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1.
Cancer ; 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38881266

ABSTRACT

BACKGROUND: Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear. METHODS: The ADT & Metabolism Study was a single-center, 24-week, prospective observational study that enrolled ADT-naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non-ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks. RESULTS: At 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], -2.10 to 4.43; p = .47) or skeletal muscle (-3.2; 95% CI, -7.07 to 0.66; p = .10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non-ADT group. Men undergoing ADT gained 3.7 kg of fat mass. CONCLUSIONS: In men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short-term ADT.

2.
Ann Intern Med ; 168(5): 309-316, 2018 03 06.
Article in English | MEDLINE | ID: mdl-29310138

ABSTRACT

Background: 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. Objective: 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. Design: Multicenter, single-blind, randomized trial. Setting: 8 centers in the United States. Participants: 1635 community-dwelling adults, aged 70 to 89 years, with functional limitations. Intervention: A structured, moderate-intensity physical activity program incorporating aerobic, resistance, and flexibility activities or a health education program consisting of workshops and stretching exercises. Measurements: 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. Results: 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). Limitation: Frailty status was neither an entry criterion nor a randomization stratum. Conclusion: 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. Primary Funding Source: National Institute on Aging, National Institutes of Health.


Subject(s)
Exercise , Frail Elderly , Frailty/rehabilitation , Aged , Aged, 80 and over , Disability Evaluation , Female , Geriatric Assessment , Humans , Male , Quality of Life , Single-Blind Method , Treatment Outcome , United States
3.
Ann Intern Med ; 165(2): 77-86, 2016 Jul 19.
Article in English | MEDLINE | ID: mdl-27183035

ABSTRACT

BACKGROUND: Few remedies effectively treat long-term pain and disability from knee osteoarthritis. Studies suggest that Tai Chi alleviates symptoms, but no trials have directly compared Tai Chi with standard therapies for osteoarthritis. OBJECTIVE: To compare Tai Chi with standard physical therapy for patients with knee osteoarthritis. DESIGN: Randomized, 52-week, single-blind comparative effectiveness trial. (ClinicalTrials.gov: NCT01258985). SETTING: An urban tertiary care academic hospital. PATIENTS: 204 participants with symptomatic knee osteoarthritis (mean age, 60 years; 70% women; 53% white). INTERVENTION: Tai Chi (2 times per week for 12 weeks) or standard physical therapy (2 times per week for 6 weeks, followed by 6 weeks of monitored home exercise). MEASUREMENTS: The primary outcome was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 12 weeks. Secondary outcomes included physical function, depression, medication use, and quality of life. RESULTS: At 12 weeks, the WOMAC score was substantially reduced in both groups (Tai Chi, 167 points [95% CI, 145 to 190 points]; physical therapy, 143 points [CI, 119 to 167 points]). The between-group difference was not significant (24 points [CI, -10 to 58 points]). Both groups also showed similar clinically significant improvement in most secondary outcomes, and the benefits were maintained up to 52 weeks. Of note, the Tai Chi group had significantly greater improvements in depression and the physical component of quality of life. The benefit of Tai Chi was consistent across instructors. No serious adverse events occurred. LIMITATION: Patients were aware of their treatment group assignment, and the generalizability of the findings to other settings remains undetermined. CONCLUSION: Tai Chi produced beneficial effects similar to those of a standard course of physical therapy in the treatment of knee osteoarthritis. PRIMARY FUNDING SOURCE: National Center for Complementary and Integrative Health of the National Institutes of Health.


Subject(s)
Osteoarthritis, Knee/therapy , Physical Therapy Modalities , Tai Ji , Comparative Effectiveness Research , Depression/therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Osteoarthritis, Knee/psychology , Quality of Life , Single-Blind Method , Treatment Outcome
4.
J Aging Phys Act ; 25(3): 453-463, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28095099

ABSTRACT

This cluster-randomized trial was designed to determine the efficacy of a 6-month exercise-nutritional supplement program (ENP) on physical function and nutritional status for older adults and the feasibility of implementing this program in a senior living setting. Twenty senior-living facilities were randomized to either a 3 day per week group-based ENP led by a trained facility staff member or a health education program (SAP). Participants (N = 121) completed a short physical performance battery, 400-m walk, handgrip strength test, and mini-nutrition assessment. 25-hydroxyvitamin D [25(OH)D], insulin-like growth-factor 1 (IGF-1), and activity level were also measured. The ENP did not significantly improve physical function or nutritional status compared with the SAP. Compared with baseline, participants in the ENP engaged in 39 min less physical activity per week at 6 months. Several facility characteristics hindered implementation of the ENP. This study highlights the complexity of implementing an evidence-based program in a field setting.


