Effect of Diet and Exercise on Knee Pain in Patients With Osteoarthritis and Overweight or Obesity: A Randomized Clinical Trial.

Importance: Some weight loss and exercise programs that have been successful in academic center-based trials have not been evaluated in community settings. Objective: To determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up. Design, Setting, and Participants: Assessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina. Patients were men and women aged 50 years or older with knee osteoarthritis and overweight or obesity (body mass index ≥27). Enrollment (N = 823) occurred between May 2016 and August 2019, with follow-up ending in April 2021. Interventions: Patients were randomly assigned to either a diet and exercise intervention (n = 414) or an attention control (n = 409) group for 18 months. Main Outcomes and Measures: The primary outcome was the between-group difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain score (range, 0 [none] to 20 [severe]; minimum clinically important difference, 1.6) over 18 months, tested using a repeated-measures mixed linear model with adjustments for covariates. There were 7 secondary outcomes including body weight. Results: Among the 823 randomized patients (mean age, 64.6 years; 637 [77%] women), 658 (80%) completed the trial. At 18-month follow-up, the adjusted mean WOMAC pain score was 5.0 in the diet and exercise group (n = 329) compared with 5.5 in the attention control group (n = 316) (adjusted difference, -0.6; 95% CI, -1.0 to -0.1; P = .02). Of 7 secondary outcomes, 5 were significantly better in the intervention group compared with control. The mean change in unadjusted 18-month body weight for patients with available data was -7.7 kg (8%) in the diet and exercise group (n = 289) and -1.7 kg (2%) in the attention control group (n = 273) (mean difference, -6.0 kg; 95% CI, -7.3 kg to -4.7 kg). There were 169 serious adverse events; none were definitely related to the study. There were 729 adverse events; 32 (4%) were definitely related to the study, including 10 body injuries (9 in diet and exercise; 1 in attention control), 7 muscle strains (6 in diet and exercise; 1 in attention control), and 6 trip/fall events (all 6 in diet and exercise). Conclusions and Relevance: Among patients with knee osteoarthritis and overweight or obesity, diet and exercise compared with an attention control led to a statistically significant but small difference in knee pain over 18 months. The magnitude of the difference in pain between groups is of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02577549.

Effect of High-Intensity Strength Training on Knee Pain and Knee Joint Compressive Forces Among Adults With Knee Osteoarthritis: The START Randomized Clinical Trial.

Importance: Thigh muscle weakness is associated with knee discomfort and osteoarthritis disease progression. Little is known about the efficacy of high-intensity strength training in patients with knee osteoarthritis or whether it may worsen knee symptoms. Objective: To determine whether high-intensity strength training reduces knee pain and knee joint compressive forces more than low-intensity strength training and more than attention control in patients with knee osteoarthritis. Design, Setting, and Participants: Assessor-blinded randomized clinical trial conducted at a university research center in North Carolina that included 377 community-dwelling adults (≥50 years) with body mass index (BMI) ranging from 20 to 45 and with knee pain and radiographic knee osteoarthritis. Enrollment occurred between July 2012 and February 2016, and follow-up was completed September 2017. Interventions: Participants were randomized to high-intensity strength training (n = 127), low-intensity strength training (n = 126), or attention control (n = 124). Main Outcomes and Measures: Primary outcomes at the 18-month follow-up were Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) knee pain (0 best-20 worst; minimally clinically important difference [MCID, 2]) and knee joint compressive force, defined as the maximal tibiofemoral contact force exerted along the long axis of the tibia during walking (MCID, unknown). Results: Among 377 randomized participants (mean age, 65 years; 151 women [40%]), 320 (85%) completed the trial. Mean adjusted (sex, baseline BMI, baseline outcome values) WOMAC pain scores at the 18-month follow-up were not statistically significantly different between the high-intensity group and the control group (5.1 vs 4.9; adjusted difference, 0.2; 95% CI, -0.6 to 1.1; P = .61) or between the high-intensity and low-intensity groups (5.1 vs 4.4; adjusted difference, 0.7; 95% CI, -0.1 to 1.6; P = .08). Mean knee joint compressive forces were not statistically significantly different between the high-intensity group and the control group (2453 N vs 2512 N; adjusted difference, -58; 95% CI, -282 to 165 N; P = .61), or between the high-intensity and low-intensity groups (2453 N vs 2475 N; adjusted difference, -21; 95% CI, -235 to 193 N; P = .85). There were 87 nonserious adverse events (high-intensity, 53; low-intensity, 30; control, 4) and 13 serious adverse events unrelated to the study (high-intensity, 5; low-intensity, 3; control, 5). Conclusions and Relevance: Among patients with knee osteoarthritis, high-intensity strength training compared with low-intensity strength training or an attention control did not significantly reduce knee pain or knee joint compressive forces at 18 months. The findings do not support the use of high-intensity strength training over low-intensity strength training or an attention control in adults with knee osteoarthritis. Trial Registration: ClinicalTrials.gov Identifier: NCT01489462.

Long-Term Effects of Telephone-Delivered Psychotherapy for Late-Life GAD.

OBJECTIVE: To examine the long-term effects of telephone-delivered cognitive-behavioral therapy (CBT-T) compared with nondirective supportive therapy (NST-T) in rural older adults with generalized anxiety disorder (GAD). METHODS: 141 adults aged 60 years and older with a principal/co-principal diagnosis of GAD were randomized to either CBT-T or NST-T. CBT-T consisted of up to 11 sessions (9 were required) focused on recognition of anxiety symptoms, relaxation, cognitive restructuring and use of coping statements, problem-solving, worry control, behavioral activation, exposure therapy, and relapse prevention, with optional chapters on sleep and pain. NST-T consisted of 10 sessions focused on providing a supportive atmosphere in which participants could share and discuss their feelings and did not provide any direct suggestions. Primary outcomes included interviewer-rated anxiety severity and self-report worry severity measured at 9 months and 15 months after randomization. Mood-specific secondary outcomes included self-report GAD symptoms and depressive symptoms. RESULTS: At 15 months, after adjustment for multiple testing, there was a significantly greater decline in general anxiety symptoms (difference in improvement: 3.31; 95% CI: 0.45-6.17; t = 2.29; df = 136; p = 0.024) and worry (difference in improvement: 3.13; 95% CI: 0.59-5.68; t = 2.43; df = 136; p = 0.016) among participants in CBT-T compared with those in the NST-T group. There were no significant differences between the conditions in terms of depressive symptoms (difference in improvement: 2.88; 95% CI: 0.17-5.60; t = 2.10; df = 136; p = 0.0376) and GAD symptoms (difference in improvement: 1.65; 95% CI: -0.20 to 3.50; t = 1.76; df = 136; p = 0.080). CONCLUSIONS: CBT-T is superior to NST-T in reducing worry and anxiety symptoms 1 year after completing treatment.

Gait speed response to aerobic versus resistance exercise training in older adults.

BACKGROUND: Little is known about the comparative effect of aerobic training (AT) versus resistance training (RT) on gait speed, a strong predictor of disability. AIMS: To compare the effect of AT versus RT on gait speed and other functional measures. METHODS: Overweight and obese [body mass index (BMI) ≥27.0 kg/m2] sedentary men and women aged 65-79 years engaged in 5 months of either 4 days/weeks moderate-intensity treadmill walking, AT, (n = 44) or 3 days/weeks moderate-intensity RT (n = 56). Usual-pace gait speed, fast-pace gait speed and short physical performance battery (SPPB) were evaluated in all participants before and after training. Peak oxygen consumption (VO2peak) was assessed in AT participants only, and knee extensor strength was assessed in RT participants. RESULTS: Both AT and RT resulted in clinically significant improvements in usual-pace gait speed (0.08 ± 0.14 and 0.08 ± 0.17 m/s, respectively, both p < 0.05) and SPPB (0.53 ± 1.40 and 0.53 ± 1.20 points, both p < 0.05) and chair rise time (-1.2 ± 3.2 and -1.7 ± 3.0 s, p < 0.05). Only AT improved fast-pace gait speed (0.11 ± 0.10 m/s, p < 0.05). In the RT participants, lower baseline knee strength was associated with less improvement in usual-pace gait speed. In AT participants, lower baseline VO2peak was associated with less improvement in chair rise time and self-reported disability. DISCUSSION: While both AT and RT improved usual-pace gait speed, only AT improved fast-pace gait speed. Lower baseline fitness was associated with less improvement with training. CONCLUSION: Research to directly compare which mode of training elicits the maximum improvement in older individuals with specific functional deficits could lead to better intervention targeting.

Weight-loss and exercise for communities with arthritis in North Carolina (we-can): design and rationale of a pragmatic, assessor-blinded, randomized controlled trial.

BACKGROUND: Recently, we determined that in a rigorously monitored environment an intensive diet-induced weight loss of 10% combined with exercise was significantly more effective at reducing pain in men and women with symptomatic knee osteoarthritis (OA) than either intervention alone. Compared to previous long-term weight loss and exercise trials of knee OA, our intensive diet-induced weight loss and exercise intervention was twice as effective at reducing pain intensity. Whether these results can be generalized to less intensively monitored cohorts is unknown. Thus, the policy relevant and clinically important question is: Can we adapt this successful solution to a pervasive public health problem in real-world clinical and community settings? This study aims to develop a systematic, practical, cost-effective diet-induced weight loss and exercise intervention implemented in community settings and to determine its effectiveness in reducing pain and improving other clinical outcomes in persons with knee OA. METHODS/DESIGN: This is a Phase III, pragmatic, assessor-blinded, randomized controlled trial. Participants will include 820 ambulatory, community-dwelling, overweight and obese (BMI ≥ 27 kg/m2) men and women aged ≥ 50 years who meet the American College of Rheumatology clinical criteria for knee OA. The primary aim is to determine whether a community-based 18-month diet-induced weight loss and exercise intervention based on social cognitive theory and implemented in three North Carolina counties with diverse residential (from urban to rural) and socioeconomic composition significantly decreases knee pain in overweight and obese adults with knee OA relative to a nutrition and health attention control group. Secondary aims will determine whether this intervention improves self-reported function, health-related quality of life, mobility, and is cost-effective. DISCUSSION: Many physicians who treat people with knee OA have no practical means to implement weight loss and exercise treatments as recommended by numerous OA treatment guidelines. This study will establish the effectiveness of a community program that will serve as a blueprint and exemplar for clinicians and public health officials in urban and rural communities to implement a diet-induced weight loss and exercise program designed to reduce knee pain and improve other clinical outcomes in overweight and obese adults with knee OA. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02577549 October 12, 2015.

