human
***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: BACKGROUND Infantile spasms , which comprise a severe infantile seizure disorder , have a high morbidity and are difficult to treat . Hormonal treatments ( adrenocorticotropic hormone and prednisolone ) have been the main therapy for decades , although little evidence supports their use . Vigabatrin has been recorded to have a beneficial effect in this disorder . We aim ed to compare the effects of vigabatrin with those of prednisolone and tetracosactide in the treatment of infantile spasms . METHODS The United Kingdom Infantile Spasms Study assessed these treatments in a multicentre , r and omised controlled trial in 150 hospitals in the UK . The primary outcome was cessation of spasms on days 13 and 14 . Minimum doses were vigabatrin 100 mg/kg per day , oral prednisolone 40 mg per day , or intramuscular tetracosactide depot 0.5 mg ( 40 IU ) on alternate days . Analysis was by intention to treat . FINDINGS Of 208 infants screened and assessed , 107 were r and omly assigned to vigabatrin ( n=52 ) or hormonal treatments ( prednisolone n=30 , tetracosactide n=25 ) . None was lost to follow-up . Proportions with no spasms on days 13 and 14 were : 40 ( 73 % ) of 55 infants assigned hormonal treatments ( prednisolone 21/30 [ 70 % ] , tetracosactide 19/25 [ 76 % ] ) and 28 ( 54 % ) of 52 infants assigned vigabatrin ( difference 19 % , 95 % CI 1%-36 % , p=0.043 ) . Two infants allocated tetracosactide and one allocated vigabatrin received prednisolone .  Adverse events were reported in 30 ( 55 % ) of 55 infants on hormonal treatments and 28 ( 54 % ) of 52 infants on vigabatrin . No deaths were recorded . INTERPRETATION Cessation of spasms was more likely in infants given hormonal treatments than those given vigabatrin .  Adverse events were common with both treatments Using a r and omized parallel group study design , we compared the cognit i ve effects of carbamazepine ( CBZ ) , phenobarbital ( PB ) , and valproate ( VPA ) in children with epilepsy . Seventy-three children with newly diagnosed epilepsy were tested with the Wechsler Intelligence Scale for Children-Revised ( WISC-R ) , Bender-Gestalt test , and auditory event-related potentials ( P 300 ) before and 6 and 12 months after antiepileptic drug ( AED ) treatment . There were no significant differences in WISC-R IQs and Bender-Gestalt scores for children in any group at any of the three sessions . P 300 latencies were increased in the children receiving PB but not in children receiving CBZ and VPA . P 300 amplitudes were significantly reduced in treated children in all three groups , but amplitudes were not significantly different among the three groups . These findings suggest that PB may affect cognitive function of epileptic children and that the P 300 may be a sensitive additional procedure that can be used to assess the cognitive effect of AEDs Cognitive and behavioral effects of phenobarbital in toddlers were assessed in a r and omized , placebo-controlled study of patients who had had a febrile seizure . There were no significant differences in IQ ( Binet or Bayley Scales ) between placebo and phenobarbital groups after eight to 12 months of therapy . However , detrimental effects of phenobarbital were found in memory , for which serum level influenced scores , and in comprehension , in that length of treatment time affected performance . Hyperactivity was not seen . Behavioral changes , reported by parents , were increased fussiness and a characteristic disturbance of sleep . These changes varied in severity and were classified as transient , dose related , or unacceptable . After 12 months in the study , most parents could not distinguish between phenobarbital and placebo . Our data suggest that although most toddlers do not have major side effects from phenobarbital therapy when treated for a year , serum levels and length of time on phenobarbital should be kept at a minimum to reduce negative cognitive and behavioral effects BACKGROUND The use of phenobarbital for childhood epilepsy is controversial because of reported behavioural side-effects ; however , whether this research can validly be extrapolated to developing countries is not clear . We undertook a r and omised comparison of phenobarbital and phenytoin to assess the acceptability and efficacy of phenobarbital as monotherapy for childhood epilepsy in rural India . METHODS Between August , 1995 , and February , 1996 , 109 unselected children aged 2 - 18 years with partial and generalised tonic-clonic epilepsy were identified by population screening . 15 families declined to take part . 