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.

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.

Background It is currently unknown whether 6 months of supervised treadmill exercise has a durable benefit on 6-minute walk performance, even after exercise is completed, in people with peripheral artery disease. Methods and Results A total of 156 participants with peripheral artery disease were randomized to 1 of 3 groups: supervised treadmill exercise, supervised resistance training, or attention control. Participants received supervised sessions during months 1 to 6 and telephone contact during months 6 to 12. Primary outcomes were change in 6-minute walk distance and short physical performance battery at 6-month follow-up and have been reported previously. Secondary outcomes were change in 6-minute walk and short physical performance battery at 12-month follow-up and are reported here. A group of 134 participants (86%) completed the 12-month follow-up. At 6-month follow-up, compared with control, 6-minute walk distance improved in the treadmill exercise group (+36.1 m, 95% CI =13.9-58.3, P=0.001). Between 6- and 12-month follow-up, 6-minute walk distance significantly declined (-28.6 m, 95% CI=-52.6 to -4.5, P=0.020) and physical activity declined -272 activity units (95% CI =-546 to +2, P=0.052) in the treadmill exercise group compared with controls. At 12-month follow-up, 6 months after completing supervised treadmill exercise, change in 6-minute walk distance was not different between the treadmill exercise and control groups (+7.5, 95% CI =-17.5 to +32.6, P=0.56). There were no differences in short physical performance battery change between either exercise group and control at 6-month or 12-month follow-up. Conclusions A 6-month supervised treadmill exercise intervention that improved 6-minute walk distance at 6-month follow-up did not have persistent benefit at 12-month follow-up. These results do not support a durable benefit of supervised treadmill exercise in peripheral artery disease. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Identifier: NCT 00106327.

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; P<.001). The use of higher-than-recommended dose was related to decline (beta=-2.26; SE=0.47; P<.001), and use of lower doses was not (beta=-0.53; SE=0.46; P=.246). Long-term use (>or=3 years) was related to decline (beta=-1.65; SE=0.34; P<.001), whereas recent and past use were not. Similar results were obtained when restricting the sample to those without disability at baseline. CONCLUSION:This study provides evidence that older women who used benzodiazepines were at risk for decline in physical performance. Subgroup analyses indicated that risk was greater with use of higher-than-recommended doses or for long duration (>or=3 years). These findings highlight the importance of using benzodiazepines at the lowest effective dose for a limited duration in older women.

Objectives

To determine whether benzodiazepine use is associated with incident disability in mobility and activities of daily living (ADLs) in older individuals.

Design

A prospective cohort study.

Setting

Four sites of the Established Populations for Epidemiologic Studies of the Elderly.

Participants

This study included 9,093 subjects (aged > or =65) who were not disabled in mobility or ADLs at baseline.

Measurements

Mobility 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.

Results

At 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.

Conclusion

Older 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.

Background

We compared the incidence of depression, defined by a Geriatric Depression Score (GDS) ≥6, between people with versus without peripheral artery disease (PAD). We determined whether depressive symptoms were associated with increased mortality in people with and without PAD.

Methods and results

Nine hundred and fifty-one PAD patients and 478 non-PAD patients were recruited from Chicago medical centers and followed prospectively. At baseline and annually, participants completed the GDS (0-15 scale, score ≥6=depression) and 6-minute walk. Cause of death was confirmed with death certificates. The prevalence of a GDS ≥6 at baseline was 186/951 (19.6%) among PAD versus 63/478 (13.2%) among non-PAD participants (P=0.003). During a mean follow-up of 2.7±1.2 years, 122/712 (17.1%) of participants with PAD versus 51/403 (12.7%) without PAD developed a GDS ≥6 (P=0.047). Adjusting for age, sex, race, comorbidities, and other confounders, PAD participants had an increased rate of developing a GDS ≥6 compared to non-PAD participants (hazard ratio=1.54 (95% CI=1.05-2.25, P=0.026). This association was not statistically significant after adjusting for 6-minute walk (P=0.258). Among PAD participants, a baseline GDS ≥6 was associated with increased all-cause mortality, adjusting for confounders (hazard ratio=1.57, 95% CI=1.12-2.21, P=0.009). This association was not significant after adjusting for 6-minute walk (P=0.224).

Conclusions

People with PAD have a higher incidence of depressive symptoms than people without PAD. In PAD, depressive symptoms are associated with increased all-cause and cardiovascular mortality. These associations are explained in part by poorer 6-minute walk among people with PAD and among depressed people with PAD, respectively.

Background In people with lower-extremity peripheral artery disease, the effects of exercise on patient-reported outcomes remain unclear. Methods and Results Four hundred four people with peripheral artery disease in 3 clinical trials were randomized to exercise (N=205) or a control group (N=199) and completed the 6-minute walk and the Walking Impairment Questionnaire distance score (score 0-100, 100=best) at baseline and 6-month follow-up. Compared with the control group, exercise improved 6-minute walk distance by +39.8 m (95% CI, 26.8-52.8, P<0.001) and the Walking Impairment Questionnaire distance score by +7.3 (95% CI, 2.4-12.1, P=0.003). In all, 2828 individual Walking Impairment Questionnaire distance score questions were completed at baseline and follow-up. Among participants who perceived no change in ability to walk 1 or more distances between baseline and follow-up, 6-minute walk improved in the exercise group and declined in the control group (+26.8 versus -6.5 m, P<0.001). Among participants who perceived that their walking ability worsened for 1 or more distances between baseline and follow-up, the 6-minute walk improved in the exercise group and declined in the control group (+18.4 versus -27.3 m, P<0.001). Among participants who reported worsening calf symptoms at follow-up, the exercise group improved and the control group declined (+28.9 versus -12.5 m, P<0.01). Conclusions In 3 randomized trials, exercise significantly improved the 6-minute walk distance in people with peripheral artery disease, but many participants randomized to exercise reported no change or decline in walking ability. These findings suggest a significant discrepancy in objectively measured walking improvement relative to perceived walking improvement in people with peripheral artery disease. Registration Information clinicaltrials.gov. Identifiers: NCT00106327, NCT01408901.

