Publications by authors named "Todd M Manini"

198 Publications

Differences in Health-Related Quality of Life Among Adults with a Potential Dihydropyridine Calcium Channel Blocker-Loop Diuretic Prescribing Cascade.

Drugs Aging 2021 Jun 7. Epub 2021 Jun 7.

Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, 1225 Center Dr, Gainesville, FL, 32610, USA.

Background: Dihydropyridine calcium channel blockers (DH CCBs) are commonly used for hypertension in older adults. However, loop diuretics can be inappropriately added to treat DH CCB-induced edema, putting individuals at increased risk for adverse events and potential decreases in quality of life.

Methods: We conducted a cross-sectional analysis using United States Medical Expenditure Panel Survey (MEPS) data from 2003 to 2015. Adults aged ≥ 55 years without congestive heart failure, nephrotic syndrome, chronic kidney disease, renal failure, and cirrhosis who had consecutive rounds of DH CCB use (round 1 and 2 or round 3 and 4) and completed the self-administered questionnaire (SAQ) were included. Patients initiated on loop diuretics in round 2 or 4 were compared to those not initiated. Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were analyzed using multivariable linear regression models.

Results: Among 5,458,467 DH CCB users (weighted), 3.4% of individuals were identified with new loop diuretic use (185,130 weighted). After adjusting for covariates, DH CCB plus loop diuretic use was associated with a PCS score 3.12 units lower (95% confidence interval - 5.40 to - 0.83; p = 0.008) than DH CCB use alone. We observed no significant difference in MCS score (p = 0.160) among DH CCB plus loop diuretic users compared to DH CCB users alone.

Conclusions: New loop diuretic use was associated with lower physical functioning among DH CCB users. These findings suggest that this potential prescribing cascade may result in both significant and clinically meaningful decreases in health-related quality of life. It is important for clinicians to avoid or intervene on this inappropriate prescribing cascade when possible.
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http://dx.doi.org/10.1007/s40266-021-00868-0DOI Listing
June 2021

Age Differences in Estimating Physical Activity by Wrist Accelerometry Using Machine Learning.

Sensors (Basel) 2021 May 12;21(10). Epub 2021 May 12.

Department of Aging and Geriatric Research, College of Medicine, University of Florida, Gainesville, FL 32610, USA.

Accelerometer-based fitness trackers and smartwatches are proliferating with incessant attention towards health tracking. Despite their growing popularity, accurately measuring hallmark measures of physical activities has yet to be accomplished in adults of all ages. In this work, we evaluated the performance of four machine learning models: decision tree, random forest, extreme gradient boosting (XGBoost) and least absolute shrinkage and selection operator (LASSO), to estimate the hallmark measures of physical activities in young (20-50 years), middle-aged (50-70 years], and older adults (70-89 years]. Our models were built to recognize physical activity types, recognize physical activity intensities, estimate energy expenditure (EE) and recognize individual physical activities using wrist-worn tri-axial accelerometer data (33 activities per participant) from a large sample of participants ( = 253, 62% women, aged 20-89 years old). Results showed that the machine learning models were quite accurate at recognizing physical activity type and intensity and estimating energy expenditure. However, models performed less optimally when recognizing individual physical activities. F1-Scores derived from XGBoost's models were high for sedentary (0.955-0.973), locomotion (0.942-0.964) and lifestyle (0.913-0.949) activity types with no apparent difference across age groups. Low (0.919-0.947), light (0.813-0.828) and moderate (0.846-0.875) physical activity intensities were also recognized accurately. The root mean square error range for EE was approximately 1 equivalent of resting EE [0.835-1.009 METs]. Generally, random forest and XGBoost models outperformed other models. In conclusion, machine learning models to label physical activity types, activity intensity and energy expenditure are accurate and there are minimal differences in their performance across young, middle-aged and older adults.
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http://dx.doi.org/10.3390/s21103352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150764PMC
May 2021

Study Protocol Modeling Evoked Pain in Older African Americans with Knee Osteoarthritis.

Nurs Res 2021 May 5. Epub 2021 May 5.

University of Florida College of Nursing, Gainesville, FL University of Connecticut School of Nursing, Storrs, CT University of Florida College of Medicine, Gainesville, FL University of Florida College of Dentistry, Gainesville, FL.

Background: African American (AA) older adults with knee osteoarthritis experience more severe chronic pain and advanced physical disability. One of the most prominent stimuli that provoke knee pain is movement. Research suggests that compared to White Americans, AAs report significantly higher movement-evoked pain (MEP) in the knee. However, little is known about the biopsychosocial-behavioral mechanisms underlying MEP.

Objectives: To present a study protocol to (a) characterize the biopsychosocial-behavioral mechanisms that predict MEP in AAs with knee osteoarthritis, and (b) develop a targeted, mechanism-based, self-management intervention to reduce MEP and maximize movement.

Methods: An observational, mixed-methods cohort study will enroll 90 AA/Black adults (ages 55-90) to understand intra-individual and interindividual effects on MEP. Participants will complete assessments of MEP, function and gait, biopsychosocial-behavioral questionnaires, quantitative sensory testing, and 7-day ecological momentary assessments of pain and related symptoms. For the qualitative phase, focus groups will be conducted to co-construct a mechanism-based, pain self-management intervention.

Results: We will develop phenotypes of MEP based on biopsychosocial-behavioral predictors and correlate measures of MEP with function. Our central hypothesis is that higher levels of MEP will predict lower self-reported function and poorer performance on functional tasks and multiple biopsychosocial and behavioral factors will be associated with MEP and function. Predictors may serve as risk or protective factors for MEP and physical function. In targeting the biopsychosocial-behavioral mechanisms of MEP, we anticipate that older AAs may request that intervention components include culturally tailored self-management education, movement/physical activity training, treatment decision-making skills, coaching, spirituality, and social/kinship support.

Conclusion: Osteoarthritis is now the single most common cause of disability, mobility limitations, and persistent pain in older adults-especially AA older adults. To our knowledge, this will be the first study to systematically phenotype MEP in an older racial minority population with knee osteoarthritis and will be relevant for reducing knee pain and improving function.
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http://dx.doi.org/10.1097/NNR.0000000000000520DOI Listing
May 2021

The Effect of Sensor Placement and Number on Physical Activity Recognition and Energy Expenditure Estimation in Older Adults: Validation Study.

JMIR Mhealth Uhealth 2021 05 3;9(5):e23681. Epub 2021 May 3.

Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, United States.

Background: Research has shown the feasibility of human activity recognition using wearable accelerometer devices. Different studies have used varying numbers and placements for data collection using sensors.

Objective: This study aims to compare accuracy performance between multiple and variable placements of accelerometer devices in categorizing the type of physical activity and corresponding energy expenditure in older adults.