94 children were r and omly allocated treatment with phenobarbital ( 1.5 mg/kg daily for 2 weeks ; maintenance dose 3.0 mg/kg daily ; n = 47 ) or phenytoin ( 2.5 mg/kg daily then 5.0 mg/kg daily ; n = 47 ) . Children were followed up for 12 months . The primary outcome measure was the frequency of behavioural side-effects ; behaviour was assessed by the Conners parent rating scale for children aged 6 years and older , and by the preschool behaviour screening question naire ( BSQ ) for those aged 2 - 5 years , at 12 months or at withdrawal from treatment . Analysis was by intention to treat . FINDINGS The mean log-transformed scores on the behaviour rating scales did not differ significantly between the phenobarbital and phenytoin groups ( Conners 2.64 [ SD 0.71 ] vs 2.65 [ 0.89 ] , p = 0.97 ; n = 32 in each group : BSQ 2.12 [ 1.31 ] vs 2.18 [ 1.02 ] , p = 0.94 ; n = 4 vs 3 ) . The odds ratio for behavioural problems  ( phenobarbital vs phenytoin ) was 0.51 ( 95 % CI 0.16 - 1.59 ) . There was no excess in parental reports of side-effects for phenobarbital . We found no difference in efficacy between the study drugs ( adjusted hazard ratio for time to first seizure from r and omisation 0.97 [ 0.28 - 3.30 ] ) . INTERPRETATION This evidence supports the acceptability of phenobarbital as a first-line drug for childhood epilepsy in rural setting s in developing countries Some pediatric neurologists maintain that mephobarbital ( Mebaral ) causes fewer behavioral side effects than phenobarbital . Because this hypothesis has not been previously tested , we conducted a prospect i ve , double-blind , r and omized , crossover study of these two anticonvulsants . Both drugs were equally effective in reducing the frequency of seizure , although serum phenobarbital levels were significantly higher when the patients were taking phenobarbital compared to mephobarbital . As measured by the Abbott Parent Question naire , there was no significant deterioration of behavior with either phenobarbital or mephobarbital , regardless of which drug was administered first . J Child Neurol 1986;1:361 - 363 Phenytoin and carbamazepine are effective and inexpensive anti-epileptic drugs ( AEDs ) . As with many AEDs , a broad range of doses is used , with the final " maintenance " dose normally determined by trial and error . Although many genes could influence response to these medicines , there are obvious c and i date s. Both drugs target the alpha-subunit of the sodium channel , encoded by the SCN family of genes . Phenytoin is principally metabolized by CYP2C9 , and both are probable substrates of the drug transporter P-glycoprotein . We therefore assessed whether variation in these genes associates with the clinical use of carbamazepine and phenytoin  in cohorts of 425 and 281 patients , respectively . We report that a known functional polymorphism in CYP2C9 is highly associated with the maximum dose of phenytoin ( P = 0.0066 ) . We also show that an intronic polymorphism in the SCN1A gene shows significant association with maximum doses in regular usage of both carbamazepine and phenytoin ( P = 0.0051 and P = 0.014 , respectively ) . This polymorphism disrupts the consensus sequence of the 5 ' splice donor site of a highly conserved alternative exon ( 5N ) , and it significantly affects the proportions of the alternative transcripts in individuals with a history of epilepsy . These results provide evidence of a drug target polymorphism associated with the clinical use of AEDs and set the stage for a prospect i ve evaluation of how pharmacogenetic diagnostics can be used to improve dosing decisions in the use of phenytoin and carbamazepine . Although the case made here is compelling , our results can not be considered definitive or ready for clinical application until they are confirmed by independent replication The results of a prospect i ve assessment of antiepileptic drug treatment carried out over a 12-month period , in the context of existing community health care in a rural area of a developing country ( a highl and region of northern Ecuador ) , are reported . A house to house survey defined all patients in the area with a history of epileptic seizures , and 192 patients with active epilepsy were recruited into the programme . These patients were r and omised to treatment with carbamazepine or phenobarbital  , and 139 completed the assessment . Treatment was carried out by health visitors and rural doctors , monitored by a team of neurologists , and st and ard treatment regimens were used . Treatment was effective in controlling seizures , 53 % of the patients were rendered entirely seizure free in the second 6 months of therapy , and a further 14 % had a 50 % or more reduction in seizures . These results were similar to those reported in hospital based studies in developed countries . No significant differences were found between the efficacy and safety of phenobarbital or carbamazepine . Antiepileptic drug levels were monitored during the study , and ranges similar to those found in developed countries were recorded . Compliance was good . In view of the successful treatment in this community control programme , we would recommend that community programmes for the control of epilepsy in rural setting s should be given a higher priority in the planning of health care provision than is commonly the case . Finally , the programme afforded the opportunity to study the efficacy of treatment in patients with chronic long-st and ing epilepsy , who had not been previously treated , and the results of this treatment were good The effect of phenobarbital on total sleep time , night awakenings , and lengthy awakenings was examined as part of a r and omized trial of children with febrile seizures ; information about sleep patterns was gathered by parental observation . Children were between ages 8 - 36 months at enrollment and were examined subsequently for 2 1/2 years .  