Christine Kee Liu

All Publications

• Complex Patterns of Antihypertensive Treatment Changes in Long-Term Care Residents. Journal of the American Medical Directors Association Liu, X., Jing, B., Graham, L. A., Liu, C. K., Lee, S. J., Steinman, M. A., Dave, C. V., Manja, V., Li, Y., Fung, K., Odden, M. C. 2024: 105119

  Abstract

  Antihypertensive treatment changes are common in long-term care residents, yet data on the frequency and predictors of changes are lacking. We described the patterns of antihypertensive changes and examined the triggering factors.Retrospective cohort study.A total of 24,870 Department of Veterans Affairs (VA) nursing home residents ≥65 years with long-term stays (≥180 days) from 2006 to 2019.We obtained data from the VA Corporate Data Warehouse. Based on Bar Code Medication Administration medication data, we defined 2 types of change events in 180 days of admission: deprescribing (reduced number of antihypertensives or dose reduction of ≥30% compared with the previous week and maintained for at least 2 weeks) and intensification (opposite of deprescribing). Mortality was identified within 2 years after admission.More than 85% of residents were prescribed antihypertensives and 68% of them experienced ≥1 change event during the first 6 months of the nursing home stay. We categorized residents into 10 distinct patterns: no change (27%), 1 deprescribing (11%), multiple deprescribing (5%), 1 intensification (10%), multiple intensification (7%), 1 deprescribing followed by 1 intensification (3%), 1 intensification followed by 1 deprescribing (4%), 3 changes with mixed events (7%), >3 changes with mixed events (10%), and no antihypertensive use (15%). Treatment changes were more frequent in residents with better physical function and/or cognitive function. Potentially triggering factors differed by the type of antihypertensive change: incident high blood pressure and cardiovascular events were associated with intensification, and low blood pressure, weight loss, and falls were associated with deprescribing. Death occurred in 7881 (32%) residents over 2 years. The highest mortality was for those without antihypertensive medication (incidence = 344/1000 person-years).Patterns of medication changes existing in long-term care residents are complex. Future studies should explore the benefits and harms of these antihypertensive treatment changes.

  View details for DOI 10.1016/j.jamda.2024.105119

  View details for PubMedID 38950584

• Frailty in Kidney Disease: A Comprehensive Review to Advance Its Clinical and Research Applications. American journal of kidney diseases : the official journal of the National Kidney Foundation Nair, D., Liu, C. K., Raslan, R., McAdams-DeMarco, M., Hall, R. K. 2024

  Abstract

  Frailty is a multi-system syndrome of decreased physiologic reserve that has been shown to strongly and independently predict morbidity and mortality. Frailty is prevalent in patients living with kidney disease and occurs earlier in individuals with kidney disease as compared to the general population. In this comprehensive review, we aim to advance the clinical and research applications of frailty in kidney disease populations. Specifically, we clarify the definition of frailty and address its common misconceptions; review the mechanisms and epidemiology of frailty in kidney disease; discuss challenges and limitations in frailty measurement; and provide updated evidence related to risk factors for frailty, its associated adverse outcomes, and interventions. We further add to the literature in this topic by highlighting potential applications of frailty measurement in care of patients with kidney disease and conclude with our recommendations for future research related to this important syndrome.

  View details for DOI 10.1053/j.ajkd.2024.04.018

  View details for PubMedID 38906506

• Going From Point A to Point B: Changes in the Mobility of Older Persons With CKD. American journal of kidney diseases : the official journal of the National Kidney Foundation Alfaro, A. J., Liu, C. K. 2024

  View details for DOI 10.1053/j.ajkd.2024.03.015

  View details for PubMedID 38829291

• Effects of residential socioeconomic polarization on high blood pressure among nursing home residents. Health & place Abdel Magid, H. S., Jaros, S., Li, Y., Steinman, M. A., Lee, S., Peralta, C., Jing, B., Fung, K., Liu, C. K., Liu, X., Graham, L. A., Odden, M. C. 2024; 87: 103243

  Abstract

  Neighborhood concentration of racial, income, education, and housing deprivation is known to be associated with higher rates of hypertension. The objective of this study is to examine the association between tract-level spatial social polarization and hypertension in a cohort with relatively equal access to health care, a Veterans Affairs nursing home.41,973 long-term care residents aged ≥65 years were matched with tract-level Indices of Concentration at the Extremes across four socioeconomic domains. We modeled high blood pressure against these indices controlling for individual-level cardiovascular confounders.We found participants who had resided in the most disadvantaged quintile had a 1.10 (95% 1.01, 1.19) relative risk of high blood pressure compared to those in the other quintiles for the joint measuring race/ethnicity and income domain.We achieved our objective by demonstrating that concentrated deprivation is associated with worse cardiovascular outcomes even in a population with equal access to care. Measures that jointly consider economic and racial/ethnic polarization elucidate larger disparities than single domain measures.

  View details for DOI 10.1016/j.healthplace.2024.103243

  View details for PubMedID 38663339

• Ripple Effects: CKD and Physical Function. Kidney medicine Alfaro, A. J., Liu, C. K. 2024; 6 (2): 100786

  View details for DOI 10.1016/j.xkme.2023.100786

  View details for PubMedID 38317760

  View details for PubMedCentralID PMC10840117

• Statins, Mortality, and Major Adverse Cardiovascular Events Among US Veterans With Chronic Kidney Disease. JAMA network open Barayev, O., Hawley, C. E., Wellman, H., Gerlovin, H., Hsu, W., Paik, J. M., Mandel, E. I., Liu, C. K., Djoussé, L., Gaziano, J. M., Gagnon, D. R., Orkaby, A. R. 2023; 6 (12): e2346373

  Abstract

  There are limited data for the utility of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and death in adults with chronic kidney disease (CKD).To evaluate the association of statin use with all-cause mortality and major adverse cardiovascular events (MACE) among US veterans older than 65 years with CKD stages 3 to 4.This cohort study used a target trial emulation design for statin initiation among veterans with moderate CKD (stages 3 or 4) using nested trials with a propensity weighting approach. Linked Veterans Affairs (VA) Healthcare System, Medicare, and Medicaid data were used. This study considered veterans newly diagnosed with moderate CKD between 2005 and 2015 in the VA, with follow-up through December 31, 2017. Veterans were older than 65 years, within 5 years of CKD diagnosis, had no prior ASCVD or statin use, and had at least 1 clinical visit in the year prior to trial baseline. Eligibility criteria were assessed for each nested trial, and Cox proportional hazards models with bootstrapping were run. Analysis was conducted from July 2021 to October 2023.Statin initiation vs none.Primary outcome was all-cause mortality; secondary outcome was time to first MACE (myocardial infarction, transient ischemic attack, stroke, revascularization, or mortality).Included in the analysis were 14 828 veterans. Mean (SD) age at CKD diagnosis was 76.9 (8.2) years, 14 616 (99%) were men, 10 539 (72%) White, and 2568 (17%) Black. After expanding to person-trials and assessing eligibility at each baseline, there were 151 243 person-trials (14 685 individuals) of nonstatin initiators and 2924 person-trials (2924 individuals) of statin initiators included. Propensity score adjustment via overlap weighting with nonparametric bootstrapping resulted in covariate balance, with mean (SD) follow-up of 3.6 (2.7) years. The hazard ratio for all-cause mortality was 0.91 (95% CI, 0.85-0.97) comparing statin initiators to noninitiators. The hazard ratio for MACE was 0.96 (95% CI, 0.91-1.02). Results remained consistent in prespecified subgroup analyses.In this target trial emulation of statin initiation in US veterans older than 65 years with CKD stages 3 to 4 and no prior ASCVD, statin initiation was significantly associated with a lower risk of all-cause mortality but not MACE. Results should be confirmed in a randomized clinical trial.

  View details for DOI 10.1001/jamanetworkopen.2023.46373

  View details for PubMedID 38055276

  View details for PubMedCentralID PMC10701610

• FRAILTY AND COGNITIVE IMPAIRMENT: RESULTS FROM A DIVERSE SAMPLE OF OLDER PERSONS RECEIVING HEMODIALYSIS Alfaro, A., Bryan, R., Balantrapu, S., Liu, C. OXFORD UNIV PRESS. 2023: 1045

  View details for Web of Science ID 001178258405150

• Structured Moderate Exercise and Biomarkers of Kidney Health in Sedentary Older Adults: The Lifestyle Interventions and Independence for Elders Randomized Clinical Trial. Kidney medicine Sheshadri, A., Lai, M., Hsu, F. C., Bauer, S. R., Chen, S. H., Tse, W., Jotwani, V., Tranah, G. J., Lai, J. C., Hallan, S., Fielding, R. A., Liu, C., Ix, J. H., Coca, S. G., Shlipak, M. G. 2023; 5 (11): 100721

  Abstract

  In the Lifestyle Interventions and Independence for Elders (LIFE) trial, a structured exercise intervention slowed kidney function decline in sedentary older adults. Biomarkers of kidney health could distinguish potential mechanisms for this beneficial effect.Randomized controlled trial.A total of 1,381 sedentary adults aged 70-89 years enrolled in the LIFE trial.Structured, 2-year, moderate-intensity exercise intervention versus health education.Physical activity was measured by step count. Primary outcomes were changes in 14 serum and urine biomarkers of kidney health collected at baseline, year 1, and year 2. We determined the effect of randomization on changes in kidney measures and then evaluated observational associations of achieved activity on each measure.Participants assigned to exercise walked on average 291 more steps per day than participants assigned to health education. The intervention was not significantly associated with changes in biomarkers of kidney health. In observational analyses, persons in the highest versus lowest quartile of activity (≥3,470 vs <1,568 steps/day) had significant improvement in urine albumin (mean, -0.22 mg albumin/g urine creatinine [interquartile range (IQR), -0.37 to -0.06]), alpha-1-microglobulin (-0.18 mg/L [-0.28 to -0.08]), trefoil factor-3 (-0.24 pg/mL [-0.35 to -0.13]), epidermal growth factor (0.19 pg/mL [0.06-0.32]), uromodulin (0.06 pg/mL [0.00-0.12]), interleukin 18 (-0.09 pg/mL [-0.15 to -0.03]), neutrophil gelatinase-associated lipocalin (-0.16 pg/mL [-0.24 to -0.07]), monocyte chemoattractant protein-1 (-0.25 pg/mL [-0.36 to -0.14]), clusterin (-0.16 pg/mL [-0.30 to -0.02]), serum tumor necrosis factor receptor-1 (-0.25 mg/dL [-0.39 to -0.11]) and tumor necrosis factor receptor-2 (-0.30 mg/dL [-0.44 to -0.16]). In sensitivity analyses, incremental changes in activity were most impactful on urine interleukin 18 and serum tumor necrosis factor-1.The original study was not designed to assess the impact on kidney health. Non-white individuals and patients with advanced chronic kidney disease are underrepresented.Randomization to structured exercise did not improve kidney health at a group level. However, higher exercise was associated with concurrent improvements in biomarkers of glomerular injury, tubular function/repair, tubular injury, generalized inflammation, and tubulointerstitial repair/fibrosis.In the Lifestyle Interventions For Elders (LIFE) study, randomization to an exercise and physical activity intervention improved the slope of estimated glomerular filtration rate over 2 years compared with health education among older adults. In this study, we sought to determine whether there were specific biomarkers of kidney health that were affected by the exercise and physical activity intervention to investigate potential mechanisms for this positive impact on kidney decline. We found that randomization to the intervention did not improve any of the 14 measures of kidney tubule health. However, in observational analyses, higher activity was independently associated with improvements in several domains, especially tubular injury and generalized inflammation. These results help to clarify the impact of physical activity on kidney health.

