Background.

We wished to determine if a marker of endothelial dysfunction/activation soluble vascular cell adhesion molecule (s-VCAM)—was related to functional status and mortality in community-dwelling older adults independent of the known effects of markers of inflammation and coagulation.

Methods.

Data came from the third and fourth in-person waves of the Duke Established Populations for Epidemiologic Studies of the Elderly. Participants (aged ≥ 71 years) had participated in a blood draw (N = 1,551) from which concentrations of s-VCAM, interleukin-6, and D-dimer were determined. Information was gathered in-person on demographics, health behaviors, chronic health conditions, and functional status (Katz, Rosow–Breslau, Nagi). Death was determined through the National Death Index. Multivariable regression analysis was used to examine the adjusted association of s-VCAM with functional status; Cox proportional hazards models ascertained hazard of mortality.

Results.

Controlled analyses indicated that cross-sectionally, but not longitudinally (4 years later), greater s-VCAM concentrations were associated with poorer function as measured by the Katz and Rosow–Breslau scales (p < .05 for both), independent of interleukin-6 and D-dimer. In controlled analyses, s-VCAM (p = .002), D-dimer (p = .008), and interleukin-6 (p = .01) were independently related to 4-year mortality; 1 SD increase in log concentration conferred 1.2-, 1.1-, and 1.2-fold increases in mortality, respectively. The greatest hazard of mortality was observed within the first year after measurement. s-VCAM concentrations were not predictive of 15-year mortality.

Conclusions.

Independent of inflammation and coagulation markers, endothelial dysfunction serves as a marker of, and potentially contributes causally to, poor function and death in community-dwelling older adults.

Background

Despite a pressing and well-documented need for better sharing of information on clinical trials data quality assurance methods, many research organizations remain reluctant to publish descriptions of and results from their internal auditing and quality assessment methods.

Purpose

We present findings from a review of a decade of internal data quality audits performed at the Duke Clinical Research Institute, a large academic research organization that conducts data management for a diverse array of clinical studies, both academic and industry-sponsored. In so doing, we hope to stimulate discussions that could benefit the wider clinical research enterprise by providing insight into methods of optimizing data collection and cleaning, ultimately helping patients and furthering essential research.

Methods

We present our audit methodologies, including sampling methods, audit logistics, sample sizes, counting rules used for error rate calculations, and characteristics of audited trials. We also present database error rates as computed according to two analytical methods, which we address in detail, and discuss the advantages and drawbacks of two auditing methods used during this ten-year period.

Results

Our review of the DCRI audit program indicates that higher data quality may be achieved from a series of small audits throughout the trial rather than through a single large database audit at database lock. We found that error rates trended upward from year to year in the period characterized by traditional audits performed at database lock (1997–2000), but consistently trended downward after periodic statistical process control type audits were instituted (2001–2006). These increases in data quality were also associated with cost savings in auditing, estimated at 1000 hours per year, or the efforts of one-half of a full time equivalent (FTE).

Limitations

Our findings are drawn from retrospective analyses and are not the result of controlled experiments, and may therefore be subject to unanticipated confounding. In addition, the scope and type of audits we examine here are specific to our institution, and our results may not be broadly generalizable.

Conclusions

Use of statistical process control methodologies may afford advantages over more traditional auditing methods, and further research will be necessary to confirm the reliability and usability of such techniques. We believe that open and candid discussion of data quality assurance issues among academic and clinical research organizations will ultimately benefit the entire research community in the coming era of increased data sharing and re-use.

Background and Aims

Comorbid cognitive impairment is common among visually impaired older adults. This study investigated whether baseline cognitive status predicts functional trajectories among older adults in low vision rehabilitation (LVR) for macular disease.

Methods

The Telephone Interview for Cognitive Status – modified (TICS-m) was administered to macular disease patients aged ≥ 65 years receiving outpatient LVR. Mixed models assessed the rate of change in instrumental activities of daily living and visual function measures over a mean follow-up of 115 days.

Results

Of 91 participants, 17 (18.7%) had cognitive impairment (TICS-m score ≤ 27) and 23 (25.3%) had marginal impairment (TICS-m scores 28 to 30). Controlling for age and gender, baseline cognitive status did not predict most functional outcomes. However, participants with marginal cognitive impairment experienced worse functional trajectories in ability to prepare meals (p=0.03).and activities that require distance vision (p = 0.05).

Conclusion

Patients with mild to moderate cognitive impairment should not be excluded from LVR, but programs should be prepared to detect and accommodate a range of cognitive ability.