Night awakenings were not more common in children assigned to phenobarbital except for those who were poor sleepers at the beginning of the study . Total sleep time was no different in children assigned to phenobarbital than in those assigned to placebo . It is concluded that sleep problems reported in most young children with febrile seizures treated with  phenobarbital  did not exceed those reported in children treated with placebo , but a subset of predisposed children did experience an increase in night awakenings A r and omized double-blind study was carried out comparing single daily dose phenobarbital plus antipyretic instruction to a placebo plus antipyretic instruction to prevent a recurrent seizure following an initial simple febrile seizure . Parents of 138 consecutive children presenting to an emergency room with a first simple febrile convulsion received verbal and written instructions about fever control . Seventy-nine then agreed to participate in this study . Children were r and omized to receive either placebo with riboflavin tracer ( n = 40 ) or phenobarbital 5 mg/kg in a single daily dose with a riboflavin tracer ( n = 39 ) for 12 months or until another seizure occurred . Urine fluorescence for riboflavin was used to monitor compliance in all patients . Serum phenobarbital levels were obtained at each follow-up visit and averaged 1.4 mg/dl throughout the study . The significant difference ( P less than 0.02 ) in the incidence of recurrent seizures between patients receiving phenobarbital ( 2/39 ) and those receiving placebo ( 10/40 ) suggests that a single daily dose of phenobarbital is more effective than counseling parents about antipyretic therapy in preventing recurrent seizures following an initial febrile seizure Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCT 
    Output:
    
agent
There is no evidence for a difference in antiepileptic efficacy between phenobarbital and any other compared AED , yet no evidence for absolute efficacy .
No convincing evidence exists for an excess of behavioural adverse effects , over other AEDs , attributable to phenobarbital .
Masked studies of phenobarbital in childhood epilepsy have shown no significant differences in behavioural or cognitive adverse effects compared to other AEDs .
This is in contrast to the excess of such adverse effects reported in studies open to observer bias .
However , the one finding of reduction in cognitive ability associated with phenobarbital treatment for febrile convulsions remains a concern .
***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: BACKGROUND Infantile spasms , which comprise a severe infantile seizure disorder , have a high morbidity and are difficult to treat . Hormonal treatments ( adrenocorticotropic hormone and prednisolone ) have been the main therapy for decades , although little evidence supports their use . Vigabatrin has been recorded to have a beneficial effect in this disorder . We aim ed to compare the effects of vigabatrin with those of prednisolone and tetracosactide in the treatment of infantile spasms . METHODS The United Kingdom Infantile Spasms Study assessed these treatments in a multicentre , r and omised controlled trial in 150 hospitals in the UK . The primary outcome was cessation of spasms on days 13 and 14 . Minimum doses were vigabatrin 100 mg/kg per day , oral prednisolone 40 mg per day , or intramuscular tetracosactide depot 0.5 mg ( 40 IU ) on alternate days . Analysis was by intention to treat . FINDINGS Of 208 infants screened and assessed , 107 were r and omly assigned to vigabatrin ( n=52 ) or hormonal treatments ( prednisolone n=30 , tetracosactide n=25 ) . None was lost to follow-up . Proportions with no spasms on days 13 and 14 were : 40 ( 73 % ) of 55 infants assigned hormonal treatments ( prednisolone 21/30 [ 70 % ] , tetracosactide 19/25 [ 76 % ] ) and 28 ( 54 % ) of 52 infants assigned vigabatrin ( difference 19 % , 95 % CI 1%-36 % , p=0.043 ) . Two infants allocated tetracosactide and one allocated vigabatrin received prednisolone .  Adverse events were reported in 30 ( 55 % ) of 55 infants on hormonal treatments and 28 ( 54 % ) of 52 infants on vigabatrin . No deaths were recorded . INTERPRETATION Cessation of spasms was more likely in infants given hormonal treatments than those given vigabatrin .  