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: Background Although the precise etiology of multiple sclerosis ( MS ) is unknown , it seems that both genetic and environmental factors are important . Recent studies suggest that low serum vitamin D levels are important environmental factor in MS . The aim of this study was to compare the serum levels of vitamin D between MS patients and healthy subjects , and to determine its association with disability  in MS patients . Methods In this cross-sectional study , a total of 52 patients with MS were r and omly recruited and matched for age and sex with 52 healthy subjects .  Demographic characteristics and serum vitamin D levels for both groups , as well as duration of disease Exp and ed Disability Status Scale ( EDSS ) for MS patients were evaluated . Statistical analysis was performed by independent sample s t-test and multiple linear regression analysis . Results The mean serum vitamin D levels were 26.5 ± 16.3 ng/ml in MS patients vs. 37.1 ±19.7 in healthy subjects ( P = 0.003 ) . A linear regression analysis showed no significant association between vitamin D levels and EDSS score of patients with MS ( P = 0.345 ) , after adjusting for the covariates . Conclusion Our findings did not suggest a protective association for serum vitamin D levels against disability in MS patients CONTEXT Epidemiological and experimental evidence suggests that high levels of vitamin D , a potent immunomodulator , may decrease the risk of  multiple sclerosis .  There are no prospect i ve studies addressing this hypothesis . OBJECTIVE To examine whether levels of 25-hydroxyvitamin D  are associated with risk of multiple sclerosis . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , nested case-control study among more than 7 million US military personnel who have serum sample s stored in the Department of Defense Serum Repository . Multiple sclerosis cases were identified through Army and Navy physical disability data bases for 1992 through 2004 , and diagnoses were confirmed by medical record review . Each case ( n = 257 ) was matched to 2 controls by age , sex , race/ethnicity , and date s of blood collection . Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum sample s collected before the date of initial multiple sclerosis symptoms . MAIN OUTCOME MEASURES Odds ratios of multiple sclerosis associated with continuous or categorical levels ( quantiles or a priori-defined categories ) of serum 25-hydroxyvitamin D within each racial/ethnic group . RESULTS Among whites ( 148 cases , 296 controls ) , the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D ( odds ratio [ OR ] for a 50-nmol/L increase in 25-hydroxyvitamin D , 0.59 ; 95 % confidence interval , 0.36 - 0.97 ) . In categorical analyses using the lowest quintile ( < 63.3 nmol/L ) as the reference , the ORs for each subsequent quintile were 0.57 , 0.57 , 0.74 , and 0.38 ( P = .02 for trend across quintiles ) . Only the OR for the highest quintile , corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L , was significantly different from 1.00 ( OR , 0.38 ; 95 % confidence interval , 0.19 - 0.75 ; P = .006 ) . The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years . Among blacks and Hispanics ( 109 cases , 218 controls ) , who had lower 25-hydroxyvitamin D levels than whites , no significant associations between vitamin D and multiple sclerosis risk were found . CONCLUSION The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis IMPORTANCE It remains unclear whether vitamin D insufficiency , which is common in individuals with multiple sclerosis ( MS ) , has an adverse effect on MS outcomes . OBJECTIVES To determine whether serum concentrations of 25-hydroxyvitamin D ( 25[OH]D ) , a marker of vitamin D status , predict disease activity and prognosis in patients with a first event suggestive of MS ( clinical ly isolated syndrome ) . DESIGN , SETTING , AND PARTICIPANTS The Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment study was a r and omized trial originally design ed to evaluate the impact of early vs delayed interferon beta-1b treatment in patients with clinical ly isolated syndrome .  Serum 25(OH)D concentrations were measured at baseline and 6 , 12 , and 24 months . A total of 465 of the 468 patients r and omized had at least 1 25(OH)D measurement , and 334 patients had them at both the 6- and 12-month ( seasonally asynchronous ) measurements . Patients were followed up for 5 years clinical ly and by magnetic resonance imaging . MAIN OUTCOMES AND MEASURES New active lesions , increased T2 lesion volume , and brain volume on magnetic resonance imaging , as well as MS relapses and disability ( Exp and ed Disability Status Scale score ) . RESULTS Higher 25(OH)D levels predicted reduced MS activity and a slower rate of progression . A 50-nmol/L ( 20-ng/mL ) increment in average serum 25(OH)D levels within the first 12 months predicted a 57 % lower rate of new active lesions ( P < .001 ) , 57 % lower relapse rate ( P = .03 ) , 25 % lower yearly increase in T2 lesion volume ( P < .001 ) , and 0.41 % lower yearly loss in brain volume ( P = .07 ) from months 12 to 60 . Similar associations were found between 25(OH)D measured up to 12 months and MS activity or progression from months 24 to 60 . In analyses using dichotomous 25(OH)D levels , values greater than or equal to 50 nmol/L ( 20 ng/mL ) at up