Varughese A.M.,University of Cincinnati |
Rampersad S.E.,University of Washington |
Whitney G.M.,Vanderbilt University |
Flick R.P.,Mayo Clinic Childrens Center |
Anton B.,Johns Hopkins University
Anesthesia and Analgesia | Year: 2013
Health care quality and value are leading issues in medicine today for patients, health care professionals, and policy makers. Outcome, safety, and service - the components of quality - have been used to define value when placed in the context of cost. Health care organizations and professionals are faced with the challenge of improving quality while reducing health care related costs to improve value. Measurement of quality is essential for assessing what is effective and what is not when working toward improving quality and value. However, there are few tools currently for assessing quality of care, and clinicians often lack the resources and skills required to conduct quality improvement work. In this article, we provide a brief review of quality improvement as a discipline and describe these efforts within pediatric anesthesiology. Copyright © 2013 International Anesthesia Research Society.
Robinson A.B.,Rainbow Babies and Childrens Hospital |
Hoeltzel M.F.,University of Missouri - Kansas City |
Wahezi D.M.,Childrens Hospital at Montefiore |
Becker M.L.,University of Missouri - Kansas City |
And 6 more authors.
Arthritis Care and Research | Year: 2014
Objective To investigate aspects of juvenile dermatomyositis (DM), including disease characteristics and treatment, through a national multicenter registry. Methods Subjects meeting the modified Bohan and Peter criteria for definite juvenile DM were analyzed from the cross-sectional Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry between 2010 and 2012 from 55 US pediatric rheumatology centers. Demographics, disease characteristics, diagnostic assessments, and medication exposure data were collected at enrollment. Results A total of 384 subjects met the criteria for analysis. At enrollment, the median Childhood Myositis Assessment Scale score was 51 (interquartile range [IQR] 46-52), the median Childhood Health Assessment Questionnaire score was 0 (IQR 0-0.5), and the median physician and subject global assessment scores were 1 (IQR 0-2) and 1 (IQR 0-3), respectively, out of a maximum of 10. Of the diagnostic assessments, magnetic resonance imaging was more likely than electromyography or muscle biopsy to show abnormalities. A total of 329 subjects had ≥2 diagnostic studies performed, and >34% of these subjects reported ≥1 negative study. Ninety-five percent had been treated with corticosteroids and 92% with methotrexate, suggesting that these medications were almost universally prescribed for juvenile DM in the US. Conclusion In 2 years, the ongoing CARRA Registry has collected clinical data on 384 children with juvenile DM and has the potential to become one of the largest juvenile DM cohorts in the world. More research is needed about prognostic factors in juvenile DM, and differences in therapy based on manifestations of disease need to be explored by practitioners. This registry provides the infrastructure needed to advance clinical and translational research and represents a major step toward improving outcomes of children with juvenile DM. Copyright © 2014 by the American College of Rheumatology.
Mehta H.,Royal Manchester Childrens Hospital |
Mehta H.,KGP Children Hospital |
Kashyap R.,Mayo Clinic Childrens Center |
Trivedi S.,Mayo Clinic Childrens Center
Indian Journal of Critical Care Medicine | Year: 2014
Aim of the Study: End tidal carbon dioxide (EtCO 2 ) monitoring is considered to reflect real-time estimation of partial pressure of carbon dioxide in arterial blood (PaCO 2 ) noninvasively. However, knowledge about its relationship with PaCO 2 in critically ill pediatric and neonatal patients is limited. The primary objective was to evaluate predictive capability of end tidal carbon dioxide monitoring and secondary objective was to determine the influence of severity of lung disease on EtCO 2 and PaCO 2 relationship. Materials and Methods: This was a prospective, nonrandomized, consecutive enrollment study carried out in neonatal and pediatric intensive care units of a tertiary care children hospital. It was conducted in 66 neonates and 35 children receiving mechanical ventilation. Severity of lung disease was estimated by ventilation index and PaO 2 /FiO 2 (P/F) ratio. Simultaneous recording of EtCO 2 and PaCO 2 levels was done and data were analyzed for correlation and agreement. Results: In neonates, 150 EtCO 2 and PaCO 2 pairs were recorded. The mean weight ± SD of patients was 2.1 ± 0.63 kg. PaCO 2 had a positive correlation with EtCO 2 (r = 0.836, 95% CI = 0.78-0.88). P/F ratio <200 adversely affected relationship. In infants and children, 96 pairs were recorded. Mean age ± SD of patients was 4.20 ± 4.92 years and mean weight ± SD was 13.1 ± 9.49 kg. PaCO 2 had an excellent correlation with EtCO 2 (r = 0.914, 95% CI = 0.87 and 0.94). P/F ratio <200 adversely affected relationship. Conclusion: EtCO 2 monitoring displayed a good validity to predict PaCO 2. Correlation was affected by low P/F ratio (<200); hence, it is recommended that blood gases be measured in these patients until such time that a good relation can be established between end tidal and arterial CO 2 values.