Subject(s)
Dietary Supplements , Exercise Therapy/methods , Homes for the Aged , Mobility Limitation , Nursing Homes , Physical Fitness/physiology , Aged , Cluster Analysis , Female , Hand Strength/physiology , Humans , Insulin-Like Growth Factor I/analysis , Male , Nutritional Status , Task Performance and Analysis , Treatment Outcome , Vitamin D/analogs & derivatives , Vitamin D/analysis
5.
JAMA ; 314(8): 781-90, 2015 Aug 25.
Article in English | MEDLINE | ID: mdl-26305648

ABSTRACT

IMPORTANCE: Epidemiological evidence suggests that physical activity benefits cognition, but results from randomized trials are limited and mixed. OBJECTIVE: To determine whether a 24-month physical activity program results in better cognitive function, lower risk of mild cognitive impairment (MCI) or dementia, or both, compared with a health education program. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial, the Lifestyle Interventions and Independence for Elders (LIFE) study, enrolled 1635 community-living participants at 8 US centers from February 2010 until December 2011. Participants were sedentary adults aged 70 to 89 years who were at risk for mobility disability but able to walk 400 m. INTERVENTIONS: A structured, moderate-intensity physical activity program (n = 818) that included walking, resistance training, and flexibility exercises or a health education program (n = 817) of educational workshops and upper-extremity stretching. MAIN OUTCOMES AND MEASURES: Prespecified secondary outcomes of the LIFE study included cognitive function measured by the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale (score range: 0-133; higher scores indicate better function) and the revised Hopkins Verbal Learning Test (HVLT-R; 12-item word list recall task) assessed in 1476 participants (90.3%). Tertiary outcomes included global and executive cognitive function and incident MCI or dementia at 24 months. RESULTS: At 24 months, DSC task and HVLT-R scores (adjusted for clinic site, sex, and baseline values) were not different between groups. The mean DSC task scores were 46.26 points for the physical activity group vs 46.28 for the health education group (mean difference, -0.01 points [95% CI, -0.80 to 0.77 points], P = .97). The mean HVLT-R delayed recall scores were 7.22 for the physical activity group vs 7.25 for the health education group (mean difference, -0.03 words [95% CI, -0.29 to 0.24 words], P = .84). No differences for any other cognitive or composite measures were observed. Participants in the physical activity group who were 80 years or older (n = 307) and those with poorer baseline physical performance (n = 328) had better changes in executive function composite scores compared with the health education group (P = .01 for interaction for both comparisons). Incident MCI or dementia occurred in 98 participants (13.2%) in the physical activity group and 91 participants (12.1%) in the health education group (odds ratio, 1.08 [95% CI, 0.80 to 1.46]). CONCLUSIONS AND RELEVANCE: Among sedentary older adults, a 24-month moderate-intensity physical activity program compared with a health education program did not result in improvements in global or domain-specific cognitive function. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01072500.


Subject(s)
Cognitive Dysfunction/prevention & control , Dementia/prevention & control , Executive Function , Exercise Therapy/methods , Health Promotion , Sedentary Behavior , Age Factors , Aged , Aged, 80 and over , Cognitive Dysfunction/epidemiology , Dementia/epidemiology , Female , Health Education , Humans , Male , Muscle Stretching Exercises , Resistance Training , Treatment Outcome , Upper Extremity , Walking
6.
Calcif Tissue Int ; 95(5): 393-404, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25148876

