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Steven R Cummings

Publications and source records attributed to Steven R Cummings.

At least 37 records · Page 2Linked to original sources
PubMed2006

Alcohol intake and its relationship with bone mineral density, falls, and fracture risk in older men.

OBJECTIVES: To examine the association between alcohol intake and problem drinking history and bone mineral density (BMD), falls and fracture risk. DESIGN: Cross-sectional and prospective cohort study. SETTING: Six U.S. clinical centers. PARTICIPANTS: Five thousand nine hundred seventy-four men aged 65 and older. MEASUREMENTS: Alcohol intake and problem drinking histories were ascertained at baseline. Follow-up time was 1 year for falls and a mean of 3.65 years for fractures. RESULTS: Two thousand one hundred twenty-one participants (35.5%) reported limited alcohol intake (<12 drinks/y); 3,156 (52.8%) reported light intake (<14 drinks/wk), and 697 (11.7%) reported moderate to heavy intake (> or =14 drinks/wk) in the year before baseline. One thousand one men (16.8%) had ever had problem drinking. In multivariate models, as alcohol intake increased, so did hip and spine BMD (P for trend < .001). Greater alcohol intake was not associated with greater risk for nonspine or hip fractures. Men with light intake, but not moderate to heavy intake, had a lower risk of two or more incident falls (light intake: relative risk (RR) = 0.77, 95% confidence interval (CI) = 0.65-0.92; moderate to heavy intake: RR = 0.83, 95% CI = 0.63-1.10) than abstainers. Men with problem drinking had higher femoral neck (+1.3%) and spine BMD (+1.4%), and a higher risk of two or more falls (RR = 1.59; 95% CI = 1.30-1.94) than those without a history of problem drinking and similar total hip BMD and risk of fracture. CONCLUSION: In older men, recent alcohol intake is associated with higher BMD. Alcohol intake and fracture risk is unclear. Light alcohol intake may decrease the risk of falling, but a history of problem drinking increased fall risk.

Accidental Falls↗
PubMed2006

BMD and risk of hip and nonvertebral fractures in older men: a prospective study and comparison with older women.

UNLABELLED: In a prospective study of 5384 older men, hip BMD was a very strong predictor of hip fracture, much stronger than spine BMD. The relationship between hip BMD and hip fracture risk seemed to be stronger than observed in a large prospective study of women. Hip BMD is an excellent test for predicting fracture risk in men. INTRODUCTION: There have been few studies of the relationship between BMD and risk of fractures in men and none for the association between lumbar spine BMD and risk of hip and nonvertebral fractures. There is also controversy about whether the associations between BMD and risk of fracture are the same in men and women. MATERIALS AND METHODS: We measured proximal femur and lumbar spine BMD in 5384 men, 5384 men, >or= 65 years of age. We compared the results to the very similar cohort of 7871 women >or=65 of age. During 4.4 years of 99% complete follow-up, we validated 317 nonvertebral (59 hip) fractures in men and 1169 nonvertebral (208 hip) fractures in women. RESULTS: Total hip BMD was very strongly associated with risk hip fracture in men (3.2-fold increased risk per sex-specific SD decrease in BMD; 95% CI, 2.4-4.1). The association was stronger than observed in SOF (2.1; 95% CI, 1.8, 2.4; p < 0.001 for interaction). Among the men, lumbar spine BMD was weakly associated with risk of hip fracture (relative risk [RR] per sex-specific SD decrease in BMD: 1.5; 95% CI, 1.2, 2.0). The association between total hip BMD and risk of nonvertebral fractures was somewhat stronger for men (RR = 1.6; 95% CI, 1.5, 1.8) than found for women (p = 0.01 for interaction). The risk of nonvertebral fracture was substantially higher in women than in men for all T scores of hip BMD, regardless of whether sex-specific or female reference values were used. CONCLUSIONS: Hip BMD is strongly associated with risk of nonvertebral, and especially hip fracture, in older men. These associations are at least as strong as in women. As in women, lumbar spine BMD in men is only weakly associated with risk of hip fracture. Regardless of whether sex-specific or female reference values were used, T scores indicated different risks of fractures in men than in women.

