***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: Objectives : To examine the neuropsychological side effects of valproate ( VPA ) given to prevent post-traumatic seizures . Methods : In a r and omized , double-masked , parallel group clinical trial , we compared the seizure prevention and neuropsychological effects of 1 or 6 months of VPA to 1 week of phenytoin . We studied 279 adult subjects who were r and omized within 24 hours of injury and examined with a battery of neuropsychological measures at 1 , 6 , and 12 months after injury . We examined drug effects cross-sectionally at 1 , 6 , and 12 months and longitudinally by examining differential change from 1 to 6 months and from 6 to 12 months as a function of protocol -dictated changes in treatment . Results : No significant adverse or beneficial neuropsychological effects of VPA were detected . Conclusions : Valproate ( VPA ) appears to have a benign neuropsychological side effects profile , making it a cognitively safe antiepileptic drug to use for controlling established seizures or stabilizing mood . However , based on this study , VPA should not be used for prophylaxis of posttraumatic seizures because it does not prevent posttraumatic seizures , there was a trend toward more deaths in the VPA groups , and it did not have positive effects on cognition Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Abstract Intravenous phenytoin has come under increased scrutiny with the introduction of the prodrug , fosphenytoin . We evaluated adverse events and length-of-stay using parenteral the two drugs in routine emergency department use . Open-label r and omization of phenytoin or fosphenytoin in 256 Emergency Department patients prescribed 279 parenteral doses of a phenytoin-equivalent . All phenytoin was administered intravenously , and fosphenytoin was given intravenously or intramuscularly ( physician preference ) . Adverse events and Emergency Department length-of-stay were recorded ; re-presentation to the Emergency Department within three months was review ed for evidence of the purple glove syndrome . Nonparametric statistics were used to analyze the data . Seventy-seven patients received phenytoin and 202 fosphenytoin ; 28 ( 10.0 % ) received  intramuscular fosphenytoin . The mean phenytoin-equivalent dose was similar between the groups . Eighteen patients required reduction in infusion rates because of an adverse event ( phenytoin = 6.5 % , fosphenytoin = 6.4 % ; OR 0.9 , 95 % CI 0.42.6 ; p = 1.0 ) . Adverse events occurred with similar frequency ( phenytoin 9.1 % , fosphenytoin 15.8 % ; OR 0.7 , 95 % CI 0.31.4 ; p = 0.3 ) . The most common events were : pruritis , pain on infusion , and paresthesias . One patient developed hypotension  ( fosphenytoin ) ; there were no other serious adverse events , including phlebitis . Median Emergency Department length-of-stay was 6.7 h for phenytoin and 5.7 h for fosphenytoin ( p = 0.6 ) . In routine Emergency Department use , our data do not support formulary conversion from phenytoin to fosphenytoin , based on the incidence of adverse events or Emergency Department length-of-stay In this article the efficacy of carbamazepine for seizure prophylaxis in severe head injuries is tested . In addition , conditions with high risk of seizures requiring prophylactic regimen , were defined . One hundred and thirty-nine patients above 15 years of age with severe head injuries were included in the study . They were r and omly divided into two groups -- carbamazepine versus placebo . Prophylaxis was started immediately after the accident and was continued for one and a half to two years . Carbamazepine dosage was adjusted individually to provide serum levels within therapeutic range . In case of a seizure all the necessary clinical management was initiated . Patients on carbamazepine showed a lower probability of post-traumatic seizures than those on placebo ( p less than 0.05 ) . This difference was statistically significant with regard to early seizures within the first week and with regard to the follow-up time in total , but not regarding late seizures per se . Brain lesions with a high risk of post-traumatic seizures were situated in the parietal and temporal areas and included acute subdural haematomas in all locations , temporal lobe contusions , parietal epidural haematomas accompanied by other lesions and the deep stages of coma . Brain stem contusions were accompanied by a rather low probability of seizures . The above mentioned types and locations of brain lesions with the exception of brain stem contusions justify antiepileptic prophylaxis . The regimen consists of oral carbamazepine 100 mg three times daily by gastric tube during the first two days increasing to about 200 mg three times daily on the third day corresponding to the serum level . If oral medication is not possible within the initial twelve hours , phenytoin in a dose of 750 mg Phenhydan-Infusion Konzentrate is given on the first day , followed by an intravenous dose of 250 - 500 mg on the second day or until oral carbamazepine administration is tolerated . Treatment should be continued for one year OBJECTIVE : To determine the incidence of intravenous site reactions to phenytoin and valproate in a large population of patients with neurotrauma . DESIGN : Retrospective chart review