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: Objective : To assess the efficacy and safety of modafinil for the treatment of fatigue in multiple sclerosis ( MS ) . Methods : Patients aged 18–65 years with a diagnosis of MS , a stable disability level ≤6 on the Kurtzke extended disability status scale ( EDSS ) , and a mean score > 4 on the fatigue severity scale ( FSS ) were eligible for the 9 week , single blind , phase 2 , two centre study . Exclusion criteria included a diagnosis of narcolepsy , sleep apnoea , or clinical ly significant major systemic disease and recent use of medications affecting fatigue . All patients , who remained blinded for the treatment regimen , received placebo during weeks 1–2 , 200 mg/day modafinil during weeks 3–4 , 400 mg/day modafinil during weeks 5–6 , and placebo during weeks 7–9 . Safety was evaluated by unblinded investigators . Efficacy was evaluated by self rating scales , using the FSS , the modified fatigue impact scale ( MFIS ) , a visual analogue scale for fatigue ( VAS-F ) , and the Epworth sleepiness scale ( ESS ) . Adverse events were recorded . Results : Seventy two patients ( MS type : 74 % relapsing-remitting ; 7 % primary progressive ; 19 % secondary progressive ) received treatment . After treatment with 200 mg/day modafinil for 2 weeks , a significant improvement in fatigue versus placebo run in was demonstrated . Mean scores after treatment with 200 mg/day modafinil were : FSS , 4.7 versus 5.5 for placebo ( p<0.001 ) ; MFIS , 37.7 versus 44.7 ( p<0.001 ) ; and VAS-F , 5.4 versus 4.5 ( p=0.003 ) . Fatigue scores for 400 mg/day modafinil were not significantly improved versus placebo run in . Mean ESS scores were significantly improved ( p<0.001 ) with 200 mg/day modafinil ( 7.2 ) and 400 mg/day ( 7.0 ) versus the score at baseline ( 9.5 ) . Serious adverse events were not found at either dose . The most common adverse events were headache , nausea , and aesthenia . Sixty five patients ( 90 % ) completed the study . Conclusions : These data suggest that 200 mg/day modafinil significantly improves fatigue and is well tolerated in patients with MS Abstract Rationale . Modafinil , a novel wake-promoting agent , has been shown to have a similar clinical profile to that of conventional stimulants such as methylpheni date . We were therefore interested in assessing whether modafinil , with its unique pharmacological mode of action , might offer similar potential as a cognitive enhancer , without the side effects commonly experienced with amphetamine-like drugs . Objectives . The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests . Methods . Sixty healthy young adult male volunteers received either a single oral dose of placebo , or 100 mg or 200 mg modafinil prior to performing a variety of tasks design ed to test memory and attention . A r and omised double-blind , between-subjects design was used . Results . Modafinil significantly enhanced performance on tests of digit span , visual pattern recognition memory , spatial planning and stop-signal reaction time . These performance improvements were complemented by a slowing in latency on three tests : delayed matching to sample , a decision-making task and the spatial planning task . Subjects reported feeling more alert , attentive and energetic on drug . The effects were not clearly dose dependent , except for those seen with the stop-signal paradigm . In contrast to previous findings with methylpheni date , there were no significant effects of drug on spatial memory span , spatial working memory , rapid visual information processing or attentional set-shifting . Additionally , no effects on paired associates learning were identified . Conclusions . These data indicate that modafinil selectively improves neuropsychological task performance . This improvement may be attributable to an enhanced ability to inhibit pre-potent responses . This effect appears to reduce impulsive responding , suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder Background : Cognitive decline has been recognised as a frequent symptom in multiple sclerosis ( MS ) .  