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 A st and ard phenotype of frailty was associated with an increased risk of adverse outcomes including mortality in a recent study of older adults . However , the predictive validity of this phenotype for fracture outcomes and across risk subgroups is uncertain . METHODS To determine whether a st and ard frailty phenotype was independently associated with risk of adverse health outcomes in older women and to evaluate the consistency of associations across risk subgroups defined by age and body mass index ( BMI ) , we ascertained frailty status in a cohort of 6724 women > or=69 years and followed them prospect ively for incident falls , fractures , and mortality . Frailty was defined by the presence of three or more of the following criteria : unintentional weight loss , weakness , self-reported poor energy , slow walking speed , and low physical activity . Incident recurrent falls were defined as at least two falls during the subsequent year . Incident fractures ( confirmed with x-ray reports ) , including hip fractures , and deaths were ascertained during an average of 9 years of follow-up . RESULTS After controlling for multiple confounders such as age , health status , medical conditions , functional status , depressive symptoms , cognitive function , and bone mineral density , frail women were subsequently at increased risk of recurrent falls ( multivariate odds ratio=1.38 , 95 % confidence interval [ CI ] , 1.02 - 1.88 ) , hip fracture ( multivariate hazards ratio [MHR]=1.40 , 95 % CI , 1.03 - 1.90 ) , any nonspine fracture ( MHR=1.25 , 95 % CI , 1.05 - 1.49 ) , and death ( MHR=1.82 , 95 % CI , 1.56 - 2.13 ) . The associations between frailty and these outcomes persisted among women > or=80 years . In addition , associations between frailty and an increased risk of falls , fracture , and mortality were consistently observed across categories of BMI , including BMI > or=30 kg/m2 . CONCLUSION Frailty is an independent predictor of adverse health outcomes in older women , including very elderly women and older obese women Osteoporosis is responsible for about 1.3 million fractures in the United States each year [ 1 ] . Further , recent research has shown that the risk for most types of fracture in elderly women is related to low bone mass ; thus , the public health impact of osteoporosis may , in fact , be much greater [ 2 ] and is projected to increase over the next several decades [ 3 ] . Postmenopausal estrogen replacement is the current recommended therapy for the prevention of osteoporosis [ 4 ] . However , the use of estrogen is not widespread among elderly women [ 5 ] . Clearly , more options for the prevention of osteoporosis and fracture need to be developed and explored . One option is the use of thiazide diuretics . Thiazide diuretics are known to reduce urinary excretion of calcium [ 6 , 7 ] and may also decrease bone resorption [ 6 ] and bone turnover [ 8 ] . The use of thiazide diuretics has been associated with a reduced risk for fracture , with risk ratios ranging from 0.3 to 0.8 [ 9 - 18 ] . For example , in a casecontrol study that excluded patients taking other drugs thought to affect bone mass , Ray and colleagues [ 15 ] found a 50 % reduction in the risk for hip fracture among patients who had used thiazide diuretics  for 6 years . In addition , LaCroix and colleagues [ 16 ] reported a 30 % lower risk for hip fracture in current users compared with nonusers . The Framingham Study also showed a lower risk for hip fracture among users of pure thiazide drugs when compared with those using agents that combined thiazide diuretics with other antihypertensive drugs [ 17 ] . However , all of these studies have been observational , which allows the possibility that users of thiazide diuretics have a lower risk for hip fracture because of other confounding factors . In addition , the more recent data of Heidrich and colleagues [ 19 ] conflict with these results . These investigators found a crude odds ratio for thiazide use and hip fracture of 1.1 , which is not statistically significant . However , when they adjusted for the potentially confounding effects of nursing-home residence ; previous hospitalizations ; history of stroke , alcoholism or organic brain syndrome ; body weight ; leg paralysis ; and use of phenobarbital , corticosteroids , or other diuretics , a significantly increased risk for hip fracture was found among women who reported current use of thiazide diuretics  [ 19 ] . No study has prospect ively evaluated the relation between thiazide diuretics and other