Individuals diagnosed with impaired glucose tolerance (i.e., prediabetes) are at increased risk for developing diabetes. We proposed a clinical trial with a novel adaptive randomization designed to examine the impact of a home-based physical activity (PA) counseling intervention on metabolic risk in prediabetic elders. This manuscript details the lessons learned relative to recruitment, study design, and implementation of a 12-month randomized controlled PA counseling trial. A detailed discussion on how we responded to unforeseen challenges is provided. A total of 302 older patients with prediabetes were randomly assigned to either PA counseling or usual care. A novel adaptive design that reallocated counseling intensity based on self-report of adherence to PA was initiated but revised when rates of non-response were lower than projected. This study presents baseline participant characteristics and discusses unwelcome adaptations to a highly innovative study design to increase PA and enhance glucose metabolism when the best-laid plans went awry.

Background.

Metabolic profiling might provide insight into the biologic underpinnings of disability in older adults.

Methods.

A targeted mass spectrometry–based platform was used to identify and quantify 45 plasma acylcarnitines in 77 older men with a mean age of 79 years and average body mass index of 28.4 kg/m2. To control for type I error inherent in a test of multiple analytes, principal components analysis was employed to reduce the acylcarnitines from 45 separate metabolites, into a single “acylcarnitine factor.” We then tested for an association between this acylcarnitine factor and multiple indices of physical performance and self-reported function.

Results.

The acylcarnitine factor accounted for 40% of the total variance in 45 acylcarnitines. Of the metabolites analyzed, those that contributed most to our one-factor solution were even-numbered medium and long-chain species with side chains containing 10–18 carbons (factor loadings ≥0.70). Odd-numbered chain species, in contrast, had factor loadings 0.50 or less. Acylcarnitine factor scores were inversely related to physical performance as measured by the Short Physical Performance Battery total score, two of its three component scores (gait and chair stands Short Physical Performance Battery), and usual and maximal gait speeds (ρ = −0.324, −0.348, −0.309, −0.241, and −0.254, respectively; p < .05).

Conclusions.

Higher acylcarnitine factor scores were associated with lower levels of objectively measured physical performance in this group of older, largely overweight men. Metabolic profiles of rodents exhibiting lipid-induced mitochondrial dysfunction show a similar phenotypic predominance of medium- and long-chain acylcarnitines.

Background

Objective measures are needed to quantify dietary adherence during caloric restriction (CR) while participants are free-living. One method to monitor adherence is to compare observed weight loss to the expected weight loss during a prescribed level of CR. Normograms (graphs) of expected weight loss can be created from mathematical modeling of weight change to a given level of CR, conditional on the individual's set of baseline characteristics. These normograms can then be used by counselors to help the participant adhere to their caloric target.

Purpose

(1) To develop models of weight loss over a year of caloric restriction given demographics (age and sex), and well defined measurements of of Body Mass Index, total daily energy expenditure (TDEE) and %CR. (2) To utilize these models to develop normograms given level of caloric restriction, and measures of these variables.

Methods

Seventy-seven individuals completing a 6-12 month CR intervention (CALERIE) had body weight and body composition measured frequently. Energy intake (and %CR) was estimated from TDEE (by doubly labeled water) and body composition (by DXA) at baseline and months 1, 3, 6 and 12. Body weight was modeled to determine the predictors and distribution of the expected trajectory of percent weight change over 12 months of caloric restriction.

Results

As expected, CR was related to change in body weight. Controlling for time-varying measures, initially simple models of the functional form indicated that the trajectory of percent weight change was predicted by a non-linear function of initial age, TDEE, %CR, and sex. Using these estimates, normograms for the weight change expected during a 25%CR were developed. Our model estimates that the mean weight loss (% change from baseline weight) for an individual adherent to a 25% CR regimen is -10.9±6.3% for females and -13.9±6.4% for men after 12 months.

Limitations

There are several limitations. Sample sizes are small (n=77), and, by design, the protocols, including prescribed CR, for the interventions differed by site, and not all subjects completed a year of follow-up. In addition, the inclusion of subjects by age and initial BMI was constricted so that these results may no generalize to other older, obese subjects.

Conclusions

The trajectory of percent weight change during CR interventions in the presence of well measured covariates can be modeled using simple non-linear functions, and is related level of CR, the percent change in TDEE, gender, and age. Displayed on a normogram, individually tailored trajectories can be used by counselors and participants to monitor weight loss and adherence to a CR regimen.