ABSTRACT

Prospective controlled evidence supporting the efficacy of long-term exercise to prevent physical decline and reduce falls in old age is lacking. The present study aimed to assess the effects of long-term music-based multitask exercise (i.e., Jaques-Dalcroze eurhythmics) on physical function and fall risk in older adults. A 3-year follow-up extension of a 1-year randomized controlled trial (NCT01107288) was conducted in Geneva (Switzerland), in which 134 community-dwellers aged ≥65 years at increased risk of falls received a 6-month music-based multitask exercise program. Four years following original trial enrolment, 52 subjects (baseline mean ± SD age, 75 ± 8 years) who (i) have maintained exercise program participation through the 4-year follow-up visit ("long-term intervention group", n = 23) or (ii) have discontinued participation following original trial completion ("control group", n = 29) were studied. They were reassessed in a blind fashion, using the same procedures as at baseline. At 4 years, linear mixed-effects models showed significant gait (gait speed, P = 0.006) and balance (one-legged stance time, P = 0.015) improvements in the long-term intervention group, compared with the control group. Also, long-term intervention subjects did better on Timed Up & Go, Five-Times-Sit-to-Stand and handgrip strength tests, than controls (P < 0.05, for all comparisons). Furthermore, the exercise program reduced the risk of falling (relative risk, 0.69; 95% confidence interval, 0.5-0.9; P = 0.008). These findings suggest that long-term maintenance of a music-based multitask exercise program is a promising strategy to prevent age-related physical decline in older adults. They also highlight the efficacy of sustained long-term adherence to exercise for falls prevention.


Subject(s)
Accidental Falls/prevention & control , Exercise Therapy/methods , Frail Elderly , Aged , Female , Gait , Humans , Male , Postural Balance
7.
Eur J Appl Physiol ; 114(1): 29-39, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24122149

ABSTRACT

PURPOSE: This longitudinal study examined the major physiological mechanisms that determine the age-related loss of lower extremity muscle power in two distinct groups of older humans. We hypothesized that after ~3 years of follow-up, mobility-limited older adults (mean age: 77.2 ± 4, n = 22, 12 females) would have significantly greater reductions in leg extensor muscle power compared to healthy older adults (74.1 ± 4, n = 26, 12 females). METHODS: Mid-thigh muscle size and composition were assessed using computed tomography. Neuromuscular activation was quantified using surface electromyography and vastus lateralis single muscle fibers were studied to evaluate intrinsic muscle contractile properties. RESULTS: At follow-up, the overall magnitude of muscle power loss was similar between groups: mobility-limited: -8.5 % vs. healthy older: -8.8 %, P > 0.8. Mobility-limited elders had significant reductions in muscle size (-3.8 %, P < 0.01) and strength (-5.9 %, P < 0.02), however, these parameters were preserved in healthy older (P ≥ 0.7). Neuromuscular activation declined significantly within healthy older, but not in mobility-limited participants. Within both groups, the cross-sectional areas of type I and IIA muscle fibers were preserved while substantial increases in single fiber peak force (>30 %), peak power (>200 %) and unloaded shortening velocity (>50 %) were elicited at follow-up. CONCLUSION: Different physiological mechanisms contribute to the loss of lower extremity muscle power in healthy older and mobility-limited older adults. Neuromuscular changes may be the critical early determinant of muscle power deficits with aging. In response to major whole muscle decrements, major compensatory mechanisms occur within the contractile properties of surviving single muscle fibers in an attempt to restore overall muscle power and function with advancing age.


Subject(s)
Aging/physiology , Lower Extremity/physiology , Mobility Limitation , Muscle Contraction , Muscle Fibers, Skeletal/physiology , Muscle Strength , Quadriceps Muscle/physiology , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Longitudinal Studies , Lower Extremity/diagnostic imaging , Lower Extremity/innervation , Male , Quadriceps Muscle/diagnostic imaging , Quadriceps Muscle/innervation , Tomography, X-Ray Computed
8.
Bone ; 181: 117039, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38325649

