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 For adults , vitamin D intake of 100 mcg ( 4000 IU)/day is physiologic and safe . The adequate intake ( AI ) for older adults is 15 mcg ( 600 IU)/day , but there has been no report focusing on use of this dose . Methods We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded , r and omized trial . In Study 1 , 64 out patients ( recruited if summer 2001 25(OH)D < 61 nmol/L ) were given 15 or 100 mcg/day vitamin D in December 2001 . Biochemical responses were followed at subsequent visits that were part of clinical care ; 37 patients completed a wellbeing question naire in December 2001 and February 2002 . Subjects for Study 2 were recruited if their 25(OH)D was < 51 nmol/L in summer 2001 . 66 out patients were given vitamin D ;  51 completed a wellbeing question naire in both December 2002 and February 2003 . Results In Study 1 , basal summer 25-hydroxyvitamin D [ 25(OH)D ] averaged 48 ± 9 ( SD ) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 ± 30 nmol/L for the 15 mcg/day group , and 112 ± 41 nmol/L for the 100 mcg/day group . Both doses lowered plasma parathyroid hormone with no effect on plasma calcium . Between December and February , wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group ( 1-tail Mann-Whitney p = 0.036 ) . In Study 2 , 25(OH)D averaged 39 ± 9 nmol/L , and winter wellbeing scores improved with both doses of vitamin D ( two-tail p < 0.001 ) . Conclusion The highest AI for vitamin D  brought summertime 25(OH)D to > 40 nmol/L , lowered PTH , and its use was associated with improved wellbeing . The 100 mcg/day dose produced greater responses . Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients , we can not rule out a placebo wellbeing response , particularly for those on the lower dose . This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin Background Controversies are common in medicine . Some arise when the conclusions of research publications directly contradict each other , creating uncertainty for frontline clinicians . Discussion In this paper , we review how research ers can look at very similar data yet have completely different conclusions based purely on an over-reliance of statistical significance and an unclear underst and ing of confidence intervals . The dogmatic adherence to statistical significant thresholds can lead authors to write dichotomized absolute conclusions while ignoring the broader interpretations of very consistent findings . We describe three examples of controversy around the potential benefit of a medication , a comparison between new medications , and a medication with a potential harm . The examples include the highest levels of evidence , both meta-analyses and r and omized controlled trials . We will show how in each case the confidence intervals and point estimates were very similar . The only identifiable differences to account for the contrasting conclusions arise from the serendipitous finding of confidence intervals that either marginally cross or just fail to cross the line of statistical significance . Summary These opposing conclusions are false disagreements that create unnecessary clinical uncertainty . We provide helpful recommendations in approaching conflicting conclusions when they are associated with remarkably similar results OBJECTIVE To compare the effects of dydrogesterone and calcium plus vitamin D in women with severe premenstrual syndrome ( PMS ) . METHOD In this r and omized , double-blind , placebo-controlled study , 180 Shiraz University students with PMS used question naires daily to rate their symptoms for 2 menstrual cycles . Then , the students were r and omly assigned to take a tablet containing either 5 mg of dydrogesterone , 500 mg of calcium plus 200 mg of vitamin D , or a placebo twice daily from the 15th to the 24th day of the cycle for 2 more cycles , and to use the same question naires during the intervention cycles . The collected data were then analyzed by repeated-measurement design and multilevel modeling tests . RESULT Treatment with dydrogesterone or calcium plus vitamin D  decreased symptom severity in a similar way ( by 4.64 % and 4.20 % , respectively ) and placebo was associated with a 3.42 % decrease . CONCLUSION Treatment with dydrogesterone or calcium plus vitamin D had a similar effect on symptom severity in women with PMS OBJECTIVE : Observational studies suggest that serum levels of 25-hydroxyvitamin D ( 25[OH]D ) are inversely associated with acute respiratory infections ( ARIs ) . We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs . METHODS : By using cluster r and omization , classrooms of 744 Mongolian schoolchildren were r and omly assigned to different treatments in winter ( January – March ) . This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk ( control ; n = 104 ) or milk fortified with 300 IU of vitamin D3 ( n = 143 ) . This comparison was double-blinded . The primary outcome was the number of parent-reported ARIs over the past 3 months . RESULTS : At baseline , the median serum 25(OH)D level was 7 ng/mL ( interquartile range : 5–10 ng/mL ) . At the end of the trial , follow-up was 99 % ( n = 244 ) , and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different ( 7 vs 19 ng/mL ; P < .001 ) . Compared with controls , children receiving vitamin D reported significantly fewer ARIs during the study period ( mean : 0.80 vs 0.45 ; P = .047 ) , with a rate ratio of 0.52 ( 95 % confidence interval : 0.31–0.89 ) . Adjusting for age , gender , and history of wheezing , vitamin D continued to halve the risk of ARI ( rate ratio : 0.50 [ 95 % confidence interval : 0.28–0.88 ] ) . Similar results were found among children either below or above the median 25(OH)D level at baseline ( rate ratio : 0.41 vs 0.57 ; Pinteraction = .27 ) . CONCLUSIONS : Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency OBJECTIVES To determine the prevalence of vitamin D deficiency in older people in residential care and the influence that the level of vitamin D may have on their incidence of falls . DESIGN Prospect i ve cohort . SETTING Residential care facilities for older people in several states of Australia . PARTICIPANTS Six hundred sixty-seven women in low-level care and 952 women in high-level care , mean age 83.7 years . MEASUREMENTS  Serum 25-hydroxyvitamin D ( 25D ) levels and recognized risk factors for falls including current medication use , a history of previous fractures , weight , tibial length ( as a surrogate for height ) , cognitive function , walking ability , and frequency of going outdoors were determined . The women in low-level care and high-level care were followed for an average of 145 and 168 days , respectively . Falls were recorded prospect ively in diaries completed monthly by residential care staff . RESULTS  Vitamin D deficiency ( defined as a serum 25D level below 25 nmol/L ) was present in 144 ( 22 % ) women in low-level care and 428 ( 45 % ) in high-level care . After excluding 358 bed-bound residents and adjusting for weight , cognitive status , psychotropic drug use , previous Colles fracture , and the presence of w and ering behavior , log serum 25D level remained independently associated with time to first fall . The adjusted hazards ratio was 0.74 ( 95 % confidence interval=0.59 - 0.94 ; P=.01 ) , implying a 20 % reduction in the risk of falling with a doubling of the vitamin D level . CONCLUSION Vitamin D deficiency is common in residential care in Australia . A low level of serum vitamin D is an independent predictor of incident falls BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk  of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P < 0.03 ) . With the use of logistic regression , the unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P < 0.005 ) but did not change significantly for the Ca-only group . In multiple logistic regression models , both treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces  all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170 BACKGROUND Epidemiological evidence supports a relationship between vitamin D and mental well-being , although evidence from large-scale placebo-controlled intervention trials is lacking . AIMS To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women ; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms ; and if there is an association between serum 25-hydroxyvitamin D levels and mental health . METHOD A double-blind , r and omised , placebo-controlled trial of women aged 70 or older ( the Vital D Study : IS RCT N83409867 and ACTR12605000658617 ) . Participants were r and omly assigned to receive 500 000 IU vitamin D(3 ) ( cholecalciferol ) orally or placebo every autumn/winter for 3 - 5 consecutive years . The tools utilised at various time points were the General Health Question naire , the 12-item Short Form Health Survey , the Patient Global Impression-Improvement scale and the WHO Well-Being Index . Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants . RESULTS In this non- clinical population , no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health . Serum 25-hydroxyvitamin D levels in the vitamin D group were 41 % higher than the placebo group 12 months following their annual dose . Despite this difference , scores from the question naires did not differ . Furthermore , there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups . CONCLUSIONS The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3 ) is a practical intervention to prevent depressive symptoms in older community-dwelling women BACKGROUND To our knowledge , no rigorously design ed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza . OBJECTIVE We investigated the effect of vitamin D supplements on the incidence of  seasonal influenza A in schoolchildren . DESIGN From December 2008 through March 2009 , we conducted a r and omized , double-blind , placebo-controlled trial comparing vitamin D(3 ) supplements ( 1200 IU/d ) with placebo  in schoolchildren . The primary outcome was the incidence of influenza A , diagnosed with influenza antigen testing with a nasopharyngeal swab specimen . RESULTS Influenza A occurred in 18 of 167 ( 10.8 % ) children in the vitamin D(3 ) group compared with 31 of 167 
    Output:
    
agent
The evidence shows that vitamin D supplementation provides some benefit in fracture prevention ( likely ∼10–15 % relative reduction ) , particularly at a dose ≥800 IU and with calcium ; a likely benefit in the rate of falls , though it is less clear whether the number of fallers changes ; and a possible small ( ∼5 % ) relative reduction in mortality .