Effects of Telephone-Delivered Cognitive-Behavioral Therapy and Nondirective Supportive Therapy on Sleep, Health-Related Quality of Life, and Disability.

OBJECTIVES: The purpose of this study was to compare the effects of cognitive-behavioral therapy delivered by telephone (CBT-T) and telephone-delivered nondirective supportive therapy (NST-T) on sleep, health-related quality of life, and physical disability in rural older adults with generalized anxiety disorder. METHODS: This was a secondary analysis of a randomized clinical trial on 141 rural-dwelling adults 60 years and older diagnosed with generalized anxiety disorder. Sleep was assessed with the Insomnia Severity Index. Health-related quality of life was assessed with the 36-item Short-Form Health Survey (SF-36). Physical disability was assessed with the Pepper Center Tool for Disability. Assessments occurred at baseline, 4 months, 9 months, and 15 months. RESULTS: Insomnia declined in both groups from baseline to 4 months, with a significantly greater improvement among participants who received CBT-T. Similarly, Mental and Physical Component Summaries of the SF-36 declined in both groups, with a differential effect favoring CBT-T. Participants in both interventions reported declines in physical disability, although there were no significant differences between the two interventions. Improvements in insomnia were maintained at the 15-month assessment, whereas between-group differences shrank on the Mental and Physical Component Summaries of the SF-36 by the 15-month assessment. CONCLUSION: CBT-T was superior to NST-T in reducing insomnia and improving health-related quality of life. The effects of CBT-T on sleep were maintained 1 year after completing the treatment.

Intermediate and long-term risk of new-onset heart failure after hospitalization for pneumonia in elderly adults.

BACKGROUND: Pneumonia is associated with high risk of heart failure (HF) in the short term (30 days) postinfection. Whether this association persists beyond this period is unknown. METHODS: We studied 5,613 elderly (≥65 years) adults enrolled in the Cardiovascular Health Study between 1989 and 1994 at 4 US communities. Participants had no clinical diagnosis of HF at enrollment, and they were followed up through December 2010. Hospitalizations for pneumonia were identified using validated International Classification of Disease Ninth Revision codes. A centralized committee adjudicated new-onset HF events. Using Cox regression, we estimated adjusted hazard ratios (HRs) of new-onset HF at different time intervals after hospitalization for pneumonia. RESULTS: A total of 652 participants hospitalized for pneumonia during follow-up were still alive and free of clinical diagnosis of HF by day 30 posthospitalization. Relative to the time of their hospitalization, new-onset HF occurred in 22 cases between 31 and 90 days (HR 6.9, 95% CI 4.46-10.63, P < .001), 14 cases between 91 days and 6 months (HR 3.2, 95% CI 1.88-5.50, P < .001), 20 cases between 6 months and 1 year (HR 2.6, 95% CI 1.64-4.04, P < .001), 76 cases between 1 and 5 years (HR 1.7, 95% CI 1.30-2.12, P < .001), and 71 cases after 5 years (HR 2.0, 95% CI 1.56-2.58, P < .001). Results were robust to sensitivity analyses using stringent definitions of pneumonia and extreme assumptions for potential informative censoring. CONCLUSION: Hospitalization for pneumonia is associated with increased risk of new-onset HF in the intermediate and long term. Studies should characterize the mechanisms of this association in order to prevent HF in elderly pneumonia survivors.

Barriers to Mental Health Treatment in Rural Older Adults.

OBJECTIVES: The purpose of this study was to identify the barriers to seeking mental health treatment experienced by rural older adults. We also examined if barriers differed by age and worry severity. METHODS: Participants were 478 rural older adults responding to a flyer for a psychotherapy intervention study. Interested participants were screened by telephone, and barriers to mental health treatment were assessed. Participants completed a demographic questionnaire and the Penn State Worry Questionnaire-Abbreviated. RESULTS: The most commonly reported barrier to treatment was the personal belief that "I should not need help." Other commonly reported barriers included practical barriers (cost, not knowing where to go, distance), mistrust of mental health providers, not thinking treatment would help, stigma, and not wanting to talk with a stranger about private matters. Multivariable analyses indicated that worry severity and younger age were associated with reporting more barriers. CONCLUSIONS: Multiple barriers interfere with older adults seeking treatment for anxiety and depression. Older age is associated with fewer barriers, suggesting that the oldest old may have found strategies for overcoming these barriers. Young-old adults may benefit from interventions addressing personal beliefs about mental health and alternative methods of service delivery.

Association between hospitalization for pneumonia and subsequent risk of cardiovascular disease.

IMPORTANCE: The risk of cardiovascular disease (CVD) after infection is poorly understood. OBJECTIVE: To determine whether hospitalization for pneumonia is associated with an increased short-term and long-term risk of CVD. DESIGN, SETTINGS, AND PARTICIPANTS: We examined 2 community-based cohorts: the Cardiovascular Health Study (CHS, n = 5888; enrollment age, ≥65 years; enrollment period, 1989-1994) and the Atherosclerosis Risk in Communities study (ARIC, n = 15,792; enrollment age, 45-64 years; enrollment period, 1987-1989). Participants were followed up through December 31, 2010. We matched each participant hospitalized with pneumonia to 2 controls. Pneumonia cases and controls were followed for occurrence of CVD over 10 years after matching. We estimated hazard ratios (HRs) for CVD at different time intervals, adjusting for demographics, CVD risk factors, subclinical CVD, comorbidities, and functional status. EXPOSURES: Hospitalization for pneumonia. MAIN OUTCOMES AND MEASURES: Incident CVD (myocardial infarction, stroke, and fatal coronary heart disease). RESULTS: Of 591 pneumonia cases in CHS, 206 had CVD events over 10 years after pneumonia hospitalization. CVD risk after pneumonia was highest in the first year. CVD occurred in 54 cases and 6 controls in the first 30 days (HR, 4.07; 95% CI, 2.86-5.27); 11 cases and 9 controls between 31 and 90 days (HR, 2.94; 95% CI, 2.18-3.70); and 22 cases and 55 controls between 91 days and 1 year (HR, 2.10; 95% CI, 1.59-2.60). Additional CVD risk remained elevated into the tenth year, when 4 cases and 12 controls developed CVD (HR, 1.86; 95% CI, 1.18-2.55). In ARIC, of 680 pneumonia cases, 112 had CVD over 10 years after hospitalization. CVD occurred in 4 cases and 3 controls in the first 30 days (HR, 2.38; 95% CI, 1.12-3.63); 4 cases and 0 controls between 31 and 90 days (HR, 2.40; 95% CI, 1.23-3.47); 11 cases and 8 controls between 91 days and 1 year (HR, 2.19; 95% CI, 1.20-3.19); and 8 cases and 7 controls during the second year (HR, 1.88; 95% CI, 1.10-2.66). After the second year, the HRs were no longer statistically significant. CONCLUSIONS AND RELEVANCE: Hospitalization for pneumonia was associated with increased short-term and long-term risk of CVD, suggesting that pneumonia may be a risk factor for CVD.

Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction.

Heart failure (HF) with preserved ejection fraction (HFPEF) is the most common form of HF in older persons. The primary chronic symptom in HFPEF is severe exercise intolerance, and its pathophysiology is poorly understood. To determine whether skeletal muscle abnormalities contribute to their severely reduced peak exercise O2 consumption (Vo2), we examined 22 older HFPEF patients (70 ± 7 yr) compared with 43 age-matched healthy control (HC) subjects using needle biopsy of the vastus lateralis muscle and cardiopulmonary exercise testing to assess muscle fiber type distribution and capillarity and peak Vo2. In HFPEF versus HC patients, peak Vo2 (14.7 ± 2.1 vs. 22.9 ± 6.6 ml·kg(-1)·min(-1), P < 0.001) and 6-min walk distance (454 ± 72 vs. 573 ± 71 m, P < 0.001) were reduced. In HFPEF versus HC patients, the percentage of type I fibers (39.0 ± 11.4% vs. 53.7 ± 12.4%, P < 0.001), type I-to-type II fiber ratio (0.72 ± 0.39 vs. 1.36 ± 0.85, P = 0.001), and capillary-to-fiber ratio (1.35 ± 0.32 vs. 2.53 ± 1.37, P = 0.006) were reduced, whereas the percentage of type II fibers was greater (61 ± 11.4% vs. 46.3 ± 12.4%, P < 0.001). In univariate analyses, the percentage of type I fibers (r = 0.39, P = 0.003), type I-to-type II fiber ratio (r = 0.33, P = 0.02), and capillary-to-fiber ratio (r = 0.59, P < 0.0001) were positively related to peak Vo2. In multivariate analyses, type I fibers and the capillary-to-fiber ratio remained significantly related to peak Vo2. We conclude that older HFPEF patients have significant abnormalities in skeletal muscle, characterized by a shift in muscle fiber type distribution with reduced type I oxidative muscle fibers and a reduced capillary-to-fiber ratio, and these may contribute to their severe exercise intolerance. This suggests potential new therapeutic targets in this difficult to treat disorder.

Telephone-delivered psychotherapy for rural-dwelling older adults with generalized anxiety disorder: study protocol of a randomized controlled trial.

