05). There was no difference in source of infection between the two selleck screening library groups. Therapeutic interventions performed during the study are listed in Table Table2.2. There was no significant difference in therapeutic interventions between the two groups. Because the use of rhAPC has not been approved for the treatment of severe sepsis in Japan, no patient in either group underwent rhAPC.Table 1Baseline characteristics and diagnostic data of the study populationaTable 2Therapeutic interventions in the study populationaEffect of treatment on mortalityThe 28-day crude mortality rate was 25% (five of twenty patients) in the rhTM group and 47% (21 of 45 patients) in the control group. There was no difference between the two groups in unadjusted mortality (P = 0.09 by log-rank test).

Because a significant difference existed in baseline severity of illness between the two groups, we performed Cox regression analysis to adjust for these possible confounders. We assessed a total of seven possible confounders related to outcome: age, sex, APACHE II score at study entry, SOFA score at study entry, platelet count on day 0, CRP level on day 0 and administration of rhTM. Consequently, three prognostic variables were selected: sex, APACHE II score and administration of rhTM. After adjusting for APACHE II score and sex, rhTM administration was the only parameter identified as an independent significant predictor of the probability of 28-day mortality (adjusted hazard ratio, 0.303; 95% confidence interval, 0.106 to 0.871; P = 0.027) (Table (Table3).3).

The survival curves of the prediction model calculated by Cox regression analysis are shown in Figure Figure22.Table 3Independent variables in final multiple regression models by Cox regression analysisaFigure 2Adjusted estimated survival curves by covariates of APACHE II score and sex in final multivariate Cox regression models. The solid line represents patients in the rhTM group, and the dotted line represents patients in the control group. Treatment with …Effect of treatment on organ damageThe serial changes in SOFA score in the two groups are shown in Figure Figure3.3. There was a significant difference in the change of SOFA score from baseline to day 28 between the two groups (P = 0.028). In the post hoc test, the SOFA score rapidly decreased Batimastat on day 1 in the rhTM group as compared to the control group (P < 0.05), and a significant difference between the two groups continued to day 3.Figure 3Serial changes from baseline in SOFA score in the two groups. Data are expressed as group means �� standard error of the mean. SOFA score decreased over time in both groups (P = 0.016). The degree of decrease in SOFA score was significantly greater …