Excessive production of inflammatory mediators during invasive @entity281 plays a key role in the pathogenesis of @entity326 . In an attempt to improve survival of @entity1 with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Despite promising preclinical results, several different mediator-specific anti-inflammatory agents failed to demonstrate significant benefit in @entity1 . There was, however, a significant difference in mortality between preclinical and clinical trials. The median control mortality in preclinical trials, performed almost uniformly in highly lethal @entity295 models, was 88%. In clinical trials however, the median control mortality rate was much lower, at 41%. A recent meta-regression analysis of these preclinical and clinical trials in combination with prospective confirmatory studies demonstrated that risk of @entity204 as assessed by control group mortality rate significantly altered the treatment effect of these agents in both @entity1 and animals. While anti-inflammatory agents were very beneficial in groups with high control mortality rates, they were ineffective or harmful in groups with low control mortality rates. Thus, variation in the risk of @entity204 due to @entity295 provides a basis for the marked difference in the efficacy of these anti-inflammatory agents in preclinical and clinical trials over the last decade. In contrast to mediator-specific anti-inflammatory agents, glucocorticoids and activated protein C have recently demonstrated significant beneficial effects in individual clinical trials. However, glucocorticoids were studied only in @entity1 with vasopressor-dependent @entity326 , which is associated with a high control mortality rate (i.e. 61%) similar to the level at which mediator-specific agents would have been expected to be markedly beneficial. Furthermore, consistent with earlier findings for mediator-specific anti-inflammatory agents, analysis of the activated protein C study also demonstrated a relationship between risk of @entity204 and effect of treatment. Developing better methods to define high-risk septic populations for treatment with anti-inflammatory agents will increase the efficacy of this therapeutic approach and minimize its potential for harm.

Increasing the efficacy of anti-inflammatory agents used in the treatment of XXXX .

@entity1 :: ('9606', 'Species') :: ['humans', 'patients'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity326 :: ('MESH:D012772', 'Disease') :: ['septic shock'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death']
@entity295 :: (MESH:D018805,Disease) :: ['sepsis']
