Impact of Ventilator-Associated Pneumonia on Resource Utilization and Patient Outcome

Abstract Objective: To assess the effect of ventilator-associated pneumonia on resource utilization, morbidity, and mortality. Design: Retrospective matched cohort study based on prospectively collected data. Setting: Medical intensive care unit of a university teaching hospital. Patients: Case-patients were all patients receiving mechanical ventilation for 48 hours or more who experienced an episode of ventilator-associated pneumonia. Control-patients were matched for number of discharge diagnoses, duration of mechanical support before the onset of pneumonia among case-patients, age, admission diagnosis, gender, and study period. Results: One hundred six cases of ventilator-associated pneumonia were identified in 452 patients receiving mechanical ventilation. The matching procedure selected 97 pairs. Length of stay in the intensive care unit and duration of mechanical ventilation were greater among case-patients by a mean of 7.2 days (P< .001) and 5.1 days (P< .001), respectively. Median costs were $24,727 (interquartile range,$18,348 to $39,703) among case-patients and$17,438 (interquartile range, $12,261 to$24,226) among control-patients (P< .001). The attributable mortality rate was 7.3% (P = .26). The attributable extra hospital stay was 10 days with an extra cost of $15,986 per episode of pneumonia. Conclusion: Ventilator-associated pneumonia negatively affects patient outcome and represents a significant burden on intensive care unit and hospital resource

Automatic Alerts for Methicillin-Resistant Staphylococcus aureus Surveillance and Control: Role of a Hospital Information System

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an escalating problem in hospitals worldwide. The hospital reservoir for MRSA includes recognized and unrecognized colonized or infected patients, as well as previously colonized or infected patients readmitted to the hospital. Early and appropriate infection control measures (ICM) are key elements to reduce MRSA transmission and to control the hospital reservoir. Objective: To describe the role of an expert system applied to the control of MRSA at a large medical center (1,600 beds) with high endemic rates. Methods: The University Hospital of Geneva has an extended hospital information system (HIS), DIOGENE, structured with an open distributed architecture. It includes administrative, medical, nursing, and laboratory applications with their relational databases. Among available patient databases, clinical microbiology laboratory and admission-discharge-transfer (ADT) databases are used to generate computer alerts. A laboratory alert (lab alert) is printed daily in the Infection Control Program (ICP) offices, listing all patients with cultures positive for MRSA detected within the preceding 24 hours. Patients might be either newly detected patients colonized or infected with MRSA, or previously recognized MRSA patients having surveillance cultures. The ICP nurses subsequently go to the ward or call the ward personnel to implement ICM. A second alert, the "readmission alert,” detects readmission to the hospital of any patient previously colonized or infected with MRSA by periodic queries (q 1 min) to the ADT database. The readmission alert is printed in the ICP offices, but also forwarded with added guidelines to the emergency room. Results: During the first 12 months of application (July 1994 to June 1995), the lab alert detected an average of 4.6 isolates per day, corresponding to 314 hospital admissions (248 patients); the use of this alert saved time for the ICP nurses by improving work organization. There were 438 readmission alerts (1.2 alerts per day) over the study period; of 347 patients screened immediately upon readmission, 114 (33%) were positive for MRSA carriage. Delayed recognition of readmitted MRSA carriers decreased significantly after the implementation of this alert; the proportion of MRSA patients recognized at the time of admission to the hospital increased from 13% in 1993 to 40% in 1995 (P<.001). Conclusions: Hospital information system-based alerts can play an important role in the surveillance and early prevention of MRSA transmission, and it can help to recognize patterns of colonization and transmissio

Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion

IntroductionHigh mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of the present study.MethodsOne hundred sixty eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level 1 Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room before the administration of any fluid resuscitation. HMGB1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, von Willebrand Factor (vWF), angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared to outcome measures obtained from the electronic medical record and trauma registry.ResultsPlasma levels of HMGB1 were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis as well with a systemic inflammatory response and activation of complement. Non-survivors had significantly higher plasma levels of HMGB1 than survivors. Finally, patients who later developed organ injury, (acute lung injury and acute renal failure) had also significantly higher plasma levels of HMGB1 early after trauma.ConclusionsThe results of this study demonstrate for the first time that HMGB1 is released into the bloodstream early after severe trauma in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response

HMGB1 Accelerates Alveolar Epithelial Repair via an IL-1β- and αvβ6 Integrin-dependent Activation of TGF-β1

High mobility group box 1 (HMGB1) protein is a danger-signaling molecule, known to activate an inflammatory response via TLR4 and RAGE. HMGB1 can be either actively secreted or passively released from damaged alveolar epithelial cells. Previous studies have shown that IL-1β, a critical mediator acute lung injury in humans that is activated by HMGB1, enhances alveolar epithelial repair, although the mechanisms are not fully understood. Herein, we tested the hypothesis that HMGB1 released by wounded alveolar epithelial cells would increase primary rat and human alveolar type II cell monolayer wound repair via an IL-1β-dependent activation of TGF-β1. HMGB1 induced in primary cultures of rat alveolar epithelial cells results in the release of IL-1β that caused the activation of TGF-β1 via a p38 MAPK-, RhoA- and αvβ6 integrin-dependent mechanism. Furthermore, active TGF-β1 accelerated the wound closure of primary rat epithelial cell monolayers via a PI3 kinase α-dependent mechanism. In conclusion, this study demonstrates that HMGB1 released by wounded epithelial cell monolayers, accelerates wound closure in the distal lung epithelium via the IL-1β-mediated αvβ6-dependent activation of TGF-β1, and thus could play an important role in the resolution of acute lung injury by promoting repair of the injured alveolar epithelium