Baruth J.M.,Mayo Medical School |
Wall C.A.,Mayo Medical School |
Patterson M.C.,Mayo Clinic Childrens Center |
Port J.D.,Mayo Medical School
Autism Research | Year: 2013
Proton magnetic resonance spectroscopy (1H-MRS) is a safe, noninvasive way of quantifying in vivo biochemical and metabolite concentration levels in individuals with Autism Spectrum Disorders (ASD). Findings to date suggest ASD is associated with widespread reduction in N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol (mI), and glutamate plus glutamine plus gamma-Aminobutyric Acid (Glx); however, variable findings, and even substantial increases, are not uncommon depending on the study and/or region-of-interest. Widespread reduction of NAA, Cr, Cho, mI, and Glx in ASD likely reflects impaired neuronal function and/or metabolism related to abnormal neurodevelopmental processes. Future studies should attempt to relate 1H-MRS findings to histological findings and control for variability in subject age and functioning level; this would assist in evaluating the relationship between 1H-MRS metabolic levels and neuronal and glial cell densities, as well as neurodevelopmental process associated with ASD. Furthermore, more longitudinal 1H-MRS studies are needed in both control and ASD subjects to attempt to standardize metabolite levels across different developmental periods in well-defined endophenotypes. This will provide for a standard rubric for which metabolic aberrations (as well as treatment responses) can be measured. With higher magnetic field strengths and spectral-editing techniques capable of quantifying less-concentrated metabolites, 1H-MRS will continue to be an important tool in ASD research. Autism Res 2013, 6: 119-133. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Isaya G.,Mayo Clinic Childrens Center
Frontiers in Pharmacology | Year: 2014
Growing evidence supports a role for mitochondrial iron metabolism in the pathophysiology of neurodegenerative disorders such as Friedreich ataxia (FRDA) and Parkinson disease (PD) as well as in the motor and cognitive decline associated with the aging process. Iron-sulfur enzyme deficits and regional iron accumulation have been observed in each of these conditions. In spite of significant etiological, clinical and pathological differences that exist between FRDA and PD, it is possible that defects in mitochondrial iron-sulfur clusters (ISCs) biogenesis represent a common underlying mechanism leading to abnormal intracellular iron distribution with mitochondrial iron accumulation, oxidative phosphorylation deficits and oxidative stress in susceptible cells and specific regions of the nervous system. Moreover, a similar mechanism may contribute to the age-dependent iron accumulation that occurs in certain brain regions such as the globus pallidus and the substantia nigra. Targeting chelatable iron and reactive oxygen species appear as possible therapeutic options for FRDA and PD, and possibly other age-related neurodegenerative conditions. However, new technology to interrogate ISC synthesis in humans is needed to (i) assess how defects in this pathway contribute to the natural history of neurodegenerative disorders and (ii) develop treatments to correct those defects early in the disease process, before they cause irreversible neuronal cell damage. © 2014 Isaya.
Dhamija R.,Mayo Medical School |
Wirrell E.,Mayo Clinic Childrens Center |
Falcao G.,Avera Childrens Hospital and Clinics |
Kirmani S.,Mayo Medical School |
Wong-Kisiel L.C.,Mayo Clinic Childrens Center
Pediatric Neurology | Year: 2013
Background Migrating focal seizures of infancy are characterized by seizure onset within 7 months of age, migrating focal motor seizures with multifocal ictal electroencephalography discharges intractable to conventional antiepileptic drugs, and poor prognosis. Reported genetic etiologies include SCN1A and KCNT1 mutations and homozygous deletion of the PLCB1 gene. Here we report a novel SCN2A mutation in a child with this syndrome. Patient A 7-week-old girl was admitted to our hospital for management of status epilepticus. She was the product of a full-term unremarkable pregnancy. Seizures started around 5 weeks of age and remained medically refractory. Electroencephalography showed multifocal epileptiform discharges as well as seizures arising from multifocal regions in both cerebral hemispheres. Based on her phenotype, a diagnosis of migrating focal seizures of infancy was made. Result A novel de novo missense mutation was identified in the SCN2A gene, exon 22 (coding for voltage-gated sodium channel type II): c.3977T>A (p.V1326D). This mutation affects a highly evolutionarily conserved area of the gene and replaces hydrophobic nonpolar valine with polar aspartic acid; thus, it is predicted to affect protein function and is presumed pathogenic. Discussion This report expands our knowledge of the genetic basis of migrating focal seizures of infancy to include mutations in SCN2A gene. © 2013 Elsevier Inc. All rights reserved.