Methods: In total, 93 participants (mean age 72.2 years, SD 7.1) completed a total of 32 activities of daily life in a laboratory setting. Activities were classified as sedentary versus nonsedentary, locomotion versus nonlocomotion, and lifestyle versus nonlifestyle activities (eg, leisure walk vs computer work). A portable metabolic unit was worn during each activity to measure metabolic equivalents (METs). Accelerometers were placed on 5 different body positions: wrist, hip, ankle, upper arm, and thigh. Accelerometer data from each body position and combinations of positions were used to develop random forest models to assess activity category recognition accuracy and MET estimation.

Results: Model performance for both MET estimation and activity category recognition were strengthened with the use of additional accelerometer devices. However, a single accelerometer on the ankle, upper arm, hip, thigh, or wrist had only a 0.03-0.09 MET increase in prediction error compared with wearing all 5 devices. Balanced accuracy showed similar trends with slight decreases in balanced accuracy for the detection of locomotion (balanced accuracy decrease range 0-0.01), sedentary (balanced accuracy decrease range 0.05-0.13), and lifestyle activities (balanced accuracy decrease range 0.04-0.08) compared with all 5 placements. The accuracy of recognizing activity categories increased with additional placements (accuracy decrease range 0.15-0.29). Notably, the hip was the best single body position for MET estimation and activity category recognition.

Conclusions: Additional accelerometer devices slightly enhance activity recognition accuracy and MET estimation in older adults. However, given the extra burden of wearing additional devices, single accelerometers with appropriate placement appear to be sufficient for estimating energy expenditure and activity category recognition in older adults.
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http://dx.doi.org/10.2196/23681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129874PMC
May 2021

Deep CHORES: Estimating Hallmark Measures of Physical Activity Using Deep Learning.

AMIA Annu Symp Proc 2020 25;2020:803-812. Epub 2021 Jan 25.

University of Florida, Gainesville, Florida, USA.

Wrist accelerometers for assessing hallmark measures of physical activity (PA) are rapidly growing with the advent of smartwatch technology. Given the growing popularity of wrist-worn accelerometers, there needs to be a rigorous evaluation for recognizing (PA) type and estimating energy expenditure (EE) across the lifespan. Participants (66% women, aged 20-89 yrs) performed a battery of 33 daily activities in a standardized laboratory setting while a tri-axial accelerometer collected data from the right wrist. A portable metabolic unit was worn to measure metabolic intensity. We built deep learning networks to extract spatial and temporal representations from the time-series data, and used them to recognize PA type and estimate EE. The deep learning models resulted in high performance; the F1 score was: 0.82, 0.81, and 95 for recognizing sedentary, locomotor, and lifestyle activities, respectively. The root mean square error was 1.1 (+/-0.13) for the estimation of EE.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075495PMC
June 2021

Sustained physical activity in peripheral artery disease: Associations with disease severity, functional performance, health-related quality of life, and subsequent serious adverse events in the LITE randomized clinical trial.

Vasc Med 2021 Apr 8:1358863X21989430. Epub 2021 Apr 8.

Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

This study investigated cross-sectional associations of peripheral artery disease (PAD) severity (defined by the ankle-brachial index (ABI)) and amounts of daily sustained physical activity (PA) (defined as > 100 activity counts per minute lasting 5 consecutive minutes or more). This study also investigated associations of amounts of daily sustained PA with 6-minute walk (6MW) distance and the Short Form-36 physical functioning domain (SF-36 PF) score in cross-sectional analyses and with serious adverse events (SAEs) in longitudinal analyses of people with PAD. PA was measured continuously for 10 days using a tri-axial accelerometer at baseline in 277 participants with PAD randomized to the LITE clinical trial. In regression analyses, each 0.15 lower ABI value was associated with a 5.67% decrease in the number of daily bouts of sustained PA (95% CI: 3.85-6.54; < 0.001). Every additional bout of sustained PA per day was associated with a 4.56-meter greater 6MW distance (95% CI: 2.67-6.46; < 0.0001), and a 0.81-point improvement in SF-36 PF score (95% CI: 0.34-1.28; < 0.001). Participants with values of daily bouts of sustained PA below the median had higher rates of SAEs during follow-up, compared to participants above the median (41% vs 24%; = 0.002). In conclusion, among participants with PAD, lower ABI values were associated with fewer bouts of daily sustained PA. A greater number of bouts of daily sustained PA were associated with better 6MW performance and SF-36 PF score, and, in longitudinal analyses, lower rates of SAEs.
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http://dx.doi.org/10.1177/1358863X21989430DOI Listing
April 2021

Elevated IL-6 and CRP levels are associated with incident self-reported major mobility disability: A pooled analysis of older adults with slow gait speed.

J Gerontol A Biol Sci Med Sci 2021 Apr 5. Epub 2021 Apr 5.

University of Florida, Gainesville, FL.

Background: Elevated Interleukine-6 (IL-6) and C-reactive protein (CRP) are associated with aging-related reductions in physical function, but little is known about their independent and combined relationships with major mobility disability (MMD), defined as the self-reported inability to walk a quarter-mile.

Methods: We estimated the absolute and relative effect of elevated baseline IL-6, CRP, and their combination on self-reported MMD risk among older adults (≥68 years; 59% female) with slow gait speed (<1.0m/s). Participants were MMD-free at baseline. IL-6 and CRP were assessed using a central laboratory. The study combined a cohort of community dwelling high-functioning older adults (Health ABC) with two trials of low-functioning adults at risk of MMD (LIFE-P, LIFE). Analyses utilized Poisson regression for absolute MMD incidence and proportional hazards models for relative risk.

Results: We found higher MMD risk per unit increase in log IL-6 [HR=1.26 (95% CI 1.13 to 1.41)]. IL-6 meeting pre-determined threshold considered to be high (>2.5 pg/mL) was similarly associated with higher risk of MMD [HR=1.31 (95% CI: 1.12 to 1.54)]. Elevated CRP (CRP >3.0 mg/L) was also associated with increased MMD risk [HR=1.38 (95% CI: 1.10 to 1.74)]. The CRP effect was more pronounced among participants with elevated IL-6 [HR=1.62 (95% CI: 1.12 to 2.33)] compared to lower IL-6 levels [HR=1.19 (95% CI: 0.85 to 1.66)].

Conclusions: High baseline IL-6 and CRP were associated with increased risk of MMD among older adults with slow gait speed. A combined biomarker model suggests CRP was associated with MMD when IL-6 was elevated.
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http://dx.doi.org/10.1093/gerona/glab093DOI Listing
April 2021

Evaluation of a Strength-Training Program on Clinical Outcomes in Older Adults.

JAMA 2021 03;325(11):1111

Ohio Musculoskeletal and Neurological Institute, Ohio University, Athens.

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http://dx.doi.org/10.1001/jama.2021.0298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148633PMC
March 2021

Ratings of Perceived Exertion during Walking: Predicting Major Mobility Disability and Effect of Structured Physical Activity in Mobility-Limited Older Adults.

J Gerontol A Biol Sci Med Sci 2021 Feb 15. Epub 2021 Feb 15.

