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Gilles Clermont

Publications and source records attributed to Gilles Clermont.

At least 19 recordsLinked to original sources
PubMed2007

Perceptions of safety culture vary across the intensive care units of a single institution.

OBJECTIVE: To determine whether safety culture factors varied across the intensive care units (ICUs) of a single hospital, between nurses and physicians, and to explore ICU nursing directors' perceptions of their personnel's attitudes. DESIGN: Cross-sectional surveys using the Safety Attitudes Questionnaire-ICU version, a validated, aviation industry-based safety culture survey instrument. It assesses culture across six factors: teamwork climate, perceptions of management, safety climate, stress recognition, job satisfaction, and work environment. SETTING: Four ICUs in one tertiary care hospital. SUBJECTS: All ICU personnel. MEASUREMENTS AND MAIN RESULTS: We conducted the survey from January 1 to April 1, 2003, and achieved a 70.2% response rate (318 of 453). We calculated safety culture factor mean and percent-positive scores (percentage of respondents with a mean score of > or =75 on a 0-100 scale for which 100 is best) for each ICU. We compared mean ICU scores by ANOVA and percent-positive scores by chi-square. Mean and percent-positive scores by job category were modeled using a generalized estimating equations approach and compared using Wald statistics. We asked ICU nursing directors to estimate their personnel's mean scores and generated ratios of their estimates to the actual scores.Overall, factor scores were low to moderate across all factors (range across ICUs: 43.4-74.9 mean scores, 8.6-69.4 percent positive). Mean and percent-positive scores differed significantly (p < .0083, Bonferroni correction) across ICUs, except for stress recognition, which was uniformly low. Compared with physicians, nurses had significantly lower mean working conditions and perceptions of management scores. ICU nursing directors tended to overestimate their personnel's attitudes. This was greatest for teamwork, for which all director estimates exceeded actual scores, with a mean overestimate of 16%. CONCLUSIONS: Significant safety culture variation exists across ICUs of a single hospital. ICU nursing directors tend to overestimate their personnel's attitudes, particularly for teamwork. Culture assessments based on institutional level analysis or director opinion may be flawed.

Analysis of Variance↗
PubMed2006

RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis.

INTRODUCTION: The lack of a standard definition for acute kidney injury has resulted in a large variation in the reported incidence and associated mortality. RIFLE, a newly developed international consensus classification for acute kidney injury, defines three grades of severity--risk (class R), injury (class I) and failure (class F)--but has not yet been evaluated in a clinical series. METHODS: We performed a retrospective cohort study, in seven intensive care units in a single tertiary care academic center, on 5,383 patients admitted during a one year period (1 July 2000-30 June 2001). RESULTS: Acute kidney injury occurred in 67% of intensive care unit admissions, with maximum RIFLE class R, class I and class F in 12%, 27% and 28%, respectively. Of the 1,510 patients (28%) that reached a level of risk, 840 (56%) progressed. Patients with maximum RIFLE class R, class I and class F had hospital mortality rates of 8.8%, 11.4% and 26.3%, respectively, compared with 5.5% for patients without acute kidney injury. Additionally, acute kidney injury (hazard ratio, 1.7; 95% confidence interval, 1.28-2.13; P < 0.001) and maximum RIFLE class I (hazard ratio, 1.4; 95% confidence interval, 1.02-1.88; P = 0.037) and class F (hazard ratio, 2.7; 95% confidence interval, 2.03-3.55; P < 0.001) were associated with hospital mortality after adjusting for multiple covariates. CONCLUSION: In this general intensive care unit population, acute kidney 'risk, injury, failure', as defined by the newly developed RIFLE classification, is associated with increased hospital mortality and resource use. Patients with RIFLE class R are indeed at high risk of progression to class I or class F. Patients with RIFLE class I or class F incur a significantly increased length of stay and an increased risk of inhospital mortality compared with those who do not progress past class R or those who never develop acute kidney injury, even after adjusting for baseline severity of illness, case mix, race, gender and age.