Objective

To describe the relationship between lower extremity physical performance, self-reported mobility difficulty and self-reported use of compensatory strategies for mobility inside the home.

Design

Cross sectional, exploratory study.

Setting

Community-dwelling elders.

Participants

Disabled, cognitively-intact women ≥65 years old (n=1002), from the Women’s Health and Aging Study I.

Interventions

N/A

Main Outcome Measures

Compensatory strategy (CS) scale: No CS, Behavioral Modifications (BM) only, Durable Medical Equipment (DME) with or without use of behavioral modifications, and any use of Human Help (HH); and 3 dichotomous CS measures: Any CS (vs none); DME±HH (vs BM only, among users of any CS); Any HH (vs DME only, among users of any DME/HH).

Results

Self reported mobility difficulty and physical performance were significantly correlated with one another (r=−0.57, p<0.0001) and with the CS Scale (r=0.51, p<0.001 and r=−0.54, p<0.0001 respectively). Sequential logistic regressions showed self reported difficulty and physical performance were significant independent predictors of each category of CS. For the Any CS and DME±HH models, the Odds Ratio (OR) for self reported difficulty decreased by ~50% when physical performance was included in the model, compared to difficulty alone (18.0 to 8.6 and 7.3 to 3.8 respectively), but both physical performance and difficulty remained significant predictors (p<0.0001). The effects of covariates differed for the various CS categories, with some covariates having independent relationships to compensatory strategy, and others appearing to have moderating or mediating effects on the relationship of self reported difficulty or physical performance to CS.

Conclusions

Physical performance, self reported difficulty, health conditions, and contextual factors have complex effects on the way elders carry out mobility inside the home.

Background.

Older women experience disability more commonly than their male peers. This disparity may be due, in part, to sex-based differences in the prevalence or the disabling effects of common medical conditions. The objectives of this analysis were to (a) quantify the extent to which excess disability in women is explained by higher prevalence of selected medical conditions and (b) evaluate whether the same conditions have differing effects on disability in men and women.

Methods.

We analyzed cross-sectional data from 5,888 community-dwelling older men and women. Disability was defined as difficulty with greater than or equal to one activity of daily living. Thirteen medical conditions were assessed by self-report, testing, or record review.

Results.

Controlling for age, race, education, and marital status, women were more likely to experience disability (odds ratio = 1.70, 95% confidence interval = 1.36–2.11). Higher prevalence of arthritis and obesity in women explained 30.2% and 12.9%, respectively, of the sex-based difference in disability rates, whereas male prevalent diseases like vascular conditions and emphysema narrowed the disability gap. Women with arthritis, hearing problems, coronary artery disease, congestive heart failure, stroke, and claudication were more likely to exhibit disability compared with men with the same conditions (p < .001).

Conclusions.

Efforts to lessen sex-based inequality in disability should focus on reducing the prevalence of arthritis and obesity. Future generations may see greater functional disparity if rates of vascular disease and emphysema rise among women. Several conditions were more often associated with disability in women, suggesting additional sex-based differences in the disablement process.

Background.

To ascertain accuracy of self-reported height, weight (and hence body mass index) in African American and white women and men older than 70 years of age.

Method.

The sample consisted of cognitively intact participants at the third in-person wave (1992–1993) of the Duke Established Populations for Epidemiologic Studies of the Elderly (age 71 and older, N = 1761; residents of five adjacent counties, one urban, four rural). During in-person, in-home interviews using trained interviewers, height and weight were self-reported (and measured later in the same visit using a standardized protocol), and information were obtained on race, sex, and age.

Results.

Accuracy of self-reported height and weight was high (intraclass correlation coefficient 0.85 and 0.97, respectively) but differed as a function of race and age. On average, all groups overestimated their height; whereas (non-Hispanic) white men and women underestimated their weight, African Americans overestimated their weight. Overestimation of height and weight was more marked in persons 85 years and older. Specificity for overweight (body mass index [kg/m2] ≥ 25) and obesity (body mass index ≥ 30) ranged from 0.90 to 0.99 for African Americans and whites, but sensitivity was better for African Americans (overweight: 0.81, obesity: 0.89), than for whites (0.66 and 0.57, respectively).

Conclusions.

Height and weight self-reported by African Americans and whites over the age of 70 can be used in epidemiological studies, with greater caution needed for self-reports of whites, and of persons 85 years of age or older.

Abstract

Background

The specific health benefits of meeting physical activity guidelines are unclear in older adults. We examined the association between meeting, not meeting, or change in status of meeting physical activity guidelines through walking and the 5-year incidence of metabolic syndrome in older adults.