Gravity Gradient Earth Sensor experiment on REXUS 11

This experiment is the first test of the concept for a novel attitude determination sensor in freefall, that utilizes the Earth`s gravity gradient as a reference. Current sensors require multiple optical heads with access on all faces of a satellite that might point towards the Earth [1]. Earth sensors determine the Earth vector by sensing the position of the Earth’s horizon, detecting the Earth`s IR emission against the background of space [2]. The gravity-gradient based approach does not require optical access for the sensor, and one single, compact unit can be located anywhere inside the satellite, and provide complete 4π steradian field of view. The sensor principle is based on the use of a Micro Electro Mechanical System (MEMS) device that can measure the Gravity Gradient Torque (GGT) [3]. We describe the design of the experiment to test the MEMS GGT sensor on a REXUS flight and present the results obtained

Comparing seminorms on homology

International audienceWe compare the l1-seminorm ̇1 and the manifold seminorm ̇man on n-dimensional integral homology classes. Crowley and Löh showed that for any topological space X and any α ε Hn.(X;Z) with n ≠ 3, the equality αman =α1 holds. We compute the simplicial volume of the 3-dimensional Tomei manifold and apply Gaifullin's desingularization to establish the existence of a constant δ3≈0.0115416, with the property that for any X and any α εH3(XI Z) one has the inequality

Function of the epithelial sodium channel ENaC in acute lung injury

L objectif de cette thèse est de mettre en évidence le rôle des canaux ioniques de l épithélium alvéolaire dans la pathogenèse du syndrome de détresse respiratoire aiguë. Des études cliniques ont montré que l absorption anormale de l œdème pulmonaire par l épithélium alvéolaire secondaire à la libération de médiateurs inflammatoires est une manifestation caractéristique du syndrome de détresse respiratoire aiguë. Dans une première étude, nous avons démontré que l activité élevée du transforming growth factor -b1 (TGF-b1) présent dans les alvéoles lors de détresse respiratoire aiguë provoque un œdème pulmonaire en réduisant le transport vectoriel de sodium et de fluides à travers l épithélium alvéolaire. Puis, nous avons montré que l interleukine -1b (IL-1b) permet l activation de TGF-b1 via un mécanisme cellulaire dépendant de l intégrine avb6. Finalement, dans une dernière étude, nous avons montré que IL-1b affecte directement et indirectement le transport vectoriel de sodium et d eau à travers l épithélium alvéolaire. Cette réduction de transport de fluides s est révélée être due en majeure partie à une diminution de la présence du canal sodium épithélial (ENaC) à la membrane apicale des cellules épithéliales alvéolaires, causée par l'inhibition de l activité du promoteur d ENaC par un mécanisme dépendant des MAP kinases. L ensemble de ces études démontre que TGF-b1 et IL-1b affectent la biosynthèse d ENaC, et suggère un rôle clé pour ces médiateurs dans la persistance de l'œdème pulmonaire chez les patients atteints de détresse respiratoire aiguë.The objective of this thesis is to investigate the role of abnormalities in alveolar epithelial ion channel function in the pathogenesis of acute lung injury. Clinical studies have demonstrated that impaired alveolar fluid clearance associated with the release of inflammatory mediators within the distal airspace of the lung is a characteristic feature of acute lung injury. Therefore, we examined the potential effect of these mediators on ion transport across the alveolar epithelium. In the first study, we demonstrated that increased transforming growth factor -b1 (TGF-b1) activity in distal airspaces during acute lung injury promoted pulmonary edema by reducing alveolar epithelial sodium and fluid transport. In the second study we showed that in alveolar epithelial cells, interleukin -1b (IL-1b) activated TGF-b1 via an integrin avb6-dependent mechanism. Finally in the last study, we demonstrated that IL-1b could also directly and independently reduce the alveolar epithelial sodium and fluid transport. The reduction in fluid transport was shown to be attributable in large part to a decrease in apical membrane expression of the epithelial sodium channel (ENaC) in lung epithelial cells. The decreased cell surface expression of ENaC was mediated through a MAP kinase-dependent inhibition of ENaC promoter activity. In summary, the studies presented here demonstrate that IL-1b and TGF-b1 down-regulate ENaC biosynthesis and indicate a critical role for these mediators in the impaired fluid clearance of patients with acute lung injury.NICE-BU Sciences (060882101) / SudocSudocFranceF

Reaction Wheels Desaturation Using Magnetorquers and Static Input Allocation

International audienceConsidering the most widely spread configuration of actuators for low orbit satellites, namely a set of reaction wheels and a set of magnetorquers, we revisit the classical " cross product control law " solution for achieving attitude stabilization and momentum dumping. We show how the classical solution has a quasi-cascade structure that, under a suitable input-to-state (ISS) assumption, can be stabilized by high gain, thereby making the actuators more inclined to saturate. Motivated by this, we propose a revisited version of this control law that transforms the quasi-cascade into a real cascade. Then we show that both strategies are such that the attitude control is affected by the momentum dumping, and that they both require a suitable ISS property. To overcome these drawbacks, we propose a new allocation-based controller which makes the attitude dynamics completely independent of the momentum dumping and induces global asymptotic stability without any ISS requirement. Several formal statements and simulation results support our discussions and highlight the pros and cons of the different control strategies