to 12 months predicted lower disability ( Exp and ed Disability Status Scale score , -0.17 ; P = .004 ) during the subsequent 4 years . CONCLUSIONS AND RELEVANCE Among patients with MS mainly treated with interferon beta-1b  , low 25(OH)D levels early in the disease course are a strong risk factor for long-term MS activity and progression Objective : There is increasing evidence that vitamin D can be protective against the development of multiple sclerosis ( MS ) , but it may also be beneficial for the clinical course of the disease . Our objective was to prospect ively investigate if 25-hydroxy-vitamin D ( 25-OH-D ) levels are associated with exacerbation risk in MS in a study with frequent serum measurements . Methods : This was a prospect i ve longitudinal study in 73 patients with relapsing-remitting MS .  Blood sample s for 25-OH-D measurements were taken every 8 weeks . Associations between 25-OH-D levels and exacerbation rates were assessed using Poisson regression ( generalized estimating equations ) with the individual serum levels as time-dependent variable . Results : During follow-up ( mean 1.7 years ) , 58 patients experienced a total of 139 exacerbations . Monthly moving averages of 25-OH-D levels were categorized into low ( < 50 nmol/L ) , medium ( 50–100 nmol/L ) , and high ( > 100 nmol/L ) levels . Exacerbation risk decreased significantly with higher serum vitamin D levels : respective relative exacerbation rates for the medium and high-level category as compared to the low-level category were 0.7 and 0.5 ( p value for trend : p = 0.007 ) . The association between 25-OH-D concentrations and exacerbation rate was log linear without a threshold . With each doubling of the serum 25-OH-D concentration the exacerbation rate decreased by 27 % ( 95 % confidence interval 8%–42 % , p = 0.008 ) . Conclusions : Our finding that higher vitamin D levels are associated with decreased exacerbation risk in relapsing-remitting MS suggests a beneficial effect of vitamin D on disease course in MS . However , the possibility of reverse causality can not be ruled out completely . R and omized intervention studies are therefore needed to investigate the effect of vitamin D supplementation in MS Objective : Low vitamin D status has been associated with multiple sclerosis ( MS ) prevalence and risk , but the therapeutic potential of vitamin D in established MS has not been explored . Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical , immunologic , and clinical outcomes in patients with MS prospect ively . Methods : An open-label r and omized prospect i ve controlled 52-week trial matched patients with MS for demographic and disease characteristics , with r and omization to treatment or control groups . Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [ 25(OH)D ] rapidly and assess tolerability , followed by 10,000 IU/day ( 12 weeks ) , and further downtitrated to 0 IU/day . Calcium ( 1,200 mg/day ) was given throughout the trial . Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups . Secondary endpoints included 25(OH)D and other biochemical measures , immunologic biomarkers , relapse events , and Exp and ed Disability Status Scale ( EDSS ) score . Results : Forty-nine patients ( 25 treatment , 24 control ) were enrolled [ mean age 40.5 years , EDSS 1.34 , and 25(OH)D 78 nmol/L ] . All calcium-related measures within and between groups were normal . Despite a mean peak 25(OH)D of 413nmol/L , no significant adverse events occurred . Although there may have been confounding variables in clinical outcomes , treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls . Conclusions : High-dose vitamin D ( ∼10,000 IU/day ) in multiple sclerosis is safe , with evidence of immunomodulatory effects . Classification of evidence : This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation . The trial , however , lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures ( relapses and Exp and ed Disability Status Scale scores ) , providing only Class level IV evidence for these outcomes The aim of this preliminary study was to evaluate the effect of low-dose oral vitamin D in combination with current disease-modifying therapy on the prevention of progression of relapsing-remitting multiple sclerosis ( RRMS ) . A phase II double-blind placebo-controlled r and omized clinical trial conducted between October 2007 and October 2008 included 50 patients with confirmed RRMS aged 25 to 57 years and normal serum 25-hydroxyvitamin D. They were r and omly allocated to receive 12 months of treatment with either escalating calcitriol doses up to 0.5 μg/day or placebo combined with disease-modifying therapy . Response to treatment was assessed at eight-week intervals . In both groups , the mean relapse rate decreased significantly ( P < 0.001 ) . In the 25 patients treated with placebo , the mean ( SD ) Exp and ed Disability Status Scale ( EDSS ) increased from 1.70 ( 1.21 ) at baseline to 1.94 ( 1.41 ) at the end of study period ( P < 0.01 ) . Average EDSS and relapse rate at the end of trial did not differ between groups . Adding low-dose vitamin D to routine disease-modifying therapy had no significant effect on the EDSS score or relapse rate . A larger phase III multicenter study of vitamin D in RRMS is warranted to more assess the efficacy of this intervention 
    Output:
    
agent
