***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 efficacy of different antipyretic agents and their highest recommended doses for preventing febrile seizures . DESIGN R and omized , placebo-controlled , double-blind trial . SETTING Five hospitals , each working as the only pediatric hospital in its region . PARTICIPANTS A total of 231 children who experienced their first febrile seizure between January 1 , 1997 , and December 31 , 2003 . The children were observed for 2 years . INTERVENTIONS All febrile episodes during follow-up were treated first with either rectal diclofenac or placebo . After 8 hours , treatment was continued with oral ibuprofen , acetaminophen , or placebo . MAIN OUTCOME MEASURE Recurrence of febrile seizures . RESULTS The children experienced 851 febrile episodes , and 89 of these included a febrile seizure . Febrile seizure recurrences occurred in 54 of the 231 children ( 23.4 % ) . There were no significant differences between the groups in the main measure of effect , and the effect estimates were similar , as the rate was 23.4 % ( 46 of 197 ) in those receiving antipyretic agents and 23.5 % ( 8 of 34 ) in those receiving placebo ( difference , 0.2 ; 95 % confidence interval , -12.8 to 17.6 ; P = .99 ) . Fever was significantly higher during the episodes with seizure than in those without seizure ( 39.7 degrees C vs 38.9 degrees C ; difference , 0.7 degrees C ; 95 % confidence interval , -0.9 degrees C to -0.6 degrees C ; P < .001 ) , and this phenomenon was independent of the medication given . CONCLUSIONS Antipyretic agents are ineffective for the prevention of recurrences of febrile seizures and for the lowering of body temperature in patients with a febrile episode that leads to a recurrent febrile seizure OBJECTIVE To compare the effectiveness of tepid sponging and antipyretic drug versus only antipyretic drug among febrile children . DESIGN R and omized controlled trial . SETTING Tertiary care hospital . PARTICIPANTS 150 children 6 mo - 12 yr age with axillary temperature 101F . INTERVENTION Tepid sponging and antipyretic drug ( Paracetamol ) ( n=73 ) or only antipyretic drug ( Paracetamol ) ( n=77 ) . MAIN OUTCOME MEASURES Reduction of body temperature and level of comfort . RESULTS The reduction of body temperature in the tepid sponging and antipyretic drug group was significantly faster than only antipyretic group ; however , by the end of 2 hours both groups had reached the same degree of temperature . The children in tepid sponging and antipyretic drug had significantly higher discomfort than only antipyretic group , but the discomfort was mostly mild . CONCLUSION Apart from the initial rapid temperature reduction , addition of tepid sponging to antipyretic administration does not offer any advantage in ultimate reduction of temperature ; moreover it may result in additional discomfort Procoagulant alterations and thrombocytopenia in falciparum malaria correlate with parasitemia , serum levels of tumor necrosis factor alpha ( TNF alpha ) , and clinical severity . Thus , heparin or acetylsalicylic acid ( ASA ) , which are used frequently to prevent thrombosis and ( in the case of ASA ) to control fever , could be potentially beneficial . We r and omized 97 patients with falciparum malaria into three groups : 33 patients received low-dose heparin subcutaneously  , 31  received ASA intravenously , and 33 did not receive either drug . All patients received appropriate antiparasitic treatment . Eighteen of 97 patients ( seven receiving heparin , five receiving ASA , and 6 in the control group ) had complications upon admission . During therapy , elevated TNF alpha and lactate dehydrogenase levels and decreased platelet counts returned to normal values . Except for a minimal partial thromboplastin time prolongation with heparin , heparin or ASA did not affect any laboratory parameter , duration of parasitemia , fever clearance , or the length of hospitalization . Thus , it appears that ASA and heparin do not influence the course of falciparum malaria . Hence , in view of possible side effects , these substances should not be recommended for routine use in the treatment of human malaria A controlled clinical study compared the effectiveness of sponging with tepid water , ice water , and equal parts of 70 per cent isopropyl alcohol and water in addition to orally administered acetaminophen to reduce  fever in children . More rapid reduction of fever was demonstrated when sponging was combined with the oral antipyretic drug . Sponging with ice water or with alcohol in water  were equally effective and significantly superior to sponging with tepid water ; however , sponging with tepid water  afforded significantly better comfort during the sponging procedure Investigations in animals have suggested that conjugation of paracetamol may be reduced in malaria . We have measured plasma concentrations and the urinary excretion of paracetamol  and its phase II metabolites in eight Thai patients during uncomplicated falciparum malaria and in convalescence , following a 1000 mg single oral dose . The apparent oral clearance ( Malaria , 3.6 ; Convalescence , 3.9 ; ml·min−1·kg−1 ) , the elimination half-life ( Malaria , 3.8 ; Convalescence , 3.7 h ) and apparent volume of distribution ( Malaria , 1.2 ; Convalescence , 1.2 ; l·kg−1 ) of paracetamol were similar during malaria and convalescence . In addition , the urinary excretion of paracetamol and its major phase II metabolites and their formation clearances from paracetamol were not significantly different between the two study phases . These data show that clinical malaria infection has no effect on the conjugation of paracetamol in man The effects of quinine and paracetamol on fever were studied in 21 adult patients with acute uncomplicated falciparum malaria .  Quinine alone ( n = 7 ) had no significant effect on fever , whereas paracetamol given 2 h after quinine ( n = 7 ) or 2 h before quinine ( n = 7 ) reduced temperature by a mean of 2.1 degrees C ( st and ard deviation [ SD ] 0.95 ) and 2.1 degrees C ( SD 0.79 ) respectively . A temperature reduction of 1 degree C was associated with a mean decrement of 9.7 beats/min ( SD 3.3 ) in the pulse rate .  Quinine does not possess useful antipyretic activity Background Antipyretic drugs are widely used in children with fever , though there is a controversy about the benefit of reducing fever in children with malaria . In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon , a r and omized double blind placebo controlled trial , was design ed . Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study . For the treatment of fever , all patients " received " mechanical treatment when the temperature rose above 37.5 ° C . In addition to the mechanical treatment , continuous fanning and cooling blanket , patients were assigned r and omly to receive ibuprofen ( 7 mg/kg body weight , every eight hours ) or placebo . Results The fever clearance time using a fever threshold of 37.5 ° C was similar in children receiving ibuprofen compared to those receiving placebo . The difference was also not statistically significant using a fever threshold of 37.8 ° C or 38.0 ° C . However , the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group . Conclusion Ibuprofen is effective in reducing the time with fever . The effect on fever clearance is less obvious and depends on definition of the fever threshold . Trial registration The trial registration number is : Background The current guidelines for treatment of malaria include paracetamol to children with fever . No convincing evidence for the beneficial effects of this practice exists . Studies show that time to parasite clearance is significantly longer in children treated with paracetamol  , which questions the policy . Whether this is of clinical importance has not been investigated . Methods Children with Plasmodium falciparum monoinfection and ≥20 parasites per 200 leucocytes at the B and i m Health Centre , Guinea-Bissau were r and omized to receive paracetamol or placebo together with chloroquine for three days in a double blind r and omized study . Temperature and symptoms were recorded twice daily during treatment and on day 3 . The participants were interviewed and a malaria film taken once weekly until day 35 . The data is in the form of grouped failure-times , the outcome of interest being time until parasitaemia during follow-up . Mantel-Haenszel weighted odds ratios are given . Other differences between and within the two groups have been tested using the Chi-square test and Mann-Whitney U test . Results In the evening of the day of inclusion , the temperature was slightly , but statistically insignificant , higher in the placebo group and significantly more children complained of headache . At no other time was a significant difference in temperature or symptoms detected . However , 6 children from  the placebo-group as compared to two children from the paracetamol-group were admitted to hospital with high fever and convulsions by day 3 . No differences in the cumulative percentages of children with adequate clinical and parasitological response were found in the intention-to-treat analysis or in the per- protocol analysis . Conclusion Fewer children had early treatment failure and the mean temperature was slightly lower in the afternoon on day 0 in the paracetamol group . However , the cumulative adequate clinical and parasitological cure rates were not significantly different during the period of study . It is doubtful whether adding paracetamol to the treatment of uncomplicated malaria in children is beneficial . Trial registration NCT00137566 A comparison of different antipyretics in children with malaria showed a small effect of naproxen , but not of metamizol , on the reduction of fever peaks .  Antipyretic treatment had no effect on fever clearance and therefore should be used cautiously in the treatment of malaria Sulfadoxine/pyrimethamine ( SP ) is increasingly used against malaria in sub-Saharan Africa because of chloroquine resistance . However , chloroquine may have a beneficial antipyretic effect . We therefore compared the combination of SP plus chloroquine , chloroquine alone , SP alone , and SP plus paracetamol in the treatment of uncomplicated Plasmodium falciparum malaria in 175 Tanzanian children ( 1 - 4 years old ) in a r and omized trial . Outcome variables were axillary temperatures every six hours , daily parasitemias , and serum levels of IgG antibodies to P. falciparum . Lower mean temperatures ( 6 - 48 hours ) were achieved with SP plus chloroquine or paracetamol than with SP alone ( P < 0.001 ) or chloroquine alone ( P < 0.05 ) . All three SP-treated groups showed high and similar parasite reduction ( 0 - 48 hours ) , whereas treatment with chloroquine alone was much less effective . Levels of IgG antibodies to P. falciparum increased significantly ( P < 0.001 ) and similarly in the four treatment groups between days 0 , 2 , and 3 . Thus , the addition of chloroquine or paracetamol to SP improved the clinical outcome , but did not affect the parasitologic response or antibody production Fever almost invariably accompanies uncomplicated falciparum malaria . In a r and omized , double-'blind ' study , we compared a single dose of ibuprofen ( 10 mg/kg , n = 8) with paracetamol ( 15 mg/kg , n = 8) for the treatment of  fever > 38.5 degrees C due to uncomplicated falciparum malaria .  Ibuprofen was significantly more effective than paracetamol in lowering temperatures throughout the first 4.5 h after dosing ( P = 0.016 ) and should be considered as an antipyretic agent in the management of uncomplicated falciparum infections , providing there is no contraindication to its use A clinial trial comparing a single dose of a fixed drug combination containing chloroquine and paracetamol with chloroquine and paracetamol given as separate tablets has been conducted among 154 patients seen in the Endemic Disease Clinic of the Lagos University Teaching Hospital and at two other clinics in Nigeria . There was no statistically significant difference in the preference between the different types of prescription among the sujects in the two groups . However , a greater degree of parasite clearance was achieved sooner in those who received the fixed drug combination taken in a single or in only two doses than among those whose therapy extended over 3 days or longer using separate tablets of chloroquine and paracetamol To examine whether antipyretic therapy in young children is associated with potential risks ( interference with enhanced host defences at febrile temperatures ) or benefits ( improved comfort and behaviour ) , a r and omised , double-blind , placebo-controlled trial of paracetamol was conducted among 225 children 6 months to 6 years of age who presented with acute ( less than or equal to 4 days ) fever ( greater than or equal to 38 degrees C per rectum ) without evident bacterial focus of infection . Parents were asked to give paracetamol liquid 10 - 15 mg/kg or placebo every 4 h as needed for 
    Output:
    
Some trials detected an impact of antipyretic drugs on fever clearance time , while others did not .
No difference in the number or severity of adverse events between antipyretic drugs and control was detected .
We do not know whether antipyretics alter parasite clearance time .