of two double-blind , r and omized clinical trials evaluating the use of antiepileptic drugs to prevent posttraumatic seizures in patients with neurotrauma :  phenytoin versus placebo  ( n = 390 ) , and valproate versus phenytoin with placebo  ( n = 385 ) . Information collected from the charts included the number , type , and location of intravenous lines and intravenous site events . SETTING : Tertiary care trauma and university teaching hospital . MAIN RESULTS : Intravenous site reactions occurred in 18 % and 25 % of patients receiving valproate or phenytoin , respectively , with the majority of events ( 70 % ) occurring in the first intravenous site . Patients received the neurosurgery study drug ( NSSD ) by either central or peripheral lines ; all intravenous site reactions occurred in peripheral administration sites . When patients who received the drug by central line during the course of therapy were excluded , the estimated incidence of site reactions was 21 % and 30 % for valproate and phenytoin , respectively ( p = 0.056 ) . The time to the first event was shorter with phenytoin compared with valproate ( 2.0 ± 1.3 vs. 3.0 ± 1.9 d ; p = 0.009 ) . Fewer adverse events were noted with phenytoin in the phenytoin-without-valproate study than in the phenytoin-with-valproate study , with 4.3 % and 8.2 % of intravenous site events recorded in patients receiving placebo or phenytoin , respectively . There was no significant difference in the number of intravenous lines per patient used during NSSD drug infusion for phenytoin versus placebo or phenytoin versus valproate . CONCLUSIONS : Both intravenous phenytoin and valproate result ed in intravenous site reactions , with the loading doses responsible for the majority of the events A r and omised , controlled , double-blind clinical trial design ed to determine the effectiveness of phenytoin in preventing epilepsy in patients who had suffered a serious head injury is reported . One hundred and sixty-four patients were r and omly assigned to treatment with phenytoin or placebo capsules for one year . Patients who had a fit within one week of injury were excluded .  Drug levels were monitored throughout with appropriate dosage adjustment ; however only 48 % of the phenytoin group had plasma levels greater than 40 mumol/l . There were seven deaths during the study . Only 11 patients ( six in the phenytoin group and five in the placebo group ) developed post-traumatic epilepsy within one year ; a further four patients developed seizures between 1 and 2 years after injury . This low incidence of post-traumatic epilepsy ( 7 % ( SE 2 % ) at one year and 10 ( SE 2 % ) at two years ) means that future clinical trials of prophylaxis will have to be much larger ( at least six fold ) Levetiracetam ( LEV ) has antiepileptogenic effects in animals and is a c and i date for prevention of epilepsy after traumatic brain injury . Pharmacokinetics of LEV in TBI patients was unknown . We report pharmacokinetics of TBI subjects≥6years with high PTE risk treated with LEV 55mg/kg/day orally , nasogastrically or intravenously for 30days starting ≤8h after injury in a phase II safety and pharmacokinetic study . Forty-one subjects ( 26 adults and 15 children ) were r and omized to PK studies on treatment days 3 and 30 . Thirty-six out of forty-one r and omized subjects underwent PK study on treatment day 3 , and 24/41 subjects underwent PK study on day 30 . On day 3 , mean T(max ) was 2.2h , C(max ) was 60.2μg/ml and AUC was 403.7μg/h/ml . T(max ) was longer in the elderly than in children and non-elderly adults ( 5.96h vs. 1.5h and 1.8h ; p=0.0001 ) . AUC was non-significantly lower in children compared with adults and the elderly ( 317.4μg/h/ml vs. 461.4μg/h/ml and 450.2μg/h/ml ; p=0.08 ) . C(max ) trended higher in i.v.- versus tablet- or n.g.-treated subjects ( 78.4μg/ml vs. 59μg/ml and 48.2μg/ml ; p=0.07 ) . AUC of n.g . and i.v . administrations was 79 % and 88 % of AUC of oral administration . There were no significant PK differences between days 3 and 30 . Treatment of TBI patients with high PTE risk  with 55mg/kg/day LEV , a dose with antiepileptogenic effect in animals , results in plasma LEV levels comparable to those in animal studies PURPOSE Preventing posttraumatic epilepsy has been a difficult challenge . In this study we evaluated the association between glucocorticoid administration after traumatic brain injury ( TBI ) and posttraumatic seizures . METHODS We examined a seizure-prevention trial data base of 404 patients with severe TBI for exposure to glucocorticoids in the early ( < 1 week ) posttraumatic period . After controlling for seizure risk , we compared the odds of developing first and second late posttraumatic seizures between those that received glucocorticoids and those that did not . RESULTS Patients dosed with gluc 
    Output:
    
This review found low- quality evidence that early treatment with an AED compared with placebo or st and ard care reduced the risk of early post-traumatic seizures .
There was no evidence to support a reduction in the risk of late seizures or mortality .
There was insufficient evidence to make any conclusions regarding the effectiveness or safety of other neuroprotective agents compared with placebo or for the comparison of phenytoin , a traditional AED , with another AED