Age Factors↗
PubMed2005

Cystatin C and mortality risk in the elderly: the health, aging, and body composition study.

Kidney dysfunction is known to decrease life expectancy in the elderly. Cystatin C is a novel biomarker of kidney function that may have prognostic utility in older adults. The association of cystatin C with mortality was evaluated in a biracial cohort of black and white ambulatory elderly and compared with that of serum creatinine concentrations. The Health, Aging and Body Composition study is a cohort of well-functioning elderly that was designed to evaluate longitudinal changes in weight, body composition, and function. A total of 3075 participants who were aged 70 to 79 yr and had no disability were recruited at sites in Memphis, TN, and Pittsburgh, PA, between April 1997 and June 1998 with a follow-up of 6 yr. At entry, the mean cystatin C was 1.05 mg/L and the mean creatinine was 1.06 mg/dl. After 6 yr of follow-up, 557 participants had died. The mortality rates in each ascending cystatin C quintile were 1.7, 2.7, 2.9, 3.1, and 5.4%/yr. After adjustment for demographic risk factors, comorbid health conditions, and inflammatory biomarkers (C-reactive protein, IL-6. and TNF-alpha), each quintile of cystatin C was significantly associated with increased mortality risk compared with the lowest: Hazard ratios (HR; 95% confidence intervals) quintile 1, -1.0 (referent); quintile 2, -1.74 (1.21 to 2.50); quintile 3, -1.51 (1.05 to 2.18); quintile 4, -1.49 (1.04 to 2.13); and quintile 5, -2.18 (1.53 to 3.10). These associations did not differ by gender or race. Results were consistent for cardiovascular and other-cause mortality, but not cancer mortality. Creatinine quintiles were not associated with mortality after multivariate adjustment (HR: 1.0 [referent], 1.00 [0.72 to 1.39], 0.95 [0.68 to 1.32], 1.11 [0.79 to 1.57], 1.16 [0.86 to 1.58]). Cystatin C is a strong, independent risk factor for mortality in the elderly. Future studies should investigate whether cystatin C has a role in clinical medicine.

Aged↗
PubMed2005

Lipoprotein peroxidation and mobility limitation: results from the Health, Aging, and Body Composition Study.

BACKGROUND: Oxidative damage plays an important role in leading to major health-related events. The aim of this study was to assess the predictive value of a lipoprotein peroxidation marker, oxidized low-density lipoprotein (oxLDL) for incident mobility limitation (ML). METHODS: Data are from 2985 well-functioning elders enrolled in the Health ABC study (median follow-up, 4.1 years). All oxLDL levels were measured at the baseline assessment. The oxLDL/LDL cholesterol (LDL-C) ratio (log value) was used as a measure of lipoprotein peroxidation. Mobility limitation was defined by 2 consecutive semiannual reports of any difficulty either walking 1/4 mile or climbing up 10 steps without resting. Severe ML was defined by 2 consecutive reports of great difficulty or inability to do the same tasks. Cox proportional hazards models were performed to assess hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The mean (SD) age of the sample was 74.2 (2.9) years. After adjustment for potential confounders (sociodemographic factors, smoking, physical activity, body mass index, clinical conditions, biological markers, and medications), the relationship between the oxLDL/LDL-C ratio and disability events was statistically significant (per log-unit difference in the oxLDL/LDL-C ratio) (for ML: HR, 1.22; 95% CI, 1.06-1.41; for severe ML: HR, 1.43; 95% CI, 1.15-1.79). Consistent results were found when interleukin 6 level was included as a covariate in the adjusted models (ML: HR, 1.13; 95% CI, 0.98-1.31; severe ML: HR, 1.31; 95% CI, 1.05-1.64). No significant sex, race, interleukin 6 level, or clinical conditions interaction was found with the oxLDL/LDL-C ratio and mobility disability. CONCLUSIONS: Lipoprotein peroxidation predicts the onset of ML in older persons. The oxLDL predictive value for ML is partly explained by interleukin 6 levels.

Aged↗
PubMed2005

Association of estrogen receptor alpha polymorphisms with breast cancer risk in older Caucasian women.

