0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Paper |

Multivariate Analysis of 9 Disease-Associated Variables for Outcome Prediction in Patients With Sepsis FREE

Steve E. Calvano, PhD; Susette M. Coyle, RN; Karen S. Barbosa; Philip S. Barie, MD; Stephen F. Lowry, MD
[+] Author Affiliations

From the Division of Surgical Sciences, Department of Surgery, University of Medicine and Dentistry of New Jersey[[ndash]]Robert Wood Johnson Medical School, New Brunswick (Drs Calvano and Lowry and Ms Coyle), and Department of Surgery, Cornell University Medical College, New York, NY (Ms Barbosa and Dr Barie).


Arch Surg. 1998;133(12):1347-1350. doi:10.1001/archsurg.133.12.1347.
Text Size: A A A
Published online

Objective  To assess the ability of 9 clinical or biological variables to predict outcome (survival or nonsurvival) using multiple regression and classification analyses.

Design  Prospective, descriptive cohort study with no interventions.

Setting  Surgical intensive care unit of a tertiary care hospital and a medical school research laboratory.

Patients  Eighteen patients with a documented source of infection who met currently accepted criteria for sepsis syndrome or septic shock.

Main Outcome Measures  Prediction of survival or nonsurvival based on analysis of clinical (Multiple Organ Dysfunction score, Acute Physiology and Chronic Health Evaluation III scores) and biological (plasma levels of cortisol, interleukin 6, interleukin 10, phospholipase A2, soluble tumor necrosis factor receptor p75, and monocyte membrane tumor necrosis factor receptor levels) variables, with comparison of predicted and actual outcomes.

Results  Plasma interleukin 6, interleukin 10, and phospholipase A2 concentrations were not significantly (P>.05) different between survivors and nonsurvivors. By standard, forward stepwise, and backward stepwise multiple regression analyses, only monocyte membrane tumor necrosis factor receptor levels measured at the onset of sepsis significantly predicted outcome in all 3 analyses. However, by both standard and backward stepwise analyses, Multiple Organ Dysfunction scores based on evaluation at the onset of sepsis and 24 hours later were also significant predictors of outcome. Classification analysis showed that assignment to outcome group was statistically significant when based on monocyte membrane tumor necrosis factor receptor levels determined at the onset of sepsis or on Multiple Organ Dysfunction scores assessed 24 hours after sepsis was diagnosed.

Conclusion  Although these findings were based on a relatively small cohort, both multiple regression and classification analyses indicated that only monocyte membrane tumor necrosis factor receptor levels are able to discriminate survivors from nonsurvivors at the onset of sepsis.

Figures in this Article

THERE IS consensus that systemic inflammation is the sine qua non for both sepsis and systemic inflammatory response syndrome (SIRS) and that this inflammation is the result of a cascade of more proximal cell-derived mediators.15 The identification of such mediators presumably would permit the development of rational strategies for early diagnosis and intervention. Unfortunately, and despite considerable efforts and great expense, no cell- or mediator-based diagnostic test or therapeutic compound has proved to be of more than marginal value in sepsis or SIRS.1,613

Appropriate classification of patients with sepsis or SIRS to outcome categories according to indexes based on overall health (including age), acute physiological characteristics, severity of injury, and the extent of organ system dysfunction has been reported.1421 However, there is controversy regarding the robustness of such classification schemes, especially at times shortly after the onset of sepsis or SIRS. Unfortunately, it is at just such early time points that outcome classification may be most critical for assigning those with an unfavorable prognosis to aggressive, novel, and resource-intensive therapies.22

Previous reports have shown that peripheral-blood monocyte tumor necrosis factor receptor (MTNFR) levels were significantly lower at diagnosis of sepsis in patients who subsequently did not survive.23,24 However, in those studies, no efforts were made to quantitate the MTNFR level as a predictor variable for outcome. In the present study, multivariate statistical methods were used to assess the ability of MTNFR levels to predict outcome and to compare the predictive capability of MTNFR with those of other clinical and biological variables reportedly related to outcome in patients with sepsis or SIRS.

