125 research outputs found

    EFFECTS OF INTENSIVE DIET AND EXERCISE ON KNEE JOINT LOADS, INFLAMMATION, AND CLINICAL OUTCOMES AMONG OVERWEIGHT AND OBESE ADULTS WITH KNEE OSTEOARTHRITIS

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    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; Δexercise vs diet + exercise = 0.39 pg/mL; 95% CI, −0.03 to 0.81; P = .007; Δexercise 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, Δexercise vs diet + exercise = 1.02; 95% CI, 0.33 to 1.71; Ppain = .004; 18.4; 95% CI, 16.9 to 19.9; Δexercise vs diet + exercise, 4.29; 95% CI, 2.07 to 6.50; Pfunction < .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; Δexercise 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

    A Population Proportion approach for ranking differentially expressed genes

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    <p>Abstract</p> <p>Background</p> <p>DNA microarrays are used to investigate differences in gene expression between two or more classes of samples. Most currently used approaches compare mean expression levels between classes and are not geared to find genes whose expression is significantly different in only a subset of samples in a class. However, biological variability can lead to situations where key genes are differentially expressed in only a subset of samples. To facilitate the identification of such genes, a new method is reported.</p> <p>Methods</p> <p>The key difference between the Population Proportion Ranking Method (PPRM) presented here and almost all other methods currently used is in the quantification of variability. PPRM quantifies variability in terms of inter-sample ratios and can be used to calculate the relative merit of differentially expressed genes with a specified difference in expression level between at least some samples in the two classes, which at the same time have lower than a specified variability within each class.</p> <p>Results</p> <p>PPRM is tested on simulated data and on three publicly available cancer data sets. It is compared to the t test, PPST, COPA, OS, ORT and MOST using the simulated data. Under the conditions tested, it performs as well or better than the other methods tested under low intra-class variability and better than t test, PPST, COPA and OS when a gene is differentially expressed in only a subset of samples. It performs better than ORT and MOST in recognizing non differentially expressed genes with high variability in expression levels across all samples. For biological data, the success of predictor genes identified in appropriately classifying an independent sample is reported.</p

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

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    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
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