Background Among people with lower extremity peripheral artery disease, obesity is associated with faster functional decline than normal weight. The association of weight loss with functional decline in peripheral artery disease is unknown. Methods and Results Adults with an ankle-brachial index <0.90 were identified from Chicago-area hospitals in 2002-2004. Weight and 6-minute walk distance were measured annually. Weight change categories were weight loss or gain (≥5 pounds/year at ≥1 visit) or stable (weight change <5 pounds at each visit). Participants reported whether weight loss was "intentional" or "unintentional." Calf muscle area was measured with computed tomography every 2 years. Associations of weight change with changes in calf muscle area and 6-minute walk distance were analyzed using mixed-effects models and adjusted for age, body mass index, ankle-brachial index, physical activity, and other confounders. Among 389 participants, mean ankle-brachial index was 0.63±0.16, mean age was 74.5±7.8, and mean body mass index was 28.1±5.1 kg/m². Over 3.23±1.37 years, muscle area declined more in adults with intentional weight loss versus stable or gain (pair-wise comparisons, P<0.001). Intentional weight loss was associated with less annual decline in 6-minute walk distance than weight gain (intentional loss, 3.7 m; stable, -14.0 m; gain, -28.5 m; unintentional loss, -20.8 m; pair-wise comparison intentional loss versus gain, P=0.003). Conclusions Despite a greater loss of calf muscle area, adults with peripheral artery disease who intentionally lost ≥5 pounds experienced less functional decline than those who gained weight. A randomized trial is needed to establish whether benefits of weight loss in peripheral artery disease outweigh potential adverse effects.

Objective

The 6-minute walk test is a common outcome measure in clinical trials of people with lower extremity peripheral artery disease (PAD). However, what constitutes a meaningful change in the 6-minute walk distance has not been well defined for people with PAD. The present study related the change in the 6-minute walk distance to the degree of participant-reported improvement or decline in the 6-minute walk distance to define a meaningful change in the 6-minute walk distance for those with PAD.

Methods

Participants with PAD from three observational longitudinal studies completed the walking impairment questionnaire (WIQ) distance score and 6-minute walk at baseline and 1 year later. The WIQ distance score measures participants' perceived difficulty walking seven different distances without stopping (ranging from walking around the home to walking 5 blocks) on a 0 to 4 Likert scale, with 0 representing an inability to walk the distance and 4 representing no difficulty. The mean changes in the 6-minute walk distance corresponding to the participants' report of no change, 1-unit change, or 2-unit change, respectively, in the Likert scale score between the baseline and 1-year follow-up measures were calculated for each WIQ distance.

Results

A total of 777 participants with PAD (mean age, 71.2 ± 8.8 years; mean baseline 6-minute walk distance, 350.1 ± 118.1 meters) completed 5439 questions about their difficulty walking each WIQ distance at baseline and follow-up. Participants with PAD who reported no change in their difficulty in walking each WIQ distance between baseline and follow-up had a decline of 7.2 meters (95% confidence interval [CI], -11.6 to -2.8 meters) in the 6-minute walk test. Relative to those reporting no change in difficulty walking, the participants reporting 1- and 2-point improvements in walking ability showed 6-minute walk distance improvements of 7.8 meters (95% CI, -0.3 to 15.9 meters) and 20.1 meters (95% CI, 1.1-39.2 meters), respectively. Relative to those reporting no change in walking difficulty, those reporting 1- and 2-point declines in perceived walking difficulty showed declines of -11.2 meters (95% CI, -19.0 to -3.4 meters) and -23.8 meters (95% CI, -37.4 to -10.3 meters) in the 6-minute walk distance.

Conclusions

Among people with PAD, ∼8- and ∼20-meter improvements in the 6-minute walk distance represent small and large improvements in walking ability, respectively. People with PAD who reported no change in their ability to walk distances over 1 year simultaneously declined by a mean of 7 meters in the 6-minute walk test. These findings will be useful for interpreting the results from randomized trials of interventions to improve the walking performance of people with PAD.

Functional impairment, functional decline, and mobility loss are major public health problems in people with lower extremity peripheral artery disease (PAD). Few medical therapies significantly improve walking performance in PAD. We describe methods for the PROgenitor cell release Plus Exercise to improve functionaL performance in PAD (PROPEL) Study, a randomized controlled clinical trial designed to determine whether granulocyte-macrophage colony stimulating factor (GM-CSF) combined with supervised treadmill walking exercise improves six-minute walk distance more than GM-CSF alone, more than supervised treadmill exercise alone, and more than placebo plus attention control in participants with PAD, respectively. PROPEL Study participants are randomized to one of four arms in a 2 by 2 factorial design. The four study arms are GM-CSF plus supervised treadmill exercise, GM-CSF plus attention control, placebo plus supervised exercise therapy, or placebo plus attention control. The primary outcome is change in six-minute walk distance at 12-week follow-up. Secondary outcomes include change in brachial artery flow-mediated dilation (FMD), change in maximal treadmill walking time, and change in circulating CD34+ cells at 12-week follow-up. Outcomes are also measured at six-week and six-month follow-up. Results of the PROPEL Study will have important implications for understanding mechanisms of improving walking performance and preventing mobility loss in the large and growing number of men and women with PAD.