PATIENTS AND EXPERIMENTAL DESIGN

All studies were approved by the appropriate institutional review board. Informed consent was obtained from each patient or a designated relative.

Eighteen patients in the surgical intensive care unit were studied. Entry criteria were those of sepsis syndrome plus documentation of a source of infection as described by Ziegler et al.7 A 10-mL arterial blood sample was obtained from each patient on entry to the study (baseline) and at 24 and 72 hours. An aliquot of blood was removed and immediately evaluated for MTNFR level. The remaining blood was centrifuged at 900g and the plasma was removed, aliquoted, and frozen (−70°C) for subsequent assays.

BIOLOGICAL ASSESSMENTS

Plasma interleukin 6, interleukin 10, phospholipase A2, and soluble tumor necrosis factor receptor p75 were quantified by sandwich enzyme-linked immunosorbent assay.11,25 Plasma cortisol concentrations were determined by direct radioimmunoassay.26 As reported previously,23,24,27,28 MTNFR levels were assessed by first lysing the erythrocytes in an aliquot of whole blood. Leukocytes so obtained were stained with biotinylated tumor necrosis factor α followed by counterstaining with phycoerythrin-conjugated streptavidin. Using flow cytometry, monocytes were identified by their simultaneous side and forward light scatter intensities on a 2-parameter dot plot. An elliptical gate was placed over the monocyte cluster, and the gated cells were then analyzed for fluorescence intensity as measured by mean channel fluorescence.

CLINICAL ASSESSMENTS

On entry to the study (baseline) and at 24 and 72 hours, patients were examined and assigned a Multiple Organ Dysfunction (MOD) score according to the method of Marshall et al14 and an Acute Physiology and Chronic Health Evaluation III score as described by Knaus et al.15

DATA ANALYSIS

Data were analyzed using STATISTICA (StatSoft, Tulsa, Okla). Two-way (outcome × time), repeated-measures analyses of variance were used for assessing overall effects of each dependent variable. Variables that showed statistically significant differences on outcome by analysis of variance were then subjected to standard, forward stepwise, and backward stepwise multiple regression (R) analyses for identification of predictor variables. The α was set at .05 for all analyses. Analyses by χ2 were used for determining significance in 2 × 2 classification tables.

There were no significant differences by analysis of variance between survivors and nonsurvivors for plasma interleukin 6, interleukin 10, or phospholipase A2 levels, so these variables were excluded from further analyses. The remaining variables were analyzed for fit with the expected normal distributions and found to be acceptable, with no values for any variable being greater or less than 3 SDs from their respective means.

Standard, forward stepwise, and backward stepwise multiple R analyses were performed, and the adjusted R2 values were greater than 0.8 in all 3 analyses, indicating the presence of significant predictor variables in the data set. Only MTNFR level at baseline was a significant predictor of outcome in all 3 multiple R analyses. However, MOD scores at baseline and at 24 hours also manifested significant predictive abilities in the standard and backward multiple R analyses.

Correlations between MTNFR level at baseline, MOD scores at baseline and at 24 hours, and the standardized predicted values were compared using the backward stepwise model (Figure 1). (Figure 1 shows scatterplots of single predictor variables vs standardized predicted values. The latter are the standardized predicted outcomes based on the multiple regression equations, which are weighted linear combinations of the predictor variables. Because in these analyses outcome is dichotomous [either survivor or nonsurvivor], any standardized predicted value that is >0 represents a predicted survivor and any value <0 represents a predicted nonsurvivor.) The superiority of MTNFR level at baseline as a predictor of outcome is apparent for this model (r = 0.79) as it was for the other 2 models (data not shown).

Place holder to copy figure label and caption

Scatterplots of outcome prediction for monocyte tumor necrosis factor receptor (MTNFR) level at baseline (A), Multiple Organ Dysfunction (MOD) score at baseline (B), and MOD score at 24 hours (C) as assessed by backward stepwise multiple R analysis. Open circles represent actual survivors; solid circles, actual nonsurvivors. Dotted lines enclose 95% confidence limits.