ABSTRACT

CONTEXT: People living with spinal cord injury (SCI) are at high risk for bone fractures. Neural, hormonal and metabolic contributors to bone microarchitectural alterations are incompletely understood. OBJECTIVE: To determine the relationship of physical, metabolic and endocrine characteristics with bone microarchitecture, characterized using high-resolution peripheral quantitative computed tomography (HRpQCT) in SCI. DESIGN: Cross-sectional analyses of bone properties in people with SCI. PARTICIPANTS: Twenty adults with SCI and paraplegia (12) or motor incomplete quadriplegia (8). OUTCOME MEASURES: Distal tibia and radius HRpQCT parameters, including density, microstructure and strength by microfinite element anaysis (µFEA); sex hormones; metabolic and inflammatory markers. RESULTS: The mean age of the participants with SCI was 41.5 ± 10.3 years, BMI 25.7 ± 6.2 kg/m2, time since injury 10.4 ± 9.0 years. Participants with SCI had significantly lower median total (Z score - 3.3), trabecular (-2.93), and cortical vBMD (-1.87), and Failure Load by µFEA (-2.48) at the tibia than controls. However, radius vBMD, aBMD and microarchitecture were similar in participants with SCI and un-injured controls. Unexpectedly, C-Reactive Protein (CRP) was positively associated with tibial trabecular vBMD (ß = 0.77, p = 0.02), thickness (ß = 0.52, p = 0.04) and number (ß = 0.92, p = 0.02). At the radius, estradiol level was positively associated with total vBMD (ß = 0.59, p = 0.01), trabecular thickness (ß = 0.43, p = 0.04), cortical thickness (ß = 0.63, p = 0.01) and cortical porosity (ß = 0.74 p = 0.04). CONCLUSIONS: Radius vBMD and microarchitecture is preserved but tibial total, cortical and trabecular vBMD, and estimated bone strength are markedly lower and bone microarchitectural parameters substantially degraded in people with SCI. The alterations in bone microarchitecture in people with SCI are likely multifactorial, however marked degradation of bone microarchitecture in tibia but not radius suggests that unloading is an important contributor of site-specific alterations of bone microarchitecture after SCI. Fracture prevention in SCI should focus on strategies to safely increase bone loading. CLINICALTRIALS: gov registration #: (NCT03576001).


Subject(s)
Fractures, Bone , Spinal Cord Injuries , Adult , Humans , Middle Aged , Bone Density , Absorptiometry, Photon/methods , Cross-Sectional Studies , Radius , Tibia/diagnostic imaging , Gonadal Steroid Hormones
9.
Int J Geriatr Psychiatry ; 28(12): 1239-50, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23589390

ABSTRACT

BACKGROUND: Computer-administered assessment of cognitive function is being increasingly incorporated in clinical trials; however, its performance in these settings has not been systematically evaluated. DESIGN: The Seniors Health and Activity Research Program pilot trial (N = 73) developed a computer-based tool for assessing memory performance and executive functioning. The Lifestyle Interventions and Independence for Elders investigators incorporated this battery in a full-scale multicenter clinical trial (N = 1635). We describe relationships that test scores have with those from interviewer-administered cognitive function tests and risk factors for cognitive deficits and describe performance measures (completeness, intraclass correlations [ICC]). RESULTS: Computer-based assessments of cognitive function had consistent relationships across the pilot and full-scale trial cohorts with interviewer-administered assessments of cognitive function, age, and a measure of physical function. In the Lifestyle Interventions and Independence for Elders cohort, their external validity was further demonstrated by associations with other risk factors for cognitive dysfunction: education, hypertension, diabetes, and physical function. Acceptable levels of data completeness (>83%) were achieved on all computer-based measures; however, rates of missing data were higher among older participants (odds ratio = 1.06 for each additional year; p < 0.001) and those who reported no current computer use (odds ratio = 2.71; p < 0.001). ICCs among clinics were at least as low (ICC < 0.013) as for interviewer measures (ICC < 0.023), reflecting good standardization. All cognitive measures loaded onto the first principal component (global cognitive function), which accounted for 40% of the overall variance. CONCLUSION: Our results support the use of computer-based tools for assessing cognitive function in multicenter clinical trials of older individuals.


