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Introduction: An adverse event (AE) is a negative consequence of health care that results in unintended injury or illness. The study investigates whether simulation-based event analysis is different from traditional event analysis in uncovering root causes and generating recommendations when analyzing AEs in hospitalized children., Methods: Two simulation scenarios were created based on real-life AEs identified through the hospital's Safety Reporting System. Scenario A involved an error of commission (inpatient drug error) and scenario B involved detecting an error that already occurred (drug infusion error). Each scenario was repeated 5 times with different, voluntary clinicians. Content analysis, using deductive and inductive approaches to coding, was used to analyze debriefing data. Causes and recommendations were compiled and compared with the traditional event analysis., Results: Errors were reproduced in 60% (3/5) of scenario A. In scenario B, participants identified the error in 100% (5/5) of simulations (average time to error detection = 15 minutes). Debriefings identified reasons for errors including product labeling, memory aid interpretation, and lack of standard work for patient handover. To prevent error, participants suggested improved drug labeling, specialized drug kits, alert signs, and handoff checklists. Compared with traditional event analysis, simulation-based event analysis revealed unique causes for error and new recommendations., Conclusions: Using simulation to analyze AEs increased unique error discovery and generated new recommendations. This method is different from traditional event analysis because of the immediate clinician debriefings in the clinical environment. Hospitals should consider simulation-based event analysis as an important addition to the traditional process.

S28463 (S28), a ligand for Toll-like receptor 7/8, has been shown to have antiinflammatory properties in rodent models of allergic asthma. The principle goal of this study was to assess whether these antiinflammatory effects can also be observed in a nonhuman primate (NHP) model of allergic asthma. NHPs were sensitized then challenged with natural allergen, Ascaris suum extract. The animals were treated with S28 orally before each allergen challenge. The protective effect of S28 in NHPs was assessed by measuring various asthma-related phenotypes. We also characterized the metabolomic and proteomic signatures of the lung environment and plasma to identify markers associated with the disease and treatment. Our data demonstrate that clinically relevant parameters, such as wheal and flare response, blood IgE levels, recruitment of white blood cells to the bronchoalveolar space, and lung responsiveness, are decreased in the S28-treated allergic NHPs compared with nontreated allergic NHPs. Furthermore, we also identified markers that can distinguish allergic from nonallergic or allergic and drug-treated NHPs, such as metabolites, phosphocreatine and glutathione, in the plasma and BAL fluid, respectively; and inflammatory cytokines, IL-5 and IL-13, in the bronchoalveolar lavage fluid. Our preclinical study demonstrates that S28 has potential as a treatment for allergic asthma in primate species closely related to humans. Combined with our previous findings, we demonstrate that S28 is effective in different models of asthma and in different species, and has the antiinflammatory properties clinically relevant for the treatment of allergic asthma.

Objective: A standardized handover curriculum (I-PASS) has been shown to reduce preventable adverse events in a large multicenter study. We aimed to study the real-world impact of the implementation of this curriculum on handover quality, duration, and identification of unstable patients., Methods: A prospective intervention study was conducted. We implemented the I-PASS curriculum via faculty education and resident workshops. Resident handover on the clinical teaching unit was videorecorded, and written handover documents were collected for 2 weeks before and after the intervention. We examined the inclusion of key elements on handover documents before and after intervention using logistic regression models accounting for multiple handovers per patient. Duration of handover was compared using a linear regression model adjusting for number of patients. Qualitative content analysis was used to describe observable differences in verbal handover recordings and written critical care consultations., Results: A total of 1275 handovers were included, comprising 364 inpatients. There was a significant increase (P < .05) in 7 of 11 key elements and a significant decrease in written physical examination findings after the intervention. No significant change was found in handover duration. Qualitative video analysis revealed observable differences in handover collaboration and organization. After the intervention, patients with critical care needs overnight were correctly identified as requiring close monitoring during handover., Conclusions: Handover training resulted in consistent inclusion of key elements and was characterized by collaboration between participants and improved organization without significant increase in handover duration. Appropriate identification and response to clinically deteriorating patients was also found using the I-PASS model., (Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objectives: 1) To determine the levels of glial fibrillary acidic protein (GFAP) in both cerebrospinal fluid and serum; 2) to determine whether serum GFAP levels correlate with functional outcome; and 3) to determine whether therapeutic hypothermia, as compared with normothermia, alters serum GFAP levels in children with severe traumatic brain injury (TBI)., Design: Laboratory-based analyses; postrandomized, controlled trial., Setting: Four Canadian pediatric intensive care units and a university-affiliated laboratory., Patients: Twenty-seven children, aged 2-17 yrs, with severe TBI (Glasgow Coma Scale score of ≤ 8)., Interventions: Hypothermia therapy (32.5°C) for 24 hrs with cooling started within 8 hrs of injury and rewarming at a rate of 0.5°C every 2 hrs or normothermia (37.0°C)., Measurements and Main Results: GFAP was measured in cerebrospinal fluid and serum, using enzyme-linked immunosorbent assay. Levels of GFAP were maximal on day 1 post-TBI, with cerebrospinal fluid GFAP (15.5 ± 6.1 ng/mL) 25-fold higher than serum GFAP (0.6 ± 0.2 ng/mL). Cerebrospinal fluid GFAP normalized by day 7, whereas serum GFAP decreased gradually to reach a steady state by day 10. Serum GFAP measured on day 1 correlated with Pediatric Cerebral Performance Category scores determined at 6 months post-TBI (ρ = 0.527; p = .008) but failed to correlate with the injury scoring on admission, physiologic variables, or indices of injury measured on computerized tomography imaging. The areas under the receiver operating characteristic curves for pediatric intensive care unit day 1 serum GFAP in determining good outcome were 0.80 (pediatric cerebral performance category, 1-2; normal-mild disability) and 0.91 (pediatric cerebral performance category, 1-3; normal-moderate disability). For a serum GFAP cutoff level of 0.6 ng/mL, sensitivity and specificity were 88% to 90% and 43% to 71%, respectively. Serum GFAP levels were similar among children randomized to either therapeutic hypothermia or normothermia., Conclusions: GFAP was markedly elevated in cerebrospinal fluid and serum in children after severe TBI and serum GFAP measured on pediatric intensive care unit day 1 correlated with functional outcome at 6 months. Hypothermia therapy did not alter serum GFAP levels compared with normothermia after severe TBI in children. Serum GFAP concentration, together with other biomarkers, may have prognostic value after TBI in children.

