The Arthritis, Diet and Activity Promotion Trial (ADAPT): design, rationale, and baseline results

Controlled Clinical Trials 24 (2003) 462–480

Design paper

The Arthritis, Diet and Activity Promotion Trial (ADAPT): design, rationale, and baseline results Gary D. Miller, Ph.D.a,*, W. Jack Rejeski, Ph.D.a, Jeff D. Williamson, M.D., M.P.H.b, Timothy Morgan, Ph.D.c, Mary Ann Sevick, Ph.D.c, Richard F. Loeser, M.D.b, Walt H. Ettinger, M.D.b, Stephen P. Messier, Ph.D.a for the ADAPT investigators a

Department of Health and Exercise Science Wake Forest University, Winston-Salem, North Carolina, USA b Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA c Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA Manuscript received May 7, 2002; manuscript accepted March 19, 2003

Abstract Osteoarthritis (OA) of the knee leads to restrictions of physical activity and ability to perform activities of daily living. Obesity is a risk factor for knee OA and it appears to exacerbate knee pain and disability. The Arthritis, Diet, and Activity Promotion Trial (ADAPT) was developed to test the efficacy of lifestyle behavioral changes on physical function, pain, and disability in obese, sedentary older adults with knee OA. This controlled trial randomized 316 sedentary overweight and obese older adults in a two-by-two factorial design into one of four 18-month duration intervention groups: Healthy Lifestyle Control; Dietary Weight Loss; Structured Exercise; or Combined Exercise and Dietary Weight Loss. The weight-loss goal for the diet groups was a 5% loss at 18 months. The intervention was modeled from principles derived from the group dynamics literature and social cognitive theory. Exercise training consisted of aerobic and strength training for 60 minutes, three times per week in a group and home-based setting. The primary outcome measure was self-report of physical function using the Western Ontario and McMaster University Osteoarthritis Index. Other measurements included timed stair climb, distance walked in 6 minutes, strength, gait, knee pain, health-related quality of life, knee radiographs, body weight, dietary intake, and cost-effectiveness of the interventions. We report baseline data stratified by level of overweight and obesity focusing on self-reported physical function and physical performance tasks. The results from ADAPT will provide

* Corresponding author: Gary Miller, Box 7868 Reynolda Station, Wake Forest University, Winston-Salem, NC 27109. Tel.: ⫹1-336-758-1901; fax: ⫹1-336-758-4680. E-mail address: [email protected] 0197-2456/03/$—see front matter 쑕 2003 by Elsevier Inc. All rights reserved. doi:10.1016/S0197-2456(03)00063-1

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approaches clinicians should recommend for behavioral therapies that effectively reduce the incidence of disability associated with knee OA. 쑕 2003 by Elsevier Inc. All rights reserved. Keywords: Exercise; Physical function; Disability; Health-related quality of life

Introduction Osteoarthritis (OA) is the most prevalent chronic joint condition and the leading cause of disability in the United States, with the majority of those afflicted being over the age of 65 [1,2]. An estimated 43 million individuals had arthritis in 1997. By the year 2020, as many as 60 million persons may be affected by this disease [3]. Symptomatic or radiographic evidence of knee OA is present in 10–33% of adults over the age of 65 [4,5]. Prevalence rates of self-reported arthritis increase dramatically with age [3]. The disease is more common in women than men and more often observed in African-American than Caucasian women [3,6]. In 1997 arthritis was reported to be a cause of activity limitations in 8 million persons in the United States [3]. Knee OA and its associated symptoms are a major cause of physical disability, leading to a loss of independence in older adults. Several studies have shown that older adults with knee OA are more likely to have restrictions with mobility and transfer activities and a reduced ability to perform instrumental activities of daily living when compared to age-matched healthy controls [7–9]. Although the cause of knee OA is unknown, obesity is a primary risk factor [10–12]. Crosssectional data indicate that individuals clinically defined as obese with a body mass index (BMI) ⬎ 30.0 kg·m⫺2 were four times more likely to have knee OA than those with a BMI in the desirable range of ⭐25.0 kg·m⫺2 [5]. The degree of obesity at an early age also affects the risk of developing knee OA later in life. For example, men and women in the top quartile of BMI at age 40 have a three- and ninefold greater risk, respectively, for developing knee OA at age 50 compared to persons at the lowest BMI quartile at age 40 [13]. Observational evidence from the Framingham Knee OA Study showed that a lower weight of 5.1 kg decreased the risk of developing knee OA by over 50% in women with a baseline BMI above 25 kg·m⫺2 [10]. Prior work from our group has shown that higher BMI levels are associated with increased pain and decline in both self-reported and performance-based measures of function in older adults with knee OA [14]. However, there are no data from randomized controlled clinical trials that relate weight loss to the prevention of incident knee OA or its progression. The mechanism for obesity as a causative agent for knee OA is hypothesized to be mechanical [15]. The excessive forces on the joint produce changes in chondrocytes that alter the synthesis and degradation of the constituents of hyaline cartilage [16]. Furthermore, an increase in forces has been observed in the lower extremity of obese individuals with knee OA [17]. Another proposed mechanism is that endocrine products from adipose tissue, such as tumor necrosis factor-alpha, the interleukins, or leptin may play a role in the development and progression of OA. This is based on the work by Toda and colleagues, which demonstrated that the changes in radiographic knee OA were correlated with reductions in body fat but not associated with changes in body weight from a weight-loss program [18].