  View details for DOI 10.1016/j.xkme.2023.100721

  View details for PubMedID 37915963

  View details for PubMedCentralID PMC10616412

• Stakeholder Perspectives on Factors Related to Deprescribing Potentially Inappropriate Medications in Older Adults Receiving Dialysis. Clinical journal of the American Society of Nephrology : CJASN Hall, R. K., Rutledge, J., Lucas, A., Liu, C. K., St Clair Russell, J., St Peter, W., Fish, L. J., Colón-Emeric, C. 2023

  Abstract

  Potentially inappropriate medications, or medications that generally carry more risk of harm than benefit in older adults, are commonly prescribed to older adults receiving dialysis. Deprescribing, a systematic approach to reducing or stopping a medication, is a potential solution to limit potentially inappropriate medications use. Our objective was to identify clinicians and patient perspectives on factors related to deprescribing to inform design of a deprescribing program for dialysis clinics.We conducted rapid qualitative analysis of semi-structured interviews and focus groups with clinicians (dialysis clinicians, primary care providers (PCPs), and pharmacists) and patients (adults receiving hemodialysis aged ≥65 years and those aged 55-64 years who were pre-frail or frail ) from March 2019 to December 2020.We interviewed 76 participants [53 clinicians (8 focus groups and 11 interviews) and 23 patients]. Among clinicians, 24 worked in dialysis clinics, 18 worked in primary care, and 11 were pharmacists. Among patients, 13 (56%) were aged ≥65 years, 14 (61%) were Black race, and 16 (70%) reported taking at least one potentially inappropriate medication. We identified four themes (and corresponding subthemes) of contextual factors related to deprescribing potentially inappropriate medications: 1) system-level barriers to deprescribing (limited electronic medical record interoperability, time constraints and competing priorities), 2) undefined co-management among clinicians (unclear role delineation, clinician caution about prescriber boundaries), 3) limited knowledge about potentially inappropriate medications (knowledge limitations among clinicians and patients), and 4) patients prioritize symptom control over potential harm (clinicians expect resistance to deprescribing, patient weigh risks and benefits).Challenges to integration of deprescribing into dialysis clinics included siloed health systems, time constraints, co-management behaviors, and clinician and patient knowledge and attitudes towards deprescribing.

  View details for DOI 10.2215/CJN.0000000000000229

  View details for PubMedID 37499693

• Immunogenicity of adjuvanted versus high-dose inactivated influenza vaccines in older adults: a randomized clinical trial. Immunity & ageing : I & A Schmader, K. E., Liu, C. K., Flannery, B., Rountree, W., Auerbach, H., Barnett, E. D., Schlaudecker, E. P., Todd, C. A., Poniewierski, M., Staat, M. A., Harrington, T., Li, R., Broder, K. R., Walter, E. B. 2023; 20 (1): 30

  Abstract

  Adjuvanted inactivated influenza vaccine (aIIV) and high-dose inactivated influenza vaccine (HD-IIV) are U.S.-licensed for adults aged ≥ 65 years. This study compared serum hemagglutination inhibition (HAI) antibody titers for the A(H3N2) and A(H1N1)pdm09 and B strains after trivalent aIIV3 and trivalent HD-IIV3 in an older adult population.The immunogenicity population included 342 participants who received aIIV3 and 338 participants who received HD-IIV3. The proportion of participants that seroconverted to A(H3N2) vaccine strains after allV3 (112 participants [32.8%]) was inferior to the proportion of participants that seroconverted after HD-IIV3 (130 participants [38.5%]) at day 29 after vaccination (difference, - 5.8%; 95%CI, - 12.9% to 1.4%). There were no significant differences between the vaccine groups in percent seroconversion to A(H1N1)pdm09 or B vaccine strains, in percent seropositivity for any of the strains, or in post-vaccination GMT for the A(H1N1)pdm09 strain. The GMTs for the post-vaccination A(H3N2) and B strains were higher after HD-IIV than after aIIV3.Overall immune responses were similar after aIIV3 and HD-IIV3. For the primary outcome, the aIIV3 seroconversion rate for H3N2 did not meet noninferiority criteria compared with HD-IIV3, but the HD-IIV3 seroconversion rate was not statistically superior to the aIIV3 seroconversion rate.ClinicalTrials.gov Identifier: NCT03183908.

  View details for DOI 10.1186/s12979-023-00355-7

  View details for PubMedID 37393237

  View details for PubMedCentralID PMC10314373

• Decision-making about dialysis: Beyond just dialysis or death. Journal of the American Geriatrics Society Liu, C. K., Taffel, L., Russell, M., Wong, S. P., Russell, H., Vig, E. K. 2023

  Abstract

  Nearly half of the persons receiving dialysis in the United States are aged 65 years or older. Kidney failure occurs most frequently in older adults, and typically triggers a discussion regarding dialysis treatment. In this Special Article, we describe the journey of Mr. Howard Russell, an older adult who experienced kidney failure and underwent dialysis. Using the experience of Mr. Russell, we illustrate the complexity of dialysis decision-making, including how disease trajectory and health policy can potentially impede older adults from achieving "what matters." Our intent is to provide guidance regarding these barriers and support to clinicians who are sharing similar journeys with older adults making decisions about dialysis. Based on Mr. Russell's journey, we suggest that when discussing dialysis with an older adult, four points be considered: (1) recognize if dialysis is needed long-term; (2) understand what matters for the older adult; (3) sync the treatment plan when what matters changes; and (4) set up with resources for kidney failure, which is limited but evolving.

  View details for DOI 10.1111/jgs.18256

  View details for PubMedID 36790053

• Geriatric syndromes and health-related quality of life in older adults with chronic kidney disease. Kidney360 Liu, C. K., Miao, S., Giffuni, J., Katzel, L. I., Fielding, R. A., Seliger, S. L., Weiner, D. E. 2023

  Abstract

  Geriatric syndromes, which are multi-factorial conditions common in older adults, predict health-related quality of life (HRQOL). Although chronic kidney disease (CKD) is associated with lower HRQOL, whether geriatric syndromes contribute to HRQOL in CKD is unknown. Our objective was to compare associations of geriatric syndromes and medical conditions with HRQOL in older adults with CKD.This was a secondary analysis of a parallel-group randomized controlled clinical trial evaluating a 12- month exercise intervention in persons ≥55 years with CKD Stage 3b-4. Participants were assessed for baseline geriatric syndromes (cognitive impairment, poor appetite, dizziness, fatigue, and chronic pain), and medical conditions (diabetes, hypertension, coronary artery disease, cancer, or chronic obstructive pulmonary disease). Participants' HRQOL was assessed with the Short Form Health Survey-36 (SF-36), EuroQol 5 Dimensions-5 Level, and the EuroQol Visual Analogue Scale. We examined the cross-sectional and longitudinal associations of geriatric syndromes and medical conditions with HRQOL using multiple linear regression.Among 99 participants, the mean age was 68.0 years, 25% were female, and 62% were Black. Participants had a baseline mean of 2.0 geriatric syndromes and 2.1 medical conditions; 49% had ≥ two geriatric syndromes and ≥ two medical conditions concurrently. Sixty-seven participants (68%) underwent 12-month assessments. In models using geriatric syndromes and medical conditions as concurrent exposures, the number of geriatric syndromes was cross-sectionally associated with SF-36 scores for general health (β = -0.385), role limitations due to physical health (β=-0.374), physical functioning (β= -0.300, all p < 0.05). The number of medical conditions was only associated with SF-36 score for role limitations due to physical health (β = -0.205).In older adults with CKD Stage 3b-4, geriatric syndromes are common and are associated with lower HRQOL. Addressing geriatric conditions is a potential approach to improve HRQOL for older adults with CKD.

  View details for DOI 10.34067/KID.0000000000000078

  View details for PubMedID 36790849

• Effect of Long-term Exercise Training on Physical Performance and Cardiorespiratory Function in Adults With CKD: A Randomized Controlled Trial. American journal of kidney diseases : the official journal of the National Kidney Foundation Weiner, D. E., Liu, C. K., Miao, S., Fielding, R., Katzel, L. I., Giffuni, J., Well, A., Seliger, S. L. 2022

  Abstract

  RATIONALE AND OBJECTIVE: The safety and efficacy of long-term exercise training in reducing physical functional loss in older adults with advanced CKD and co-morbidity is uncertain.STUDY DESIGN: Multi-center, parallel group, randomized controlled trial.SETTINGS AND PARTICIPANTS: Adults 55 years and older with CKD stage G3b-4 enrolled from centers in Baltimore and Boston.INTERVENTION: Twelve months of in-center supervised exercise training incorporating majority aerobic but also muscle strengthening activities or a group health education control intervention, randomly assigned in 1:1 ratio.OUTCOMES: Primary outcomes were cardiorespiratory fitness and submaximal gait at 6 and 12 months quantified by peak oxygen consumption (VO2peak) on graded exercise treadmill test and distance walked on the six-minute walk test, respectively. Secondary outcomes were changes in lower extremity function, renal function, glycemia, blood pressure, and body mass index.RESULTS: Among 99 participants, mean age was 68 years, 62% were African American, and mean eGFR 33 mL/min/1.73m2; 59% had diabetes and 29% had coronary artery disease. Among those randomized to exercise, 59% of exercise sessions were attended in the initial 6 months. Exercise was well tolerated without excess occurrence of adverse events. At 6 months, aerobic capacity was higher among exercise participants (17.9±5.5 vs. 15.9±7.0 ml/kg/min, p=0.03), but differences were not sustained at 12-months. The 6-minute walk distance improved more in the exercise (adjusted differences: 98 feet, p=0.02; p=0.03 for treatment-by-time interaction). The exercise group had greater improvements on the get up and go test (p=0.04) but not the short physical performance battery (p=0.8).LIMITATIONS: Planned sample size was not reached. Loss to follow-up and dropout were greater than anticipated.CONCLUSIONS: Among adults ≥55 years with CKD stages G3b-4 and a high level of medical comorbidity, a 12-month program of in-center aerobic and resistance exercise training was safe and associated with improvements in physical functioning.

