchanged from admission) were greater for E-CPR (40% [237 of 591] and 27% [133 of 496]) versus C-CPR patients (27% [862 of 3165] and 18% [512 of 2840]). Odds ratios (ORs) for survival to hospital discharge and survival with favorable neurological outcome were greater for E-CPR versus C-CPR. After adjustment for covariates, patients receiving E-CPR had higher odds of survival to discharge (OR, 2.80; 95% confidence interval, 2.13-3.69; P<0.001) and survival with favorable neurological outcome (OR, 2.64; 95% confidence interval, 1.91-3.64; P<0.001) than patients who received C-CPR. This association persisted when analyzed by propensity score-matched cohorts (OR, 1.70; 95% confidence interval, 1.33-2.18; P<0.001; and OR, 1.78; 95% confidence interval, 1.31-2.41; P<0.001, respectively]. Conclusion - For children with in-hospital CPR of ≥10 minutes duration, E-CPR was associated with improved survival to hospital discharge and survival with favorable neurological outcome compared with C-CPR. © 2015 American Heart Association, Inc.

Martin M.,Childrens Hospital Of Philadelphiapa | Haines D.,Childrens Hospital And Research Center Oaklandca
Clinical Journal of Oncology Nursing | Year: 2016

Background: Thalassemia is a chronic inherited blood disorder that reduces hemoglobin production, causing chronic hemolytic anemia. Patients often are diagnosed via newborn screening programs. Patients diagnosed with the most severe form of thalassemia often require chronic red blood cell transfusions to control their anemia. The side effect of chronic transfusions is cumulative iron overload for which chelation therapy is required. The incidence of thalassemia is low; therefore, care is best delivered at specialized treatment centers that offer multidisciplinary coordination. Objectives: This article reviews the diagnosis, management, and curative options for thalassemia. Methods: This review follows a hypothetical patient with thalassemia and his family through the major stages of the disease: diagnosis, treatment, long-term monitoring, and continued support from childhood through adulthood. Findings: Increasing knowledge about thalassemia and its management among healthcare providers can improve patient outcomes and quality of life. © 2016 by the Oncology Nursing Society.

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