Acute Kidney Injury↗
PubMed2006

A reduced mathematical model of the acute inflammatory response II. Capturing scenarios of repeated endotoxin administration.

Bacterial lipopolysaccharide (LPS; endotoxin) is a potent immunostimulant that can induce an acute inflammatory response comparable to a bacterial infection. Experimental observations demonstrate that this biological response can be either blunted (tolerance) or augmented (potentiation) with repeated administration of endotoxin. Both phenomena are of clinical relevance. We show that a four-dimensional differential equation model of this response reproduces many scenarios involving repeated endotoxin administration. In particular, the model can display both tolerance and potentiation from a single parameter set, under different administration scenarios. The key determinants of the outcome of our simulations are the relative time-scales of model components. These findings support the hypothesis that endotoxin tolerance and other related phenomena can be considered as dynamic manifestations of a unified acute inflammatory response, and offer specific predictions related to the dynamics of this response to endotoxin.

Acute Disease↗
PubMed2006

A reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammation.

The acute inflammatory response, triggered by a variety of biological or physical stresses on an organism, is a delicate system of checks and balances that, although aimed at promoting healing and restoring homeostasis, can result in undesired and occasionally lethal physiological responses. In this work, we derive a reduced conceptual model for the acute inflammatory response to infection, built up from consideration of direct interactions of fundamental effectors. We harness this model to explore the importance of dynamic anti-inflammation in promoting resolution of infection and homeostasis. Further, we offer a clinical correlation between model predictions and potential therapeutic interventions based on modulation of immunity by anti-inflammatory agents.

Acute Disease↗
PubMed2006

Healthcare costs and long-term outcomes after acute respiratory distress syndrome: A phase III trial of inhaled nitric oxide.

OBJECTIVE: To determine the costs and long-term outcomes of acute respiratory distress syndrome (ARDS) in previously healthy adults. To determine whether treatment with inhaled nitric oxide affects these costs and outcomes. DESIGN: One-year follow-up of a randomized trial of inhaled nitric oxide. Hospital bills were collected, and follow-up was performed at hospital discharge, 6 months, and 1 year. SETTING: Forty-six U.S. centers. PATIENTS: Three hundred and eighty-five previously healthy adults with ARDS. INTERVENTIONS: Subjects were randomized to 5 ppm inhaled nitric oxide or placebo gas. MEASUREMENTS AND MAIN RESULTS: One-year survival was 67.8%, with no difference by treatment arm (67.3% vs. 68.3% for inhaled nitric oxide vs. placebo, p = .71). Hospital costs from enrollment to discharge were high and similar in the inhaled nitric oxide and placebo arms ($48,500 vs. $47,800, p = 0.8). There were also no differences in length of stay or Therapeutic Intervention Scoring System points. Almost half (43.4%) of subjects were discharged to another healthcare facility or to home with professional help, and 24.1% were readmitted in 6 months, with no differences between groups. At 1 year, survivors reported low quality of life with no differences by treatment arm (Quality of Well-Being score [range 0-1], 0.61 vs. 0.64 for inhaled nitric oxide vs. placebo, p = .11) and poor function with no differences by treatment arm (32.5% returned to </=5 points of baseline Activities of Daily Living [range 0-100], 63.3% returned to </=10 points, and the remaining 36.7% suffered a mean decrement of 27 points). CONCLUSIONS: ARDS, even in previously healthy adults, not only is followed by poor survival, quality of life, and function but also is associated with high costs of care and postdischarge resource use. Inhaled nitric oxide at 5 ppm had no effect on these outcomes.

Administration, Inhalation↗
PubMed2006

In silico models of acute inflammation in animals.

