***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 BACKGROUND Centenarians are characterized by weakness , decreasing mental health , impaired mobility , and poor endurance . L-Carnitine is an important contributor to cellular energy metabolism . OBJECTIVE This study evaluated the efficacy of L-carnitine on physical and mental fatigue and on cognitive functions of centenarians . DESIGN This was a placebo-controlled , r and omized , double-blind , 2-phase study . Sixty-six centenarians with onset of fatigue after even slight physical activity were recruited to the study . The 2 groups received either 2 g levocarnitine once daily ( n = 32 ) or placebo ( n = 34 ) . Efficacy measures included changes in total fat mass , total muscle mass , serum triacylglycerol , total cholesterol , HDL cholesterol , LDL cholesterol , Mini-Mental State Examination ( MMSE ) , Activities of Daily Living , and a 6-min walking corridor test . RESULTS At the end of the study period , the levocarnitine-treated centenarians , compared with the placebo group , showed significant improvements in the following markers : total fat mass ( -1.80 compared with 0.6 kg ; P < 0.01 ) , total muscle mass ( 3.80 compared with 0.8 kg ; P < 0.01 ) , plasma concentrations of total carnitine ( 12.60 compared with -1.70 mumol ; P < 0.05 ) , plasma long-chain acylcarnitine ( 1.50 compared with -0.1 micromol ; P < 0.001 ) , and plasma short-chain acylcarnitine ( 6.0 compared with -1.50 micromol ; P < 0.001 ) . Significant differences were also found in physical fatigue ( -4.10 compared with -1.10 ; P < 0.01 ) , mental fatigue ( -2.70 compared with 0.30 ; P < 0.001 ) , fatigue severity ( -23.60 compared with 1.90 ; P < 0.001 ) , and MMSE ( 4.1 compared with 0.6 ; P < 0.001 ) . CONCLUSIONS Our study indicates that oral administration of levocarnitine produces a reduction of total fat mass , increases total muscular mass , and facilitates an increased capacity for physical and cognitive activity by reducing fatigue and improving cognitive functions Nutritional factors and comedications are among the postulated causes of fatigue , a highly prevalent symptom in the multiple sclerosis ( MS ) population , with serious impact on patients ’ quality of life . Deficiency of carnitine may play a role by reducing energy production through fatty acid oxidation and numerous MS therapies can induce fatigue syndrome . The aim of this prospect i ve open-labelled study was to collect and study serum carnitine levels in MS patients with and without disease-modifying treatment-induced fatigue syndrome . We investigated whether restoration of the carnitine pool might improve treatment-induced fatigue in MS patients . In our study , there was no statistical difference in fatigue frequency between treated and untreated patients ( P=0.5 ) . Matched to age , gender and treatments , carnitine levels were lower for MS treated patients compared to untreated MS patients ( P<0.05 ) or controls ( P<0.001 ) . Consecutive patients with low plasma carnitine levels who experienced fatigue were substituted . Treatment consisted of oral levocarnitine , 3 - 6 g daily . All patients achieved normal plasma carnitine levels . For 63 % of patients treated with immunosuppressive or immunomodulatory therapies , oral levocarnitine adjunction decreased fatigue intensity , especially in patients treated with cyclophosphamide and interferon beta 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 Aim Levocarnitine is an important contributor to cellular energy metabolism . This study aims to evaluate the effects of levocarnitine supplementation on body composition , lipid profile and fatigue in elderly subjects with rapid muscle fatigue . Method This was a placebo-controlled , r and omised , double-blind , two-phase study . Eighty-four elderly subjects with onset of fatigue following slight physical activity were recruited to the study . Prior to r and omisation all patients entered a 2-week normalisation phase where they were given an ‘ ad libitum ’ diet , according to the National Cholesterol Education Program ( Step 2 ) . Subjects were asked to record their daily food intake every 2 days . Before the 30-day treatment phase , subjects were r and omly assigned to two groups ( matched for male/female ratio , age and body mass index ) . One group received levocarnitine 2 g twice daily ( n = 42 ) and the other placebo ( n = 42 ) . Efficacy measures included changes in total fat mass , total muscle mass , serum triglyceride , total cholesterol , high-density lipoprotein-cholesterol ( HDL-C ) , low-density lipoprotein-cholesterol ( LDL-C ) , apolipoprotein (apo)A1 , and apoB