***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 test the hypothesis that short-term use of ibuprofen increases  asthma morbidity in children . METHODS A r and omized , double-blind , acetaminophen-controlled clinical trial was conducted . Children who had asthma and a febrile illness were r and omly assigned to receive either acetaminophen suspension or ibuprofen suspension for fever control . Rates of hospitalization and outpatient visits for asthma during follow-up were compared by r and omization group . RESULTS A total of 1879 children receiving asthma medications were studied .  Rates of hospitalization for asthma did not vary significantly by antipyretic assignment ; compared with children who were r and omized to acetaminophen , the relative risk for children who were assigned to ibuprofen was 0.63 ( 95 % confidence interval : 0.25 - 1.6 ) . However , the risk of an outpatient visit for asthma was significantly lower in the ibuprofen group ; compared with children who were r and omized to acetaminophen , the relative risk for children who were assigned to ibuprofen was 0.56 ( 95 % confidence interval : 0.34 - 0.95 ) . CONCLUSIONS Rather than supporting the hypothesis that ibuprofen increases asthma morbidity among children who are not known to be sensitive to aspirin or other nonsteroidal antiinflammatory drugs , these data suggest that compared with acetaminophen , ibuprofen may reduce such risks . Whether the observed difference in morbidity according to treatment group is attributable to increased risk after acetaminophen use or a decrease after ibuprofen can not be determined . These data provide evidence of the relative safety of ibuprofen use in children with asthma Background . Recently ibuprofen has been introduced as a nonprescription analgesic/antipyretic for use in children . Objective . To compare the incidence of serious adverse clinical events among children < 2 years old given ibuprofen and acetaminophen to control fever . Study Design . A practitioner-based , r and omized clinical trial . A total of 27 065 febrile children were r and omized to receive acetaminophen ( 12 mg/kg ) , ibuprofen ( 5 mg/kg ) , or ibuprofen ( 10 mg/kg ) . Rates of hospitalization for acute gastrointestinal bleeding , acute renal failure , anaphylaxis , Reye 's syndrome , asthma , bronchiolitis , and vomiting/gastritis were compared by r and omization group . Results . The risk of hospitalization with any diagnosis in the 4 weeks after enrollment was 1.4 % ( 95 % confidence interval , 1.3%–1.6 % ) and did not vary by antipyretic assignment . No children were hospitalized for acute renal failure , anaphylaxis , or Reye 's syndrome . Three children were hospitalized with gastrointestinal bleeding ; all 3 had been assigned to treatment with ibuprofen . The risk of hospitalization with gastrointestinal bleeding among children r and omized to ibuprofen was 17 per 100 000 ( 95 % confidence interval , 3.5–49 per 100 000 ) but was not significantly greater than the risk among children given acetaminophen . The risk of hospitalization with asthma , bronchiolitis , or vomiting/gastritis did not differ by antipyretic assignment . Conclusions . The risk of serious adverse clinical events among children < 2 years old receiving short-term treatment with either acetaminophen or ibuprofen suspension was small and did not vary by choice of medication . These data do not provide any information on the safety of these medications when used for prolonged periods or when used together , regardless of duration Objective To determine if use of paracetamol in early life is an independent risk factor for  childhood asthma .  Design Prospect i ve birth cohort study . Setting Melbourne Atopy Cohort Study . Participants 620 children with a family history of allergic disease , with paracetamol use prospect ively documented on 18 occasions from birth to 2 years of age , followed until age 7 years . Main outcome measures The primary outcome was childhood asthma , ascertained by question naire at 6 and 7 years . Secondary outcomes were infantile wheeze , allergic rhinitis , eczema , and skin prick test positivity . Results Paracetamol had been used in 51 % ( 295/575 ) of children by 12 weeks of age and in 97 % ( 556/575 ) by 2 years . Between 6 and 7 years , 80 % ( 495/620 ) were followed up ; 