Davidson A.,Royal Melbourne Hospital |
Flick R.P.,Mayo Clinic Childrens Center
Clinics in Perinatology | Year: 2013
Laboratory studies have shown that general anesthetics may cause accelerated apoptosis and other adverse morphologic changes in neurons of the developing brain. The mechanism may be related to the neuronal quiescence or inactivity associated with anesthetic exposure. Few data exist on how brief anesthetic exposure may affect neurodevelopment in the newborn. Good evidence however shows that untreated pain and stress have an adverse effect on neurodevelopment, and therefore, at this stage, providing effective analgesia, sedation, and anesthesia would seem to be more important than concern over neurotoxicity. © 2013 Elsevier Inc.
Bosenberg A.,University of Washington |
Flick R.P.,Mayo Clinic Childrens Center
Clinics in Perinatology | Year: 2013
Optimal pain management can significantly impact the surgical outcome and length of stay in the neonatal intensive care unit (NICU). Regional anesthesia is an effective alternative that can be used in both term and preterm neonates. A variety of neuraxial and peripheral nerve blocks have been used for specific surgical and NICU procedures. Ultrasound guidance has increased the feasibility of using these techniques in neonates. Education and training staff in the use of continuous epidural infusions are important prerequisites for successful implementation of regional anesthesia in NICU management protocols. © 2013 Elsevier Inc.
Zhang Y.,Mayo Clinic Childrens Center |
Galardy P.J.,Mayo Clinic Childrens Center
Chromosome Research | Year: 2016
For over a century, the abnormal movement or number of centrosomes has been linked with errors of chromosomes distribution in mitosis. While not essential for the formation of the mitotic spindle, the presence and location of centrosomes has a major influence on the manner in which microtubules interact with the kinetochores of replicated sister chromatids and the accuracy with which they migrate to resulting daughter cells. A complex network has evolved to ensure that cells contain the proper number of centrosomes and that their location is optimal for effective attachment of emanating spindle fibers with the kinetochores. The components of this network are regulated through a series of post-translational modifications, including ubiquitin and ubiquitin-like modifiers, which coordinate the timing and strength of signaling events key to the centrosome cycle. In this review, we examine the role of the ubiquitin system in the events relating to centriole duplication and centrosome separation, and discuss how the disruption of these functions impacts chromosome segregation. © 2015, Springer Science+Business Media Dordrecht.
Vaubel R.A.,Mayo Clinic Childrens Center |
Isaya G.,Mayo Clinic Childrens Center
Molecular and Cellular Neuroscience | Year: 2013
Friedreich ataxia (FRDA) is an autosomal recessive, multi-systemic degenerative disease that results from reduced synthesis of the mitochondrial protein frataxin. Frataxin has been intensely studied since its deficiency was linked to FRDA in 1996. The defining properties of frataxin - (i) the ability to bind iron, (ii) the ability to interact with, and donate iron to, other iron-binding proteins, and (iii) the ability to oligomerize, store iron and control iron redox chemistry - have been extensively characterized with different frataxin orthologs and their interacting protein partners. This very large body of biochemical and structural data [reviewed in (Bencze et al., 2006)] supports equally extensive biological evidence that frataxin is critical for mitochondrial iron metabolism and overall cellular iron homeostasis and antioxidant protection [reviewed in (Wilson, 2006)]. However, the precise biological role of frataxin remains a matter of debate. Here, we review seminal and recent data that strongly link frataxin to the synthesis of iron-sulfur cluster cofactors (ISC), as well as controversial data that nevertheless link frataxin to additional iron-related processes. Finally, we discuss how defects in ISC synthesis could be a major (although likely not unique) contributor to the pathophysiology of FRDA via (i) loss of ISC-dependent enzymes, (ii) mitochondrial and cellular iron dysregulation, and (iii) enhanced iron-mediated oxidative stress. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'. © 2012 Elsevier Inc.