types of fracture . The mechanism by which thiazide diuretics might protect against hip fracture is not known . Thiazide diuretics may decrease fracture risk by preserving bone mass [ 10 , 11 , 20 - 23 ] . Cross-sectional studies have shown that users of thiazide diuretics have slightly higher cortical and trabecular bone mass than nonusers . Two r and omized clinical studies of the effect of thiazide diuretics on bone loss had conflicting results [ 24 , 25 ] . If thiazide diuretics reduce the risk for hip fracture by slowing bone loss , then these agents should also protect against other types of fracture that are associated with reduced bone mass [ 2 ] . On the other h and , thiazide diuretics could increase the risk for fractures by increasing the risk for falls [ 26 ] . Thiazide diuretics might do this by causing dizziness or postural hypotension [ 27 ] , although the association of diuretic use with falling is not consistent [ 28 ] . More than 90 % of hip fractures are related to falls [ 29 ] . No previous study has included a comprehensive analysis of the effects of thiazide diuretics on bone mass , the risk for falls , and the risk for all fractures in a single population . In our prospect i ve study of 9704 women who were 65 years or older ( the Study of Osteoporotic Fractures ) , we assessed thiazide diuretic use and bone mass at baseline and conducted follow-up examinations every 4 months for the occurrence of fractures and falls . Methods Study Sample From September 1986 through October 1988 , women who were at least 65 years old were recruited for the Study of Osteoporotic Fractures in four areas of the United States : Portl and , Oregon ; Minneapolis , Minnesota ; Baltimore County , Maryl and ; and the Monongahela Valley region near Pittsburgh , Pennsylvania . Age-eligible women were recruited through several sources : health maintenance organizations ; lists of residents that had been compiled for other epidemiologic studies ; jury- selection lists ; voter- registration lists ; and lists of driver 's license holders [ 30 ] . We excluded black women because of their lower incidence of fractures , women who were unable to walk without the assistance of another person , and women who had bilateral hip replacements . Measurement of Bone Mass Bone mineral content ( g/cm ) and density ( g/cm2 ) were measured using single-photon absorptiometry ( OsteoAnalyzer , Siemens-Osteon , Wahiawa , Hawaii ) . Details of these methods have been reported elsewhere [ 30 ] . We scanned three sites : the distal radius , the proximal radius , and the calcaneus . The distal radius is composed of about 60 % cortical bone and 40 % trabecular bone , the proximal radius is about 99 % cortical bone [ 31 ] , and the calcaneus is about 97 % trabecular bone [ 32 ] . The reproducibility of the bone mass measurements , expressed as coefficients of variation , ranged from 1.3 % to 2.0 % among individuals and from 0.4 % to 1.2 % among scanners [ 30 ] . Diuretic Use Information on diuretic use was obtained at the baseline clinic interview . Participants were asked to bring all current medications to the clinic for verification . In addition , pictures of tablets were presented to participants to assist them in the re collection of previously prescribed diuretics . Diuretics , including combination drugs , were classified as thiazide diuretics according to the American Medical Association drug evaluations [ 33 ] . Separate histories were obtained from participants for use of thiazide and nonthiazide diuretics . Chlorthalidone was classified as a thiazide diuretic because its effects on calcium excretion are similar to those of thiazide diuretics . Analyses in which chlorthalidone was not considered as a thiazide diuretic yielded similar results . Women were asked whether they had ever taken diuretics ; at what age they had started taking diuretics ; whether they were currently using diuretics and , if not , when they had stopped ; whether they took diuretics the entire time or stopped for a few years ; and the name of the medication they were currently using . Duration of diuretic use was calculated as the total number of years that they reported using diuretics . No information was collected on dose at the baseline visit , but dose-related data were recorded at the first annual telephone interview . Information on duration of thiazide diuretic use was missing in 15 women . These women were excluded from all analyses . Other Measurements Reported health status , type of menopause , alcohol consumption , and cigarette smoking were assessed using a question naire that was review ed with the participant by a trained interviewer . Women were considered to have had a surgical menopause if they reported having had a bilateral oophorectomy at the age at which they stopped menstruating . Regarding alcohol consumption , participants were asked how much they had consumed during the past 30 days and how many times they had consumed three or more drinks per day and five or more drinks per day during the past 30 days . The measure of alcohol consumption used in our study was drinks per week , which was adjusted for atypical drinking , particularly heavy drinking over the last 30 days .  