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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.

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.

Dhall G.,Childrens Hospital Los Angeles | Khatua S.,Primary Childrens Medical Center | Finlay J.L.,Childrens Hospital Los Angeles
Current Opinion in Neurology | Year: 2010

Purpose of review: Pineal tumors are rare in children, with pineoblastoma and germ cell tumors (GCTs) being the most common. Here we discuss recent advances in treatment and controversies in the management of these tumors. Recent findings: There is significant heterogeneity in the clinical behavior of pineoblastoma in children. We will discuss differences in outcome of children with pineoblastoma who are less than and greater than 3 years of age, and between pineoblastoma and nonpineal supratentorial primitive neuro-ectodermal tumors when treated with multiple different strategies. Significant controversies exist in the treatment of GCTs as well, including the levels of tumor markers in the blood and cerebrospinal fluid that are required to establish without biopsy the diagnosis of a GCT, the role of surgery in GCTs and the optimal treatment for germinomas as well as mixed malignant GCTs. Summary: Although pineoblastoma in infants and very young children still remains a therapeutic challenge, significant progress has been made in the treatment of pineal GCTs with treatment strategies using a combination of chemotherapy and reduced dose and volume irradiation, resulting in increased survival rates and reduced long-term morbidity. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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.

Ventre K.,Primary Childrens Medical Center
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infection in infants and is responsible for many hospitalizations annually. Ribavirin is approved for treatment of these infections, but its use is controversial because of questions about its efficacy, concerns about occupational exposure, and its high cost. OBJECTIVES: The objective of this review is to assess the efficacy of aerosolized ribavirin for infants and children with lower respiratory tract infection due to RSV. SEARCH STRATEGY: We performed an updated electronic search of the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database (EED) (The Cochrane Library 2006, issue 3) which contains the Acute Respiratory Infections Group's specialized register; MEDLINE (Ovid) (2004 to September Week 3 2006); and EMBASE (WebSpirs) (2004 to June 2006). SELECTION CRITERIA: Randomized trials comparing ribavirin with placebo in infants and children with lower respiratory tract infection attributable to RSV. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. Unpublished data were requested from trial authors when necessary. MAIN RESULTS: Twelve trials were included. All trials enrolled infants below the age of six months. In four trials with 158 participants, mortality with ribavirin was 5.8% compared with 9.7% with placebo (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.18 to 1.85). In three trials with 116 participants the probability of respiratory deterioration with ribavirin was 7.1% compared with 18.3% with placebo (OR 0.37; 95% CI 0.12 to 1.18). In three studies with 104 ventilated participants, the mean difference in days of hospitalization was 1.9 fewer days with ribavirin (95% CI -4.6 to +0.9) and the mean difference in days of ventilation was 1.8 fewer days with ribavirin (95% CI -3.4 to -0.2). No statistically significant differences in long-term pulmonary function or in incidence of recurrent wheezing following RSV infection were associated with the use of ribavirin. AUTHORS' CONCLUSIONS: Trials of ribavirin for RSV lack sufficient power to provide reliable estimates of the effects. The cumulative results of three small trials show that ribavirin may reduce the duration of mechanical ventilation and may reduce days of hospitalization. In addition, use of ribavirin may be associated with a decrease in the long-term incidence of recurrent wheezing following RSV disease. A large randomized controlled trial of ribavirin for ventilated and other high-risk participants is indicated.

Larsen G.Y.,Primary Childrens Medical Center | Mecham N.,University of Utah | Greenberg R.,Primary Childrens Medical Center | Greenberg R.,University of Utah
Pediatrics | Year: 2011

BACKGROUND: Unrecognized and undertreated septic shock increases morbidity and mortality. Septic shock in children is defined as sepsis and cardiovascular organ dysfunction, not necessarily with hypotension. OBJECTIVE: Cases of unrecognized and undertreated septic shock in our emergency department (ED) were reviewed with a focus on (1) increased recognition at triage and (2) more aggressive treatment once recognized. We hypothesized that septic shock protocol and care guideline would expedite identification of septic shock, increase compliance with recommended therapy, and improve outcomes. METHODS: We developed an ED septic shock protocol and care guideline to improve recognition beginning at triage and evaluated all eligible ED patients from January 2005 to December 2009. RESULTS: We identified 345 pediatric ED patients (49% male, median age: 5.6 years), and 297 (86.1%) met septic shock criteria at triage. One hundred ninety-six (56.8%) had ≥1 chronic complex condition. Hypotension was present in 34% (n = 120); the most common findings were tachycardia (n = 251 [73%]) and skin-color changes (n = 269 [78%]). The median hospital length of stay declined over the study period (median: 181-140 hours; P < .05); there was no change in mortality rate, which averaged 6.3% (22 of 345). The greatest gains in care included more complete recording of triage vital signs, timely fluid resuscitation and antibiotic administration, and serum lactate determination. CONCLUSIONS: Implementation of an ED septic shock protocol and care guideline improved compliance in delivery of rapid, aggressive fluid resuscitation and early antibiotic and oxygen administration and was associated with decreased length of stay. Copyright © 2011 by the American Academy of Pediatrics.

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.

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.

Christensen R.D.,Primary Childrens Medical Center | Christensen R.D.,y Dee Hospital Center
Neonatology | Year: 2011

Platelet transfusions were introduced into clinical medicine about 60 years ago when they were shown to reduce the mortality rate of patients with leukemia who were bleeding secondary to hyporegenerative thrombocytopenia. In modern neonatology units, platelet transfusions are integral and indeed lifesaving for some neonates. However, the great majority of platelet transfusions currently administered in neonatal intensive care units (NICUs) are not given in the original paradigm to treat thrombocytopenic hemorrhage, but instead are administered prophylactically with the hope that they will reduce the risk of spontaneous bleeding. Weighing the risks and benefits of platelet transfusion, although imprecise, should be attempted each time a platelet transfusion is ordered. Adopting guidelines specific for platelet transfusion will improve consistency of care and will also generally reduce transfusion usage, thereby reducing costs and conserving valuable blood bank resources. Initiating specific programs to improve compliance with transfusion guidelines can further improve NICU transfusion practice. Copyright © 2011 S. Karger AG.

Kestle J.R.W.,Primary Childrens Medical Center
Journal of Neurosurgery: Pediatrics | Year: 2011

In summary, I congratulate the authors on their effort. I caution readers that the output is only as good as the quality of studies that go into the review. Even more importantly, we cannot assess the impact of studies that did not make it into the review due to the well-known publication bias in favor of positive studies. Finally, I note that 4 of the 5 authors have declared relationships with industry. It appears to me that they undertook this review with the best intentions, reasonably followed appropriate methods for systematic reviews, and hired a statistical consultant to do the analysis. Still, I wonder whether the paper would have been written if the results were negative. I wholeheartedly agree with their statement that this review of their product "does not replace the need for a randomized trial.".

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