Background: The Institute of Medicine calls for the use of clinical guidelines and practice parameters to promote "best practices" and improve patient outcomes. In 2006, The Trauma Association of Canada Pediatric Committee set out to create an evidence-based, national pediatric cervical spine (c-spine) clearance guideline based on the literature, existing algorithms from each pediatric trauma center and from expert opinion from across Canada., Methods: A review of the literature took place in September 2006 using the PubMed database. Search criteria were "cervical spine," "c-spine," "clearance," and "trauma." Limits that were applied were "Languages: English," "Humans," "Type of Article: Meta-Analysis, Practice Guidelines, Randomized Control Trial, Review," and "Ages: all child 0-18 years." These search criteria were repeated in December 2007, April 2009, and October 2009. A total of 248 articles were identified. Existing guidelines were identified and their practices examined as models of care. Two draft guidelines were created for discussion: one for the pediatric patient with a reliable clinical examination and the other for the pediatric patient with an unreliable clinical examination. Via email, telephone, and two national videoconferences, the content of the guidelines was reviewed, discussed, and amended. The final article was prepared and circulated for author input until consensus was reached., Results: A consensus was reached on two pathways to evaluate the pediatric cervical spine: a patient with a reliable clinical examination and a patient with an unreliable examination., Conclusion: Presented herein are the consensus Trauma Association of Canada, National Pediatric Cervical Spine Evaluation Pathways for the patient with a reliable clinical examination, and the patient with and unreliable clinical examination.

Chemokine receptors CXCR4 and CCR5 play a key role in Human Immunodeficiency Virus (HIV) entry into CD4+ monocytic cells. Alteration in the expression levels of these receptors by immunoregulatory cytokines may influence viral entry and hence susceptibility to HIV infection, viral tropism, and disease progression. Helper T cell type 2 (Th2) cytokines interleukin (IL)-4 and IL-13, which share a subunit of their receptor components and exhibit similar biological effects, have been shown to play a key role in HIV infection and disease progression. In this study, we investigated the effects of IL-4 and IL-13 on the expression of CXCR4 and CCR5, and the biological implications of alteration of CXCR4 and CCR5 regulation on monocytic cells with respect to their migration in response to chemokines, HIV entry, and its replication. The results suggest that both IL-4 and IL-13 inhibited the expression of CXCR4, in contrast to CCR5, which was inhibited by IL-13 alone. The downregulation of CXCR4 and CCR5 was correspondingly associated with the inhibition of their respective ligand-induced chemotaxis. Although IL-13 inhibited the expression of both CXCR4 and CCR5, this downregulation of chemokine receptor expression was not sufficient to prevent virus entry. Furthermore, both IL-4 and IL-13 inhibited viral replication in monocytic cells, suggesting that inhibition of chemokine receptor expression per se by these cytokines may not be sufficient to prevent virus entry, and indicating these cytokines may be inhibiting viral replication by targeting pathways subsequent to virus entry.