Estrogens exert their effect on the breast through the estrogen receptor. We prospectively investigated breast cancer risk associated with 2 polymorphic sites in the estrogen receptor alpha gene (ESR1). A total of 4,248 Caucasian women from the Study of Osteoporotic Fractures were genotyped for the -401 T/C and -354 A/G polymorphisms in ESR1. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between genotypes and breast cancer. During a mean follow-up of 12.4 years, 252 (5.9%) women developed breast cancer. The HR (95% CI) for breast cancer were 0.928 (0.708, 1.22) and 0.834 (0.538, 1.29) for the -354 A/G and A/A genotypes, respectively. Interactions with -354 variant were observed for smoking (HR = 1.52 and 1.56 for A/G and A/A smokers, respectively; HR = 0.74 and 0.60 for A/G and A/A non-smokers, respectively; interaction p = 0.03) and walking (HR = 0.75 and 1.15 for A/G and A/A walkers, respectively; HR = 0.18 and 0.49 for A/G and A/A non-walkers, respectively; interaction p = 0.01). There were no differences in the HR for the -401 T/C genotypes. An interaction between parity and carriage of the T allele was found (HR = 0.60 vs. 1.12 for nulliparous vs. parous women; interaction p = 0.03). ESR1 polymorphisms in combination with lifestyle factors may be associated with breast cancer risk in older Caucasian women.

Aged↗
PubMed2005

Familial aggregation of bone mineral density and bone mineral content in a Chinese population.

Familial aggregation of bone mineral density (BMD) and bone mineral content (BMC) has been shown in twin and familial studies, but most sample sizes were small. We here report a large familial aggregation study in a Chinese population. A total of 13,973 siblings aged 25-64 years from 3,882 families were enrolled from Anhui, China. We assessed the whole-body, hip and lumbar spine BMD and BMC by dual-energy X-ray absorptiometry (DXA). Intra-class correlation coefficients of BMD and BMC between siblings varied among different skeletal sites and between different age groups of male sib-pairs and premenopausal and postmenopausal female sib-pairs, with a range of 0.228 to 0.397. The sibling recurrence risk ratio (lambdas) of osteoporosis was 2.6 in our population. We also evaluated the joint association of the BMD values of the first siblings and the second siblings with the risk of low BMD (defined as less than the 10th percentile of the same group population) of their younger siblings. If both the first and second siblings' BMDs were in the lowest tertile, the odd ratios (ORs) of low BMD in their subsequent siblings were 8.32 [95% confidence interval (CI) 5.59-12.39)], 8.71 (95% CI 5.74-13.22) and 5.90 (95% CI 3.57-9.76) for total body, total hip and lumbar spine, respectively. This study demonstrates a significant familial aggregation of BMD and BMC in a large sample of rural Chinese adults.

Absorptiometry, Photon↗
PubMed2005

Incidence rates and life-time risk of hip fractures in Mexicans over 50 years of age: a population-based study.

The vast majority of hip fractures in the 21st century will occur in the developing countries. The rates and life-time hip fracture risk are not known for Mexico, and for this reason, we studied the incidence of hip fractures, and the remaining life-time probability of having a hip fracture at the age of 50 years in Mexican men and women. All hip fracture cases registered during the year 2000 were collected at all the main tertiary-care hospitals in the two major health systems in México City, Instituto Mexicano del Seguro Social (IMSS) and Ministry of Health (SS), and the diagnosis was validated by chart review in all cases. The annual rates of hip fracture were 169 in women and 98 in men per 100,000 person-years. The life-time probability of having a hip fracture at 50 years of age was 8.5% in Mexican women and 3.8% in Mexican men. We conclude that hip fractures are an important health problem in Mexico and that Mexican health authorities should consider public health programs to prevent hip fractures.

Age Distribution↗
PubMed2005

Relationship between osteoporosis and cardiovascular disease in postmenopausal women.