Dietary calcium  was assessed by a food frequency question naire and an interview using st and ardized food models to estimate portion sizes [ 34 ] . In our study , total calcium intake included dietary and supplemental calcium . Women were also asked if they had ever taken the following medications : thyroid hormones , medicine for seizures , vitamin D or multivitamins containing vitamin D , TUMS , calcium supplements , antacids , prednisone , cortisone , other steroid pills , birth control pills , estrogen pills , estrogen skin patches , estrogen vaginal cream or suppositories , estrogen injections , and progestins . Information was obtained on current use , duration of use , and specific drug and dosage used for the longest period . Functional status was measured by a respondent 's answers to questions about her ability to perform six instrumental activities of daily living by herself and without using special aids or equipment . These activities were as follows : walking two or three blocks outside on level ground ; climbing up 10 steps without stopping ; walking down 10 steps ; preparing one 's own meals ; doing heavy housework ; and doing one 's own shopping for groceries or clothes . The measure used in these analyses is the total number of activities ( ranging from 0 to 6 ) that a woman reported she was unable to do or had difficulty doing . Additionally , women were asked to rate their health status as very good , good , fair , poor , or very poor . During the clinic examination , body weight was measured ( after removal of shoes and heavy outer clothing ) using a balance beam scale . Height was measured ( after removal of shoes ) using a Harpenden stadiometer ( Holtain , Ltd. , Dyved , United Kingdom ) . Height and weight were used to calculate the body mass index ( kg/m2 ) . Ascertainment of Prevalent Vertebral Deformities The prevalence of vertebral deformities as shown by lateral thoracic and lumbar spine films was obtained on 2992 women ( 31 % of the cohort ) who were between 65 and 70 years old . The methods used to identify vertebral deformities have been described previously [ 35 ] . In summary , six points for each vertebral body , T4 through L4 , were marked with a translucent digitizer . We calculated three heights ( anterior , posterior , and middle ) and three ratios : anterior-to-posterior height ( wedge ) ; mid-to-posterior height ( endplate ) ; and the posterior height of each vertebra to the posterior height of the adjacent vertebrae ( crush ) . We classified a vertebral body Background and Purpose — The association between cerebral white matter lesions ( WMLs ) and the risk of falls in older people is uncertain , with no supporting prospect i ve evidence . We aim ed to determine the risk of incident falls associated with WML volume , and the interactions between WML volume , gait , and other sensorimotor factors leading to falls . Methods — We conducted a prospect i ve , population -based study ( n=294 , mean age 72.3 years , independently mobile ) .  Volumetric MRI , computerized gait measures , and sensorimotor measures of falls risk  were obtained at baseline . Incident falls were recorded prospect ively over a 12-month period . Using regression modeling , we estimated the risk of incident falls associated with baseline WML volume . Results — Increasing baseline WML volume was independently associated with any incident fall ( P=0.01 ) and multiple incident falls ( P=0.02 ) . The risk of incident falls was doubled in people with lesion volumes in the highest quintile of its distribution compared with the lowest ( adjusted relative risk , 2.32 ; 95 % CI , 1.28–4.14 ) . Greater lesion volume was also associated with poorer gait and greater gait variability ( 
    Output:
    
agent
ORs were generally higher for recurrent fallers than for all fallers .
This meta- analysis provides comprehensive evidence -based assessment of risk factors for falls in older people , confirming their multifactorial etiology .
