Moore J.,University of California at San Diego |
Hegde S.,University of California at San Diego |
El-Said H.,University of California at San Diego |
Beekman III R.,Cincinnati Childrens Hospital |
And 8 more authors.
JACC: Cardiovascular Interventions | Year: 2013
This review discusses the current safety issues related to U.S. Food and Drug Administration approved atrial septal defect devices and proposes a potential avenue to gather additional safety data including factors, which may be involved in device erosion. © 2013 American College of Cardiology Foundation.
Lee S.,University of Florida |
Ashizawa A.T.,University of Florida |
Kim K.S.,Johns Hopkins Childrens Center |
Falk D.J.,University of Florida |
Notterpek L.,University of Florida
PLoS ONE | Year: 2013
While a wealth of literature for tissue-specific liposomes is emerging, optimal formulations to target the cells of the peripheral nervous system (PNS) are lacking. In this study, we asked whether a novel formulation of phospholipid-based liposomes could be optimized for preferential uptake by microvascular endothelia, peripheral neurons and Schwann cells. Here, we report a unique formulation consisting of a phospholipid, a polymer surfactant and cholesterol that result in enhanced uptake by targeted cells. Using fluorescently labeled liposomes, we followed particle internalization and trafficking through a distinct route from dextran and escape from degradative compartments, such as lysosomes. In cultures of non-myelinating Schwann cells, liposomes associate with the lipid raft marker Cholera toxin, and their internalization is inhibited by disruption of lipid rafts or actin polymerization. In contrast, pharmacological inhibition of clathrin-mediated endocytosis does not significantly impact liposome entry. To evaluate the efficacy of liposome targeting in tissues, we utilized myelinating explant cultures of dorsal root ganglia and isolated diaphragm preparations, both of which contain peripheral neurons and myelinating Schwann cells. In these models, we detected preferential liposome uptake into neurons and glial cells in comparison to surrounding muscle tissue. Furthermore, in vivo liposome administration by intramuscular or intravenous injection confirmed that the particles were delivered to myelinated peripheral nerves. Within the CNS, we detected the liposomes in choroid epithelium, but not in myelinated white matter regions or in brain parenchyma. The described nanoparticles represent a novel neurophilic delivery vehicle for targeting small therapeutic compounds, biological molecules, or imaging reagents into peripheral neurons and Schwann cells, and provide a major advancement toward developing effective therapies for peripheral neuropathies. © 2013 Lee et al.
Molleston J.P.,Indiana University |
Schwimmer J.B.,University of California at San Diego |
Schwimmer J.B.,Rady Childrens Hospital |
Yates K.P.,Johns Hopkins University |
And 6 more authors.
Journal of Pediatrics | Year: 2014
Objective To investigate the histological spectrum of nonalcoholic fatty liver disease (NAFLD) in children with normal, mildly elevated (26-50 U/L boys, 23-44 U/L girls), or elevated (>50 U/L in boys, >44 U/L in girls) serum alanine aminotransferase (ALT) levels. Study design The Nonalcoholic Steatohepatitis Clinical Research Network enrolls children aged 5-18 years with NAFLD. We analyzed baseline clinical and histological data from 91 children with suspected NAFLD and normal or mildly elevated ALT and liver biopsy analysis within 180 days of ALT measurement, and compared them with data from 392 children with elevated ALT. Results Seventeen of the 91 children with suspected NAFLD (19%) had a normal ALT level, and 74 (81%) had a mildly elevated ALT level. Overall, 45% of the biopsy specimens analyzed had steatosis ≥33%, 22% had grade ≥2 lobular inflammation, 81% had portal inflammation, 29% had ballooned hepatocytes, 35% had "suspicious/borderline" steatohepatitis, 8% had definite nonalcoholic steatohepatitis, 34% had an NAFLD activity score ≥4, and 46% had fibrosis (38% mild/moderate and 8% bridging/cirrhosis). Marked steatosis (50% vs 24%) and fibrosis (54% vs 12%) were significantly more common in the patients with mildly elevated ALT compared with those with normal ALT, with no difference in ballooning, inflammation, or NAFLD activity score ≥4 between the 2 groups. Fibrosis stage 3/4 was seen in none of the children with normal ALT, in 9% of those with mildly elevated ALT, and in 15% of those with elevated ALT. Conclusion Liver biopsy specimens from children with NAFLD with normal or mildly elevated ALT levels show significant histological abnormalities, including advanced fibrosis in children with mildly elevated ALT. Thus, measurement of ALT may underestimate liver injury in NAFLD. The use of appropriate ALT cutoff levels can help identify children at risk for more severe disease. © 2014 Mosby Inc. All rights reserved.