  View details for DOI 10.1053/j.ajkd.2022.06.008

  View details for PubMedID 35944747

• The Impact of Care Partners on the Mobility of Older Adults Receiving Hemodialysis. Kidney medicine Liu, C. K., Seo, J., Lee, D., Wright, K., Tamura, M. K., Moye, J., Weiner, D. E., Bean, J. F. 2022; 4 (6): 100473

  Abstract

  Rationale & Objective: Many older adults receiving hemodialysis have mobility limitations and rely on care partners, yet data are sparse regarding the support provided by care partners. Our aim was to examine how care partners support the mobility of an older adult receiving hemodialysis.Study Design: Qualitative study.Setting & Participants: Using purposive sampling, we recruited persons aged 60 years or more receiving maintenance hemodialysis and care partners aged 18 years or more who were providing support to an older adult receiving hemodialysis. We conducted in-person semi-structured interviews about mobility with each individual.Analytical Approach: We conducted descriptive and focused coding of interview transcripts and employed thematic analysis. Our outcome was to describe perceived mobility supports provided by care partners using qualitative themes.Results: We enrolled 31 older adults receiving hemodialysis (42% women, 68% Black) with a mean age of 73±8 years and a mean dialysis duration of 4.6±3.5 years. Of these, 87% of patients used assistive devices and 90% had care partners. We enrolled 12 care partners (75% women, 33% Black) with a mean age of 54±16 years. From our patient and care partner interviews, we found three themes: (1) what care partners see, (2) what care partners do, and (3) what care partners feel. Regarding what they see, care partners witness a decline in patient mobility. Regarding what they do, care partners guide and facilitate activities and manage others who also assist. Regarding what they feel, care partners respect the patient's autonomy but experience frustration and worry about the patient's future mobility.Limitations: Modest sample size; single geographic area.Conclusions: In older adults receiving hemodialysis, care partners observe a decline in mobility and provide support for mobility. They respect the patient's autonomy but worry about future mobility losses. Future research should incorporate care partners in interventions that address mobility in older adults receiving hemodialysis.

  View details for DOI 10.1016/j.xkme.2022.100473

  View details for PubMedID 35663231

• Pilot study of autologous fecal microbiota transplants in nursing home residents: Feasibility and safety. Contemporary clinical trials communications Liu, C. K., Seo, J., Pravodelov, V., Frazier, S., Guy, M., Concilio, K., Lau-Ng, R., Brandeis, G., Watson, J., van der Velde, J., Olesen, S. W., Budree, S., Njenga, M., Kassam, Z., Osman, M. 2022; 27: 100906

  Abstract

  Introduction: Antibiotic resistant bacterial infections (ARBIs) are extremely common in nursing home residents. These infections typically occur after a course of antibiotics, which eradicate both pathological and beneficial organisms. The eradication of beneficial organisms likely facilitates subsequent ARBIs. Autologous fecal microbiota transplant (aFMT) has been proposed as a potential treatment to reduce ARBIs in nursing home residents. Our objective was to determine the feasibility and safety of aFMT in a nursing home population.Methods: Pilot clinical trial. We evaluated feasibility as total number of stool samples collected for aFMT production and safety as the number and relatedness of serious (SAE) and non-serious adverse events (AE).Results: We screened 468 nursing home residents aged ≥18 years for eligibility; 67 enrolled, distributed among three nursing homes. Participants were 62.7% female and 35.8% Black. Mean age was 82.2±8.5 years. Thirty-three participants underwent successful stool collection. Seven participants received antibiotics; four participants underwent aFMT. There were 40 SAEs (17 deaths) and 11 AEs. In the aFMT group, there were 3 SAEs (2 deaths) and 10 AEs. All SAEs and AEs were judged unrelated to the study intervention.Conclusions: In this pilot study of aFMT in nursing home residents, less than half were able to provide adequate stool samples for aFMT. There were no related SAEs or AEs during the study. In sum, we conclude aFMT has limited feasibility in a nursing home population due to logistic and technical challenges but is likely safe.Trial registration: ClinicalTrials.gov Identifier: NCT03061097.

  View details for DOI 10.1016/j.conctc.2022.100906

  View details for PubMedID 35299780

• Mobility and What Matters: Moving Kidney Care Toward the 4Ms of an Age-Friendly Health System. Kidney medicine Liu, C. K. 2022; 4 (6): 100481

  View details for DOI 10.1016/j.xkme.2022.100481

  View details for PubMedID 35620084

• Trends in blood pressure diagnosis, treatment, and control among VA nursing home residents, 2007-2018. Journal of the American Geriatrics Society Odden, M. C., Li, Y., Graham, L. A., Steinman, M. A., Marcum, Z. A., Liu, C. K., Jing, B., Fung, K. Z., Peralta, C. A., Lee, S. J. 2022

  Abstract

  BACKGROUND: Inadequate treatment of high blood pressure (BP) can lead to preventable adverse events in nursing home residents, while excessive treatment can lead to associated harms.METHODS: Data were extracted from the VA electronic health record and Bar Code Medication Administration system on 40,079 long-term care residents aged ≥65years from October 2006 through September 2018 (FY2007-2018). Hypertension prevalence at admission was identified by ICD code(s) in the year prior, and antihypertensive medication use was defined as administration ≥50% of days. BP measures were averaged over 2-year epochs.RESULTS: The age-standardized prevalence of hypertension diagnosis at admission increased from 75.2% in FY2007-2008 to 85.1% in FY2017-2018 (p-value for trend <0.001). Rates of BP treatment and control among residents with hypertension at admission declined slightly over time (p-values for trend <0.001) but remained high (80.3% treated in FY2017-2018, 80.1% with average BP <140/90mmHg). The age-adjusted prevalence of chronic low BP (average <90/60mmHg) also declined from 11.1% in FY2007-2008 to 4.7% in FY2017-2018 (p-value for trend <0.001). Persons identified as Black race or Hispanic ethnicity and those with a history of diabetes, stroke, and renal disease were less likely to have an average BP <140/90mmHg.CONCLUSIONS: Hypertension is well controlled in VA nursing homes, and recent trends of less intensive BP control were accompanied by a lower prevalence of chronic low BP. Nonetheless, some high-risk populations have average BP levels >140/90mmHg. Future research is needed to better understand the benefits and harms of BP control in nursing home residents.

  View details for DOI 10.1111/jgs.17821

  View details for PubMedID 35524763

• Effect of Structured, Moderate Exercise on Kidney Function Decline in Sedentary Older Adults: An Ancillary Analysis of the LIFE Study Randomized Clinical Trial. JAMA internal medicine Shlipak, M. G., Sheshadri, A., Hsu, F., Chen, S., Jotwani, V., Tranah, G., Fielding, R. A., Liu, C. K., Ix, J., Coca, S. G., LIFE Investigators, Pahor, M., Guralnik, J. M., Leeuwenburgh, C., Caudle, C., Crump, L., Holmes, L., Leeuwenburgh, J., Lu, C., Miller, M. E., Espeland, M. A., Ambrosius, W. T., Applegate, W., Beavers, D. P., Byington, R. P., Cook, D., Furberg, C. D., Harvin, L. N., Henkin, L., Hepler, J., Hsu, F., Lovato, L., Roberson, W., Rushing, J., Rushing, S., Stowe, C. L., Walkup, M. P., Hire, D., Rejeski, W. J., Katula, J. A., Brubaker, P. H., Mihalko, S. L., Jennings, J. M., Hadley, E. C., Romashkan, S., Patel, K. V., Bonds, D., McDermott, M. M., Spring, B., Hauser, J., Kerwin, D., Domanchuk, K., Graff, R., Rego, A., Church, T. S., Blair, S. N., Myers, V. H., Monce, R., Britt, N. E., Harris, M., McGucken, A., Rodarte, R., Millet, H. K., Tudor-Locke, C., Butitta, B. P., Donatto, S., Cocreham, S. H., King, A. C., Castro, C. M., Haskell, W. L., Stafford, R. S., Pruitt, L. A., Berra, K., Yank, V., Fielding, R. A., Nelson, M. E., Folta, S. C., Phillips, E. M., Liu, C. K., McDavitt, E. C., Reid, K. F., Kirn, D. R., Pasha, E. P., Kim, W. S., Beard, V. E., Tsiroyannis, E. X., Hau, C., Manini, T. M., Anton, S. D., Nayfield, S., Buford, T. W., Marsiske, M., Sandesara, B. D., Knaggs, J. D., Lorow, M. S., Marena, W. C., Korytov, I., Morris, H. L., Fitch, M., Singletary, F. F., Causer, J., Radcliff, K. A., Newman, A. B., Studenski, S. A., Goodpaster, B. H., Glynn, N. W., Lopez, O., Nadkarni, N. K., Williams, K., Newman, M. A., Grove, G., Bonk, J. T., Rushing, J., Kost, P., Ives, D. G., Kritchevsky, S. B., Marsh, A. P., Brinkley, T. E., Demons, J. S., Sink, K. M., Kennedy, K., Shertzer-Skinner, R., Wrights, A., Fries, R., Barr, D., Gill, T. M., Axtell, R. S., Kashaf, S. S., de Rekeneire, N., McGloin, J. M., Wu, K. C., Shepard, D. M., Fennelly, B., Iannone, L. P., Mautner, R., Sweeney Barnett, T., Halpin, S. N., Brennan, M. J., Bugaj, J. A., Zenoni, M. A., Mignosa, B. M., Williamson, J., Hendrie, H. C., Rapp, S. R., Verghese, J., Woolard, N., Espeland, M., Jennings, J., Wilson, V. K., Pepine, C. J., Ariet, M., Handberg, E., Deluca, D., Hill, J., Szady, A., Chupp, G. L., Flynn, G. M., Hankinson, J. L., Vaz Fragoso, C. A., Groessl, E. J., Kaplan, R. M. 2022

  Abstract

  Importance: Observational evidence suggests that higher physical activity is associated with slower kidney function decline; however, to our knowledge, no large trial has evaluated whether activity and exercise can ameliorate kidney function decline in older adults.Objective: To evaluate whether a moderate-intensity exercise intervention can affect the rate of estimated glomerular filtration rate per cystatin C (eGFRCysC) change in older adults.Design, Setting, and Participants: This ancillary analysis of the Lifestyle Interventions and Independence For Elders randomized clinical trial enrolled 1199 community-dwelling, sedentary adults aged 70 to 89 years with mobility limitations and available blood specimens. The original trial was conducted across 8 academic centers in the US from February 2010 through December 2013. Data for this study were analyzed from March 29, 2021, to February 28, 2022.Interventions: Structured, 2-year, partially supervised, moderate-intensity physical activity and exercise (strength, flexibility) intervention compared with a health education control intervention with 2-year follow-up. Physical activity was measured by step count and minutes of moderate-intensity activity using accelerometers.Main Outcomes and Measures: The primary outcome was change in eGFRCysC. Rapid eGFRCysC decline was defined by the high tertile threshold of 6.7%/y.Results: Among the 1199 participants in the analysis, the mean (SD) age was 78.9 (5.2) years, and 800 (66.7%) were women. At baseline, the 2 groups were well balanced by age, comorbidity, and baseline eGFRCysC. The physical activity and exercise intervention resulted in statistically significantly lower decline in eGFRCysC over 2 years compared with the health education arm (mean difference, 0.96 mL/min/1.73 m2; 95% CI, 0.02-1.91 mL/min/1.73 m2) and lower odds of rapid eGFRCysC decline (odds ratio, 0.79; 95% CI, 0.65-0.97).Conclusions and Relevance: Results of this ancillary analysis of a randomized clinical trial showed that when compared with health education, a physical activity and exercise intervention slowed the rate of decline in eGFRCysC among community-dwelling sedentary older adults. Clinicians should consider targeted recommendation of physical activity and moderate-intensity exercise for older adults as a treatment to slow decline in eGFRCysC.Trial Registration: ClinicalTrials.gov Identifier: NCT01072500.

  View details for DOI 10.1001/jamainternmed.2022.1449

  View details for PubMedID 35499834

• Conservative Care for Kidney Failure-The Other Side of the Coin. JAMA network open Liu, C. K., Kurella Tamura, M. 2022; 5 (3): e222252

  View details for DOI 10.1001/jamanetworkopen.2022.2252

  View details for PubMedID 35285925

• Noncancerous Genitourinary Conditions as a Public Health Priority: Conceptualizing the Hidden Burden. Urology Brady, S. S., Bavendam, T. G., Bradway, C. K., Conroy, B., Dowling-Castronovo, A., Epperson, C. N., Hijaz, A. K., Hsi, R. S., Huss, K., Kim, M., Lazar, J., Lee, R. K., Liu, C. K., Loizou, C. N., Miran, S., Mody, L., Norton, J. M., Reynolds, W. S., Sutcliffe, S., Zhang, N., Hokanson, J. A. 2021

  Abstract

  OBJECTIVE: To provide a conceptual framework to guide investigations into burdens of noncancerous genitourinary conditions (NCGUCs), which are extensive and poorly understood.METHODS: The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) convened a workshop of diverse, interdisciplinary researchers and health professionals to identify known and hidden burdens of NCGUCs that must be measured to estimate the comprehensive burden. Following the meeting, a subgroup of attendees (authors of this article) continued to meet to conceptualize burden.RESULTS: The Hidden Burden of Noncancerous Genitourinary Conditions Framework includes impacts across multiple levels of well-being and social ecology, including individual (i.e., biologic factors, lived experience, behaviors), interpersonal (e.g., romantic partners, family members), organizational/institutional (e.g., schools, workplaces), community (e.g., public restroom infrastructure), societal (e.g., health care and insurance systems, national workforce/economic output), and ecosystem (e.g., landfill waste) effects. The framework acknowledges that NCGUCs can be a manifestation of underlying biological dysfunction, while also leading to biological impacts (generation and exacerbation of health conditions, treatment side effects).CONCLUSIONS: NCGUCs confer a large, poorly understood burden to individuals and society. An evidence-base to describe the comprehensive burden is needed. Measurement of NCGUC burdens should incorporate multiple levels of well-being and social ecology, a life course perspective, and potential interactions between NCGUCs and genetics, sex, race, and gender. This approach would elucidate accumulated impacts and potential health inequities in experienced burdens. Uncovering the hidden burden of NCGUCs may draw attention and resources (e.g., new research and improved treatments) to this important domain of health.

  View details for DOI 10.1016/j.urology.2021.08.040

  View details for PubMedID 34536410

• Mobility in Older Adults Receiving Maintenance Hemodialysis: A Qualitative Study. American journal of kidney diseases : the official journal of the National Kidney Foundation Liu, C. K., Seo, J., Lee, D., Wright, K., Tamura, M. K., Moye, J. A., Bean, J. F., Weiner, D. E. 2021

  Abstract

  RATIONALE & OBJECTIVE: For older adults, maintaining mobility is a major priority, especially for those with advanced chronic diseases like kidney failure. However, our understanding of the factors affecting mobility in older adults receiving maintenance hemodialysis is limited.STUDY DESIGN: Descriptive qualitative study.SETTING AND PARTICIPANTS: Using purposive sampling, we recruited 1) persons aged ≥ 60 years receiving maintenance hemodialysis and 2) care partners (≥ 18 years) providing regular support to an older adult receiving hemodialysis. During a single in-person home visit, we assessed mobility using the Short Physical Performance Battery (SPPB) and conducted individual one-on-one interviews regarding important personal factors related to mobility.ANALYTIC APPROACH: Descriptive statistics were used for demographic and SPPB data. Transcripts underwent thematic coding, informed by the International Classification of Function framework of mobility. We used conceptual content analysis to inductively extract themes and subthemes.RESULTS: We enrolled 31 older adults receiving hemodialysis (42% female, 68% Black) with mean age of 73±8 years and mean dialysis duration of 4.6±3.5 years; mean SPPB was 3.6±2.8 points. Among 12 care partners (75% female, 33% Black), mean age was 54±16 years and mean SPPB was 10.1±2.4 points. Major themes extracted were: 1) mobility represents independence; 2) mobility is precarious; 3) limitations in mobility cause distress; 4) sources of encouragement and motivation are critical; and 5) adaptability is key.LIMITATIONS: Modest sample from single geographic area.CONCLUSIONS: For older adults receiving hemodialysis, mobility is severely limited and is often precarious in nature, causing distress. Older adults receiving hemodialysis and their care partners have identified sources of encouragement and motivation for mobility, and cite an adaptable mindset as important. Future studies should conceptualize mobility as a variable condition, and build upon this outlook of adaptability in the development of interventions.

  View details for DOI 10.1053/j.ajkd.2021.07.010

  View details for PubMedID 34419517

• Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: A Randomized Clinical Trial. JAMA network open Schmader, K. E., Liu, C. K., Harrington, T., Rountree, W., Auerbach, H., Walter, E. B., Barnett, E. D., Schlaudecker, E. P., Todd, C. A., Poniewierski, M., Staat, M. A., Wodi, P., Broder, K. R. 2021; 4 (1): e2031266

  Abstract

  Importance: Trivalent adjuvanted inactivated influenza vaccine (aIIV3) and trivalent high-dose inactivated influenza vaccine (HD-IIV3) are US-licensed for adults aged 65 years and older. Data are needed on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of these vaccines.Objective: To compare safety, reactogenicity, and changes in HRQOL scores after aIIV3 vs HD-IIV3.Design, Setting, and Participants: This randomized blinded clinical trial was a multicenter US study conducted during the 2017 to 2018 and 2018 to 2019 influenza seasons. Among 778 community-dwelling adults aged at least 65 years and assessed for eligibility, 13 were ineligible and 8 withdrew before randomization. Statistical analysis was performed from August 2019 to August 2020.Interventions: Intramuscular administration of aIIV3 or HD-IIV3 after age-stratification (65-79 years; ≥80 years) and randomization.Main Outcomes and Measures: Proportions of participants with moderate-to-severe injection-site pain and 14 other solicited reactions during days 1 to 8, using a noninferiority test (5% noninferiority margin), and serious adverse events (SAE) and adverse events of clinical interest (AECI), including new-onset immune-mediated conditions, during days 1 to 43. Changes in HRQOL scores before and after vaccination (days 1, 3) were also compared between study groups.Results: A total of 757 adults were randomized, 378 to receive aIIV3 and 379 to receive HD-IIV3. Of these participants, there were 420 women (55%) and 589 White individuals (78%) with a median (range) age of 72 (65-97) years. The proportion reporting moderate-to-severe injection-site pain, limiting or preventing activity, after aIIV3 (12 participants [3.2%]) (primary outcome) was noninferior compared with HD-IIV3 (22 participants [5.8%]) (difference -2.7%; 95% CI, -5.8 to 0.4). Ten reactions met noninferiority criteria for aIIV3; 4 (moderate-to-severe injection-site tenderness, arthralgia, fatigue, malaise) did not. It was inconclusive whether these 4 reactions occurred in higher proportions of participants after aIIV3. No participant sought medical care for a vaccine reaction. No AECI was observed. Nine participants had at least SAE after aIIV3 (2.4%; 95% CI,1.1% to 4.5%); 3 had at least 1 SAE after HD-IIV3 (0.8%; 95% CI, 0.2% to 2.2%). No SAE was associated with vaccination. Changes in prevaccination and postvaccination HRQOL scores were not clinically meaningful and not different between the groups.Conclusions and Relevance: Overall safety and HRQOL findings were similar after aIIV3 and HD-IIV3, and consistent with prelicensure data. From a safety standpoint, this study's results support using either vaccine to prevent influenza in older adults.Trial Registration: ClinicalTrials.gov Identifier: NCT03183908.

  View details for DOI 10.1001/jamanetworkopen.2020.31266

  View details for PubMedID 33443580

• COVID-19 Infection Risk Among Hemodialysis Patients in Long-term Care Facilities. Kidney medicine Liu, C. K., Ghai, S., Waikar, S. S., Weiner, D. E. 2020; 2 (6): 810–11

  View details for DOI 10.1016/j.xkme.2020.07.005

  View details for PubMedID 33015605

• Muscle strength is increased in mice that are colonized with microbiota from high-functioning older adults. Experimental gerontology Fielding, R. A., Reeves, A. R., Jasuja, R., Liu, C., Barrett, B. B., Lustgarten, M. S. 2019; 127: 110722

  Abstract

  Evidence in support of a gut-muscle axis has been reported in rodents, but studies in older adult humans are limited. Accordingly, the primary goals of the present study were to compare gut microbiome composition in older adults that differed in terms of the percentage of whole body lean mass and physical functioning (high-functioning, HF, n = 18; low-functioning, LF, n = 11), and to evaluate the causative role of the gut microbiome on these variables by transferring fecal samples from older adults into germ-free mice. Family-level Prevotellaceae, genus-level Prevotella and Barnesiella, and the bacterial species Barnesiella intestinihominis were higher in HF older adults at the initial study visit, at a 1-month follow-up visit, in HF human fecal donors, and in HF-colonized mice, when compared with their LF counterparts. Grip strength was significantly increased by 6.4% in HF-, when compared with LF-colonized mice. In contrast, despite significant differences for the percentage of whole body lean mass and physical functioning when comparing the human fecal donors, the percentage of whole body lean mass and treadmill endurance capacity were not different when comparing human microbiome-containing mice. In sum, these data suggest a role for gut bacteria on the maintenance of muscle strength, but argue against a role for gut bacteria on the maintenance of the percentage of whole body lean mass or endurance capacity, findings that collectively add to elucidation of the gut-muscle axis in older adults.

