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Watson J.R.,Ohio State University | Hains D.S.,Childrens Foundation Research Institute | Cohen D.M.,Ohio State University | Spencer J.D.,Ohio State University | And 3 more authors.
Pediatric Research | Year: 2016

Background: Pediatricians frequently use urinalysis to diagnose urinary tract infection (UTI) while awaiting urine culture results, but sensitivity and specificity of urinalysis are limited. This study evaluated the diagnostic accuracy of the antimicrobial peptides (AMPs) human α-defensin 5 (HD5) and human neutrophil peptides (HNP) 1-3 as novel UTI biomarkers in children. Methods: We prospectively enrolled 199 pediatric Emergency Department or Urgent Care patients evaluated for a UTI. Urine concentrations of HD5 and HNP1-3 were measured by enzyme-linked immunosorbent assay. Urine culture was the reference standard. Sensitivities and specificities of leukocyte esterase (LE), HD5, HNP1-3, and test combinations were compared. Results: For predicting positive urine culture, the areas under the receiver-operating characteristic curves for HD5 and HNP1-3 were 0.86 (95% confidence interval (CI): 0.81-0.92) and 0.88 (95% CI: 0.82-0.93), respectively. Compared to LE ≥ trace, the combination test "LE and HD5" increased specificity by 6% (95% CI: 3-10%) without decreasing sensitivity. In the subgroup whose urine was collected by a clean-catch method, combination tests "LE and HD5" and "HD5 and HNP1-3" increased specificity by > 10% compared to LE alone. Conclusion: Urine AMP profiles are a promising novel strategy as an adjunct to urinalysis to aid UTI diagnosis in children. Copyright © 2016 International Pediatric Research Foundation, Inc. Source


Yiu A.J.,151 Research Service | Kalejaiye A.,151 Research Service | Kalejaiye A.,The Surgical Center | Amdur R.L.,Biostatistics Core | And 2 more authors.
International Journal of Oral and Maxillofacial Surgery | Year: 2016

To further define potential factors that may contribute to stone formation in salivary glands (sialolithiasis), a retrospective chart review was performed of patients diagnosed with sialolithiasis between March 1, 1998 and February 29, 2012. Information on salivary gland stone number, location and size, medical history, medications, and serum electrolyte levels were collected. Associations between electrolyte levels and stone characteristics (such as stone number and size) were examined. Fifty-nine patients were identified; their median age was 58 years (range 25-89 years) and most were male (95%). Salivary stones were most commonly located in the submandibular glands (83%). Thirty-five patients (59%) had a smoking history, with 16 (27%) reported as current smokers. There was a significant association between current smoker status and stone size (mean largest stone size 12.4 ± 8.8 mm vs. 7.5 ± 4.8 mm in current smokers vs. non-smokers; P = 0.03). Serum sodium levels (r = 0.32, P = 0.014) and serum potassium levels (r = 0.31, P = 0.017) showed significant positive correlations with stone size. While the aetiology of sialolithiasis remains unclear, smoking (which can contribute to reduced saliva flow) and higher serum sodium levels (which can reflect volume depletion) are associated with larger salivary stones. © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Source


Flanigan K.M.,Center for Gene Therapy | Campbell K.,Center for Vaccines and Immunity | Viollet L.,Center for Gene Therapy | Wang W.,Biostatistics Core | And 3 more authors.
Human Gene Therapy | Year: 2013

