Outcome measures for clinical research in sepsis: A report of the 2nd Cambridge Colloquium of the International Sepsis Forum

Marshall, John C.; Vincent, Jean‐Louis; Guyatt, Gordon; Angus, Derek C.; Abraham, Edward; Bernard, Gordon R.; Bombardier, Claire; Calandra, Thierry; Jørgensen, Henrik; Sylvester, Richard; Boers, Maarten

doi:10.1097/01.ccm.0000174478.70338.03

Cited by 136 publications

(91 citation statements)

References 74 publications

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“…Indeed, short-term survival can be considered a surrogate measure. In addition, long-term survival is confounded by deaths from other causes [30].…”

Section: Previous Studies In Copd Patients Have Suggested Thatmentioning

confidence: 99%

Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia

Rello

Rodríguez²,

Torres³

et al. 2006

European Respiratory Journal

158

113

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The mortality rate of chronic obstructive pulmonary disease (COPD) patients with community-acquired pneumonia (CAP) is reported to be low. However, studies carried out to date have included ,20% of critically ill patients.The current authors performed a secondary analysis of a prospective study evaluating 428 immunocompetent patients admitted to the intensive care unit (ICU) for severe CAP.In total, 176 COPD patients were compared with 252 non-COPD patients. In COPD patients, ICU mortality (odds ratio (OR) 1.58; 95% confidence interval (CI) 1.01-1.43) and mechanical ventilation (OR 2.78; 95% CI 1.63-4.74) rates were higher than in non-COPD patients. The ICU mortality was 39% for COPD patients initially intubated and 50% for those who failed noninvasive ventilation. The proportion of patients who were males, aged o70 yrs, smokers and who had chronic heart disease or Pseudomonas aeruginosa were higher in COPD patients. Inappropriate empirical antibiotic therapy was associated with higher mortality (OR 3.8; 95% CI 1.19-12.6). ICU mortality in COPD patients with adequate therapy was associated with bilateral pneumonia (OR 2.32; 95% CI 1.18-4.53) and shock (OR 3.53; 95% CI 1.31-9.71).In conclusion, chronic obstructive pulmonary disease patients hospitalised with communityacquired pneumonia in the intensive care unit had higher mortality and need of mechanical ventilation when compared with patients without chronic obstructive pulmonary disease.

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“…Indeed, short-term survival can be considered a surrogate measure. In addition, long-term survival is confounded by deaths from other causes [30].…”

Section: Previous Studies In Copd Patients Have Suggested Thatmentioning

confidence: 99%

Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia

Rello

Rodríguez²,

Torres³

et al. 2006

European Respiratory Journal

158

113

View full text Add to dashboard Cite

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“…First, septic shock is a syndrome rather than a distinct disease entity, and is thus characterized by broad heterogeneity with regard to etiology, physiologic consequences, morbidity, and mortality (2,4). Consequently, defining an optimal population for interventional clinical trials has been challenging, almost to the point of being not feasible.…”

mentioning

confidence: 99%

“…One potential solution for achieving sufficient statistical power is to involve a large number of pediatric centers; the recent RESOLVE trial involved 104 pediatric centers from 18 countries (3). Although this strategy holds potential for a valid outcome having broad relevance, it also has the potential to introduce additional patient heterogeneity and high variability of ''standard'' therapy, both of which can be profound confounders for bringing successful trials to fruition (4).…”

mentioning

confidence: 99%

Interleukin-8 as a Stratification Tool for Interventional Trials Involving Pediatric Septic Shock