Department of Aging and Geriatric Research, University of Florida.

Background: This study evaluated the association between ratings of perceived exertion (RPE) of walking and major mobility disability (MMD), as well as their transitions in response to a physical activity (PA) compared to a health education (HE) program.

Methods: Older adults (n=1633) at risk for mobility impairment were randomized to structured PA or HE programs. During a 400m walk, participants rated exertion as "light" or "hard". An MMD event was defined as the inability to walk 400m. MMD events and RPE values were assessed every 6-months for an average of 2.6 years.

Results: Participants rating their exertion as "hard" had a nearly 3-fold higher risk of MMD compared with those rating their exertion as "light" (HR: 2.61, 95%CI: 2.19-3.11). The association held after adjusting for disease conditions, depression, cognitive function and walking speed (HR: 2.24, 95%CI: 1.87-2.69). The PA group was 25% more likely to transition from "light" to "hard" RPE than the HE group (1.25, 1.05-1.49). Additionally, the PA group was 27% (0.73, 0.55 - 0.97) less likely to transition from a "hard" RPE to inability to walk 400m and was more likely to recover their ability to walk 400m by transitioning to a "hard" RPE (2.10, 1.39-3.17) than the HE group.

Conclusions: Older adults rating "hard" effort during a standardized walk test were at increased risk of subsequent MMD. A structured PA program enabled walking recovery, but was more likely to increase transition from "light" to "hard" effort, which may reflect greater capacity to perform the test.
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http://dx.doi.org/10.1093/gerona/glab036DOI Listing
February 2021

The Temporal Relationship Between Ecological Pain and Life-Space Mobility in Older Adults With Knee Osteoarthritis: A Smartwatch-Based Demonstration Study.

JMIR Mhealth Uhealth 2021 01 13;9(1):e19609. Epub 2021 Jan 13.

Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, United States.

Background: Older adults who experience pain are more likely to reduce their community and life-space mobility (ie, the usual range of places in an environment in which a person engages). However, there is significant day-to-day variability in pain experiences that offer unique insights into the consequences on life-space mobility, which are not well understood. This variability is complex and cannot be captured with traditional recall-based pain surveys. As a solution, ecological momentary assessments record repeated pain experiences throughout the day in the natural environment.

Objective: The aim of this study was to examine the temporal association between ecological momentary assessments of pain and GPS metrics in older adults with symptomatic knee osteoarthritis by using a smartwatch platform called Real-time Online Assessment and Mobility Monitor.

Methods: Participants (n=19, mean 73.1 years, SD 4.8; female: 13/19, 68%; male: 6/19, 32%) wore a smartwatch for a mean period of 13.16 days (SD 2.94). Participants were prompted in their natural environment about their pain intensity (range 0-10) at random time windows in the morning, afternoon, and evening. GPS coordinates were collected at 15-minute intervals and aggregated each day into excursion, ellipsoid, clustering, and trip frequency features. Pain intensity ratings were averaged across time windows for each day. A random effects model was used to investigate the within and between-person effects.

Results: The daily mean pain intensities reported by participants ranged between 0 and 8 with 40% reporting intensities ≥2. The within-person associations between pain intensity and GPS features were more likely to be statistically significant than those observed between persons. Within-person pain intensity was significantly associated with excursion size, and others (excursion span, total distance, and ellipse major axis) showed a statistical trend (excursion span: P=.08; total distance: P=.07; ellipse major axis: P=.07). Each point increase in the mean pain intensity was associated with a 3.06 km decrease in excursion size, 2.89 km decrease in excursion span, 5.71 km decrease total distance travelled per day, 31.4 km decrease in ellipse area, 0.47 km decrease ellipse minor axis, and 3.64 km decrease in ellipse major axis. While not statistically significant, the point estimates for number of clusters (P=.73), frequency of trips (P=.81), and homestay (P=.15) were positively associated with pain intensity, and entropy (P=.99) was negatively associated with pain intensity.

Conclusions: In this demonstration study, higher intensity knee pain in older adults was associated with lower life-space mobility. Results demonstrate that a custom-designed smartwatch platform is effective at simultaneously collecting rich information about ecological pain and life-space mobility. Such smart tools are expected to be important for remote health interventions that harness the variability in pain symptoms while understanding their impact on life-space mobility.
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http://dx.doi.org/10.2196/19609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840291PMC
January 2021

Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults.

Cells 2020 12 2;9(12). Epub 2020 Dec 2.

Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL 32611, USA.

Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial-iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope (Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score ≤ 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores ≥ 11 (high-functioning, HF). The mtDNA relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability.
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http://dx.doi.org/10.3390/cells9122579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760001PMC
December 2020

Association between a Deficit Accumulation Frailty Index and Mobility Outcomes in Older Adults: Secondary Analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study.

J Clin Med 2020 Nov 22;9(11). Epub 2020 Nov 22.

Institute on Aging, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.

Frailty is a geriatric syndrome represented by susceptibility to precipitating health events and reduced functional reserve. Frailty can be difficult to measure in clinical practice and research. One approach to approximate frailty is based on a deficit accumulation approach, which assesses a larger number of less specific measures such as the presence of comorbidities, physical or cognitive assessments, and lab tests, and summarizes these as a frailty index. The objective of this study was to develop such an index using the Lifestyle Interventions and Independence for Elders (LIFE) Study and evaluate the validity of the frailty measure derived based on baseline information via its association with the primary outcomes of the trial, namely major mobility disability (MMD) and persistent MMD (pMMD). Further, this study aimed to evaluate the effectiveness of the physical activity intervention among participants based on their baseline frailty score. Subjects in the LIFE Study were evaluated at baseline for demographics, clinical history, and a battery of physical and cognitive functioning assessments. In total, 75 possible deficits were scored either as present (yes/no) or based on each score's quintiles for score-based assessments. The frailty index was measured as the total sum of deficits divided by the total number of possible deficits on a continuous scale between 0 and 100 (i.e., percent of deficits present). The frailty index was further divided into quintiles for comparison. A proportional hazards model was estimated for the MMD outcome controlling for other baseline information. A data driven approach was also used to determine relevant cut-offs in the frailty index where the trial intervention appeared to be modified. Among 1635 trial participants, the mean frailty index was 30.4 ± 6.6 and normally distributed. Over 2.5 years of average follow-up, 14.6%, 16.5%, 18.6%, 22.6%, and 27.6% of participants experienced MMD in quintiles 1-5, respectively. Each 1-unit increase in the frailty index increased the hazard of MMD by 4% (2-5%), and there was a nearly 2-fold increase in MMD between the highest and lowest frailty quintiles. Using log-rank criteria, a cut-point at the median was identified. Further, iterations tested for a frailty cut-off and indicated a subgroup beyond the 85th percentile wherein the physical activity intervention appeared to be no longer be effective. This internally derived deficit accumulation frailty index was uniquely able to identify individuals at higher risk of MMD and pMMD and showed that along the spectrum of frailty, the physical activity intervention remained effective for the majority of participants.
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http://dx.doi.org/10.3390/jcm9113757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700674PMC
November 2020

Survey-reported medication changes among older adults during the SARS-CoV-2 (COVID-19) pandemic.