  View details for DOI 10.1016/j.exger.2019.110722

  View details for PubMedID 31493521

  View details for PubMedCentralID PMC6823114

• Effect of Losartan and Fish Oil on Plasma IL-6 and Mobility in Older Persons. The ENRGISE Pilot Randomized Clinical Trial. The journals of gerontology. Series A, Biological sciences and medical sciences Pahor, M., Anton, S. D., Beavers, D. P., Cauley, J. A., Fielding, R. A., Kritchevsky, S. B., Leeuwenburgh, C., Lewis, K. H., Liu, C. K., Lovato, L. C., Lu, J., Manini, T. M., McDermott, M. M., Miller, M. E., Newman, A. B., Radziszewska, B., Stowe, C. L., Tracy, R. P., Walkup, M. P., Wu, S. S., Ambrosius, W. T. 2019; 74 (10): 1612-1619

  Abstract

  Low-grade chronic inflammation, characterized by elevations in plasma Interleukin-6 (IL-6), is an independent risk factor of impaired mobility in older persons. Angiotensin receptor blockers and omega-3 polyunsaturated fatty acids (ω-3) may reduce IL-6 and may potentially improve physical function. To assess the main effects of the angiotensin receptor blocker losartan and ω-3 as fish oil on IL-6 and 400 m walking speed, we conducted the ENRGISE Pilot multicenter randomized clinical trial.The ENRGISE Pilot enrolled participants between April 2016 and June 2017, who participated for 12 months. Participants were aged ≥70 years with mobility impairment, had IL-6 between 2.5 and 30 pg/mL, and were able to walk 400 m at baseline. Participants were randomized in three strata 2 × 2 factorial to: (i) losartan 50-100 mg/d or placebo (n = 43), (ii) fish oil 1,400-2,800 mg/d or placebo (n = 180), and (iii) with both (n = 66).Two hundred eighty-nine participants were randomized (mean age 78.3 years, 47.4% women, 17.0% black). There was no effect of losartan (difference of means = -0.065 ± 0.116 [SE], 95% confidence interval [CI]: -0.293-0.163, p = .58) or fish oil (-0.020 ± 0.077, 95% CI: -0.171-0.132, p = .80) on the log of IL-6. Similarly, there was no effect of losartan (-0.025 ± 0.026, 95% CI: -0.076-0.026, p = .34) or fish oil (0.010 ± 0.017, 95% CI: -0.025-0.044, p = .58) on walking speed (m/s).These results do not support the use of these interventions to prevent mobility loss in older adults at risk of disability with low-grade chronic inflammation.Clinicaltrials.gov NCT02676466.

  View details for DOI 10.1093/gerona/gly277

  View details for PubMedID 30541065

  View details for PubMedCentralID PMC6748815

• Progressive Resistance Training Improves Torque Capacity and Strength in Mobility-Limited Older Adults. The journals of gerontology. Series A, Biological sciences and medical sciences Englund, D. A., Price, L. L., Grosicki, G. J., Iwai, M., Kashiwa, M., Liu, C., Reid, K. F., Fielding, R. A. 2019; 74 (8): 1316-1321

  Abstract

  Progressive resistance training (PRT) is consistently shown to improve muscle strength in older adults. The efficacy of PRT to improve muscle fatigue in older adults with demonstrated mobility limitations remains unclear.Mobility-limited (Short Physical Performance Battery [SPPB] ≤ 9) older adults (age 70-92 years) were recruited for this study and randomized to either PRT or home-based flexibility (FLEX) 3 d/wk for 12 weeks. Muscle fatigue and strength outcomes were assessed at baseline and 12 weeks. The primary outcome was torque capacity, a composite measure of strength and fatigue, defined as the sum of peak torques from an isokinetic fatigue test.Seventy participants were randomized (mean [SD] age 78.9 [5.4] years; 60% female; mean [SD] SPPB 7.5 [1.6]). At follow-up, the PRT group improved significantly in torque capacity, mean between-group difference (95% confidence interval) 466.19 (138.4, 793.97) Nm (p = .006), and maximal strength 127.3 (60.96, 193.61) Nm (p = .0003), when compared with FLEX group. Neither group demonstrated significant changes in muscle fatigue or torque variability.Twelve weeks of PRT improved torque capacity, as well as strength in mobility-limited older adults. These results demonstrate PRT improves multiple age-related muscular impairments.

  View details for DOI 10.1093/gerona/gly199

  View details for PubMedID 30165595

  View details for PubMedCentralID PMC6625591

• Translating the Lifestyle Interventions and Independence for Elders Clinical Trial to Older Adults in a Real-World Community-Based Setting. The journals of gerontology. Series A, Biological sciences and medical sciences Reid, K. F., Laussen, J., Bhatia, K., Englund, D. A., Kirn, D. R., Price, L. L., Manini, T. M., Liu, C. K., Kowaleski, C., Fielding, R. A. 2019; 74 (6): 924-928

  Abstract

  The Lifestyle Interventions and Independence for Elders (LIFE) clinical trial demonstrated that a structured program of physical activity (PA) reduced mobility-disability in older adults by up to 28%. It remains unknown whether the benefits of LIFE PA can be translated to older adults at risk for mobility-disability in real-world community-based settings. To address this knowledge gap, we conducted the ENhancing independence using Group-based community interventions for healthy AGing in Elders (ENGAGE) pilot study and examined the safety, feasibility, and preliminary effectiveness of translating LIFE PA to a community-based senior center.Forty older adults with severe lower extremity functional limitations (age: 76.9 ± 7.3 years; body mass index: 32.7 ± 8 kg/m2; 85% female; short physical performance battery score: 6.3 ± 2.2) were randomized to 24 weeks of PA or a health education control intervention.Community-based PA was safe (serious adverse events: PA vs health education, 0:2; nonserious adverse events: PA vs health education, 3:1) and participants successfully adhered to the PA intervention (65.2%). Compared to health education, PA participants who attended ≥25% of scheduled visits had meaningful and sustained short physical performance battery improvements at follow-up (between group short physical performance battery score differences: ~0.7 units).ENGAGE has demonstrated the preliminary safety, feasibility, and effectiveness of LIFE PA in a real-world community-based setting. Larger-scale translational studies are needed to further disseminate the benefits of LIFE PA to vulnerable older adults in a variety of community-based settings.

  View details for DOI 10.1093/gerona/gly152

  View details for PubMedID 30010808

  View details for PubMedCentralID PMC6521918

• Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trial BMC MEDICINE Liu, Z., Hsu, F., Trombetti, A., King, A. C., Liu, C. K., Manini, T. M., Fielding, R. A., Pahor, M., Newman, A. B., Kritchevsky, S., Gill, T. M., LIFE Study Investigators 2018; 16

  View details for DOI 10.1186/s12916-018-1174-8

  View details for Web of Science ID 000448124500001

• Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis. Ageing research reviews Custodero, C., Mankowski, R. T., Lee, S. A., Chen, Z., Wu, S., Manini, T. M., Hincapie Echeverri, J., Sabbà, C., Beavers, D. P., Cauley, J. A., Espeland, M. A., Fielding, R. A., Kritchevsky, S. B., Liu, C. K., McDermott, M. M., Miller, M. E., Tracy, R. P., Newman, A. B., Ambrosius, W. T., Pahor, M., Anton, S. D. 2018; 46: 42-59

  Abstract

  Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and C-reactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials. Six compounds met all five inclusion criteria for our systematic review and meta-analysis: angiotensin II receptor blockers (ARBs), metformin, omega-3, probiotics, resveratrol and vitamin D. We searched in MEDLINE, PubMed and EMBASE database until January 2017. A total of 49 articles fulfilled the selection criteria. Effect size of each study and pooled effect size for each compound were measured by the standardized mean difference. I2 was computed to measure heterogeneity of effects across studies. The following compounds showed a significant small to large effect in reducing IL-6 levels: probiotics (-0.68 pg/ml), ARBs (-0.37 pg/ml) and omega-3 (-0.19 pg/ml). For CRP, a significant small to medium effect was observed with probiotics (-0.43 mg/L), ARBs (-0.2 mg/L), omega-3 (-0.17 mg/L) and metformin (-0.16 mg/L). Resveratrol and vitamin D were not associated with any significant reductions in either biomarker. These results suggest that nutritional and pharmaceutical compounds can significantly reduce established biomarkers of systemic inflammation in middle-age and older adults. The findings should be interpreted with caution, however, due to the evidence of heterogeneity across the studies.

  View details for DOI 10.1016/j.arr.2018.05.004

  View details for PubMedID 29803716

  View details for PubMedCentralID PMC6235673

• A Comparison of Self-report Indices of Major Mobility Disability to Failure on the 400-m Walk Test: The LIFE Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Chen, H., Rejeski, W., Gill, T. M., Guralnik, J., King, A. C., Newman, A., Blair, S. N., Conroy, D., Liu, C., Manini, T. M., Pahor, M., Ambrosius, W. T., Miller, M. E., LIFE Study 2018; 73 (4): 513–18

  Abstract

  The objective assessment of major mobility disability (objective MMD) by a 400-m walk test (400 MWT) is important but not always practical. Previous research on the relationship between self-reported MMD (SR MMD) and objective MMD is sparse and limited to cross-sectional data.We evaluated agreement between SR MMD and objective MMD using longitudinal data from the Lifestyle Interventions for Elders (LIFE) study. The SR MMD indices were defined based on having a lot of difficulty or inability to walk a quarter of a mile (SR-1/4MILE), walk several blocks (SR-BLOCKS), and climb one flight of stairs (SR-STAIRS).Using objective MMD as the gold standard, SR-1/4MILE and SR-BLOCKS had relatively low sensitivity (around 0.4) and high specificity (around 0.9) for prevalence. Their overall sensitivity and specificity for cumulative incident objective MMD were approximately 0.6 and 0.8, respectively. While the annual probability of staying MMD free was similar for objective MMD, SR-1/4MILE, and SR-BLOCKS (90% for all), the probability of recovering from SR MMD was higher (50%) than that of objective MMD (22%). The development of objective MMD (439 events), SR-1/4MILE (356 events), and SR-BLOCKS (379 events) had a similar trajectory over time with substantially overlapping survival curves. SR-STAIRS generally did not agree well with objective MMD. Incorporating SR-STAIRS with either SR-1/4MILE or SR-BLOCKS did not significantly improve the agreement between SR MMD and objective MMD.Simple SR-1/4MILE and SR-BLOCKS are reasonable candidates to define MMD if the primary outcome of interest is incident MMD.

  View details for PubMedID 28958023

  View details for PubMedCentralID PMC5861858

• Effect of Physical Activity on Frailty Secondary Analysis of a Randomized Controlled Trial ANNALS OF INTERNAL MEDICINE Trombetti, A., Hars, M., Hsu, F., Reid, K. F., Church, T. S., Gill, T. M., King, A. C., Liu, C. K., Manini, T. M., McDermott, M. M., Newman, A. B., Rejeski, W., Guralnik, J. M., Pahor, M., Fielding, R. A., LIFE Study Investigators 2018; 168 (5): 309-+

  Abstract

  Limited evidence suggests that physical activity may prevent frailty and associated negative outcomes in older adults. Definitive data from large long-term randomized trials are lacking.To determine whether a long-term, structured, moderate-intensity physical activity program is associated with a lower risk for frailty and whether frailty status alters the effect of physical activity on the reduction in major mobility disability (MMD) risk.Multicenter, single-blind, randomized trial.8 centers in the United States.1635 community-dwelling adults, aged 70 to 89 years, with functional limitations.A structured, moderate-intensity physical activity program incorporating aerobic, resistance, and flexibility activities or a health education program consisting of workshops and stretching exercises.Frailty, as defined by the SOF (Study of Osteoporotic Fractures) index, at baseline and 6, 12, and 24 months, and MMD, defined as the inability to walk 400 m, for up to 3.5 years.Over 24 months of follow-up, the risk for frailty (n = 1623) was not statistically significantly different in the physical activity versus the health education group (adjusted prevalence difference, -0.021 [95% CI, -0.049 to 0.007]). Among the 3 criteria of the SOF index, the physical activity intervention was associated with improvement in the inability to rise from a chair (adjusted prevalence difference, -0.050 [CI, -0.081 to -0.020]). Baseline frailty status did not modify the effect of physical activity on reducing incident MMD (P for interaction = 0.91).Frailty status was neither an entry criterion nor a randomization stratum.A structured, moderate-intensity physical activity program was not associated with a reduced risk for frailty over 2 years among sedentary, community-dwelling older adults. The beneficial effect of physical activity on the incidence of MMD did not differ between frail and nonfrail participants.National Institute on Aging, National Institutes of Health.