UNLABELLED: In the placebo group of the MORE study, including 2576 postmenopausal women (mean age, 66.5 years), the authors describe a strong linear association between the severity grade of osteoporosis (from low BMD to presence of severe vertebral fractures) and the future risk of cardiovascular events. Accordingly, treatment of postmenopausal osteoporosis should include consideration of measures to prevent adverse cardiovascular outcomes. INTRODUCTION: Observations indicate an inverse association between BMD and the severity of peripheral atherosclerosis in postmenopausal women. The predictive value of osteoporosis and its different severity stages for the risk of acute cardiovascular events remains unknown. MATERIALS AND METHODS: Participants were 2576 women (mean age, 66.5 years) assigned to placebo and followed for 4 years in an osteoporosis treatment trial. Those with at least one vertebral fracture or total hip BMD T score < or = -2.5 at baseline were defined as having osteoporosis, whereas those without vertebral fracture and total hip BMD T score between -2.5 and -1 were defined as having low bone mass. The primary outcome for these posthoc analyses was the incidence of adjudicated fatal or nonfatal cardiovascular events. RESULTS: After adjustment for potential confounders, women with osteoporosis had a 3.9-fold (95% CI, 2.0-7.7; p < 0.001) increased risk for cardiovascular events compared with women with low bone mass. Under the same boundaries, a total hip BMD T score < or = -2.5 versus a T score between -2.5 and -1 was associated with a 2.1-fold (95% CI, 1.2-3.6; p < 0.01) increase in risk, whereas presence of at least one vertebral fracture versus no vertebral fracture at baseline was associated with a 3.0-fold (95% CI, 1.8-5.1; p < 0.001) increase in risk. The risk of cardiovascular events increased incrementally with the number and increasing severity of baseline vertebral fractures (both p < 0.001). CONCLUSIONS: Postmenopausal women with osteoporosis are at an increased risk for cardiovascular events that is proportional to the severity of osteoporosis at the time of the diagnosis. Treatment of postmenopausal osteoporosis should include consideration of measures to prevent cardiovascular outcomes.

Aged↗
PubMed2005

Skeletal effects of raloxifene after 8 years: results from the continuing outcomes relevant to Evista (CORE) study.

UNLABELLED: In the CORE breast cancer trial of 4011 women continuing from MORE, the incidence of nonvertebral fractures at 8 years was similar between placebo and raloxifene 60 mg/day. CORE had limitations for assessing fracture risk. In a subset of 386 women, 7 years of raloxifene treatment significantly increased lumbar spine and femoral neck BMD compared from the baseline of MORE. INTRODUCTION: The multicenter, double-blind Continuing Outcomes Relevant to Evista (CORE) trial assessed the effects of raloxifene on breast cancer for 4 additional years beyond the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) osteoporosis treatment trial. MATERIALS AND METHODS: In CORE, placebo-treated women from MORE continued with placebo (n = 1286), whereas those previously given raloxifene (60 or 120 mg/day) received raloxifene 60 mg/day (n = 2725). As a secondary endpoint, new nonvertebral fractures were analyzed as time-to-first event in 4011 postmenopausal women at 8 years. A substudy assessed lumbar spine and femoral neck BMD at 7 years, with the primary analysis based on 386 women (127 placebo, 259 raloxifene) who did not take other bone-active agents from the fourth year of MORE and who were > or =80% compliant with study medication in CORE. RESULTS: The risk of at least one new nonvertebral fracture was similar in the placebo (22.9%) and raloxifene (22.8%) groups (hazard ratio [HR], 1.00; Bonferroni-adjusted CI, 0.82, 1.21). The incidence of at least one new nonvertebral fracture at six major sites (clavicle, humerus, wrist, pelvis, hip, lower leg) was 17.5% in both groups. Posthoc Poisson analyses, which account for multiple events, showed no overall effect on nonvertebral fracture risk, and a decreased risk at six major nonvertebral sites in women with prevalent vertebral fractures (HR, 0.78; 95% CI, 0.63, 0.96). At 7 years after MORE randomization, the differences in mean lumbar spine and femoral neck BMD with raloxifene were 1.7% (p = 0.30) and 2.4% (p = 0.045), respectively, from placebo. Compared with MORE baseline, after 7 years, raloxifene treatment significantly increased lumbar spine (4.3% from baseline, 2.2% from placebo) and femoral neck BMD (1.9% from baseline, 3.0% from placebo). BMDs were significantly increased from MORE baseline at all time-points at both sites with raloxifene. CONCLUSION: Raloxifene therapy had no effect on nonvertebral fracture risk after 8 years, although CORE had limitations for fracture risk assessment. BMD increases were maintained after 7 years of raloxifene.