Some nonspecific indicators of high baseline risk were also strong predictors of the risk of falling
***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 A st and ard phenotype of frailty was associated with an increased risk of adverse outcomes including mortality in a recent study of older adults . However , the predictive validity of this phenotype for fracture outcomes and across risk subgroups is uncertain . METHODS To determine whether a st and ard frailty phenotype was independently associated with risk of adverse health outcomes in older women and to evaluate the consistency of associations across risk subgroups defined by age and body mass index ( BMI ) , we ascertained frailty status in a cohort of 6724 women > or=69 years and followed them prospect ively for incident falls , fractures , and mortality . Frailty was defined by the presence of three or more of the following criteria : unintentional weight loss , weakness , self-reported poor energy , slow walking speed , and low physical activity . Incident recurrent falls were defined as at least two falls during the subsequent year . Incident fractures ( confirmed with x-ray reports ) , including hip fractures , and deaths were ascertained during an average of 9 years of follow-up . RESULTS After controlling for multiple confounders such as age , health status , medical conditions , functional status , depressive symptoms , cognitive function , and bone mineral density , frail women were subsequently at increased risk of recurrent falls ( multivariate odds ratio=1.38 , 95 % confidence interval [ CI ] , 1.02 - 1.88 ) , hip fracture ( multivariate hazards ratio [MHR]=1.40 , 95 % CI , 1.03 - 1.90 ) , any nonspine fracture ( MHR=1.25 , 95 % CI , 1.05 - 1.49 ) , and death ( MHR=1.82 , 95 % CI , 1.56 - 2.13 ) . The associations between frailty and these outcomes persisted among women > or=80 years . In addition , associations between frailty and an increased risk of falls , fracture , and mortality were consistently observed across categories of BMI , including BMI > or=30 kg/m2 . CONCLUSION Frailty is an independent predictor of adverse health outcomes in older women , including very elderly women and older obese women Osteoporosis is responsible for about 1.3 million fractures in the United States each year [ 1 ] . Further , recent research has shown that the risk for most types of fracture in elderly women is related to low bone mass ; thus , the public health impact of osteoporosis may , in fact , be much greater [ 2 ] and is projected to increase over the next several decades [ 3 ] . Postmenopausal estrogen replacement is the current recommended therapy for the prevention of osteoporosis [ 4 ] . However , the use of estrogen is not widespread among elderly women [ 5 ] . Clearly , more options for the prevention of osteoporosis and fracture need to be developed and explored . One option is the use of thiazide diuretics . Thiazide diuretics are known to reduce urinary excretion of calcium [ 6 , 7 ] and may also decrease bone resorption [ 6 ] and bone turnover [ 8 ] . The use of thiazide diuretics has been associated with a reduced risk for fracture , with risk ratios ranging from 0.3 to 0.8 [ 9 - 18 ] . For example , in a casecontrol study that excluded patients taking other drugs thought to affect bone mass , Ray and colleagues [ 15 ] found a 50 % reduction in the risk for hip fracture among patients who had used thiazide diuretics  for 6 years . In addition , LaCroix and colleagues [ 16 ] reported a 30 % lower risk for hip fracture in current users compared with nonusers . The Framingham Study also showed a lower risk for hip fracture among users of pure thiazide drugs when compared with those using agents that combined thiazide diuretics with other antihypertensive drugs [ 17 ] . However , all of these studies have been observational , which allows the possibility that users of thiazide diuretics have a lower risk for hip fracture because of other confounding factors . In addition , the more recent data of Heidrich and colleagues [ 19 ] conflict with these results . These investigators found a crude odds ratio for thiazide use and hip fracture of 1.1 , which is not statistically significant . However , when they adjusted for the potentially confounding effects of nursing-home residence ; previous hospitalizations ; history of stroke , alcoholism or organic brain syndrome ; body weight ; leg paralysis ; and use of phenobarbital , corticosteroids , or other diuretics , a significantly increased risk for hip fracture was found among women