Subject(s)
Cognition Disorders/diagnosis , Diagnosis, Computer-Assisted , Aged , Aged, 80 and over , Cognition Disorders/etiology , Cognition Disorders/prevention & control , Cognitive Behavioral Therapy , Cohort Studies , Female , Humans , Life Style , Male , Pilot Projects , Risk Factors
10.
J Appl Gerontol ; 42(3): 447-455, 2023 03.
Article in English | MEDLINE | ID: mdl-36314597

ABSTRACT

We used qualitative methods to better understand wearable activity monitor (WAM) use and its relationship with physical activity (PA) among older adults. Four focus groups, stratified by current/past ("ever") WAM users and "never" WAM users, were conducted with 57 participants aged ≥60 years. Data were coded with deductive and inductive approaches. Among ever WAM users, those with low pre-WAM PA levels reported higher PA related to WAM use while those with high pre-WAM PA levels reported they used WAM for tracking and monitoring their activity. Ever WAM users were motivated to increase PA through rewards and social support. Many never WAM users reported that WAM was unnecessary. WAM may be helpful for some older adults to increase their PA, particularly those who are motivated by setting and achieving PA goals. The results could help develop strategies to overcome barriers to WAM adoption and promote WAM use among older adults.


Subject(s)
Exercise , Fitness Trackers , Humans , Aged , Qualitative Research , Focus Groups
11.
Andrology ; 11(1): 93-102, 2023 01.
Article in English | MEDLINE | ID: mdl-36181480

ABSTRACT

BACKGROUND: Most men diagnosed with prostate cancer today have organ-confined disease and low risk of disease recurrence after radical prostatectomy. Testosterone deficiency in prostate cancer survivors contributes to impaired health-related quality of life but testosterone treatment is viewed as a contraindication in this population. OBJECTIVES: We describe the design of the first randomized trial to determine the safety and efficacy of testosterone treatment in men who have undergone prostatectomy for non-aggressive prostate cancer and have symptomatic testosterone deficiency. METHODS: Surviving Prostate cancer while Improving quality of life through Rehabilitation with Testosterone Trial is a randomized, placebo-controlled, double-blind, parallel group trial in 142 men, ≥ 40 years, who have undergone radical prostatectomy for organ-confined prostate cancer, Gleason score ≤ 7 (3+4), Stage pT2, N0, M0 lesions and have symptomatic testosterone deficiency and undetectable prostate specific antigen for > 2 years after surgery. Eligible participants are randomized to weekly intramuscular injections of 100-mg testosterone cypionate or placebo for 12 weeks and followed for another 12 weeks. Primary endpoint is change from baseline in sexual activity. Secondary outcomes include change in sexual desire, erectile function, energy, lean and fat mass, physical and cognitive performance. Safety is assessed by monitoring prostate-specific antigen, lower urinary tract symptoms, hemoglobin, and adverse events. RESULTS: The trial is being conducted at two trial sites in Boston, MA and Baltimore, MD. As of July 30, 2022, 42 participants have been randomized. No prostate-specific antigen or clinical recurrence has been noted to-date. DISCUSSION: Recruitment was slowed by coronavirus disease 2019-related closures, slow subsequent ramp-up of research activities, and patient concerns about safety of testosterone treatment. Despite these challenges, participant retention has been high. CONCLUSION: The Surviving Prostate cancer while Improving quality of life through Rehabilitation with Testosterone Trial, a placebo-controlled, randomized trial, will determine whether testosterone replacement therapy is safe and efficacious in correcting symptoms of testosterone deficiency in prostate cancer survivors, and potentially inform clinical practice.


Subject(s)
COVID-19 , Cancer Survivors , Prostatic Neoplasms , Male , Humans , Quality of Life , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Prostate-Specific Antigen , Testosterone/therapeutic use , Treatment Outcome , Randomized Controlled Trials as Topic
12.
J Clin Endocrinol Metab ; 108(8): 1968-1980, 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-36740954

ABSTRACT

CONTEXT: Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases. OBJECTIVE: We evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, ß-nicotinamide mononucleotide (MIB-626, Metro International Biotech, Worcester, MA), in adults at risk for age-related conditions. METHODS: Thirty overweight or obese adults, ≥ 45 years, were randomized in a 2:1 ratio to 2 MIB-626 tablets each containing 500 mg of microcrystalline ß-nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics. RESULTS: Adverse events were similar between groups. MIB-626 treatment substantially increased circulating concentrations of NAD and its metabolites. Body weight (difference -1.9 [-3.3, -0.5] kg, P = .008); diastolic blood pressure (difference -7.01 [-13.44, -0.59] mmHg, P = .034); total cholesterol (difference -26.89 [-44.34, -9.44] mg/dL, P = .004), low-density lipoprotein (LDL) cholesterol (-18.73 [-31.85, -5.60] mg/dL, P = .007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 group than placebo. Changes in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ significantly between groups. Insulin sensitivity and hepatic and intra-abdominal fat did not change in either group. CONCLUSIONS: MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure. These data provide the rationale for larger trials to assess the efficacy of NAD augmentation in improving cardiometabolic outcomes in older adults.


