***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objectives : To examine the incidence of infections and to describe them and their outcome in intensive care unit ( ICU ) patients . Design and setting : International prospect i ve cohort study in which all patients admitted to the 28 participating units in eight countries between May 1997 and May 1998 were followed until hospital discharge . Patients : A total of 14,364 patients were admitted to the ICUs , 6011 of whom stayed less than 24 h and 8353 more than 24 h. Results : Overall 3034 infectious episodes were recorded at ICU admission ( crude incidence : 21.1 % ) . In ICU patients hospitalised longer than 24 h there were 1581 infectious episodes ( crude incidence : 18.9 % ) including 713 ( 45 % ) in patients already infected at ICU admission . These rates varied between ICUs . Respiratory , digestive , urinary tracts , and primary bloodstream infections represented about 80 % of all sites . Hospital-acquired and ICU-acquired infections were documented more frequently microbiologically than community-acquired infections ( 71 % and 86 % , respectively vs. 55 % ) . About 28 % of infections were associated with sepsis , 24 % with severe sepsis and 30 % with septic shock , and 18 % were not classified . Crude hospital mortality rates ranged from 16.9 % in non-infected patients to 53.6 % in patients with hospital-acquired infections at the time of ICU admission and acquiring infection during the ICU stay . Conclusions : The crude incidence of ICU infections remains high , although the rate varies between ICUs and patient subsets , illustrating the added burden of nosocomial infections in the use of ICU re sources We aim ed to characterize the pharmacokinetics and pharmacodynamics of drotrecogin alfa ( activated ) ( recombinant human activated protein C ) in patients with severe sepsis BACKGROUND In November 2001 , the Food and Drug Administration ( FDA ) approved drotrecogin alfa ( activated ) ( DrotAA ) for adults who had severe sepsis and a high risk of death . The FDA required a study to evaluate the efficacy of DrotAA for adults who had severe sepsis and a low risk of death . METHODS We r and omly assigned adult patients with severe sepsis and a low risk of death ( defined by an Acute Physiology and Chronic Health Evaluation [ APACHE II ] score < 25 or single-organ failure ) to receive an intravenous infusion of placebo or DrotAA ( 24 microg per kilogram of body weight per hour ) for 96 hours in a double-blind , placebo-controlled , multicenter trial . The prospect ively defined primary end point was death from any cause and was assessed 28 days after the start of the infusion . In-hospital mortality within 90 days after the start of the infusion was measured , and safety information was collected . RESULTS Enrollment in the trial was terminated early because of a low likelihood of meeting the prospect ively defined objective of demonstrating a significant reduction in the 28-day mortality rate with the use of DrotAA .  The study enrolled 2640 patients and collected data on 2613 ( 1297 in the placebo group and 1316 in the DrotAA group ) at the 28-day follow-up . There were no statistically significant differences between the placebo group and the DrotAA group in 28-day mortality ( 17.0 percent in the placebo group vs. 18.5 percent in the DrotAA group ; P=0.34 ; relative risk , 1.08 ; 95 percent confidence interval , 0.92 to 1.28 ) or in in-hospital mortality ( 20.5 percent vs. 20.6 percent ; P=0.98 ; relative risk , 1.00 ; 95 percent confidence interval , 0.86 to 1.16 ) . The rate of serious bleeding was greater in the DrotAA group than in the placebo group during both the infusion ( 2.4 percent vs. 1.2 percent , P=0.02 ) and the 28-day study period ( 3.9 percent vs. 2.2 percent , P=0.01 ) . CONCLUSIONS The absence of a beneficial treatment effect , coupled with an increased incidence of serious bleeding complications , indicates that DrotAA should not be used in patients with severe sepsis who are at low risk for death , such as those with single-organ failure or an APACHE II score less than 25 Objective : To determine long-term survival for subjects with severe sepsis enrolled in the previous multiple-center trial ( PROWESS ) of