who reported current use of thiazide diuretics  [ 19 ] . No study has prospect ively evaluated the relation between thiazide diuretics and other types of fracture . The mechanism by which thiazide diuretics might protect against hip fracture is not known . Thiazide diuretics may decrease fracture risk by preserving bone mass [ 10 , 11 , 20 - 23 ] . Cross-sectional studies have shown that users of thiazide diuretics have slightly higher cortical and trabecular bone mass than nonusers . Two r and omized clinical studies of the effect of thiazide diuretics on bone loss had conflicting results [ 24 , 25 ] . If thiazide diuretics reduce the risk for hip fracture by slowing bone loss , then these agents should also protect against other types of fracture that are associated with reduced bone mass [ 2 ] . On the other h and , thiazide diuretics could increase the risk for fractures by increasing the risk for falls [ 26 ] . Thiazide diuretics might do this by causing dizziness or postural hypotension [ 27 ] , although the association of diuretic use with falling is not consistent [ 28 ] . More than 90 % of hip fractures are related to falls [ 29 ] . No previous study has included a comprehensive analysis of the effects of thiazide diuretics on bone mass , the risk for falls , and the risk for all fractures in a single population . In our prospect i ve study of 9704 women who were 65 years or older ( the Study of Osteoporotic Fractures ) , we assessed thiazide diuretic use and bone mass at baseline and conducted follow-up examinations every 4 months for the occurrence of fractures and falls . Methods Study Sample From September 1986 through October 1988 , women who were at least 65 years old were recruited for the Study of Osteoporotic Fractures in four areas of the United States : Portl and , Oregon ; Minneapolis , Minnesota ; Baltimore County , Maryl and ; and the Monongahela Valley region near Pittsburgh , Pennsylvania . Age-eligible women were recruited through several sources : health maintenance organizations ; lists of residents that had been compiled for other epidemiologic studies ; jury- selection lists ; voter- registration lists ; and lists of driver 's license holders [ 30 ] . We excluded black women because of their lower incidence of fractures , women who were unable to walk without the assistance of another person , and women who had bilateral hip replacements . Measurement of Bone Mass Bone mineral content ( g/cm ) and density ( g/cm2 ) were measured using single-photon absorptiometry ( OsteoAnalyzer , Siemens-Osteon , Wahiawa , Hawaii ) . Details of these methods have been reported elsewhere [ 30 ] . We scanned three sites : the distal radius , the proximal radius , and the calcaneus . The distal radius is composed of about 60 % cortical bone and 40 % trabecular bone , the proximal radius is about 99 % cortical bone [ 31 ] , and the calcaneus is about 97 % trabecular bone [ 32 ] . The reproducibility of the bone mass measurements , expressed as coefficients of variation , ranged from 1.3 % to 2.0 % among individuals and from 0.4 % to 1.2 % among scanners [ 30 ] . Diuretic Use Information on diuretic use was obtained at the baseline clinic interview . Participants were asked to bring all current medications to the clinic for verification . In addition , pictures of tablets were presented to participants to assist them in the re collection of previously prescribed diuretics . Diuretics , including combination drugs , were classified as thiazide diuretics according to the American Medical Association drug evaluations [ 33 ] . Separate histories were obtained from participants for use of thiazide and nonthiazide diuretics . Chlorthalidone was classified as a thiazide diuretic because its effects on calcium excretion are similar to those of thiazide diuretics . Analyses in which chlorthalidone was not considered as a thiazide diuretic yielded similar results . Women were asked whether they had ever taken diuretics ; at what age they had started taking diuretics ; whether they were currently using diuretics and , if not , when they had stopped ; whether they took diuretics the entire time or stopped for a few years ; and the name of the medication they were currently using . Duration of diuretic use was calculated as the total number of years that they reported using diuretics . No information was collected on dose at the baseline visit , but dose-related data were recorded at the first annual telephone interview . Information on duration of thiazide diuretic use was missing in 15 women . These