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: Objective : Assessment of the effectiveness and safety of high daily 125 μg ( 5000 IU ) or 250 μg ( 10 000IU ) doses of vitamin D2 during 3 months , in rapidly obtaining adequate 25 hydroxyvitamin D ( 25OHD ) levels . Design : Longitudinal study .Subjects : Postmenopausal osteopenic/osteoporotic women ( n=38 ) were studied during winter and spring . Median age ( 25–75th percentile ) was 61.5 ( 57.00–66.25 ) years , and mean bone mineral density ( BMD ) was 0.902 (0.800–1.042)g/cm2 . Subjects were r and omly divided into three groups : control group ( n=13 ) : no vitamin D2 , 125 μg/day ( n=13 ) and 250 μg/day ( n=12 ) of vitamin D2 groups , all receiving 500 mg calcium/day . Serum calcium , phosphate , bone alkaline phosphatase ( BAP ) , C-telopeptide ( CTX ) , 25OHD , mid-molecule parathyroid hormone ( mmPTH ) , daily urinary calcium and creatinine excretion were determined at baseline and monthly . Results : For all subjects ( n=38 ) , the median baseline 25 hydroxyvitamin D ( 25OHD ) level was 36.25 ( 27.5–48.12 ) nmol/l . After 3 months , 8 % of the patients in the control group , 50 % in the 125 μg/day group and 75 % in the 250 μg/day group had 25OHD values above 85 nmol/l ( 34 ng/ml ) . Considering both vitamin D2 groups together , mmPTH and BAP levels diminished significantly after 3 months ( P<0.02 ) , unlike those of CTX . Serum calcium remained within normal range during the follow-up . Conclusions : The oral dose of vitamin D2 required to rapidly achieve adequate levels of 25OHD is seemingly much higher than the usual recommended vitamin D3 dose ( 20 μg/day ) . During 3 months , 250 μg/day of vitamin D2 most effectively raised 25OHD levels to 85 nmol/l in 75 % of the postmenopausal osteopenic/osteoporotic women treated BACKGROUND The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known , particularly within ranges comparable to the probable physiologic supply of the vitamin . OBJECTIVES The objectives were to establish the quantitative relation between steady state cholecalciferol input and the result ing serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores . DESIGN Cholecalciferol was administered daily in controlled oral doses labeled at 0 , 25 , 125 , and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha ( 41.2 degrees N latitude ) . The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment . RESULTS From a mean baseline value of 70.3 nmol/L , equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose , with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input . The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study ( ie , in the autumn ) was 12.5 micro g ( 500 IU)/d , whereas the total amount from all sources ( supplement , food , tissue stores ) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g ( approximately 3800 IU)/d . By difference , the tissue stores provided approximately 78 - 82 micro g/d . CONCLUSIONS Healthy men seem to use 3000 - 5000 IU cholecalciferol/d , apparently meeting > 80 % of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months . Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin AIMS A significant proportion of cardiac surgical patients develop critical post-operative complications . We aim ed to investigate the association of pre-operative 25-hydroxyvitamin D ( 25(OH)D ) levels with major cardiac and cerebrovascular events ( MACCE ) in cardiac surgical patients . METHODS AND RESULTS From January 2010 to August 2011 , we consecutively measured circulating 25(OH)D in 4418 operated patients . Of the study cohort , 38.0 % had deficient 25(OH)D values ( < 30 nmol/L ) and additional 32.3 % had insufficient values ( 30 - 49.9 nmol/L ) , whereas only 3.1 % had values > 100 nmol/L. The incidence of MACCE was 11.5 % . In multivariable-adjusted logistic regression models , the odds ratio of MACCE at deficient , inadequate , and high 25(OH)D levels was 2.23 [ 95 % confidence interval ( CI ) : 1.31 - 3.79 ] , 1.73 ( 95 % CI : 1.01 - 2.96 ) and 2.34 ( 95 % CI : 1.12 - 4.89 ) , respectively , compared with 25(OH)D levels of 75 - 100 nmol/L. A U-shaped association with circulating 25(OH)D was also present for duration of mechanical ventilatory support and intensive care unit stay . Multivariable-adjusted 6- and 12-month mortality were higher in patients with deficient 25(OH)D levels compared with patients with 25(OH)D levels of 75 - 100 nmol/L. CONCLUSION Deficient 25(OH)D levels are prevalent in cardiac surgical patients in Central Europe and are independently associated with the risk of MACCE . Further research should clarify the potential of vitamin D supplements in reducing cardiovascular risk in vitamin D-deficient patients and also the mechanisms leading to adverse effects on the cardiovascular system in the small group of patients with 25(OH)D levels > 100 OBJECTIVES To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents . DESIGN Secondary data analysis of a previously conducted r and omized clinical trial . SETTING Seven hundred twenty-five-bed long-term care facility . PARTICIPANTS One hundred twenty-four