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Grant M.J.C.,Primary Childrens Medical Center | Scoppettuolo L.A.,Childrens Hospital Boston | Wypij D.,Childrens Hospital Boston | Curley M.A.Q.,University of Pennsylvania
Critical Care Medicine | Year: 2012

Objectives: Sedation-related adverse events in critically ill pediatric patients lack reproducible operational definitions and reference standards. Understanding these adverse events is essential to improving the quality of patient care and for developing prevention strategies in critically ill children. The purpose of this study was to test operational definitions and estimate the rate and site-to-site heterogeneity of sedation-related adverse events. Design: Prospective cohort study. Setting: Twenty-two pediatric intensive care units in the United States enrolling baseline patients into a prerandomization phase of a multicenter trial on sedation management. Patients: Pediatric patients intubated and mechanically ventilated for acute respiratory failure. DATA EXTRACTION:: Analysis of adverse event data using consistent operational definitions from a Web-based data management system. Measurements and Main Results: There were 594 sedation-related adverse events reported in 308 subjects, for a rate of 1.9 adverse events per subject and 16.6 adverse events per 100 pediatric intensive care unit days. Fifty-four percent of subjects had at least one adverse event. Seven (1%) adverse events were classified as severe, 347 (58%) as moderate, and 240 (40%) as mild. Agitation (30% of subjects, 41% of events) and pain (27% of subjects, 29% of events) were the most frequently reported events. Eight percent of subjects (n = 24) experienced 54 episodes of clinically significant iatrogenic withdrawal. Unplanned endotracheal tube extubation occurred at a rate of 0.82 per 100 ventilator days, and 32 subjects experienced postextubation stridor. Adverse events with moderate intraclass correlation coefficients included: Inadequate sedation management (intraclass correlation coefficient = 0.130), clinically significant iatrogenic withdrawal (intraclass correlation coefficient = 0.088), inadequate pain management (intraclass correlation coefficient = 0.080), and postextubation stridor (intraclass correlation coefficient = 0.078). Conclusions: Operational definitions for sedation-related adverse events were consistently applied across multiple pediatric intensive care units. Adverse event rates were different from what has been previously reported in single-center studies. Many adverse events have moderate intraclass correlation coefficients, signaling site-to-site heterogeneity. © 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Source


Kulkarni A.V.,Hospital for Sick Children | Riva-Cambrin J.,Primary Childrens Medical Center | Browd S.R.,Seattle Childrens Hospital
Journal of Neurosurgery: Pediatrics | Year: 2011

Object. Published case series of endoscopic third ventriculostomy (ETV) for childhood hydrocephalus have reported widely varying success rates. The authors recently developed and internally validated the ETV Success Score (ETVSS); this is a simplified means of predicting the 6-month success rate of ETV for a child with hydrocephalus, based on age, etiology of hydrocephalus, and presence of a previous shunt. The authors hypothesized that the ETVSS would be able to predict with reasonable accuracy the actual ETV success rate reported among published case series. Methods. A literature search was performed to identify published pediatric ETV papers that contained enough information with which to calculate an aggregate, mean predicted ETVSS for the cohort. This was then compared with the actual ETV success rate in the cohort. Data were extracted independently in triplicate, including by 2 individuals who were not involved with the development of the ETVSS. Results. Fifteen papers reporting on 322 patients were included. Interrater reliability was very high in determining the predicted ETVSS (intraclass correlation coefficient 0.99). The predicted ETVSS for each paper agreed strongly with the actual ETV success rate reported in each paper (reliability intraclass correlation coefficient 0.81). There was no significant difference in the magnitude of the predicted ETVSS and the actual ETV success (p = 0.98, paired t-test). In a linear regression model, the predicted ETVSS explained 62% of the variation in actual ETV success. When the entire cohort was combined and analyzed together, the overall mean predicted ETVSS was 57.9%, which was nearly identical to the actual ETV success rate of 59.2%. Conclusions. The ETVSS closely predicts the actual ETV success rate reported in selected papers published over the last 20 years and explains much of the variation. Source


Karlsen K.A.,Primary Childrens Medical Center | Trautman M.,Indiana University | Price-Douglas W.,Johns Hopkins Hospital | Smith S.,University of Utah
Pediatrics | Year: 2011