To sum up , low vitamin D  levels are associated with an increased risk of MS
***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: Background Although the precise etiology of multiple sclerosis ( MS ) is unknown , it seems that both genetic and environmental factors are important . Recent studies suggest that low serum vitamin D levels are important environmental factor in MS . The aim of this study was to compare the serum levels of vitamin D between MS patients and healthy subjects , and to determine its association with disability  in MS patients . Methods In this cross-sectional study , a total of 52 patients with MS were r and omly recruited and matched for age and sex with 52 healthy subjects .  Demographic characteristics and serum vitamin D levels for both groups , as well as duration of disease Exp and ed Disability Status Scale ( EDSS ) for MS patients were evaluated . Statistical analysis was performed by independent sample s t-test and multiple linear regression analysis . Results The mean serum vitamin D levels were 26.5 ± 16.3 ng/ml in MS patients vs. 37.1 ±19.7 in healthy subjects ( P = 0.003 ) . A linear regression analysis showed no significant association between vitamin D levels and EDSS score of patients with MS ( P = 0.345 ) , after adjusting for the covariates . Conclusion Our findings did not suggest a protective association for serum vitamin D levels against disability in MS patients CONTEXT Epidemiological and experimental evidence suggests that high levels of vitamin D , a potent immunomodulator , may decrease the risk of  multiple sclerosis .  There are no prospect i ve studies addressing this hypothesis . OBJECTIVE To examine whether levels of 25-hydroxyvitamin D  are associated with risk of multiple sclerosis . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , nested case-control study among more than 7 million US military personnel who have serum sample s stored in the Department of Defense Serum Repository . Multiple sclerosis cases were identified through Army and Navy physical disability data bases for 1992 through 2004 , and diagnoses were confirmed by medical record review . Each case ( n = 257 ) was matched to 2 controls by age , sex , race/ethnicity , and date s of blood collection . Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum sample s collected before the date of initial multiple sclerosis symptoms . MAIN OUTCOME MEASURES Odds ratios of multiple sclerosis associated with continuous or categorical levels ( quantiles or a priori-defined categories ) of serum 25-hydroxyvitamin D within each racial/ethnic group . RESULTS Among whites ( 148 cases , 296 controls ) , the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D ( odds ratio [ OR ] for a 50-nmol/L increase in 25-hydroxyvitamin D , 0.59 ; 95 % confidence interval , 0.36 - 0.97 ) . In categorical analyses using the lowest quintile ( < 63.3 nmol/L ) as the reference , the ORs for each subsequent quintile were 0.57 , 0.57 , 0.74 , and 0.38 ( P = .02 for trend across quintiles ) . Only the OR for the highest quintile , corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L , was significantly different from 1.00 ( OR , 0.38 ; 95 % confidence interval , 0.19 - 0.75 ; P = .006 ) . The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years . Among blacks and Hispanics ( 109 cases , 218 controls ) , who had lower 25-hydroxyvitamin D levels than whites , no significant associations between vitamin D and multiple sclerosis risk were found . CONCLUSION The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis IMPORTANCE It remains unclear whether vitamin D insufficiency , which is common in individuals with multiple sclerosis ( MS ) , has an adverse effect on MS outcomes . OBJECTIVES To determine whether serum concentrations of 25-hydroxyvitamin D ( 25[OH]D ) , a marker of vitamin D status , predict disease activity and prognosis in patients with a first event suggestive of MS ( clinical ly isolated syndrome ) . DESIGN , SETTING , AND PARTICIPANTS The Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment study was a r and omized trial originally design ed to evaluate the impact of early vs delayed interferon beta-1b treatment in patients with clinical ly isolated syndrome .  Serum 25(OH)D concentrations were measured at baseline and 6 , 12 , and 24 months . A total of 465 of the 468 patients r and omized had at least 1 25(OH)D measurement , and 334 patients had them at both the 6- and 12-month ( seasonally asynchronous ) measurements . Patients were followed up for 5 years clinical ly and by magnetic resonance imaging . MAIN OUTCOMES AND MEASURES New active lesions , increased T2 lesion volume , and brain volume on magnetic resonance imaging , as well as MS relapses and disability ( Exp and ed Disability Status Scale score ) . RESULTS Higher 25(OH)D levels predicted reduced MS activity and a slower rate of progression . A 50-nmol/L ( 20-ng/mL ) increment in average serum 25(OH)D levels within the first 12 months predicted a 57 % lower rate of new active lesions ( P < .001 ) , 57 % lower relapse rate ( P = .03 ) , 25 % lower yearly increase in T2 lesion volume ( P < .001 ) , and 0.41 % lower yearly loss in brain volume ( P = .07 ) from months 12 to 60 . Similar associations were found between 25(OH)D measured up to 12 months and MS activity or progression from months 24 to 60 . In analyses using dichotomous 25(OH)D levels , values greater