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ObjectivesTo 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.MethodsThis 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.ResultsAmong 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.ConclusionAmong 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.

BackgroundMechanisms linking cognitive and physical functioning in older adults are unclear. We sought to determine whether brain pathological changes relate to the level or rate of physical performance decline.MethodsThis study analyzed data from 305 participants in the autopsy subcohort of the prospective Adult Changes in Thought (ACT) study. Participants were aged 65+ and free of dementia at enrollment. Physical performance was measured at baseline and every two years using the Short Physical Performance Battery (SPPB). Data from 3174 ACT participants with ≥2 SPPB measurements were used to estimate two physical function measures: 1) rate of SPPB decline defined by intercept and slope; and 2) estimated SPPB 5 years prior to death. Neuropathology findings at autopsy included neurofibrillary tangles (Braak stage), neuritic plaques (CERAD level), presence of amyloid angiopathy, microinfarcts, cystic infarcts, and Lewy bodies. Associations (adjusted for sex, age, body mass index and education) between dichotomized neuropathologic outcomes and SPPB measures were estimated using modified Poisson regression with inverse probability weights (IPW) estimated via Generalized Estimating Equations (GEE). Relative risks for the 20th, 40th, and 60th percentiles (lowest levels and highest rates of decline) relative to the 80th percentile (highest level and lowest rate of decline) were calculated.ResultsDecedents with the least vs. most SPPB decline (slope > 75th vs.

BackgroundResults 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.MethodsWe 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.ResultsAt 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.ConclusionsAnticholinergic 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.

Objective: The growing deprescribing field is challenged by a lack of consensus around evidence and knowledge gaps. The objective of this overview of systematic reviews was to summarize the review evidence for deprescribing interventions in older adults. Methods: 11 databases were searched from 1st January 2005 to 16th March 2023 to identify systematic reviews. We summarized and synthesized the results in two steps. Step 1 summarized results reported by the included reviews (including meta-analyses). Step 2 involved a narrative synthesis of review results by outcome. Outcomes included medication-related outcomes (e.g., medication reduction, medication appropriateness) or twelve other outcomes (e.g., mortality, adverse events). We summarized outcomes according to subgroups (patient characteristics, intervention type and setting) when direct comparisons were available within the reviews. The quality of included reviews was assessed using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). Results: We retrieved 3,228 unique citations and assessed 135 full-text articles for eligibility. Forty-eight reviews (encompassing 17 meta-analyses) were included. Thirty-one of the 48 reviews had a general deprescribing focus, 16 focused on specific medication classes or therapeutic categories and one included both. Twelve of 17 reviews meta-analyzed medication-related outcomes (33 outcomes: 25 favored the intervention, 7 found no difference, 1 favored the comparison). The narrative synthesis indicated that most interventions resulted in some evidence of medication reduction while for other outcomes we found primarily no evidence of an effect. Results were mixed for adverse events and few reviews reported adverse drug withdrawal events. Limited information was available for people with dementia, frailty and multimorbidity. All but one review scored low or critically low on quality assessment. Conclusion: Deprescribing interventions likely resulted in medication reduction but evidence on other outcomes, in particular relating to adverse events, or in vulnerable subgroups or settings was limited. Future research should focus on designing studies powered to examine harms, patient-reported outcomes, and effects on vulnerable subgroups. Systematic Review Registration: PROSPERO CRD42020178860. [ABSTRACT FROM AUTHOR]