Aged↗
PubMed2005

Chronic kidney disease and cognitive impairment in the elderly: the health, aging, and body composition study.

Previous studies suggest a link between chronic kidney disease (CKD) and cognitive impairment. Whether the longitudinal course of cognitive impairment differs among people with or without CKD is unknown. Data collected in 3034 elderly individuals who participated in the Health, Aging, and Body Composition study were analyzed. Cognitive function was assessed with the Modified Mini-Mental State Exam (3MS) at baseline and then 2 and 4 yr after baseline. Cognitive impairment was defined as a 3MS score <80 or a decline in 3MS >5 points after 2 or 4 yr of follow-up among participants with baseline 3MS scores > or =80. Participants with CKD, defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2, were further divided into two eGFR strata. Unadjusted mean baseline 3MS scores and mean declines in 3MS scores over 4 yr were significantly more pronounced for participants with lower baseline eGFR. More advanced stages of CKD were associated with an increased risk for cognitive impairment: Odds ratio (OR) 1.32 (95% confidence interval [CI] 1.03 to 1.69) and OR 2.43 (95% CI, 1.38 to 4.29) for eGFR 45 to 59 ml/min per 1.73 m2 and <45 ml/min per 1.73 m2, respectively, adjusted for case mix, baseline 3MS scores, and other potential confounders. CKD is associated with an increased risk for cognitive impairment in the elderly that cannot be fully explained by other well-established risk factors. Studies aimed at understanding the mechanism(s) responsible for cognitive impairment in CKD and efforts to interrupt this decline are warranted.

Age Factors↗
PubMed2005

Bone mineral density and the risk of incident nonspinal fractures in black and white women.

CONTEXT: Black women have a lower rate of fracture than white women, but whether bone mineral density (BMD) predicts fracture risk as well in black women as it does in white women is not established. OBJECTIVE: To examine the association between BMD and incident nonspinal fractures in older black and white women. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of baseline data collected from 1986 through 1990 (7334 white women aged 67-99 years) and from 1996 through 1998 (636 black women aged 65-94 years) at 4 US clinical centers in the Study of Osteoporotic Fractures; mean (SD) follow-up of 6.1 (1.5) years until October 1, 2004. MAIN OUTCOME MEASURES: Incident nonspinal fractures were confirmed by radiograpic report. Total hip and femoral neck BMD and bone mineral content were measured by dual energy x-ray absorptiometry. RESULTS: A total of 58 black women had a combined total of 61 fractures and 1606 white women had a combined total of 1712 fractures. In age-adjusted proportional hazard models, a 1-SD decrease in femoral neck BMD was associated with a 37% increased risk of fracture in black women (relative risk [RR], 1.37; 95% confidence interval [CI], 1.08-1.74) and a 49% increase in fracture in white women (RR, 1.49; 95% CI, 1.40-1.58). Adjustment for body weight and other risk factors for fracture weakened the association between BMD and fracture, especially among black women (multivariable adjusted RR per 1-SD decrease in femoral neck BMD for black vs white women: RR, 1.20 [95% CI, 0.93-1.55] vs RR, 1.42 [95% CI, 1.32-1.52]). The absolute incidence of fracture across the pooled BMD distribution was 30% to 40% lower among black women at every BMD tertile. The lower risk of fracture among black compared with white women was independent of BMD and other risk factors (RR, 0.48; 95% CI, 0.36-0.64). CONCLUSIONS: Decreased total hip and femoral neck BMD is associated with an increased risk of fracture in both older black and white women, but this relationship was largely explained by other risk factors in black women. Black women have a lower fracture risk than white women at every level of BMD. Race-specific normative databases may be appropriate for the densitometric definition of osteoporosis.

Aged↗
PubMed2005

Population structure, admixture, and aging-related phenotypes in African American adults: the Cardiovascular Health Study.