Subject(s)
Insulin Resistance , Overweight , Middle Aged , Humans , Aged , NAD/metabolism , NAD/therapeutic use , Nicotinamide Mononucleotide/therapeutic use , Obesity , Body Weight , Cholesterol
13.
J Cachexia Sarcopenia Muscle ; 14(5): 1932-1948, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37671529

ABSTRACT

In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia.


Subject(s)
Cachexia , Neoplasms , Humans , Cachexia/therapy , Cachexia/complications , Hand Strength , Neoplasms/complications , Neoplasms/therapy , Quality of Life , Research Design
14.
Exerc Sport Sci Rev ; 40(1): 4-12, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22016147

ABSTRACT

Muscle power declines earlier and more precipitously with advancing age compared with muscle strength. Peak muscle power also has emerged as an important predictor of functional limitations in older adults. Our current working hypothesis is focused on examining lower extremity muscle power as a more discriminant variable for understanding the relationships between impairments, functional limitations, and resultant disability with aging.


Subject(s)
Aging/physiology , Muscle Strength , Muscle, Skeletal , Physical Fitness , Adult , Aged , Female , Humans , Lower Extremity/physiology , Male , Middle Aged , Mobility Limitation , Muscle Contraction , Psychomotor Performance/physiology , Resistance Training
15.
Eur J Appl Physiol ; 112(6): 2289-301, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22005960

ABSTRACT

This study investigated the physiological and gender determinants of the age-related loss of muscle power in 31 healthy middle-aged adults (aged 40-55 years), 28 healthy older adults (70-85 years) and 34 mobility-limited older adults (70-85 years). We hypothesized that leg extensor muscle power would be significantly lower in mobility-limited elders relative to both healthy groups and sought to characterize the physiological mechanisms associated with the reduction of muscle power with aging. Computed tomography was utilized to assess mid-thigh body composition and calculate specific muscle power and strength. Surface electromyography was used to assess rate of neuromuscular activation and muscle biopsies were taken to evaluate single muscle fiber contractile properties. Peak muscle power, strength, muscle cross-sectional area, specific muscle power and rate of neuromuscular activation were significantly lower among mobility-limited elders compared to both healthy groups (P ≤ 0.05). Mobility-limited older participants had greater deposits of intermuscular adipose tissue (P < 0.001). Single fiber contractile properties of type I and type IIA muscle fibers were preserved in mobility-limited elders relative to both healthy groups. Male gender was associated with greater decrements in peak and specific muscle power among mobility-limited participants. Impairments in the rate of neuromuscular activation and concomitant reductions in muscle quality are important physiological mechanisms contributing to muscle power deficits and mobility limitations. The dissociation between age-related changes at the whole muscle and single fiber level suggest that, even among older adults with overt mobility problems, contractile properties of surviving muscle fibers are preserved in an attempt to maintain overall muscle function.


Subject(s)
Muscle Contraction/physiology , Muscle Fibers, Skeletal/physiology , Muscle Strength/physiology , Age Factors , Aged , Cross-Sectional Studies/methods , Electromyography/methods , Female , Humans , Leg/physiology , Male , Middle Aged , Sex Factors
16.
Article in English | MEDLINE | ID: mdl-37885833