drotrecogin alfa ( activated ) ( DrotAA ) vs. placebo . Design : Retrospective , cross-sectional , blinded follow-up of subjects enrolled in a previous r and omized , controlled trial . Setting : One hundred sixty-four tertiary care institutions in 11 countries . Participants : The 1,690 subjects with severe sepsis enrolled and treated with study drug in PROWESS , of whom 1,220 were alive at 28 days ( the end of the original PROWESS follow-up ) . Interventions : DrotAA ( n = 850 ) , 24 & mgr;g/kg/hr for 96 hrs , or placebo ( n = 840 ) . Measurements and Main Results : Long-term survival data were collected . We had follow-up information on 100 % of subjects at 28 days , 98 % at hospital discharge , 94 % at 3 months , and 93 % at 1 yr . The longest follow-up was 3.6 yrs . Hospital survival was higher with DrotAA vs. placebo ( 70.3 % vs. 65.1 % , p = .03 ) . There was no statistically significant difference in duration of survival time or in l and mark survival rates in subjects who received DrotAA compared with those who received placebo ( median duration of survival = 1113 days vs. 846 days for DrotAA vs. placebo , p = .10 ; l and mark survival rates for DrotAA vs. placebo , 66.1 % vs. 62.4 % at 3 months [ p = .11 ] , 62.2 % vs. 60.3 % at 6 months [ p = .44 ] , 58.9 % vs. 57.2 % at 1 yr [ p = .49 ] , and 52.6 % vs. 49.3 % at 2½ yrs [ p = .21 ] ) . There was a significant interaction ( p = .0008 ) between treatment assignment and baseline Acute Physiology and Chronic Health Evaluation ( APACHE ) II scores , suggesting qualitative differences in treatment effect with severity of illness . Subjects with APACHE II ≥25 had better survival time with DrotAA ( median duration of survival : 450 vs. 71 days , p = .0005 ) . Survival rates were also higher at l and mark time points ( DrotAA vs. placebo , 58.9 % vs. 48.4 % at 3 months [ p = .003 ] , 55.2 % vs. 45.3 % at 6 months [ p = .005 ] , 52.1 % vs. 41.3 % at 1 yr [ p = .002 ] , and 45.6 % vs. 33.8 % at 2½ yrs [ p = .001 ] ) . In the APACHE II < 25 group there was no significant difference in survival time or survival rates at l and mark time points except at 1 yr ( DrotAA vs. placebo , 65.5 % vs. 72.0 % at 1 yr , p = .04 ) . Conclusions : The acute survival benefit observed in subjects with severe sepsis who received DrotAA persists to hospital discharge . The survival benefit loses statistical significance thereafter . Post hoc analysis suggests the effect of DrotAA varies by APACHE II score with improved long-term survival in subjects with APACHE II scores ≥25 but no benefit in those with lower scores BACKGROUND We conducted a retrospective evaluation of the overall safety of drotrecogin alfa ( activated ) in surgical patients with severe sepsis enrolled in PROWESS . METHODS A blinded Surgical Evaluation Committee ( SEC ) verified surgical patients as having undergone a significant operative procedure within 30 days prior to enrollment . Serious and treatment-emergent bleeding events , both during the study drug infusion period ( 120 h ) and the entire 28-day study period were analyzed by surgical status and by treatment assignment . Statistical analysis was performed using Fisher 's exact test . RESULTS Serious bleeding rates during infusion in the surgical patients were 3.1 % ( 7/228 ) and 0 % ( 0/246 ) in the drotrecogin alfa ( activated ) and placebo groups , respectively ( p = 0.006 ) . Treatment-emergent bleeding rates during infusion in the surgical patients were 16.7 % ( 38/228 ) and 7.7 % ( 19/246 ) in the drotrecogin alfa ( activated ) and placebo groups , respectively ( p = 0.003 ) . None of the treatment-emergent bleeding events was fatal . Of seven drotrecogin alfa ( activated ) serious bleeding events , six were procedure-related . The serious bleeding rates within each treatment group were statistically indistinguishable between the medical and surgical patients . However , the medical patients had numerically higher treatment-emergent bleeding rates than the surgical patients within each treatment group . Despite this observation , overall surgical patients received more transfusions of red blood cells , of platelets , and of fresh frozen plasma than their medical counterparts . CONCLUSIONS Although treatment of surgical patients with drotrecogin alfa ( activated ) for severe sepsis is associated with a higher incidence of serious bleeding and subsequent treatment- emergent bleeding events , the magnitude of this increase is small and clinical ly acceptable Objective : To compare differences in hospital mortality and re source use in adult severe sepsis subjects r and omized to receive drotrecogin alfa ( activated ) ( DrotAA ) or placebo in the PROWESS trial . Design : Retrospective , cross-sectional , blinded follow-up of subjects enrolled in a previous r and omized , controlled trial . Setting : One hundred sixty-four tertiary care institutions in 11 countries . Participants : The 1,690 subjects with severe sepsis enrolled and treated with study drug in PROWESS , of whom 1,220 were alive at 28 days ( the end of the original PROWESS follow-up ) . Interventions : DrotAA ( n = 850 ) , 24 & mgr;g/kg/hr for 96 hrs , or placebo ( n = 840 ) . Measurements and Main Results : New follow-up data through hospital discharge were merged with existing 28-day follow-up data . Hospital mortality was calculated for design ated subgroups . Intensive care unit and hospital length of stay and Simplified Therapeutic Intervention Scoring System-28 ( TISS-28 ) scores were calculated overall and in design ated subgroups . Hospital discharge location was recorded . The 95 % confidence interval of most subgroups contained the relative risk estimate for overall 28-day and hospital mortality . Median hospital length of stay and intensive care unit length of stay were similar in both treatment groups : 16 vs. 17 days ( p = .22 ) and 9 vs. 9 days ( p = .7 ) for placebo vs. DrotAA . No significant difference in TISS-28 scores was observed between treatment groups overall or in subgroups of disease severity . In subjects for whom discharge destination was reported , 42.8 % of placebo subjects and 46.8 % of DrotAA subjects ( two thirds of survivors in each group ) were discharged directly to home . Conclusions : Reduction in hospital mortality with DrotAA in most of the subgroups of PROWESS is consistent with the reduction in 28-day and hospital mortality observed in the overall PROWESS population . Additional survivors created with DrotAA treatment did not increase per-patient re source use or intensive care unit or hospital length of stay Evidence -based medicine ( EBM ) is an important strategy for assessing the vast amounts of published data and applying them appropriately to our patients . However , in intensive care medicine , there is a shortage of " gold st and ard " r and omized controlled trial evidence to support ( or not support ) therapeutic decisions . In addition , even when well-conducted r and omized trials have been performed , we are still left with unanswered questions . In the last 5 years , several clinical trials have yielded positive results with a number of interventions being shown to improve outcomes . Here , we will outline the limitations and advances of EBM in intensive care medicine , by discussing the key findings in the last few years from studies of therapeutic agents for ICU patients Objective In the multinational PROWESS trial , drotrecogin alfa ( activated ) significantly reduced mortality rate in patients with severe sepsis compared with placebo . The use of large multiple-center trials can potentially complicate interpretation of results in severe sepsis population s because of variability in medical attitudes and practice s and the frequency of confounding events such as protocol violations . The objective of this study was to perform a blinded , critical , integrated review of data from the 1,690 severe sepsis patients from 164 medical centers enrolled in the PROWESS trial using a Clinical Evaluation Committee . Design Blinded , critical , integrated review of data . Setting Participating sites . Patients The 1,690 severe sepsis patients from 164 medical centers enrolled in the PROWESS trial . Interventions We performed analyses of the optimal cohort , defined 
    Output:
    
This review suggests that APC should not be used in sepsis with an APACHE II score of less than 25 or , in paediatric patients .
There is very weak evidence supporting APC use in patients with severe sepsis and at high-risk of death .