Unlabelled: OBJECTIVE. Although infants living in the north of Canada have been reported to have one of the highest rates of hospital admission for bronchiolitis in the world, the economic effects of this condition have not been reported. Passive immunization against the Respiratory Syncytial Virus, the most common causative agent of infant bronchiolitis, is available., Methods: We tabulated transportation, in-hospital care and family accommodation costs for infants of less than 12 months of age residing in the Baffin Region of Nunavut aged who were admitted to Baffin Regional Hospital in Iqaluit, Nunavut, and the Children's Hospital of Eastern Ontario in Ottawa, Ontario, with a primary diagnosis of bronchiolitis or viral pneumonia, over a 36-month period, between April 1999 and March 2002., Results: One hundred fifty-nine infants were admitted a total of 210 times, with 196 admissions to Baffin Regional Hospital, and 14 to the Children's Hospital of Eastern Ontario, during the study period. The overall, annual, population-based admission rate for the Baffin Region of Nunavut was 197 admissions per thousand infants per year. Total costs were $2,997,373 ($2,357,747 for Baffin Regional Hospital, $639,625 for the Children's Hospital of Eastern Ontario). Overall average costs were $14,273 per admission, $12,029 for infants admitted to Baffin Regional Hospital and $45,688 for infants admitted to the Children's Hospital of Eastern Ontario., Conclusions: Infant bronchiolitis in the Baffin Region of Nunavut represents a significant burden on the territorial health care system.

Alterations in the expression of CXCR4 and CCR5, the co-receptors for HIV entry, may be associated with susceptibility of monocytic cells to HIV infection. Interferon (IFN)-gamma has been shown to inhibit HIV replication in monocytic cells, but the molecular mechanism involved is not well understood. To determine if IFN-gamma regulates HIV replication by altering CXCR-4/CCR-5 expression and hence virus entry into monocytic cells, we investigated the effects of IFN-gamma on CXCR-4 and CCR-5 expression and its biological implications with respect to HIV entry, replication and chemotaxis towards the CXCR-4 and CCR-5 ligands SDF-1 and MIP-1alpha, respectively. IFN-gamma decreased CXCR-4 and CCR-5 expression on monocytes derived from HIV-negative adults, HIV-positive adults and HIV-negative cord blood. This down-regulation of chemokine receptor expression did not result in a corresponding change in mRNA expression but was associated with elevated levels of the endogenously produced chemokines SDF-1 and RANTES. Furthermore, IFN-gamma inhibited chemotaxis in response to SDF-1 and MIP-1alpha, inhibited HIV replication, but failed to inhibit virus entry in monocytic cells. These results suggest that although IFN-gamma-induced down-regulation of CXCR-4 and CCR-5 expression is associated with an inhibition of SDF-1-/MIP-1alpha-mediated chemotaxis, IFN-gamma-induced inhibition of HIV replication may be mediated at levels subsequent to the virus entry.

We investigated the expression of membrane-bound CD14 (mCD14) on monocytes and soluble CD14 (sCD14) released into the culture supernatants of peripheral blood lymphocytes (PBMC) from human immunodeficiency virus (HIV)-infected individuals. Monocytes from HIV-positive individuals exhibited both enhanced mCD14 expression and sCD14 production in the PBMC culture supernatants compared to the levels of mCD14 and sCD14 in HIV-negative individuals. This enhanced mCD14 expression and sCD14 production in HIV-infected individuals may be due to the effects of cytokines, the bacterial product lipopolysaccharide (LPS), and/or the HIV regulatory antigens Tat and Nef. Interleukin-10 (IL-10), an immunoregulatory cytokine, as well as LPS enhanced mCD14 expression and the release of sCD14 in the culture supernatants. HIV-Nef, unlike Tat, enhanced mCD14 expression on monocytes but did not induce the release of sCD14 into the culture supernatants. Studies conducted to investigate the mechanism underlying HIV-Nef-induced mCD14 expression revealed that HIV-Nef upregulated mCD14 expression via a mechanism that does not involve endogenously produced IL-10. In contrast, LPS upregulated the expression of mCD14 and increased the release of sCD14 via a mechanism that involves, at least in part, endogenously produced IL-10. Furthermore, dexamethasone, an anti-inflammatory and immunosuppressive agent, inhibited HIV-Nef-induced CD14 expression in an IL-10-independent manner. In contrast, dexamethasone inhibited IL-10-dependent LPS-induced CD14 expression by interfering with IL-10-induced signals but not by blocking IL-10 production. These results suggest that HIV-Nef and IL-10 constitute biologically important modulators of CD14 expression which may influence immunobiological responses to bacterial infections in HIV disease.

Pneumatosis intestinalis (PI) was first described by DuVernou in 1730. Since then, there have been reports of a benign form of PI occurring in both children and adults. Pneumatosis has been associated with a great many diseases, but to our knowledge there are no reports of pneumatosis in patients with acquired immune deficiency syndrome (AIDS). In this paper we report the incidental finding of PI in an AIDS patient. With ever-increasing numbers of AIDS patients, this entity may be seen more often, and clinicians should be aware of its clinical significance.