Improving the quality of medication use and medication safety are important priorities for healthcare providers who care for older adults. The objective of this article was to identify four exemplary articles with this focus in 2022. We selected high‐quality studies from an OVID search and hand searching of major high impact journals that advanced the field of research forward. The chosen articles cover domains related to deprescribing, medication safety, and optimizing medication use. The MedSafer Study, a cluster randomized clinical trial in Canada, evaluated whether patient specific deprescribing reports generated by electronic decision support software resulted in reduced adverse drug events in the 30 days post hospital discharge in older adults (domain: deprescribing). The second study, a retrospective cohort study using data from Premier Healthcare Database, examined in‐hospital adverse clinical events associated with perioperative gabapentin use among older adults undergoing major surgery (domain: medication safety). The third study used an open‐label parallel controlled trial in 39 Australian aged‐care facilities to examine the effectiveness of a pharmacist‐led intervention to reduce medication‐induced deterioration and adverse reactions (domain: optimizing medication use). Lastly, the fourth study engaged experts in a Delphi method process to develop a consensus list of clinically important prescribing cascades that adversely affect older persons' health to aid clinicians to identify, prevent, and manage prescribing cascades (domain: optimizing medication use). Collectively, this review succinctly highlights pertinent topics related to promoting safe use of medications and promotes awareness of optimizing older adults' medication regimens. [ABSTRACT FROM AUTHOR]

ObjectivesTo compare the ability of the commonly used Women's Health Initiative (WHI) and Cardiovascular Health Study (CHS) frailty phenotypes to predict falls, hip fracture, and death in WHI Clinical Trial participants aged 65 and older.DesignLongitudinal cohort study.SettingWHI Clinical Trial.ParticipantsParticipants with data for WHI and CHS frailty phenotypes (N = 3,558).MeasurementsFrailty was operationally defined in the CHS as the presence of three or more of weight loss, poor energy, weakness, slowness, and low physical activity. WHI operationalized frailty similarly but with the RAND-36 physical function scale substituted for slowness and weakness (RAND-36 physical function scale score 78 = 0 points). Frailty was defined as a summary score of 3 or greater, prefrailty as a score of 2 or 1, and nonfrailty as a score of 0. Outcomes were modeled using Cox regression. Harrell C-statistics were compared for models containing alternative instruments.ResultsApproximately 5% of participants were frail based on the CHS or WHI phenotype. The WHI frailty phenotype was associated with higher rates of falls (hazard ratio (HR) = 1.48, P = .003), hip fracture (HR = 1.87, P = .04), and death (HR = 2.32, P < .001). Comparable HRs in CHS-phenotype frail women were 1.32 (P = .04), 1.08 (P = .83), and 1.91 (P < .001), respectively. Harrell C-statistics revealed marked but insignificant differences in predicting abilities between CHS and WHI phenotype models (P > .50 for all).ConclusionThe WHI phenotype, which does not require direct measurements of physical performance, might offer a practical advantage for epidemiological and clinical needs.

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.

BackgroundFew studies have compared the risk of recurrent falls across various antidepressant agents-using detailed dosage and duration data-among community-dwelling older adults, including those who have a history of a fall/fracture.ObjectiveTo examine the association of antidepressant use with recurrent falls, including among those with a history of falls/fractures, in community-dwelling elders.MethodsThis was a longitudinal analysis of 2948 participants with data collected via interview at year 1 from the Health, Aging and Body Composition study and followed through year 7 (1997-2004). Any antidepressant medication use was self-reported at years 1, 2, 3, 5, and 6 and further categorized as (1) selective serotonin reuptake inhibitors (SSRIs), (2) tricyclic antidepressants, and (3) others. Dosage and duration were examined. The outcome was recurrent falls (≥2) in the ensuing 12-month period following each medication data collection.ResultsUsing multivariable generalized estimating equations models, we observed a 48% greater likelihood of recurrent falls in antidepressant users compared with nonusers (adjusted odds ratio [AOR] = 1.48; 95% CI = 1.12-1.96). Increased likelihood was also found among those taking SSRIs (AOR = 1.62; 95% CI = 1.15-2.28), with short duration of use (AOR = 1.47; 95% CI = 1.04-2.00), and taking moderate dosages (AOR = 1.59; 95% CI = 1.15-2.18), all compared with no antidepressant use. Stratified analysis revealed an increased likelihood among users with a baseline history of falls/fractures compared with nonusers (AOR = 1.83; 95% CI = 1.28-2.63).ConclusionAntidepressant use overall, SSRI use, short duration of use, and moderate dosage were associated with recurrent falls. Those with a history of falls/fractures also had an increased likelihood of recurrent falls.

BackgroundGait speed decline, an early marker of functional impairment, is a sensitive predictor of adverse health outcomes in older adults. The effect of potentially inappropriate medications, including drug-disease and drug-drug interactions, on gait speed decline is not well known.ObjectiveThe aim of this study was to determine if drug interactions impair functional status as measured by gait speed.MethodsThe sample included 2402 older adults with medication and gait speed data from the Health, Aging and Body Composition study. The independent variable was the frequency of drug-disease and/or drug-drug interactions at baseline and 3 additional years. The main outcome was a clinically meaningful gait speed decline of ≥0.1 m/s the year following drug interaction assessment. Adjusted odds ratios and 95 % confidence intervals (CIs) were calculated using multivariate generalized estimating equations for both the overall sample and a sample stratified by gait speed at time of drug interaction assessment.ResultsThe prevalence of drug-disease and drug-drug interactions ranged from 7.6 to 9.3 and 10.5 to 12.3 %, respectively, with few participants (3.8-5.7 %) having multiple drug interactions. At least 22 % of participants had a gait speed decline of ≥0.1 m/s annually. Drug interactions were not significantly associated with gait speed decline overall or in the stratified sample of fast walkers. There was some evidence, however, that drug interactions increased the risk of gait speed decline among those participants with slower gait speeds, though p values did not reach statistical significance (adjusted odds ratio 1.22; 95 % CIs 0.96-1.56; p = 0.11). Moreover, a marginally significant dose-response relationship was seen with multiple drug interactions and gait speed decline (adjusted odds ratio 1.40; 95 % CIs 0.95-2.04; p = 0.08).ConclusionsDrug interactions may increase the likelihood of gait speed decline among older adults with evidence of preexisting debility. Future studies should focus on frail elders with less physiological reserve who may be more susceptible to the harms associated with potentially inappropriate medications.

Purpose of the studyTo compare the prevalence and cardiometabolic health impact of sleep disturbance among postmenopausal Veteran and non-Veteran participants in the Women's Health Initiative (WHI).Design and methodsThe prevalence of five categories of sleep disturbance--medication/alcohol use for sleep; risk for insomnia; risk for sleep disordered breathing [SDB]; risk for comorbid insomnia and SDB (insomnia + SDB); and aberrant sleep duration [SLD]--was compared in 3,707 Veterans and 141,354 non-Veterans using logistic or multinomial regression. Cox proportional hazards models were used to evaluate the association of sleep disturbance and incident cardiovascular disease (CVD) and Type 2 diabetes in Veterans and non-Veterans.ResultsWomen Veterans were more likely to have high risk for insomnia + SDB relative to non-Veteran participants. However, prevalence of other forms of sleep disturbance was similar across groups. Baseline sleep disturbance was not differentially associated with cardiometabolic health outcomes in Veteran versus non-Veteran women. Risks for SDB and insomnia + SDB were both linked to heightened risk of CVD and diabetes; SLD was consistently linked with greater risk of CVD and diabetes in non-Veterans but less strongly and consistently in Veterans.ImplicationsEfforts to identify and treat sleep disturbances in postmenopausal women are needed and may positively contribute to the attenuation of cardiometabolic morbidity risk. Increased awareness of women Veterans' vulnerability to postmenopausal insomnia + SDB may be particularly important for health care providers who treat this population.

Purpose of the studyPostmenopausal osteoporosis can impact quality-of-life even prefracture. To determine whether osteoporosis should be a greater concern in women Veterans versus non-Veterans, we compared fracture rates and bone mineral density (BMD) for Veterans and non-Veterans using Women's Health Initiative data.Design and methodsIn this cohort study, participants were women aged 50-79 years. Outcomes were hip, central body, and limb fractures occurring during up to 19 years of follow-up and hip, spine, and whole body BMD collected three times over a 6-year period in a participant subsample. Covariates comprised risk factors for fracture, including fall history and other components of the World Health Organization Fracture Risk Assessment Tool (FRAX). Cox Proportional Hazards models were used to examine fracture rates for Veterans compared with non-Veterans.ResultsOf 161,808 women, 145,521 self-identified as Veteran (n = 3,719) or non-Veteran (n = 141,802). Baseline FRAX scores showed that Veterans had higher 10-year probabilities for any major fracture (13.3 vs 10.2; p < .01) and hip fracture (4.1 vs 2.2; p < .01) compared with non-Veterans. The age-adjusted rate of hip fracture per 1,000 person-years for Veterans was 3.3 versus 2.4 for non-Veterans (p < .01). After adjustment, the hazards ratio for hip fracture was 1.24 (95% confidence interval 1.03-1.49) for Veterans versus non-Veterans. Hazards ratios at other anatomic sites did not differ by Veteran status. Mean BMD at baseline and at Years 3 and 6 also did not differ by Veteran status at any site.ImplicationsWomen Veterans had an increased hip fracture rate not explained by differences in well-recognized fracture risk factors.

BackgroundDespite wide-spread use of antihypertensives in older adults, the literature is unclear about their association with incident recurrent falls over time.MethodsHealth, Aging and Body Composition study participants (n = 2,948) who were well functioning at baseline (1997) were followed to Year 7 (2004). The main outcome was recurrent falls (≥2) in the ensuing 12 months. Antihypertensive use was examined as: (a) any versus none, (b) long- versus short-term (≥2 vs

BackgroundAlthough it is generally accepted that anticholinergic use may lead to a fall, results from studies assessing the association between anticholinergic use and falls are mixed. In addition, direct evidence of an association between use of anticholinergic medications and recurrent falls among community-dwelling elders is not available.ObjectiveTo assess the association between anticholinergic use across multiple anticholinergic subclasses, including over-the-counter medications, and recurrent falls.MethodsThis was a longitudinal analysis of 2948 participants, with data collected via interview at year 1 from the Health, Aging and Body Composition study and followed through year 7 (1997-2004). Self-reported use of anticholinergic medication was identified at years 1, 2, 3, 5, and 6 as defined by the list from the 2015 American Geriatrics Society Beers Criteria. Dosage and duration were also examined. The main outcome was recurrent falls (≥2) in an ensuing 12-month period from each medication data collection.ResultsUsing multivariable generalized estimating equation models, controlling for demographic, health status/behaviors, and access-to-care factors, a 34% increase in likelihood of recurrent falls in anticholinergic users (adjusted odds ratio = 1.34; 95% CI = 0.93-1.93) was observed, but the results were not statistically significant; similar results were found with higher doses and longer duration of use.ConclusionIncreased point estimates suggest an association of anticholinergic use with recurrent falls, but the associations did not reach statistical significance. Future studies are needed for more definitive evidence and to examine other measures of anticholinergic burden and associations with more intermediate adverse effects such as cognitive function.

BackgroundAnticholinergic medication use has been associated with several negative health outcomes in older adults, but little is known about its risk for fractures.ObjectiveTo examine the association between anticholinergic medication use and fracture outcomes in community-dwelling postmenopausal women.MethodsUtilizing 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.ResultsAt 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.ConclusionAnticholinergic 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.

ObjectivesTo examine the association between statin use and objectively assessed decline in gait speed in community-dwelling older adults.DesignLongitudinal cohort study.SettingHealth, Aging and Body Composition (Health ABC) Study.ParticipantsTwo thousand five participants aged 70-79 at baseline with medication and gait speed data at 1998-99, 1999-2000, 2001-02, and 2002-03.MeasurementsThe independent variables were any statin use and their standardized daily doses (low, moderate, high) and lipophilicity. The primary outcome measure was decline in gait speed of 0.1 m/s or more in the following year of statin use. Multivariable generalized estimating equations were used, adjusting for demographic characteristics, health-related behaviors, health status, and access to health care.ResultsStatin use increased from 16.2% in 1998-99 to 25.6% in 2002-03. The overall proportions of those with decline in gait speed of 0.1 m/s or more increased from 22.2% in 1998 to 23.9% in 2003. Statin use was not associated with decline in gait speed of 0.1 m/s or more (adjusted odds ratio (AOR) = 0.90, 95% confidence interval (CI) = 0.77-1.06). Similar nonsignificant trends were also seen with the use of hydrophilic or lipophilic statins. Users of low-dose statins were found to have a 22% lower risk of decline in gait speed than nonusers (AOR = 0.78, 95% CI = 0.61-0.99), which was mainly driven by the results from 1999-2000 follow-up.ConclusionThese results suggest that statin use did not increase decline in gait speed in community-dwelling older adults.

BackgroundWe sought to examine whether frailty is associated with dementia, Alzheimer's disease (AD), and non-AD dementia risk.MethodsThis is a prospective population-based cohort derived from an integrated health maintenance organization. The sample consisted of 2,619 participants aged 65 and older without dementia at baseline followed from 1994 to 2010. Frailty was defined as having at least 3 of the following criteria: weakness (grip strength), slowness (walking speed), weight loss, low physical activity, and self-reported exhaustion. Follow-up occurred every 2 years to identify incident dementia, possible or probable AD, and non-AD dementia using standard research criteria. Covariates came from self-report and study measures. We used adjusted Cox proportional hazards models to examine the association between frailty and each outcome.ResultsOver a mean follow-up of 6.5 years, 521 participants developed dementia (of which 448 developed AD). In the model adjusted for age, sex, education, and race, the hazard ratio for frailty was 1.78 (95% confidence interval [CI] 1.32-2.40). In the fully adjusted models, the hazard ratio for frailty was 1.20 for all-cause dementia (95% CI 0.85-1.69), 1.08 for AD (95% CI 0.74-1.57), and 2.57 for non-AD dementia (95% CI 1.08-6.11). For all-cause dementia, we found an interaction between baseline cognitive score and frailty (p = .02); hazard ratio for frailty was 1.78 for those with higher global cognition (95% CI 1.14-2.78) and 0.79 for those with lower global cognition (95% CI 0.50-1.26).ConclusionFrailty was associated with dementia when adjusting only for demographic variables but not in the fully adjusted model. Frailty was associated with higher risk of developing non-AD dementia but not AD. Although frailty was not associated with all-cause dementia in the entire sample, an association did exist in participants with higher cognitive scores. Mechanisms underlying these associations remain to be elucidated.

BackgroundThe impact of evidence-based guidelines and controlled trial data on use of cholesterol-lowering medications in older adults is unclear.ObjectiveTo examine whether utilization patterns of cholesterol-lowering medications in community-dwelling older adults changed following the release of the National Cholesterol Education Program Adult Treatment Panel III guidelines and results from the Prospective Study of Pravastatin in the Elderly at Risk in 2002.MethodsCommunity-dwelling elderly individuals who were enrolled in the Health, Aging and Body Composition Study in 1997-1998 were followed for up to 11 years. An interrupted time series analysis with multivariable generalized estimating equations (GEEs) was used to examine changes in level and trend in cholesterol-lowering medication use before and after 2002, adjusting for sociodemographics, health-related behaviors, and health status.ResultsCholesterol-lowering medication use increased nearly 3-fold from 14.9% in 1997-1998 to 42.6% in 2007-2008, with statins representing the most common class used (87-94%). Multivariable GEE results revealed no significant difference in the level of cholesterol-lowering medication use after 2002 (adjusted OR 0.95; 95% CI 0.89-1.02). Multivariable GEE results revealed that trend changes in the rate of increase in cholesterol-lowering medication declined after 2002 (adjusted ratio of ORs 0.92; 95% CI 0.89-0.95).ConclusionsThe use of cholesterol-lowering medication increased substantially over a decade in community-dwelling elderly individuals but was not related to a change in level or trend following the release of the guidelines and evidence-based data.

ObjectivesTo examine associations between angiotensin-converting enzyme (ACE) inhibitor and statin medications and baseline and mean annual change in physical performance measures and muscle strength in older women.DesignProspective cohort study.ParticipantsParticipants from the Women's Health Initiative Clinical Trials aged 65 to 79 at baseline who had physical performance measures, self-report of health insurance, and no prior history of stroke or congestive heart failure were included (N = 5,777). Women were recruited between 1993 and 1998.MeasurementsMedication use was ascertained through a baseline inventory. Physical performance measures (timed 6-m walk, repeated chair stands in 15 seconds) and grip strength were assessed at baseline and follow-up Years 1, 3, and 6. Multivariable-adjusted linear repeated-measures models were adjusted for demographic and health characteristics.ResultsACE inhibitor use was associated with lower mean grip strength at baseline (22.40 kg, 95% confidence interval (CI) = 21.89-22.91 vs 23.18 kg, 95% CI 23.02-23.34; P = .005) and greater mean annual change in number of chair stands (-0.182, 95% CI -0.217 to -0.147 vs -0.145, 95% CI -0.156 to -0.133; P = .05) than nonuse. Statin use was not significantly associated with baseline measures or mean annual change for any outcome. A subgroup analysis suggested that statin use was associated with less mean annual change in chair stands (P = .006) in the oldest women.ConclusionThese results do not support an association between statin or ACE inhibitor use and slower decline in physical performance or muscle strength and thus do not support the use of these medications for preserving functional status in older adults.

ObjectivesTo examine the associations between depressive symptoms, antidepressant use, and duration of use with incident frailty 3 years later in nonfrail women aged 65 and older.DesignSecondary analysis of the Women's Health Initiative Observational Study (WHI-OS), a prospective cohort study.SettingWHI-OS was conducted in 40 U.S. clinical centers.ParticipantsWomen aged 65 to 79, not frail at baseline.MeasurementsAntidepressant use was assessed through medication container inspection at baseline. Four groups were created according to baseline use and Burnam depression screen (range 0-1, 0.06 cutoff): antidepressant nonusers without depressive symptoms (reference group), antidepressant nonusers with depressive symptoms, antidepressant users without depressive symptoms, and antidepressant users with depressive symptoms. Frailty components included slowness or weakness, exhaustion, low physical activity, and unintended weight loss, ascertained through self-report and physical measurements at baseline and Year 3.ResultsOf 27,652 women at baseline, 1,350 (4.9%) were antidepressant users and 1,794 (6.5%) were categorized as depressed. At Year 3, 4,125 (14.9%) were frail. All groups had a greater risk of incident frailty than the reference group. Odds ratios (ORs) ranged from 1.73 (95% confidence interval (CI) = 1.41-2.12) in antidepressant users who were not depressed to 3.63 in antidepressant users who were depressed (95% CI = 2.37-5.55). All durations of use were associated with incident frailty (3 years OR = 1.60, 95% CI = 1.20-2.14).ConclusionIn older adult women, depressive symptoms and antidepressant use were associated with frailty after 3 years of follow-up.

BackgroundProton 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]).MethodsThis 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.ResultsDuring 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.ConclusionUse of PPIs was not associated with hip fractures but was modestly associated with clinical spine, forearm or wrist, and total fractures.

BackgroundThe immune and blood coagulation systems have been implicated in the pathophysiology of the geriatric syndrome of frailty, but limited prospective data examining the relationship of clotting/inflammation biomarkers to risk of incident frailty exist.MethodsThis prospective analysis was derived from a nested case-control study within the Women's Health Initiative. Among women 65 to 79 years free of frailty at enrollment, we randomly selected 900 incident cases from those developing frailty within 3 years; 900 non-frail controls were individually matched on age, ethnicity, and blood collection date. Biomarkers assessed for risk of incident frailty included fibrinogen, factor VIII, D-dimer, C-reactive protein, interleukin-6, and tissue plasminogen activator (t-PA).ResultsWhen examined by quartiles in multivariable adjusted models, higher D-dimer and t-PA levels were each associated with increased risk of frailty (P trend = .04). Relative to the lowest quartile, the odds ratios for frailty compared with the upper quartile were 1.52 (95% confidence interval, 1.05-2.22) for t-PA and 1.57 (95% confidence interval, 1.11-2.22) for D-dimer. For women having high t-PA and high D-dimer compared with women having lower levels of both biomarkers, the odds of frailty was 2.20 (1.29-3.75). There was little evidence for association between coagulation factor VIII, fibrinogen, C-reactive protein, or interleukin-6 levels and incident frailty.ConclusionThis prospective analysis supports the role of markers of fibrin turnover and fibrinolysis as independent predictors of incident frailty in postmenopausal women.

ObjectivesTo examine the associations between current use, duration, and potency of angiotensin-converting enzyme (ACE) inhibitors and incident frailty in women aged 65 and older who were not frail at baseline.DesignData were from the Women's Health Initiative Observational Study (WHI-OS), a prospective study conducted at 40 U.S. clinical centers.ParticipantsWomen aged 65 to 79 at baseline who were not frail (N=27,378).MeasurementsCurrent ACE inhibitor use was ascertained through direct inspection of medicine containers at baseline. Components of frailty were self-reported low physical function or impaired walking, exhaustion, low physical activity, and unintended weight. Frailty was ascertained through self-reported and physical measurements data at baseline and 3-year clinic contacts.ResultsBy the 3-year follow-up, 3,950 (14.4%) women had developed frailty. Current ACE inhibitor use had no association with incident frailty (multivariate adjusted odds ratio=0.96, 95% confidence interval=0.82-1.13). Duration and potency of ACE inhibitor use were also not significantly associated with incident frailty. A similar pattern of results was observed when incident cardiovascular disease events were studied as a separate outcome or when the sample was restricted to subjects with hypertension.ConclusionOverall, incidence of frailty was similar in current ACE inhibitor users and nonusers.

BackgroundInflammatory biomarkers have shown consistent associations with disability and frailty in older adults. Statin medications may reduce the incidence the frailty because of their anti-inflammatory effects. This study examines associations between current use, duration, and potency of statin medications and incident frailty in initially nonfrail women 65 years old or older.MethodsThe authors conducted a prospective analysis of data from the Women's Health Initiative Observational Study (WHI-OS) conducted at 40 clinical centers in the United States. Eligible women were nonfrail and 65-79 years old at baseline (n = 25,378). Current statin use at baseline was ascertained through direct inspection of medicine containers during clinic visits. Frailty was ascertained through self-reported indicators and physical measurements at baseline and 3-year clinic contacts. Components of frailty included self-reported low physical function, exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models were used to adjust for covariates predicting incident frailty.ResultsAmong the 25,378 eligible women, 3453 (13.6%) developed frailty by the 3-year follow-up contact. Current statin use had no association with incident frailty (multivariate-adjusted odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.85-1.16). Duration and potency of statin use were also not significantly associated with incident frailty. Among low potency statin users, longer duration of use was associated with reduced risk of frailty (p for trend =.02). A similar pattern of results was observed when frailty was studied in the absence of intervening, incident cardiovascular events.ConclusionsOverall, incidence of frailty was similar in current statin users and nonusers.

BACKGROUND: Polypharmacy is common among older people and may be associated with adverse drug events (ADEs) and poor health outcomes. Pharmacists are well-positioned to reduce polypharmacy and potentially inappropriate medications. OBJECTIVE: The objective of this narrative review was to summarize the results from randomized-controlled trials that evaluated pharmacist-led interventions with the goal or effect to deprescribe medications in older individuals. DATA SOURCES: We searched Medline, Embase, CINAHL Complete, APA PsycInfo, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials. DATA SYNTHESIS: Of the 25 studies included, the interventions were conducted in nursing facilities (n = 8), outpatient/community dwellings (n = 8), or community pharmacies (n = 9). Interventions were categorized as comprehensive medication reviews (n = 10), comprehensive medication reviews with pharmacist follow-up (n = 11), and educational interventions provided to patients and/or providers (n = 4). Pharmacist-led interventions had a beneficial effect on 22 out of 32 total medication-related outcomes (eg, number of medications, potentially inappropriate medications, or discontinuation). Most (n = 18) studies reported no evidence of an effect for other outcomes such as health care use, mortality, patient-centered outcomes (falls, cognition, function, quality of life), and ADEs. DISCUSSION: Interventions led to improvement in 69% of the medication-related outcomes examined across study settings. Five studies measured ADEs with none accounting for adverse drug-withdrawal events. Large well-designed studies that are powered to find an effect on patient-centered outcomes are needed. CONCLUSION: Pharmacist-led interventions had a significant beneficial effect on medication-related outcomes. There was little evidence of benefit on other outcomes. [ABSTRACT FROM AUTHOR]

