***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 Efficacy and tolerability of tiagabine was evaluated in patients with non-controlled partial seizures in a multicentre , open-label , parallel group study . Tiagabine was administered either two ( b.i.d . ) or three times daily ( t.i.d . ) as adjunctive therapy and titrated stepwise to a target of 40 mg/day during a 12-week , fixed-schedule titration period ; this was followed by a 12-week flexible continuation period . The primary efficacy endpoint was the proportion of patients completing the fixed-schedule titration period . A total of 243 patients were r and omised and received treatment , 123 to b.i.d . and 120 to t.i.d . dosing . Fewer patients in the b.i.d . ( 76 and 62 % ) than in the t.i.d . ( 87 and 72 % ) group completed the fixed-schedule titration period ( OR : 0.562 ; 95 % CI : 0.309 - 1.008 ; P=0.0532 ) . The median percentage decrease in all types of seizure ( excluding status epilepticus ) during the fixed schedule titration period was 33.4 % for the b.i.d . and 23.8 % for the t.i.d . groups ( P=0.9634 ; Van Elteren 's test ) . The proportion of responders was similar for the b.i.d . and t.i.d . groups . There were no significant differences between dosage regimens in the change in median seizure rates from baseline . Adverse events were more frequent during the titration than the continuation period . Most events were mild and related to the central nervous system . Although their incidence was similar between treatment groups , severity was more frequent in the b.i.d . group . Our results suggest that during titration tiagabine is better tolerated with t.i.d . dosing , but during long-term maintenance , a t.i.d . schedule is as effective and well tolerated as b.i.d Summary : Tiagabine ( TGB ) HC1 , a new antiepilepticcompound , is a potent and specific inhibitor of γ‐aminobutyric acid ( GABA ) uptake . In conjunction with threephase I studies , the pharmacokinetics of TGB were examined in 58 healthy male volunteers . Study I involvedsingle increasing doses ( 2–24 mg TGB HC1 ) ; study II involved doses of 2–10 mg given once daily for 5 days ; study III explored one dose daily ( 6 or 12 mg ) for 14consecutive days . Plasma TGB concentrations were measured by high‐performance liquid chromatography(HPLC ) . Pharmacokineticprofiles were similar in all three studies and indicated thatthe processes of absorption and elimination of TGB werelinear . The drug was rapidly absorbed , and half‐life (tV2)averaged 5–8 h. The accumulation ratio was fairly low:1.4 in most subjects . Secondary peaks in plasma concentration‐time profiles suggested enterohepatic recycling . Lack of significant effects on antipyrine clearanceindicated that TGB does not induce or inhibit hepaticmicrosomal enzyme systems We report an open-label study of 25 children with complex partial seizures that assessed the pharmacokinetics and safety of a single dose of approximately 0.1 mg/kg tiagabine . The children received their usual individualized regimen of one concomitant antiepilepsy drug ( AED ) throughout the study . Seventeen children were receiving an inducing AED ( carbamazepine or phenytoin ) ; eight were receiving valproate . Tiagabine  was well tolerated . Dose-normalized Cmax was higher in children taking valproate ( 18.2 ± 5.0 ng/mL/mg ) than in the induced children ( 14.8 ± 6.9 ng/mL/mg ) , but the difference was not statistically significant . Dose-normalized area under the plasma concentration-time curve from time zero to infinite time was significantly higher ( p = 0.002 ) in children taking valproate ( 176.5 ± 54.7 ng * hr/mL/mg ) than in induced children ( 92.4 ± 56.7 ng * hr/mL/mg ) . Similarly , oral clearance in the children taking valproate ( 96 ± 39 mL/min ) was half that of the induced children ( 207 ± 91 mL/min ) . Half-life in children taking valproate ( 5.7 hr ) was almost twice that for the induced children ( 3.2 hr ) , and the elimination rate constant was significantly lower ( p < 0.02 ) for the children taking valproate than for the induced children . Volume of distribution was similar in the children taking valproate ( 52 ± 9 L ) and the induced children ( 59 ± 29 L ) . This is consistent with observations in adults taking tiagabine with inducing AEDs or valproate . Exploratory regressions on these data in children and previous data in adults showed fairly strong relationships between body size and tiagabine clearance and volume of distribution , with body size explaining about 40 to 50 % of the variability . When adjusted per kg body weight , clearance and volume were greater in children than adults . When adjusted per m2 body surface area , clearance and volume were more similar in adults and children OBJECTIVE To determine the efficacy and tolerability of tiagabine , a new antiepileptic drug ( AED ) that inhibits gamma-aminobutyric acid ( GABA ) uptake , at 3 dose levels vs placebo as adjunctive therapy in patients with intractable complex partial seizures ( CPS ) . DESIGN R and omized , double-blind , placebo-controlled study with a parallel-group , add-on design , starting with a 12-week unblinded baseline phase followed by