Trauma and hemorrhagic shock elicit an acute inflammatory response, predisposing patients to sepsis, organ dysfunction, and death. Few approved therapies exist for these acute inflammatory states, mainly due to the complex interplay of interacting inflammatory and physiological elements working at multiple levels. Various animal models have been used to simulate these phenomena, but these models often do not replicate the clinical setting of multiple overlapping insults. Mathematical modeling of complex systems is an approach for understanding the interplay among biological interactions. We constructed a mathematical model using ordinary differential equations that encompass the dynamics of cells and cytokines of the acute inflammatory response, as well as global tissue dysfunction. The model was calibrated in C57Bl/6 mice subjected to (1) various doses of lipopolysaccharide (LPS) alone, (2) surgical trauma, and (3) surgery + hemorrhagic shock. We tested the model's predictive ability in scenarios on which it had not been trained, namely, (1) surgery +/- hemorrhagic shock + LPS given at times after the beginning of surgical instrumentation, and (2) surgery + hemorrhagic shock + bilateral femoral fracture. Software was created that facilitated fitting of the mathematical model to experimental data, as well as for simulation of experiments with various inflammatory challenges and associated variations (gene knockouts, inhibition of specific cytokines, etc.). Using this software, the C57Bl/6-specific model was recalibrated for inflammatory analyte data in CD14-/- mice and was used to elucidate altered features of inflammation in these animals. In other experiments, rats were subjected to surgical trauma +/- LPS or to bacterial infection via fibrin clots impregnated with various inocula of Escherichia coli. Mathematical modeling may provide insights into the complex dynamics of acute inflammation in a manner that can be tested in vivo using many fewer animals than has been possible previously.

Animals↗
PubMed2006

The role of initial trauma in the host's response to injury and hemorrhage: insights from a correlation of mathematical simulations and hepatic transcriptomic analysis.

Trauma and hemorrhagic shock (HS) elicit severe physiological disturbances that predispose the victims to subsequent organ dysfunction and death. The general lack of effective therapeutic options for these patients is mainly due to the complex interplay of interacting inflammatory and physiological elements working at multiple levels. Systems biology has emerged as a new paradigm that allows the study of large portions of physiological networks simultaneously. Seeking a better understanding of the interplay among known inflammatory pathways, we constructed a mathematical model encompassing the dynamics of the acute inflammatory response that incorporates the intertwined effects of inflammation and global tissue damage. The model was calibrated using data from C57Bl/6 mice subjected to endotoxemia, sham operation (i.e., surgical trauma induced by cannulation [ST]) or ST + HS+ resuscitation (ST-HS-R). An in silico simulation, made at whole-organism level, suggested that similar pathways of different magnitudes were operant as the degree of total body damage increased. We sought to validate this hypothesis by subjecting mice to HS and comparing the models predictions to circulating markers of inflammation and tissue injury as well as the global transcriptomic response of the liver. C57Bl/6 mice were subjected to ST or ST-HS (without resuscitation). Liver gene expression was assessed using an Affymetrix DNA microarray (GeneChip Mouse Expression Set 430A, Affymetrix, Santa Clara, CA), which contains 22,621 probe sets and effectively interrogates 12,341 mouse genes. The microarray data sets were subjected to hierarchical clustering and pathway analysis. In agreement with model predictions, circulating levels of inflammation/tissue injury markers and the microarray analysis both demonstrated that ST alone accounts for a substantial proportion of the observed phenotypic and genetic/molecular changes versus untreated animals. The addition of HS further increased the magnitude of gene expression, but relatively few additional genes were recruited. Mathematical simulations and DNA microarrays, both systems biology tools, may provide valuable insight into the complex global physiological interactions that occur in response to trauma and hemorrhagic shock.

Animals↗
PubMed2006

Medical emergency teams: a strategy for improving patient care and nursing work environments.