levels . The Wessely and Powell scale was used to evaluate physical and mental fatigue . Subjects were assessed at the beginning and end of the study period . Results At the end of the study , compared with placebo , the levocarnitine-treated patients showed significant improvements in the following parameters : total fat mass ( −3.1 vs −0.5 kg ) , total muscle mass ( + 2.1 vs + 0.2 kg ) , total cholesterol ( −1.2 vs + 0.1 mmol/L ) , LDL-C ( −1.1 vs −0.2 mmol/L ) , HDL-C ( + 0.2 vs + 0.01 mmol/ L ) , triglycerides ( −0.3 vs 0.0 mmol/L ) , apoA1 ( −0.2 vs 0.0 g/L ) , and apoB ( −0.3 vs −0.1 g/L ) . Wessely and Powell scores decreased significantly by 40 % ( physical fatigue ) and 45 % ( mental fatigue ) in subjects taking levocarnitine , compared with 11 % and 8 % , respectively , in the placebo group ( p < 0.001 vs placebo for both parameters ) . No adverse events were reported in any treatment group . Conclusion Administration of levocarnitine to healthy elderly subjects result ed in a reduction of total fat mass , an increase of total muscle mass , and appeared to exert a favourable effect on fatigue and serum lipids Background Modafinil is a unique wake-promoting agent that is chemically distinct from traditional stimulants . Results of a placebo-controlled study showed it to improve fatigue in multiple sclerosis ( MS ) at a dose of 200 mg daily , but not at a dose of 400 mg daily . Objective To establish the efficacy , safety and appropriate dose of modafinil in the treatment of fatigue and sleepiness in patients with multiple sclerosis . Method A total of 50 patients diagnosed with MS ( mean age 40.4 ± 10.3 years , 30 females/20 males ; MS type : 36 relapsing remitting , 1 primary progressive , 13 secondary progressive ; mean disability level 3.8 ± 1.5 on the Kurtzke EDSS ) and complaining of chronic fatigue were enrolled in a prospect i ve 3-month , two-center , open-label study . Efficacy was evaluated with the Fatigue Severity Scale ( FSS , score range 0 - 42 ) , the Epworth Sleepiness Scale ( ESS , score range 0 - 24 ) and by subjective patient appraisal of change of fatigue , quality of life and overall satisfaction with treatment . Adverse effects ( AEs ) were recorded throughout the study . Treatment was started with a single daily dose of 100 mg in all patients . In non-responders the dose was increased by 100 mg increments up to a maximum daily dose of 400 mg . Results Three patients discontinued modafinil because of AEs ( nervousness , dizziness ) . Two patients ( 4 % ) were treated with 50 mg , 25 ( 50 % ) with 100 mg , 21 ( 42 % ) with 200 mg and 2 ( 4 % ) with 300 mg daily . No patient required 400 mg daily . Mean FSS scores were 30.3 ± 8.5 at baseline and 25.4 ± 3.7 at 3 months ( p < 0.0001 ) . Mean ESS scores were 9.7 ± 3.9 at baseline and 4.9 ± 2.9 at 3 months ( p < 0.0001 ) . Self- appraisal of change of fatigue showed clear improvement in 41 patients ( 87.2 % ) , some improvement in 4 ( 8.5 % ) and no change in 2 ( 4.3 % ) . Overall clinical condition was clearly improved in 43 patients ( 91.5 % ) , somewhat improved in 1 patient ( 2.1 % ) , and unchanged in 3 patients ( 6.4 % ) . No patient reported worsening of overall clinical condition . Conclusions Treatment with modafinil significantly improves fatigue and sleepiness and is well tolerated by patients with MS . Unlike the higher dose regimen required in narcolepsy , a low-dose regimen of modafinil is effective in MS Multiple sclerosis ( MS ) patients of an inpatient rehabilitation program have been r and omly assigned to an exercise training ( MS-ET ) or nontraining group ( MS-NI ) . Before and after 4 weeks of aerobic exercise training , a grade d maximal exercise test with measurement of gas exchange and a lung function test was administered to all 26 patients fulfilling the inclusion criteria .  Activity level , fatigue and health perception were measured by means of question naires . Twenty-six healthy persons served as control group and were matched in respect of age , gender and activity level . Training intervention consisted of 5 × 30 min sessions per week of bicycle exercise with individualised intensity . Compared with baseline , the MS training group demonstrated a significant rightward placement of the aerobic threshold ( AT ) ( VO2 + 13 % ; work rate [WR])+11 % ) , an improvement of health perception ( vitality+46 % ; social interaction+36 % ) , an increase of activity level ( + 17 % ) and a tendency to less fatigue . No changes were observed for the MS-NI group and the control groups . Maximal aerobic capacity 
    Output:
    
There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators