Nitrate medications may increase bone mineral density (BMD), although information on fracture outcomes is sparse. We examined the association of nitrate medications with fractures (hip, wrist/arm, and total fractures) and changes in BMD (hip, spine, and whole body) in the Women's Health Initiative (WHI) Clinical Trials and Observational Study. A total of 139,211 postmenopausal women 50 to 79 years old without history of hip fracture were included in this prospective study. Medication use was ascertained directly from drug containers at baseline during in-person interviews in 1993 to 1998. Exposure measures included any use (use/non-use), type of nitrate (as-needed, maintenance) and duration of use (≤5 years, >5 years). We used separate multivariable Cox proportional hazard models to analyze associations between each exposure and fracture outcome, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Multivariable linear regression models were used to examine 3-year and 6-year changes in BMD. At baseline, 1.2% (n = 1647) women were using a nitrate. During the mean ± SD follow-up of 7.7 ± 1.5 years through 2005, women experienced 1582 hip fractures, 5156 wrist or arm fractures, and 22, 589 total fractures. After adjustment for confounders, nitrate use was not statistically associated with risk for hip (HR, 0.81; 95% CI, 0.56 to 1.18), wrist/arm (HR, 0.95; 95% CI, 0.74 to 1.23), or total fractures (HR, 0.96; 95% CI, 0.85 to 1.08). As-needed nitrate use, but not maintenance therapy, was associated with a lower risk of total fractures (HR, 0.77; 95% CI, 0.62 to 0.95) and wrist/arm fractures (HR, 0.57; 95% CI, 0.34 to 0.98). Nitrate use was not associated with 3-year or 6-year changes in BMD at any site. We conclude that any nitrate use was not significantly associated with lower risk of fractures or higher BMD; however, as-needed nitrate use was associated with lower risks of total and wrist/arm fractures. © 2016 American Society for Bone and Mineral Research.

Objectives

This study examined the association between benzodiazepine use and incident disability with an emphasis on elucidating whether the underlying health conditions that result in benzodiazepine use (confounding factors) or intrinsic adverse effects of benzodiazepine use were responsible for functional decline.

Design

Cohort study with follow-up of 4 to 5 years.

Setting

A health maintenance organization (HMO) in western Washington.

Participants

Individuals aged 65 and older from a random sample of HMO enrollees who participated in a health promotion intervention trial (n = 1,519).

Measurements

Benzodiazepine use was ascertained from computerized pharmacy records. Self-reported functional status was assessed using a six-item physical function scale ranging from vigorous activity to self-care activities of daily living (ADLs). Two outcomes were examined: decline in overall physical function and limitations in self-care ADLs. Multivariate models were examined that included demographic characteristics, health status, and health behaviors that were likely to be confounders. Several analyses were conducted to examine whether benzodiazepine use or confounding factors were responsible for functional decline.

Results

Benzodiazepine use was significantly associated with incident loss of physical function (hazard ratio (HR) = 1.51, 95% confidence interval (CI) = 1.02-2.24) in the fully adjusted model. Although use of benzodiazepines was associated with limitations in ADLs, it was not significant when adjusting for other factors (HR = 1.71, 95% CI = 0.87-3.34). Several of our findings suggest that the health conditions leading to benzodiazepine use may partly or fully explain these associations: (1) use of anxiolytic benzodiazepines (HR = 1.95, 95% CI = 1.24-3.07), but not hypnotic agents (HR = 1.21, 95% CI = 0.73-2.00), was associated with functional decline; (2) adjustment for health status variables minimized these associations; and (3) there was little evidence of dose response.

Conclusions

A modestly increased risk for decline in physical function was associated with benzodiazepine use, especially of anxiolytic agents. The health conditions that result in benzodiazepine use may be more important in the pathogenesis of disability than benzodiazepine use itself. Although there are many reasons for avoiding benzodiazepines in older adults, it is still unclear whether use contributes independently to functional decline.