Graphic Jump Location

Table 1 shows a classification analysis for outcome using backward stepwise multiple R as the model and MTNFR level at baseline, MOD score at baseline, and MOD score at 24 hours as predictor variables. Backward stepwise multiple R was chosen as the model because the correlations between predictor variables and the standardized predicted values were highest in this model (Figure 1). The MTNFR level at baseline was again the best single predictor of outcome.

Table Graphic Jump LocationClassification Analysis for Outcome With Backward Stepwise Multiple R as the Model and MTNFR at Baseline and MOD at Baseline and 24 Hours as Predictor Variables*

Previous reports23,24 suggested that the MTNFR level might be a reasonable predictor of outcome in patients with sepsis. However, this suggestion was based on simple inspection of the MTNFR levels, which seemed to be uniformly low for nonsurviving patients and relatively normal for patients who ultimately survived. This was contrasted with, for example, plasma soluble tumor necrosis factor receptor concentrations, which were low in normal controls, middling in surviving patients, and high in nonsurviving patients. Thus, it was suggested that the relatively dichotomous nature of MTNFR levels in surviving vs nonsurviving patients might make this variable a good predictor of outcome in patients with sepsis.

The present results support the notion of the MTNFR level as a predictor of outcome. Only MTNFR level at baseline was a significant predictor of outcome in standard, forward, and backward multiple R analyses. However, MOD scores at baseline and at 24 hours were also significant predictors in the standard and backward models. Although MTNFR level at baseline was the strongest predictor, the overall predictability improved greatly when this variable was combined with others in the multiple R analyses. This is shown in Figure 1, where the nonsurvivors (closed circles) without exception had standardized predicted values less than 0 and survivors without exception had standardized predicted values greater than 0. Thus, when multiple weighted variables including MTNFR level at baseline and MOD scores were considered in the multiple R analyses, prediction of outcome was perfect in this small cohort.

It is not surprising that the MTNFR level was a significant early predictor of outcome. Previous reports27,28 have shown that a significant decline in MTNFR levels occurs as little as 1 hour after the administration of endotoxin to normal controls. Furthermore, modulation of MTNFR levels may be one of the most sensitive indicators of the presence of proinflammatory mediators. In a large number of studies performed with the normal human endotoxemia model, changes in MTNFR levels can still be detected, albeit attenuated, in the presence of proinflammatory cytokine antagonists and cytokine and endotoxin neutralizing agents.

The cohort evaluated in this study was small. Because extreme outliers can have profound effects in multiple R analyses, especially those with small numbers of subjects, all variables were checked for homogeneity of variance. A general rule of thumb is that a data point be considered an outlier when it is greater or less than 3 SDs from its respective mean.29 In the present study, no data for any variable met this criterion, so there is little concern that outliers influenced the results of the multiple R analyses.

The standard predicted value of 0 in the backward multiple R model was used to estimate the MTNFR level at baseline that best discriminates between survivors and nonsurvivors (Figure 1). With the use of this value, a classification analysis was then performed (Table 1). By this technique, the sensitivity and specificity were 75% and 100%, respectively. This compares favorably with the Multiple Organ Failure Scoring System of Hebert et al,16 where these values were 51% and 87%, respectively. With the use of the same method, MOD score at baseline did not classify patients as well as did MOD score at 24 hours. This also has been reported by Marshall et al14 and Barie and Hydo.21 The latter investigators found that daily MOD scores in patients whose stay in the surgical intensive care unit was more than 21 days did not distinguish survivors from nonsurvivors until day 2 of the stay. However, from day 2 on, MOD scores were predictive of outcome.

In conclusion, both multiple R and classification analyses indicate that the MTNFR level is perhaps the earliest significant predictor of 28-day mortality in patients with sepsis. It is proposed that cellular biologically based indicators such as MTNFR levels will likely enhance the early prediction of SIRS- or sepsis-related complications and mortality.