Duchenne muscular dystrophy (DMD) typically occurs as a result of truncating mutations in the DMD gene that result in a lack of expression of the dystrophin protein in muscle fibers. Various therapies under development are directed toward restoring dystrophin expression at the subsarcolemmal membrane, including gene transfer. In a trial of intramuscular adeno-associated virus (AAV)-mediated delivery of a therapeutic minidystrophin construct, we identified in two of six subjects the presence of a population of T cells that had been primed to recognize dystrophin epitopes before transgene delivery. As the presence of preexisting T cell immunity may have a significant effect on the success of therapeutic approaches for restoring dystrophin, we sought to determine the prevalence of such immunity within a DMD cohort from our Muscular Dystrophy Association clinic. Dystrophin-specific T cell immunity was evaluated in subjects with DMD who were either receiving the glucocorticoid steroid prednisone (n=24) or deflazacort (n=29), or who were not receiving steroids (n=17), as well as from normal age-matched control subjects (n=21). We demonstrate that increasing age correlates with an increased risk for the presence of anti-dystrophin T cell immunity, and that treatment with either corticosteroid decreases risk compared with no treatment, suggesting that steroid therapy in part may derive some of its benefit through modulation of T cell responses. The frequency of dystrophin-specific T cells detected by enzyme-linked immunospot assay was lower in subjects treated with deflazacort versus prednisone, despite similar overall corticosteroid exposure, suggesting that the effects of the two corticosteroids may not be identical in patients with DMD. T cells targeted epitopes upstream and downstream of the dystrophin gene mutation and involved the CD4+ helper and/or CD8+ cytotoxic subsets. Our data confirm the presence of preexisting circulating T cell immunity to dystrophin in a sizable proportion of patients with DMD, and emphasize the need to consider this in the design and interpretation of clinical gene therapy trials. © Copyright 2013, Mary Ann Liebert, Inc. Source


Swenson D.W.,Brown University | Darge K.,Childrens Hospital of Philadelphia | Ziniel S.I.,Biostatistics Core | Chow J.S.,Boston Childrens Hospital
Pediatric Radiology | Year: 2015

Background: Radiologists commonly evaluate children first diagnosed with urinary tract dilation on prenatal ultrasound (US). Objective: To establish how North American pediatric radiologists define and report findings of urinary tract dilation on US. Materials and methods: A web-based survey was sent to North American members of the Society for Pediatric Radiology (SPR) from January to February 2014. Reporting practices and interpretation of three image-based cases using free text were queried. Responses to close-ended questions were analyzed with descriptive statistics, while free-text responses to the three cases were categorized and analyzed as (1) using either descriptive terminology or an established numerical grading system and (2) as providing a quantitative term for the degree of dilation. Results: Two hundred eighty-four pediatric radiologists answered the survey resulting in a response rate of 19.0%. There is a great variety in the terms used to describe urinary tract dilation with 66.2% using descriptive terminology, 35.6% using Society for Fetal Urology (SFU) grading system and 35.9% measuring anterior-posterior diameter (APD) of the renal pelvis. There is no consensus for a normal postnatal APD or the meaning of hydronephrosis. For the same images, descriptions vary widely in degree of severity ranging from normal to mild to severe. Similar variability exists among those using the SFU system. Ninety-seven percent say they believe a unified descriptive system would be helpful and 87.7% would use it if available. Conclusion: Pediatric radiologists do not have a standardized method for describing urinary tract dilation but have a great desire for such a system and would follow it if available. © 2014, Springer-Verlag Berlin Heidelberg. Source


Juarez D.T.,University of Hawaii at Hilo | Ma C.,University of Hawaii at Hilo | Kumasaka A.,University of Hawaii at Hilo | Shimada R.,University of Hawaii at Manoa | Davis J.,Biostatistics Core
Population Health Management | Year: 2014

The objectives of this study were to describe patient characteristics and types of medications taken by those with poor glycemic control (A1c>7%) despite being adherent to antidiabetic medications. This is a retrospective analysis of administrative data from adult patients with diabetes enrolled in a large health plan in Hawaii (n=21,267 observations for 11,013 individuals) and adherent to their antidiabetic medications. Multivariable logistic regressions were estimated to determine characteristics and types of medications associated with poor glycemic control. Separate models were estimated to examine category of medication (insulin only, 1 oral medication, multiple oral medications, both oral medications and insulin) and specific therapeutic class of oral antidiabetic medications. Despite being adherent to their medications, 56.1% of patients had poor glycemic control. Compared to patients taking combination sulfonylureas, patients had a higher odds of having A1c>7% for all other oral diabetic medications, with odds ratios ranging from OR=2.07 for sulfonylureas alone to OR=1.33 for combination DPP-4 inhibitors. More than half of patients in this study had poor A1c control despite being adherent to their medications. This suggests that physicians, pharmacists, and other providers may need to monitor treatment regimens more carefully, encourage healthy behaviors, and intensify pharmacological treatment as needed. (Population Health Management 2014;17:218-223) © Copyright 2014, Mary Ann Liebert, Inc. 2014. Source

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