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Randomized controlled trials have shown that exercise therapy improves knee pain, physical activity, physical function, and self-reported disability in individuals with knee OA compared to sedentary controls [14,19–22]. These benefits have been observed with strength training and a variety of aerobic exercise modalities, including fitness walking, aerobic exercise, and cycling [23,24]. We previously found in the Fitness Arthritis and Seniors Trial (FAST) that 18 months of aerobic exercise training for 1 hour per day, three times per week, produced up to 12% improvement in self-reported physical disability, knee pain, and performance on physical tasks as compared to a health education control group [14]. In addition, a resistance-trained group also showed beneficial effects on these measures as compared to a health education control group [14]. Based on these and other findings, the American College of Rheumatology guidelines for treating individuals with OA recommend that exercise be a vital component of therapy [25]. The benefits obtained from the exercise intervention utilized in FAST has led us to examine the effect of a lifestyle intervention to promote weight loss on disability from knee OA, radiographic progression of knee OA, health-related quality of life, and gait biomechanics in older adults. Although obesity is a major risk factor for OA, no large randomized controlled trials had previously been conducted that examined weight loss on physical disability in obese older adults. Similarly, no trials have evaluated the relative benefits of weight loss, alone or in combination with exercise, on these measures. The Arthritis, Diet, and Activity Promotion Trial (ADAPT) tested the relative effectiveness of weight loss and exercise and their combination in reducing disability and pain in older, obese, sedentary adults with knee OA. The specific aims of the study were: 1. To compare the effectiveness of a dietary weight-loss intervention, an exercise intervention, and their combination on self-reported disability and physical function in older, overweight and obese, sedentary adults with knee OA. 2. To determine the effectiveness of the interventions on radiographic progression of knee OA, knee pain, performance measures of function, exercise capacity, and health-related quality of life in this population. 3. To determine the effectiveness of the interventions on gait biomechanics, with a specific emphasis on forces and moments at the knee joint. 4. To determine the incremental cost-effectiveness of the interventions in producing the outcomes under investigation. The purpose of this paper is to present the design for the trial, to describe the population in ADAPT, and to report analysis of the baseline data focusing on self-reported physical function and physical performance tasks. In addition, analysis on the baseline data was performed to examine the differences in physical function and physical performance tasks by degree of overweight and obesity.

Research design and methods ADAPT was a single-center, 18-month randomized controlled trial. A two-by-two factorial design was utilized for comparing the effects of dietary weight loss and exercise interventions

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on physical function and disability in older adults with knee OA (see Fig. 1). There were four arms to the study: Healthy Lifestyle Controls, Dietary Weight Loss, Structured Exercise, or Combined Exercise and Dietary Weight Loss. The data collectors in the study were blinded to the intervention assignment of the participants but the interventionists and participants were not blinded. Participants were instructed and reminded at every visit to not provide any information to staff regarding their intervention. Study population Participant recruitment for the study was performed in six waves over an 18-month period from November 1996 through June 1998. A total of 316 community-dwelling women and men were randomized into the four arms of the study with each group having approximately 78 participants. Older (⭓60 years), overweight, and obese (BMI ⭓ 28.0 kg·m⫺2) sedentary adults with radiographic evidence of knee OA were recruited for the study. Potential participants were asked a single question about their participation in physical activity. They were considered sedentary for inclusion in this study if, in the past 6 months, they had not engaged in a formal exercise program defined by ⭓1 sessions per week of formal exercise for 20 minutes or more, or expending ⭓200 calories per week in moderate- to high-intensity activities. Examples of activities were suggested to the participant that would satisfy this energy expenditure. The inclusion and exclusion criteria (Table 1) were developed to give the highest level of assurance that physical disability was due to knee OA and that the trial included persons who were likely to benefit from a weight-loss and physical activity intervention. In addition, current conditions that prevented individuals from beginning or completing the interventions were a rationale for exclusion from the trial.

Fig. 1. Two-by-two design scheme.

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Table 1. Inclusion and exclusion criteria Inclusion • Age ⭓ 60 years old • Overweight or obese with BMI ⭓ 28.0 kg·m⫺2 • Sedentary activity pattern and not actively participating in a formal exercise program within the past 6 months (defined by 20 minutes or more of formal exercise ⭓1 session per week or expending ⭓200 calories per week in moderate- to high-intensity activities) • Symptomatic knee OA (radiographic grade II–III using Kellgren and Lawrence criteria) of one or both knees • Self-reported difficulty in at least one of the following activities attributed to knee pain: lifting and carrying groceries, walking one-quarter mile, getting in and out of a chair, or going up and down stairs Exclusion • Significant comorbid disease that would pose a safety threat or impair ability to participate, including: coronary artery disease, severe hypertension, peripheral vascular disease, stroke, congestive heart failure, chronic obstructive pulmonary disease, insulin-dependent diabetes, psychiatric disease, renal disease, liver disease, anemia, dementia, inability to walk without an assistive device or blindness • Inability or unwillingness to modify dietary or exercise behaviors due to environment or to speak and read English • Excessive alcohol use with a cutoff of ⭓14 drinks per week • Unable to finish the 18-month study or unlikely to be compliant, including living more than 50 miles from the site or planning to leave the area for 3 months or more during the next 18 months

