Dobbs M.B.,St Louis Childrens Hospital |
Gurnett C.A.,University of Washington
Clinical Orthopaedics and Related Research | Year: 2017
Background: Clubfoot is one of the most common pediatric orthopaedic disorders. While the Ponseti method has revolutionized clubfoot treatment, it is not effective for all patients. When the Ponseti method does not correct the foot, patients are at risk for lifelong disability and may require more-extensive surgery. Questions/Purposes: (1) What genetic and morphologic abnormalities contribute to the development of clubfoot? (2) How can this information be used to devise personalized treatment paradigms for patients with clubfoot? Methods: Human gene sequencing, molecular genetic engineering of mouse models of clubfoot, MRI of clubfoot, and development of new treatment methods all have been used by our group to understand the biological basis and improve therapy for this group of disorders. Results: We gained new insight into clubfoot pathogenesis from our discovery that mutations in the PITX1-TBX4-HOXC transcriptional pathway cause familial clubfoot and vertical talus in a small number of families, with the unique lower limb expression of these genes providing an explanation for the lack of upper extremity involvement in these disorders. MRI studies revealed corresponding morphologic abnormalities, including hypomorphic muscle, bone, and vasculature, that are not only associated with these gene mutations, but also are biomarkers for treatment-resistant clubfoot. Conclusions: Based on an understanding of the underlying biology, we improved treatment methods for neglected and syndromic clubfoot, developed new treatment for congenital vertical talus based on the principles of the Ponseti method, and designed a new dynamic clubfoot brace to improve strength and compliance. © 2017 The Association of Bone and Joint Surgeons®
Allan B.F.,Washington University in St. Louis |
Goessling L.S.,Washington University in St. Louis |
Storch G.A.,St Louis Childrens Hospital |
Thach R.E.,Washington University in St. Louis
Emerging Infectious Diseases | Year: 2010
Efforts to identify wildlife reservoirs for tick-borne pathogens are frequently limited by poor understanding of tick - host interactions and potentially transient infectivity of hosts under natural conditions. To identify reservoir hosts for lone star tick (Amblyomma americanum)-associated pathogens, we used a novel technology. In field-collected ticks, we used PCR to amplify a portion of the 18S rRNA gene in remnant blood meal DNA. Reverse line blot hybridization with host-specific probes was then used to subsequently detect and identify amplified DNA. Although several other taxa of wildlife hosts contribute to tick infection rates, our results confirm that the white-tailed deer (Odocoileus virginianus) is a reservoir host for several A. americanum - associated pathogens. Identification of host blood meal frequency and reservoir competence can help in determining human infection rates caused by these pathogens.
Yang J.S.,University of Washington |
Dobbs M.B.,St Louis Childrens Hospital
The Journal of bone and joint surgery. American volume | Year: 2015
BACKGROUND: The most common historical treatment method for congenital vertical talus is extensive soft-tissue release surgery. A minimally invasive treatment approach that relies primarily on serial cast correction was introduced almost ten years ago, with promising early results. The purpose of this study was to assess the long-term outcome of patients with congenital vertical talus managed with the minimally invasive technique and compare them with a cohort treated with extensive soft-tissue release surgery.METHODS: The records of twenty-seven consecutive patients with vertical talus (forty-two feet) were retrospectively reviewed at a mean of seven years (range, five to 11.3 years) after initial correction was achieved. The minimally invasive method was used to treat sixteen patients (twenty-four feet), and extensive soft-tissue release surgery was used to treat eleven patients (eighteen feet). Patient demographics, ankle range of motion, the PODCI (Pediatric Outcomes Data Collection Instrument) questionnaire, and radiographic measurements were analyzed.RESULTS: At the latest follow-up, the mean range of motion of patients treated with the minimally invasive method was 42.4° compared with 12.7° for patients treated with extensive surgery (p < 0.0001). The PODCI normative pain and global function scores were superior in the minimally invasive treatment group compared with the extensive soft-tissue release group. Greater correction of hindfoot valgus (anteroposterior talar axis-first metatarsal base angle) was achieved in the minimally invasive treatment group compared with the extensive surgery group (40.1° versus 27.9°, p = 0.03), although all other radiographic values were similar between the two groups (p > 0.1 for all). Subgroup analysis of patients with isolated vertical talus also showed superior range of motion and PODCI normative global function scores in the minimally invasive group.CONCLUSIONS: The minimally invasive treatment method for vertical talus resulted in better long-term ankle range of motion and pain scores compared with extensive soft-tissue release surgery. Longer-term studies are necessary to determine whether the improved outcomes are maintained into adulthood and whether the superior outcome is related to reduced scarring. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.