Objectives

The authors examined patterns of benzodiazepine use in older adults. Specifically, they describe prevalence and incidence of benzodiazepine use during the index year, describe persistence and intensity of benzodiazepine use over a 4-year period; and examine factors associated with benzodiazepine use in the upcoming year.

Methods

Authors performed a secondary analysis of data collected as part of a health promotion intervention trial conducted from 1986 to 1992 in older health maintenance organization enrollees (N=1,505). Benzodiazepine use was ascertained from computerized pharmacy records. Demographic characteristics, health status, and health behaviors were ascertained from mailed questionnaires.

Results

During the index year, the prevalence and incidence of benzodiazepine use was 12.3% and 6.6%, respectively. Of those using during the index year, 16% of new users and 63% of previous users continued to use for the following 3 years. The factors significantly associated with benzodiazepine use in the following year were female gender, high school education, higher chronic disease score, higher levels of self-reported pain and stress, low-to-normal body mass index (BMI), and self-reported nervous disorder.

Conclusions

New users had low intensity of use and a low probability of continuing use over the following 3 years. A very small percentage of this sample had evidence of daily use for 4 years. Of concern, benzodiazepines were used by the segment of the sample that were at greatest risk for hip fractures (women with normal/low BMI). Clinicians should assess the need for continued benzodiazepine use at regular intervals.

Objectives

To describe the prevalence of, types of, and characteristics associated with self-reporting multiple (≥ 2) barriers to medication use in older women using long-term cardiovascular and oral hypoglycemic medications.

Methods

This cross-sectional study set at the Women's Health Initiative during 2005-2010 included women who were using any chronic medication from 3 target classes (i.e., antilipemics, antihypertensives, oral hypoglycemics) for at least 1 month and who had answered questions about barriers to medication use at year 4 (2009) of the study period (N = 59,054). Measurements included common self-reported barriers to medication use, and sociodemographic, health characteristic, medication use, and access to care variables were evaluated. Multivariable logistic regression models were used to examine associations between participant characteristics and barriers to medication use.

Results

Among the participants, 47,846 (81%) reported no barriers, 7105 (12%) reported 1 barrier, and 4103 (6.9%) reported 2 or more barriers to medication use. The most common barriers reported were having concerns about adverse effects, not liking to take medications, and medications costing too much. Several characteristics were found to be associated with reporting 2 or more barriers in multivariable modeling, including demographic (e.g., lower age, black race, Hispanic ethnicity) and health or medication (e.g., lower quality of life, lower physical function, higher number of concurrent medications) characteristics.

Conclusion

Among older women using chronic cardiovascular and oral hypoglycemic medications, approximately 20% reported at least 1 barrier to medication use, with 7% of women reporting multiple barriers. Pharmacists should prioritize identifying barriers to medication use in older women using chronic medications to improve patient care.

Background

Anticholinergic medication use has been associated with several negative health outcomes in older adults, but little is known about its risk for fractures.

Objective

To examine the association between anticholinergic medication use and fracture outcomes in community-dwelling postmenopausal women.

Methods

Utilizing a prospective cohort design, we examined data collected from 137,408 women aged 50-79 years from the Women's Health Initiative observational study and clinical trials not reporting hip fracture at baseline. Medications with moderate or strong anticholinergic effects were identified directly from drug containers during in-person interviews. The main outcome was fractures (hip, lower arm/wrist and total fractures). We performed multivariable Cox proportional hazard survival modelling to assess the association between anticholinergic use and the risk of fractures.

Results

At baseline, 10.6% of the women were using an anticholinergic medication, of which antihistamines were the most common medication class (48.4%). The multivariable-adjusted hazard ratios for anticholinergic medication use were 1.08 (95% confidence interval [CI] 0.89-1.30) for hip fracture, 1.01 (95% CI 0.91-1.13) for lower arm/wrist fracture and 1.03 (95% CI 0.98-1.09) for total fractures. We observed no association according to subclass or count of anticholinergic medications, or trends between the duration of anticholinergic use and any of the fracture outcomes.