Methods

A total of 1,863 Health, Aging, and Body Composition (Health ABC) Study participants aged 70–79 were followed for 5 years (1997–1998 to 2002–2003). Four walking groups were created based on self-report during years 1 and 6: Sustained low (Year 1, <150 min/week, and year 6, <150 min/week), decreased (year 1, >150 min/week, and year 6, <150 min/week), increased (year 1, <150 min/week, and year 6, >150 min/week), and sustained high (year 1, >150 min/week, and year 6, >150 min/week). Based on the Adult Treatment Panel III (ATP III) panel guidelines, the metabolic syndrome criterion was having three of five factors: Large waist circumference, elevated blood pressure, triglycerides, blood glucose, and low high-density lipoprotein (HDL) levels.

Results

Compared to the sustained low group, the sustained high group had a 39% reduction in odds of incident metabolic syndrome [adjusted odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.40–0.93], and a significantly lower likelihood of developing the number of metabolic syndrome risk factors that the sustained low group developed over 5 years (β = −0.16, P = 0.04).

Conclusions

Meeting or exceeding the physical activity guidelines via walking significantly reduced the odds of incident metabolic syndrome and onset of new metabolic syndrome components in older adults. This protective association was found only in individuals who sustained high levels of walking for physical activity.

Objectives

Physical activity (PA) has potential to improve outcomes in both arthritis and diabetes, but these conditions are rarely examined together. Our objective was to explore whether persons with arthritis alone or those with both arthritis and diabetes could improve amounts of PA with a home-based counseling intervention.

Methods

As part of the Veterans LIFE Study, veterans ages 70–92 were randomized to usual care or a twelve month PA counseling program. Arthritis and diabetes were assessed via self-report. Mixed models were used to compare trajectories for minutes of endurance and strength training PA for persons with no arthritis (n=85), arthritis (n=178), and arthritis plus diabetes (n=84).

Results

Recipients of PA counseling increased minutes of PA per week independent of disease status (treatment arm by time interaction P<0.05 for both; endurance training time P=0.0006 and strength training time P<0.0001). Although PA was lower at each wave among persons with arthritis, and even more so among persons with arthritis plus diabetes, the presence of these conditions did not significantly influence response to the intervention (Arthritis/Diabetes group X time interactions P>0.05 for both outcomes) as each group experienced a nearly two-fold or more increase in PA.

Conclusions

A home-based PA intervention was effective in increasing minutes of weekly moderate intensity endurance and strength training PA in older veterans, even among those with arthritis or arthritis plus diabetes. This program may serve as a useful model to improve outcomes in older persons with these pervasive diseases.

Background

The specific health benefits of meeting physical activity guidelines are unclear in older adults. We examined the association between meeting, not meeting, or change in status of meeting physical activity guidelines through walking and the 5-year incidence of metabolic syndrome in older adults.

Methods

A total of 1,863 Health, Aging, and Body Composition (Health ABC) Study participants aged 70–79 were followed for 5 years (1997–1998 to 2002–2003). Four walking groups were created based on self-report during years 1 and 6: Sustained low (Year 1, <150 min/week, and year 6, <150 min/week), decreased (year 1, >150 min/week, and year 6, <150 min/week), increased (year 1, <150 min/week, and year 6, >150 min/week), and sustained high (year 1, >150 min/week, and year 6, >150 min/week). Based on the Adult Treatment Panel III (ATP III) panel guidelines, the metabolic syndrome criterion was having three of five factors: Large waist circumference, elevated blood pressure, triglycerides, blood glucose, and low high-density lipoprotein (HDL) levels.

Results

Compared to the sustained low group, the sustained high group had a 39% reduction in odds of incident metabolic syndrome [adjusted odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.40–0.93], and a significantly lower likelihood of developing the number of metabolic syndrome risk factors that the sustained low group developed over 5 years (β = −0.16, P = 0.04).

Conclusions

Meeting or exceeding the physical activity guidelines via walking significantly reduced the odds of incident metabolic syndrome and onset of new metabolic syndrome components in older adults. This protective association was found only in individuals who sustained high levels of walking for physical activity.

Objectives

To explore 1) Whether arthritis associates with poorer self-efficacy and motivation for, and participation in, two specific types of physical activity (PA): Endurance training (ET) and strength training (ST), and 2) If the added burden of diabetes contributes to a further reduction in these PA determinants and types.