Clancy C.M.,Agency for Healthcare Research and Quality |
Margolis P.A.,Cincinnati Childrens Hospital Medical Center |
Miller M.,Childrens Hospital Association |
Miller M.,Johns Hopkins Childrens Center
Pediatrics | Year: 2013
Moving significant therapeutic discoveries beyond early biomedical translation or T1 science and into practice involves: (1) T2 science, identifying "the right treatment for the right patient in the right way at the right time" (eg, patient-centered outcomes research) and tools to implement this knowledge (eg, guidelines, registries); and (2) T3 studies addressing how to achieve health care delivery change. Collaborative improvement networks can serve as large-scale, health system laboratories to engage clinicians, researchers, patients, and parents in testing approaches to translate research into practice. Improvement networks are of particular importance for pediatric T2 and T3 research, as evidence to establish safety and efficacy of therapeutic interventions in children is often lacking. Networks for improvement and research are also consistent with the Institute of Medicine's Learning Healthcare Systems model in which learning networks provide a system for improving care and outcomes and generate new knowledge in near real-time. Creation of total population registries in collaborative network sites provides large, representative study samples with high-quality data that can be used to generate evidence and to inform clinical decision-making. Networks use collaboration, data, and quality-improvement methods to standardize practice. Therefore, variation in outcomes due to unreliable and unnecessary care delivery is reduced, increasing statistical power, and allowing a consistent baseline from which to test new strategies. In addition, collaborative networks for improvement and research offer the opportunity to not only make improvements but also to study improvements to determine which interventions and combination of strategies work best in what settings.
Crocetti M.,Johns Hopkins Bayview Medical Center |
Thompson R.,Johns Hopkins Childrens Center
Annals of Pediatric Cardiology | Year: 2010
Objective: The primary objective of this study was to evaluate pediatric residents' ability to correctly identify electrocardiogram (ECG) findings and pair them to a corresponding cardiac diagnosis. Methods: Forty-six pediatric residents from the Johns Hopkins Children's Center were surveyed to evaluate their ability to interpret ECGs and factors affecting that ability. Included in the survey was a packet of 10 patient vignettes each accompanied by a 12-lead ECG. The primary outcome variable was the resident's score of correctly paired ECG findings with the appropriate cardiac diagnosis. One point was given for each pair correctly identified for a maximum of 10 points. Simple and multiple linear regression was used to estimate the magnitude and significance of any association between score of correct responses and resident year, completion of a pediatric cardiology rotation, self-rated ability to read ECGs, and training received in reading ECGs. Results: The mean number of correct ECG findings and cardiac diagnosis pairings out of 10 for the PGY 1 group was 4.1 3, PGY 2 group 4.9 2.9, PGY 3 group 6.6 2, and the PGY 4 group 6.8 1.7. In the unadjusted linear regression model, the PGY 3 group correctly identified 2.4 more pairings compared to the PGY 1 group (P =0.02). Those who completed a pediatric cardiology rotation correctly identified 2.5 more pairings compared to those who did not complete a rotation (P=0.001). Conclusions: ECG interpretation significantly improved from PGY 1 to PGY 3. Educational programs involving ECG interpretation should target those diagnoses with high clinical severity and average to poor resident knowledge.
Bulua A.C.,U.S. National Institutes of Health |
Mogul D.B.,U.S. National Institutes of Health |
Mogul D.B.,Johns Hopkins Childrens Center |
Aksentijevich I.,U.S. National Institutes of Health |
And 8 more authors.