ObjectivesTo determine whether benzodiazepine use is associated with incident disability in mobility and activities of daily living (ADLs) in older individuals.DesignA prospective cohort study.SettingFour sites of the Established Populations for Epidemiologic Studies of the Elderly.ParticipantsThis study included 9,093 subjects (aged > or =65) who were not disabled in mobility or ADLs at baseline.MeasurementsMobility disability was defined as inability to walk half a mile or climb one flight of stairs. ADL disability was defined as inability to perform one or more basic ADLs (bathing, eating, dressing, transferring from a bed to a chair, using the toilet, or walking across a small room). Trained interviewers assessed outcomes annually.ResultsAt baseline, 5.5% of subjects reported benzodiazepine use. In multivariable models, benzodiazepine users were 1.23 times as likely as nonusers (95% confidence interval (CI) = 1.09-1.39) to develop mobility disability and 1.28 times as likely (95% CI = 1.09-1.52) to develop ADL disability. Risk for incident mobility was increased with short- (hazard ratio (HR) = 1.27, 95% CI = 1.08-1.50) and long-acting benzodiazepines (HR = 1.20, 95% CI = 1.03-1.39) and no use. Risk for ADL disability was greater with short- (HR = 1.58, 95% CI = 1.25-2.01) but not long-acting (HR = 1.11, 95% CI = 0.89-1.39) agents than for no use.ConclusionOlder adults taking benzodiazepines have a greater risk for incident mobility and ADL disability. Use of short-acting agents does not appear to confer any safety benefits over long-acting agents.

ObjectivesTo 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.DesignProspective study, the Women's Health Initiative Observational Study.SettingForty U.S. clinical centers.ParticipantsForty thousand six hundred fifty-seven women aged 65 to 79 at baseline.MeasurementsComponents 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.ResultsBaseline 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.ConclusionThese 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.

OBJECTIVES:To determine whether benzodiazepine use in older women increased the risk of decline in physical function. DESIGN:A four-year prospective cohort study. SETTING:The communities of Iowa and Washington counties, Iowa. PARTICIPANTS:Eight hundred eighty-five women aged 70 and older who had completed physical performance tests in 1988 and 1992. MEASUREMENTS:Benzodiazepine use was determined during in-home interviews and classified by dose, duration, indication for use, and half-life. Physical performance tests included an assessment of standing balance, walking speed (8-foot distance), and repeated chair raises. RESULTS:Ninety (10.2%) reported benzodiazepine use at baseline. After adjustment for baseline physical performance score and potential confounders, benzodiazepine use was associated with a greater decline in physical performance over 4 years than nonuse (beta=-1.16; standard error (SE)=0.25; Por=3 years) was related to decline (beta=-1.65; SE=0.34; Por=3 years). These findings highlight the importance of using benzodiazepines at the lowest effective dose for a limited duration in older women.

ObjectivesThe 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.MethodsAuthors 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.ResultsDuring 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.ConclusionsNew 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.

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.

ObjectivesThis 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.DesignCohort study with follow-up of 4 to 5 years.SettingA health maintenance organization (HMO) in western Washington.ParticipantsIndividuals aged 65 and older from a random sample of HMO enrollees who participated in a health promotion intervention trial (n = 1,519).MeasurementsBenzodiazepine 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.ResultsBenzodiazepine 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.ConclusionsA 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.