This study was supported by grant GM-34695 from the Public Health Service, Bethesda, Md.

Presented as a poster at the 18th Annual Meeting of the Surgical Infection Society, New York, NY, May 1-2, 1998.

Reprints: Steve E. Calvano, PhD, Division of Surgical Sciences, Department of Surgery, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, Clinical Academic Building, Room 7078B, 125 Paterson St, New Brunswick, NJ 08903 (e-mail: calvanst@umdnj.edu).

Lowry  SFCalvano  SEHoward  RJedSimmons  RJed Soluble cytokine and hormonal mediators of immunity and inflammation. Surgical Infectious Diseases. 3rd ed. Norwalk, Conn Appleton & Lange1995;313- 326
Cerra  FBHoward  RJedSimmons  RJed Infection, the inflammatory response, and multiple organ dysfunction. Surgical Infectious Diseases. 3rd ed. Norwalk, Conn Appleton & Lange1995;387- 400
Beutler  BARoth  BLedNielsen  TBedMcKee  AEed Orchestration of septic shock by cytokines: the role of cachectin (tumor necrosis factor). Molecular and Cellular Mechanisms of Septic Shock. New York, NY Alan R Liss Inc1989;219- 235
Bone  RC The pathogenesis of sepsis. Ann Intern Med. 1991;115457- 469
Link to Article
Rackow  ECAstiz  ME The pathophysiology and treatment of septic shock. JAMA. 1991;266548- 554
Link to Article
Wenzel  RP Anti-endotoxin monclonal antibodies. N Engl J Med. 1992;3261151- 1152
Link to Article
Ziegler  EJFisher  CJSprung  CI  et al.  Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. N Engl J Med. 1991;324429- 436
Link to Article
Greenman  RLSchein  RMNMartin  MA  et al.  A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. JAMA. 1991;2661097- 1102
Link to Article
Opal  SMFisher Jr  CJDhainaut  J-F  et al.  Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Crit Care Med. 1997;251115- 1124
Link to Article
Zeni  FFreeman  BNatanson  C Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med. 1997;251095- 1100
Link to Article
Van Zee  KJKohno  TFischer  ERock  CSMoldawer  LLLowry  SF Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive TNF-α in vitro and in vivo. Proc Natl Acad Sci U S A. 1992;894845- 4849
Link to Article
Marano  MAFong  YMoldawer  LL  et al.  Serum cachectin/TNF in critically ill burn patients correlates with infection and mortality. Surg Gynecol Obstet. 1990;17032- 38
Fisher Jr  CJAgosti  JMOpal  SM  et al.  Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. N Engl J Med. 1996;3341697- 1702
Link to Article
Marshall  JCCook  DJChristou  NVBernard  GRSprung  CLSibbald  WJ Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;231638- 1652
Link to Article
Knaus  WAWagner  DPDraper  EA  et al.  The APACHE III prognostic system: risk prediction of hospital mortality for critically ill hospitalized adults. Chest. 1991;1001619- 1636
Link to Article
Hebert  PCDrummon  AJSinger  JBernard  GRRussell  JA A simple multiple system organ failure scoring system predicts mortality of patients who have sepsis syndrome. Chest. 1993;104230- 235
Link to Article
Knaus  WAHarrell  FEFisher  CJ  et al.  The clinical evaluation of new drugs for sepsis: a prospective study design based on survival analysis. JAMA. 1993;2701233- 1241
Link to Article
Barriere  SLLowry  SF An overview of mortality risk prediction in sepsis. Crit Care Med. 1995;23376- 393
Link to Article
Meek  MMunster  AMWinchurch  RADickerson  C The Baltimore Sepsis Scale: measurement of sepsis in patients with burns using a new scoring system. J Burn Care Rehabil. 1991;12564- 568
Link to Article
Casey  LCBalk  RABone  RC Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med. 1993;119771- 778
Link to Article
Barie  PSHydo  LJ Influence of multiple organ dysfunction syndrome on duration of critical illness and hospitalization. Arch Surg. 1996;1311318- 1323
Link to Article
Knaus  WAHarrell Jr  FELa Brecque  JF  et al.  Use of predicted risk of mortality to evaluate the efficacy of anticytokine therapy in sepsis: the rhIL-1ra Phase III Sepsis Syndrome Study Group. Crit Care Med. 1996;2446- 56
Link to Article
Calvano  SEvan der Poll  TCoyle  SMBarie  PSMoldawer  LLLowry  SF Monocyte tumor necrosis factor receptor levels as a predictor of risk in human sepsis. Arch Surg. 1996;131434- 437
Link to Article
Calvano  SEThompson  WACoyle  SM  et al.  Changes in monocyte and soluble TNF receptors during endotoxemia or sepsis. Surg Forum. 1993;44114- 116
Van Zee  KJCoyle  SMCalvano  SE  et al.  Influence of IL-1 receptor blockade on the human response to endotoxemia. J Immunol. 1995;1541499- 1507
Calvano  SEAlbert  JDLegaspi  A  et al.  Comparison of numerical and phenotypic leukocyte changes during constant hydrocortisone infusion in normal subjects with those in thermally-injured patients at 24-48 hours following burn. Surg Gynecol Obstet. 1987;164509- 520
van der Poll  TCalvano  SEKumar  A  et al.  Endotoxin induces downregulation of tumor necrosis factor receptors on circulating monocytes and granulocytes in humans. Blood. 1995;862754- 2759
van der Poll  TCalvano  SEKumar  ACoyle  SMLowry  SF Epinephrine attenuates down-regulation of monocyte tumor necrosis factor receptors during human endotoxemia. J Leukoc Biol. 1997;61156- 160
Not Available, Linear regression Electronic Statistics Textbook. Tulsa, Okla StatSoft Inc1997;Web site. Available at:http://www.statsoft.com/textbook/stathome.htmlAccessed March 28, 1998