Methods

Self-efficacy and motivation for exercise and minutes per week of ET and ST were measured in 347 older Veterans enrolled in a home-based PA counseling intervention. Regression analyses were used to compare high versus low self-efficacy and motivation and PA minutes in persons without arthritis, with arthritis alone, and with arthritis plus diabetes.

Results

Persons with arthritis alone reported lower self-efficacy for ET and ST than those without arthritis (Odds ratio[OR]ET 0.71 (0.39,1.20); ORST 0.69 (0.39,1.20)). A further reduction in self-efficacy for these two types of PA was observed for those with both arthritis and diabetes (ORET 0.65 (0.44,0.92); ORST 0.64 (0.44,0.93); trend P<0.001). There was no trend towards a reduction in motivation for PA in those with arthritis alone or arthritis and diabetes. Persons with arthritis exhibited higher motivation for ET than those without arthritis (ORET 1.85 (1.12,3.33). There were no significant differences between the three groups in minutes of ET (P=0.93), but persons with arthritis plus diabetes reported significantly less ST compared to individuals with arthritis only (P=0.03).

Conclusions

Despite reduced self-efficacy for ET and ST and less ST in older persons with arthritis, motivation for both PA types remains high, even in the presence of diabetes.

The prevalence of comorbid cognitive impairment among older adults referred to LVR for macular disease is unknown. We performed cognitive testing on 101 adults aged 65 years or older with macular disease who were referred to The Duke LVR Clinic between September 2007 and March 2008. Scores on the telephone interview for cognitive status-modified (TICS-m) ranged from 7 to 44, with 18.8% of scores below an established cutoff for cognitive impairment (≤ 27) and an additional 27.7% of scores considered marginal (28-30). On letter fluency, 46% of participants scored at least 1 × S.D. below the mean for their age, gender, race, and education level, and 18% of participants scored at least 2 × S.D. below their demographic mean. On logical memory, 26% of participants scored at least 1 × S.D. below the mean for their age group and race and 6% scored at least 2 × S.D. below their demographic mean. High prevalence of cognitive impairment, with particular difficulty in verbal fluency and verbal memory, may compromise the success of low vision rehabilitation interventions among macular disease patients. Additional work is needed to develop strategies to maximize function in older adults with this common comorbidity.

Context

Research on “vascular depression” has used two approaches to subtype late life depression (LLD) based on executive dysfunction or white matter hyperintensity (WMH) severity.

Objective

Evaluate the relationship of neuropsychological performance and WMH to clinical response in LLD.

Design

2-site prospective nonrandomized controlled trial.

Setting

Outpatient clinics at Washington University and Duke University.

Participants

217 subjects age ≥ 60 met DSM-IV criteria for major depression, scored ≥ 20 (MADRS), received vascular risk factor (VRF) scores, neuropsychological testing and MRI scan; were excluded for cognitive impairment or severe medical disorders. Fazekas rating was conducted to grade WMH lesions.

Intervention

12 weeks of sertraline treatment, titrated by clinical response.

Outcome

Montgomery-Asberg Depression Rating Scale (MADRS) score over time.

Results

Baseline neuropsychological factor scores correlated negatively with baseline Fazekas scores. A mixed model examined effects of predictor variables on MADRS scores over time. Baseline episodic memory (p = 0.002); language (p = 0.007); working memory (p = 0.01); processing speed (p = 0.0001); executive function factor scores (p = 0.002), and categorical Fazekas ratings (p = 0.049) predicted MADRS scores, controlling for age, education, age of onset and race. Controlling for baseline MADRS scores these factors remained significant predictors of decrease in MADRS scores except working memory and Fazekas ratings. 33% of subjects achieved remission (MADRS ≤ 7). Remitters differed from non-remitters in baseline cognitive processing speed, executive function, language, episodic memory and VRF scores.

Discussion

Comprehensive neuropsychological function and WMH severity predicted MADRS scores prospectively over a 12 week SSRI treatment course in LLD. Baseline neuropsychological function differentiated remitters from non-remitters and predicted time to remission in a proportional hazards model. Predictor variables correlated highly with VRF severity. These data support the vascular depression hypothesis and highlight the importance of linking subtypes based on neuropsychological function and white matter integrity.

Objective

Research has shown an association between depression and functional limitations in older adults. Our aim was to explore the latent traits of trajectories of limitations in mobility and instrumental activities of daily living (IADL) tasks in a sample of older adults diagnosed with major depression.