  View details for PubMedID 29310138

• ENabling Reduction of Low-grade Inflammation in SEniors Pilot Study: Concept, Rationale, and Design. Journal of the American Geriatrics Society Manini, T. M., Anton, S. D., Beavers, D. P., Cauley, J. A., Espeland, M. A., Fielding, R. A., Kritchevsky, S. B., Leeuwenburgh, C., Lewis, K. H., Liu, C., McDermott, M. M., Miller, M. E., Tracy, R. P., Walston, J. D., Radziszewska, B., Lu, J., Stowe, C., Wu, S., Newman, A. B., Ambrosius, W. T., Pahor, M. 2017; 65 (9): 1961-1968

  Abstract

  To test two interventions to reduce interleukin (IL)-6 levels, an indicator of low-grade chronic inflammation and an independent risk factor for impaired mobility and slow walking speed in older adults.The ENabling Reduction of low-Grade Inflammation in SEniors (ENRGISE) Pilot Study was a multicenter, double-blind, placebo-controlled randomized pilot trial of two interventions to reduce IL-6 levels.Five university-based research centers.Target enrollment was 300 men and women aged 70 and older with an average plasma IL-6 level between 2.5 and 30 pg/mL measured twice at least 1 week apart. Participants had low to moderate physical function, defined as self-reported difficulty walking one-quarter of a mile or climbing a flight of stairs and usual walk speed of less than 1 m/s on a 4-m usual-pace walk.Participants were randomized to losartan, omega-3 fish oil (ω-3), combined losartan and ω-3, or placebo. Randomization was stratified depending on eligibility for each group. A titration schedule was implemented to reach a dose that was safe and effective for IL-6 reduction. Maximal doses were 100 mg/d for losartan and 2.8 g/d for ω-3.IL-6, walking speed over 400 m, physical function (Short Physical Performance Battery), other inflammatory markers, safety, tolerability, frailty domains, and maximal leg strength were measured.Results from the ENRGISE Pilot Study will provide recruitment yields, feasibility, medication tolerance and adherence, and preliminary data to help justify a sample size for a more definitive randomized trial.The ENRGISE Pilot Study will inform a larger subsequent trial that is expected to have important clinical and public health implications for the growing population of older adults with low-grade chronic inflammation and mobility limitations.

  View details for DOI 10.1111/jgs.14965

  View details for PubMedID 28734043

  View details for PubMedCentralID PMC5642998

• Exercise's effect on mobility disability in older adults with and without obesity: The LIFE study randomized clinical trial OBESITY Kritchevsky, S. B., Lovato, L., Handing, E. P., Blair, S., Botoseneanu, A., Guralnik, J. M., Liu, C., King, A., Marsh, A. P., Pahor, M., Rejeski, W., Spring, B., Manini, T. 2017; 25 (7): 1199–1205

  Abstract

  Some data suggest that obesity blunts the benefits of exercise on mobility in older adults. This study tested the homogeneity of the effect of a physical activity intervention on major mobility disability (MMD) across baseline obesity classifications in the Lifestyle Interventions and Independence for Elders (LIFE) Study. LIFE randomized 1,635 sedentary men and women aged 70 to 89 years to a moderate-intensity physical activity (PA) or health education program.MMD, defined as the inability to walk 400 m, was determined over an average follow-up of 2.6 years. Participants were divided into four subgroups: (1) nonobese (BMI < 30 kg/m2 ; n = 437); (2) nonobese with high waist circumference (WC > 102 cm [men], > 88 cm [women]; n = 434); (3) class 1 obesity (30 kg/m2  ≤ BMI < 35 kg/m2 ; n = 430); and (4) class 2 + obesity (BMI ≥ 35 kg/m2 ; n = 312). Cox proportional hazard modeling was used to test an obesity by intervention interaction.The PA intervention had the largest benefit in participants with class 2 + obesity (hazard ratio 0.69, 95% confidence interval 0.48, 0.98). However, there was no statistically significant difference in benefit across obesity categories.A structured PA program reduced the risk of MMD even in older adults with extreme obesity.

  View details for PubMedID 28653499

  View details for PubMedCentralID PMC5567861

• The Effect of Chronic Kidney Disease on a Physical Activity Intervention: Impact on Physical Function, Adherence, and Safety. Journal of clinical nephrology and renal care Liu, C. K., Milton, J., Hsu, F. C., Beavers, K. M., Yank, V., Church, T., Shegog, J. D., Kashaf, S., Nayfield, S., Newman, A., Stafford, R. S., Nicklas, B., Weiner, D. E., Fielding, R. A. 2017; 3 (1)

  Abstract

  Because chronic kidney disease (CKD) is associated with muscle wasting, older adults with CKD are likely to have physical function deficits. Physical activity can improve these deficits, but whether CKD attenuates the benefits is unknown. Our objective was to determine if CKD modified the effect of a physical activity intervention in older adults.This is an exploratory analysis of the LIFE-P study, which compared a 12-month physical activity program (PA) to a successful aging education program (SA) in older adults. CKD was defined as a baseline eGFR < 60 mL/min/1.73 m2. We examined the Short Physical Performance Battery (SPPB) at baseline, 6 and 12 months. Secondary outcomes included serious adverse events (SAE) and adherence to intervention frequency. Linear mixed models were adjusted for age, sex, diabetes, hypertension, CKD, intervention, site, visit, baseline SPPB, and interactions of intervention and visit and of intervention, visit, and baseline CKD.The sample included 368 participants. CKD was present in 105 (28.5%) participants with a mean eGFR of 49.2 ± 8.1 mL/min/1.73 m2. Mean SPPB was 7.38 ± 1.41 in CKD participants; 7.59 ± 1.44 in those without CKD (p = 0.20). For CKD participants in PA, 12-month SPPBs increased to 8.90 (95% CI 8.32, 9.47), while PA participants without CKD increased to 8.40 (95% CI 8.01, 8.79, p = 0.43). For CKD participants in SA, 12-month SPPBs increased to 7.67 (95% CI 7.07, 8.27), while participants without CKD increased to 8.12 (95% CI 7.72, 8.52, p = 0.86). Interaction between CKD and intervention was non-significant (p = 0.88). Number and type of SAEs were not different between CKD and non-CKD participants (all p > 0.05). In PA, adherence for CKD participants was 65.5 ± 25.4%, while for those without CKD was 74.0 ± 22.2% (p = 0.12).Despite lower adherence, older adults with CKD likely derive clinically meaningful benefits from physical activity with no apparent impact on safety, compared to those without CKD.

  View details for DOI 10.23937/2572-3286.1510021

  View details for PubMedID 29745380

  View details for PubMedCentralID PMC5937279

• Effect of a Long-Term Physical Activity Intervention on Resting Pulse Rate in Older Persons: Results from the Lifestyle Interventions and Independence for Elders Study. Journal of the American Geriatrics Society Ó Hartaigh, B., Lovato, L. C., Pahor, M., Buford, T. W., Dodson, J. A., Forman, D. E., Buman, M. P., Demons, J. L., Santanasto, A. J., Liu, C., Miller, M. E., McDermott, M. M., Gill, T. M. 2016; 64 (12): 2511-2516

  Abstract

  To assess the utility of a long-term physical activity (PA) intervention for reducing resting pulse rate (RPR) in older persons.Community.Lifestyle Interventions and Independence for Elders Study.Individuals aged 70 to 89 (N = 1,635, 67.2% women) were randomized to a moderate-intensity PA intervention (n = 818) or a health education-based successful aging (SA) intervention (n = 817).RPR was recorded at baseline and 6, 18, and 30 months. Longitudinal changes in RPR of intervention groups were compared using a mixed-effects analysis of covariance model for repeated-measure outcomes, generating least squares means with standard errors (SEs) or 95% confidence intervals (CIs).Mean duration of the study was 2.6 years (median 2.7 years, interquartile range 2.3-3.1 years). The average effect of the PA intervention on RPR over the course of the study period was statistically significant but clinically small (average intervention difference = 0.84 beats/min; 95% CI = 0.17-1.51; Paverage = .01), with the most pronounced effect observed at 18 months (PA, 66.5 beats/min (SE 0.32 beats/min); SA, 67.8 beats/min (SE 0.32 beats/min); difference = 1.37 beats/min, 95% CI = 0.48-2.26 beats/min). The relationship became somewhat weaker and was not statistically significant at 30 months. There were no significant differences between several prespecified subgroups.A long-term moderate-intensity PA program was associated with a small and clinically insignificant slowing of RPR in older persons. Whether PA can deliver a beneficial reduction in RPR requires further examination in older adults.

  View details for DOI 10.1111/jgs.14380

  View details for PubMedID 27787876

  View details for PubMedCentralID PMC5173403

• Effect of Structured Physical Activity on Respiratory Outcomes in Sedentary Elderly Adults with Mobility Limitations. Journal of the American Geriatrics Society Vaz Fragoso, C. A., Beavers, D. P., Anton, S. D., Liu, C. K., McDermott, M. M., Newman, A. B., Pahor, M., Stafford, R. S., Gill, T. M. 2016; 64 (3): 501-509

  Abstract

  To evaluate the effect of structured physical activity on respiratory outcomes in community-dwelling elderly adults with mobility limitations.Multicenter, randomized trial of physical activity vs health education, with respiratory variables prespecified as tertiary outcomes over an intervention period of 24-42 months. Physical activity included walking (goal of 150 min/week) and strength, flexibility, and balance training. Health education included workshops on topics relevant to older adults and upper extremity stretching exercises.Lifestyle Interventions and Independence in Elders (LIFE) Study.Community-dwelling persons aged 70-89 with Short Physical Performance Battery scores less than 10 (N = 1,635).Dyspnea severity (defined as moderate to severe according to a Borg index >2 immediately after a 400-m walk), forced expiratory volume in 1 second (FEV1) (

  View details for DOI 10.1111/jgs.14013

  View details for PubMedID 27000324

• Biomarkers of oxidative stress are associated with frailty: the Framingham Offspring Study. Age (Dordrecht, Netherlands) Liu, C. K., Lyass, A., Larson, M. G., Massaro, J. M., Wang, N., D'Agostino, R. B., Benjamin, E. J., Murabito, J. M. 2016; 38 (1): 1