TeKippe E.M.,University of Washington |
Shuey S.,St Louis Childrens Hospital |
Winkler D.W.,St Louis Childrens Hospital |
Butler M.A.,St Louis Childrens Hospital |
Burnham C.-A.D.,University of Washington
Journal of Clinical Microbiology | Year: 2013
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) can be used as a method for the rapid identification of microorganisms. This study evaluated the Bruker Biotyper (MALDI-TOF MS) system for the identification of clinically relevant Gram-positive organisms. We tested 239 aerobic Gram-positive organisms isolated from clinical specimens. We evaluated 4 direct-smear methods, including "heavy" (H) and "light" (L) smears, with and without a 1-=l direct formic acid (FA) overlay. The quality measure assigned to a MALDI-TOF MS identification is a numerical value or "score." We found that a heavy smear with a formic acid overlay (H+FA) produced optimal MALDI-TOF MS identification scores and the highest percentage of correctly identified organisms. Using a score of>2.0, we identified 183 of the 239 isolates (76.6%) to the genus level, and of the 181 isolates resolved to the species level, 141 isolates (77.9%) were correctly identified. To maximize the number of correct identifications while minimizing misidentifications, the data were analyzed using a score of>1.7 for genus- and species-level identification. Using this score, 220 of the 239 isolates (92.1%) were identified to the genus level, and of the 181 isolates resolved to the species level, 167 isolates (92.2%) could be assigned an accurate species identification. We also evaluated a subset of isolates for preanalytic factors that might influence MALDI-TOF MS identification. Frequent subcultures increased the number of unidentified isolates. Incubation temperatures and subcultures of the media did not alter the rate of identification. These data define the ideal bacterial preparation, identification score, and medium conditions for optimal identification of Gram-positive bacteria by use of MALDI-TOF MS. Copyright © 2013, American Society for Microbiology.
Boulet J.R.,Research and Data Resources |
Murray D.J.,St Louis Childrens Hospital |
Murray D.J.,Washington University in St. Louis
Anesthesiology | Year: 2010
Simulations have taken a central role in the education and assessment of medical students, residents, and practicing physicians. The introduction of simulation-based assessments in anesthesiology, especially those used to establish various competencies, has demanded fairly rigorous studies concerning the psychometric properties of the scores. Most important, major efforts have been directed at identifying, and addressing, potential threats to the validity of simulation-based assessment scores. As a result, organizations that wish to incorporate simulation-based assessments into their evaluation practices can access information regarding effective test development practices, the selection of appropriate metrics, the minimization of measurement errors, and test score validation processes. The purpose of this article is to provide a broad overview of the use of simulation for measuring physician skills and competencies. For simulations used in anesthesiology, studies that describe advances in scenario development, the development of scoring rubrics, and the validation of assessment results are synthesized. Based on the summary of relevant research, psychometric requirements for practical implementation of simulation-based assessments in anesthesiology are forwarded. As technology expands, and simulation-based education and evaluation takes on a larger role in patient safety initiatives, the groundbreaking work conducted to date can serve as a model for those individuals and organizations that are responsible for developing, scoring, or validating simulation-based education and assessment programs in anesthesiology.
Lieu J.E.C.,University of Washington |
Tye-Murray N.,University of Washington |
Karzon R.K.,University of Washington |
Karzon R.K.,St Louis Childrens Hospital |
Piccirillo J.F.,University of Washington
Pediatrics | Year: 2010
OBJECTIVE: To determine whether children with unilateral hearing loss (UHL) demonstrate worse language skills than their siblings with normal hearing, and whether children with UHL are more likely to receive extra assistance at school. PATIENTS AND METHODS: We conducted a case-control study of 6- to 12-year-old children with UHL compared with sibling controls (74 pairs, n = 148). Scores on the oral portion of the Oral and Written Language Scales (OWLS) were the primary outcome measure. Multivariable analysis was used to determine whether UHL independently predicted OWLS scores after we controlled for potential confounding variables. RESULTS: Children with UHL had worse scores than their siblings on language comprehension (91 vs 98; P=.003), oral expression (94 vs 101; P=.007), and oral composite (90 vs 99; P=.001). UHL independently predicted these OWLS scores when multivariable regression was used with moderate effect sizes of 0.3 to 0.7. Family income and maternal education were also independent predictors of oral expression and oral composite scores. No differences were found between children with right- or left-ear UHL or with varying severity of hearing loss. Children with UHL were more likely to have an individualized education plan (odds ratio: 4.4 [95% confidence interval: 2.0-9.5]) and to have received speech-language therapy (odds ratio: 2.6 [95% confidence interval: 1.3-5.4]). CONCLUSIONS: School-aged children with UHL demonstrated worse oral language scores than did their siblings with normal hearing. These findings suggest that the common practice of withholding hearing-related accommodations from children with UHL should be reconsidered and studied, and that parents and educators should be informed about the deleterious effects of UHL on oral language skills. Copyright © 2010 by the American Academy of Pediatrics.
