***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: The topiramate study was a 12-month r and omized placebo-controlled trial in patients with ALS . Follow-up evaluation of the  placebo group ( n = 97 ) constituted a well-described cohort of patients with ALS , in whom multiple outcome measures were assessed at 3-month intervals . During the 12-month study period , the decline of forced vital capacity ( FVC% ) and ALS functional rating scale ( ALSFRS ) was linear , whereas the decline of maximum voluntary isometric contraction – arm ( MVIC-arm ) and MVIC-grip Z scores was curvilinear . Rates of FVC% and ALFRS decline , but not of MVIC-arm or MVIC-grip , were independent predictors of survival Our objective was to determine the effect of creatine monohydrate on disease progression in patients with amyotrophic lateral sclerosis ( ALS ) . One hundred and seven patients with the diagnosis of probable or definite ALS , of less than five years duration from symptom onset , were r and omized to either treatment with daily creatine monohydrate ( 5 g/d ) or placebo . In this multicenter , double-blinded study we followed changes in disease progression : using quantitative measures of strength via maximal isometric voluntary contraction , forced vital capacity , ALSFRS , quality of life , fatigue and survival . Patients were followed for nine months . The results showed that creatine monohydrate did not significantly improve motor , respiratory or functional capacity in this patient population . The drug was well tolerated and the study groups well balanced , especially considering the absence of forced vital capacity criteria for entrance into the study . There was a trend toward improved survival in patients taking daily creatine monohydrate and this was identical to the trend seen in another recently published report of creatine in ALS patients 1 . In conclusion , creatine monohydrate ( 5 g/d ) did not have an obvious benefit on the multiple markers of disease progression measured over nine months . We measured fatigue during isometric contraction and found no significant improvement despite anecdotal patient reports prior to and during the study . The trend toward improved survival was also found in another recently completed blinded trial using creatine monohydrate . Further investigation on the possible survival benefit of creatine in this patient population is ongoing The ALS Functional Rating Scale ( ALSFRS ) is a vali date d rating instrument for monitoring the progression of disability in patients with amyotrophic lateral sclerosis ( ALS ) . One weakness of the ALSFRS as originally design ed was that it granted disproportionate weighting to limb and bulbar , as compared to respiratory , dysfunction . We have now vali date d a revised version of the ALSFRS , which incorporates additional assessment s of dyspnea , orthopnea , and the need for ventilatory support . The Revised ALSFRS ( ALSFRS-R ) retains the properties of the original scale and shows strong internal consistency and construct validity . ALSFRS-R scores correlate significantly with quality of life as measured by the Sickness Impact Profile , indicating that the quality of function is a strong determinant of quality of life in ALS The Scottish Motor Neuron Disease Register ( SMNDR ) is a prospect i ve , collaborative , population -based project which has been collecting data on incident patients since 1989 . In this report we present the clinical features of 229 patients with motor neuron disease ( 218 sporadic and 11 familial ) diagnosed in 1989 and 1990 and compare their prognosis with previous studies of survival . The overall 50 % survival from symptom onset was 2.5 years ( 95 % CI , 2.2–3.0 ) and 5-year survival 28 % ( 95 % Cl , 20–36 % ) . The presence of progressive bulbar palsy ( PBP ) , either at presentation or developing during the course of the illness , significantly reduced survival and was the most important prognostic indicator . Patients who survived longer than 5 years from symptom onset did not have BP as part of their presenting illness . The prognosis was worse for women , and this was in part related to the higher frequency of PBP in older women , but age was also an independent adverse risk factor . Differences in survival between this and previous series can probably be explained on the basis of variation in case definition and ascertainment methods Background : In recent years , there has been a paradigm shift in the method of healthcare delivery to amyotrophic lateral sclerosis ( ALS ) patients with the emergence of multidisciplinary ALS