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 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 SETTING Vitamin D deficiency is associated with susceptibility to active tuberculosis ( TB ) in many setting s. In vitro studies and studies on human volunteers showed that two of the first-line anti-tuberculosis drugs , isoniazid and rifampicin , reduce 25-hydroxy vitamin D ( 25[OH]D ) concentrations . OBJECTIVE To study changes in vitamin D status during treatment of Tanzanian hospitalised patients with pulmonary TB ( PTB ) . DESIGN We compared serum 25[OH]D concentrations in 81 Tanzanian PTB patients before and after 2 months of treatment . RESULTS Median serum 25[OH]D concentrations increased from 91 nmol/l at baseline to 101 nmol/l after 2 months of TB treatment ( median increase 6.0 nmol/l , IQR -0.7 - 25.0 , P = 0.001 ) . Median serum parathyroid hormone concentrations increased from 1.6 to 2.0 pmol/l ( median increase 0.46 , IQR -0.2 - 1.1 , P < 0.001 ) . CONCLUSION 25[OH]D serum concentrations increased during the first 2 months of TB treatment in 81 PTB patients in northern Tanzania . Improved dietary intake and increased sunlight exposure may have contributed to the increased 25[OH]D concentrations OBJECTIVE To investigate the clinical features , molecular phenotypes and clinical prognosis of breast cancer patients with type-2 diabetes mellitus , thereby providing a basis for individualized therapy of breast cancer . METHODS 105 breast cancer patients with type-2 diabetes mellitus ( DM ) presenting from January 2005 to December 2010 were enrolled in this study . 200 breast cancer non-diabetic patients in the same period were r and omly selected as the control group . The clinical data of DM group and control group were retrospectively analyzed . The SPSS12.0 software was used for statistics and survival analysis . RESULTS The mean age of the patients in DM group were of 57.2∓11.8 years , which was older compared with the control group . The percentage of postmenopausal patients was 71.4 % and the ratio of grade II+III was 98.8 % , which was higher than the control group . The  neoadjuvant chemotherapy response rate of DM group was 67.5 % , which was lower than control group . The patients in DM group had later clinical stage and more lymph metastasis . The proportion of advanced breast cancer was 68.57 % and the ratio of lymph node metastasis was 66.01 % . All the difference was significant ( P<0.05 ) . But there was no significant difference in tumor size and molecular phenotype between the diabetic group with breast cancer and the control group . Disease-free survival and overall survival rates of DM group were 80.2 % and 84.2 % , which were worse than those in the control group . All the differences were significant ( P<0.05 ) . After excluding the patients with other causes of death , results of overall survival still showed worse in DM group , but the difference was not statistically significant ( P>0.05 ) . Serum insulin at fasting and two hours postpr and ial were higher than normal value in DM group , but serum insulin levels in the control group changed in the normal range . CONCLUSION There were older patients , higher proportion of high pathological grade , more lymph node metastasis , later clinical stages in the diabetic group with breast cancer . Breast cancer patients with type-2 diabetes mellitus were at risk of a poor prognosis . Hyperinsulinemia may be the real cause of poor prognosis in breast cancer patients with type-2 diabetes BACKGROUND Vitamin D has potent anticancer properties , especially against digestive-system cancers . Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure . Here , we considered multiple determinants of vitamin D exposure ( dietary and supplementary vitamin D , skin pigmentation , adiposity , geographic residence , and leisure-time physical activity-to estimate sunlight exposure ) in relation to cancer risk in the Health Professionals Follow-Up Study . METHODS Among 1095 men of this cohort , we quantified the relation of these six determinants to plasma  25-hydroxy-vitamin D [ 25(OH)D ] level by use of a multiple linear regression model . We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics . We then prospect ively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models . RESULTS From 1986 through January 31 , 2000 , we documented 4286 incident cancers ( excluding organ-confined prostate cancer and nonmelanoma skin cancer ) and 2025 deaths from cancer . From multivariable models , an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17 % reduction in total cancer incidence ( multivariable relative risk [ RR ] = 0.83 , 95 % confidence interval [ CI ] = 0.74 to 0.92 ) , a 29 % reduction in total cancer mortality ( RR = 0.71 , 95 % CI = 0.60 to 0.83 ) , and a 45 % reduction in digestive-system cancer mortality ( RR = 0.55 , 95 % CI = 0.41 to 0.74 ) . The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile ; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality . Results were similar when we controlled further for body mass index or physical activity level . CONCLUSIONS Low levels of vitamin D may be associated with increased cancer incidence and mortality in men , particularly for digestive-system cancers . The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases . The authors aim ed to investigate whether serum 25-hydroxyvitamin D ( 25(OH)D ) level predicts mortality from cardiovascular disease ( CVD ) . The study was based on the Mini-Finl and Health Survey and included 6,219 men and women aged > or = 30 years who were free from CVD at baseline ( 1978 - 1980 ) . During follow-up through 2006 , 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified . Levels of 25(OH)D were determined from serum collected at baseline .  