Yamada M.,University of Washington |
Buller R.,University of Washington |
Bledsoe S.,St Louis Childrens Hospital |
Storch G.A.,University of Washington
Pediatric Infectious Disease Journal | Year: 2012
Macrolide-resistant Mycoplasma pneumoniae is widespread in Asia, and severe cases of pneumonia have been described in children. Little information is available about the resistance pattern in the United States. We collected respiratory samples from 49 patients with Mycoplasma infection in the central United States between 2007 and 2010. We found a macrolide resistance rate of 8.2%. Resistance should be considered when patients with M. pneumoniae infection do not have a satisfactory response to macrolides. Alternative antibiotics include tetracyclines or fluoroquinolones. © 2012 by Lippincott Williams & Wilkins.
Spencer D.H.,University of Washington |
Sellenriek P.,St Louis Childrens Hospital |
Burnham C.-A.D.,University of Washington
American Journal of Clinical Pathology | Year: 2011
Blood cultures positive for gram-positive cocci in clusters can pose a dilemma for empiric antimicrobial therapy because they could represent coagulase-negative staphylococcus or Staphylococcus aureus bacteremia. The GeneXpert MRSA/SA BC Assay (Cepheid, Sunnyvale, CA) is a polymerase chain reaction-based method for identifying S aureus and methicillin resistance that has been approved for use in adults, but data on its use in samples from pediatric patients is limited. We validated the Xpert MRSA/SA BC Assay for use with anaerobic and polymicrobial specimens from pediatric patients and implemented it for routine presumptive identification of S aureus in our pediatric hospital. The assay was 100% sensitive and specific for methicillin-resistant S aureus and 100% sensitive and 99.5% specific for methicillin-susceptible S aureus. Time to presumptive identification of S aureus bacteremia and determination of methicillin susceptibility was reduced by more than 24 hours. We found the Xpert MRSA/SA BC Assay to be a rapid, accurate tool for detecting methicillin-resistant and methicillin-susceptible S aureus in positive pediatric blood cultures, including polymicrobial cultures and those recovered in anaerobic blood culture media. © American Society for Clinical Pathology.
Pineda R.G.,St Louis Childrens Hospital
Breastfeeding Medicine | Year: 2011
Objective: This study investigated associations between maternal and infant factors and breastfeeding practices in infants born <30 weeks gestation in the neonatal intensive care unit (NICU). Study Design: This study was a retrospective cohort. Mother and infant characteristics were investigated for associations with breastfeeding outcomes using multivariate logistic regression. Results: Seventy-eight percent of infants initiated breastmilk feedings, 48% of those continued to have breastmilk at discharge, and 52% were breastfed in the hospital. The average duration of breastmilk feedings was 43 days. Mothers who were married and had a multiple-infant birth were more likely to initiate breastmilk feeds, African American mothers and younger mothers had less success with maintaining breastmilk feeds until hospital discharge, and African American mothers and mothers of lower socioeconomic status were less likely to participate in direct breastfeeding in the NICU. Conclusions: Infant factors, such as birth weight and gestational age, were not associated with breastfeeding behaviors. Mothers can succeed with breastfeeding the premature infant. By understanding what maternal groups are at risk for breastfeeding failure, targeted interventions in the NICU can be implemented. Copyright 2011, Mary Ann Liebert, Inc.
Ackerman J.J.H.,University of Washington |
Neil J.J.,St Louis Childrens Hospital
NMR in Biomedicine | Year: 2010
As a result of the technical challenges associated with distinguishing the MR signals arising from intracellular and extracellular water, a variety of endogenous and exogenous MR-detectable molecules and ions have been employed as compartment-specific reporters of water motion. Although these reporter molecules and ions do not have the same apparent diffusion coefficients (ADCs) as water, their ADCs are assumed to be directly related to the ADC of the water in which they are solvated. This approach has been used to probe motion in the intra- and extracellular space of cultured cells and intact tissue. Despite potential interpretative challenges with the use of reporter molecules or ions and the wide variety used, the following conclusions are consistent considering all studies: (i) the apparent free diffusive motion in the intracellular space is approximately one-half of that in dilute aqueous solution; (ii) ADCs for intracellular and extracellular water are similar; (iii) the intracellular ADC decreases in association with brain injury. These findings provide support for the hypothesis that the overall brain water ADC decrease that accompanies brain injury is driven primarily by a decrease in the ADC of intracellular water. We review the studies supporting these conclusions, and interpret them in the context of explaining the decrease in overall brain water ADC that accompanies brain injury. © 2010 John Wiley & Sons, Ltd.