This observation selleck compound of higher mortality with low-dose corticosteroids after adjustment for disease severity is consistent with a previous study [13]. A recent prospective, multi-center, observational study of 2,796 patients to analyze the effectiveness of treatments recommended in the sepsis guidelines using propensity scores [19], found no benefits in administration of low-dose corticosteroids in severe sepsis. These results of the Ferrer et al. 2009 study [19] agree with the findings of CORTICUS [14]. Analysis of the pivotal trials in severe sepsis using Bayesian methodology reached very similar results, showing no benefit with low-dose corticosteroids [20]. In contrast, two recent meta-analyses of randomized clinical trial results, [16,17] demonstrated significant reduction in 28-day all cause mortality (P = 0.

02) and hospital mortality (P = 0.05) with low-dose corticosteroids given for ��5 days [16], and in a subgroup of trials published after 1997, steroids were found to be harmful in less severely ill patient populations and beneficial in more severely ill patient populations [17], with the effects of low-dose corticosteroids on mortality appearing to be dependent on severity of illness.An important finding of this study was the relatively high incidence of low-dose corticosteroid use (14.2%) in patients with severe sepsis which did not require vasopressor agents. It is likely that the low cost of corticosteroids and physician comfort prescribing this therapy are significant factors in this inappropriate usage of low dose corticosteroids.

Recommendations have stated that these patients should not receive steroids [8,15]. Because of the potential complications of corticosteroids, especially superinfection [1,13], physicians should use steroids only in those patients who have clear indications for their use. In CORTICUS [14], a trend towards increased superinfection was noted among patients who received hydrocortisone (OR = 1.27; 95% CI: 0.96 to 1.68). Interestingly, the recent Annane et al. 2009 meta-analysis [16] showed no evidence of increased risk of gastroduodenal bleeding, superinfection, or acquired neuromuscular weakness with low-dose corticosteroids; however, their use was associated with an increased risk of developing hyperglycemia and hypernatremia. Unfortunately, this large registry did not collect safety information, thus we cannot examine possible side effects of corticosteroids in our population.

The strengths of this study include the large Dacomitinib number of prospectively enrolled patients in many countries and reflected real world clinical practice. It also included rigorous statistical model development, including propensity scores, to try and compensate for observed differences in disease severity. As with any observational study, there are inherent weaknesses with the PROGRESS study.