Adverse events were common with both treatments Using a r and omized parallel group study design , we compared the cognit i ve effects of carbamazepine ( CBZ ) , phenobarbital ( PB ) , and valproate ( VPA ) in children with epilepsy . Seventy-three children with newly diagnosed epilepsy were tested with the Wechsler Intelligence Scale for Children-Revised ( WISC-R ) , Bender-Gestalt test , and auditory event-related potentials ( P 300 ) before and 6 and 12 months after antiepileptic drug ( AED ) treatment . There were no significant differences in WISC-R IQs and Bender-Gestalt scores for children in any group at any of the three sessions . P 300 latencies were increased in the children receiving PB but not in children receiving CBZ and VPA . P 300 amplitudes were significantly reduced in treated children in all three groups , but amplitudes were not significantly different among the three groups . These findings suggest that PB may affect cognitive function of epileptic children and that the P 300 may be a sensitive additional procedure that can be used to assess the cognitive effect of AEDs Cognitive and behavioral effects of phenobarbital in toddlers were assessed in a r and omized , placebo-controlled study of patients who had had a febrile seizure . There were no significant differences in IQ ( Binet or Bayley Scales ) between placebo and phenobarbital groups after eight to 12 months of therapy . However , detrimental effects of phenobarbital were found in memory , for which serum level influenced scores , and in comprehension , in that length of treatment time affected performance . Hyperactivity was not seen . Behavioral changes , reported by parents , were increased fussiness and a characteristic disturbance of sleep . These changes varied in severity and were classified as transient , dose related , or unacceptable . After 12 months in the study , most parents could not distinguish between phenobarbital and placebo . Our data suggest that although most toddlers do not have major side effects from phenobarbital therapy when treated for a year , serum levels and length of time on phenobarbital should be kept at a minimum to reduce negative cognitive and behavioral effects BACKGROUND The use of phenobarbital for childhood epilepsy is controversial because of reported behavioural side-effects ; however , whether this research can validly be extrapolated to developing countries is not clear . We undertook a r and omised comparison of phenobarbital and phenytoin to assess the acceptability and efficacy of phenobarbital as monotherapy for childhood epilepsy in rural India . METHODS Between August , 1995 , and February , 1996 , 109 unselected children aged 2 - 18 years with partial and generalised tonic-clonic epilepsy were identified by population screening . 15 families declined to take part . 94 children were r and omly allocated treatment with phenobarbital ( 1.5 mg/kg daily for 2 weeks ; maintenance dose 3.0 mg/kg daily ; n = 47 ) or phenytoin ( 2.5 mg/kg daily then 5.0 mg/kg daily ; n = 47 ) . Children were followed up for 12 months . The primary outcome measure was the frequency of behavioural side-effects ; behaviour was assessed by the Conners parent rating scale for children aged 6 years and older , and by the preschool behaviour screening question naire ( BSQ ) for those aged 2 - 5 years , at 12 months or at withdrawal from treatment . Analysis was by intention to treat . FINDINGS The mean log-transformed scores on the behaviour rating scales did not differ significantly between the phenobarbital and phenytoin groups ( Conners 2.64 [ SD 0.71 ] vs 2.65 [ 0.89 ] , p = 0.97 ; n = 32 in each group : BSQ 2.12 [ 1.31 ] vs 2.18 [ 1.02 ] , p = 0.94 ; n = 4 vs 3 ) . The odds ratio for behavioural problems  ( phenobarbital vs phenytoin ) was 0.51 ( 95 % CI 0.16 - 1.59 ) . There was no excess in parental reports of side-effects for phenobarbital . We found no difference in efficacy between the study drugs ( adjusted hazard ratio for time to first seizure from r and omisation 0.97 [ 0.28 - 3.30 ] ) . INTERPRETATION This evidence supports the acceptability of phenobarbital as a first-line drug for childhood epilepsy in rural setting s in developing countries Some pediatric neurologists maintain that mephobarbital ( Mebaral ) causes fewer behavioral side effects than phenobarbital . Because this hypothesis has not been previously tested , we conducted a prospect i ve , double-blind , r and omized , crossover study of these two anticonvulsants . Both drugs were equally effective in reducing the frequency of seizure , although serum phenobarbital levels were significantly higher when the patients were taking phenobarbital compared to mephobarbital . As measured by the Abbott Parent Question naire , there was no significant deterioration of behavior with either phenobarbital or mephobarbital , regardless of which drug was administered first . J Child Neurol 1986;1:361 - 363 Phenytoin and carbamazepine are effective and inexpensive anti-epileptic drugs ( AEDs ) . As with many AEDs , a broad range of doses is used , with the final " maintenance " dose normally determined by trial and error . Although many genes could influence response to these medicines , there are obvious c and i date s. Both drugs target the alpha-subunit of the sodium channel , encoded by the SCN family of genes . Phenytoin is principally metabolized by CYP2C9 , and both are probable substrates of the drug transporter P-glycoprotein . We therefore assessed