Cox 's proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death . After adjustment for potential confounders , the hazard ratio for total CVD death was 0.76 ( 95 % confidence interval ( 95 % CI ) : 0.60 , 0.95 ) for the highest quintile of 25(OH)D level versus the lowest . The association was evident for cerebrovascular death ( hazard ratio = 0.48 , 95 % CI : 0.31 , 0.75 ) but not coronary death ( hazard ratio = 0.91 , 95 % CI : 0.70 , 1.18 ) . A low vitamin D level may be associated with higher risk of a fatal CVD event , particularly cerebrovascular death . These findings need to be replicated in other population s. To demonstrate a causal link between vitamin D and CVD , r and omized controlled trials are required CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and  C-reactive protein ( CRP ) are associated with development of  type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P<.001 ) and CRP ( P<.001 ) were significantly higher among cases than among controls . The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis In spite of the controversy over the role of r and omized clinical trials  in medical research , the rationale underlying such trials remains persuasive as compared to recent suggestions for alternative non-r and omized studies such as those relying on the use of historical controls and adjustment technics . Others have suggested that recent statistical innovations for improving clinical trials , including adaptive allocation of treatment to patients and sequential stopping procedures , are underutilized . These innovations , though theoretically interesting , are not easily adapted to large-scale , complex medical trials in which there may be multiple end points and delayed response times . Ethical considerations suggest that r and omized trials are more suitable than uncontrolled experimentation in protecting the interests of patients . R and omized clinical trials remain the most reliable method for evaluating the efficacy of therapies BACKGROUND Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials . However , r and omized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking . METHODS We conducted a r and omized , double-blind , placebo- 
    Output:
    
agent
The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health .
Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D , which would explain why low vitamin D status is reported in a wide range of disorders .
In elderly people , restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival
***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 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 SETTING Vitamin D deficiency is associated with susceptibility to active tuberculosis ( TB ) in many setting s. In vitro studies and studies on human volunteers showed that two of the first-line anti-tuberculosis drugs , isoniazid and rifampicin , reduce 25-hydroxy vitamin D ( 25[OH]D ) concentrations . OBJECTIVE To study changes in vitamin D status during treatment of Tanzanian hospitalised patients with pulmonary TB ( PTB ) . DESIGN We compared serum 25[OH]D concentrations in 81 Tanzanian PTB patients before and after 2 months of treatment . RESULTS Median serum 25[OH]D concentrations increased from 91 nmol/l at baseline to 101 nmol/l after 2 months of TB treatment ( median increase 6.0 nmol/l , IQR -0.7 - 25.0 , P = 0.001 ) . Median serum parathyroid hormone concentrations increased from 1.6 to 2.0 pmol/l ( median increase 0.46 , IQR -0.2 - 1.1 , P < 0.001 ) . CONCLUSION 25[OH]D serum concentrations increased during the first 2 months of TB treatment in 81 PTB patients in northern Tanzania . Improved dietary intake and increased sunlight exposure may have contributed to the increased 25[OH]D concentrations OBJECTIVE To investigate the clinical features , molecular phenotypes and clinical prognosis of breast cancer patients with type-2 diabetes mellitus , thereby providing a basis for individualized therapy of breast cancer . METHODS 105 breast cancer patients with type-2 diabetes mellitus ( DM ) presenting from January 2005 to December 2010 were enrolled in this study . 200 breast cancer non-diabetic patients in the same period were r and omly selected as the control group . The clinical data of DM group and control group were retrospectively analyzed . The SPSS12.0 software was used for statistics and survival analysis . RESULTS The mean age of the patients in DM group were of 57.2∓11.8 years , which was older compared with the control group . The percentage of postmenopausal patients was 71.4 % and the ratio of grade II+III was 98.8 % , which was higher than the control group . The  neoadjuvant chemotherapy response rate of DM group was 67.5 % , which was lower than control group . The patients in DM group had later clinical stage and more lymph metastasis . The proportion of advanced breast cancer was 68.57 % and the ratio of lymph node metastasis was 66.01 % . All the difference was significant ( P<0.05 ) . But there was no significant difference in tumor size and molecular phenotype between the diabetic group with breast cancer