Evidence does not support the use of vitamin D supplementation for the prevention of cancer , respiratory infections or rheumatoid arthritis .
Similarly , evidence does not support vitamin D supplementation for the treatment of multiple sclerosis and rheumatoid arthritis or for improving depression/mental well-being .
Regular testing of 25-hydroxyvitamin D is generally not required , and mega-doses ( ≥300,000 IU ) appear to increase harms .
***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 For adults , vitamin D intake of 100 mcg ( 4000 IU)/day is physiologic and safe . The adequate intake ( AI ) for older adults is 15 mcg ( 600 IU)/day , but there has been no report focusing on use of this dose . Methods We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded , r and omized trial . In Study 1 , 64 out patients ( recruited if summer 2001 25(OH)D < 61 nmol/L ) were given 15 or 100 mcg/day vitamin D in December 2001 . Biochemical responses were followed at subsequent visits that were part of clinical care ; 37 patients completed a wellbeing question naire in December 2001 and February 2002 . Subjects for Study 2 were recruited if their 25(OH)D was < 51 nmol/L in summer 2001 . 66 out patients were given vitamin D ;  51 completed a wellbeing question naire in both December 2002 and February 2003 . Results In Study 1 , basal summer 25-hydroxyvitamin D [ 25(OH)D ] averaged 48 ± 9 ( SD ) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 ± 30 nmol/L for the 15 mcg/day group , and 112 ± 41 nmol/L for the 100 mcg/day group . Both doses lowered plasma parathyroid hormone with no effect on plasma calcium . Between December and February , wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group ( 1-tail Mann-Whitney p = 0.036 ) . In Study 2 , 25(OH)D averaged 39 ± 9 nmol/L , and winter wellbeing scores improved with both doses of vitamin D ( two-tail p < 0.001 ) . Conclusion The highest AI for vitamin D  brought summertime 25(OH)D to > 40 nmol/L , lowered PTH , and its use was associated with improved wellbeing . The 100 mcg/day dose produced greater responses . Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients , we can not rule out a placebo wellbeing response , particularly for those on the lower dose . This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin Background Controversies are common in medicine . Some arise when the conclusions of research publications directly contradict each other , creating uncertainty for frontline clinicians . Discussion In this paper , we review how research ers can look at very similar data yet have completely different conclusions based purely on an over-reliance of statistical significance and an unclear underst and ing of confidence intervals . The dogmatic adherence to statistical significant thresholds can lead authors to write dichotomized absolute conclusions while ignoring the broader interpretations of very consistent findings . We describe three examples of controversy around the potential benefit of a medication , a comparison between new medications , and a medication with a potential harm . The examples include the highest levels of evidence , both meta-analyses and r and omized controlled trials . We will show how in each case the confidence intervals and point estimates were very similar . The only identifiable differences to account for the contrasting conclusions arise from the serendipitous finding of confidence intervals that either marginally cross or just fail to cross the line of statistical significance . Summary These opposing conclusions are false disagreements that create unnecessary clinical uncertainty . We provide helpful recommendations in approaching conflicting conclusions when they are associated with remarkably similar results OBJECTIVE To compare the effects of dydrogesterone and calcium plus vitamin D in women with severe premenstrual syndrome ( PMS ) . METHOD In this r and omized , double-blind , placebo-controlled study , 180 Shiraz University students with PMS used question naires daily to rate their symptoms for 2 menstrual cycles . Then , the students were r and omly assigned to take a tablet containing either 5 mg of dydrogesterone , 500 mg of calcium plus 200 mg of vitamin D , or a placebo twice daily from the 15th to the 24th day of the cycle for 2 more cycles , and to use the same question naires during the intervention cycles . The collected data were then analyzed by repeated-measurement design and multilevel modeling tests . RESULT Treatment with dydrogesterone or calcium plus vitamin D  decreased symptom severity in a similar way ( by 4.64 % and 4.20 % , respectively ) and placebo was associated with a 3.42 % decrease . CONCLUSION Treatment with dydrogesterone or calcium plus vitamin D had a similar effect on symptom severity in women with PMS OBJECTIVE : Observational studies suggest that serum levels of 25-hydroxyvitamin D ( 25[OH]D ) are inversely associated with acute respiratory infections ( ARIs ) . We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs . METHODS : By using cluster r and omization , classrooms of 744 Mongolian schoolchildren were r and omly assigned to different treatments in winter ( January – March ) . This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk ( control ; n = 104 ) or milk fortified with 300 IU of vitamin D3 ( n = 143 ) . This