***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 
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    ***EXAMPLES*** 
    Input: Objective To evaluate the safety and physiologic actions of ibuprofen in patients with severe sepsis . Design R and omized , double-blind , placebo-controlled trial . Setting Three university hospital medical ICUs . Patients Twenty-nine patients with clinical evidence of sepsis and the need for hemodynamic monitoring with a pulmonary artery flotation catheter . Interventions Thirteen patients received placebo and 16 received ibuprofen that consisted of 600 mg ( n = 11 ) or 800 mg ( n = 5 ) iv over 20 mins , followed by three 800-mg doses administered as a rectal solution every 6 hrs . The initial iv dose was given within 4 hrs of the presumptive diagnosis of sepsis . Measurements and Main Results The peak circulating total ibuprofen concentration after the iv dose ( 49.4 ± 4.5 μg/mL , mean ± SEM ) was higher than peak concentrations after the three rectal doses ( 17.0 ± 2.7 , 16.4 ± 3.0 , 16.0 ± 3.1 μg/ mL ) . Both routes of ibuprofen administration were well tolerated . Frequent monitoring for gastrointestinal bleeding and assessment of renal and hepatic function failed to demonstrate significant differences between ibuprofen and placebo . Because a trend for reduced creatinine clearance was observed at 8 hrs in the ibuprofen group , nephrotoxicity of this drug in sepsis can not be excluded . Temperature decreased significantly within 4 hrs of the initial dose of investigational therapy in patients who received ibuprofen ( 38.5 ± 0.3 ° to 37.0 ± 0.2 ° C , p < .001 ) . However , despite this significant change in temperature , we were unable to detect significant differences in hemodynamic and respiratory values or survival  when ibuprofen-treated patients were compared with controls . Conclusions Ibuprofen was well tolerated when administered iv and rectally to patients with severe sepsis , although drug absorption was poor with the rectal route . Significant antipyretic effects of ibuprofen were demonstrated . Although an excellent safety profile characterized ibuprofen in this study , the absence of ibuprofen-associated toxicity may have been secondary to poor rectal absorption of the drug . Our results support the continued clinical investigation of ibuprofen in sepsis , using an all-intravenous route of administration Introduction The purpose of the present study was to evaluate the effects of intravenous lornoxicam on haemodynamic and biochemical parameters , serum cytokine levels and patient outcomes in severe sepsis . Methods A total of 40 patients with severe sepsis were included , and were r and omly assigned ( 20 per group ) to receive either lornoxicam ( 8 mg administered intravenously every 12 hours for six doses ) or placebo . For both groups the following were recorded : haemodynamic parameters ( heart rate , mean arterial pressure ) , nasopharyngeal body temperature , arterial blood gas changes ( pH , partial oxygen tension , partial carbon dioxide tension ) , plasma cytokine levels ( IL-1β , IL-2 receptor , IL-6 , IL-8 , tumour necrosis factor-α ) , biochemical parameters ( lactate , leucocytes , trombocytes , creatinine , total bilirubin , serum glutamate oxalate transaminase ) , length of stay in the intensive care unit , duration of mechanical ventilation and mortality . All measurements were obtained at baseline ( before the start of the study ) and at 24 , 48 and 72 hours from the start of lornoxicam/placebo administration . Results No significant differences were found between the intravenous lornoxicam and placebo groups in major cytokines , duration of ventilation and length of intensive care unit stay , and inspired fractional oxygen/arterial oxygen tension ratio ( P > 0.05 ) . Conclusion In these patients with severe sepsis , we found intravenous lornoxicam to exert no effect on haemodynamic and biochemical parameters , cytokine levels , or patient outcomes . Because of the small number of patients included in the study and the short period of observation , these findings require confirmation by larger clinical trials of intravenous lornoxicam , administered in a dose titrated manner A double-blind , placebo-controlled trial was conducted to study the effects of over-the-counter analgesic/antipyretic medications on virus shedding , immune response , and clinical status in the common cold . Sixty healthy volunteers were challenged intranasally with rhinovirus type 2 and r and omized to one of four treatment arms : aspirin , acetaminophen , ibuprofen , or placebo .  Fifty-six volunteers were successfully infected and shed virus on at least 4 days after challenge . Virus shedding , antibody levels , clinical symptoms and signs , and blood leukocyte levels were carefully monitored . Use of aspirin and acetaminophen was associated with suppression of serum neutralizing antibody response ( P less than .05 vs. placebo ) and increased nasal symptoms and signs ( P less than .05 vs. placebo ) . A concomitant rise in circulating monocytes suggested that the suppression of antibody response may be mediated through drug effects on monocytes and /or mononuclear phagocytes . There were no significant differences in viral shedding among the four groups , but a trend toward longer duration of virus shedding was observed in the aspirin and acetaminophen groups Forty-six patients with severe nonpenetrating brain injury [ Glasgow Coma Scale ( GCS ) 4 - 7 ] were r and omized to st and ard management at 37 degrees C ( n = 22 ) and to  st and ard management with systemic hypothermia to 32 to 33 degrees C ( n = 24 ) . The two groups were balanced in terms of age ( Wilcoxon 's rank sum test , p > 0.95 ) , r and omizing GCS ( chi-square test , p = 0.54 ) , and primary diagnosis . Cooling was begun within 6 h of injury by use of cooling blankets . Metocurine and morphine were given hourly during induction and maintenance of hypothermia . Rewarming was at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature had reached 33 degrees C. Muscle relaxants and sedation were continued until core temperature reached 35 degrees C. There were no cardiac or coagulopathy-related complications . Seizure incidence was lower in the