Interventions The delivery of the intervention for each arm of the study was conducted independent of the other groups to eliminate cross-contamination of the treatments. The exercise program was conducted 3 days per week for 60 minutes per session and was similar for the Exercise and Exercise-Diet groups. The exercise interventionists were exercise physiologists with more than 2 years of experience in working with the older adult population in the clinical setting. They were trained in behavioral techniques by the health psychologist. Participants engaged in a structured, facility-based training program for the first 4 months of the intervention. Individuals in the exercise groups were instructed on techniques to promote retention in the program. Subsequent to this initial period, participants had the option to choose to continue exercising in the facility for the remaining 14 months of the intervention, or to transition to a home-based exercise program for the duration of the study, or to combine both facility and home-based approaches. Before moving to a home-based program, participants were instructed on behavioral techniques to facilitate adherence and then were transitioned during months 5 and 6 of the intervention, tapering the number of visits to the facility and increasing the number of exercise sessions at home [26,27]. In the facility, the exercise program consisted of a warm-up phase (5 minutes), an aerobic phase (15 minutes), a strength phase (20 minutes), a second aerobic phase (15 minutes), and a cooldown phase (5 minutes). The primary mode of aerobic training consisted of walking and was patterned after FAST [14]. Participants were allowed flexibility in choosing their mode for aerobic training. The exercise intensity for the aerobic exercise was 50–85% of the heart rate reserve using the symptom-limited maximum heart rate obtained from a graded exercise test. Participants regularly monitored and recorded their heart rate during the exercise sessions. Strength training included four stations: leg extension, leg curl, heel raise, and step-ups using ankle cuff weights and a weighted vest. Two sets of 12 repetitions were performed at each

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station. Resistance was progressively increased during the intervention as strength improved. Lower-body flexibility exercises were also performed at each session. Weights were provided to the participants if they chose to perform home-based exercises. Both Diet and Exercise-Diet groups were prescribed similar dietary intervention strategies. The diet intervention was conducted by trained registered dietitians, holding master of science degrees, with experience working with older adults and adult education. They worked with the health psychologist in the development and delivery of the behavioral aspects of the intervention. The weight-loss goal for these two groups was a mean loss of ⭓5% of initial body weight. The dietary intervention was modeled on principles derived from the group dynamics literature and social cognitive theory [28,29]. In the Trial of Nonpharmacological Treatment in the Elderly (TONE), obese, hypertensive, older adults (60–80 years) were able to maintain a 5.4% decrease in body weight over a 30-month period with monthly contacts during the 22-month maintenance phase [30]. We anticipated achieving a similar weight loss since participants in the two studies were of similar age and ADAPT utilized many of the same weight-loss strategies and techniques used in TONE. We hypothesized that this level of weight loss would be efficacious in relieving symptoms of knee OA. Specifically, Toda et al. showed that a 5.6% decrease in body weight over a 6-week period produced a significant decrease in symptoms of knee OA in women over the age of 45 years [18]. Both group and individual diet sessions were utilized throughout the duration of the investigation with one in every four sessions being an individual appointment. The first session was an introductory, individual meeting with the interventionist to establish weight-loss goals and to orient the participant to the study and facilities. The first 4 months were termed the intensive phase with weekly meetings conducted by a registered dietitian trained in the intervention strategy. The topics in the intensive phase focused on healthful food selection with portion and dietary fat control to decrease energy intake, emphasizing an increased awareness in the consequence of, and the need to change, dietary habits. Participants were individually counseled on reducing energy intake by ⬃500 calories per day in order to achieve the desired weight loss. Examples of group program topics included Healthy Eating, Reading Labels, Shopping, Food Preparation, Meal Ideas, Restaurants, Ethnic Eating, Special Occasions, and Old and New Routines. Self-regulatory skills were taught by the interventionists, including self-monitoring, goal setting, environmental management, stimulus control, and cognitive restructuring. Group sessions included problem solving, education on a specific topic, and tasting of nutritious foods consistent with the intervention. Individual sessions included a review of participant progress, problem solving, goal setting, and answering specific questions. Biweekly meetings were held during months 5 and 6 of the transition period. The emphasis of this phase was to maintain and prevent relapse in participants who reached their weightloss goals and to reestablish new goals for those who did not reach their goals. During the maintenance period of months 7–18, diet meetings were held monthly. In addition to these meetings, phone contacts were alternated every 2 weeks to provide interventionistparticipant contact on a biweekly basis. Further contact was facilitated through regularly distributed newsletters that provided pertinent nutrition information and a schedule of events for the intervention groups. The goals of the maintenance phase included assisting in weight maintenance for those who had achieved their weight-loss goals and providing counsel for