Wong¹,

Cvijanovich²,

Wheeler³

et al. 2008

Am J Respir Crit Care Med

130

103

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Rationale: Interventional clinical trials involving children with septic shock would benefit from an efficient preenrollment stratification strategy. Objectives: To test the predictive value of interleukin (IL)-8 for 28-day mortality in pediatric septic shock. Methods: A training data set (n 5 40) identified a serum IL-8 of greater than 220 pg/ml as having a 75% sensitivity and specificity for predicting 28-day mortality. This cutoff was then subjected to a series of validation steps. Measurements and Main Results: Subjects were drawn from two large, independent pediatric septic shock databases. Prospective application of the IL-8 cutoff to validation data set 1 (n 5 139) demonstrated 78% sensitivity and 64% specificity for 28-day mortality. A serum IL-8 level of 220 pg/ml or less, however, had a negative predictive value for 28-day mortality of 95% in validation data set 1, which was subsequently applied to an independently generated data set of children with septic shock (validation set 2, n 5 193). A serum IL-8 level of 220 pg/ml or less had a negative predictive value for 28-day mortality of 94% when applied to validation set 2. Conclusions: A serum IL-8 level of 220 pg/ml or less, obtained within 24 hours of admission, predicts a high likelihood of survival in children with septic shock. We propose that IL-8 can be used to exclude such patients from interventional clinical trials and ultimately derive a study population with a more favorable risk to benefit ratio when subjected to a study agent.

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“…Despite recent advances in antibiotics and critical care therapy, sepsis is still the leading cause of mortality in critically ill patients (Marshall et al, 2005). Its progression leads to septic shock and sequential multiple organ failure, which correlate with poor outcome (Karima et al, 1999).…”

mentioning

confidence: 99%

Up-Regulation of Histamine H₄Receptors Contributes to Splenic Apoptosis in Septic Mice: Counteraction of the Antiapoptotic Action of Nuclear Factor-κB

Matsuda¹,

Teramae²,

Futatsugi³

et al. 2009

J Pharmacol Exp Ther

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The histamine H 4 receptor is the most recently identified receptor and is considered to play a role in a variety of inflammatory diseases. Histamine levels in the plasma are known to be elevated in animal models of sepsis and in septic patients. The aim of this study was to test the hypothesis that the H 4 receptor may play a significant role in the pathophysiology of sepsis. Polymicrobial sepsis was induced by cecal ligation and puncture in BALB/c mice. Although the H 4 receptor gene was undetectable in normal peripheral key organs, with the exception of the spleen, the expression levels of this gene were highly up-regulated in all those organs of septic mice. In vivo transfection of nuclear factor-B (NF-B) decoy oligodeoxynucleotide, but not of its scrambled form, resulted in a great inhibition of sepsis-induced overexpression of the H 4 receptor gene. In septic mice, marked increases in caspase-3 activation and follicular lymphocyte apoptosis in spleens were strongly suppressed by systemic treatment with synthetic small interfering RNA (siRNA) targeted to the H 4 receptor. This was associated with the up-regulation of a number of antiapoptotic proteins. These antiapoptotic effects of H 4 receptor siRNA treatment were all inhibited by further application of NF-B decoy oligonucleotide. Our results suggest that superinduction of the histamine H 4 receptor gene in peripheral key organs, including the spleen, that is promoted by sepsis is transcriptionally controlled by NF-B, whereas stimulation of this receptor is involved in the development of sepsis-induced splenic apoptosis through counteraction of the antiapoptotic action of NF-B.

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Outcome measures for clinical research in sepsis: A report of the 2nd Cambridge Colloquium of the International Sepsis Forum

Abstract: The development of explicit, hypothesis-driven, and iterative approaches to outcome measure development, patterned on approaches used in the fields of rheumatology and oncology, may improve the conduct of clinical studies in the critically ill.

Cited by 136 publications

References 74 publications

Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia

Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia

Interleukin-8 as a Stratification Tool for Interventional Trials Involving Pediatric Septic Shock

Up-Regulation of Histamine H₄Receptors Contributes to Splenic Apoptosis in Septic Mice: Counteraction of the Antiapoptotic Action of Nuclear Factor-κB

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Outcome measures for clinical research in sepsis: A report of the 2nd Cambridge Colloquium of the International Sepsis Forum

Abstract: The development of explicit, hypothesis-driven, and iterative approaches to outcome measure development, patterned on approaches used in the fields of rheumatology and oncology, may improve the conduct of clinical studies in the critically ill.

Cited by 136 publications

References 74 publications

Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia

Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia

Interleukin-8 as a Stratification Tool for Interventional Trials Involving Pediatric Septic Shock

Up-Regulation of Histamine H4Receptors Contributes to Splenic Apoptosis in Septic Mice: Counteraction of the Antiapoptotic Action of Nuclear Factor-κB

Contact Info

Product

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Up-Regulation of Histamine H₄Receptors Contributes to Splenic Apoptosis in Septic Mice: Counteraction of the Antiapoptotic Action of Nuclear Factor-κB