Res Social Adm Pharm 2020 Nov 12. Epub 2020 Nov 12.

Institute on Aging, Division of Epidemiology and Data Science in Gerontology, Department of Aging and Geriatric Research, University of Florida College of Medicine, Gainesville, FL, USA. Electronic address:

Background: Speculation on benefits and harms of prescription, over-the-counter and complementary medications has been widespread during the SARS-CoV-2 (or COVID-19) pandemic. This community-based survey assessed self-reported changes in medications including those stopped, started, or if access had been impacted.

Methods: A survey was collected via Research Electronic Data Capture (REDCap). The survey was advertised in the community through social media, email lists, websites, and post-cards. Survey responses were collected between 5/21/2020 and 6/24/2020. Variables included demographic characteristics such as age, sex, race, marital status, education, employment, income, and community type. Questions related to medication changes included: "Have you started any medication due to COVID-19?", "Have you stopped any medication due to COVID-19?" and "Have you had issues getting your prescription medications?". Respondents aged 50 years or older were included.

Results: There were N = 1397 responses of which 1169 were older adults ≥50 years-old. Of these, 1141 responded to the medication changes survey questions and 28 had missing responses and were excluded from the survey sample for this analysis. Among these, 31 (2.7%) reported a medication change included 5 (0.4%) reported stopping a medication, 18 (1.6%) reported starting a medication, and 8 (0.7%) reported trouble obtaining medications. Medications started included mostly vitamins or other supplements including zinc (n = 9), vitamin C (6), and other supplements (3). Among prescription medications, antidepressants and anti-anxiety medications (4) were reported as well as aspirin (1), losartan (1), and low dose naltrexone (1). One respondent reported unidentified homeopathy. There were no significant differences between those with medication changes and those with none.

Conclusions: In this community-based survey sample of over one thousand older adults, only a small percentage (2.7%; n = 31) reported any changes to medications during the pandemic. As essential workers during this crisis, pharmacists have played a critical role in providing medication information and continued access.
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http://dx.doi.org/10.1016/j.sapharm.2020.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659512PMC
November 2020

Innovations in Geroscience to enhance mobility in older adults.

Exp Gerontol 2020 12 22;142:111123. Epub 2020 Oct 22.

University of Florida, Department of Psychology, 945 Center Drive, Gainesville, FL 32611, United States. Electronic address:

Aging is the primary risk factor for functional decline; thus, understanding and preventing disability among older adults has emerged as an important public health challenge of the 21st century. The science of gerontology - or geroscience - has the practical purpose of "adding life to the years." The overall goal of geroscience is to increase healthspan, which refers to extending the portion of the lifespan in which the individual experiences enjoyment, satisfaction, and wellness. An important facet of this goal is preserving mobility, defined as the ability to move independently. Despite this clear purpose, this has proven to be a challenging endeavor as mobility and function in later life are influenced by a complex interaction of factors across multiple domains. Moreover, findings over the past decade have highlighted the complexity of walking and how targeting multiple systems, including the brain and sensory organs, as well as the environment in which a person lives, can have a dramatic effect on an older person's mobility and function. For these reasons, behavioral interventions that incorporate complex walking tasks and other activities of daily living appear to be especially helpful for improving mobility function. Other pharmaceutical interventions, such as oxytocin, and complementary and alternative interventions, such as massage therapy, may enhance physical function both through direct effects on biological mechanisms related to mobility, as well as indirectly through modulation of cognitive and socioemotional processes. Thus, the purpose of the present review is to describe evolving interventional approaches to enhance mobility and maintain healthspan in the growing population of older adults in the United States and countries throughout the world. Such interventions are likely to be greatly assisted by technological advances and the widespread adoption of virtual communications during and after the COVID-19 era.
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http://dx.doi.org/10.1016/j.exger.2020.111123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581361PMC
December 2020

A Simulated Graphical Interface for Integrating Patient-Generated Health Data From Smartwatches With Electronic Health Records: Usability Study.

JMIR Hum Factors 2020 Oct 30;7(4):e19769. Epub 2020 Oct 30.

Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, United States.

Background: Wearable technology, such as smartwatches, can capture valuable patient-generated data and help inform patient care. Electronic health records provide logical and practical platforms for including such data, but it is necessary to evaluate the way the data are presented and visualized.

Objective: The aim of this study is to evaluate a graphical interface that displays patients' health data from smartwatches, mimicking the integration within the environment of electronic health records.

Methods: A total of 12 health care professionals evaluated a simulated interface using a usability scale questionnaire, testing the clarity of the interface, colors, usefulness of information, navigation, and readability of text.

Results: The interface was positively received, with 14 out of the 16 questions generating a score of 5 or greater among at least 75% of participants (9/12). On an 8-point Likert scale, the highest rated features of the interface were quick turnaround times (mean score 7.1), readability of the text (mean score 6.8), and use of terminology/abbreviations (mean score 6.75).

Conclusions: Collaborating with health care professionals to develop and refine a graphical interface for visualizing patients' health data from smartwatches revealed that the key elements of the interface were acceptable. The implementation of such data from smartwatches and other mobile devices within electronic health records should consider the opinions of key stakeholders as the development of this platform progresses.
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http://dx.doi.org/10.2196/19769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665942PMC
October 2020

Effect of a Multifactorial Fall Injury Prevention Intervention on Patient Well-Being: The STRIDE Study.

J Am Geriatr Soc 2021 Jan 9;69(1):173-179. Epub 2020 Oct 9.

Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background/objectives: In the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study, a multifactorial intervention was associated with a nonsignificant 8% reduction in time to first serious fall injury but a significant 10% reduction in time to first self-reported fall injury relative to enhanced usual care. The effect of the intervention on other outcomes important to patients has not yet been reported. We aimed to evaluate the effect of the intervention on patient well-being including concern about falling, anxiety, depression, physical function, and disability.

Design: Pragmatic cluster-randomized trial of 5,451 community-living persons at high risk for serious fall injuries.

Setting: A total of 86 primary care practices within 10 U.S. healthcare systems.

Participants: A random subsample of 743 persons aged 75 and older.

Measurements: The well-being measures, assessed at baseline, 12 months, and 24 months, included a modified version of the Fall Efficacy Scale, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression scales, and Late-Life Function and Disability Instrument.

