***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: Amyotrophic lateral sclerosis ( ALS ) is a fatal neurodegenerative disease that imposes a great burden on the patient , the patient 's family and society . However , we lack information about the total disease burden at a national level , especially regarding costs before and after diagnosis and the consequences for spouses . We aim ed to estimate the factual direct and indirect costs of ALS in a national sample . Using records from the Danish National Patient Registry ( 1998–2009 ) , 2,394 patients with ALS were identified and subsequently compared with 9,575 r and omly chosen control subjects matched for age , gender and geographic area/civil status .  Direct costs , including frequencies of primary and sector contacts and procedures , and medication from primary and secondary sectors , were obtained from the Danish Ministry of Health , the Danish Medicines Agency , and the National Health Security . Indirect costs included labour supply and social transfer payments , and were based on income data derived from Coherent Social Statistics . Patients with a diagnosis of ALS had poor survival .  The average ( 95 % CI ) 5-year survival rate was 0.278 ( 0.358–0.298 ) compared with 0.865 ( 0.858–0.872 ) among controls . Patients with ALS had significantly higher rates of health-related contact and medication use and higher socioeconomic costs . They also had very low employment rates , while those in employment had a lower income level than control subjects . The annual mean excess health-related cost was € 18,918 for each ALS patient . However , spouses showed no excess health usage ; in fact , their employment and income rates were higher , and the net cost was reduced by −€3,420 . We conclude that ALS has serious mortality , health and socioeconomic consequences for patients . However , the consequences for spouses are complex ; they tend to compensate for the social consequences to patients by increasing their net income after ALS diagnosis 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 Non‐invasive positive pressure ventilation ( NPPV ) can improve survival in ALS patients with advanced respiratory impairment , but it is not known if it is beneficial earlier in the disease course . A retrospective cohort study of patients with ALS was performed comparing survival from time of diagnosis in subjects who started NPPV use when their FVC was ⩾65 % predicted ( Early NPPV ) with subjects who started NPPV when their FVC was below 65 % predicted ( St and ard NPPV ) . The Early group ( n = 25 ) and the St and ard group ( n = 67 ) were similar except for pulmonary function ( mean FVC in Early NPPV group = 74.3±10.1 % predicted and 48.3±11.3 in St and ard group , p<0.001 ) . The median time from ALS diagnosis to death was significantly longer in the Early NPPV group ( 2.7 years vs. 1.8 years , p = 0.045 ) . This remained significant after adjustment for potential confounding factors ( H.R. = 0.55 , 95 % CI 0.31–0.98 ) . Survival from time of diagnosis was nearly one year longer in the Early group . Until more definitive data are available from r and omized trials , our findings suggest that clinicians either encourage earlier use of NPPV or use more sensitive tests for respiratory muscle impairment than upright FVC Background Geographical differences in the incidence of amyotrophic lateral sclerosis ( ALS ) have been reported in the literature but comparisons across previous studies are limited by different methods in case ascertainment and by the relatively small size of the studied population s. To address these issues , the authors undertook a pooled analysis of European population based ALS registries . Methods All new incident ALS cases in subjects aged 18 years old and older were identified prospect ively in six population based registries in three European countries ( Irel and , UK and Italy ) in the 2 year period 1998–1999 , with a reference population of almost 24 million . Results Based on 1028 identified incident cases , the crude annual incidence rate of ALS in the general European population was 2.16 per 100 000 person years ; 95 % CI 2.0 to 2.3 ) , with similar incidence rates across all registries . The incidence was higher among men ( 3.0 per 100 000 person years ; 95 % CI 2.8 to 3.3 ) than among women ( 2.4 per 100 000 person years ; 95 % CI 2.2 to 2.6 ) . Spinal onset ALS was more common among men compared with women , particularly in the 70–80 year age group . Disease occurrence decreased rapidly after 80 years of age . Conclusions ALS incidence is homogeneous across Europe . Sex differences in incidence may be explained by the higher incidence of spinal onset ALS among men , and the age related disease pattern suggests that ALS occurs within a susceptible group within