BACKGROUND: Generalized Anxiety Disorder (GAD), characterized by excessive and uncontrollable worry, has a negative impact on the health, well-being, and functioning of older adults. Cognitive behavioral therapy has demonstrated efficacy in reducing anxiety and worry in older adults, but the generalizability of these findings to community-dwelling older adults is unknown. The aim of the current study is to examine the efficacy of a cognitive-behavioral intervention delivered by telephone in reducing anxiety and worry in rural community-dwelling older adults with GAD. METHODS/DESIGN: We propose a randomized controlled trial comparing telephone-delivered cognitive behavioral therapy (CBT-T) with nondirective supportive therapy (NST-T). One hundred seventy six adults 60 years and older diagnosed with GAD will be randomized to one of the two treatment conditions. The primary outcomes are self-report worry and clinician-rated anxiety. Secondary outcomes include depressive symptoms, sleep, quality of life, and functional status. DISCUSSION: It is hypothesized that CBT-T will be superior to NST-T in reducing anxiety and worry among older adults with GAD. Further, CBT-T is hypothesized to be superior to NST-T in reducing problems with depressive symptoms, sleep, functional status and quality of life. If this program is successful, it could be implemented as a low-cost program to treat late-life anxiety, especially in rural areas or in circumstances where older adults may not have access to qualified mental health providers. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01259596.

Percutaneous biopsies of skeletal muscle and adipose tissue in individuals older than 70: methods and outcomes in the Study of Muscle, Mobility and Aging (SOMMA).

Biopsies of muscle and adipose tissue (AT) are useful tools to gain insights into the aging processes in these tissues. However, they are invasive procedures and their risk/benefit profile in older adults can be altered by sarcopenia, frailty, poor healing, and multimorbidity. Their success rates, safety, and tolerability in a geriatric population have not been reported in detail. Investigators in the Study of Muscle, Mobility, and Aging (SOMMA) performed biopsies of muscle and AT in older adults and prospectively collected data on biopsy success rates, safety, and tolerability. We report here the methods and outcomes of these two procedures. In total, 861 participants (aged 70-94) underwent percutaneous biopsies of the Vastus lateralis muscle with a Bergstrom needle. A subset (n = 241) also underwent percutaneous biopsies of the abdominal subcutaneous AT with the tumescent liposuction technique. Success rate was assessed by the percentage of biopsies yielding adequate specimens for analyses; tolerability by pain scores; and safety by frequency of adverse events. All data were prospectively collected. The overall muscle biopsy success rate was 97.1% and was modestly lower in women. The AT biopsy success rate was 95.9% and slightly lower in men. Minimal or no pain was reported in 68% of muscle biopsies and in 83% of AT biopsies. Adverse events occurred in 2.67% of muscle biopsies and 4.15% of AT biopsies. None was serious. In older adults, percutaneous muscle biopsies and abdominal subcutaneous AT biopsies have an excellent safety profile, often achieve adequate tissue yields for analyses, and are well tolerated.

Clinical, Health-Related Quality of Life, and Gait Differences Among Obesity Classes in Adults With Knee Osteoarthritis.

OBJECTIVE: The purpose of this study was to determine whether clinical, health-related quality of life (HRQL), and gait characteristics in adults with knee osteoarthritis (OA) differed by obesity category. METHODS: This cross-sectional analysis of 823 older adults (mean age 64.6 years, SD 7.8 years) with knee OA and overweight or obesity compared clinical, HRQL, and gait outcomes among obesity classifications (overweight or class I, body mass index [BMI] 27.0-34.9; class II, BMI 35.0-39.9; class III BMI ≥40.0). RESULTS: Patients with class III obesity had worse Western Ontario McMasters Universities Arthritis Index knee pain (0-20) than the overweight or class I (mean 8.6 vs 7.0; difference 1.5; 95% confidence interval [CI] 1.0-2.1; P < 0.0001) and class II (mean 8.6 vs 7.4; difference 1.1; 95% CI 0.6-1.7; P = 0.0002) obesity groups. The Short Form 36 physical HRQL measure was lower in the class III obesity group compared to the overweight or class I (mean 31.0 vs 37.3; difference -6.2; 95% CI -7.8 to -4.7; P < 0.0001) and class II (mean 31.0 vs 35.0; difference -3.9; 95% CI -5.6 to -2.2; P < 0.0001) obesity groups. The class III obesity group had a base of support (cm) during gait that was wider than that for the overweight or class I (mean 14.0 vs 11.6; difference 3.3; 95% CI 2.6-4.0; P < 0.0001) and class II (mean 14.0 vs 11.6; difference 2.4; 95% CI 1.6-3.2; P < 0.0001) obesity groups. CONCLUSION: Among adults with knee OA, those with class III obesity had significantly higher pain levels and worse physical HRQL and gait characteristics compared to adults with overweight or class I or class II obesity.

Strength Training for Arthritis Trial (START): design and rationale.