clinics that cater exclusively for patients with this condition . The impact of multidisciplinary management has not been previously evaluated . Methods : Using data from the Irish ALS Register , we conducted a prospect i ve , population based study of all ALS cases diagnosed in Irel and over a five year period to evaluate the effectiveness of a multidisciplinary clinic on ALS survival . Results : Eighty two ( 24 % ) patients attended the multidisciplinary ALS clinic , with the remaining 262 ( 76 % ) cases followed in a general neurology clinic . The ALS clinic cohort was an average of five years younger ( 60.1 v 65.6 years ) and were more likely to receive riluzole than the general neurology cohort ( 99 % v 61 % ) . The median survival of the ALS clinic cohort was 7.5 months longer than for patients in the general neurology cohort ( logrank = 15.4 , p < 0.0001 ) . Overall , one year mortality was decreased by 29.7 % . Prognosis of bulbar onset patients was extended by 9.6 months if they attended the ALS clinic . Using multivariate analysis , attendance at the ALS clinic was an independent covariate of survival ( HR = 1.47 , p = 0.02 ) . Conclusions : ALS patients who received their care at a multidisciplinary clinic  had a better prognosis than patients attending a general neurology clinic . The data suggest that active and aggressive management enhances survival , particularly among ALS patients with bulbar dysfunction . The effect of clinic type must be considered in future clinical trials design Objective : To determine the incidence , prevalence , and mortality rates of ALS in the province of Modena , Northern Italy , from 1990 through 1999 . Methods : A retrospective epidemiologic study was conducted , ascertaining cases from all neurologic centers and hospitals of the province , death certificates , and the Italian ALS Association , section of Modena . All clinical records were review ed , and only patients fulfilling the El Escorial revised diagnostic criteria were included . Results : During the period considered ( 1990 to 1999 ) , 143 residents ( 67 men and 76 women ) entered the study . The average annual incidence was 2.16 per 100,000 , with a peak in the age class of 75 to 79 years . Mean prevalence rate was 4.02 per 100,000 , and mean mortality rate was 1.69 per 100,000 . The incidence rate remained constant over time , whereas the prevalence and mortality rates increased owing to a rise in survival time ( ALS mean duration was 17.38 months in 1990 , 43.18 months in 1999 ) . In the mountainous areas , where agricultural work is more common , the incidence , prevalence , and mortality rates were higher than in urban areas and the disease onset occurred 10 years later . Of the risk factors examined , only agricultural work and rural residence were significant . Conclusions : The incidence , prevalence , and mortality rates agree with those in recent Italian surveys and with most international studies , but the distribution of cases varied with higher rates in mountainous areas . Further prospect i ve studies are required ALS is a progressive motor neuron disease with no effective treatment . The anti-excitotoxic drug riluzole ( 100 mg/day ) has been shown to decrease mortality and muscular deterioration in ALS patients . To confirm and extend the therapeutic effect of riluzole , we performed a double-blind , placebo-controlled , multicenter , international , dose-ranging ( 50 , 100 , 200 mg/day ) , stratified study in 959 ALS out patients treated for up to 18 months . Primary efficacy criterion was survival and the effect of treatment was analyzed before ( Wilcoxon and log rank tests ) and after adjustment on prognostic factors ( Cox model ) . Secondary efficacy criterion was disease progression assessed through change in functional measures . Tracheostomy-free survival rates were : 50.4 % ( placebo ) , 55.3 % ( 50 mg riluzole ) ( p = 0.23 , Wilcoxon test ; p = 0.25 , log-rank test ) , 56.8 % ( 100 mg riluzole ) ( p = 0.05 , Wilcoxon test ; p = 0.076 , log-rank test ) , and 57.8 % ( 200 mg riluzole ) ( p = 0.061 , Wilcoxon test ; p = 0.075 , log-rank test ) . At the end of the 18-month study , there was a significant dose-related decrease in risk of death or tracheostomy ( p = 0.04 ) . Adjustment for baseline prognostic factors showed a 35 % decreased risk of death with the 100-mg dose compared with placebo ( p = 0.002 ) . No significant treatment effects were detected for the functional assessment s. The most frequent dose-related adverse events included nausea , asthenia , and elevated liver enzyme levels . This study confirms