OBJECTIVE: Neonatal transport in the United States is a complex process; however, little is known about the neonatal transport team (NTT) workforce. The purpose of this national study was to describe the US NTT workforce. PARTICIPANTS AND METHODS: An exploratory, descriptive design that used a Web-based survey questionnaire was used. We identified 398 NTTs, and 345 (86.7%) were enrolled. One survey was completed per team. RESULTS: Ten NTTs did not complete the survey (response rate: 84.2%). Of the 335 completed surveys, 229 (68.4%) were from unit-based teams and 106 (31.6%) were from dedicated teams. Twenty-six different NTT compositions were used. All except 1 (n = 334) had a registered nurse or a neonatal nurse practitioner as a team member. A registered nurse-respiratory therapist team composition was the most common for unit-based (40.2%) and dedicated (44.3%) teams. Dedicated teams used rotor and fixed-wing modes of travel more frequently, transported further distances, and had higher transport volumes than unit-based teams. The median transport volumes reported suggest that as many as 68 797 critically ill neonates are transported each year. CONCLUSIONS: There is wide variation in many aspects of neonatal transport, including orientation, determination of readiness for independent transport, use of protocols to guide transport care, and quality assurance activities. These results will be useful for (1) evaluating existing transport services, (2) guiding necessary changes in training or services, and (3) aiding programs that seek to develop a neonatal transport program. Copyright © 2011 by the American Academy of Pediatrics. Source


Verma A.,Primary Childrens Medical Center | Verma A.,University of Utah | Warner S.L.,University of Utah | Vankayalapati H.,University of Utah | And 2 more authors.
Molecular Cancer Therapeutics | Year: 2011

Receptor tyrosine kinases (RTK) are cell-surface transmembrane receptors that contain regulated kinase activity within their cytoplasmic domain and play an important role in signal transduction in both normal and malignant cells. The mammalian TAM RTK family includes 3 closely related members: Tyro-3, Axl, and Mer. Overexpression or ectopic expression of the TAM receptors has been detected in a wide array of human cancers. Growth arrest-specific gene 6 has been identified as the major ligand for these TAM RTKs, and its binding to the receptors has been shown to promote proliferation and survival of cancer cells in vitro. Abnormal expression and activation of Axl or Mer can provide a survival advantage for certain cancer cells. Inhibition of Axl and Mer may enhance the sensitivity of cancer cells to cytotoxic agents and would potentially be a therapeutic strategy to target cancer cells. This review elucidates the role of Axl and Mer in normal cellular function and their role in oncogenesis. In addition, we review the potential to inhibit these RTKs for the development of therapeutic targets in treatment of cancer. ©2011 AACR. Source


Kolko D.J.,University of Pittsburgh | Iselin A.M.R.,Duke University | Gully K.J.,Primary Childrens Medical Center
Child Abuse and Neglect | Year: 2011

This paper examines the sustainability and outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) as delivered by practitioners in a community-based child protection program who had received training in the model several years earlier. Formerly described as Abuse-Focused CBT, AF-CBT is an evidence-based treatment (EBT) for child physical abuse and family aggression/conflict that was included in the National Child Traumatic Stress Network's initial EBT dissemination efforts in 2002. Seven practitioners participated in a year-long learning collaborative in AF-CBT and in similar training programs for 4 other EBTs. The agency's routine data collection system was used to document the clinical and adjustment outcomes of 52 families presenting with a physically abused child who received their services between 2 and 5 years after the AF-CBT training had ended. Measures of the use of all 5 EBTs documented their frequency, internal consistency, and intercorrelations. Controlling for the unique content of the other four EBTs, the amount of AF-CBT Abuse-specific content delivered was related to improvements on standardized parent rating scales (i.e., child externalizing behavior, anger, anxiety, social competence) and both parent and clinician ratings of the child's adjustment at discharge (i.e., child more safe, less scared/sad, more appropriate with peers). The amount of AF-CBT General content was related to a few discharge ratings (better child prognosis, helpfulness to parents). These novel data provide suggestive evidence for the sustainability and clinical benefits of AF-CBT in an existing community clinic serving physically abused children and their families, and are discussed in the context of key developments in the treatment model and dissemination literature. © 2011 Elsevier Ltd. Source

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