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participants who had a difficult time in losing weight and adhering to the intervention. As in TONE, both individual and group sessions were tailored to consider the older adult learner including sensory and motor changes, alterations in cognitive function, and cohort and situational differences [30]. Intervention groups were approximately 12–14 participants in size. Adherence to the exercise and dietary interventions was monitored based on attendance to sessions and completion of routine exercise logs. Exercise interventionists routinely monitored the logs for completeness and quality of data entry. If logs were incomplete, the interventionists reminded participants that these records needed to be complete and, as appropriate, to recall and fill in missing records. Individuals transitioned to home-based exercise also submitted regular exercise logs detailing the day of week, exercise duration, and heart rate achieved for each exercise session. Participants randomized to the healthy lifestyle group met monthly for 1 hour over the first 3 months of the trial. Topics for these sessions included osteoarthritis, obesity, and exercise. In addition, phone contacts were established on a monthly (for months 4–6) and bimonthly (months 7–18) basis. Information on pain, medications, illnesses, and hospitalization was obtained during the phone contacts. Recruitment Recruitment strategies combined advertising through media exposure and mass mailings. A commercially available computer-based mailing list of age-eligible households was used to identify a target audience for mass mailings. The minority recruitment goal was 30%, with most of these expected to be African-Americans (26%), along with a representation of Hispanics (1%), Native Americans (1%), and Asian-Americans (0.5%). Strategies to target recruitment of minorities included: (1) oversampling in zip codes with a large minority population; (2) working for endorsements by leaders in the minority community and promoting the study in minority neighborhoods through churches and civic organizations; (3) performing screening in senior residential sites and shopping centers in minority neighborhoods; (4) developing culturally sensitive recruitment materials for each minority subgroup; (5) providing transportation for eligible subjects who otherwise would not be able to participate in the intervention or data collection; and (6) advertising in ethnic-specific newspapers and radio stations. Recruitment for the study was conducted through a central core and sponsored by a Claude D. Pepper Older Americans Grant. Screening and outcome measurement periods Screening A total of 2209 persons contacted the recruitment core personnel and were screened via phone for major eligibility criteria. Participants who passed the phone screen were scheduled for an initial screening visit, which included obtaining the written informed consent following requirements of the Institutional Review Board at Wake Forest University School of Medicine, background demographics (occupation history, income, education, community involvement), medical history, medication use, physical examination, self-report of disability, knee pain, physical activity, body weight, and screening blood tests. If individuals met the initial

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eligibility criteria, a knee X-ray was obtained. Based on these results a second screening visit was scheduled and a physician-supervised treadmill graded exercise test was administered to assess the safety of engaging in an exercise intervention and to develop the exercise prescription for those subsequently randomized. An interventionist interviewed participants to assess their ability to comply with the intervention. Following eligibility confirmation, 316 individuals were randomized to one of the four interventions. During the randomization visit, data were collected on health-related quality of life, social support, and physical performance [31,32]. Approximately one-third and one-half of the participants were randomized into subsets for measurements of dietary assessment and biomechanics/strength, respectively. Follow-up Additional measurements were obtained at follow-up visits scheduled for months 6 and 18 of the intervention. A complete list of measurements obtained and their scheduling is found in Table 2. Outcome measures Study staff who administered questionnaires and conducted testing procedures were trained in these procedures and followed standard operating protocols. These staff members were not interventionists and were blinded to group assignments. Physical function The measurement of physical function was assessed through self-report questionnaires and physical performance tests. Self-report Self-reported physical function was measured using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the FAST Functional Performance Inventory [14,33]. The WOMAC has been validated and is recommended by the Osteoarthritis Research Society as the measure of choice [33]. The 24-item WOMAC instrument was developed for use by individuals who have OA of the hip or knee and is a health status instrument that assesses participant’s perception of pain, joint stiffness, and physical function. The primary outcome measurement for ADAPT is the mean response for the 17 questions in WOMAC that are directed toward physical function. Although the WOMAC is a self-report assessment, it is the most common primary measure in previous clinical trials of OA. The FAST Functional Performance Inventory, developed for that study, utilizes 23 questions directed toward assessing self-reported difficulties in performing physical tasks required for daily living, which was a secondary outcome measure [14]. This instrument provides distinct dimensions in basic activities of daily living (e.g., dressing one’s self), complex instrumental activities of daily living (e.g., doing light housework), ambulation and climbing (e.g., climbing stairs), transfer (e.g., getting into and out of a car), and upper extremities (e.g., lifting heavy objects). The dimensions have good internal consistency (all Cronbach alphas ⬎0.80) and have statistically significant relationships with objective measures of function [34].

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Performance Laboratory tests used to assess physical performance included the 6-minute walk distance and stair climb time. Briefly, for the first test, participants were instructed to walk as far as possible in a 6-minute time period on an established course. They were not allowed to carry a watch and were not provided with feedback during the trial. Performance was measured by the total distance covered. This test is significantly correlated to treadmill time and symptomlimited maximal oxygen consumption (r ⫽ 0.52 and r ⫽ 0.53, respectively) and has a 3-month test-retest reliability of 0.86 [34]. The second performance test was a timed stair climb that involved ascending and descending a flight of five stairs as quickly as possible. During the ascent, participants were told to hang on to the handrail with their left hand and, without hesitation, turn around on the platform at the top and climb down using the same Table 2. List and timing of outcome measures Measures