a 20-week double-blind treatment phase . SETTING Twenty-one US medical centers . PATIENTS Patients ( N = 297 ) aged 12 to 77 years , previously diagnosed as having CPS and receiving stable regimens of 1 to 3 hepatic enzyme-inducing AEDs ; divalproex sodium or valproic acid was allowed in combination with any of these drugs . INTERVENTIONS Placebo or tiagabine 4 times a day at 16 , 32 , or 56 mg daily . MAIN OUTCOME MEASURES Median change in 4-week CPS frequency and adverse events . RESULTS Median decreases in 4-week CPS frequency for the 32-mg ( -2.2 ) and 56-mg ( -2.8 ) tiagabine groups were significantly greater than for the placebo ( -0.7 ) group ( P = .03 and P < .03 , respectively ) ; 20 % and 29 % of patients in the 32- and 56-mg groups had a 50 % or greater reduction in the frequency of CPS vs 4 % in the placebo group ( P = .002 and P < .001 , respectively ) . Adverse effects were similar for placebo and tiagabine except for a significantly greater incidence of dizziness in the 32-mg tiagabine group , tremor in the 32- and 56-mg groups , abnormal thinking ( usually mental lethargy or difficulty concentrating ) in the 56-mg group , and depressed mood in the 16- and 56-mg groups . CONCLUSIONS Tiagabine is efficacious and well tolerated as adjunctive therapy for CPS ; there is a clear dose-response relationship Tiagabine ( TGB ) hydrochloride is a potential new antiepileptic drug ( AED ) undergoing clinical development . Experience in humans amounts to 1,810 patient-years of exposure . TGB was found to be tolerated in an integrated safety analysis of five double-blind , add-on therapy trials involving approximately 1,000 patients with epilepsy with difficult-to-control seizures with existing AEDs . Discontinuation result ing from adverse events were infrequent , occurring in 15 % of patients receiving TGB compared to 5 % receiving placebo . The most frequently reported adverse event was dizziness , which was usually transient and did not require medical intervention . Adverse events that were statistically significantly more common with TGB than placebo were dizziness , asthenia , nervousness , tremor , diarrhea , and depression ( not major depression ) . Adverse events were usually mild to moderate in severity and transient , and most were associated with dose titration . The incidence , type , and severity of adverse events in long-term studies were comparable with those in short-term studies . Serious adverse events were uncommon and no idiosyncratic events were reported Tiagabine blocks the uptake by neurons or glia of synaptically released GABA result ing in prolonged GABAergic activity and decreased likelihood of epileptic seizures . We evaluated the cognitive and quality of life effects of tiagabine in a double-blind , add-on , placebo-controlled , parallel , multicenter , dose-response efficacy study in patients with focal epilepsy whose complex partial seizures were difficult to control . One hundred sixty-two patients provided cognitive and quality of life data for the analyses and received the following treatments : placebo ( n = 57 ) , 16 mg/d tiagabine ( n = 34 ) , 32 mg/d tiagabine ( n = 45 ) , or 56 mg/d tiagabine ( n = 26 ) at a fixed-dose for 12 weeks after a 4-week dose titration period . Eight  cognitive tests  and  three measures of mood and adjustment  were administered during the baseline period and again during the double-blind period near the end of treatment ( or at the time of dropout ) . The patient groups were similar at entry into the study . Results showed no clinical ly important changes with the addition of tiagabine on the test battery . Although this is an encouraging finding , it remains for future investigations to determine the cognitive and behavioral effects of tiagabine either as monotherapy or in relation to other antiepileptic drugs Remission of seizures is a crucial measure of outcome in epilepsy . The National General Practice Study of Epilepsy ( NGPSE ) aim ed to investigate the remission of  patients with epilepsy  and the effect of various factors on the likelihood of remission . The NGPSE is a prospect i ve population -based study free from major selection bias . We enrolled 1091 patients with newly diagnosed or suspected epilepsy who attended one of 275 general practice s throughout the UK between 1984 and 1987 .  Remission was analysed in those patients who were classified after 6 months as having definite epilepsy ( n = 564 ) or possible epilepsy ( n = 228 ) . After 9 years from the index seizure , 86 % ( 95 % CI 81 - 90 ) of patients with definite epilepsy had achieved a remission of 3 years and 68 % ( 61 - 75 ) a remission of 5 years . For the complete cohort , including those with possible epilepsy , the remission rates at 9 years were 87 % (  
    Output:
    
Dizziness and tremor were significantly associated with tiagabine therapy .
For cognitive and quality -of-life outcomes , the limited available data suggested no significant effects on cognition , mood , or adjustment .
Tiagabine reduced seizure frequency but was associated with some adverse effects when used as an add-on treatment in people with drug-resistant focal epilepsy .