comparison was double-blinded . The primary outcome was the number of parent-reported ARIs over the past 3 months . RESULTS : At baseline , the median serum 25(OH)D level was 7 ng/mL ( interquartile range : 5–10 ng/mL ) . At the end of the trial , follow-up was 99 % ( n = 244 ) , and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different ( 7 vs 19 ng/mL ; P < .001 ) . Compared with controls , children receiving vitamin D reported significantly fewer ARIs during the study period ( mean : 0.80 vs 0.45 ; P = .047 ) , with a rate ratio of 0.52 ( 95 % confidence interval : 0.31–0.89 ) . Adjusting for age , gender , and history of wheezing , vitamin D continued to halve the risk of ARI ( rate ratio : 0.50 [ 95 % confidence interval : 0.28–0.88 ] ) . Similar results were found among children either below or above the median 25(OH)D level at baseline ( rate ratio : 0.41 vs 0.57 ; Pinteraction = .27 ) . CONCLUSIONS : Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency OBJECTIVES To determine the prevalence of vitamin D deficiency in older people in residential care and the influence that the level of vitamin D may have on their incidence of falls . DESIGN Prospect i ve cohort . SETTING Residential care facilities for older people in several states of Australia . PARTICIPANTS Six hundred sixty-seven women in low-level care and 952 women in high-level care , mean age 83.7 years . MEASUREMENTS  Serum 25-hydroxyvitamin D ( 25D ) levels and recognized risk factors for falls including current medication use , a history of previous fractures , weight , tibial length ( as a surrogate for height ) , cognitive function , walking ability , and frequency of going outdoors were determined . The women in low-level care and high-level care were followed for an average of 145 and 168 days , respectively . Falls were recorded prospect ively in diaries completed monthly by residential care staff . RESULTS  Vitamin D deficiency ( defined as a serum 25D level below 25 nmol/L ) was present in 144 ( 22 % ) women in low-level care and 428 ( 45 % ) in high-level care . After excluding 358 bed-bound residents and adjusting for weight , cognitive status , psychotropic drug use , previous Colles fracture , and the presence of w and ering behavior , log serum 25D level remained independently associated with time to first fall . The adjusted hazards ratio was 0.74 ( 95 % confidence interval=0.59 - 0.94 ; P=.01 ) , implying a 20 % reduction in the risk of falling with a doubling of the vitamin D level . CONCLUSION Vitamin D deficiency is common in residential care in Australia . A low level of serum vitamin D is an independent predictor of incident falls BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk  of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P < 0.03 ) . With the use of logistic regression , the unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P < 0.005 ) but did not change significantly for the Ca-only group . In multiple logistic regression models , both treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces  all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170 BACKGROUND Epidemiological evidence supports a relationship between vitamin D and mental well-being , although evidence from large-scale placebo-controlled intervention trials is lacking . AIMS To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women ; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms ; and if there is an association between serum 25-hydroxyvitamin D levels and mental health . METHOD A double-blind , r and omised , placebo-controlled trial of women aged 70 or older ( the Vital D Study : IS RCT N83409867 and ACTR12605000658617 ) . Participants were r and omly assigned to receive 500 000 IU vitamin D(3 ) ( cholecalciferol ) orally or placebo every autumn/winter for 3 - 5 consecutive years . The tools utilised at various time points were the General Health Question naire , the 12-item Short Form Health Survey , the Patient Global Impression-Improvement scale and the WHO Well-Being Index . Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants . RESULTS In this non- clinical population , no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health . Serum 25-hydroxyvitamin D levels in the vitamin D group were 41 % higher than the placebo group 12 months following their annual dose . Despite this difference , scores from the question naires did not differ . Furthermore , there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups . CONCLUSIONS The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3 ) is a practical intervention to prevent depressive symptoms in older community-dwelling women BACKGROUND To our knowledge , no rigorously design ed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza . OBJECTIVE We investigated the effect of vitamin D supplements on the incidence of  seasonal influenza A in schoolchildren . DESIGN From December 2008 through March 2009 , we conducted a r and omized , double-blind , placebo-controlled trial comparing vitamin D(3 ) supplements ( 1200 IU/d ) with placebo  in schoolchildren . The primary outcome was the incidence of influenza A , diagnosed with influenza antigen testing with a nasopharyngeal swab specimen . RESULTS Influenza A occurred in 18 of 167 ( 10.8 % ) children in the vitamin D(3 ) group compared with 31 of 167 
    Output:
    