Baseline at screening and randomization

6-month follow-up

18-month follow-up

Eligibility screen Informed consent Demographics Blood draw Questionnaires Medical history MMSEa Medications Social supportb SF 36c Sleepd WOMACe Self/body image [38] Knee pain scale [34] Physical functionf Physical exam X-ray Height/weight Stair climb 6-minute walk Graded exercise test Biomechanics/strengthg Dietary intakeh Cost-effectiveness

X X X X

X

X

X X X X X X X X

X

X

X X X X X X

X X X X X X

X

X

X

X X X X X X X X X X

X

X X X X X X X X X X

a b c d e f g h

X X X X X X

Mini-Mental State Examination [36]. Medical Outcomes Social Support Survey [32]. Medical Outcomes Study 36-item Short Form Health Survey [31]. Sleep Disturbance Questionnaire. Western Ontario McMaster University Osteoarthritis Index [33]. FAST Functional Performance Inventory [14]. Only performed on a randomized subset of one-fourth of the cohort. Only performed on a randomized subset of one-third of the cohort.

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hand to hold onto the rail. Performance was measured as the time required to complete the task. This test has a correlation value of r ⫽ ⫺0.49 with maximal functional capacity and a testretest reliability over a 3-month period of 0.75–0.87 [34]. Knee pain Knee pain was assessed using the WOMAC and the knee pain scale (KPS). The WOMAC has five questions that allow the participant to rate their pain from “none” to “extreme” while sitting, lying in bed, standing, walking, and ascending and descending stairs. The KPS instrument was developed from FAST with a focus on measuring knee pain in persons with knee OA [34]. It assesses the frequency and intensity of knee pain in relation to the performance of daily activities that involve ambulation/climbing and transfer. Two-week test-retest reliability exceeds 0.84 for all subscales of the KPS. Health-related quality of life Participant’s overall health-related quality of life was determined by the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) [31]. This widely used scale is multidimensional. It has two summary sources for physical and mental health as well as eight subscale scores: physical functioning, role limitations due to physical and emotional problems, pain, general health perceptions, vitality, social functioning, emotional well-being, and health transition. It has been validated in patients with osteoarthritis [35]. Other psychological assessments The Mini-Mental State Examination was administered to assess cognitive performance [36]. This instrument was administered by study staff with proper training and experience. Depressive symptoms were measured by the Centers for Epidemiologic Studies-Depression instrument with self/body image measured using a body satisfaction scale [37,38]. Radiographic disease severity Anteroposterior standing knee X-rays were obtained at baseline and 18 months to determine the effects of the interventions on radiographic disease. A foot map was drawn at the first X-ray to ensure identical positioning for comparing baseline and end-of-study measurements. Knee X-ray films were read by a single physician masked to assignment, treatment group, and timing of the X-ray (baseline or 18 months). Severity of OA was assessed using a classification scheme adapted from Altman et al. [39]. Both the medial and lateral compartments were graded for osteophytes, subchondral cysts, and joint space narrowing on a 0 to 3 Likert scale using an atlas. The scores for each feature were added to compute a summary severity score from 0 to 24 for the most affected knee. Gait and strength analysis One-half of the participants in the study were randomized to gait and strength testing. These measurements were conducted and supervised by a staff member with a master of science degree in biomechanics with specific training in gait and strength analyses. These measurements were overseen by the principal investigator for the study (S. Messier). Prior to testing, subjects’ freely chosen walking speeds were assessed using a Lafayette Model

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63501 photoelectric control system. Three-dimensional high-speed video analysis (60 Hz) was performed using a four-camera (60 Hz) Motion Analysis Corporation motion analysis system. A low-pass Butterworth digital filter with a cutoff frequency of 6 Hz smoothed the raw coordinate data and Orthotrak software calculated the relevant kinematic and temporal variables. Kinetic data were gathered in synchrony with the kinematic data using an AMTI force platform set to sample data at 1000 Hz. Knee joint forces were calculated using an inverse dynamics model developed by DeVita and Hortobagyi [40]. Knee concentric/eccentric extension muscular strength was assessed using a Kin-Com 125E isokinetic dynamometer. Prior to testing, a warm-up period was provided to habituate the subjects to the testing equipment. The order of testing was concentric/eccentric extension followed by concentric/eccentric flexion at a velocity of 30⬚ second⫺1. Gravity effect torque was calculated based on the subject’s leg weight at a 45⬚ angle. The activation force for each muscle group was set at 50% of maximal voluntary isometric contraction. Knee extensors were tested through a joint arc from 90⬚ to 30⬚ (0⬚ ⫽ full extension). The first and last 10⬚ were subsequently deleted to account for the acceleration and deceleration of the dynamometer at the ends of the range of motion, and also to account for possible inconsistent effort [41]. Hence, average force was calculated as the average force between joint angles of 40⬚ and 80⬚. Two maximal reproducible trials were averaged and the maximum number of trials for each test was six. Subsequently, knee concentric/eccentric flexion tests were conducted through the same range of motion used for the extension tests. Cost-effectiveness and cost-benefit A cost-effectiveness analysis was performed from a payer perspective (i.e., including those cost and outcome elements that would be realized by an insurer). The cost variables considered in this study included: (1) the economic value of the intervention, (2) the cost of any adverse events resulting from intervention activities, (3) the cost associated with additional referrals for medical care made by intervention staff, and (4) any cost savings from reduced utilization of health-care services. Process measures Body weight and height Body weight and height were measured at baseline, 6 months, and 18 months. Both were obtained in comfortable clothes, with shoes and outer garments removed. The scale was calibrated prior to baseline and at each follow-up testing assessment. Dietary intake A registered dietitian from the General Clinical Research Center at Wake Forest University Baptist Medical Center, who was not involved with the delivery of the intervention, obtained a 24-hour recall at baseline, 6 months, and 18 months on one-third of the cohort. Data management Dietary intake recalls were processed and summary nutrition measures were performed using the Nutrient Data System (NDS) developed by the Nutrition Coordinating Center at