women were excluded from all analyses . Other Measurements Reported health status , type of menopause , alcohol consumption , and cigarette smoking were assessed using a question naire that was review ed with the participant by a trained interviewer . Women were considered to have had a surgical menopause if they reported having had a bilateral oophorectomy at the age at which they stopped menstruating . Regarding alcohol consumption , participants were asked how much they had consumed during the past 30 days and how many times they had consumed three or more drinks per day and five or more drinks per day during the past 30 days . The measure of alcohol consumption used in our study was drinks per week , which was adjusted for atypical drinking , particularly heavy drinking over the last 30 days .  Dietary calcium  was assessed by a food frequency question naire and an interview using st and ardized food models to estimate portion sizes [ 34 ] . In our study , total calcium intake included dietary and supplemental calcium . Women were also asked if they had ever taken the following medications : thyroid hormones , medicine for seizures , vitamin D or multivitamins containing vitamin D , TUMS , calcium supplements , antacids , prednisone , cortisone , other steroid pills , birth control pills , estrogen pills , estrogen skin patches , estrogen vaginal cream or suppositories , estrogen injections , and progestins . Information was obtained on current use , duration of use , and specific drug and dosage used for the longest period . Functional status was measured by a respondent 's answers to questions about her ability to perform six instrumental activities of daily living by herself and without using special aids or equipment . These activities were as follows : walking two or three blocks outside on level ground ; climbing up 10 steps without stopping ; walking down 10 steps ; preparing one 's own meals ; doing heavy housework ; and doing one 's own shopping for groceries or clothes . The measure used in these analyses is the total number of activities ( ranging from 0 to 6 ) that a woman reported she was unable to do or had difficulty doing . Additionally , women were asked to rate their health status as very good , good , fair , poor , or very poor . During the clinic examination , body weight was measured ( after removal of shoes and heavy outer clothing ) using a balance beam scale . Height was measured ( after removal of shoes ) using a Harpenden stadiometer ( Holtain , Ltd. , Dyved , United Kingdom ) . Height and weight were used to calculate the body mass index ( kg/m2 ) . Ascertainment of Prevalent Vertebral Deformities The prevalence of vertebral deformities as shown by lateral thoracic and lumbar spine films was obtained on 2992 women ( 31 % of the cohort ) who were between 65 and 70 years old . The methods used to identify vertebral deformities have been described previously [ 35 ] . In summary , six points for each vertebral body , T4 through L4 , were marked with a translucent digitizer . We calculated three heights ( anterior , posterior , and middle ) and three ratios : anterior-to-posterior height ( wedge ) ; mid-to-posterior height ( endplate ) ; and the posterior height of each vertebra to the posterior height of the adjacent vertebrae ( crush ) . We classified a vertebral body Background and Purpose — The association between cerebral white matter lesions ( WMLs ) and the risk of falls in older people is uncertain , with no supporting prospect i ve evidence . We aim ed to determine the risk of incident falls associated with WML volume , and the interactions between WML volume , gait , and other sensorimotor factors leading to falls . Methods — We conducted a prospect i ve , population -based study ( n=294 , mean age 72.3 years , independently mobile ) .  Volumetric MRI , computerized gait measures , and sensorimotor measures of falls risk  were obtained at baseline . Incident falls were recorded prospect ively over a 12-month period . Using regression modeling , we estimated the risk of incident falls associated with baseline WML volume . Results — Increasing baseline WML volume was independently associated with any incident fall ( P=0.01 ) and multiple incident falls ( P=0.02 ) . The risk of incident falls was doubled in people with lesion volumes in the highest quintile of its distribution compared with the lowest ( adjusted relative risk , 2.32 ; 95 % CI , 1.28–4.14 ) . Greater lesion volume was also associated with poorer gait and greater gait variability ( 
    Output:
    