BACKGROUND: Muscle loss and fat gain contribute to the disability, pain, and morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk factor for it. However, while all published treatment guidelines recommend muscle strengthening exercise to combat loss of muscle mass and strength in knee OA patients, previous strength training studies either used intensities or loads below recommended levels for healthy adults or were generally short, lasting only 6 to 24 weeks. The efficacy of high-intensity strength training in improving OA symptoms, slowing progression, and affecting the underlying mechanisms has not been examined due to the unsubstantiated belief that it might exacerbate symptoms. We hypothesize that in addition to short-term clinical benefits, combining greater duration with high-intensity strength training will alter thigh composition sufficiently to attain long-term reductions in knee-joint forces, lower pain levels, decrease inflammatory cytokines, and slow OA progression. METHODS/DESIGN: This is an assessor-blind, randomized controlled trial. The study population consists of 372 older (age ≥ 55 yrs) ambulatory, community-dwelling persons with: (1) mild-to-moderate medial tibiofemoral OA (Kellgren-Lawrence (KL) = 2 or 3); (2) knee neutral or varus aligned knee ( -2° valgus ≤ angle ≤ 10° varus); (3) 20 kg.m-2 ≥ BMI ≤ 45 kg.m-2; and (3) no participation in a formal strength-training program for more than 30 minutes per week within the past 6 months. Participants are randomized to one of 3 groups: high-intensity strength training (75-90% 1Repetition Maximum (1RM)); low-intensity strength training (30-40%1RM); or healthy living education. The primary clinical aim is to compare the interventions' effects on knee pain, and the primary mechanistic aim is to compare their effects on knee-joint compressive forces during walking, a mechanism that affects the OA disease pathway. Secondary aims will compare the interventions' effects on additional clinical measures of disease severity (e.g., function, mobility); disease progression measured by x-ray; thigh muscle and fat volume, measured by computed tomography (CT); components of thigh muscle function, including hip abductor strength and quadriceps strength, and power; additional measures of knee-joint loading; inflammatory and OA biomarkers; and health-related quality of life. DISCUSSION: Test-retest reliability for the thigh CT scan was: total thigh volume, intra-class correlation coefficients (ICC) = 0.99; total fat volume, ICC = 0.99, and total muscle volume, ICC = 0.99. ICC for both isokinetic concentric knee flexion and extension strength was 0.93, and for hip-abductor concentric strength was 0.99. The reliability of our 1RM testing was: leg press, ICC = 0.95; leg curl, ICC = 0.99; and leg extension, ICC = 0.98. Results of this trial will provide critically needed guidance for clinicians in a variety of health professions who prescribe and oversee treatment and prevention of OA-related complications. Given the prevalence and impact of OA and the widespread availability of this intervention, assessing the efficacy of optimal strength training has the potential for immediate and vital clinical impact. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01489462.

Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial.

IMPORTANCE: Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity. OBJECTIVE: To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone. DESIGN, SETTING, AND PARTICIPANTS: Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA. INTERVENTIONS: Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise. MAIN OUTCOMES AND MEASURES: Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100). RESULTS: Three hundred ninety-nine participants (88%) completed the study. Mean weight loss for diet + exercise participants was 10.6 kg (11.4%); for the diet group, 8.9 kg (9.5%); and for the exercise group, 1.8 kg (2.0%). After 18 months, knee compressive forces were lower in diet participants (mean, 2487 N; 95% CI, 2393 to 2581) compared with exercise participants (2687 N; 95% CI, 2590 to 2784, pairwise difference [Δ](exercise vs diet )= 200 N; 95% CI, 55 to 345; P = .007). Concentrations of IL-6 were lower in diet + exercise (2.7 pg/mL; 95% CI, 2.5 to 3.0) and diet participants (2.7 pg/mL; 95% CI, 2.4 to 3.0) compared with exercise participants (3.1 pg/mL; 95% CI, 2.9 to 3.4; Δ(exercise vs diet + exercise) = 0.39 pg/mL; 95% CI, -0.03 to 0.81; P = .007; Δ(exercise vs diet )= 0.43 pg/mL; 95% CI, 0.01 to 0.85, P = .006). The diet + exercise group had less pain (3.6; 95% CI, 3.2 to 4.1) and better function (14.1; 95% CI, 12.6 to 15.6) than both the diet group (4.8; 95% CI, 4.3 to 5.2) and exercise group (4.7; 95% CI, 4.2 to 5.1, Δ(exercise vs diet + exercise) = 1.02; 95% CI, 0.33 to 1.71; P(pain) = .004; 18.4; 95% CI, 16.9 to 19.9; Δ(exercise vs diet + exercise), 4.29; 95% CI, 2.07 to 6.50; P(function )< .001). The diet + exercise group (44.7; 95% CI, 43.4 to 46.0) also had better physical health-related quality of life scores than the exercise group (41.9; 95% CI, 40.5 to 43.2; Δ(exercise vs diet + exercise) = -2.81; 95% CI, -4.76 to -0.86; P = .005). CONCLUSIONS AND RELEVANCE: Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00381290.

Skeletal Muscle Mitochondrial Respiration and Exercise Intolerance in Patients With Heart Failure With Preserved Ejection Fraction.