Results: Participants in the intervention (n = 384) and control groups (n = 359) were comparable in age: mean (standard deviation) of 81.9 (4.7) versus 81.8 (5.0) years. Mean scores were similar between groups at 12 and 24 months for concern about falling, physical function, and disability, whereas the intervention group's mean scores on anxiety and depression were .7 points lower (i.e., better) at 12 months and .6 to .8 points lower at 24 months. For each of these outcomes, differences between the groups' adjusted least square mean changes from baseline to 12 and 24 months, respectively, were quantitatively small. The overall difference in means between groups over 2 years was statistically significant only for depression, favoring the intervention: -1.19 (99% confidence interval, -2.36 to -.02), with 3.5 points representing a minimally important difference.

Conclusions: STRIDE's multifactorial intervention to reduce fall injuries was not associated with clinically meaningful improvements in patient well-being.
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http://dx.doi.org/10.1111/jgs.16854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178516PMC
January 2021

Impact of Anticholinergic Medication Burden on Mobility and Falls in the Lifestyle Interventions for Elders (LIFE) Study.

J Clin Med 2020 Sep 16;9(9). Epub 2020 Sep 16.

Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, FL 32611, USA.

Anticholinergic cognitive burden (ACB) may be associated with detrimental effects on mobility and physical independence in older adults. We evaluated the incidence of major mobility disability (MMD), persistent major mobility disability (PMMD), and injurious falls among participants within the Lifestyle Interventions for Elders (LIFE) trial according to varied anticholinergic burden levels. Participants aged 70-89 years were randomized to a physical activity (PA) or successful aging (SA) intervention and evaluated by ACB medication use as a summed score of a previously developed ACB scale. Confounders included demographic characteristics, physical function, cognitive function, and fall history. Average participant follow-up was 2.6 years and included outcome assessment for MMD, PMMD, and injurious falls every six months. Adjusted proportional hazards models evaluated the independent effects of ACB scores as well as interaction effects with the intervention. Of the 1635 participants, 986 (60%) used ≥1 anticholinergic medication. Compared to those with no burden, participants with an ACB score of 1 demonstrated increased MMD (HR = 1.42 [1.13-1.78]), PMMD (HR = 1.53 [1.12-2.09]), and injurious falls (HR = 1.60 [1.10-2.32]). Results similar in magnitude were observed for all other ACB levels versus the no burden group. Stepwise dose-response comparisons between ACB groupings did not demonstrate significant differences in outcomes. Stratification by PA or SA interventions demonstrated few differences from the combined overall trial results. Compared to those not taking anticholinergic medications, participants taking anticholinergic medications generally demonstrated increased risk of MMD, PMMD, and injurious falls. Total anticholinergic burden was not associated with a stepwise dose-response relationship in mobility disability and may lack sensitivity to capture varied responses.
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http://dx.doi.org/10.3390/jcm9092989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564216PMC
September 2020

Relative contribution of muscle strength, lean mass, and lower extremity motor function in explaining between-person variance in mobility in older adults.

BMC Geriatr 2020 07 28;20(1):255. Epub 2020 Jul 28.

Ohio Musculoskeletal and Neurological Institute (OMNI), Ohio University, 250 Irvine Hall, 1, Athens, OH, 43147, USA.

Background: Approximately 35% of individuals > 70 years have mobility limitations. Historically, it was posited lean mass and muscle strength were major contributors to mobility limitations, but recent findings indicate lean mass and muscle strength only moderately explain mobility limitations. One likely reason is that lean mass and muscle strength do not necessarily incorporate measures globally reflective of motor function (defined as the ability to learn, or to demonstrate, the skillful and efficient assumption, maintenance, modification, and control of voluntary postures and movement patterns). In this study we determined the relative contribution of lean mass, muscle strength, and the four square step test, as an index of lower extremity motor function, in explaining between-participant variance in mobility tasks.

Methods: In community-dwelling older adults (N = 89; 67% women; mean 74.9 ± 6.7 years), we quantified grip and leg extension strength, total and regional lean mass, and time to complete the four square step test. Mobility was assessed via 6-min walk gait speed, stair climb power, 5x-chair rise time, and time to complete a complex functional task. Multifactorial linear regression modeling was used to determine the relative contribution (via semi-partial r) for indices of lean mass, indices of muscle strength, and the four square step test.

Results: When aggregated by sex, the four square step test explained 17-34% of the variance for all mobility tasks (p <  0.01). Muscle strength explained ~ 12% and ~ 7% of the variance in 6-min walk gait speed and 5x-chair rise time, respectively (p <  0.02). Lean mass explained 32% and ~ 4% of the variance in stair climb power and complex functional task time, respectively (p <  0.02). When disaggregated by sex, lean mass was a stronger predictor of mobility in men.

Conclusion: The four square step test is uniquely associated with multiple measures of mobility in older adults, suggesting lower extremity motor function is an important factor for mobility performance.

Trial Registration: NCT02505529 -2015/07/22.
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http://dx.doi.org/10.1186/s12877-020-01656-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385889PMC
July 2020

Trajectories of Short Physical Performance Battery Are Strongly Associated with Future Major Mobility Disability: Results from the LIFE Study.

J Clin Med 2020 Jul 22;9(8). Epub 2020 Jul 22.

Institute on Aging, Department of Aging and Geriatric Research, University of Florida College of Medicine, Gainesville, FL 32610, USA.

Short Physical Performance Battery (SPPB) assessment is a widely used measure of lower extremity function, strength, and balance. In the Lifestyles Interventions and Independence for Elders (LIFE) Study, baseline SPPB and changes throughout the trial were strongly associated with major mobility disability (MMD). This study further investigated this association by identifying trajectories of SPPB and evaluating the predictive validity of SPPB trajectories for future MMD. Participants ( = 1635) aged 70-89 years were randomized to a physical activity or health education intervention and assessed every 6 months for MMD. We used group-based trajectory models (GBTMs) to identify trajectories of a binary outcome for a decrease from baseline SPPB of ≥1. Multinomial logistic regression explored baseline factors associated with group membership. Survival analyses evaluated the association between trajectories with MMD. The GBTM identified a 3-group model which included a "No Decline" group (46.0%), "Late Decline" group (27.7%), and an "Early Decline" group (26.3%). Adjusting for all other baseline characteristics, group assignment during the previous follow-up visit was strongly associated with MMD at the subsequent period. Comparisons between groups showed a 2-to-3-fold increase in MMD comparing the "Late" to "No" decline group and a 4-to-5-fold increase in MMD comparing the "Early" to "No" decline group. Group membership and impact on MMD was not different between intervention arms. Group-based trajectories of SPPB scores identified distinct subgroups in LIFE Study participants. Using these group assignments in outcome models were highly associated with MMD. GBTMs have potential to identify and improve prediction of aging-related decline to better design and identify patients for interventions.
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http://dx.doi.org/10.3390/jcm9082332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465072PMC
July 2020

Identification of Sarcopenia Components That Discriminate Slow Walking Speed: A Pooled Data Analysis.

J Am Geriatr Soc 2020 07 7;68(7):1419-1428. Epub 2020 Jul 7.

California Pacific Medical Research Institute, San Francisco, California, USA.