Cholinesterase inhibitors ( ChEIs ) are employed for the treatment of Alzheimer ’s disease , but there is some evidence that ChEIs might also be effective in MS patients with cognitive deficits , particularly deficits of memory function . Objective : The aim of this study was to evaluate efficacy on memory function and safety of the ChEI rivastigmine in MS patients with cognitive deficits as measured by the change from baseline of the total recall score of the selective reminding test ( SRT ) after 16 weeks of treatment . Methods : Efficacy and safety of rivastigmine were analysed in a 16-week , multicentre , double-blind , r and omised , placebo-controlled study , followed by an optional one-year open-label treatment phase . Effects of rivastigmine and placebo were compared by an analysis of covariance . Results : In total , 86 patients were enrolled . Patients who received rivastigmine ( n = 43 ) showed a non-significant increase in total recall score ( sum of all words immediately recalled over all six trials ) over placebo ( n = 38 ) after 16 weeks of treatment ( p = 0.2576 ) . Other outcome measures provided no evidence supporting benefits of rivastigmine . Treatment with rivastigmine was well tolerated . Conclusions : With the results of this study , the need for an effective therapy in cognitively impaired MS patients is still required . Thus , intensive and continued clinical research is required to explore therapeutic options for cognitive deficits in MS patients Objective : To assess whether modafinil , a wakefulness-promoting agent , is useful for fatigue in patients with multiple sclerosis ( MS ) . Methods : Patients with MS with stable disability , and a baseline score of 45 or more on the Modified Fatigue Impact Scale ( MFIS ) , were eligible for the 5-week r and omized , double-blind , placebo-controlled , parallel group study . The initial daily dose of modafinil was 200 mg for 1 week . Depending on tolerance , the dose was increased by 100 mg every week up to 400 mg/day and remained unchanged between day 21 and day 35 . The primary outcome variable was the change of MFIS score at day 35 . Results : A total of 115 patients with MS were enrolled in the study and in the intention to treat analysis . The mean MFIS score at baseline was 63 ± 9 in the placebo group and 63 ± 10 in the modafinil group . MFIS scores improved between day 0 and day 35 in both placebo-treated and modafinil-treated groups , but no significant difference was detected between the two groups . There was no major safety concern . Conclusions : There was no improvement of fatigue in patients with multiple sclerosis treated with modafinil vs placebo according to the Modified Fatigue Impact Scale PURPOSE / OBJECTIVE To assess the efficacy of modafinil for the treatment of new learning and memory deficits and fatigue in multiple sclerosis . Only 1 previous study in the literature , to our knowledge , examined the effect of modafinil on cognition specifically in persons with multiple sclerosis . RESEARCH METHOD / DESIGN Sixteen patients with a diagnosis of multiple sclerosis ( MS ) and documented new learning impairment completed the study . In a 5-week r and omized , double-blinded , crossover design , participants received either a single daily oral dose of modafinil ( 200 mg ) or placebo for 2 weeks . A 1-week washout period was included between study arms . RESULTS No effect of modafinil was noted on learning and memory performance . Participants taking 200 mg of modafinil showed improvement in 1 of the 2 working memory measures administered , the Wechsler Adult Intelligence Scale-III ( WAIS-III ) Letter-Number Sequencing task , as compared with those on placebo . Treatment with modafinil did not have a beneficial effect in reducing self-reported fatigue . No changes were noted on the Modified Fatigue Impact Scale or the Fatigue Severity Scale with the treatment of modafinil , as compared with placebo . CONCLUSIONS / IMPLICATION S Findings indicate that 200 mg of modafinil has the potential to improve working memory in persons with MS . These findings suggest that modafinil may enhance aspects of cognition in persons with MS and may be an effective adjunct to clinical rehabilitation interventions Objectives : The goal of this study was to determine if memory would be improved by donepezil as compared to placebo in a multicenter , double-blind , r and omized clinical trial ( RCT ) . Methods : Donepezil 10 mg daily was compared to placebo to treat memory impairment . Eligibility criteria included the following : age 18–59 years , clinical ly definite multiple sclerosis ( MS ) , and performance ≤½ SD below published norms on the Rey Auditory Verbal Learning Test ( RAVLT ) .  Neuropsychological assessment s were performed at baseline and 24 weeks . Primary outcomes were change on the Selective Reminding Test ( SRT ) of verbal memory and the participant 's impression of memory change . Secondary outcomes included changes on other neuropsychological tests and the evaluating clinician 's impression of memory change . Results : A total of 120 participants were enrolled and r and omized to either donepezil or placebo . No significant treatment effects were found between groups on either primary outcome of memory or any secondary cognitive outcomes . A trend was noted for the clinician 's impression of memory change in favor of donepezil ( 37.7 % ) vs placebo ( 23.7 % ) ( p = 0.097 ) . No serious or unanticipated adverse events attributed to study medication developed . Conclusions : Donepezil did not improve memory as compared to placebo on either of the primary outcomes in this study . Classification of evidence : This study provides Class I evidence which does not support the hypothesis that 10 mg of donepezil daily for 24 weeks is superior to placebo in improving cognition as measured by the SRT in people with MS whose baseline RAVLT score was 0.5 SD or more below average Introduction Cognitive impairment is common and debilitating among persons with multiple sclerosis ( MS ) and might be managed with exercise training . However , the effects of exercise training on viscoelastic brain properties in this population are unknown . The present pilot study adopted a single-blind r and omized controlled trial ( RCT ) design and is the first to examine the effect of an aerobic exercise training intervention on learning and memory and hippocampal viscoelasticity using magnetic resonance elastography ( MRE ) in persons with MS . Methods Eight fully ambulatory females with MS were r and omly assigned into exercise training intervention or waitlist control conditions . The intervention condition involved 12 weeks of supervised , progressive treadmill walking exercise training . All participants underwent measures of learning and memory ( i.e. , California Verbal Learning Test-II ; CVLT-II ) and further underwent MRE scans for measurement of shear stiffness ( μ ) and damping ratio ( ξ ) of the hippocampus before and after the 12-week period . Results Overall , there were small-to-moderate intervention effects on CVLT-II performance ( d = 0.34 ) and large intervention effects on hippocampal μ ( d = 0.94 ) and hippocampal ξ ( d = −1.20 ) . Change in CVLT-II scores was strongly associated with change in μ ( r = 0.93 , p < 0.01 ) and ξ ( r = −.96 , p < 0.01 ) of the hippocampus . Conclusion This small pilot RCT provides exciting proof-of-concept data supporting progressive treadmill walking exercise training for potentially improving learning and memory and underlying hippocampal viscoelastic properties in persons with MS . This is important given the high prevalence and burden of MS-related memory impairment Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Rationale Multiple sclerosis ( MS ) commonly affects cognitive function , most frequently presenting as impaired processing speed ( PS ) . There are currently no approved treatments for PS in this population , but previous studies suggest amphetamines may be beneficial . Objective The objective of this study is to determine if mixed amphetamine salts , extended release ( MAS-XR ) has the potential to improve impaired PS in MS patients in a r and omized controlled pre- and post-dose testing study . Methods Fifty-two MS patients demonstrating PS impairment on either the  Symbol Digit Modalities Test ( SDMT ) or  Paced Auditory Serial Addition Test ( PASAT ) were r and omized to a single dose of 5 mg MAS-XR ( n = 18 ) , 10 mg MAS-XR ( n = 20 ) , or placebo ( n = 14 ) . Subjects were evaluated a second time , after taking the blinded medication . ANOVA was used to compare the change on the SDMT and PASAT in each of the treatment groups compared to the placebo . Cohen ’s d was used to calculate effect size . Results At baseline , the mean SDMT score was 43.3 ± 7.2 and the mean PASAT was 34.8 ± 13.4 , with 47 ( 90.4 % ) and 25 ( 48. 
    Output:
    
agent
Whilst there was only a limited pool of relatively small trials and a number of different compounds , we found that collectively , both AChEIs ( donepezil and rivastigmine ) and stimulants ( methylpheni date , modafinil , l‐amphetamine sulfate and lisdexamfetamine dimesylate ) offered no significant benefits over placebo on measures of processing speed , working memory , verbal fluency , verbal memory , visuospatial memory or executive functioning
***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 assess the efficacy and safety of modafinil for the treatment of fatigue in multiple sclerosis ( MS ) . Methods : Patients aged 18–65 years with a diagnosis of MS , a stable disability level ≤6 on the Kurtzke extended disability status scale ( EDSS ) , and a mean score > 4 on the fatigue severity scale ( FSS ) were eligible for the 9 week , single blind , phase 2 , two centre study . Exclusion criteria included a diagnosis of narcolepsy , sleep apnoea , or clinical ly significant major systemic disease and recent use of medications affecting fatigue . All patients , who remained blinded for the treatment regimen , received placebo during weeks 1–2 , 200 mg/day modafinil during weeks 3–4 , 400 mg/day modafinil during weeks 5–6 , and placebo during weeks 7–9 . Safety was evaluated by unblinded investigators . Efficacy was evaluated by self rating scales , using the FSS , the modified fatigue impact scale ( MFIS ) , a visual analogue scale for fatigue ( VAS-F ) , and the Epworth sleepiness scale ( ESS ) . Adverse events were recorded . Results : Seventy two patients ( MS type : 74 % relapsing-remitting ; 7 % primary progressive ; 19 % secondary progressive ) received treatment . After treatment with 200 mg/day modafinil for 2 weeks , a significant improvement in fatigue versus placebo run in was demonstrated . Mean scores after treatment with 200 mg/day modafinil were : FSS , 4.7 versus 5.5 for placebo ( p<0.001 ) ; MFIS , 37.7 versus 44.7 ( p<0.001 ) ; and VAS-F , 5.4 versus 4.5 ( p=0.003 ) . Fatigue scores for 400 mg/day modafinil were not significantly improved versus placebo run in . Mean ESS scores were significantly improved ( p<0.001 ) with 200 mg/day modafinil ( 7.2 ) and 400 mg/day ( 7.0 ) versus the score at baseline ( 9.5 ) . Serious adverse events were not found at either dose . The most common adverse events were headache , nausea , and aesthenia . Sixty five patients ( 90 % ) completed the study . Conclusions : These data suggest that 200 mg/day modafinil significantly improves fatigue and is well tolerated in patients with MS Abstract Rationale . Modafinil , a novel wake-promoting agent , has been shown to have a similar clinical profile to that of conventional stimulants such as methylpheni date . We were therefore interested in assessing whether modafinil , with its unique pharmacological mode of action , might offer similar potential as a cognitive enhancer , without the side effects commonly experienced with amphetamine-like drugs . Objectives . The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests . Methods . Sixty healthy young adult male volunteers received either a single oral dose of placebo , or 100 mg or 200 mg modafinil prior to performing a variety of tasks design ed to test memory and attention . A r and omised double-blind , between-subjects design was used . Results . Modafinil significantly enhanced performance on tests of digit span , visual pattern recognition memory , spatial planning and stop-signal reaction time . These performance improvements were complemented by a slowing in latency on three tests : delayed matching to sample , a decision-making task and the spatial planning task . Subjects reported feeling more alert , attentive and energetic on drug . The effects were not clearly dose dependent , except for those seen with the stop-signal paradigm . In contrast to previous findings with methylpheni date , there were no significant effects of drug on spatial memory span , spatial working memory , rapid visual information processing or attentional set-shifting . Additionally , no effects on paired associates learning were identified . Conclusions . These data indicate that modafinil selectively improves neuropsychological task performance . This improvement may be attributable to an enhanced ability to inhibit pre-potent responses . This effect appears to reduce impulsive responding , suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder Background : Cognitive decline has been recognised as a frequent symptom in multiple sclerosis ( MS ) .  Cholinesterase inhibitors ( ChEIs ) are employed for the treatment of Alzheimer ’s disease , but there is some evidence that ChEIs might also be effective in MS patients with cognitive deficits , particularly deficits of memory function . Objective : The aim of this study was to evaluate efficacy on memory function and safety of the ChEI rivastigmine in MS patients with cognitive deficits as measured by the change from baseline of the total recall score of the selective reminding test ( SRT ) after 16 weeks of treatment . Methods : Efficacy and safety of rivastigmine were analysed in a 16-week , multicentre , double-blind , r and omised , placebo-controlled study , followed by an optional one-year open-label treatment phase . Effects of rivastigmine and placebo were compared by an analysis of covariance . Results : In total , 86 patients were enrolled . Patients who received rivastigmine ( n = 43 ) showed a non-significant increase in total recall score ( sum of all words immediately recalled over all six trials ) over placebo ( n = 38 ) after 16 weeks of treatment ( p = 0.2576 ) . Other outcome measures provided no evidence supporting benefits of rivastigmine . Treatment with rivastigmine was well tolerated . Conclusions : With the results of this study , the need for an effective therapy in cognitively impaired MS patients is still required . Thus , intensive and continued clinical research is required to explore therapeutic options for cognitive deficits in MS patients Objective : To assess whether modafinil , a wakefulness-promoting agent , is useful for fatigue in patients with multiple sclerosis ( MS ) . Methods : Patients with MS with stable disability , and a baseline score of 45 or more on the Modified Fatigue Impact Scale ( MFIS ) , were eligible for the 5-week r and omized , double-blind , placebo-controlled , parallel group study . The initial daily dose of modafinil was 200 mg for 1 week . Depending on tolerance , the dose was increased by 100 mg every week up to 400 mg/day and remained unchanged between day 21 and day 35 . The primary outcome variable was the change of MFIS score at day 35 . Results : A total of 115 patients with MS were enrolled in the study and in the intention to treat analysis . The mean MFIS score at baseline was 63 ± 9 in the placebo group and 63 ± 10 in the modafinil group . MFIS scores improved between day 0 and day 35 in both placebo-treated and modafinil-treated groups , but no significant difference was detected between the two groups . There was no major safety concern . Conclusions : There was no improvement of fatigue in patients with multiple sclerosis treated with modafinil vs placebo according to the Modified Fatigue Impact Scale PURPOSE / OBJECTIVE To assess the efficacy of modafinil for the treatment of new learning and memory deficits and fatigue in multiple sclerosis . Only 1 previous study in the literature , to our knowledge , examined the effect of modafinil on cognition specifically in persons with multiple sclerosis . RESEARCH METHOD / DESIGN Sixteen patients with a diagnosis of multiple sclerosis ( MS ) and documented new learning impairment completed the study . In a 5-week r and omized , double-blinded , crossover design , participants received either a single daily oral dose of modafinil ( 200 mg ) or placebo for 2 weeks . A 1-week washout period was included between study arms . RESULTS No effect of modafinil was noted on learning and memory performance . Participants taking 200 mg of modafinil showed improvement in 1 of the 2 working memory measures administered , the Wechsler Adult Intelligence Scale-III ( WAIS-III ) Letter-Number Sequencing task , as compared with those on placebo . Treatment with modafinil did not have a beneficial effect in reducing self-reported fatigue . No changes were noted on the Modified Fatigue Impact Scale or the Fatigue Severity Scale with the treatment of modafinil , as compared with placebo . CONCLUSIONS / IMPLICATION S Findings indicate that 200 mg of modafinil has the potential to improve working memory in persons with MS . These findings suggest that modafinil may enhance aspects of cognition in persons with MS and may be an effective adjunct to clinical rehabilitation interventions Objectives : The goal of this study was to determine if memory would be improved by donepezil as compared to placebo in a multicenter , double-blind , r and omized clinical trial ( RCT ) . Methods : Donepezil 10 mg daily was compared to placebo to treat memory impairment . Eligibility criteria included the following : age 18–59 years , clinical ly definite multiple sclerosis ( MS ) , and performance ≤½ SD below published norms on the Rey Auditory Verbal Learning Test ( RAVLT ) .  