AIM: This paper reports a study of nurses' perceptions about medical emergency teams and their impact on patient care and the nursing work environment. BACKGROUND: In many acute care hospitals, nurses can summon emergency help by calling a medical emergency team, which is a team of expert critical care professionals adept at handling patient crisis scenarios. Critical care nurses form the core of such teams. In addition, of all the healthcare professionals, nurses are the ones who most often need and call for medical emergency team assistance. METHODS: A simple anonymous questionnaire distributed amongst 300 staff nurses at two sites of an acute care teaching hospital in the United States of America in mid-January of 2005. RESULTS: A total of 248 nurses responded to the survey (response rate = 82.7%). Ninety-three per cent of the nurses reported that medical emergency teams improved patient care and 84% felt that they improved the nursing work environment. Veteran nurses (with at least 10 years of experience) and new nurses (<1 year's experience) were more likely to perceive an improvement in patient care than other nurses (P = 0.025). Nurses who had called a medical emergency team on more than one occasion were more likely to value their ability to call a team (P = 0.002). Nearly sixty-five per cent of respondents said they would consider institutional medical emergency team response as a factor when seeking a new job in the future. Only 7% suggested a change in the team response process, and 4% suggested a change in activation criteria. CONCLUSIONS: Most nurses surveyed had a favourable opinion of the medical emergency team. Our findings suggest that other institutions should consider implementing a medical emergency team programme as a strategy to improve patient care and nurse working environment.

Attitude of Health Personnel↗
PubMed2006

Predicting late anemia in critical illness.

INTRODUCTION: Identifying critically ill patients most likely to benefit from pre-emptive therapies will become increasingly important if therapies are to be used safely and cost-effectively. We sought to determine whether a predictive model could be constructed that would serve as a useful decision support tool for the pre-emptive management of intensive care unit (ICU)-related anemia. METHODS: Our cohort consisted of all ICU patients (n = 5,170) admitted to a large tertiary-care academic medical center during the period from 1 July 2000 to 30 June 2001. We divided the cohort into development (n = 3,619) and validation (n = 1,551) sets. Using a set of demographic and physiologic variables available within six hours of ICU admission, we developed models to predict patients who either received late transfusion or developed late anemia. We then constructed a point system to quantify, within six hours of ICU admission, the likelihood of developing late anemia. RESULTS: Models showed good discrimination with receiver operating characteristic curve areas ranging from 0.72 to 0.77, although predicting late transfusion was consistently less accurate than predicting late anemia. A five-item point system predicted likelihood of late anemia as well as existing clinical trial inclusion criteria but resulted in pre-emptive intervention more than two days earlier. CONCLUSION: A rule-based decision support tool using information available within six hours of ICU admission may lead to earlier and more appropriate use of blood-sparing strategies.

Adult↗
PubMed2006

Severe sepsis in community-acquired pneumonia: when does it happen, and do systemic inflammatory response syndrome criteria help predict course?

STUDY OBJECTIVES: Most natural history studies of severe sepsis are limited to ICU populations. We describe the onset and timing of severe sepsis during the hospital course for patients hospitalized with community-acquired pneumonia (CAP). We also determine the ability of the systemic inflammatory response syndrome (SIRS) and other proposed risk stratification scores measured at emergency department (ED) presentation to predict progression to severe sepsis, septic shock, or death. DESIGN: Retrospective analysis of a prospective observational outcome study from the Pneumonia Patient Outcomes Research Team (PORT). SETTING: Four academic medical centers in the United States and Canada between October 1991 and March 1994. PARTICIPANTS: The 1,339 patients hospitalized for CAP in the PORT study cohort, and a random subset of 686 patients for whom we had information for SIRS criteria. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: All subjects had infection (CAP). Severe sepsis was defined as new-onset acute organ dysfunction in this cohort, using consensus criteria. Severe sepsis developed in one half of the patients (n = 639, 48%), nonpulmonary organ dysfunction developed in 520 patients (39%), and septic shock developed in 61 subjects (4.5%). Severe sepsis and septic shock were present at ED presentation in 457 patients (71% of severe sepsis cases) and 27 patients (44% of septic shock cases), respectively. While SIRS was common at presentation (82% of the subset of 686 had two SIRS criteria), it was not associated with increased odds for progression to severe sepsis (odds ratios [ORs], 0.65 and 0.89 for two or more SIRS criteria and three or more SIRS criteria, respectively), septic shock (ORs, 0.80 and 0.55), or death (ORs, 0.65 and 0.39), with poor discrimination (all receiver operating characteristic [ROC] areas under the curve < 0.5). The pneumonia severity index was associated with severe sepsis (p < 0.001) with moderate discrimination (ROC, 0.63). CONCLUSIONS: Severe sepsis is common in hospitalized CAP patients, occurring early in the hospital course. SIRS criteria do not appear to be useful predictors for progression to severe sepsis in CAP.