  Abstract

  Cardiovascular disease and frailty frequently occur together. Both are associated with inflammation, which may be partially triggered by oxidative stress, especially in cardiovascular disease. We investigated whether inflammatory and oxidative stress biomarkers linked to cardiovascular disease were associated with frailty and the related outcome of gait speed. We report cross-sectional associations of biomarkers and frailty assessed at Framingham Offspring Study cycle eight. Participants ≥60 years were eligible if they had information on frailty and at least one of the following: C-reactive protein, interleukin-6, tumor necrosis factor receptor 2, 8-epi-FGFα isoprostanes (isoprostanes), lipoprotein phospholipase A2 (LpPLA2) mass or activity, osteoprotegerin, intracellular adhesion molecule-1, monocyte chemoattractant protein-1 or P-selectin. Stepwise logistic models were utilized for frailty and stepwise linear models for gait speed. Covariates included age, sex, body mass index, smoking, and co-morbidities. Odds ratios (ORs) and slope estimates (B) are reported per standard deviation increase of loge-transformed biomarker. Of the 1919 participants, 142 (7 %) were frail. In a stepwise model, frailty odds increased with higher interleukin-6 (OR 1.90, 95 % CI 1.51, 2.38), isoprostanes (OR 1.46, 95 % CI 1.12, 1.92), and LpPLA2 mass (OR 1.29, 95 % CI 1.00, 1.65). Stepwise regression found that slower gait speeds were associated with interleukin-6 (B = -0.025 m/s, 95 % CI 0.04, -0.01), isoprostanes (B = -0.019, 95 % CI -0.03, -0.008), LpPLA2 mass (B = -0.016, 95 % CI -0.03, -0.004), and osteoprotegerin (B = -0.015, 95 % CI -0.03, -0.002, all p < 0.05). Interleukin-6, isoprostanes, and LpPLA2 mass were associated with greater frailty odds and slower gait speeds. Oxidative stress may be a mechanism contributing to frailty.

  View details for DOI 10.1007/s11357-015-9864-z

  View details for PubMedID 26695510

  View details for PubMedCentralID PMC5005887

• Sedentary time is associated with the metabolic syndrome in older adults with mobility limitations - The LIFE Study EXPERIMENTAL GERONTOLOGY Mankowski, R. T., Aubertin-Leheudre, M., Beavers, D. P., Botoseneanu, A., Buford, T. W., Church, T., Glynn, N. W., King, A. C., Liu, C., Manini, T. M., Marsh, A. P., McDermott, M., Nocera, J. R., Pahor, M., Strotmeyer, E. S., Anton, S. D. 2015; 70: 32-36

  Abstract

  Epidemiological and objective studies report an association between sedentary time and lower risk of the metabolic syndrome (MetS) and its risk factors in young and middle-age adults. To date, there is a lack of objective data on the association between sedentary time and MetS among older adults.The association between objectively measured sedentary time (accelerometry) with MetS and MetS components was examined in a large sample of older adults with mobility limitations (N=1198; mean age=78.7 ± 5.3 years) enrolled in the Lifestyle Interventions and Independence for Elders (LIFE) study. Participants were divided into tertiles according to percentage of daily sedentary time, and the relation between sedentary time with MetS and MetS components was examined after adjusting for age, sex, ethnicity, and BMI.Participants in the highest sedentary time tertile had significantly higher odds of MetS (OR=1.54) (95% CI 1.13 to 2.11) in comparison with participants in the lowest tertile (p=0.03). Participants in the highest sedentary time tertile had larger waist circumference (p=0.0001) and lower HDL-C (p=0.0003) than participants in the lowest sedentary time tertile.Sedentary time was strongly related to higher odds of MetS. These results, based on objectively measured sedentary time, suggest that sedentary time may represent an important risk factor for the development of MetS in older adults with high likelihood for disability.

  View details for DOI 10.1016/j.exger.2015.06.018

  View details for PubMedID 26130060

• Effect of Structured Physical Activity on Sleep-Wake Behaviors in Sedentary Elderly Adults with Mobility Limitations. Journal of the American Geriatrics Society Vaz Fragoso, C. A., Miller, M. E., King, A. C., Kritchevsky, S. B., Liu, C. K., Myers, V. H., Nadkarni, N. K., Pahor, M., Spring, B. J., Gill, T. M. 2015; 63 (7): 1381-1390

  Abstract

  To evaluate the effect of structured physical activity on sleep-wake behaviors in sedentary community-dwelling elderly adults with mobility limitations.Multicenter, randomized trial of moderate-intensity physical activity versus health education, with sleep-wake behaviors prespecified as a tertiary outcome over a planned intervention period ranging from 24 to 30 months.Lifestyle Interventions and Independence for Elders Study.Community-dwelling persons aged 70 to 89 who were initially sedentary and had a Short Physical Performance Battery score less than 10 (N = 1,635).Sleep-wake behaviors were evaluated using the Insomnia Severity Index (ISI) (≥8 defined insomnia), Epworth Sleepiness Scale (ESS) (≥10 defined daytime drowsiness), and Pittsburgh Sleep Quality Index (PSQI) (>5 defined poor sleep quality) administered at baseline and 6, 18, and 30 months.The randomized groups were similar in terms of baseline demographic variables, including mean age (79) and sex (67% female). Structured physical activity resulted in a significantly lower likelihood of having poor sleep quality (adjusted odds ratios (aOR) for PSQI >5 = 0.80, 95% confidence interval (CI) = 0.68-0.94), including fewer new cases (aOR for PSQI >5 = 0.70, 95% CI = 0.54-0.89), than health education but not in resolution of prevalent cases (aOR for PSQI ≤5 = 1.13, 95% CI = 0.90-1.43). No significant intervention effects were observed for the ISI or ESS.Structured physical activity resulted in a lower likelihood of developing poor sleep quality (PSQI >5) over the intervention period than health education but had no effect on prevalent cases of poor sleep quality or on sleep-wake behaviors evaluated using the ISI or ESS. These results suggest that the benefit of physical activity in this sample was preventive and limited to sleep-wake behaviors evaluated using the PSQI.

  View details for DOI 10.1111/jgs.13509

  View details for PubMedID 26115386

• The Vitality, Independence, and Vigor in the Elderly 2 Study (VIVE2): Design and methods. Contemporary clinical trials Kirn, D. R., Koochek, A., Reid, K. F., von Berens, Å., Travison, T. G., Folta, S., Sacheck, J., Nelson, M., Liu, C., Phillips, E., Åberg, A. C., Nydahl, M., Gustafsson, T., Cederholm, T., Fielding, R. A. 2015; 43: 164-71

  Abstract

  Nutritional supplementation may potentiate the increase in skeletal muscle protein synthesis following exercise in healthy older individuals. Whether exercise and nutrition act synergistically to produce sustained changes in physical functioning and body composition has not been well studied, particularly in mobility-limited older adults.The VIVE2 study was a multi-center, randomized controlled trial, conducted in the United States and Sweden. This study was designed to compare the effects of a 6-month intervention with a once daily, experimental, 4 fl.oz. liquid nutritional supplement providing 150 kcal, whey protein (20 g), and vitamin D (800 IU) (Nestlé Health Science, Vevey, Switzerland), to a low calorie placebo drink (30 kcal, non-nutritive; identical format) when combined with group-based exercise in 150 community-dwelling, mobility-limited older adults. All participants participated in a structured exercise program (3 sessions/week for 6 months), which included aerobic, strength, flexibility, and balance exercises.The primary outcome was 6-month change in 400 m walk performance (m/s) between supplement and placebo groups. Secondary outcomes included 6 month change in: body composition, muscle cross-sectional area, leg strength, grip strength, stair climb time, quality of life, physical performance, mood/depressive symptoms and nutritional status. These outcomes were selected based on their applicability to the health and well-being of older adults.The results of this study will further define the role of nutritional supplementation on physical functioning and restoration of skeletal muscle mass in older adults. Additionally, these results will help refine the current physical activity and nutritional recommendations for mobility-limited older adults.

  View details for DOI 10.1016/j.cct.2015.06.001

  View details for PubMedID 26044464

• Combined Reduced Forced Expiratory Volume in 1 Second (FEV1) and Peripheral Artery Disease in Sedentary Elders With Functional Limitations JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION Fragoso, C. A., Hsu, F., Brinkley, T., Church, T., Liu, C. K., Manini, T., Newman, A. B., Stafford, R. S., McDermott, M. M., Gill, T. M. 2014; 15 (9): 665-670

  Abstract

  Because they are potentially modifiable and may coexist, we evaluated the combined occurrence of a reduced forced expiratory volume in 1 second (FEV1) and peripheral artery disease (PAD), including its association with exertional symptoms, physical inactivity, and impaired mobility, in sedentary elders with functional limitations.Cross sectional.Lifestyle Interventions and Independence in Elder (LIFE) Study.A total of 1307 sedentary community-dwelling persons, mean age 78.9, with functional limitations (Short Physical Performance Battery [SPPB] <10).A reduced FEV1 was defined by a z-score less than -1.64 (

  View details for DOI 10.1016/j.jamda.2014.05.008

  View details for Web of Science ID 000341167700011

  View details for PubMedID 24973990

  View details for PubMedCentralID PMC4145029

• Effect of Structured Physical Activity on Prevention of Major Mobility Disability in Older Adults The LIFE Study Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Pahor, M., Guralnik, J. M., Ambrosius, W. T., Blair, S., Bonds, D. E., Church, T. S., Espeland, M. A., Fielding, R. A., Gill, T. M., Groessl, E. J., King, A. C., Kritchevsky, S. B., Manini, T. M., McDermott, M. M., Miller, M. E., Newman, A. B., Rejeski, W. J., Sink, K. M., Williamson, J. D. 2014; 311 (23): 2387-2396

  Abstract

  In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability.To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability.The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban, and rural communities at 8 centers throughout the United States. We randomized a volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m.Participants were randomized to a structured, moderate-intensity physical activity program (n = 818) conducted in a center (twice/wk) and at home (3-4 times/wk) that included aerobic, resistance, and flexibility training activities or to a health education program (n = 817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises.The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m.Incident major mobility disability occurred in 30.1% (246 participants) of the physical activity group and 35.5% (290 participants) of the health education group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98], P = .03).Persistent mobility disability was experienced by 120 participants (14.7%) in the physical activity group and 162 participants (19.8%) in the health education group (HR, 0.72 [95% CI, 0.57-0.91]; P = .006). Serious adverse events were reported by 404 participants (49.4%) in the physical activity group and 373 participants (45.7%) in the health education group (risk ratio, 1.08 [95% CI, 0.98-1.20]).A structured, moderate-intensity physical activity program compared with a health education program reduced major mobility disability over 2.6 years among older adults at risk for disability. These findings suggest mobility benefit from such a program in vulnerable older adults.clinicaltrials.gov Identifier: NCT01072500.