Methods

Participants were 248 patients enrolled in a naturalistic depression treatment study. Mobility/IADL tasks included walking ¼ mile, going up/down stairs, getting around the neighborhood, shopping, handling money, taking care of children, cleaning house, preparing meals, and doing yardwork/gardening. Latent class trajectory analysis was used to identify classes of mobility/IADL function over a 4-year period. Class membership was then used to predict functional status over time.

Results

Using time as the only predictor, three latent class trajectories were identified: 1) Patients with few mobility/IADL limitations (42%), 2) Patients with considerable mobility/IADL limitations (37%), and 3) Patients with basically no limitations (21%). The classes differed primarily in their initial functional status, with some immediate improvement followed by no further change for patients in classes 1 and 2, and a stable course for patients in class 3. In a repeated measures mixed model controlling for potential confounders, class was a significant predictor of functional status. The effect of baseline depression score, cognitive status, self-perceived health, and sex on mobility/IADL score differed by class.

Conclusions

These findings show systematic variability in functional status over time among older patients with major depression, indicating that a single trajectory may not reflect the pattern for all patients.

This study assessed the sustained effect of a physical activity (PA) counseling intervention on PA one year after intervention, predictors of sustained PA participation, and three classes of post-intervention PA trajectories (improvers, maintainers, and decliners) in 238 older Veterans. Declines in minutes of PA from 12 to 24 months were observed for both the treatment and control arms of the study. PA at 12 months was the strongest predictor of post-intervention changes in PA. To our surprise, those who took up the intervention and increased PA levels the most, had significant declines in post-intervention PA. Analysis of the three post-intervention PA trajectories demonstrated that the maintenance group actually reflected a group of nonresponders to the intervention who had more comorbidities, lower self-efficacy, and worse physical function than the improvers or decliners. Results suggest that behavioral counseling/support must be ongoing to promote maintenance. Strategies to promote PA appropriately to subgroups of individuals are needed.

Background

Clinical trial networks were created to provide a sustaining infrastructure for the conduct of multisite clinical trials. As such, they must withstand changes in membership. Centralization of infrastructure including knowledge management, portfolio management, information management, process automation, work policies, and procedures in clinical research networks facilitates consistency and ultimately research.

Purpose

In 2005, the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) transitioned from a distributed data management model to a centralized informatics infrastructure to support the network’s trial activities and administration. We describe the centralized informatics infrastructure and discuss our challenges to inform others considering such an endeavor.

Methods

During the migration of a clinical trial network from a decentralized to a centralized data center model, descriptive data were captured and are presented here to assess the impact of centralization.

Results

We present the framework for the informatics infrastructure and evaluative metrics. The network has decreased the time from last patient-last visit to database lock from an average of 7.6 months to 2.8 months. The average database error rate decreased from 0.8% to 0.2%, with a corresponding decrease in the interquartile range from 0.04%–1.0% before centralization to 0.01%–0.27% after centralization. Centralization has provided the CTN with integrated trial status reporting and the first standards-based public data share. A preliminary cost-benefit analysis showed a 50% reduction in data management cost per study participant over the life of a trial.

Limitations

A single clinical trial network comprising addiction researchers and community treatment programs was assessed. The findings may not be applicable to other research settings.

Conclusions

The identified informatics components provide the information and infrastructure needed for our clinical trial network. Post centralization data management operations are more efficient and less costly, with higher data quality.

Background:

Digital infrared thermal imaging is a means of measuring the heat radiated from the skin surface. Our goal was to develop and assess the reproducibility of serial infrared measurements of the knee and to assess the association of knee temperature by region of interest with radiographic severity of knee Osteoarthritis (rOA).

Methods:

A total of 30 women (15 Cases with symptomatic knee OA and 15 age-matched Controls without knee pain or knee OA) participated in this study. Infrared imaging was performed with a Meditherm Med2000™ Pro infrared camera. The reproducibility of infrared imaging of the knee was evaluated through determination of intraclass correlation coefficients (ICCs) for temperature measurements from two images performed 6 months apart in Controls whose knee status was not expected to change. The average cutaneous temperature for each of five knee regions of interest was extracted using WinTes software. Knee x-rays were scored for severity of rOA based on the global Kellgren-Lawrence grading scale.

Results:

The knee infrared thermal imaging procedure used here demonstrated long-term reproducibility with high ICCs (0.50–0.72 for the various regions of interest) in Controls. Cutaneous temperature of the patella (knee cap) yielded a significant correlation with severity of knee rOA (R = 0.594, P = 0.02).