and the control group . Disease-free survival and overall survival rates of DM group were 80.2 % and 84.2 % , which were worse than those in the control group . All the differences were significant ( P<0.05 ) . After excluding the patients with other causes of death , results of overall survival still showed worse in DM group , but the difference was not statistically significant ( P>0.05 ) . Serum insulin at fasting and two hours postpr and ial were higher than normal value in DM group , but serum insulin levels in the control group changed in the normal range . CONCLUSION There were older patients , higher proportion of high pathological grade , more lymph node metastasis , later clinical stages in the diabetic group with breast cancer . Breast cancer patients with type-2 diabetes mellitus were at risk of a poor prognosis . Hyperinsulinemia may be the real cause of poor prognosis in breast cancer patients with type-2 diabetes BACKGROUND Vitamin D has potent anticancer properties , especially against digestive-system cancers . Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure . Here , we considered multiple determinants of vitamin D exposure ( dietary and supplementary vitamin D , skin pigmentation , adiposity , geographic residence , and leisure-time physical activity-to estimate sunlight exposure ) in relation to cancer risk in the Health Professionals Follow-Up Study . METHODS Among 1095 men of this cohort , we quantified the relation of these six determinants to plasma  25-hydroxy-vitamin D [ 25(OH)D ] level by use of a multiple linear regression model . We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics . We then prospect ively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models . RESULTS From 1986 through January 31 , 2000 , we documented 4286 incident cancers ( excluding organ-confined prostate cancer and nonmelanoma skin cancer ) and 2025 deaths from cancer . From multivariable models , an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17 % reduction in total cancer incidence ( multivariable relative risk [ RR ] = 0.83 , 95 % confidence interval [ CI ] = 0.74 to 0.92 ) , a 29 % reduction in total cancer mortality ( RR = 0.71 , 95 % CI = 0.60 to 0.83 ) , and a 45 % reduction in digestive-system cancer mortality ( RR = 0.55 , 95 % CI = 0.41 to 0.74 ) . The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile ; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality . Results were similar when we controlled further for body mass index or physical activity level . CONCLUSIONS Low levels of vitamin D may be associated with increased cancer incidence and mortality in men , particularly for digestive-system cancers . The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases . The authors aim ed to investigate whether serum 25-hydroxyvitamin D ( 25(OH)D ) level predicts mortality from cardiovascular disease ( CVD ) . The study was based on the Mini-Finl and Health Survey and included 6,219 men and women aged > or = 30 years who were free from CVD at baseline ( 1978 - 1980 ) . During follow-up through 2006 , 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified . Levels of 25(OH)D were determined from serum collected at baseline .  Cox 's proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death . After adjustment for potential confounders , the hazard ratio for total CVD death was 0.76 ( 95 % confidence interval ( 95 % CI ) : 0.60 , 0.95 ) for the highest quintile of 25(OH)D level versus the lowest . The association was evident for cerebrovascular death ( hazard ratio = 0.48 , 95 % CI : 0.31 , 0.75 ) but not coronary death ( hazard ratio = 0.91 , 95 % CI : 0.70 , 1.18 ) . A low vitamin D level may be associated with higher risk of a fatal CVD event , particularly cerebrovascular death . These findings need to be replicated in other population s. To demonstrate a causal link between vitamin D and CVD , r and omized controlled trials are required CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and  C-reactive protein ( CRP ) are associated with development of  type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P<.001 ) and CRP ( P<.001 ) were significantly higher among cases than among controls . The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis In spite of the controversy over the role of r and omized clinical trials  in medical research , the rationale underlying such trials remains persuasive as compared to recent suggestions for alternative non-r and omized studies such as those relying on the use of historical controls and adjustment technics . Others have suggested that recent statistical innovations for improving clinical trials , including adaptive allocation of treatment to patients and sequential stopping procedures , are underutilized . These innovations , though theoretically interesting , are not easily adapted to large-scale , complex medical trials in which there may be multiple end points and delayed response times . Ethical considerations suggest that r and omized trials are more suitable than uncontrolled experimentation in protecting the interests of patients . R and omized clinical trials remain the most reliable method for evaluating the efficacy of therapies BACKGROUND Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials . However , r and omized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking . METHODS We conducted a r and omized , double-blind , placebo- 
    Output:
    