  View details for DOI 10.1001/jama.2014.5616

  View details for Web of Science ID 000337301500019

• Respiratory Impairment and Dyspnea and Their Associations with Physical Inactivity and Mobility in Sedentary Community-Dwelling Older Persons JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Fragoso, C. A., Beavers, D. P., Hankinson, J. L., Flynn, G., Berra, K., Kritchevsky, S. B., Liu, C. K., McDermott, M., Manini, T. M., Rejeski, W. J., Gill, T. M. 2014; 62 (4): 622-628

  Abstract

  To evaluate the prevalence of respiratory impairment and dyspnea and their associations with objectively measured physical inactivity and performance-based mobility in sedentary older persons.Cross-sectional.Lifestyle Interventions and Independence for Elders Study.Community-dwelling older persons (n = 1,635, mean age 78.9) who reported being sedentary (<20 min/wk of regular physical activity and <125 min/wk of moderate physical activity in past month).Respiratory impairment was defined as low ventilatory capacity (forced expiratory volume in 1 second less than lower limit of normal (LLN)) and respiratory muscle weakness (maximal inspiratory pressure

  View details for DOI 10.1111/jgs.12738

  View details for Web of Science ID 000334289900004

  View details for PubMedCentralID PMC3989438

• Chronic kidney disease defined by cystatin C predicts mobility disability and changes in gait speed: the Framingham Offspring Study. The journals of gerontology. Series A, Biological sciences and medical sciences Liu, C. K., Lyass, A., Massaro, J. M., D'Agostino, R. B., Fox, C. S., Murabito, J. M. 2014; 69 (3): 301-7

  Abstract

  As creatinine-based estimates of renal function are inaccurate in older adults, an alternative is an estimated glomerular filtration rate (eGFR(cys)) based on cystatin C. We examined the prospective association between chronic kidney disease (CKD(cys)) as determined by eGFR(cys) with the primary outcome of incident mobility disability and the secondary outcome of change in gait speed.Framingham Offspring Study participants older than 60 years and free of mobility disability at baseline (1998-2001) were eligible. Baseline CKD(cys) was defined as eGFR(cys) less than 60 mL/min/1.73 m(2). At follow-up (2005-2008), the outcomes of mobility disability, defined as self-reported inability to walk 1/2 mile and/or climb a flight of stairs, and gait speed were measured. Logistic and linear regression models were adjusted for age, sex, body mass index, smoking, diabetes, C reactive protein, and physical activity.Of 1,226 participants, 230 (19%) had CKD(cys) at baseline. After a mean follow-up of 6.6 years, 185 (15%) developed mobility disability. Of those with CKD(cys), 60 (26%) developed mobility disability. Those with CKD(cys) had greater odds of mobility disability in the age- and sex-adjusted (odds ratio [OR] 1.91, 95% CI 1.32, 2.75) and fully adjusted (OR 1.55, 95% CI 1.05, 2.31) models compared with those without CKD(cys). In fully adjusted models, participants with CKD(cys) had greater gait speed declines than those without CKD(cys) (β = 0.07 [SE 0.02], p = .0022).CKD(cys) was associated with higher odds of incident mobility disability and greater decline in gait speed, highlighting the loss of physical independence in elders with CKD.

  View details for DOI 10.1093/gerona/glt096

  View details for PubMedID 23913929

  View details for PubMedCentralID PMC3976137

• The impact of sarcopenia on a physical activity intervention: the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). The journal of nutrition, health & aging Liu, C. K., Leng, X., Hsu, F. C., Kritchevsky, S. B., Ding, J., Earnest, C. P., Ferrucci, L., Goodpaster, B. H., Guralnik, J. M., Lenchik, L., Pahor, M., Fielding, R. A. 2014; 18 (1): 59-64

  Abstract

  To determine if sarcopenia modulates the response to a physical activity intervention in functionally limited older adults.Secondary analysis of a randomized controlled trial.Three academic centers.Elders aged 70 to 89 years at risk for mobility disability who underwent dual-energy x-ray absorptiometry (DXA) for body composition at enrollment and follow-up at twelve months (N = 177).Subjects participated in a physical activity program (PA) featuring aerobic, strength, balance, and flexibility training, or a successful aging (SA) educational program about healthy aging.Sarcopenia as determined by measuring appendicular lean mass and adjusting for height and total body fat mass (residuals method), Short Physical Performance Battery score (SPPB), and gait speed determined on 400 meter course.At twelve months, sarcopenic and non-sarcopenic subjects in PA tended to have higher mean SPPB scores (8.7±0.5 and 8.7±0.2 points) compared to sarcopenic and non-sarcopenic subjects in SA (8.3±0.5 and 8.4±0.2 points, p = 0.24 and 0.10), although the differences were not statistically significant. At twelve months, faster mean gait speeds were observed in PA: 0.93±0.4 and 0.95±0.03 meters/second in sarcopenic and non-sarcopenic PA subjects, and 0.89±0.4 and 0.91±0.03 meters/second in sarcopenic and non-sarcopenic SA subjects (p = 0.98 and 0.26), although not statistically significant. There was no difference between the sarcopenic and non-sarcopenic groups in intervention adherence or number of adverse events.These data suggest that older adults with sarcopenia, who represent a vulnerable segment of the elder population, are capable of improvements in physical performance after a physical activity intervention.

  View details for DOI 10.1007/s12603-013-0369-0

  View details for PubMedID 24402391

  View details for PubMedCentralID PMC4111145

• JC virus binds to primary human glial cells, tonsillar stromal cells, and B-lymphocytes, but not to T lymphocytes. Journal of neurovirology Wei, G., Liu, C. K., Atwood, W. J. 2000; 6 (2): 127-36

  Abstract

  The human polyomavirus, JCV, is the etiological agent of the fatal central nervous system demyelinating disease, progressive multifocal leukoencephalopathy (PML). In PML patients, JC Virus (JCV) can be detected in glial cells in the central nervous system (CNS); in B-lymphocytes in the peripheral blood, bone marrow, spleen, and tonsil; and in tonsillar stromal cells. In vitro, JCV infects glial cells, tonsillar stromal cells, and to a limited extent B-lymphocytes. The presence or absence of as yet unidentified cell type specific transcription factors contributes to the restricted tropism of JCV for these cell types. However, several studies indicate that cell surface receptors may also contribute to the limited host range of JCV. To examine this latter possibility we measured the binding of purified JCV virions to primary cultures of glial cells, tonsillar stromal cells, peripheral blood lymphocytes, and to several established cell lines. Our results demonstrate that JCV binds to primary glial cells, stromal cells, and B cells, but does not bind to primary T cells. In contrast, JCV bound to all cell lines tested, including the Namalwa B cell line and the Jurkat T cell line. These data are novel and demonstrate that JCV selectively interacts with cells in vivo that are known to be susceptible to infection. This selectivity appears to be lost when one examines virus binding to a variety of human, monkey, or mouse tumor cell lines. We next examined the susceptibility of primary peripheral blood lymphocytes and the Namalwa B cell line to infection with JCV. Our results demonstrate that the majority of infectious JCV virions remain cell surface associated and do not efficiently establish infection of B cells. This may explain the in vivo observation that JCV DNA is frequently detected in association with lymphocytes by PCR but that JCV mRNA is rarely detected in association with lymphocytes by reverse transcriptase PCR. These results also confirm previous data regarding the association of JCV with human B cells in vivo and support the hypothesis that B cells may be involved in trafficking of JCV to the CNS.

  View details for DOI 10.3109/13550280009013156

  View details for PubMedID 10822326

• Infection of glial cells by the human polyomavirus JC is mediated by an N-linked glycoprotein containing terminal alpha(2-6)-linked sialic acids. Journal of virology Liu, C. K., Wei, G., Atwood, W. J. 1998; 72 (6): 4643-9

  Abstract

  The human JC polyomavirus (JCV) is the etiologic agent of the fatal central nervous system (CNS) demyelinating disease progressive multifocal leukoencephalopathy (PML). PML typically occurs in immunosuppressed patients and is the direct result of JCV infection of oligodendrocytes. The initial event in infection of cells by JCV is attachment of the virus to receptors present on the surface of a susceptible cell. Our laboratory has been studying this critical event in the life cycle of JCV, and we have found that JCV binds to a limited number of cell surface receptors on human glial cells that are not shared by the related polyomavirus simian virus 40 (C. K. Liu, A. P. Hope, and W. J. Atwood, J. Neurovirol. 4:49-58, 1998). To further characterize specific JCV receptors on human glial cells, we tested specific neuraminidases, proteases, and phospholipases for the ability to inhibit JCV binding to and infection of glial cells. Several of the enzymes tested were capable of inhibiting virus binding to cells, but only neuraminidase was capable of inhibiting infection. The ability of neuraminidase to inhibit infection correlated with its ability to remove both alpha(2-3)- and alpha(2-6)-linked sialic acids from glial cells. A recombinant neuraminidase that specifically removes the alpha(2-3) linkage of sialic acid had no effect on virus binding or infection. A competition assay between virus and sialic acid-specific lectins that recognize either the alpha(2-3) or the alpha(2-6) linkage revealed that JCV preferentially interacts with alpha(2-6)-linked sialic acids on glial cells. Treatment of glial cells with tunicamycin, but not with benzyl N-acetyl-alpha-D-galactosaminide, inhibited infection by JCV, indicating that the sialylated JCV receptor is an N-linked glycoprotein. As sialic acid containing glycoproteins play a fundamental role in mediating many virus-cell and cell-cell recognition processes, it will be of interest to determine what role these receptors play in the pathogenesis of PML.

  View details for DOI 10.1128/JVI.72.6.4643-4649.1998

  View details for PubMedID 9573227

  View details for PubMedCentralID PMC109982

• The human polyomavirus, JCV, does not share receptor specificity with SV40 on human glial cells. Journal of neurovirology Liu, C. K., Hope, A. P., Atwood, W. J. 1998; 4 (1): 49-58

  Abstract

  The initial event in the life cycle of a virus is its interaction with specific receptors present on the surface of a cell. Understanding these interactions is important to our understanding of viral tropism and tissue specific pathology associated with viral disease. The human polyomavirus, JCV, is the etiological agent of the fatal central nervous system (CNS) demyelinating disease, progressive multifocal leukoencephalopathy (PML). PML is the direct result of JCV infection of oligodendrocytes, the myelin producing cell in the CNS. In vivo, JCV can be detected in oligodendrocytes, astrocytes, lymphoid tissue, and peripheral blood of PML patients. In vitro, JCV infects human glial cells, tonsilar stromal cells, and, to a limited extent, human B lymphocytes. The initial step in infection of cells by JCV is at the level of attachment and entry. A specific cell surface receptor for JCV on human glial cells has not been identified. To begin to understand the nature of JCV receptors on human glial cells, large quantities of a previously characterized hybrid JC virus (Mad-1/SVEdelta) were purified. A direct virus binding assay demonstrated that these highly purified and labeled JCV virions bound to a finite number of cellular receptors on human glial cells. A competitive virus binding assay demonstrated that an excess of unlabeled JCV competed with labeled JCV more efficiently than did an excess of purified SV40. Furthermore, anti-class I antibodies which inhibited infection of glial cells by SV40 had no significant effect on infection by JCV. These results imply that JCV does not share receptor specificity with the related polyomavirus, SV40.

  View details for DOI 10.3109/13550289809113481

  View details for PubMedID 9531011