Conclusion:

The skin temperature of the patellar region correlated with x-ray severity of knee OA. This method of infrared knee imaging is reliable and as an objective measure of a sign of inflammation, temperature, indicates an interrelationship of inflammation and structural knee rOA damage.

Background

Depressive symptoms above screening thresholds have been shown to predict functional decline in older adults. Less is known about the impact of subthreshold depression, and whether more symptoms confer significantly greater risk compared to fewer symptoms.

Methods

Using data from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE) collected over ten years, we employed repeated measures mixed models to predict functional change by depression status at the prior (index) in-person interview. Depressive symptoms were measured using a modified version of the Center for Epidemiologic Studies-Depression (CES-D). Subthreshold depression was operationalized as 6–8 symptoms and CES-D defined depression as 9–20 symptoms the previous week. Three domains of functional status were assessed at the subsequent inperson interview: limitations in basic activities of daily living (ADLs), instrumental ADLs (IADLs) and mobility.

Results

Controlling for race, sex, age, education, marital status, cognitive status, health status, self-perceived health, perceived social support, and functional status at the index interview, having 6+ depressive symptoms predicted an increase of 0.12 IADL limitations 3–4 years later (p=0.03). The incremental effect of CES-D defined depression (9+ symptoms compared to 6–8 symptoms) was not significant, suggesting that the effect of more symptomatic depression did not add to that of subthreshold depression. CES-D score modeled as a continuous variable predicted functional change for all domains, but the relationship was not linear, supporting a possible threshold effect.

Conclusions

The relationship between depressive symptoms and functional change is complex, not necessarily linear, and may vary by tasks assessed.

Background

Medication underutilization, or the omission of a potentially beneficial medication indicated for disease management, is common among older adults but poorly understood.

Objectives

The aims of this work were to assess the prevalence of medication underuse and to determine whether polypharmacy or comorbidity was associated with medication underuse among physically frail older veterans transitioning from the hospital to the community.

Methods

This was a cross-sectional analysis of patients who were discharged from 11 US veterans’ hospitals to outpatient care, based on data from the Geriatric Evaluation and Management Drug Study, a substudy of the Veterans Affairs Cooperative Study of geriatric evaluation and management. Patients were enrolled between August 31, 1995, and January 31, 1999. To qualify for the study, patients had to be aged ≥65 years, hospitalized in a medical or surgical ward for >48 hours, and meet ≥2 of the following criteria: moderate functional disability; recent cerebrovascular accident with residual neurological deficit; history of ≥1 fall in the previous 3 months; documented difficulty with walking (ie, requiring personal assistance or equipment), not including preadmission use of a wheelchair with ability to transfer to and from chair independently; malnutrition (admission serum albumin of 3.5 g/dL, <80% of ideal body weight, or recent ≥15-lb weight loss reported in admission history); dementia; depression; documented diagnosis of new fracture or revision needed of older fracture; unplanned admission within 3 months of previous admission; and prolonged bed rest. Clinical pharmacist/physician pairs reviewed medical records and medication lists and independently applied the Assessment of Underutilization (AOU) index to determine omissions of indicated medications. Discordances in index ratings were resolved during clinical consensus conferences. The primary outcome measure was the percentage of patients with ≥1 medication omission detected by the AOU. Multivariable logistic regression analyses identified factors associated with underuse.

Results

A total of 384 patients were included in the study. The majority (53.6%) were between the ages of 65 and 74 years, and the mean (SD) Charlson comorbidity index was 2.44 (1.93). Overall, 374 patients (97.4%) were men and 274 (71.4%) were white. Medication undertreatment occurred in 238 participants (62.0%). Diseases of the circulatory, endocrine/nutritional, musculoskeletal, and respiratory systems were the most commonly undertreated conditions. The indicated medications most likely to be omitted were nitrates for those with a history of myocardial infarction, multivitamins in those with malnutrition, and inhaled anticholinergics for chronic obstructive airways disease. Statistically significant factors associated with medication underuse included limitations in activities of daily living (adjusted odds ratio [AOR], 2.17 [95% CI, 1.27–3.71]; P = 0.01), being white (AOR, 1.70 [95% CI, 1.06–2.71]; P = 0.03), and Charlson comorbidity index (AOR, 1.13 for each 1-point increase [95% CI, 1.00–1.27]; P = 0.04). Discharge from a general medicine service as opposed to a surgical service was associated with lower risk of medication underuse (AOR, 0.61 [95% CI, 0.38–0.98]; P = 0.04).

Conclusions

Medication underuse was relatively common in this study. Patients with greater comorbidity, but not polypharmacy, had increased odds of undertreatment.