30 % ( 148 ) had current asthma . Increasing frequency of paracetamol use was weakly associated with increased risk of childhood asthma ( crude odds ratio 1.18 , 95 % confidence interval 1.00 to 1.39 , per doubling of days of use ) . However , after adjustment for frequency of respiratory infections , this association essentially disappeared ( odds ratio 1.08 , 0.91 to 1.29 ) . Paracetamol use for non-respiratory causes was not associated with asthma ( crude odds ratio 0.95 , 0.81 to 1.12 ) . Conclusions In children with a family history of allergic diseases , no association was found between early paracetamol use and risk of subsequent allergic disease after adjustment for respiratory infections or when paracetamol use was restricted to non-respiratory tract infections . These findings suggest that early paracetamol use does not increase the risk of asthma BACKGROUND Many pediatricians recommend , and many parents administer , alternating or combined doses of ibuprofen and acetaminophen for fever . Limited data support this practice with st and ard US doses . OBJECTIVE This study compared the antipyretic effect of 3 different treatment regimens in children , using either ibuprofen alone , ibuprofen combined with acetaminophen , or ibuprofen followed by acetaminophen over a single 6-hour observation period . METHODS Febrile episodes from children aged 6 to 84 months were r and omized into the 3 treatment groups : a single dose of ibuprofen at the beginning of the observation period ; a single dose of ibuprofen plus a single dose of acetaminophen at the beginning of the observation period ; or ibuprofen followed by acetaminophen 3 hours later . Ibuprofen was administered at 10 mg/kg ; acetaminophen at 15 mg/kg . Temperatures were measured hourly for 6 hours using a temporal artery thermometer . The primary outcome was temperature difference between treatment groups . Adverse-event data were not collected in this single treatment period study . RESULTS Sixty febrile episodes in 46 children were assessed . The mean ( SD ) age of the children was 3.4 ( 2.2 ) years , and 31 ( 51.7 % ) were girls .  Differences among temperature curves were significant ( P < 0.001 ; the combined and alternating arms had significantly better antipyresis compared with the ibuprofen-alone group at hours 4 to 6 ( hour 4 , P < 0.005 ; hours 5 and 6 , P < 0.001 ) . All but one of the children in the combined and alternating groups were afebrile at hours 4 , 5 , and 6 . In contrast , for those receiving ibuprofen alone , 30 % , 40 % , and 50 % had temperatures > 38.0 ° C at hours 4 , 5 , and 6 , respectively ( hour 4 , P = 0.002 ; hours 5 and 6 , P < 0.001 ) . CONCLUSION During a single 6-hour observation period for these participating children , combined and alternating doses of ibuprofen and acetaminophen provided greater antipyresis than ibuprofen alone at 4 to 6 hours . Clinical Trials.gov identifier : NCT00267293 A controlled clinical study compared the antipyretic effectiveness of acetaminophen administered at regular 4 h intervals ( group 1,n=53 ) versus sproadic usage contingent upon a body temperature above 37.9 ° C ( group 2,n=51 ) in 104 children presenting with simple febrile convulsions .  The incidence of febrile episodes or temperature values were similar in spite of significantly larger amounts of acetaminophen administered to patients in group 1 . Four and 4 children in groups 1 and 2 , respectively , had a second episode of febrile seizures , in all of them within the first 24 h of admission . We conclude that the prophylactic administration of acetaminophen in children with  febrile seizures  is not effective in the prevention of fever , the reduction of its degree , or in preventing the early recurrence of febrile seizures Objective To estimate the cost to the NHS and to parents and carers of treating febrile preschool children with paracetamol , ibuprofen , or both  , and to compare these costs with the benefits of each treatment regimen . Design Cost consequences analysis and cost effectiveness analysis conducted as part of a three arm , r and omised controlled trial . Participants Children between the ages of 6 months and 6 years recruited from primary care and the community with axillary temperatures ≥37.8 ° C and ≤41 ° C . Interventions Paracetamol , ibuprofen , or both