Background: The Sarcopenia Definitions and Outcomes Consortium (SDOC) sought to identify cut points for muscle strength and body composition measures derived from dual-energy x-ray absorptiometry (DXA) that discriminate older adults with slow walking speed. This article presents the core analyses used to guide the SDOC position statements.

Design: Cross-sectional data analyses of pooled data.

Setting: University-based research assessment centers.

Participants: Community-dwelling men (n = 13,652) and women: (n = 5,115) with information on lean mass by DXA, grip strength (GR), and walking speed.

Measurements: Thirty-five candidate sarcopenia variables were entered into sex-stratified classification and regression tree (CART) models to agnostically choose variables and cut points that discriminate slow walkers (<0.80 m/s). Models with alternative walking speed outcomes were also evaluated (<0.60 and <1.0 m/s and walking speed treated continuously).

Results: CART models identified GR/body mass index (GRBMI) and GR/total body fat (GRTBF) as the primary discriminating variables for slowness in men and women, respectively. Men with GRBMI of 1.05 kg/kg/m or less were approximately four times more likely to be slow walkers than those with GRBMI of greater than 1.05 kg/kg/m . Women with GRTBF of less than 0.65 kg/kg were twice as likely to be slow walkers than women with GRTBF of 0.65 kg/kg or greater. Models with alternative walking speed outcomes selected only functions of GR as primary discriminators of slowness in both men and women. DXA-derived lean mass measures did not consistently discriminate slow walkers.

Conclusion: GR with and without adjustments for body size and composition consistently discriminated older adults with slowness. CART models did not select DXA-based lean mass as a primary discriminator of slowness. These results were presented to an SDOC Consensus Panel, who used them and other information to develop the SDOC Position Statements. J Am Geriatr Soc 68:1419-1428, 2020.
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http://dx.doi.org/10.1111/jgs.16524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018524PMC
July 2020

Reduced Neural Excitability and Activation Contribute to Clinically Meaningful Weakness in Older Adults.

J Gerontol A Biol Sci Med Sci 2021 Mar;76(4):692-702

Ohio Musculoskeletal and Neurological Institute (OMNI), Ohio University, Athens.

Background: Weakness is a risk factor for physical limitations and death in older adults (OAs). We sought to determine whether OAs with clinically meaningful leg extensor weakness exhibit differences in voluntary inactivation (VIA) and measures of corticospinal excitability when compared to young adults (YAs) and OAs without clinically meaningful weakness. We also sought to estimate the relative contribution of indices of neural excitability and thigh lean mass in explaining the between-subject variability in OAs leg extensor strength.

Methods: In 66 OAs (75.1 ± 7.0 years) and 20 YAs (22.0 ± 1.9 years), we quantified leg extensor strength, thigh lean mass, VIA, and motor evoked potential (MEP) amplitude and silent period (SP) duration. OAs were classified into weakness groups based on previously established strength/body weight (BW) cut points (Weak, Modestly Weak, or Not Weak).

Results: The OAs had 63% less strength/BW when compared to YAs. Weak OAs exhibited higher levels of leg extensor VIA than Not Weak OAs (14.2 ± 7.5% vs 6.1 ± 7.5%). Weak OAs exhibited 24% longer SPs compared to Not Weak OAs, although this difference was insignificant (p = .06). The Weak OAs MEPs were half the amplitude of the Not Weak OAs. Regression analysis indicated that MEP amplitude, SP duration, and thigh lean mass explained ~62% of the variance in strength, with the neural excitability variables explaining ~33% of the variance and thigh lean mass explaining ~29%.

Conclusion: These findings suggest that neurotherapeutic interventions targeting excitability could be a viable approach to increase muscle strength in order to reduce the risk of physical impairments in late life.
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http://dx.doi.org/10.1093/gerona/glaa157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011705PMC
March 2021

The relationship between interleukin-6 levels and physical performance in mobility-limited older adults with chronic low-grade inflammation: The ENRGISE Pilot study.

Arch Gerontol Geriatr 2020 Sep - Oct;90:104131. Epub 2020 May 30.

Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, United States. Electronic address:

Previous studies have found an inverse relation between serum concentrations of interleukin (IL)-6 and physical performance in seniors, however this was limited to higher functioning older adults with low to moderate levels of inflammation. We explored the consistency of this association in a cohort of mobility limited older adults with chronic low-grade inflammation. This study included 289 participants (≥ 70 years old) with IL-6 level between 2.5 and 30 pg/mL and a walking speed < 1.0 m/sec from the ENRGISE Pilot study. Physical performance was assessed using the short physical performance battery (SPPB), usual gait speed over 400 m, grip strength, and knee extensor and flexor strength measured by isokinetic dynamometry at 60 and 180°/sec. There was a significant inverse correlation between log IL-6 and knee extensor strength at 60°/sec (r= -0.20, p = 0.002), at 180°/sec (r = -0.14, p = 0.037), and knee flexor strength at 60°/sec (r = -0.15, p = 0.021). After adjustment for potential confounders, the values of knee extensor strength at 60°/sec showed a trend toward a progressive reduction across IL-6 tertiles as IL-6 levels increased (p = 0.024). No significant association was found between IL-6 and other objectively measured physical performance. The findings were generally of smaller magnitude and less consistent than previously reported, which suggests that the associations are attenuated in those with both elevated inflammation and mobility limitations. These results have implications for planning and interpreting future intervention studies in older adults with low-grade inflammation and mobility limitations.
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http://dx.doi.org/10.1016/j.archger.2020.104131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434645PMC
December 2020

Three-Year, Postintervention, Follow-up Comparison of Health Care Resource Utilization and Costs in the Lifestyle Interventions and Independence for Elders (LIFE) Study.

J Gerontol A Biol Sci Med Sci 2021 Jan;76(2):272-276

Department of Aging & Geriatric Research, University of Florida College of Medicine, Gainesville.

Background: The Lifestyle Interventions and Independence for Elders (LIFE) Study physical activity (PA) intervention was found to be cost-effective compared to health education (HE). However, long-term effects postintervention are unknown.

Method: This was a secondary analysis of LIFE Study data linked to Medicare claims data (2014-2016). Participants were linked via Social Security Numbers to Medicare claims data. Utilization and cost variables were analyzed using generalized linear models with negative binomial and Tweedie distributions. Unadjusted means and 95% confidence intervals were compared by year and overall stratified. Each model compared PA versus HE and adjusted for other baseline characteristics and stratified by study site. Additional models were stratified by baseline physical functioning assessment scores.

Results: Of the 1,635 LIFE Study participants, 804 (53.5%) were linked to Medicare claims with an average of 33 months of follow-up time during the 3-year data linkage period. Mean outpatient (6.6 vs 6.8), inpatient (0.40 vs 0.40), and other utilization metrics were similar between PA and HE groups. Costs were also similar for each group and each type of service, for example, outpatient: $2,070 versus $2,093 and inpatient: $4,704 versus $4,792. Regression results indicated no statistically significant differences between PA and HE groups.