than or equal to 50 nmol/L ( 20 ng/mL ) at up to 12 months predicted lower disability ( Exp and ed Disability Status Scale score , -0.17 ; P = .004 ) during the subsequent 4 years . CONCLUSIONS AND RELEVANCE Among patients with MS mainly treated with interferon beta-1b  , low 25(OH)D levels early in the disease course are a strong risk factor for long-term MS activity and progression Objective : There is increasing evidence that vitamin D can be protective against the development of multiple sclerosis ( MS ) , but it may also be beneficial for the clinical course of the disease . Our objective was to prospect ively investigate if 25-hydroxy-vitamin D ( 25-OH-D ) levels are associated with exacerbation risk in MS in a study with frequent serum measurements . Methods : This was a prospect i ve longitudinal study in 73 patients with relapsing-remitting MS .  Blood sample s for 25-OH-D measurements were taken every 8 weeks . Associations between 25-OH-D levels and exacerbation rates were assessed using Poisson regression ( generalized estimating equations ) with the individual serum levels as time-dependent variable . Results : During follow-up ( mean 1.7 years ) , 58 patients experienced a total of 139 exacerbations . Monthly moving averages of 25-OH-D levels were categorized into low ( < 50 nmol/L ) , medium ( 50–100 nmol/L ) , and high ( > 100 nmol/L ) levels . Exacerbation risk decreased significantly with higher serum vitamin D levels : respective relative exacerbation rates for the medium and high-level category as compared to the low-level category were 0.7 and 0.5 ( p value for trend : p = 0.007 ) . The association between 25-OH-D concentrations and exacerbation rate was log linear without a threshold . With each doubling of the serum 25-OH-D concentration the exacerbation rate decreased by 27 % ( 95 % confidence interval 8%–42 % , p = 0.008 ) . Conclusions : Our finding that higher vitamin D levels are associated with decreased exacerbation risk in relapsing-remitting MS suggests a beneficial effect of vitamin D on disease course in MS . However , the possibility of reverse causality can not be ruled out completely . R and omized intervention studies are therefore needed to investigate the effect of vitamin D supplementation in MS Objective : Low vitamin D status has been associated with multiple sclerosis ( MS ) prevalence and risk , but the therapeutic potential of vitamin D in established MS has not been explored . Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical , immunologic , and clinical outcomes in patients with MS prospect ively . Methods : An open-label r and omized prospect i ve controlled 52-week trial matched patients with MS for demographic and disease characteristics , with r and omization to treatment or control groups . Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [ 25(OH)D ] rapidly and assess tolerability , followed by 10,000 IU/day ( 12 weeks ) , and further downtitrated to 0 IU/day . Calcium ( 1,200 mg/day ) was given throughout the trial . Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups . Secondary endpoints included 25(OH)D and other biochemical measures , immunologic biomarkers , relapse events , and Exp and ed Disability Status Scale ( EDSS ) score . Results : Forty-nine patients ( 25 treatment , 24 control ) were enrolled [ mean age 40.5 years , EDSS 1.34 , and 25(OH)D 78 nmol/L ] . All calcium-related measures within and between groups were normal . Despite a mean peak 25(OH)D of 413nmol/L , no significant adverse events occurred . Although there may have been confounding variables in clinical outcomes , treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls . Conclusions : High-dose vitamin D ( ∼10,000 IU/day ) in multiple sclerosis is safe , with evidence of immunomodulatory effects . Classification of evidence : This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation . The trial , however , lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures ( relapses and Exp and ed Disability Status Scale scores ) , providing only Class level IV evidence for these outcomes The aim of this preliminary study was to evaluate the effect of low-dose oral vitamin D in combination with current disease-modifying therapy on the prevention of progression of relapsing-remitting multiple sclerosis ( RRMS ) . A phase II double-blind placebo-controlled r and omized clinical trial conducted between October 2007 and October 2008 included 50 patients with confirmed RRMS aged 25 to 57 years and normal serum 25-hydroxyvitamin D. They were r and omly allocated to receive 12 months of treatment with either escalating calcitriol doses up to 0.5 μg/day or placebo combined with disease-modifying therapy . Response to treatment was assessed at eight-week intervals . In both groups , the mean relapse rate decreased significantly ( P < 0.001 ) . In the 25 patients treated with placebo , the mean ( SD ) Exp and ed Disability Status Scale ( EDSS ) increased from 1.70 ( 1.21 ) at baseline to 1.94 ( 1.41 ) at the end of study period ( P < 0.01 ) . Average EDSS and relapse rate at the end of trial did not differ between groups . Adding low-dose vitamin D to routine disease-modifying therapy had no significant effect on the EDSS score or relapse rate . A larger phase III multicenter study of vitamin D in RRMS is warranted to more assess the efficacy of this intervention 
    Output:
    