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 Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P < 0.001 ) . The median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels < 10 ng/mL ) at baseline showed a significant reduction in exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM ) Background Recently , serum 25-hydroxyvitamin D ( 25OHD ) levels were shown to be associated with the survival of patients with colorectal cancer . However , 25OHD levels were measured a median of 6 years before diagnosis or were predicted levels . In this study , we directly measured serum 25OHD levels at surgery and examined the association with survival among patients with colorectal cancer . Methods We started a prospect i ve cohort study to find prognostic factors in patients with colorectal cancer from 2003 to 2008 and stored serum sample s and clinical data . As part of a post-hoc analysis ,  serum 25OHD levels  were measured by radioimmunoassay . Association between overall survival and serum 25OHD levels were computed using the Cox proportional hazard model adjusted for month of serum sampling as well as age at diagnosis , gender , cancer stage , residual tumor after surgery , time period of surgery , location of tumor , adjuvant chemotherapy and number of lymph nodes with metastasis at surgery . Unadjusted and adjusted hazard ratios ( HR ) and 95 % confidence intervals ( 95 % CI ) were determined . Results Serum 25OHD levels were measured in 257 patients . Only 3 % had sufficient levels ( 30 ng/ml and greater ) . Based on month of blood sampling , an annual oscillation of 25OHD levels was seen , with levels being lower in spring and higher in late summer . Higher 25OHD levels were associated with better overall survival under multi-variate analysis ( HR , 0.91 : 95 % CI , 0.84 to 0.99 , P = 0.027 ) . Conclusions These results suggest that higher 25OHD levels at surgery may be associated with a better survival rate of patients with colorectal cancer An unexplained loss of muscle strength occurs with aging . Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [ 1,25-(OH2)D3 ] to persons with low serum concentrations can improve strength . To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [ 1,25-(OH2)D3 ] , we conducted a r and omized , controlled , double blinded trial in 98 men and women volunteers over 69 yr old . Treatment consisted of 0.25 micrograms 1,25-(OH)2D3 , orally , twice per day or identical placebo for 6 months .  Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer . There was no difference between the two groups at 1 week , 1 month , or 6 months of treatment in any of the measures of muscle strength . We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons . Further research is needed to determine the etiology of the decline in muscle strength associated with aging Background —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels < 50 nmol/L ( 20 ng/mL ) received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P<0.001 ) and maintained this increase at 20 weeks . The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896 Introduction Vitamin D has been postulated to be involved in cancer prognosis . Thus far , only two studies reported on its association with recurrence and survival after breast cancer diagnosis yielding inconsistent results . Therefore , the aim of our study was to assess the effect of post-diagnostic serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations on overall survival and distant disease-free survival . Methods We conducted a prospect i ve cohort study in Germany including 1,295 incident postmenopausal breast cancer patients aged 50 - 74 years . Patients were diagnosed between 2002 and 2005 and median follow-up was 5.8 years . Cox proportional hazards models were stratified by age at diagnosis and season of blood collection and adjusted for other prognostic factors . Fractional polynomials were used to assess the true dose-response relation for 25(OH)D. Results Lower concentrations of 25(OH)D were linearly associated with higher risk of death ( hazard ratio ( HR ) = 1.08 per 10 nmol/L decrement ; 95 % confidence interval ( CI ) , 1.00 to 1.17 ) and significantly higher risk of distant recurrence ( HR = 1.14 per 10 nmol/L decrement ; 95%CI , 1.05 to 1.24 ) . Compared with the highest tertile ( ≥ 55 nmol/L ) , patients within the lowest tertile ( < 35 nmol/L ) of 25(OH)D had a HR for overall survival of 1.55 ( 95%CI , 1.00 to 2.39 ) and a HR for distant disease-free survival of 2.09 ( 95%CI , 1.29 to 3.41 ) . In addition , the association with overall survival was found to be statistically significant only for 25(OH)D levels of blood sample s collected before start of chemotherapy but not for those of sample s taken after start of chemotherapy ( P for interaction = 0.06 ) . Conclusions In conclusion , lower serum 25(OH)D concentrations may be associated with poorer overall survival and distant disease-free survival in postmenopausal breast cancer patients BACKGROUND There is a paucity of research evaluating the relation between  vitamin D  and recurrence of breast cancer after treatment . OBJECTIVE This study was design ed to evaluate the associations between circulating concentrations of  25-hydroxyvitamin D [ 25(OH)D ]  and dietary , supplemental , and total intake of vitamin D  and recurrent or new breast cancer events within the Women 's Healthy Eating and Living ( WHEL ) Study . DESIGN A prospect i ve cohort study design ( n = 3085 ) was used to evaluate the relation