drugs . Main outcome measures Costs to the NHS and to parents and carers . Cost consequences analysis at 48 hours and 5 days comparing cost with children ’s temperature , discomfort , activity , appetite , and sleep ; cost effectiveness analysis at 48 hours comparing cost with percentage of children “ recovered . ” Results Difficulties in recruiting children to the trial lowered the precision of the estimates of cost and some outcomes . At 48 hours , cost to the NHS was £ 11.33 for paracetamol , £ 8.49 for ibuprofen , and £ 8.16 for both drugs . By day 5 these costs rose to £ 19.63 , £ 18.36 , and £ 13.92 respectively . For parents and carers , the 48 hour costs were £ 23.86 for paracetamol , £ 20.60 for ibuprofen , and £ 25.07 for both , and the day 5 costs were £ 26.35 , £ 29.90 , and £ 24.02 respectively . Outcomes measured at 48 hours and 5 days were inconclusive because of lack of power ; the cost effectiveness analysis at 48 hours provided little evidence that one treatment choice was significantly more cost effective than another . At 4 hours ibuprofen and the combined treatment were superior to paracetamol in terms of the trial primary outcome of time without fever ; at 24 hours the combined treatment performed best on this outcome . Conclusions There is no strong evidence of a difference in cost between the treatments , but clinical and cost data together indicate that using both drugs together may be most cost effective over the course of the illness . This treatment option performs best and is no more expensive because of less use of healthcare re sources , result ing in lower costs to the NHS and to parents Objective To investigate whether paracetamol ( acetaminophen ) plus ibuprofen are superior to either drug alone for increasing time without fever and the relief of fever associated discomfort in febrile children managed at home . Design Individually r and omised , blinded , three arm trial . Setting Primary care and households in Engl and . Participants Children aged between 6 months and 6 years with axillary temperatures of at least 37.8 ° C and up to 41.0 ° C . Intervention Advice on physical measures to reduce temperature and the provision of , and advice to give , paracetamol plus ibuprofen , paracetamol alone , or ibuprofen alone . Main outcome measures Primary outcomes were the time without fever ( < 37.2 ° C ) in the first four hours after the first dose was given and the proportion of children reported as being normal on the discomfort scale at 48 hours . Secondary outcomes were time to first occurrence of normal temperature ( fever clearance ) , time without fever over 24 hours , fever associated symptoms , and adverse effects . Results On an intention to treat basis , paracetamol plus ibuprofen were superior to paracetamol for less time with fever in the first four hours ( adjusted difference 55 minutes , 95 % confidence interval 33 to 77 ; P<0.001 ) and may have been as good as ibuprofen ( 16 minutes , −7 to 39 ; P=0.2 ) . For less time with fever over 24 hours , paracetamol plus ibuprofen were superior to paracetamol ( 4.4 hours , 2.4 to 6.3 ; P<0.001 ) and to ibuprofen ( 2.5 hours , 0.6 to 4.4 ; P=0.008 ) . Combined therapy cleared fever 23 minutes ( 2 to 45 ; P=0.025 ) faster than paracetamol alone but no faster than ibuprofen alone ( −3 minutes , 18 to −24 ; P=0.8 ) . No benefit was found for discomfort or other symptoms , although power was low for these outcomes . Adverse effects did not differ between groups . Conclusion Parents , nurses , pharmacists , and doctors wanting to use medicines to supplement physical measures to maximise the time that children spend without fever should use ibuprofen first and consider the relative benefits and risks of using paracetamol plus ibuprofen over 24 hours . Trial registration Current Controlled Trials IS RCT N26362730 Objectives . Febrile seizures recur frequently . Factors increasing the risk of febrile seizure recurrence include young 
    Output:
    
There is some evidence that both alternating and combined antipyretic therapy may be more effective at reducing temperatures than monotherapy alone .
However , the evidence for improvements in measures of child discomfort remains inconclusive .
There is insufficient evidence to know which of combined or alternating therapy might be more beneficial .