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the University of Minnesota, Minneapolis (Nutrient Database, version 2.1). The NDS system is used because it is accurate and standardized and has a comprehensive food and nutrient database. NDS automatically prompts the interviewer to probe for complete food intake, food descriptions, variable recipe ingredients, and food preparation methods. Nutrient calculations were performed using the NDS algorithms. Strength and gait measures were electronically captured by the Kin-Com 125E isokinetic dynamometer and Motion Analysis Corporation motion analysis system equipment, respectively. These data files were converted to SAS datasets for processing and merging with other subjects research data. All other research measures were recorded on study forms and entered into a FoxPro database with built in data range checks. All files were converted to SAS data files for statistical analysis. Statistical considerations The primary objective of the trial was to test the effect of diet and exercise on selfreported physical function. The four groups comprised a two-by-two factorial design to allow the comparison of the independent and joint effects of diet and exercise interventions. An estimate of the mean and standard deviation of the WOMAC scale (32.2 ⫾ 13.8) was obtained from Bellamy et al. [33]. An estimate of the mean and standard deviation of the gait biomechanics (medial force) (49.2 ⫾ 13.2) was obtained by repeated measures analysis of variance using SAS PROC MIXED, a program for possibly missing repeated observations, based on data on over 400 participants from the FAST clinical trial [14]. The sample size was chosen to provide adequate power to detect a 20% difference in WOMAC score between the main effects groups. The main effects of weight reduction and physical activity interventions were felt to be additive or nearly additive. If the effect of one factor is additive by a factor p then the joint effect of weight reduction and lifestyle physical activity intervention would have a joint effect of 10% × (1 ⫹ p). Sample size calculations were made to allow for 75–100% additivity. The sample size calculations further assumed that the retention rate would be 85%. Our experience with FAST and TONE resulted in retention rates of 84% and 94%, respectively [14,30]. In addition, participants who dropped out after the first or second follow-up visit provided some information; therefore, these calculations were conservative. Based on these assumptions, the total evaluable sample size required to obtain 90% power to detect a 20% relative effect of each main effect in a two-way repeated measures analysis of variance was 196 or 254 if assumed 100% or 75% additivity of effects. We chose an effect size of 20% for a change in self-reported disability because we would consider that clinically meaningful and it is in the range of effect sizes noted in other studies [14,42,43]. A sample size of 254 evaluable subjects at 18-month follow-up was the goal of the study. In order to allow for 15% loss to follow-up, a total sample size of 300 to be randomized was chosen in order to have 90% power for the primary and main secondary outcome measures. The sample size of 300 would provide 90% power if the additivity was as low as 75%. Biomechanics data were obtained on one-half of the participants in the trial as this provided more than 80% power to detect a 20% difference in medial force. Nutrition data were obtained on one-third of participants in the trial as this provided more than 80% power to detect a 20% difference in nutrient intake.

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Analysis of variance and the chi-square test were used to test for differences in baseline characteristics by treatment groups. The ADAPT population was stratified by BMI into overweight (BMI ⫽ 28.0–29.9 kg·m⫺2), class I obesity (BMI ⫽ 30.0–34.9 kg·m⫺2), class II obesity (BMI ⫽ 35.0–39.9 kg·m⫺2), and class III obesity (BMI ⬎ 40.0 kg·m⫺2) [44]. Means of physical function and pain scales of the WOMAC and the physical performance tasks were compared among the four BMI categories by analysis of variance.

