Activated protein C and septic shock
Bibliographic record
Abstract
BACKGROUND: Septic shock is a highly inflammatory and procoagulant state associated with significant mortality. In a single randomized controlled trial, recombinant human activated protein C (drotrecogin alfa) reduced mortality in patients with severe sepsis at high risk of death. Further clinical trials, including a recently completed trial in patients with septic shock, failed to reproduce these results. OBJECTIVE: To evaluate the effectiveness of recombinant human activated protein C on mortality in a cohort of patients with septic shock and to explore possible reasons for inconsistent results in previous studies. DESIGN: Retrospective, 2:1 propensity-matched, multicenter cohort study. SETTING: Twenty-nine academic and community intensive care units in three countries. PATIENTS: Seven thousand three hundred ninety-two adult patients diagnosed with septic shock, of which 349 received recombinant human activated protein C within 48 hrs of intensive care unit admission between 1997 and 2007. MEASUREMENTS AND MAIN RESULTS: Our primary outcomes were mortality over 30 days and mortality stratified by Acute Physiology and Chronic Health Evaluation II quartile. Using a propensity-matched Cox proportional hazard model, we observed a 6.1% absolute reduction in 30-day mortality associated with the use of recombinant human activated protein C (108/311 [34.7%] vs. 254/622 [40.8%], hazard ratio 0.72, 95% confidence interval 0.52-1.00, p = .05) and noted consistent reductions in mortality among Acute Physiology and Chronic Health Evaluation II quartiles. A time to event analysis showed that the time to appropriate antimicrobials after documented hypotension decreased for each year of study (p = .003), a finding that was congruent with a decrease in annual mortality over the study period (odds ratio 0.96 per year [95% confidence interval 0.93-0.99], p = .003). CONCLUSIONS: In this retrospective, propensity-matched, multicenter cohort study of patients with septic shock, early use of recombinant human activated protein C was associated with reduced mortality. Improvements in general quality of care such as speed of antimicrobial delivery leading to decreasing mortality of patients with septic shock may have contributed to the null results of the recently completed trial of recombinant human activated protein C in patients with septic shock.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".