Conclusion

Anticholinergic medication use was not associated with an increased risk of fractures among community-dwelling women. Future research should make efforts to capture over-the-counter medication use and the cumulative anticholinergic burden in relation to important health outcomes for older adults.

Background

Proton pump inhibitor (PPI) medications have been inconsistently shown to be associated with osteoporotic fractures. We examined the association of PPI use with bone outcomes (fracture, bone mineral density [BMD]).

Methods

This prospective analysis included 161 806 postmenopausal women 50 to 79 years old, without history of hip fracture, enrolled in the Women's Health Initiative (WHI) Observational Study and Clinical Trials with a mean (SD) follow-up of 7.8 (1.6) years. Analyses were conducted for 130 487 women with complete information. Medication information was taken directly from drug containers during in-person interviews (baseline, year 3). The main outcome measures were self-reported fractures (hip [adjudicated], clinical spine, forearm or wrist, and total fractures) and for a subsample (3 densitometry sites), 3-year change in BMD.

Results

During 1 005 126 person-years of follow-up, 1500 hip fractures, 4881 forearm or wrist fractures, 2315 clinical spine fractures, and 21 247 total fractures occurred. The multivariate-adjusted hazard ratios for current PPI use were 1.00 (95% confidence interval [CI], 0.71-1.40) for hip fracture, 1.47 (95% CI, 1.18-1.82) for clinical spine fracture, 1.26 (95% CI, 1.05-1.51) for forearm or wrist fracture, and 1.25 (95% CI, 1.15-1.36) for total fractures. The BMD measurements did not vary between PPI users and nonusers at baseline. Use of PPIs was associated with only a marginal effect on 3-year BMD change at the hip (P = .05) but not at other sites.

Conclusion

Use of PPIs was not associated with hip fractures but was modestly associated with clinical spine, forearm or wrist, and total fractures.

BACKGROUND AND AIMS:Infections are a major cause of morbidity and mortality in older adults. Little is known about factors that alter the susceptibility to infection in the older population. This study in postmenopausal women examines health-related conditions and behavioral factors that may increase the risk of frequent infections, defined as having, on average, one or more infections per year. METHODS:A prospective cohort study with 5 years of follow-up was conducted in 1320 women aged 55 to 80 years. The subjects were Group Health Cooperative of Puget Sound (GHC) enrollees screened for a large fracture prevention trial who also participated in a survey of dietary and supplemental vitamin use. The main outcome, total number of infection events per subject, was derived from a new method of identifying outpatient infections based on the antimicrobial prescription fills recorded in GHC automated pharmacy records. RESULTS:Prevalent lung disease (OR = 6.1, 95% CI 2.8-13.4), receiving a prescription for vitamin C (OR = 2.1, 95% CI 1.4-3.4), and the second and third tertiles of the Chronic Disease Score (OR = 1.7, 95% CI 1.1-2.7 and OR = 2.4, 95% CI 1.5-3.9, respectively) were associated with 5 or more antimicrobial-treated infections during follow-up. A body mass index (BMI) of less than 22 kg/m2 (OR = 0.6, 95% CI 0.3-1.0) was suggestive of an association. CONCLUSIONS:The study provides new information on risk factors for outpatient infections and raises new questions regarding the susceptibility to frequent infections in older women. In addition, the automated pharmacy record method used in this study offers a low-cost alternative for use in future epidemiologic research.

Background

Results from studies assessing the association between anticholinergic use and falls are mixed, and prior studies are limited in their ability to control for important potential confounders. Thus, we sought to examine the association between anticholinergic medication use, including over-the-counter medications, and recurrent falls in community-dwelling older women.

