***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 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 Summary In a biopharmaceutical study of carbamazepine , the F-CBZ , DAK preparation , which contained small particles with minor variation in size , had a more rapid dissolution rate than Tegretol , which contained larger particles of more variable size . Accordingly , carbamazepine had a more rapid absorption rate from F-CBZ , DAK than from Tegretol in a comparative absorption test involving single-dose administration of 200 mg to 8 healthy volunteers . The clinical significance of the difference in absorption rates for the steady state levels of carbamazepine and carbamazepine-10,11-epoxide , and the frequency of side-effects in relation to tablet intake , were evaluated in a double-blind , r and omized , double-dummy cross-over trial of 35 days ' duration , in 21 well-adjusted epileptic patients . 9 patients were treated with Tegretol alone and 12 with Tegretol combined with other antiepileptic drugs . A lower steady state plasma level of carbamazepine  was found at 08.00 h during treatment with F-CBZ , DAK in comparison with Tegretol . The difference was small . There was no difference in the type and frequency of side-effects or seizures between the 2 preparations . The frequency of epileptic fits was not correlated with the plasma level of carbamazepine or the epoxide . Side-effects , however , had a tendency to be correlated with the concentration of the epoxide . Thus , the particle size influenced the absorption rate of carbamazepine , without having a significant correlation with the frequency of side-effects . The difference in the minimum plasma level of carbamazepine between treatments with the two preparations was modest , and appeared to be without clinical significance We evaluated the use of a new , controlled-release capsule form of carbamazepine , Carbatrol capsules , in an open-label , multicenter study of 124 patients with complex partial seizures . Ninety-one percent of the patients successfully completed the 6-month trial with good seizure control , with a significant improvement in quality of life . We conclude that switching patients with complex partial seizures from multiple daily-dose carbamazepine to twice-daily Carbatrol on a milligram-to-milligram basis is relatively safe Carbatrol ( CBR ) is a new multiple-unit , sustained-release dosage form of carbamazepine ( CBZ ) developed by Pharmavene . We present a multicenter , outpatient , r and omized , double-blind parallel group study ( No PI 101 ) carried out in two centers in Pol and .  CBR was evaluated in 47 patients with uncontrolled partial onset seizures . During the 28-day baseline period , patients were required to have at least two seizures and to take CBZ at a therapeutic level , a second antiepileptic drug was allowed but not valproic acid ( VPA ) .  Patients were r and omized to VPA or to CBR  ( dosages 800 , 1200 , 1600 mg/day ) . Criteria for escape relative to baseline were : two-fold increase in monthly seizure frequency , two-fold increase in 2-day seizure frequency , two-fold increase in weekly seizure frequency , single generalized tonic-clonic seizure ( GTCs ) if none occurred during baseline or prolongation of GTCs . The primary efficacy variable was the number of patients escaping in each treatment group . Nineteen patients on VPA and 7 on CBR met escape criteria .  CBR adverse experiences were all mild or moderate in severity . CBR therapy was effective in the treatment of partial complex seizures with or without generalization To compare the effects on attention and vigilance of conventional carbamazepine ( CBZ ) and CBZ controlled release ( CBZ-CR ) , 15 schoolchildren with epilepsy and normal intelligence receiving CBZ  were switched to CBZ-CR .  Psychological examination was performed on the day before ( day A ) and 1 month after substitution ( day B ) . Measurements of attention and vigilance were repeated throughout the day at 2-h intervals . Both on days A and B ,  CBZ plasma levels were monitored during a 12-h period . Fifteen matched healthy controls were su bmi tted to identical test programs , allowing comparisons within subjects as well as between patients and control children . Variability of performance over sessions was neither increased nor decreased with CBZ-CR . Consistent differences over sessions did not exist between patients and controls with either drug . No relation was noted between reaction time and CBZ plasma level . The pharmacologic data confirm results of earlier studies in children . We noted a reduction in intradose fluctuations of CBZ level with CBZ-CR as compared with conventional CBZ . The neuropsychological results do not show a difference between the drugs . Neither were differences noted with respect to antiepileptic efficacy and side effects . At the end of the study , all but one of the children ( and their parents ) opted to receive CBZ-CR for ease of dosage administration and overall satisfaction Pharmacokinetic properties and efficacy of a conventional ( C ) carbamazepine ( CBZ ) preparation divided into three daily doses and a slow-release CBZ preparation ( SR ) divided into two daily doses were evaluated in a r and omized , double-blind , cross-over study . The trial started with a 8-week baseline period followed by the two treatment periods each 10 weeks long . At the end of each period , a 24-h blood sample series for determination of serum CBZ and carbamazepine-10,11-epoxide ( CBZE )  was collected . The occurrence of seizures was monitored day and night during the whole study period by experienced nurses . The mean age of the 20 evaluable patients was 24.9 and the duration of epilepsy 19.2 and carbamazepine treatment 7.0 years . The bioavailability of CBZ  from the two preparations was similar . The mean fluctuation of serum CBZ concentration ( Cmax-Cmin/Css ) was 16 % smaller during SR . The mean serum CBZ concentration in the morning sample s was significantly ( P less than 0.001 ) higher during SR treatment . The mean total number of seizures was approximately four per week and did not differ between the two treatments , but during the last 2 weeks of the study period the occurrence of seizures was significantly smaller during SR ( P = 0.02 ) A multicentre open therapeutic trial comparing carbamazepine with slow-release carbamazepine was conducted in 114 epileptic patients older than 12 years . The patients received the two products successively during two periods of 1 month each . With slow-release carbamazepine the number of doses could be reduced to 2 per day without decrease in effectiveness and with less side-effects . The twice-a-day dosage should result in better compliance and consequently in a better quality of treatment in the long term The treatment of epilepsy with carbamazepine ( CBZ ) may be hampered by cognitive side effects . These side effects are thought to be related to pharmacokinetic properties of the drug . The serum concentration of CBZ is characterized by rapid absorption and a short half-life , which may lead to a considerable fluctuation of the level between doses . Cognitive defects may result from peak levels : short periods with high serum concentration . In a single-blind crossover design , cognitive performance was compared in three conditions . All patients were first tested in the steady state of conventional CBZ . The patients were then assigned r and omly to either CBZ-controlled release ( CR ) or a condition in which conventional CBZ was administered in the same tablet form and dose frequency as CR .  Psychological tests were administered four times daily , immediately after the serum sample s were taken . A nonmedication control group was tested following the same test scheme to obtain st and ards for the evaluation of changes in performance during the day . A systematic tendency was found toward higher test performance in the CR condition . This is especially evident for tests of memory and accuracy of visual information processing . The results of the repeated test procedure show that the smoothing effect of the CR condition on serum concentration fluctuations results in a more stable pattern of cognitive functioning during the day PURPOSE A new capsule dosage form of carbamazepine ( CBZ ) has been developed , consisting of three different types of beads ( immediate-release , extended-release , and enteric-release ) that may be taken sprinkled on food or swallowed for easy administration . We compared the pharmacokinetics of the extended-release dosage form of CBZ ( Carbatrol capsules ) twice daily with the conventional immediate-release formulation of CBZ four times daily . METHODS The r and omized , double-blind , two-way , cross-over study was conducted at two sites , with a planned sample size of 24 adult patients with epilepsy . Each treatment was administered for 2 weeks . At the end of the 2-week period , blood sample s were obtained hourly for a 24-h period . RESULTS The 90 % confidence intervals ( CI ) of the ratio of the means of the extended-release formulation twice daily to the immediate-release formulation four times daily were within the range of 0.80 - 1.25 for each of the pharmacokinetic parameters for CBZ and for the summation of CBZ and CBZ-epoxide ( CBZ-E ) . There was no difference in the frequency of seizures between treatment ( p = 0.103 ) . CONCLUSIONS Our results demonstrate that extended-release CBZ twice daily was bioequivalent to immediate-release CBZ four times daily , with regard to CBZ levels and summation of CBZ and CBZ-E levels , based on the pharmacokinetic parameters evaluated . Substituting one formulation for the other did not cause patients to have a significant change in seizure frequency Abstract The tolerability and pharmacokinetics of a new controlled‐release ( CR ) formulation of carbamazepine ( CBZ ) , were assessed in a multicentre , double‐blind , cross‐over trial , carried out in 48 epileptic patients ( 21 men , 27 women ; mean age 34.2 years ) on conventional CBZ monotherapy , but without complete seizure control ( n = 22 ) or with intermittent side effects ( n = 4 ) , or with both ( n = 22 ) . Eligible patients were r and omized to conventional CBZ or CR CBZ , each given in sequence at individualized daily doses , subdivided into the lowest number of administrations . Each period of the cross‐over consisted of a first phase of optimal dose finding ( lasting up to two months ) and a second one of maintenance ( lasting one month ) used for evaluation . At the end of each period , a 10‐h plasma CBZ and CBZ‐epoxide concentration profile , as well as the tolerability and the efficacy of the drugs , were evaluated . The mean CBZ daily dose increased by 16 % during the administration of the CR formulation . Fluctuations of total CBZ and 10 , 11‐epoxide plasma level daily profiles at steady‐state were significantly ( p < 0.001 ) lower during CR CBZ treatment , leading to a significant ( p < 0.001 ) decrease in intermittent side effects ( 6 patients on CR CBZ vs 26 on conventional CBZ ) . Finally , 38 patients on CR CBZ  ( vs 15 patients on conventional CBZ  ) were treated with a b.i.d . regimen A 2-week open 
    Output:
    
At present , data from trials do not confirm or refute an advantage for CR CBZ over IR CBZ for seizure frequency or adverse events in patients with newly diagnosed epilepsy .
For trials involving epilepsy patients already prescribed IR CBZ , no conclusions can be drawn concerning the superiority of CR CBZ with respect to seizure frequency .
There is a trend for CR CBZ to be associated with fewer adverse events when compared to IR CBZ .
A change to CR CBZ may therefore be a worthwhile strategy in patients with acceptable seizure control on IR CBZ but experiencing unacceptable adverse events .