Arthritis and Rheumatism | Year: 2012
Objective To investigate the efficacy of etanercept in improving the symptoms and underlying inflammation in patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Methods Fifteen patients with TRAPS were enrolled in a prospective, open-label, dose-escalation study. Patients recorded attacks, symptom severity, and use of ancillary medications in a daily diary. Blood samples were collected during each period and measured for levels of acute-phase reactants. Between 7 years and 9 years after the conclusion of the initial study, patients completed a followup survey and were evaluated to determine the long-term outcome of etanercept treatment. Results Etanercept treatment significantly attenuated the total symptom score and reduced the frequency of symptoms. Etanercept also reduced levels of acute-phase reactants, particularly during asymptomatic periods. During a 10-year followup period, patients continued to receive etanercept for a median of 3.3 years, with a number of patients switching to anti-interleukin-1β receptor therapy or not receiving biologic agents, most frequently citing injection site reactions and lack of efficacy as reasons for discontinuation. However, patients continuing to receive etanercept had reduced symptoms at followup. Conclusion Etanercept reduces symptoms and serum levels of inflammatory markers of TRAPS in a dose-dependent manner, but does not completely normalize symptoms or acute-phase reactant levels. Although long-term adherence to etanercept is poor, continuing to receive etanercept may provide continued symptomatic benefit. Copyright © 2012 by the American College of Rheumatology.
Fashoyin-Aje L.,Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Sanghavi K.,McKusick Nathans Institute of Genetic Medicine |
Bjornard K.,Johns Hopkins Childrens Center |
Bodurtha J.,McKusick Nathans Institute of Genetic Medicine
Annals of Oncology | Year: 2013
This paper provides an overview of issues in the integration of genetic (related to hereditary DNA) and genomic (related to genes and their functions) information in cancer care for individuals and families who are part of health care systems worldwide, from low to high resourced. National and regional cancer plans have the potential to integrate genetic and genomic information with a goal of identifying and helping individuals and families with and at risk of cancer. Healthcare professionals and the public have the opportunity to increase their genetic literacy and communication about cancer family history to enhance cancer control, prevention, and tailored therapies. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Husain A.,Johns Hopkins Childrens Center |
Fuchs S.,Northwestern University
Clinical Pediatric Emergency Medicine | Year: 2014
Regionalization of pediatric emergency care is a necessary and enormous task assigned to Emergency Medical Services for Children. One of the founders of medical regionalization, perinatology, has experienced difficulties over the past decade maintaining the structure and systems that had so dramatically improved patient care. Pediatric trauma regionalization, as a component of pediatric emergency care as well as adult trauma care, is foreseeing similar degradation of their system if key issues are not addressed soon. Pediatric emergency care, under the leadership of Emergency Medical Services for Children, is seeking to build strong and sustainable systems of regionalization as the next step toward improving access to high-quality emergency and definitive care for children of all ages throughout the United States. © 2014 Elsevier Inc.
Keene E.A.,Johns Hopkins Childrens Center
Pediatric nursing | Year: 2010
Health care professionals experience grief when caring for children with life-threatening conditions. Harriet Lane Compassionate Care, the pediatric palliative care program of the Johns Hopkins Children's Center, created an action plan to support health care professionals; one intervention-- the bereavement debriefing session - was specifically aimed at providing emotional support and increasing one's ability to manage grief. A structured format for conducting bereavement debriefing sessions was developed, and 113 sessions were held in a three-year period; data were collected to capture themes discussed. Bereavement debriefing sessions were conducted most frequently after unexpected deaths or deaths of long-term patients. Though attendance included all disciplines, nurses attended the sessions most often. Self-report evaluation forms revealed that health care professionals found the sessions helpful. Bereavement debriefing sessions can be one aspect of an effective approach to supporting health care professionals in managing their grief in caring for children with life-threatening conditions.
Dibs S.D.,Johns Hopkins Childrens Center
Clinical Pediatric Emergency Medicine | Year: 2012
International adoption has been part of our society for many years. Each year, thousands of children are adopted by families in the United States, and many of these children seek emergency care for one reason or another. Whereas common diseases present commonly, certain infectious and other diseases affect international adoptees more commonly than their American-born peers. A child's country of origin can sometimes help guide the clinician toward more likely etiologies of illness. Illnesses uncommon in the United States or Western Europe often occupy higher positions on the differential diagnosis list for these children. When managing illnesses in the international adoptee population, it is also important to maintain a healthy skepticism for the accuracy of preadoption immunization records and related health care information. This accentuates the importance of considering the child's country of origin and performing a thorough physical examination. © 2012 Elsevier Inc.