Figures

Place holder to copy figure label and caption

Scatterplots of outcome prediction for monocyte tumor necrosis factor receptor (MTNFR) level at baseline (A), Multiple Organ Dysfunction (MOD) score at baseline (B), and MOD score at 24 hours (C) as assessed by backward stepwise multiple R analysis. Open circles represent actual survivors; solid circles, actual nonsurvivors. Dotted lines enclose 95% confidence limits.

Graphic Jump Location

Tables

Table Graphic Jump LocationClassification Analysis for Outcome With Backward Stepwise Multiple R as the Model and MTNFR at Baseline and MOD at Baseline and 24 Hours as Predictor Variables*

References

Lowry  SFCalvano  SEHoward  RJedSimmons  RJed Soluble cytokine and hormonal mediators of immunity and inflammation. Surgical Infectious Diseases. 3rd ed. Norwalk, Conn Appleton & Lange1995;313- 326
Cerra  FBHoward  RJedSimmons  RJed Infection, the inflammatory response, and multiple organ dysfunction. Surgical Infectious Diseases. 3rd ed. Norwalk, Conn Appleton & Lange1995;387- 400
Beutler  BARoth  BLedNielsen  TBedMcKee  AEed Orchestration of septic shock by cytokines: the role of cachectin (tumor necrosis factor). Molecular and Cellular Mechanisms of Septic Shock. New York, NY Alan R Liss Inc1989;219- 235
Bone  RC The pathogenesis of sepsis. Ann Intern Med. 1991;115457- 469
Link to Article
Rackow  ECAstiz  ME The pathophysiology and treatment of septic shock. JAMA. 1991;266548- 554
Link to Article
Wenzel  RP Anti-endotoxin monclonal antibodies. N Engl J Med. 1992;3261151- 1152
Link to Article
Ziegler  EJFisher  CJSprung  CI  et al.  Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. N Engl J Med. 1991;324429- 436
Link to Article
Greenman  RLSchein  RMNMartin  MA  et al.  A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. JAMA. 1991;2661097- 1102
Link to Article
Opal  SMFisher Jr  CJDhainaut  J-F  et al.  Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Crit Care Med. 1997;251115- 1124
Link to Article
Zeni  FFreeman  BNatanson  C Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med. 1997;251095- 1100
Link to Article
Van Zee  KJKohno  TFischer  ERock  CSMoldawer  LLLowry  SF Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive TNF-α in vitro and in vivo. Proc Natl Acad Sci U S A. 1992;894845- 4849
Link to Article
Marano  MAFong  YMoldawer  LL  et al.  Serum cachectin/TNF in critically ill burn patients correlates with infection and mortality. Surg Gynecol Obstet. 1990;17032- 38
Fisher Jr  CJAgosti  JMOpal  SM  et al.  Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. N Engl J Med. 1996;3341697- 1702
Link to Article
Marshall  JCCook  DJChristou  NVBernard  GRSprung  CLSibbald  WJ Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;231638- 1652
Link to Article