U.S. populations are genetically admixed, but surprisingly little empirical data exists documenting the impact of such heterogeneity on type I and type II error in genetic-association studies of unrelated individuals. By applying several complementary analytical techniques, we characterize genetic background heterogeneity among 810 self-identified African American subjects sampled as part of a multisite cohort study of cardiovascular disease in older adults. On the basis of the typing of 24 ancestry-informative biallelic single-nucleotide-polymorphism markers, there was evidence of substantial population substructure and admixture. We used an allele-sharing-based clustering algorithm to infer evidence for four genetically distinct subpopulations. Using multivariable regression models, we demonstrate the complex interplay of genetic and socioeconomic factors on quantitative phenotypes related to cardiovascular disease and aging. Blood glucose level correlated with individual African ancestry, whereas body mass index was associated more strongly with genetic similarity. Blood pressure, HDL cholesterol level, C-reactive protein level, and carotid wall thickness were not associated with genetic background. Blood pressure and HDL cholesterol level varied by geographic site, whereas C-reactive protein level differed by occupation. Both ancestry and genetic similarity predicted the number and quality of years lived during follow-up, but socioeconomic factors largely accounted for these associations. When the 24 genetic markers were tested individually, there were an excess number of marker-trait associations, most of which were attenuated by adjustment for genetic ancestry. We conclude that the genetic demography underlying older individuals who self identify as African American is complex, and that controlling for both genetic admixture and socioeconomic characteristics will be required in assessing genetic associations with chronic-disease-related traits in African Americans. Complementary methods that identify discrete subgroups on the basis of genetic similarity may help to further characterize the complex biodemographic structure of human populations.

Black or African American↗
PubMed2005

Mammographic breast density and the Gail model for breast cancer risk prediction in a screening population.

BACKGROUND: Estimating an individual woman's absolute risk for breast cancer is essential for decision making about screening and preventive recommendations. Although the current standard, the Gail model, is well calibrated in populations, it performs poorly for individuals. Mammographic breast density (BD) may improve the predictive accuracy of the Gail model. METHODS: Prospective observational cohort of 81,777 women in the San Francisco Mammography Registry presenting for mammography during 1993 through 2002 who had no prior diagnosis of breast cancer. Breast density was rated by clinical radiologists using the Breast Imaging Reporting and Data System classification (almost entirely fat; scattered fibroglandular densities; heterogeneously dense; extremely dense). Breast cancer cases were identified through linkage to Northern California Surveillance Epidemiology End Results (SEER) program. We compared the predictive accuracy of models with Gail risk, breast density, and the combination. All models were adjusted for age and ethnicity. RESULTS: During 5.1 years of follow-up, 955 women were diagnosed with invasive breast cancer. The Gail model had modest predictive accuracy (concordance index (c-index) 0.67; 95% CI 0.65-0.68). Adding breast density to the model increased the predictive accuracy to 0.68 (95% CI .66-.70, p < 0.01 compared with the Gail model alone). The model containing only breast density adjusted for age and ethnicity had predictive accuracy equivalent to the Gail model (c-index 0.67, 95% CI 0.65-0.68). CONCLUSION: The addition of breast density measured by BI-RADS categories minimally improved the predictive accuracy of the Gail model. A model based on breast density alone adjusted for age and ethnicity was as accurate as the Gail model.

Adult↗
PubMed2005

Estrogen metabolizing polymorphisms and breast cancer risk among older white women.

OBJECTIVE: To investigate breast cancer risk according to metabolizing genes polymorphisms in older women. METHODS: A subset (43.8%) of 4248 older, white women from the Study of Osteoporotic Fractures (SOF) were genotyped for the catechol-O-methyltransferase (COMT) Val108Met polymorphism and the CYP1A1*2C locus. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between genotypes and breast cancer while controlling for potential confounders. RESULTS: During a mean follow up of 12.4 years, 252 women (5.9%) developed breast cancer. The HR (95% CI) for breast cancer was 1.24 (0.87-1.75) for COMT(Val/Met) and 1.35 (0.93-1.97) for COMT(Met/Met). No interactions with lifestyle and reproductive factors were found. The HR associated with the CYP1A1*2C Val allele was 0.80 (0.46, 1.39) with little evidence for interactions with lifestyle or reproductive factors. CONCLUSIONS: Among older white women, neither the COMT Val108/158Met polymorphism nor the CYP1A*2C Val allele plays a major role in breast cancer risk either alone or in combination with lifestyle and reproductive factors.