the population rather than being a disease of ageing Objective : To determine whether ALS patients ’ preferences for ameliorative or life-extending technologies elicited early in the disease were related to later treatment choices . Methods : In this prospect i ve cohort study , 121 patients were seen at a tertiary ALS care center and followed for a median of 12 months . At baseline , patient preferences for use of tracheostomy and percutaneous endoscopic gastrostomy ( PEG ) placement were elicited . All patients received the same educational information before being interviewed about treatment preferences . Patients were then followed to determine if patients who viewed the interventions favorably at baseline were significantly more likely to use the interventions over follow-up . Results : Six to twelve percent of patients were certain they wanted  tracheostomy  and 28.2 % wanted  PEG . Preferences were related to later treatment choices : 20 % of patients who found tracheostomy acceptable had one in the follow-up period , compared with 3.4 % of those not in favor ( p < 0.001 ) . For PEG , similar findings were obtained : 48.5 % who initially found it acceptable had PEG , versus 8.1 % of those not in favor of this treatment ( p < 0.001 ) . Patients who found the interventions acceptable were more likely to be recently diagnosed , expressed greater attachment to life , and showed greater declines in pulmonary function over follow-up . Conclusions : Patients with ALS were able to express their preferences for life-extending or ameliorative technologies  and made choices consistent with these preferences . However , patient preferences may change over time , and clinical education efforts are required throughout the course of disease 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 ) : BACKGROUND Few patients with amyotrophic lateral sclerosis currently receive non-invasive ventilation ( NIV ) , reflecting clinical uncertainty about the role of this intervention . We aim ed to assess the effect of NIV on quality of life and survival in amyotrophic lateral sclerosis in a r and omised controlled trial . METHODS 92 of 102 eligible patients participated . They were assessed every 2 months and r and omly assigned to NIV ( n=22 ) or st and ard care ( n=19 ) when they developed either orthopnoea with maximum inspiratory pressure less than 60 % of that predicted or symptomatic hypercapnia . Primary vali date d quality -of-life outcome measures were the short form 36 mental component summary ( MCS ) and the sleep apnoea quality -of-life index symptoms domain ( sym ) . Both time maintained above 75 % of baseline ( T(i)MCS and T(i)sym ) and mean improvement ( microMCS and microsym ) were measured . FINDINGS NIV improved T(i)MCS , T(i)sym , microMCS , microsym , and survival in all patients and in the subgroup with better bulbar function ( n=20 ) . This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days ( p=0.006 ) with maintained quality of life for most of this period . NIV improved some quality -of-life indices in those with poor bulbar function , including microsym ( p=0.018 ) , but conferred no survival benefit . INTERPRETATION In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction , NIV improves survival with maintenance of , and improvement in , quality of life . The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy . In patients with severe bulbar impairment , NIV improves sleep-related symptoms , but is unlikely to confer a large survival advantage BACKGROUND Although amyotrophic lateral sclerosis ( ALS ) is a rapidly progressive neurodegenerative disorder , some ALS cases can survive beyond 10 years . However , the predictors of long survival in ALS patients remain uncertain . OBJECTIVE To define clinical predictors of long survival in a cohort of ALS incident cases . METHODS One hundred-thirty incidents cases , diagnosed in 1998 - -1999 and classified according to the El Escorial criteria ( EEC ) , were enrolled from a prospect i ve population -based registry established in Puglia , Italy . All but two cases were followed-up until death or November 30 , 2006 . RESULTS Thirteen patients ( high 10 % of the survivors ) were classified as long survivors ( LS ) , 13 as  short survivors ( SS ) ( low 10 % ) , and 102 as average survivors ( AS ) . LS presented a lower frequency of bulbar onset ( 8 % versus 29 % of AS and 39 % of SS ; p=0.1 ) and a significantly longer time between symptom onset to diagnosis [ ( ODI ) : 13 months versus 10 and 6 ; p=0.0005 ] . In multivariate analysis , predictors of long survival were younger age at diagn 
    Output:
    
Costs associated with ALS were greater than that of other neurological diseases , indicating a continued need for medical advances and financial support for patients and families .