hypothermia group ( Fisher 's exact text , p = 0.019 ) . Sepsis was seen more commonly in the hypothermia group , but difference was not statistically significant ( chi-square test ) . Mean Glasgow Outcome Scale ( GOS ) score at 3 months after injury showed an absolute increase of 16 % ( i.e. , 36.4 - 52.2 % ) in the number of patients in the Good Recovery/Moderate Disability ( GR/MD ) category as compared with Severe Disability/Vegetative/Dead ( SD/V/D ) ( chi-square test , p > 0.287 ) . Based on evidence of improved neurologic outcome with minimal toxicity , we believe that phase III testing of moderate systemic hypothermia in patients with severe head injury is warranted BACKGROUND Despite the large body of evidence suggesting a beneficial role of fever in the host response , antipyretic therapy is commonly employed for febrile critically ill patients . Our objective was to evaluate the impact of antipyretic therapy strategies on the outcomes of critically ill patients . METHODS Patients admitted to the Trauma Intensive Care Unit over a nine-month period were eligible for inclusion , except those with traumatic brain injury . Patients were r and omized on day three of the ICU stay into aggressive or permissive groups . The aggressive group received acetaminophen 650 mg every 6 h for temperature of > 38.5 degrees C and a cooling blanket was added for temperature of > 39.5 degrees C. The permissive group received no treatment for temperature of > 38.5 degrees C , but instead had treatment initiated at temperature of > 40 degrees C , at which time acetaminophen and cooling blankets were used until temperature was < 40 degrees C.  Patient demographics , daily temperatures , systemic inflammatory response syndrome ( SIRS ) scores , multiple organ dysfunction syndrome ( MODS ) scores , and infections and complications were recorded . RESULTS Between December , 2002 and September , 2003 , 572 patients were screened , of whom 82 met criteria for enrollment . Forty-four patients were r and omized to the aggressive group and 38 patients were r and omized to the permissive group for a total of 961 and 751 ICU days , respectively . There were 131 infections in the aggressive group and 85 infections in the permissive group ( 4 + /- 6 vs. 3 + /- 2 infections per patient , p = 0.26 ) . There were seven deaths in the aggressive group and only one death in the permissive group ( p = 0.06 , Fisher Exact Test ) . The study was stopped after the first interim analysis due to the mortality difference , related to the issues of waiver of consent and the m and ate for minimal risk . CONCLUSIONS Aggressively treating fever in critically ill patients may lead to a higher mortality rate Arachidonic acid metabolites , especially thromboxane-A2 and prostacyclin , have been shown to be increased in experimental models of sepsis and the adult respiratory distress syndrome ( ARDS ) and play a major pathophysiologic role . This study was design ed to determine if these metabolites are increased in human sepsis syndrome and if inhibition of fatty acid cyclooxygenase affects their formation and their pathophysiologic sequelae . We conducted a double-blind , placebo-controlled trial of ibuprofen ( 800 mg given rectally every 4 h for three doses ) in 30 patients with sepsis syndrome defined by abnormal vital signs , the appearance of serious infection , and at least one major organ failure .  Urinary concentrations of the metabolite of thromboxane-A2 , 2,3-dinor-TxB2 , and prostacyclin , 2,3-dinor-6-keto-prostagl and in F2 alpha , were elevated 10 to 20 times normal and declined to four to five times normal by 12 h after entry in the ibuprofen-treated group and remained elevated in the placebo-treated patients . The urinary concentration of TxB2 and 6-keto-prostagl and in F1 alpha , which reflect renal production of TxA2 and prostacyclin , respectively , were also increased approximately 10-fold over normal and were subsequently decreased by ibuprofen . Coincident with the reduction in metabolite levels , the ibuprofen-treated group , but not the placebo-treated group , experienced a significant decline in temperature , heart rate , and peak airway pressure , and a trend towards more rapid reversal of shock ( p = 0.12 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Objectives To evaluate the feasibility , safety and effectiveness of a new method of intravascular temperature management for inducing moderate hypothermia ( MHT ) . Design and setting s Prospect i ve , international-multicenter clinical trial conducted in four university hospitals . Patients In a 2-year period 24 patients with severe head injury and refractory high ICP were treated with MHT ( 32.5 ° C )  by intravascular methods . Results Seventeen were males and seven females , with a median age of 25 years ( range 15–60 ) . The median Glasgow Coma Scale upon admission was 7 ( range 3–13 ) and the median Injury Severity Score was 22 ( range 13–43 ) . A total of 75 % of patients presented a diffuse lesion in the pre-enrollment computed tomography .  Median time from injury until reaching refractory high ICP was 71.5 h after injury ( minimum 14 h , maximum 251 h ) . Twelve patients ( 50 % ) reached this situation within the first 72 h after injury . MHT  was attained in a median time of 3 h. Pre-enrollment median ICP was 23.8 mmHg and was reduced to 16.8 mmHg upon reaching target temperature . At 6 months after injury , nine patients had died ( 37.5 % ) , six were severely disabled ( 25 % ) , two moderately disabled ( 8.3 % ) and seven had a good recovery ( 29.2 % ) . Of the nine patients who died , in four the cause was rebound ICP during rewarming , one death was attributed to accidental potassium overload , two to septic shock , one to cardiac arrest of unknown origin and the ninth to a pulmonary embolism . Conclusion Intravascular methods to induce MHT combined with precooling with cold saline at 4 ° C appear to be feasible and effective in reducing ICP in patients with high ICP refractory to first-line therapeutic measures BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effect 
    Output:
    
our study fails to identify any beneficial effect  of antipyretic therapy on ICU patients with established diagnosis of sepsis .