Aged↗
PubMed2005

An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia.

The herbal extracts kava and valerian are the leading dietary supplements used in the self-management of anxiety and insomnia, respectively. There is limited evidence to support their effectiveness for these common symptoms. The Internet has been used to a limited extent for research, but it is not known whether randomized controlled trials can be conducted entirely using Internet technology. We performed a randomized, double-blind, placebo-controlled trial using a novel Internet-based design to determine if kava is effective for reducing anxiety and if valerian is effective for improving sleep quality. E-mail recruitment letters and banner advertisements on websites were used to recruit a large pool of interested participants (1551) from 45 states over an 8-week period. Participants were first asked to read study information, complete an online informed consent process, and undergo electronic identity verification. In order to be eligible for the study, participants were required to have 1) anxiety as documented by scores of at least 0.5 standard deviations above the mean on the State-Trait Anxiety Inventory State subtest (STAI-State) on 2 separate occasions, and 2) insomnia, defined as a "problem getting to sleep or staying asleep over the past 2 weeks." We randomly assigned 391 eligible participants to 1 of the following 3 groups, and mailed 28 days' supply: kava with valerian placebo (n = 121), valerian with kava placebo (n = 135), or double placebo (n = 135). The primary outcome measures were changes from baseline in anxiety (STAI-State questionnaire) and insomnia (Insomnia Severity Index [ISI]) compared with placebo. Participants receiving placebo had a 14.4 point decrease in anxiety symptoms on the STAI-State score and an 8.3 point decrease in insomnia symptoms on the ISI. Those receiving kava had similar reductions in STAI-State score (2.7 point greater reduction in placebo compared with kava; 95% confidence interval [CI], -0.8 to +6.2). Those receiving valerian and placebo had similar improvements in sleep (0.4 point greater reduction in the placebo than the valerian group; 95% CI, -1.3 to +2.1). Results were similar when limited to the 83% of participants who adhered to study compounds for all 4 weeks. Neither kava nor valerian relieved anxiety or insomnia more than placebo. This trial demonstrates the feasibility of conducting randomized, blinded trials entirely via the Internet.

Adult↗
PubMed2005

Sex hormones, risk factors, and risk of estrogen receptor-positive breast cancer in older women: a long-term prospective study.

OBJECTIVE: Antiestrogens reduce the risk of estrogen receptor-positive (ER+) but not ER-negative (ER-) breast cancer. Women at high risk of ER+ cancer would be the most likely to benefit from these treatments, but the best approach to predicting ER+ cancer is uncertain. METHODS: We prospectively assessed putative risk factors for breast cancer and archived serum at -190 degrees C from a community-based cohort of 7,676 women ages > or =65 years who had no history of breast cancer. Follow-up for breast cancer over 10.5 years was 99% complete. Using a case-cohort design, we measured baseline levels of estradiol and testosterone in 196 cases of invasive ER+ cancer and 378 randomly selected controls. RESULTS: Women whose testosterone level in highest two quintiles had a 4-fold increased risk of ER+ breast cancer (P < 0.0001). High estradiol concentration also indicated an increased risk but was not a significant predictor after adjustment for testosterone. Women with >16 years of education had a 2.1 times increased risk (P = 0.03) of ER+ cancer, but no other risk factors were significantly related to an increased risk of ER+ cancer. Women with a family history of breast cancer had a 2.9-fold increased risk of ER- cancer (P = 0.002) but no increased risk of ER+ cancer (relative hazard = 1.2, 0.8-1.8). CONCLUSIONS: High serum testosterone and advanced education predicted ER+ breast cancer. If confirmed, high testosterone level may be more accurate than family history of breast cancer and other conventional risk factors for identifying older women who are most likely to benefit from antiestrogen chemoprevention.

Aged↗