Knaus  WAWagner  DPDraper  EA  et al.  The APACHE III prognostic system: risk prediction of hospital mortality for critically ill hospitalized adults. Chest. 1991;1001619- 1636
Link to Article
Hebert  PCDrummon  AJSinger  JBernard  GRRussell  JA A simple multiple system organ failure scoring system predicts mortality of patients who have sepsis syndrome. Chest. 1993;104230- 235
Link to Article
Knaus  WAHarrell  FEFisher  CJ  et al.  The clinical evaluation of new drugs for sepsis: a prospective study design based on survival analysis. JAMA. 1993;2701233- 1241
Link to Article
Barriere  SLLowry  SF An overview of mortality risk prediction in sepsis. Crit Care Med. 1995;23376- 393
Link to Article
Meek  MMunster  AMWinchurch  RADickerson  C The Baltimore Sepsis Scale: measurement of sepsis in patients with burns using a new scoring system. J Burn Care Rehabil. 1991;12564- 568
Link to Article
Casey  LCBalk  RABone  RC Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med. 1993;119771- 778
Link to Article
Barie  PSHydo  LJ Influence of multiple organ dysfunction syndrome on duration of critical illness and hospitalization. Arch Surg. 1996;1311318- 1323
Link to Article
Knaus  WAHarrell Jr  FELa Brecque  JF  et al.  Use of predicted risk of mortality to evaluate the efficacy of anticytokine therapy in sepsis: the rhIL-1ra Phase III Sepsis Syndrome Study Group. Crit Care Med. 1996;2446- 56
Link to Article
Calvano  SEvan der Poll  TCoyle  SMBarie  PSMoldawer  LLLowry  SF Monocyte tumor necrosis factor receptor levels as a predictor of risk in human sepsis. Arch Surg. 1996;131434- 437
Link to Article
Calvano  SEThompson  WACoyle  SM  et al.  Changes in monocyte and soluble TNF receptors during endotoxemia or sepsis. Surg Forum. 1993;44114- 116
Van Zee  KJCoyle  SMCalvano  SE  et al.  Influence of IL-1 receptor blockade on the human response to endotoxemia. J Immunol. 1995;1541499- 1507
Calvano  SEAlbert  JDLegaspi  A  et al.  Comparison of numerical and phenotypic leukocyte changes during constant hydrocortisone infusion in normal subjects with those in thermally-injured patients at 24-48 hours following burn. Surg Gynecol Obstet. 1987;164509- 520
van der Poll  TCalvano  SEKumar  A  et al.  Endotoxin induces downregulation of tumor necrosis factor receptors on circulating monocytes and granulocytes in humans. Blood. 1995;862754- 2759
van der Poll  TCalvano  SEKumar  ACoyle  SMLowry  SF Epinephrine attenuates down-regulation of monocyte tumor necrosis factor receptors during human endotoxemia. J Leukoc Biol. 1997;61156- 160
Not Available, Linear regression Electronic Statistics Textbook. Tulsa, Okla StatSoft Inc1997;Web site. Available at:http://www.statsoft.com/textbook/stathome.htmlAccessed March 28, 1998

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 10

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles