***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: Fifty-eight patients with severe , progressive multiple sclerosis were prospect ively r and omized to one of three treatments : 20 received intravenous ACTH , 20 received high-dose intravenous cyclophosphamide plus ACTH , and 18 were placed on a regimen consisting of plasma exchange , low-dose oral cyclophosphamide , and ACTH . The three groups were similar in age , sex , duration and type of disease , and degree of disability . Before treatment and six months and one year after treatment , a disability-status score , ambulation index , and functional-status score were determined , and a quantitative neurologic examination was performed . In the ACTH group , the number of patients stabilized or improved was 8 of 20 at six months and 4 of 20 at one year ; in the cyclophosphamide-ACTH group , 18 of 20 at six months and 16 of 20 at one year ; and in the plasma exchange group , 11 of 18 at six months and 9 of 18 at one year . High-dose cyclophosphamide plus ACTH was most effective in halting progression of the disease at both 6 and 12 months ( at 12 months , cyclophosphamide-ACTH vs. ACTH , P = 0.0004 ; cyclophosphamide-ACTH vs. plasma exchange , P = 0.087 ) . Thus , progressive multiple sclerosis may be stabilized by short-term , intensive immunosuppression with cyclophosphamide plus ACTH A system has been constructed to evaluate the design , implementation , and analysis of  r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Treatment with acetyl L-carnitine ( ALCAR ) has been shown to improve fatigue in patients with chronic fatigue syndrome , but there have been no trials on the effect of ALCAR for treating fatigue in multiple sclerosis ( MS ) . To compare the efficacy of ALCAR with that of amantadine , one of the drugs most widely used to treat MS-related fatigue , 36 MS patients presenting fatigue were enrolled in a r and omised , double-blind , crossover study . Patients were treated for 3 months with either amantadine ( 100 mg twice daily ) or ALCAR ( 1 g twice daily ) . After a 3-month washout period , they crossed over to the alternative treatment for 3 months . Patients were rated at baseline and every 3 months according to the Fatigue Severity Scale ( FSS ) , the primary endpoint of the study . Secondary outcome variables were : Fatigue Impact Scale ( FIS ) , Beck Depression Inventory ( BDI ) and Social Experience Checklist ( SEC ) .  Six patients withdrew from the study because of adverse reactions ( five on amantadine and one on ALCAR )  . Statistical analysis showed significant effects of ALCAR compared with amantadine for the Fatigue Severity Scale ( p = 0.039 ) . There were no significant effects for any of the secondary outcome variables . The results of this study show that ALCAR is better tolerated and more effective than amantadine for the treatment of MS-related fatigue Fatigue is a complex phenomenon that , for those not affected , is hard to underst and . To achieve better assessment s , caregivers need reliable and valid tools . The aim of this study was to investigate the reliability and validity of the Swedish version of the Fatigue Impact Scale ( FIS ) among working-aged individuals diagnosed with multiple sclerosis ( MS ) , as well as in a comparative group r and omly selected from the general population in the same geographical area . Both individuals with MS ( n=161 ) and individuals recruited from the general population ( n=194 ) participated in the study . A question naire was used for the data collection . The data were analysed using non-parametric statistical methods . Reliability of FIS was addressed by item-to-item and item-to-total correlations . Concurrent validity was tested for by analysing correlations between the FIS and general questions , and construct validity by investigation of differences in the FIS scores between known groups . The FIS was found to be homogenous , with item-to-total correlation coefficients of 0.42 ≤ rs≤0.86 ( p<0.001 ) , reflecting the instrument 's reliability . The correlations between the FIS and the general questions confirm its concurrent validity , 0.27 ≤ rs≤0.84 ( p<0.001 ) . The differences in FIS scores between known groups demonstrate its construct validity . Furthermore , the FIS showed the ability to discriminate between groups of individuals with differences in perceived impact of fatigue Fatigue is a common symptom of multiple sclerosis ( MS ) that is without an effective treatment . A double-blind , controlled study of fatigue treatment was conducted to evaluate the efficacy of amantadine hydrochloride in treating  MS-associated fatigue .  Since fatigue can not be characterized by a single symptom or behavior , a variety of neuropsychological , behavioral , and self-report measures were used to monitor changes across different systems . According to patients ' daily diary ratings , amantadine produced small but statistically significant improvements in fatigue across four of seven dimensions ( overall energy level , concentration , problem solving , and sense of well-being ) . In addition , patients with MS who were taking amantadine  performed slightly better on the Stroop Interference Test , an attentional measure of freedom from distracting information . Although retrospective reports by patients with MS did not confirm the degree of improvement recorded on a daily basis , the study 's results suggested that amantadine may offer modest benefits in alleviating the day-to-day subjective experience of fatigue As part of a larger study on the quality of life of cancer patients under treatment , the positive and negative experiences in social interaction  have been examined as compared to those of a  control group ( non patients , n = 201 ) . Two patient groups were included : 109 patients who had recently undergone surgery and 108 patients receiving chemotherapy .  The respondents returned a mailed question naire . Contrary to the assumptions based on a review from the literature , cancer patients appear to have more positive and fewer negative social experiences than a r and om sample from the ' normal ' population . Even under more severe medical circumstances ( a poor prognosis or heavy chemotherapy , a large number of chemotherapy cycles , poor progress after surgery ) the poorer the patients , medically speaking , the more help and support they perceive . The results of this study do not support the idea of stigmatization . The personality characteristics , neuroticism and self-esteem are especially important for the having of positive and negative experiences in social interaction . Positive social experiences show a relationship with self-esteem and negative social experiences show a relationship with neuroticism In a double-blind placebo-controlled crossover study of ten patients with multiple sclerosis , we found amantadine hydrochloride therapy to be effective in improving fatigability in six . Administration of the drug was associated with significantly higher levels of beta-endorphin-beta-lipotropin and responders had significantly higher levels than nonresponders . Lactate levels were significantly higher and pyruvate levels lower in nonresponders . Amantadine given for fatigue to patients with multiple sclerosis is associated with measurable changes in levels of metabolites and peptides in the circulation Objective To determine the relative efficacy of amantadine , pemoline , and placebo in treatment of multiple sclerosis (MS)-related fatigue .  Background Fatigue is a complication of MS . Both pemoline and amantadine have been used to treat MS fatigue , but their relative efficacy is not known . Methods Amantadine , pemoline , and placebo were compared in a r and omized , double-blind , placebo-controlled study using a parallel-group design . Ninety-three ambulatory MS patients completed the study . Primary outcome measures were the fatigue seventy scale ( FSS ) ; the MS-specific fatigue scale ( MS-FS ) ; and subjective response determined by verbal self-report . Secondary outcome measures consisted of assessment s of sleep , depression , and vitality . Repeated- measures analysis of variance with planned post-hoc contrasts and Fisher 's exact test were used to compare treatment response . Results Amantadine-treated patients showed a significantly greater reduction in fatigue , as measured by the MS-FS , than did patients treated with placebo ( p = 0.04 ) . By verbal report at the end of the study , 79 % of patients treated with amantadine versus 52 % treated with placebo and 32 % treated with pemoline preferred drug therapy compared with no treatment ( p = 0.03 ) . No significant differences in any primary outcome measures were noted between pemoline and placebo . Neither amantadine nor pemoline affected sleep or depression relative to placebo . Conclusion Amantadine was significantly better than placebo in treating  fatigue in MS patients , whereas pemoline was not . The benefit of amantadine was not due to changes in sleep , depression , or neurologic disability We investigated the effect of amantadine on cognitive processing in patients with multiple sclerosis ( MS ) and fatigue with objective electrophysiological measures . Behavioral methods ( Reaction Time , RT ) and two different Event Related Potential ( ERP ) components measuring i ) stimulus selection ( Selection Negativity , SN ) and ii ) response selection ( Lateralized Readiness Potential , LRP ) were employed . Twenty-four patients with clinical definite MS ( 10 relapsing remitting and 14 secondary progressive ) and confirmed fatigue in the past three months ( Fatigue Severity Scale ( FSS ) > 4 ) were included . Patients were r and omized in a double-blind , placebo-controlled cross-over design . We found a difference between the two treatments for ERP measures to stimuli with relevant colour starting at about 200 ms . This negativity had a higher amplitude during amantadine treatment regardless of treatment order . The RT did not differ significantly between the treated and untreated groups . Additional analysis indicated that patients with a disease duration of less than 7 years had a significant test position ( practice effect ) , but no treatment effect , while patients with a longer MS duration showed no practice effect , but rather an improved reaction speed and increased ERP amplitude effects when treated with amantadine . The present findings suggest that amantadine exerts beneficial effects on early cognitive processes in patients with MS , but appears to be limited to subjects with a longer duration of the disease BACKGROUND Amantadine hydrochloride and pemoline , both frequently used to treat the fatigue of multiple sclerosis ( MS ) , may also improve attention and other cognitive functions in MS . To our knowledge , these agents have never been compared in a placebo-controlled trial of patients with MS . OBJECTIVE To evaluate the effects of amantadine and pemoline on cognitive functioning in MS . METHODS A total of 45 ambulatory patients with MS and severe fatigue were treated for 6 weeks with amantadine , pemoline , or placebo using a parallel group design . They underwent comprehensive neuropsychological testing to determine treatment effects on cognitive functioning . Primary outcome measures were tests of attention ( Digit Span , Trail Making Test , and Symbol Digit Modalities Test ) , verbal memory ( Selective Reminding Test ) , nonverbal memory ( Benton Visual Retention Test ) , and motor speed ( Finger Tapping Test ) . RESULTS Fatigue did not significantly correlate with any of the neuropsychological outcome measures at baseline or after treatment . All three treatment groups improved on tests of attention ( P < .003 ) , verbal memory ( P < .001 ) , and motor speed ( P < .002 ) . There were no significant differences between amantadine , pemoline , and placebo . CONCLUSIONS Cognitive functioning in MS is independent of fatigue . Neither amantadine nor pemoline enhances cognitive performance in MS compared with placebo We carried out a double blind control study of fatigue in 32 patients with multiple sclerosis , comparing amantadine hydrochloride 100 mg twice a day and placebo . On amantadine 31 % had marked improvement ; 15.6 % moderate improvement ; 15.6 % mild improvement ; and 36.5 % unchanged . On placebo , none noted marked improvement ; one cl aim ed moderate improvement on either amantadine or placebo . 18.7 % reported mild improvement on placebo ; and most of them had similar or more response to amantadine . No patient selected placebo over amantadine at the end of the trial . Overall improvement was seen in 62.5 % of patients on amantadine and 21.8 % on placebo . Additional experience up to two years suggests continued benefit but common and important side-effects During a study of efficacy of amantadine prophylaxis of influenza A virus infection in young adults , gross and subtle side effects were monitored . Eighty-eight students were r and omly selected to receive either amantadine or placebo for four weeks or both in a sequential crossover design of two weeks each . Side effects ( i.e. , dizziness , nervousness , and insomnia ) occurred in 33 % of those receiving amantadine and in 10 % of those receiving placebo ( P less than 0.005 ) . Although side effects were well tolerated by most subjects , six volunteers discontinued amantadine because of marked complaints . Cessation of side effects occurred in more than half of those continuing amantadine .  Sixteen students receiving amantadine  had decreased performance on sustained attention tasks as compared with ones receiving placebo ( P less than 0.05 ) . 
    Output:
    
All studies reported small and inconstant improvements in fatigue , whereas the clinical relevance of these findings and the impact on patient 's functioning and health related quality of life remains undetermined .