Results Study recruitment was fulfilled in July 1998 and final data collection for the study was completed in December 1999. The total number of persons prescreened via telephone during the 18-month recruitment period was 2209. Of these, 72% were ineligible (1596/2209) and 13% declined to participate (297/2209), leaving 316 people who were randomized to one of the four treatment groups. Data analyses for the primary outcomes of ADAPT are finalized with presentation of the results forthcoming. Baseline demographics and comorbid illnesses for participants randomized into the study are described below. The mean age of the randomized participants at baseline was 68.6 years, ranging from 60–89. Nearly three-fourths of all participants were women (72.8%). Seventy-five percent were classified as white/Caucasian. Another 22% were African-American and there was representation from Native American, Asian/Pacific Islander, and Hispanic populations. Approximately 44% had an annual household income between $10,000 and $34,999, with an additional 44% earning more than $35,000 per year. The majority of participants had some post-high school education, with 33% having at least a college degree. The most prevalent comorbid condition was hypertension with almost 50% of participants being affected. Additionally, more than 28% had some form of heart disease, including angina (11.5%), congestive heart failure (3.5%), history of heart attack (4.1%), or other heart disease (21.1%). Selected outcome variables at baseline for the entire randomized ADAPT cohort are presented in Table 3. Values are presented as means (standard deviation). Prior to the initiation of the interventions, BMI was 34.5 (5.4) kg·m⫺2 with a range from 28.0 to 64.7 kg·m⫺2. The summary score for the 17 self-reported physical function items in the WOMAC scale was 24.39 (11.72), with a score of 6.95 (3.52) for the pain items in the WOMAC scale. For the FAST Functional Performance Inventory, the mean rating for the 23 items was 2.00 (0.60) (not shown in Table 3). In descriptive terms, this value coincides with “Usually did (specific activity) with a little difficulty.” In addition to self-reported physical disability, physical performance of two separate tasks were used in ADAPT to assess physical function. The mean 6-minute walk distance for all participants at baseline was 423.1 (80.6) m with a distance ranging from 140.8 to 649.8 m. The second performance task, the timed stair climb, showed a range 3.3 to 53.4 seconds with a mean value of 10.3 (6.1) seconds. Participants were stratified by class of overweight and obesity based on their BMI. The BMI range for the overweight category was 28.0 to ⬍30.0 kg·m⫺2. Class I obesity included BMI from 30.0 to ⬍35.0 kg·m⫺2; class II obesity was from 35.0 to ⬍40.0 kg·m⫺2; and class

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Table 3. Baseline measures of physical function, pain, physical and mental health, 6-minute walk distance, and stair climb time across all participants and for classes of overweight and obesity Overall meana (SD) [range] BMI (kg·m⫺2)

34.5 (5.4) [28.0–64.7] WOMAC 24.39 (11.72) [1.0–68.0] functionb WOMAC 6.95 (3.52) [0.0–20.0] Painc 6 minute walk 423.1 (80.6) distance (m) [140.8–649.8] Stair climb 10.3 (6.1) time (secs) [3.3–53.4] a b c d

BMI 28.0 to ⬍30.0 (kg·m⫺2) (n ⫽ 67) 28.8 (0.8)

BMI 30.0 to ⬍35.0 (kg·m⫺2) (n ⫽ 124) 32.4 (1.5)

BMI 35.0 to ⬍40.0 (kg·m⫺2) (n ⫽ 75) 37.0 (1.2)

BMI ⭓40.0 (kg·m⫺2) (n ⫽ 48)

Overall p-value from ANOVA

44.1 (5.0)

23.80 (10.32)1,2 22.25 (12.79)1 26.36 (10.21)2 28.46 (11.44)3 0.0062 6.68 (2.94)1,2 427.6 (86.0) 10.9 (7.6)1,2

6.42 (3.74)1 428.0 (84.4) 9.2 (4.6)1,d

7.55 (3.26)2 419.8 (64.3) 10.3 (5.8)1,2

8.00 (3.67)3

0.0211

410.1 (81.6)

0.6396

12.0 (5.6)2

0.0238

Means not sharing a common superscript within each row differ at the p ⬍ 0.05 from one another. WOMAC function is the summary score of 17 items on the WOMAC questionnaire. WOMAC pain is the summary score of 5 items on the WOMAC questionnaire. p ⫽ 0.052 for comparison between stair climb time for BMI 30–35 and ⬍30 categories.

III obesity was ⭓40.0 kg·m⫺2. Mean values of WOMAC scores for function and pain, distance walked in 6 minutes, and stair climb time for each BMI category are presented in Table 3. The lowest WOMAC score for function (indicating higher function) was observed for class I obesity, which was significantly less than the score reported in the class II and class III obesity categories. Additionally, participants who were overweight had a significantly lower score than those with class III obesity. A similar pattern was observed for the WOMAC pain scale with less pain reported by those with class I obesity than with class II or III obesity. In the timed stair climb, however, there were differences between groups with the 30–35 BMI category having the fastest time (9.2 seconds) and the ⬎40 BMI category showing the slowest time (12.0 seconds). Statistical significance was not reached in other category comparisons, although there was a trend for class I obesity to have a faster stair climb time than the overweight category (p ⫽ 0.052).

Discussion ADAPT is the first randomized controlled trial to examine the effects of weight loss, with and without exercise, on physical functional decline and disability in older, overweight and obese adults with knee OA. Prior evidence on this population from FAST has shown that both aerobic exercise and weight training reduce the decline in physical function [14]. There has previously only been observational evidence to support the effectiveness of weight loss in reducing the decline in physical function in older adults with knee OA [10]. The final data collection occurred in December 1999, culminating a 4-year period of recruitment, intervention, and testing. Previous experience with this population in our community provided us with valuable knowledge for successful recruitment as we surpassed our