nursing home residents ( average age 89 ) . INTERVENTION Participants were r and omly assigned to receive one of four vitamin D supplement doses ( 200 IU , 400 IU , 600 IU , or 800 IU ) or placebo daily for 5 months . MEASUREMENTS Number of fallers and number of falls assessed using facility incident tracking data base . RESULTS Over the 5-month study period , the proportion of participants with falls was 44 % in the placebo group ( 11/25 ) , 58 % ( 15/26 ) in the 200 IU group , 60 % ( 15/25 ) in the 400 IU group , 60 % ( 15/25 ) in the 600 IU group , and 20 % ( 5/23 ) in the 800 IU group . Participants in the 800 IU group had a 72 % lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months ( rate ratio=0.28 ; 95 % confidence interval=0.11 - 0.75 ) . No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups . CONCLUSION Nursing home residents in the highest vitamin D group ( 800 IU ) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses . Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867 We investigated the short-term effects on bone turnover markers of high doses of vitamin D3 in order to identify what initial therapeutic dose can be safely administered in vitamin D-deficient subjects . Thirty-seven elderly subjects [ mean age 75 ± 3 ( SD ) years ] were consecutively r and omized to the administration of a single oral bolus of 600000 , 300000 , or 100000 IU vitamin D3 . Blood sample s were taken at baseline and 1 , 3 , 7 , 14 , 30 , 60 , and 90 days after vitamin D3 administration . Twenty-four subjects served as controls . No relevant changes in bone turnover markers [ C-terminal telopeptides of type I collagen ( sCTX ) and bone-specific alkaline phosphatase ( BAP ) ] were observed in the controls . In treated patients a dose-dependent effect on sCTX was observed . With the administration of 600,000 IU vitamin D3 a significant increase of sCTX was observed already at day 1 , and it was sustained for 2 months . The changes in sCTX with smaller doses were considerably lower and reached statistical significance only within the first 3 days with the 300,000 IU dose . BAP remained unchanged in patients given 300,000 and 600,000 IU vitamin D3 , while it significantly rose by 15–23 % throughout the observation period in patients given 100,000 IU . Our results indicate that the use of a vitamin D bolus exceeding 
    Output:
    
agent
Conclusions This systematic review demonstrates that body weight is an important predictor of variation in circulating 25OHD in cohorts on vitamin D supplements .
Our model provides an estimate of the daily vitamin D dose that is necessary for achieving adequate circulating 25OHD levels in vitamin D-insufficient or vitamin D-deficient individuals/cohorts with different body weights and ages
***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 : Assessment of the effectiveness and safety of high daily 125 μg ( 5000 IU ) or 250 μg ( 10 000IU ) doses of vitamin D2 during 3 months , in rapidly obtaining adequate 25 hydroxyvitamin D ( 25OHD ) levels . Design : Longitudinal study .Subjects : Postmenopausal osteopenic/osteoporotic women ( n=38 ) were studied during winter and spring . Median age ( 25–75th percentile ) was 61.5 ( 57.00–66.25 ) years , and mean bone mineral density ( BMD ) was 0.902 (0.800–1.042)g/cm2 . Subjects were r and omly divided into three groups : control group ( n=13 ) : no vitamin D2 , 125 μg/day ( n=13 ) and 250 μg/day ( n=12 ) of vitamin D2 groups , all receiving 500 mg calcium/day . Serum calcium , phosphate , bone alkaline phosphatase ( BAP ) , C-telopeptide ( CTX ) , 25OHD , mid-molecule parathyroid hormone ( mmPTH ) , daily urinary calcium and creatinine excretion were determined at baseline and monthly . Results : For all subjects ( n=38 ) , the median baseline 25 hydroxyvitamin D ( 25OHD ) level was 36.25 ( 27.5–48.12 ) nmol/l . After 3 months , 8 % of the patients in the control group , 50 % in the 125 μg/day group and 75 % in the 250 μg/day group had 25OHD values above 85 nmol/l ( 34 ng/ml ) . Considering both vitamin D2 groups together , mmPTH and BAP levels diminished significantly after 3 months ( P<0.02 ) , unlike those of CTX . Serum calcium remained within normal range during the follow-up . Conclusions : The oral dose of vitamin D2 required to rapidly achieve adequate levels of 25OHD is seemingly much higher than the usual recommended vitamin D3 dose ( 20 μg/day ) . During 3 months , 250 μg/day of vitamin D2 most effectively raised 25OHD levels to 85 nmol/l in 75 % of the postmenopausal osteopenic/osteoporotic women treated BACKGROUND The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known , particularly within ranges comparable to the probable physiologic supply of the vitamin . OBJECTIVES The objectives were to establish the quantitative relation between steady state cholecalciferol input and the result ing serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores . DESIGN Cholecalciferol was administered daily in controlled oral doses labeled at 0 , 25 , 125 , and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha ( 41.2 degrees N latitude ) . The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment . RESULTS From a mean baseline value of 70.3 nmol/L , equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose , with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input . The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study ( ie , in the autumn ) was 12.5 micro g ( 500 IU)/d , whereas the total amount from all sources ( supplement , food , tissue stores ) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g ( approximately 3800 IU)/d . By difference , the tissue stores provided approximately 78 - 82 micro g/d . CONCLUSIONS Healthy men seem to use 3000 - 5000 IU cholecalciferol/d , apparently meeting > 80 % of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months . Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin AIMS A significant proportion of cardiac surgical patients develop critical post-operative complications . We aim ed to investigate the association of pre-operative 25-hydroxyvitamin D ( 25(OH)D ) levels with major cardiac and cerebrovascular events ( MACCE ) in cardiac surgical patients . METHODS AND RESULTS From January 2010 to August 2011 , we consecutively measured circulating 25(OH)D in 4418 operated patients . Of the study cohort , 38.0 % had deficient 25(OH)D values ( < 30 nmol/L ) and additional 32.3 % had insufficient values ( 30 - 49.9 nmol/L ) , whereas only 3.1 % had values > 100 nmol/L. The incidence of MACCE was 11.5 % . In multivariable-adjusted logistic regression models , the odds ratio of MACCE at deficient , inadequate , and high 25(OH)D levels was 2.23 [ 95 % confidence interval ( CI ) : 1.31 - 3.79 ] , 1.73 ( 95 % CI : 1.01 - 2.96 ) and 2.34 ( 95 % CI : 1.12 - 4.89 ) , respectively , compared with 25(OH)D levels of 75 - 100 nmol/L. A U-shaped association with circulating 25(OH)D was also present for duration of mechanical ventilatory support and intensive care unit stay . Multivariable-adjusted 6- and 12-month mortality were higher in patients with deficient 25(OH)D levels compared with patients with 25(OH)D levels of 75 - 100 nmol/L. CONCLUSION Deficient 25(OH)D levels are prevalent in cardiac surgical patients in Central Europe and are independently associated with the risk of MACCE . Further research should clarify the potential of vitamin D supplements in reducing cardiovascular risk in vitamin D-deficient patients and also the mechanisms leading to adverse effects on the cardiovascular system in the small group of patients with 25(OH)D levels > 100 OBJECTIVES To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents . DESIGN Secondary data analysis of a previously conducted r and omized clinical trial . SETTING Seven hundred twenty-five-bed long-term care facility . PARTICIPANTS One hundred twenty-four nursing home residents ( average age 89 ) . INTERVENTION Participants were r and omly assigned to receive one of four vitamin D supplement doses ( 200 IU , 400 IU , 600 IU , or 800 IU ) or placebo daily for 5 months . MEASUREMENTS Number of fallers and number of falls assessed using facility incident tracking data base . RESULTS Over the 5-month study period , the proportion of participants with falls was 44 % in the placebo group ( 11/25 ) , 58 % ( 15/26 ) in the 200 IU group , 60 % ( 15/25 ) in the 400 IU group , 60 % ( 15/25 ) in the 600 IU group , and 20 % ( 5/23 ) in the 800 IU group . Participants in the 800 IU group had a 72 % lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months ( rate ratio=0.28 ; 95 % confidence interval=0.11 - 0.75 ) . No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups . CONCLUSION Nursing home residents in the highest vitamin D group ( 800 IU ) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses . Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867 We investigated the short-term effects on bone turnover markers of high doses of vitamin D3 in order to identify what initial therapeutic dose can be safely administered in vitamin D-deficient subjects . Thirty-seven elderly subjects [ mean age 75 ± 3 ( SD ) years ] were consecutively r and omized to the administration of a single oral bolus of 600000 , 300000 , or 100000 IU vitamin D3 . Blood sample s were taken at baseline and 1 , 3 , 7 , 14 , 30 , 60 , and 90 days after vitamin D3 administration . Twenty-four subjects served as controls . No relevant changes in bone turnover markers [ C-terminal telopeptides of type I collagen ( sCTX ) and bone-specific alkaline phosphatase ( BAP ) ] were observed in the controls . In treated patients a dose-dependent effect on sCTX was observed . With the administration of 600,000 IU vitamin D3 a significant increase of sCTX was observed already at day 1 , and it was sustained for 2 months . The changes in sCTX with smaller doses were considerably lower and reached statistical significance only within the first 3 days with the 300,000 IU dose . BAP remained unchanged in patients given 300,000 and 600,000 IU vitamin D3 , while it significantly rose by 15–23 % throughout the observation period in patients given 100,000 IU . Our results indicate that the use of a vitamin D bolus exceeding 
    Output:
    