***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: 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 Treatment with rimantadine of influenza in children and the potential development of resistance in clinical isolates associated with therapy have not been previously studied . We compared rimantadine to acetaminophen therapy in a controlled , double-blind study of 91 children with influenza-like illness . Of 69 children with proven influenza A/H3N2 infection , 37 received rimantadine and 32 received acetaminophen for five days . Children receiving rimantadine showed significantly greater reduction in fever and improvement in daily scores for symptoms and severity of illness during the first three days . Viral shedding also diminished significantly during the first two days but subsequently increased such that by days 6 and 7 the proportion of children shedding virus , as well as the quantity of virus shed , was significantly greater in the rimantadine group . During the seven-day study , of the 22 children in the rimantadine group with serial isolates tested , ten ( 45.5 % ) had resistant isolates compared with two ( 12.5 % ) of those with serial isolates in the acetaminophen group ( P less than .03 ) . Thus , of the total 37 children in the rimantadine group , 27 % were found to have resistant isolated compared with 6 % in the total group receiving acetaminophen ( P less than .04 ) . Furthermore , the mean inhibitory concentration of rimantadine increased with time in the rimantadine group ( r = .4 , P = .002 ) but not in the acetaminophen group . Rimantadine therapy , thus , appears to be significantly more effective than acetaminophen in ameliorating the clinical signs and symptoms of influenza in children . Treatment with rimantadine was also associated with increased viral shedding after the medication was discontinued and with the development of resistance in the clinical isolates , the significance of which is unknown In two double-blind trials , volunteers challenged with rhinovirus were treated with aspirin or placebo . Aspirin treatment did not alter the rates of infection or illness but was associated with a moderate reduction in the frequency or severity of some symptoms . The overall benefit in rhinovirus infection was not statistically significant . Aspirin treatment appeared to cause a highly significant increase in the rate of virus shedding in treated subjects . The increase in virus shedding must be considered an adverse event that could influence the course of the disease in the individual and increase the likelihood of the spread of the infection to contacts 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 OBJECTIVES To determine the effects of acetylsalicylic acid ( ASA ) and acetaminophen on mortality due to influenza B infection in neonatal and weanling mice , as well as any synergistic , antagonistic or indifferent effects of the combined antipyretic and virus on mortality in mice pretreated with low doses of an industrial surfactant , Toximul MP8  , which has been shown to reproduce many of the features of Reye 's syndrome . In vitro studies were done to determine whether ASA or acetaminophen altered the normal , interferon-mediated antiviral responses of mammalian cells . The involvement of ASA or other commonly used xenobiotics in the induction of Reye 's syndrome following virus illness has not been resolved ; to do so , and to eluci date the underlying metabolic mechanism , requires these studies in an animal model . DESIGN Prospect i ve animal study . ANIMALS Newborn ( 945 ) and weanling ( 840 ) Swiss white mice , divided into 12 subgroups . INTERVENTIONS Some groups received Toximul MP8 before inoculation with a dose of mouse-adapted human influenza B that produces 30 % mortality ( LD30 ) ; after infection , each subgroup received either placebo , ASA or acetaminophen .  Mortality counts were taken daily . The in vitro effects of the antipyretics on interferon response were determined using st and ard virology techniques . OUTCOME MEASURE Mortality , analyzed by survival curves ( log rank test ) or cumulative daily mortality ( chi 2 analysis ) . Plaque-reducing dose ( PRD50 ) was used to determine the outcome of the in vitro analyses . RESULTS In neonatal mice , only subgroups given combined treatment with acetaminophen and Toximul MP8 had a statistically significant higher mortality rate than with the mice given influenza B alone . In weanling mice , it appeared that ASA shortened the time until death ; however , this difference was not statistically significant . In vitro studies demonstrated that both ASA and acetaminophen decreased the interferon-induced antiviral responses of cultured mammalian cells . CONCLUSION Antipyretics have the potential to exacerbate the consequences of a viral infection , although the specific effects are subtle and appear to be age-related BACKGROUND In patients with sepsis the production of arachidonic acid metabolites by cyclooxygenase increases , but the pathophysiologic role of these prostagl and ins is unclear . In animal models , inhibition of cyclooxygenase by treatment with ibuprofen before the onset of sepsis reduces physiologic abnormalities and improves survival . In pilot studies of patients with sepsis , treatment with ibuprofen led to improvements in gas exchange and airway mechanics . METHODS From October 1989 to March 1995 , we conducted a r and omized , double-blind , placebo-controlled trial of intravenous ibuprofen ( 10 mg per kilogram of body weight [ maximal dose , 800 mg ] , given every six hours for eight doses ) in 455 patients who had sepsis , defined as fever , tachycardia , tachypnea , and acute failure of at least one organ system . RESULTS In the ibuprofen group , but not the placebo group , there were significant declines in urinary levels of prostacyclin and thromboxane , temperature , heart rate , oxygen consumption , and lactic acidosis . With ibuprofen therapy there was no increased incidence of renal dysfunction , gastrointestinal bleeding , or other adverse events . However , treatment with ibuprofen did not reduce the incidence or duration of shock or the acute respiratory distress syndrome and did not significantly improve the rate of survival at 30 days ( mortality , 37 percent with ibuprofen vs 40 percent with placebo ) . CONCLUSIONS In patients with sepsis , treatment with ibuprofen reduces levels of prostacyclin and thromboxane and decreases fever , tachycardia , oxygen consumption , and lactic acidosis , but it does not prevent the development of shock or the acute respiratory distress syndrome and does not improve survival BACKGROUND Although fever is part of the normal inflammatory process after immunisation , prophylactic antipyretic drugs are sometimes recommended to allay concerns of high fever and febrile convulsion . We assessed the effect of prophylactic administration of paracetamol at vaccination on  infant febrile reaction rates and vaccine responses . METHODS In two consecutive ( primary and booster ) r and omised , controlled , open-label vaccination studies , 459 healthy infants were enrolled from ten centres in the Czech Republic . Infants were r and omly assigned with a computer-generated r and omisation list to receive three prophylactic paracetamol doses every 6 - 8 h in the first 24 h ( n=226 ) or no prophylactic paracetamol ( n=233 ) after each vaccination with a ten-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine ( PHiD-CV ) co-administered with the hexavalent diphtheria-tetanus-3-component acellular pertussis-hepatitis B-inactivated poliovirus types 1 , 2 , and 3-H influenzae type b ( DTPa-HBV-IPV/Hib ) and oral human rotavirus vaccines . The primary objective in both studies was the reduction in febrile reactions of 38.0 degrees C or greater in the total vaccinated cohort . The second objective was assessment of immunogenicity in the according-to- protocol cohort . These studies are registered with Clinical Trials.gov , numbers NCT00370318 and NCT00496015 . FINDINGS Fever greater than 39.5 degrees C was uncommon in both groups ( after primary : one of 226 participants [ < 1 % ] in prophylactic paracetamol group vs three of 233 [ 1 % ] in no prophylactic paracetamol group ; after booster : three of 178 [ 2 % ] vs two of 172 [ 1 % ] ) . The percentage of children with temperature of 38 degrees C or greater after at least one dose was significantly lower in the prophylactic paracetamol group ( 94/226 [ 42 % ] after primary vaccination and 64/178 [ 36 % ] after booster vaccination ) than in the no prophylactic paracetamol group ( 154/233 [ 66 % ] after primary vaccination and 100/172 [ 58 % ] after booster vaccination ) . Antibody geometric mean concentrations ( GMCs ) were significantly lower in the prophylactic par 
    Output:
    
Conclusion In animal models , treatment with antipyretics for influenza infection increases the risk of mortality .