Conclusions: While the LIFE Study demonstrated that PA reduced mobility disability in older adults and was cost-effective, it did not appear to affect long-term health care utilization costs posttrial. These findings suggest that it remains challenging to affect long-term health care costs using PA interventions effects.
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http://dx.doi.org/10.1093/gerona/glaa088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812479PMC
January 2021

Corrigendum: Multimodal Imaging of Brain Activity to Investigate Walking and Mobility Decline in Older Adults (Mind in Motion Study): Hypothesis, Theory, and Methods.

Front Aging Neurosci 2020 4;12:63. Epub 2020 Mar 4.

Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, United States.

[This corrects the article on p. 358 in vol. 11, PMID: 31969814.].
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http://dx.doi.org/10.3389/fnagi.2020.00063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064883PMC
March 2020

Role of Wearable Accelerometer Devices in Delirium Studies: A Systematic Review.

Crit Care Explor 2019 Sep 13;1(9):e0027. Epub 2019 Sep 13.

Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL.

We sought to determine the feasibility of using wearable accelerometer devices for determining delirium effects on patients' physical activity patterns and detecting delirium and delirium subtype.

Data Sources: PubMed, Embase, and Web of Science.

Study Selection: Screening was performed using predefined search terms to identify original research studies using accelerometer devices for studying physical activity in relation to delirium.

Data Extraction: Key data were extracted from the selected articles.

Data Synthesis: Among the 14 studies identified, there were a total of 315 patients who wore accelerometer devices to record movements related to delirium. Eight studies (57.1%) used accelerometer devices to compare the activity of delirious and nondelirious patients. Delirious patients had lower activity levels, lower restlessness index, higher number of daytime immobility minutes, lower mean activity levels during the day, and higher mean activity levels at night. Delirious patients also had lower actual sleep time, lower sleep efficiency, fewer nighttime minutes resting, fewer minutes resting over 24 hours, and smaller change in activity from day to night. Six studies (42.9%) evaluated the feasibility of using accelerometer devices for detection of delirium and its subtype. Variables including number of postural changes during daytime, frequency of ultrashort, short, and continuous movements were significantly different among the nondelirium and the three delirium subtypes.

Conclusions: The results from the studies using accelerometer devices in studying delirium demonstrate that accelerometer devices can potentially detect the differences between delirious and nondelirious patients, detect delirium, and determine delirium subtype. We suggest the following directions as the next steps for future studies using accelerometer devices for predicting delirium: benchmark studies with longer data collection, larger and more diverse population size, incorporating related factors (e.g., medications), and evaluating delirium subtype and severity.
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http://dx.doi.org/10.1097/CCE.0000000000000027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063934PMC
September 2019

Sarcopenia Definition: The Position Statements of the Sarcopenia Definition and Outcomes Consortium.

J Am Geriatr Soc 2020 07 9;68(7):1410-1418. Epub 2020 Mar 9.

California Pacific Medical Center Research Institute, San Francisco Coordinating Center, San Francisco, California.

Objectives: To develop an evidence-based definition of sarcopenia that can facilitate identification of older adults at risk for clinically relevant outcomes (eg, self-reported mobility limitation, falls, fractures, and mortality), the Sarcopenia Definition and Outcomes Consortium (SDOC) crafted a set of position statements informed by a literature review and SDOC's analyses of eight epidemiologic studies, six randomized clinical trials, four cohort studies of special populations, and two nationally representative population-based studies.

Methods: Thirteen position statements related to the putative components of a sarcopenia definition, informed by the SDOC analyses and literature synthesis, were reviewed by an independent international expert panel (panel) iteratively and voted on by the panel during the Sarcopenia Position Statement Conference. Four position statements related to grip strength, three to lean mass derived from dual-energy x-ray absorptiometry (DXA), and four to gait speed; two were summary statements.

Results: The SDOC analyses identified grip strength, either absolute or scaled to measures of body size, as an important discriminator of slowness. Both low grip strength and low usual gait speed independently predicted falls, self-reported mobility limitation, hip fractures, and mortality in community-dwelling older adults. Lean mass measured by DXA was not associated with incident adverse health-related outcomes in community-dwelling older adults with or without adjustment for body size.

Conclusion: The panel agreed that both weakness defined by low grip strength and slowness defined by low usual gait speed should be included in the definition of sarcopenia. These position statements offer a rational basis for an evidence-based definition of sarcopenia. The analyses that informed these position statements are summarized in this article and discussed in accompanying articles in this issue of the journal. J Am Geriatr Soc 68:1410-1418, 2020.
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http://dx.doi.org/10.1111/jgs.16372DOI Listing
July 2020

Impact and Lessons From the Lifestyle Interventions and Independence for Elders (LIFE) Clinical Trials of Physical Activity to Prevent Mobility Disability.

J Am Geriatr Soc 2020 04 27;68(4):872-881. Epub 2020 Feb 27.

Department of Internal Medicine and the Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: Walking independently is basic to human functioning. The Lifestyle Interventions and Independence for Elders (LIFE) studies were developed to assess whether initiating physical activity could prevent major mobility disability (MMD) in sedentary older adults.

Methods: We review the development and selected findings of the LIFE studies from 2000 through 2019, including the planning phase, the LIFE-Pilot Study, and the LIFE Study.

Results: The planning phase and the LIFE-Pilot provided key information for the successful implementation of the LIFE Study. The LIFE Study, involving 1635 participants randomized at eight sites throughout the United States, showed that compared with health education, the physical activity program reduced the risk of the primary outcome of MMD (inability to walk 400 m: hazard ratio = 0.82; 95% confidence interval = 0.69-0.98; P = .03), and that the intervention was cost-effective. There were no significant effects on cognitive outcomes, cardiovascular events, or serious fall injuries. In addition, the LIFE studies provided relevant findings on a broad range of other outcomes, including health, frailty, behavioral outcomes, biomarkers, and imaging. To date, the LIFE studies have generated a legacy of 109 peer-reviewed publications, 19 ancillary studies, and 38 independently funded grants and clinical trials, and advanced the development of 59 early career scientists. Data and biological samples of the LIFE Study are now publicly available from a repository sponsored by the National Institute on Aging (https://agingresearchbiobank.nia.nih.gov).

Conclusions: The LIFE studies generated a wealth of important scientific findings and accelerated research in geriatrics and gerontology, benefiting the research community, trainees, clinicians, policy makers, and the general public. J Am Geriatr Soc 68:872-881, 2020.
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http://dx.doi.org/10.1111/jgs.16365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187344PMC
April 2020

Multimodal Imaging of Brain Activity to Investigate Walking and Mobility Decline in Older Adults (Mind in Motion Study): Hypothesis, Theory, and Methods.

Front Aging Neurosci 2019 8;11:358. Epub 2020 Jan 8.

Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, United States.