Methods

We analyzed data from a prospective cohort study of women aged 65 to 79 years from the Women's Health Initiative Observational Study and Clinical Trials. Women were recruited between 1993 and 1998, and analyses included 61,451 women with complete information. Medications with moderate or strong anticholinergic effects were ascertained directly from drug containers during face-to-face interviews. The main outcome measure was recurrent falls (≥2 falls in previous year), which was determined from self-report within 1.5 years subsequent to the medication assessment.

Results

At baseline, 11.3 % were using an anticholinergic medication, of which antihistamines (commonly available over-the-counter) were the most common medication class (received by 45.2 % of individuals on anticholinergic medication). Using multivariable GEE models and controlling for potential confounders, the adjusted odds ratio for anticholinergic medication use was 1.51 (95 % CI, 1.43-1.60) for recurrent falls. Participants using multiple anticholinergic medications had a 100 % increase in likelihood of recurrent falls (adjusted odds ratio 2.00, 95 % CI 1.73-2.32). Results were robust to sensitivity analysis.

Conclusions

Anticholinergic medication use was associated with increased risk for recurrent falls. Our findings reinforce judicious use of anticholinergic medications in older women. Public health efforts should emphasize educating older women regarding the risk of using over-the-counter anticholinergics, such as first-generation antihistamines.

For research purposes, there are few alternatives to costly surveillance for ascertaining infections in community populations. We propose a new approach based on antibiotic prescription fills in automated pharmacy records of the Group Health Cooperative of Puget Sound, in Seattle, Washington, to identify treated infections in postmenopausal women. After excluding probable antimicrobial prophylaxis and chronic antibiotic use, four intervals between antibiotic fills (30, 45, 60, and 90 days) were tested for their ability to detect new infections. Concordance with outpatient medical record reviews was evaluated in 150 women. The sensitivity of the automated pharmacy records using the four cutpoints for detecting new infections ranged from 88 to 80%, from 30 to 90 days, respectively. Of the 81 women with no infection in the chart reviews, 75% also had no infection using the pharmacy method. Good agreement was found between the two methods for counts of infections per person over the 2-year follow-up, with the 60-day cutpoint showing the greatest overall agreement with chart reviews (kappa = 0.55). The pharmacy method presented here offers a useful new approach for infection ascertainment for epidemiologic research.

Objectives

To define frailty using simple indicators; to identify risk factors for frailty as targets for prevention; and to investigate the predictive validity of this frailty classification for death, hospitalization, hip fracture, and activity of daily living (ADL) disability.

Design

Prospective study, the Women's Health Initiative Observational Study.

Setting

Forty U.S. clinical centers.

Participants

Forty thousand six hundred fifty-seven women aged 65 to 79 at baseline.

Measurements

Components of frailty included self-reported muscle weakness/impaired walking, exhaustion, low physical activity, and unintended weight loss between baseline and 3 years of follow-up. Death, hip fractures, ADL disability, and hospitalizations were ascertained during an average of 5.9 years of follow-up.

Results

Baseline frailty was classified in 16.3% of participants, and incident frailty at 3-years was 14.8%. Older age, chronic conditions, smoking, and depressive symptom score were positively associated with incident frailty, whereas income, moderate alcohol use, living alone, and self-reported health were inversely associated. Being underweight, overweight, or obese all carried significantly higher risk of frailty than normal weight. Baseline frailty independently predicted risk of death (hazard ratio (HR)=1.71, 95% confidence interval (CI)=1.48-1.97), hip fracture (HR=1.57, 95% CI=1.11-2.20), ADL disability (odds ratio (OR)=3.15, 95% CI=2.47-4.02), and hospitalizations (OR=1.95, 95% CI=1.72-2.22) after adjustment for demographic characteristics, health behaviors, disability, and comorbid conditions.

Conclusion

These results support the robustness of the concept of frailty as a geriatric syndrome that predicts several poor outcomes in older women. Underweight, obesity, smoking, and depressive symptoms are strongly associated with the development of frailty and represent important targets for prevention.