Neuropsychological assessment s were performed at baseline and 24 weeks . Primary outcomes were change on the Selective Reminding Test ( SRT ) of verbal memory and the participant 's impression of memory change . Secondary outcomes included changes on other neuropsychological tests and the evaluating clinician 's impression of memory change . Results : A total of 120 participants were enrolled and r and omized to either donepezil or placebo . No significant treatment effects were found between groups on either primary outcome of memory or any secondary cognitive outcomes . A trend was noted for the clinician 's impression of memory change in favor of donepezil ( 37.7 % ) vs placebo ( 23.7 % ) ( p = 0.097 ) . No serious or unanticipated adverse events attributed to study medication developed . Conclusions : Donepezil did not improve memory as compared to placebo on either of the primary outcomes in this study . Classification of evidence : This study provides Class I evidence which does not support the hypothesis that 10 mg of donepezil daily for 24 weeks is superior to placebo in improving cognition as measured by the SRT in people with MS whose baseline RAVLT score was 0.5 SD or more below average Introduction Cognitive impairment is common and debilitating among persons with multiple sclerosis ( MS ) and might be managed with exercise training . However , the effects of exercise training on viscoelastic brain properties in this population are unknown . The present pilot study adopted a single-blind r and omized controlled trial ( RCT ) design and is the first to examine the effect of an aerobic exercise training intervention on learning and memory and hippocampal viscoelasticity using magnetic resonance elastography ( MRE ) in persons with MS . Methods Eight fully ambulatory females with MS were r and omly assigned into exercise training intervention or waitlist control conditions . The intervention condition involved 12 weeks of supervised , progressive treadmill walking exercise training . All participants underwent measures of learning and memory ( i.e. , California Verbal Learning Test-II ; CVLT-II ) and further underwent MRE scans for measurement of shear stiffness ( μ ) and damping ratio ( ξ ) of the hippocampus before and after the 12-week period . Results Overall , there were small-to-moderate intervention effects on CVLT-II performance ( d = 0.34 ) and large intervention effects on hippocampal μ ( d = 0.94 ) and hippocampal ξ ( d = −1.20 ) . Change in CVLT-II scores was strongly associated with change in μ ( r = 0.93 , p < 0.01 ) and ξ ( r = −.96 , p < 0.01 ) of the hippocampus . Conclusion This small pilot RCT provides exciting proof-of-concept data supporting progressive treadmill walking exercise training for potentially improving learning and memory and underlying hippocampal viscoelastic properties in persons with MS . This is important given the high prevalence and burden of MS-related memory impairment Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Rationale Multiple sclerosis ( MS ) commonly affects cognitive function , most frequently presenting as impaired processing speed ( PS ) . There are currently no approved treatments for PS in this population , but previous studies suggest amphetamines may be beneficial . Objective The objective of this study is to determine if mixed amphetamine salts , extended release ( MAS-XR ) has the potential to improve impaired PS in MS patients in a r and omized controlled pre- and post-dose testing study . Methods Fifty-two MS patients demonstrating PS impairment on either the  Symbol Digit Modalities Test ( SDMT ) or  Paced Auditory Serial Addition Test ( PASAT ) were r and omized to a single dose of 5 mg MAS-XR ( n = 18 ) , 10 mg MAS-XR ( n = 20 ) , or placebo ( n = 14 ) . Subjects were evaluated a second time , after taking the blinded medication . ANOVA was used to compare the change on the SDMT and PASAT in each of the treatment groups compared to the placebo . Cohen ’s d was used to calculate effect size . Results At baseline , the mean SDMT score was 43.3 ± 7.2 and the mean PASAT was 34.8 ± 13.4 , with 47 ( 90.4 % ) and 25 ( 48. 
    Output:
    