Cohort Studies↗
PubMed2005

Artificial neural networks as prediction tools in the critically ill.

The past 25 years have witnessed the development of improved tools with which to predict short-term and long-term outcomes after critical illness. The general paradigm for constructing the best known tools has been the logistic regression model. Recently, a variety of alternative tools, such as artificial neural networks, have been proposed, with claims of improved performance over more traditional models in particular settings. However, these newer methods have yet to demonstrate their practicality and usefulness within the context of predicting outcomes in the critically ill.

Cohort Studies↗
PubMed2005

Evaluating disorders with a complex genetics basis. the future roles of meta-analysis and systems biology.

Growing evidence suggests that complex gene and environment interactions underlie a number of diseases including chronic inflammatory diseases of the digestive system. The rapid advances in information and technology provide opportunities to discover the risks or etiology for a variety of disorders within individual patients. However, the availability of new data and new technology has outstripped the conceptual framework of simple disorders and challenges current statistical approaches. Here we address the issues surrounding study design and sample size for complex genetic traits, with special attention to meta-analysis and systems biology. We conclude that meta-analysis should play a limited role in evaluating studies of complex genetic diseases. Instead, systems biology-based approaches should be developed to integrate multiple, focused, and mechanistic association studies with the goal of assisting in the risk assessment of patients on a person-by-person basis.

Forecasting↗
PubMed2005

Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients.

OBJECTIVE: To determine whether haloperidol use is associated with lower mortality in mechanically ventilated patients. DESIGN: Retrospective cohort analysis. SETTING: A large tertiary care academic medical center. PATIENTS: A total of 989 patients mechanically ventilated for >48 hrs. MEASUREMENTS AND MAIN RESULTS: We compared differences in hospital mortality between patients who received haloperidol within 2 days of initiation of mechanical ventilation and those who never received haloperidol. Despite similar baseline characteristics, patients treated with haloperidol had significantly lower hospital mortality compared with those who never received haloperidol (20.5% vs. 36.1%; p = .004). The lower associated mortality persisted after adjusting for age, comorbidity, severity of illness, degree of organ dysfunction, admitting diagnosis, and other potential confounders. CONCLUSIONS: Haloperidol was associated with significantly lower hospital mortality. These findings could have enormous implications for critically ill patients. Because of their observational nature and the potential risks associated with haloperidol use, they require confirmation in a randomized, controlled trial before being applied to routine patient care.

Adult↗
PubMed2005

The acute inflammatory response in diverse shock states.

A poorly controlled acute inflammatory response can lead to organ dysfunction and death. Severe systemic inflammation can be induced and perpetuated by diverse insults such as the administration of toxic bacterial products (e.g., endotoxin), traumatic injury, and hemorrhage. Here, we probe whether these varied shock states can be explained by a universal inflammatory system that is initiated through different means and, once initiated, follows a course specified by the cellular and molecular mechanisms of the immune and endocrine systems. To examine this question, we developed a mathematical model incorporating major elements of the acute inflammatory response in C57Bl/6 mice, using input from experimental data. We found that a single model with different initiators including the autonomic system could describe the response to various insults. This model was able to predict a dose range of endotoxin at which mice would die despite having been calibrated only in nonlethal inflammatory paradigms. These results show that the complex biology of inflammation can be modeled and supports the hypothesis that shock states induced by a range of physiologic challenges could arise from a universal response that is differently initiated and modulated.

Acute Disease↗
PubMed2004

Dynamic microsimulation to model multiple outcomes in cohorts of critically ill patients.