Age-related brain changes likely contribute to mobility impairments, but the specific mechanisms are poorly understood. Current brain measurement approaches (e.g., functional magnetic resonance imaging (fMRI), functional near infrared spectroscopy (fNIRS), PET) are limited by inability to measure activity from the whole brain during walking. The will use cutting edge, mobile, high-density electroencephalography (EEG). This approach relies upon innovative hardware and software to deliver three-dimensional localization of active cortical and subcortical regions with good spatial and temporal resolution during walking. Our overarching objective is to determine age-related changes in the central neural control of walking and correlate these findings with a comprehensive set of mobility outcomes (clinic-based, complex walking, and community mobility measures). Our hypothesis is that age-related walking deficits are explained in part by the Compensation Related Utilization of Neural Circuits Hypothesis (CRUNCH). CRUNCH is a well-supported model that describes the over-recruitment of brain regions exhibited by older adults in comparison to young adults, even at low levels of task complexity. CRUNCH also describes the limited brain reserve resources available with aging. These factors cause older adults to quickly reach a ceiling in brain resources when performing tasks of increasing complexity, leading to poor performance. Two hundred older adults and twenty young adults will undergo extensive baseline neuroimaging and walking assessments. Older adults will subsequently be followed for up to 3 years. Aim 1 will evaluate whether brain activity during actual walking explains mobility decline. Cross sectional and longitudinal designs will be used to study whether poorer walking performance and steeper trajectories of decline are associated with CRUNCH indices. Aim 2 is to harmonize high-density EEG during walking with fNIRS (during actual and imagined walking) and fMRI (during imagined walking). This will allow integration of CRUNCH-related hallmarks of brain activity across neuroimaging modalities, which is expected to lead to more widespread application of study findings. Aim 3 will study central and peripheral mechanisms (e.g., cerebral blood flow, brain regional volumes, and connectivity, sensory function) to explain differences in CRUNCH indices during walking. Research performed in the will comprehensively characterize the aging brain during walking for developing new intervention targets.
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http://dx.doi.org/10.3389/fnagi.2019.00358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960208PMC
January 2020

Magnitude of and Characteristics Associated With the Treatment of Calcium Channel Blocker-Induced Lower-Extremity Edema With Loop Diuretics.

JAMA Netw Open 2019 12 2;2(12):e1918425. Epub 2019 Dec 2.

Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville.

Importance: Calcium channel blockers, specifically dihydropyridine calcium channel blockers (DH CCBs, eg, amlodipine), may cause lower-extremity edema. Anecdotal reports suggest this may result in a prescribing cascade, where DH CCB-induced edema is treated with loop diuretics.

Objective: To assess the magnitude and characteristics of the DH CCB prescribing cascade.

Design, Setting, And Participants: This cohort study used a prescription sequence symmetry analysis to assess loop diuretic initiation before and after the initiation of DH CCBs among patients aged 20 years or older without heart failure. Data from a private insurance claims database from 2005 to 2017 was analyzed. Use of loop diuretics associated with initiation of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and other commonly used medications was used as negative controls. Data were analyzed from March 2019 through October 2019.

Exposures: Initiation of DH CCB or negative control medications.

Main Outcomes And Measures: The temporality of loop diuretic initiation relative to DH CCB or negative control initiation. Secular trend-adjusted sequence ratios (aSRs) with 95% CIs were calculated using data from 360 days before and after initiation of DH CCBs.

Results: Among 1 206 093 DH CCB initiators, 55 818 patients (4.6%) (33 100 [59.3%] aged <65 years; 32 916 [59.0%] women) had a new loop diuretic prescription 360 days before or after DH CCB initiation, resulting in an aSR of 1.87 (95% CI, 1.84-1.90). An estimated 1.44% of DH CCB initiators experienced the prescribing cascade. The aSR was disproportionately higher among DH CCB initiators who were prescribed high doses (aSR, 2.20; 95% CI, 2.13-2.27), initiated amlodipine (aSR, 1.89; 95% CI, 1.86-1.93), were men (aSR, 1.96; 95% CI, 1.91-2.01), and used fewer antihypertensive classes (aSR, 2.55; 95% CI, 2.47-2.64). The evaluation of ACE inhibitors or ARBs as negative controls suggested hypertension progression may have tempered the incidence of the prescribing cascade (aSR for ACE inhibitors and ARBs, 1.27; 95% CI, 1.24-1.29).

Conclusions And Relevance: This study found an excessive use of loop diuretics following initiation of DH CCBs that cannot be completely explained by secular trends or hypertension progression. The prescribing cascade was more pronounced among those initially prescribed a high dose of DH CCBs.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.18425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991233PMC
December 2019

Impact of Baseline Fatigue on a Physical Activity Intervention to Prevent Mobility Disability.

J Am Geriatr Soc 2020 03 22;68(3):619-624. Epub 2019 Dec 22.

Center for Aging and Population Health, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.

Objectives: Our aim was to examine the impacts of baseline fatigue on the effectiveness of a physical activity (PA) intervention to prevent major mobility disability (MMD) and persistent major mobility disability (PMMD) in participants from the Lifestyle Interventions and Independence for Elders (LIFE) study.

Design: Prospective cohort of individuals aged 65 years or older undergoing structured PA intervention or health education (HE) for a mean of 2.6 years.

Setting: LIFE was a multicenter eight-site randomized trial that compared the efficacy of a structured PA intervention with an HE program in reducing the incidence of MMD.

Participants: Study participants (N = 1591) at baseline were 78.9 ± 5.2 years of age, with low PA and at risk for mobility impairment.

Measurements: Self-reported fatigue was assessed using the modified trait version of the Exercise-Induced Feelings Inventory, a six-question scale rating energy levels in the past week. Responses ranged from 0 (none of the time) to 5 (all of the time). Total score was calculated by averaging across questions; baseline fatigue was based on the median split: 2 or higher = more fatigue (N = 856) and lower than 2 = less fatigue (N = 735). Participants performed a usual-paced 400-m walk every 6 months. We defined incident MMD as the inability to walk 400-m at follow-up visits; PMMD was defined as two consecutive walk failures. Cox proportional hazard models quantified the risk of MMD and PMMD in PA vs HE stratified by baseline fatigue adjusted for covariates.

Results: Among those with higher baseline fatigue, PA participants had a 29% and 40% lower risk of MMD and PMMD, respectively, over the trial compared with HE (hazard ratio [HR] for MMD = .71; 95% confidence interval [CI] = .57-.90; P = .004) and PMMD (HR = .60; 95% CI = .44-.82; P = .001). For those with lower baseline fatigue, no group differences in MMD (P = .36) or PMMD (P = .82) were found. Results of baseline fatigue by intervention interaction was MMD (P = .18) and PMMD (P = .05).

Conclusion: A long-term moderate intensity PA intervention was particularly effective at preserving mobility in older adults with higher levels of baseline fatigue. J Am Geriatr Soc 68:619-624, 2020.
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http://dx.doi.org/10.1111/jgs.16274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061638PMC
March 2020