the therapeutic effect of riluzole in a large representative ALS sample , over an 18-month period . Riluzole is well tolerated and decreases the risk of death or tracheostomy in ALS patients . NEUROLOGY 1996;47(Suppl 4 ) : Creatine supplementation in humans has been reported to enhance power and strength both in normal subjects and in patients with various neuromuscular diseases . The purpose of this study was to examine the effects of supplementation on exercise performance and maximal voluntary isometric muscular contraction ( MVIC ) in Amyotrophic Lateral Sclerosis ( ALS ) patients . We report the results obtained in 28 patients with probable/definite ALS . In each patient we acquired the dynamometric measurement of MVIC in 10 muscle groups of upper and lower limbs and a measure of fatigue by means of an high-intensity intermittent protocol in elbow flexors and knee extensors muscles . All patients completed the protocol s at the baseline and after supplementation of 20 g per day for 7 days and after supplementation of 3 g per day for 3 and 6 months .  MVIC increased after 7 days of supplementation in 20 patients ( 70 % ) in knee extensors and in 15 ( 53 % ) of them also in elbow flexors . A statistically significant difference between pre and post-treatment mean values of MVIC was found both in elbow flexors ( P<0.05 ) and knee extensors ( p<0.04 ) . The analysis of the slopes of fatigue test showed a statistically significant improvement after 7 days of supplementation in 11 patients ( 39 % ) in elbow flexors and in 9 patients ( 32 % ) also in knee extensors muscles . During the 6-month follow-up period all the examined parameters showed a linear progressive decline . In conclusion , our preliminary results have demonstrated that supplementation temporary increases maximal isometric power in ALS patients so it may be of potential benefit in situations such as high intensity activity and it can be proposed as a symptomatic treatment Amyotrophic lateral sclerosis ( ALS ) is a fatal disease with no cure . In a transgenic mouse model of ALS , creatine monohydrate showed a promising increase in survival . We performed a double‐blind , placebo‐controlled , sequential clinical trial to assess the effect of creatine monohydrate on survival and disease progression in patients with ALS . Between June 2000 and December 2001 , 175 patients with probable , probable‐laboratory supported , or definite ALS were r and omly assigned to receive either creatine monohydrate or placebo 10gm daily . A sequential trial design was used with death , persistent assisted  ventilation , or tracheostomy as primary end points . Secondary outcome measurements were rate of decline of isometric arm muscle strength , forced vital capacity , functional status , and quality of life . The trial was stopped when the null hypothesis of indifference was accepted . Creatine did not affect survival ( cumulative survival probability of 0.70 in the creatine group vs 0.68 in the placebo group at 12 months , and 0.52 in the creatine group vs 0.47 in the placebo group at 16 months ) , or the rate of decline of functional measurements . Creatine intake did not cause important adverse reactions . This placebo‐controlled trial did not find evidence of a beneficial effect of creatine monohydrate on survival or disease progression in patients with ALS . Ann Neurol Amyotrophic lateral sclerosis is a rapidly progressive disease of unknown etiology result ing in tetraparalysis , dysarthria , dysphagia , and ultimately death from respiratory insufficiency . In the course of the disease , recurrent episodes of aspiration , pneumonia , dehydration , and malnutrition may necessitate nasoenteral tube placement , an inconvenient and unattractive arrangement in patients with dribbling and impaired swallowing . A percutaneous endoscopic gastrostomy seemed a better , though potentially hazardous , alternative in view of the often severely restricted pulmonary function of these patients . Therefore , we prospect ively investigated the use of percutaneous endoscopic g 
    Output:
    
Creatine was reportedly well-tolerated in all three included studies , with no evidence of renal failure or serious adverse events specifically attributable to creatine .
In patients already diagnosed with clinical ly probable or definite amyotrophic lateral sclerosis ( ALS ) , creatine at doses ranging from 5 to 10 g per day did not have a statistically significant effect on survival , ALS functional rating revised scores ( ALSFRS-R ) progression or percent predicted forced vital capacity ( FVC ) progression