Importance: The pathophysiology of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely understood. Multiple lines of evidence suggest that abnormal skeletal muscle metabolism is a key contributor, but the mechanisms underlying metabolic dysfunction remain unresolved. Objective: To evaluate the associations of skeletal muscle mitochondrial function using respirometric analysis of biopsied muscle fiber bundles from patients with HFpEF with exercise performance. Design, Setting, and Participants: In this cross-sectional study, muscle fiber bundles prepared from fresh vastus lateralis biopsies were analyzed by high-resolution respirometry to provide detailed analyses of mitochondrial oxidative phosphorylation, including maximal capacity and the individual contributions of complex I-linked and complex II-linked respiration. These bioenergetic data were compared between patients with stable chronic HFpEF older than 60 years and age-matched healthy control (HC) participants and analyzed for intergroup differences and associations with exercise performance. All participants were treated at a university referral center, were clinically stable, and were not undergoing regular exercise or diet programs. Data were collected from March 2016 to December 2017, and data were analyzed from November 2020 to May 2021. Main Outcomes and Measures: Skeletal muscle mitochondrial function, including maximal capacity and respiration linked to complex I and complex II. Exercise performance was assessed by peak exercise oxygen consumption, 6-minute walk distance, and the Short Physical Performance Battery. Results: Of 72 included patients, 50 (69%) were women, and the mean (SD) age was 69.6 (6.1) years. Skeletal muscle mitochondrial function measures were all markedly lower in skeletal muscle fibers obtained from patients with HFpEF compared with HCs, even when adjusting for age, sex, and body mass index. Maximal capacity was strongly and significantly correlated with peak exercise oxygen consumption (R = 0.69; P < .001), 6-minute walk distance (R = 0.70; P < .001), and Short Physical Performance Battery score (R = 0.46; P < .001). Conclusions and Relevance: In this study, patients with HFpEF had marked abnormalities in skeletal muscle mitochondrial function. Severely reduced maximal capacity and complex I-linked and complex II-linked respiration were associated with exercise intolerance and represent promising therapeutic targets.

Intervening on exercise and daylong movement for weight loss maintenance in older adults: A randomized, clinical trial.

OBJECTIVE: This study aimed to determine the impact of dietary weight loss (WL) plus aerobic exercise (EX) and a "move more, more often" approach to activity promotion (SitLess; SL) on WL and maintenance. METHODS: Low-active older adults (age 65-86 years) with obesity were randomized to WL+EX, WL+SL, or WL+EX+SL. Participants received a social-cognitive group-mediated behavioral WL program for 6 months, followed by a 12-month maintenance period. EX participants received guided walking exercise with the goal of walking 150 min/wk. SL attempted to achieve a step goal by moving frequently during the day. The primary outcome was body weight at 18 months, with secondary outcomes including weight regain from 6 to 18 months and objectively assessed physical activity and sedentary behavior at each time point. RESULTS: All groups demonstrated significant WL over 6 months (p < 0.001), with no group differences. Groups that received SL improved total activity time (p ≤ 0.05), and those who received EX improved moderate-to-vigorous activity time (p = 0.003). Over the 12-month follow-up period, those who received WL+EX demonstrated greater weight regain (5.2 kg; 95% CI: 3.5-6.9) relative to WL+SL (2.4 kg; 95% CI: 0.8-4.0). CONCLUSIONS: Pairing dietary WL with a recommendation to accumulate physical activity contributed to similar WL and less weight regain compared with traditional aerobic exercise.

Changes in Body Weight and Knee Pain in Adults With Knee Osteoarthritis Three-and-a-Half Years After Completing Diet and Exercise Interventions: Follow-Up Study for a Single-Blind, Single-Center, Randomized Controlled Trial.

OBJECTIVE: To determine whether long-term diet (D) and exercise (E) interventions, alone or in combination (D+E), have beneficial effects for older adults with knee osteoarthritis (OA) 3.5 years after the interventions end. METHODS: This is a secondary analysis of a subset (n = 94) of the first 184 participants who had successfully completed the Intensive Diet and Exercise in Arthritis (IDEA) trial (n = 399) and who consented to follow-up testing. Participants were older (age ≥55 years), overweight, and obese adults with radiographic and symptomatic knee OA in at least 1 knee who completed 1.5-year D+E (n = 27), D (n = 35), or E (n = 32) interventions and returned for 5-year follow-up testing an average of 3.5 years later. RESULTS: During the 3.5-years following the interventions, weight regain in D+E and D was 5.9 kg (7%) and 3.1 kg (4%), respectively, with a 1-kg (1%) weight loss in E. Compared to baseline, weight (D+E -3.7 kg [P = 0.0007], D -5.8 kg [P < 0.0001], E -2.9 kg [P = 0.003]) and Western Ontario and McMaster Universities Osteoarthritis Index pain subscale scores (D+E -1.2 [P = 0.03], D -1.5 [P = 0.001], E -1.6 [P = 0.0008]) were lower in each group at the 5-year follow-up. The effect of group assignment at the 5-year follow-up was significant for body weight, with D being less than E (-3.5 kg; P = 0.04). CONCLUSION: Older adults with knee OA who completed 1.5-year D or D+E interventions experienced partial weight regain 3.5 years later; yet, relative to baseline, they preserved statistically significant changes in weight loss and reductions in knee pain.