We previously found that vascular smooth muscle actin (SMA) is reduced in the brains of patients with late stage Alzheimer disease (AD) compared to brains of non-demented, neuropathologically normal subjects. To assess the pathogenetic significance and disease specificity of this finding, we studied 3 additional patient groups: non-demented subjects without significant AD type pathology (“Normal”, n = 20); non-demented subjects with frequent senile plaques at autopsy (“Preclinical AD”, n = 20); and subjects with frontotemporal dementia, (“FTD”, n = 10). The groups were matched for gender and age with those previously reported; SMA immunohistochemistry and image analysis were performed as previously described. Surprisingly, SMA expression in arachnoid, cerebral cortex and white matter arterioles was greater in the Preclinical AD group than in the Normal and FTD groups. The plaques were not associated with amyloid angiopathy or other vascular disease in this group. SMA expression in the brains of the Normal group was intermediate between the Preclinical AD and FTD groups. All 3 groups exhibited much greater SMA expression than in our previous report. The presence of frequent plaques and increased arteriolar SMA expression in the brains of non-demented subjects suggest that increased SMA expression might represent a physiologic response to neurodegeneration that could prevent or delay overt expression dementia in AD.

BACKGROUND

Slow gait is predictive of adverse health outcomes and increased health service utilization. Physical activity counseling (PAC) may enhance mobility among elders. Primary care settings are appropriate for PAC because most older adults see their primary care physician annually. Innovative use of automated telephone messaging facilitates physician counseling.

OBJECTIVE

To determine the effects of multi-component PAC promoting physical activity (PA) guidelines on gait speed and related measures of PA and function in older veterans.

DESIGN, SETTING, AND PARTICIPANTS

Randomized controlled trial of 398 male veterans, ages 70 and over receiving primary care at the Veterans’ Affairs Medical Center of Durham, N.C.

INTERVENTION

Twelve months of usual care (UC) or multi-component PAC consisting of baseline in-person and biweekly then monthly telephone counseling by a lifestyle counselor, one-time clinical endorsement of PA and monthly automated telephone messaging by primary care provider, and quarterly tailored mailings of progress in PA.

MEASUREMENTS

Gait speed (usual and rapid), self-reported PA, function and disability at baseline, 3, 6 and 12 months.

RESULTS

Although no between-group differences were noted for usual gait speed, rapid gait speed improved significantly more for the PAC group (1.56 (0.41) m/s to 1.68 (0.44) m/s) compared to UC (1.57 (0.40) m/sec to 1.59 (0.42) m/sec, p = 0.04). Minutes of moderate/vigorous PA increased significantly in the PAC group (from a mean (SD) 57.1 (99.3) min/wk to 126.6 (142.9) min/week) compared to the UC group (from 60.2 (116.1) to 69.6 (116.1) min/wk, p < 0.001). Changes in other functional/disability outcomes were small.

CONCLUSIONS

In this group of older male veterans, multi-component PA significantly improved rapid gait and PA. Translation from increased PA to overall functioning was not observed. Integration with primary care was successful.

Background

It is unclear if physical activity (PA) can prevent or reverse frailty. We examined different doses and types of PA and their association with the onset and severity of frailty.

Methods

Health, Aging and Body Composition (Health ABC) study participants (N = 2,964) were followed for 5 years, with frailty defined as a gait speed of less than 0.60 m/s and/or inability to rise from a chair without using one's arms. Individuals with one impairment were considered moderately frail and those with both severely frail. We examined PA doses of volume and intensity, activity types (eg, lifestyle vs exercise activities), and their associations with incident frailty and transition to severe frailty in those who became frail.

Results

Adjusted models indicated that sedentary individuals had significantly increased odds of developing frailty compared with the exercise active group (adjusted odds ratio [OR] = 1.45; 95% confidence interval [CI]: 1.04–2.01), whereas the lifestyle active did not. Number of diagnoses was the strongest predictor of incident frailty. In those who became frail during follow-up (n = 410), there was evidence that the sedentary (adjusted OR = 2.80; 95% CI: 0.98–8.02) and lifestyle active (adjusted OR = 2.81; 95% CI: 1.22–6.43) groups were more likely to have worsening frailty over time.

Conclusions

Despite the strong relationship seen between comorbid conditions and onset of frailty, this observational study suggests that participation in self-selected exercise activities is independently associated with delaying the onset and the progression of frailty. Regular exercise should be further examined as a potential factor in frailty prevention for older adults.