BACKGROUND: Existing intensive care unit (ICU) prediction tools forecast single outcomes, (e.g., risk of death) and do not provide information on timing. OBJECTIVE: To build a model that predicts the temporal patterns of multiple outcomes, such as survival, organ dysfunction, and ICU length of stay, from the profile of organ dysfunction observed on admission. DESIGN: Dynamic microsimulation of a cohort of ICU patients. SETTING: 49Forty-nine ICUs in 11 countries. PATIENTS: One thousand four hundred and forty-nine patients admitted to the ICU in May 1995. INTERVENTIONS: None. MODEL CONSTRUCTION: We developed the model on all patients (n=989) from 37 randomly-selected ICUs using daily Sequential Organ Function Assessment (SOFA) scores. We validated the model on all patients (n=460) from the remaining 12 ICUs, comparing predicted-to-actual ICU mortality, SOFA scores, and ICU length of stay (LOS). MAIN RESULTS: In the validation cohort, the predicted and actual mortality were 20.1% (95%CI: 16.2%-24.0%) and 19.9% at 30 days. The predicted and actual mean ICU LOS were 7.7 (7.0-8.3) and 8.1 (7.4-8.8) days, leading to a 5.5% underestimation of total ICU bed-days. The predicted and actual cumulative SOFA scores per patient were 45.2 (39.8-50.6) and 48.2 (41.6-54.8). Predicted and actual mean daily SOFA scores were close (5.1 vs 5.5, P=0.32). Several organ-organ interactions were significant. Cardiovascular dysfunction was most, and neurological dysfunction was least, linked to scores in other organ systems. CONCLUSIONS: Dynamic microsimulation can predict the time course of multiple short-term outcomes in cohorts of critical illness from the profile of organ dysfunction observed on admission. Such a technique may prove practical as a prediction tool that evaluates ICU performance on additional dimensions besides the risk of death.

Cohort Studies↗
PubMed2004

The dynamics of acute inflammation.

When the body is infected, it mounts an acute inflammatory response to rid itself of the pathogens and restore health. Uncontrolled acute inflammation due to infection is defined clinically as sepsis and can culminate in organ failure and death. We consider a three-dimensional ordinary differential equation model of inflammation consisting of a pathogen, and two inflammatory mediators. The model reproduces the healthy outcome and diverse negative outcomes, depending on initial conditions and parameters. We analyze the various bifurcations between the different outcomes when key parameters are changed and suggest various therapeutic strategies. We suggest that the clinical condition of sepsis can arise from several distinct physiological states, each of which requires a different treatment approach.

Acute Disease↗
PubMed2004

Comparison of Cox and Gray's survival models in severe sepsis.

BACKGROUND: Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate. OBJECTIVES: To construct and compare Gray's model and two different Cox models in a large sepsis cohort. To determine whether hazards for death after sepsis were nonproportional. To explore how well the different survival modeling approaches describe these data. DESIGN: Analysis of combined data from the treatment and placebo arms of a large, negative, sepsis trial. SETTING: Intensive care units at 136 U.S. medical centers. SUBJECTS: A total of 1090 adults aged 18 yrs or older with signs and symptoms of severe sepsis and documented or probable Gram-negative infection. MEASUREMENTS: We considered 27 potential baseline risk factors and modeled survival over the 28 days after the onset of sepsis. We tested proportionality in single-variable Cox analysis using Schoenfeld residuals and log-log plots. We constructed a traditional multivariable Cox model, a multivariable Cox model with time-varying covariates, and a multivariable Gray's model. RESULTS: In single-variable analyses, 20 of the 27 potential factors were significantly associated with mortality, and 10 of 20 had nonproportional hazards. In multivariate analysis, all three models retained a very similar set of significant covariates (two models retained the identical set of nine variables, and the third differed only in that it retained the same nine plus a tenth variable). Four of the nine common covariates had nonproportional hazards. Of the three models, Gray's model best captured these changing hazard ratios over time. CONCLUSION: We confirm that many of the important predictors of mortality in severe sepsis are nonproportional and find that Gray's model seems best suited for modeling survival in this condition.

Adult↗