Incidence, Determinants and Mortality of Heart Failure Associated With Medical-Surgical Procedures in Patients ≥ 65 Years of Age (from the Cardiovascular Health Study).

Heart failure (HF) and myocardial infarction are serious complications of major noncardiac surgery in older adults. Many factors can contribute to the development of HF during the postoperative period. The incidence of, and risk factors for, procedure-associated heart failure (PHF) occurring at the time of, or shortly after, medical procedures in a population-based sample ≥ 65 years of age have not been fully characterized, particularly in comparison with HF not proximate to medical procedures. This analysis comprises 5,121 men and women free of HF at baseline from the Cardiovascular Health Study who were followed up for 12.0 years (median). HF events were documented by self-report at semi-annual contacts and confirmed by a formal adjudication committee using a review of the participants' medical records and standardized criteria for HF. Incident HF events were additionally adjudicated as either being related or unrelated to a medical procedure (PHF and non-PHF, respectively). We estimated cause-specific hazards ratios for the association of covariates with PHF and non-PHF. There were 1,728 incident HF events in the primary analysis: 168 (10%) classified as PHF, 1,526 (88%) as non-PHF, and 34 unclassified (2%). For those 1,045 participants in whom LV ejection fraction was known at the time of the HF event, it was ≥45% in 89 of 118 participants (75%) with PHF, compared to 517 of 927 participants (55%) with non-PHF (p < 0.001). Increased age, male gender, diabetes, and angina at baseline were associated with both PHF and non-PHF (range of hazard ratios (HR): 1.04-2.05]. Being Black was inversely associated with PHF [HR: 0.46, 95% confidence interval: 0.25-0.86]. Participants with increased age, without baseline angina, and with baseline LVEF<55% were at a significantly lower risk for PHF compared to non-PHF. Among those with PHF, surgical procedures-including cardiac, orthopedic, gastrointestinal, vascular, and urologic-comprised 83.3%, while percutaneous procedures comprised 8.9% (including 6.5% represented by cardiac catheterizations and pacemaker placements). Another group composed of a variety of procedures commonly requiring large fluid volume administration comprised 7.7%. There was a lower all-cause 30-day mortality in the PHF versus the non-PHF group (2.2% vs 5.7%), with a nonsignificant odds ratio of 0.39 in a minimally adjusted model. When individuals with prior myocardial infarction (MI) were excluded in a sensitivity analysis, the proportion of incident HF with concurrent MI was greater for PHF (32.9%) than for non-PHF (19.8%). In conclusion, PHF in older adults is a common entity with relatively low 30-day mortality. Baseline angina, lower age, and LVEF ≥ 55% were associated with a higher risk of PHF compared to non-PHF. Being Black was associated with a lower risk of PHF and PHF as a proportion of HF was lower in Black than in non-Black participants. Compared to non-PHF, PHF more frequently presented with concurrent MI and with preserved LV ejection fraction.

Urine creatinine concentration and clinical outcomes in older adults: The Cardiovascular Health Study.

PURPOSE: Loss of muscle mass and strength are associated with long-term adverse health outcomes in older adults. Urine creatinine concentrations (Ucr; mg/dl) are a measure of muscle tissue mass and turnover. This study assessed the associations of a spot Ucr level with muscle mass and with risk of hospitalization, mortality, and diabetes mellitus in older adults. METHODS: We examined 3424 participants from the Cardiovascular Health Study who provided spot urine samples in 1996-1997 and who were followed through June 2015. All participants underwent baseline measurement of grip strength. In a sub-cohort, 1331 participants underwent dual energy X-ray absorptiometry (DEXA) scans, from which lean muscle mass was derived. Participants were followed for a median of 10 years for hospitalizations and mortality, and 9 years for diabetes mellitus. RESULTS: In linear regression analysis, a one standard deviation higher Ucr concentration (64.6 mg/dl) was associated with greater grip strength (kg force) ß = 0.44 [0.16, 0.72]; p = 0.002) and higher lean muscle mass (kg) (ß = 0.43 [0.08, 0.78]; p = 0.02). In Cox regression analyses, each standard deviation greater Ucr concentration was associated with lower rates of hospitalizations (0.94 [95% confidence interval, 0.90, 0.98]; p < 0.001) and lower mortality risk (0.92 [0.88, 0.97]; p < 0.001), while a one standard deviation increase in muscle mass derived from DEXA had no such significant association. Ucr levels were not associated with incident diabetes mellitus risk (0.97 [0.85, 1.11]; p = 0.65). CONCLUSION: A higher spot Ucr concentration was favorably associated with muscle mass and strength and with health outcomes in older community-living adults. The ease of obtaining a spot Ucr makes it an attractive analyte to use for gauging the health of older adults.