Early drotrecogin alpha (activated) administration in severe sepsis is associated with lower mortality: a retrospective analysis of the Canadian ENHANCE cohort.

INTRODUCTION: Early multimodal treatment of severe sepsis, including the use of drotrecogin alfa (activated) (DrotAA) when indicated, is considered essential for optimum outcome. However, predicting which infected patients will progress to severe sepsis and the need for aggressive intervention continues to be problematic. We therefore wished to explore whether there were any potential early markers that might predict improved survival in response to early use of DrotAA in patients with severe sepsis. In particular, in the dynamic setting of severe sepsis, we postulated that changes in markers reflecting evolving rather than baseline clinical status might guide therapy. METHODS: Data on a cohort of 305 Canadian patients from the open label ENHANCE trial of DrotAA in severe sepsis was retrospectively analyzed to search for potential clinical predictors of outcome in severe sepsis. Patients received a 96-hour infusion of DrotAA and were followed for 28 days. The association between time to treatment and mortality within subgroups defined by dynamic changes in various potential markers was explored. RESULTS: Mortality at 28 days was 22.6% and the variables of age, time to treatment, and early changes in serum creatinine and platelet count were identified by logistic regression as independent predictors of mortality. Across all age ranges, 28-day mortality was lower when DrotAA was administered within 24 hours of first sepsis-induced organ dysfunction compared to administration after 24 hours for both subgroups of patients defined by changes in platelet count and creatinine within the first day. CONCLUSIONS: These findings suggest that when indicated, treatment with DrotAA should be initiated as soon as possible, regardless of age. TRIAL REGISTRATION: Previous trial registration number: NCT00568893.

The short-form chronic respiratory disease questionnaire was a valid, reliable, and responsive quality-of-life instrument in acute exacerbations of chronic obstructive pulmonary disease.

OBJECTIVE: To assess the psychometric properties of the short-form chronic respiratory disease questionnaire (SF-CRQ) as a quality-of-life (QOL) instrument in chronic obstructive pulmonary disease (COPD) exacerbations. STUDY DESIGN AND SETTING: In a prospective multicenter cohort study, consecutive emergency department (ED) patients with COPD exacerbation were interviewed using the SF-CRQ and other instruments. Baseline information was collected in the ED and from follow-up data 2 weeks later. The results of the SF-CRQ were compared with the results of the other instruments and clinical variables by correlation and factor analyses. RESULTS: Of the 301 enrolled patients, 80% reported improvements across each of the domains of the SF-CRQ over the 2-week post-ED period. Overall median changes for the dyspnea, fatigue, emotional function, and mastery domains were 2, 1, 1, and 1.5, respectively (P<0.001 for each domain). Correlation and factor analyses support their convergent/divergent validity and construct validity. The reliability for the change score of the SF-CRQ was high (Cronbach's alpha coefficient, 0.82). Overall minimal clinically important difference for improvement in the SF-CRQ was 1.01 (95% confidence interval, 0.72-1.31). CONCLUSION: SF-CRQ is a valid, reliable, and responsive instrument for the assessment of short-term QOL change in patients with COPD exacerbations.