whether variation in these genes associates with the clinical use of carbamazepine and phenytoin  in cohorts of 425 and 281 patients , respectively . We report that a known functional polymorphism in CYP2C9 is highly associated with the maximum dose of phenytoin ( P = 0.0066 ) . We also show that an intronic polymorphism in the SCN1A gene shows significant association with maximum doses in regular usage of both carbamazepine and phenytoin ( P = 0.0051 and P = 0.014 , respectively ) . This polymorphism disrupts the consensus sequence of the 5 ' splice donor site of a highly conserved alternative exon ( 5N ) , and it significantly affects the proportions of the alternative transcripts in individuals with a history of epilepsy . These results provide evidence of a drug target polymorphism associated with the clinical use of AEDs and set the stage for a prospect i ve evaluation of how pharmacogenetic diagnostics can be used to improve dosing decisions in the use of phenytoin and carbamazepine . Although the case made here is compelling , our results can not be considered definitive or ready for clinical application until they are confirmed by independent replication The results of a prospect i ve assessment of antiepileptic drug treatment carried out over a 12-month period , in the context of existing community health care in a rural area of a developing country ( a highl and region of northern Ecuador ) , are reported . A house to house survey defined all patients in the area with a history of epileptic seizures , and 192 patients with active epilepsy were recruited into the programme . These patients were r and omised to treatment with carbamazepine or phenobarbital  , and 139 completed the assessment . Treatment was carried out by health visitors and rural doctors , monitored by a team of neurologists , and st and ard treatment regimens were used . Treatment was effective in controlling seizures , 53 % of the patients were rendered entirely seizure free in the second 6 months of therapy , and a further 14 % had a 50 % or more reduction in seizures . These results were similar to those reported in hospital based studies in developed countries . No significant differences were found between the efficacy and safety of phenobarbital or carbamazepine . Antiepileptic drug levels were monitored during the study , and ranges similar to those found in developed countries were recorded . Compliance was good . In view of the successful treatment in this community control programme , we would recommend that community programmes for the control of epilepsy in rural setting s should be given a higher priority in the planning of health care provision than is commonly the case . Finally , the programme afforded the opportunity to study the efficacy of treatment in patients with chronic long-st and ing epilepsy , who had not been previously treated , and the results of this treatment were good The effect of phenobarbital on total sleep time , night awakenings , and lengthy awakenings was examined as part of a r and omized trial of children with febrile seizures ; information about sleep patterns was gathered by parental observation . Children were between ages 8 - 36 months at enrollment and were examined subsequently for 2 1/2 years .  Night awakenings were not more common in children assigned to phenobarbital except for those who were poor sleepers at the beginning of the study . Total sleep time was no different in children assigned to phenobarbital than in those assigned to placebo . It is concluded that sleep problems reported in most young children with febrile seizures treated with  phenobarbital  did not exceed those reported in children treated with placebo , but a subset of predisposed children did experience an increase in night awakenings A r and omized double-blind study was carried out comparing single daily dose phenobarbital plus antipyretic instruction to a placebo plus antipyretic instruction to prevent a recurrent seizure following an initial simple febrile seizure . Parents of 138 consecutive children presenting to an emergency room with a first simple febrile convulsion received verbal and written instructions about fever control . Seventy-nine then agreed to participate in this study . Children were r and omized to receive either placebo with riboflavin tracer ( n = 40 ) or phenobarbital 5 mg/kg in a single daily dose with a riboflavin tracer ( n = 39 ) for 12 months or until another seizure occurred . Urine fluorescence for riboflavin was used to monitor compliance in all patients . Serum phenobarbital levels were obtained at each follow-up visit and averaged 1.4 mg/dl throughout the study . The significant difference ( P less than 0.02 ) in the incidence of recurrent seizures between patients receiving phenobarbital ( 2/39 ) and those receiving placebo ( 10/40 ) suggests that a single daily dose of phenobarbital is more effective than counseling parents about antipyretic therapy in preventing recurrent seizures following an initial febrile seizure Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCT 
    Output:
    