ABSTRACT

Background: Trauma exposure and posttraumatic stress are highly prevalent and comorbid with health problems. Despite the apparent systemic nature of post-traumatic stress, recommended treatments neglect trauma's deleterious effects on health. Integrative mind-body treatments for posttraumatic stress, such as Tai Chi and Qigong (TCQ), may offer a promising adjunct to first-line treatments. Method: A systematic search was conducted to identify trials that examined Tai Chi and/or Qigong as treatments for trauma-exposed populations. Studies were examined for rigor; design, sample and intervention characteristics, dropout, attendance, satisfaction, acceptability, and key findings were systematically extracted. Results: The 6 studies included are all pilot or feasibility trials with descriptive or mixed-methods outcomes. No randomized trials or rigorous studies were identified. Dropout rates ranged widely, and adverse reactions were not evident. Reported satisfaction was high and benefits of relaxation, reductions in mental health symptoms, and improvements in pain and physical and cognitive functioning were noted. Limitations: All the studies were non-rigorous and relatively small, with no comparison groups, or follow-up assessments; in many cases, posttraumatic stress symptoms were not formally assessed. Conclusions: The paucity and lack of rigor of the studies identified for this review highlights the need for larger, methodologically sound clinical trials. The reviewed studies suggest that TCQ practices have the potential to reduce symptoms and improve functioning for individuals exposed to trauma and provide evidence that TCQ is feasible, acceptable, and low risk in these populations. Possible mechanistic pathways supporting TCQ as a treatment for posttraumatic stress are considered.

17.
Am J Health Promot ; 35(5): 679-687, 2021 06.
Article in English | MEDLINE | ID: mdl-33406889

ABSTRACT

PURPOSE: To examine wearable activity monitor (WAM) use and its association with meeting the 2008 aerobic Physical Activity Guidelines (PAG) and walking among older adults. DESIGN: Cross-sectional. SETTING: FallStyles 2015 national consumer panel survey. SAMPLE: 1,317 U.S. adults aged ≥ 60 years. MEASURES: Self-reported WAM use, meeting aerobic PAG, and walking. Covariates included age, sex, race/ethnicity, education level, marital status, annual household income, and geographic region of the country. ANALYSIS: Chi-square tests to examine associations between WAM use and respondent demographic characteristics. Logistic regressions to explore associations between WAM use and meeting aerobic PAG and walking adjusted for demographics (e.g., education, income). RESULTS: Among older adults, 8.0% were current WAM users and 11.3% were past WAM users. Current WAM use was most prevalent among those aged 65-74 (16.6%), females (9.4%), college graduates (13.8%), and those with incomes $75,000-$99,999 (14.8%). Current WAM users were more likely than never WAM users to report meeting aerobic PAG (OR: 3.98; 95% CI: 2.07, 7.66) and walking (OR: 3.90; 95% CI: 1.57, 9.69). Past and never WAM use were not associated with meeting aerobic PAG or walking. CONCLUSION: We found current WAM use is associated with meeting the aerobic PAG and walking among older adults. Further longitudinal research is needed to understand whether WAM could promote increased PA among older adults.


Subject(s)
Exercise , Walking , Aged , Cross-Sectional Studies , Female , Fitness Trackers , Humans , Self Report
18.
J Gerontol A Biol Sci Med Sci ; 76(10): e264-e271, 2021 09 13.
Article in English | MEDLINE | ID: mdl-33585918

ABSTRACT

BACKGROUND: This study evaluated the association between ratings of perceived exertion (RPE) of walking and major mobility disability (MMD), as well as their transitions in response to a physical activity (PA) compared to a health education (HE) program. METHODS: Older adults (n = 1633) who were at risk for mobility impairment were randomized to structured PA or HE programs. During a 400 m walk, participants rated exertion as "light" or "hard." An MMD event was defined as the inability to walk 400 m. MMD events and RPE values were assessed every 6 months for an average of 2.6 years. RESULTS: Participants rating their exertion as "hard" had a nearly threefold higher risk of MMD compared with those rating their exertion as "light" (HR: 2.61, 95% CI: 2.19-3.11). The association was held after adjusting for disease conditions, depression, cognitive function, and walking speed (HR: 2.24, 95% CI: 1.87-2.69). The PA group was 25% more likely to transition from "light" to "hard" RPE than the HE group (HR: 1.25, 95% CI: 1.05-1.49). Additionally, the PA group was 27% (HR: 0.73, 95% CI: 0.55 - 0.97) less likely to transition from a "hard" RPE to inability to walk 400 m and was more likely to recover their ability to walk 400 m by transitioning to a "hard" RPE (HR: 2.10, 95% CI: 1.39-3.17) than the HE group. CONCLUSIONS: Older adults rating "hard" effort during a standardized walk test were at increased risk of subsequent MMD. A structured PA program enabled walking recovery, but was more likely to increase transition from "light" to "hard" effort, which may reflect the greater capacity to perform the test.


Subject(s)
Disabled Persons , Physical Exertion , Aged , Exercise , Humans , Mobility Limitation , Walking
19.
Clin Rheumatol ; 39(6): 1961-1970, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32030634

ABSTRACT

INTRODUCTION/OBJECTIVE: We aimed to establish sex-specific reference values of objective physical function tests among individuals with or at risk for knee osteoarthritis (KOA) across subsets of age, radiographic KOA severity, and body mass index (BMI). METHOD: We included Osteoarthritis Initiative participants with data for objective physical function tests, sex, age, BMI, and radiographic KOA severity (Kellgren-Lawrence [KL] grade) at baseline. Objective physical function was quantified with 20-m walk speed, chair-stand speed, 400-m walk time, and knee extension and flexion strength. We created participant characteristic subsets for sex, age, KL grade, and BMI. Reference values were created as percentiles from minimum to maximum in 10% increments for each combination of participant characteristic subsets. Previously established clinically important differences for 20-m walk speed and knee extension strength were used to highlight clinically relevant differences. RESULTS: Objective physical function reference values tables and an interactive reference value table were created across all combinations of sex, age, KL grade, and BMI among 3860 individuals with or at risk for KOA. Clinically relevant differences exist for 20-m walk speed and knee extension strength between males and females across age groups, KL grades, and BMI categories. CONCLUSIONS: Establishing an individual's relative level of objective physical function by comparing their performance to individuals with similar sex, age, KL grade, or BMI may help improve interpretation of physical function performance. The interactive reference value table will provide clinicians and researchers a clinically accessible avenue to use these reference values.Key Points• Since greater age, radiographic knee osteoarthritis severity, and body mass index are all associated with worse objective physical function, reference values should consider the complex inter-play among these patient characteristics.• This study provides objective physical function reference values among subsets of individuals across the spectrum of sex, age groups, radiographic knee osteoarthritis severity, and body mass index categories.• These reference values offer a more patient-centered approach for interpreting an individual's relative level of objective physical function by comparing them to a more homogeneous group of individuals with similar participant characteristics.• We have provided a clinically accessible interactive table that will enable clinicians and researchers to input their patient's data to quickly and efficiently determine a patient's relative objective physical function compared to individual's with similar characteristics.


Subject(s)
Knee Joint/physiopathology , Osteoarthritis, Knee/physiopathology , Aged , Body Mass Index , Female , Humans , Longitudinal Studies , Male , Middle Aged , Physical Functional Performance , Reference Values , Risk Factors , Walking
20.
Integr Med Res ; 8(3): 167-172, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31304089

ABSTRACT

Gulf War illness (GWI) is a chronic and multisymptom disorder affecting military veterans deployed to the 1991 Persian Gulf War. It is characterized by a range of acute and chronic symptoms, including but not limited to, fatigue, sleep disturbances, psychological problems, cognitive deficits, widespread pain, and respiratory and gastrointestinal difficulties. The prevalence of many of these chronic symptoms affecting Gulf War veterans occur at markedly elevated rates compared to nondeployed contemporary veterans. To date, no effective treatments for GWI have been identified. The overarching goal of this umbrella review was to critically evaluate the evidence for the potential of Tai Chi mind-body exercise to benefit and alleviate GWI symptomology. Based on the most prevalent GWI chronic symptoms and case definitions established by the Centers for Disease Control and Prevention and the Kansas Gulf War Veterans Health Initiative Program, we reviewed and summarized the evidence from 7 published systematic reviews and meta-analyses. Our findings suggest that Tai Chi may have the potential for distinct therapeutic benefits on the major prevalent symptoms of GWI. Future clinical trials are warranted to examine the feasibility, efficacy, durability and potential mechanisms of Tai Chi for improving health outcomes and relieving symptomology in GWI.

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