between dietary , supplemental , and total vitamin D intake and recurrent breast cancer , and a nested case-control study with 512 matched pairs was used for analysis of the association between 25(OH)D and breast cancer recurrence . RESULTS No relation between 25(OH)D and breast cancer recurrence was observed . Compared with women with serum concentrations of 25(OH)D ≥ 30 ng/mL , adjusted odds ratios ( 95 % CI ) for breast cancer recurrence were 1.14 ( 0.57 , 2.31 ) for those with concentrations < 10 ng/mL , 1.00 ( 0.68 - 1.48 ) for concentrations ≥ 10 and < 20 ng/mL , and 1.05 ( 0.76 , 1.47 ) for concentrations ≥ 20 and < 30 ng/mL. No significant associations were observed when analyses were stratified by pre- and postmenopausal status or for local , regional , or distant recurrence or death . Vitamin D intake was not related to breast cancer recurrence overall , although for premenopausal women there was a significant inverse association between dietary vitamin D intake and recurrence ( P for trend = 0.02 ) . CONCLUSION These results do not provide support for a relation between concentrations of 25(OH)D after treatment and the recurrence of breast cancer . This trial is registered at clinical trials.gov for the WHEL Study as NCT00003787 PURPOSE To compare the safety and activity of DN-101 , a new high-dose oral formulation of calcitriol design ed for cancer therapy , and docetaxel with placebo and docetaxel . PATIENTS AND METHODS Patients with progressive metastatic and rogen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 microg DN-101 or placebo taken orally 1 day before docetaxel . The primary end point was prostate-specific antigen ( PSA ) response within 6 months of enrollment , defined as a 50 % reduction confirmed at least 4 weeks later . RESULTS Two hundred fifty patients were r and omly assigned . Baseline characteristics were similar in both arms . Within 6 months , PSA responses were seen in 58 % in DN-101 patients and 49 % in placebo patients ( P = .16 ) . Overall , PSA response rates were 63 % ( DN-101 ) and 52 % ( placebo ) , P = .07 . Patients in the DN-101 group had a hazard ratio for death of 0.67 ( P = .04 ) in a multivariate analysis that included baseline hemoglobin and performance status . Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio , compared with 16.4 months for placebo . Grade 3/4 adverse events occurred in 58 % of DN-101 patients and in 70 % of placebo-treated patients ( P = .07 ) . Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia ( 10 % v 8 % ) , fatigue ( 8 % v 16 
    Output:
    
agent
Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements .
The effects observed for vitamin D3 supplementation remained unchanged when grouped by various characteristics .
However , for vitamin D2 supplementation , increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods .
Conclusions Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease , cancer , and other causes .
***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 Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P < 0.001 ) . The median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels < 10 ng/mL ) at baseline showed a significant reduction in exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM ) Background Recently , serum 25-hydroxyvitamin D ( 25OHD ) levels were shown to be associated with the survival of patients with colorectal cancer . However , 25OHD levels were measured a median of 6 years before diagnosis or were predicted levels . In this study , we directly measured serum 25OHD levels at surgery and examined the association with survival among patients with colorectal cancer . Methods We started a prospect i ve cohort study to find prognostic factors in patients with colorectal cancer from 2003 to 2008 and stored serum sample s and clinical data . As part of a post-hoc analysis ,  serum 25OHD levels  were measured by radioimmunoassay . Association between overall survival and serum 25OHD levels were computed using the Cox proportional hazard model adjusted for month of serum sampling as well as age at diagnosis , gender , cancer stage , residual tumor after surgery , time period of surgery , location of tumor , adjuvant chemotherapy and number of lymph nodes with metastasis at surgery . Unadjusted and adjusted hazard ratios ( HR ) and 95 % confidence intervals ( 95 % CI ) were determined . Results Serum 25OHD levels were measured in 257 patients . Only 3 % had sufficient levels ( 30 ng/ml and greater ) . Based on month of blood sampling , an annual oscillation of 25OHD levels was seen , with levels being lower in spring and higher in late summer . Higher 25OHD levels were associated with better overall survival under multi-variate analysis ( HR , 0.91 : 95 % CI , 0.84 to 0.99 , P = 0.027 ) . Conclusions These results suggest that higher 25OHD levels at surgery may be associated with a better survival rate of patients with colorectal cancer An unexplained loss of muscle strength occurs with aging . Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [ 1,25-(OH2)D3 ] to persons with low serum concentrations can improve strength . To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [ 1,25-(OH2)D3 ] , we conducted a r and omized , controlled , double blinded trial in 98 men and women volunteers over 69 yr old . Treatment consisted of 0.25 micrograms 1,25-(OH)2D3 , orally , twice per day or identical placebo for 6 months .  Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer . There was no difference between the two groups at 1 week , 1 month , or 6 months of treatment in any of the measures of muscle strength . We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons . Further research is needed to determine the etiology of the decline in muscle strength associated with aging Background —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels < 50 nmol/L ( 20 ng/mL ) received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P<0.001 ) and maintained this increase at 20 weeks . The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896 Introduction Vitamin D has been postulated to be involved in cancer prognosis . Thus far , only two studies reported on its association with recurrence and survival after breast cancer diagnosis yielding inconsistent results . Therefore , the aim of our study was to assess the effect of post-diagnostic serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations on overall survival and distant disease-free survival . Methods We conducted a prospect i ve cohort study in Germany including 1,295 incident postmenopausal breast cancer patients aged 50 - 74 years . Patients were diagnosed between 2002 and 2005 and median follow-up was 5.8 years . Cox proportional hazards models were stratified by age at diagnosis and season of blood collection and adjusted for other prognostic factors . Fractional polynomials were used to assess the true dose-response relation for 25(OH)D. Results Lower concentrations of 25(OH)D were linearly associated with higher risk of death ( hazard ratio ( HR ) = 1.08 per 10 nmol/L decrement ; 95 % confidence interval ( CI ) , 1.00 to 1.17 ) and significantly higher risk of distant recurrence ( HR = 1.14 per 10 nmol/L decrement ; 95%CI , 1.05 to 1.24 ) . Compared with the highest tertile ( ≥ 55 nmol/L ) , patients within the lowest tertile ( < 35 nmol/L ) of 25(OH)D had a HR for overall survival of 1.55 ( 95%CI , 1.00 to 2.39 ) and a HR for distant disease-free survival of 2.09 ( 95%CI , 1.29 to 3.41 ) . In addition , the association with overall survival was found to be statistically significant only for 25(OH)D levels of blood sample s collected before start of chemotherapy but not for those of sample s taken after start of chemotherapy ( P for interaction = 0.06 ) . Conclusions In conclusion , lower serum 25(OH)D concentrations may be associated with poorer overall survival and distant disease-free survival in postmenopausal breast cancer patients BACKGROUND There is a paucity of research evaluating the relation between  vitamin D  and recurrence of breast cancer after treatment . OBJECTIVE This study was design ed to evaluate the associations between circulating concentrations of  25-hydroxyvitamin D [ 25(OH)D ]  and dietary , supplemental , and total intake of vitamin D  and recurrent or new breast cancer events within the Women 's Healthy Eating and Living ( WHEL ) Study . DESIGN A prospect i ve cohort study design ( n = 3085 ) was used to evaluate the relation between dietary , supplemental , and total vitamin D intake and recurrent breast cancer , and a nested case-control study with 512 matched pairs was used for analysis of the association between 25(OH)D and breast cancer recurrence . RESULTS No relation between 25(OH)D and breast cancer recurrence was observed . Compared with women with serum concentrations of 25(OH)D ≥ 30 ng/mL , adjusted odds ratios ( 95 % CI ) for breast cancer recurrence were 1.14 ( 0.57 , 2.31 ) for those with concentrations < 10 ng/mL , 1.00 ( 0.68 - 1.48 ) for concentrations ≥ 10 and < 20 ng/mL , and 1.05 ( 0.76 , 1.47 ) for concentrations ≥ 20 and < 30 ng/mL. No significant associations were observed when analyses were stratified by pre- and postmenopausal status or for local , regional , or distant recurrence or death . Vitamin D intake was not related to breast cancer recurrence overall , although for premenopausal women there was a significant inverse association between dietary vitamin D intake and recurrence ( P for trend = 0.02 ) . CONCLUSION These results do not provide support for a relation between concentrations of 25(OH)D after treatment and the recurrence of breast cancer . This trial is registered at clinical trials.gov for the WHEL Study as NCT00003787 PURPOSE To compare the safety and activity of DN-101 , a new high-dose oral formulation of calcitriol design ed for cancer therapy , and docetaxel with placebo and docetaxel . PATIENTS AND METHODS Patients with progressive metastatic and rogen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 microg DN-101 or placebo taken orally 1 day before docetaxel . The primary end point was prostate-specific antigen ( PSA ) response within 6 months of enrollment , defined as a 50 % reduction confirmed at least 4 weeks later . RESULTS Two hundred fifty patients were r and omly assigned . Baseline characteristics were similar in both arms . Within 6 months , PSA responses were seen in 58 % in DN-101 patients and 49 % in placebo patients ( P = .16 ) . Overall , PSA response rates were 63 % ( DN-101 ) and 52 % ( placebo ) , P = .07 . Patients in the DN-101 group had a hazard ratio for death of 0.67 ( P = .04 ) in a multivariate analysis that included baseline hemoglobin and performance status . Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio , compared with 16.4 months for placebo . Grade 3/4 adverse events occurred in 58 % of DN-101 patients and in 70 % of placebo-treated patients ( P = .07 ) . Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia ( 10 % v 8 % ) , fatigue ( 8 % v 16 
    Output:
    