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initial recruitment goal of 300 participants. Overall, recruitment went very well as the various recruitment techniques provided a strategy for recruiting minorities in the study. We found that the 18-month duration of the study was a tremendous time commitment. Because of this, there were a few occasions when a participant was randomized but the start of the intervention was postponed until a later wave. These participants were much more likely to be noncompliant to their intervention. This is one of only a few studies that has attempted to achieve sustained weight loss in obese older adults with impaired physical function [18,30]. The weight-loss goal established was a 5% loss in weight from baseline. As reported, this level of weight loss is thought to be achievable in this population with the designed intervention, and a 5% weight loss has been shown to produce statistically significant alterations in knee pain in obese women. Modest weight loss of this level has also been shown to offer benefits for other metabolic comorbidities associated with obesity, including reductions in blood pressure and blood cholesterol and improvements in insulin sensitivity [45]. The recent publication of the Activity Counseling Trial showing the effectiveness of physical activity counseling in the primary care setting for improving cardiorespiratory fitness in women illustrates that implementation of a lifestyle behavior can be successful in improving health [46]. Likewise, the exercise intervention utilized in FAST provides evidence that increasing physical activity can reduce decline in physical function in participants with knee OA [14]. ADAPT builds on the intervention design and outcome from these studies by adding a second behavioral strategy with an emphasis on dietary restriction to induce weight loss. Furthermore, the ADAPT target population was older, overweight and obese adults with knee OA (BMI ⭓ 28.0 kg·m⫺2 as inclusion criteria). The exercise intervention was developed to encompass both cardiovascular fitness and strength. A unique feature of ADAPT is the combination of both of these exercise training modes into a single exercise regime that can be implemented in a facility-based setting or adapted for a home-based program. The development of an exercise intervention that allowed maximal flexibility and choices for the participants, yet still maintained a high degree of quality control for the study personnel, was also an important methodologic design advancement in ADAPT. The intent was to formally test a new intervention that allowed the participant to exercise in an environment best suited for their continued participation, whether this choice was in a facility, their home, or a combination of these two. In our earlier experience with FAST, the exercise intervention consisted of 3 months of facility-based activity followed by 15 months of mandatory home-based exercise. The overall exercise compliance in that study was nearly 70% in both aerobic and strength interventions. We anticipate that the flexibility afforded to participants in ADAPT will promote continued participation in the exercise intervention as measured by attendance at facility-based sessions and by exercise logs completed by participants exercising at home. Since time and access are the most commonly reported barriers to physical activity, we felt that the flexibility provided would reduce recidivism [47]. Comparison of the baseline data among the classes of overweight and obesity illustrate that higher classes of obesity are associated with lower levels of self-reported physical function and higher levels of pain compared to the lowest class of obesity (BMI 30.0 kg·m⫺2 to ⬍35.0). A reduction in self-reported physical function and physical performance tasks and

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an increase in pain have previously been shown to be associated with obesity [48]. Additionally, other studies have demonstrated that functional limitations assessed via self-report and objective evaluations are associated with high BMI values [48]. This is apparently independent of the presence of cardiovascular disease or other obesity-related disorders [49]. Furthermore, obese individuals have been shown to have a lower perception of their health [50]. These findings from the ADAPT cohort add to the previous literature and are unique in that the study focused on older, obese adults with knee OA. Furthermore, our results provide evidence that in the obese population, higher levels of obesity further exacerbate the impairments in physical function and pain as assessed by self-reported and objective measures. It is interesting to note that the lower physical function found in the higher BMI categories was not accompanied by differences in the 6-minute walk distance. However, the timed stair climb did show divergence among BMI levels in the same direction as the self-reported outcomes. For this population, the stair climb appears to be a more discriminating and challenging task than the 6-minute walk. This may be due to the source of disability in this population, namely knee OA. This is consistent with the reported greater difficulty in climbing stairs than walking on level ground in individuals with mild radiographic evidence of knee OA [51]. It is noteworthy that the participants in the overweight category did not report higher physical function or less pain than those in either class I or class II obesity. In fact, there was a strong trend for those with a BMI of less than 30.0 kg·m⫺2 to have a slower stairclimb time than participants with class II obesity (p ⫽ 0.052). It might be inferred that those in the overweight group would have the most progressive or advanced disease compared to class I or II obesity. In an attempt to explain these findings, we examined the age and gender distribution within the BMI groups, the hypothesis being that an increase in age and greater female distribution in the overweight group might influence the findings. The mean age for the four distributions ranged from 70.1 years for the overweight category to 66.4 years for class III obesity, with the mean age for class I and II obesity being 69.3 and 67.5 years, respectively. The percent of females in the BMI groups ranged from 81.3% for class III obesity to 68.6% for class I obesity. Overweight and class II obesity groups had 77.6% and 69.3% females, respectively. Since there are only slight differences in the age and gender distribution among the BMI groups, it is unlikely that these factors contributed to the reported observations. Although no mechanistic data have yet been analyzed, we speculate that the etiology of the disease may be different between overweight and obese individuals. The influence of the stress imposed on the knee joints and the levels of hormones that may contribute to the etiology and pathophysiology of knee OA would likely be less in the overweight group. Therefore, the cause of OA in the overweight population may arise from other factors. These may cause the overweight group to have more physical restrictions and disability than predicted based on their BMI. These findings, if replicated by others, may become valuable regarding the treatment of the disorder. It will be of interest to examine the response of the behavioral treatment in ADAPT among the different BMI categories. Knee OA is the leading cause of disability in older adults and obesity is a major risk factor for this joint disease. The results from ADAPT will provide new and valuable insights into the behavioral approaches clinicians should recommend for behavioral therapies that effectively reduce the incidence of disability associated with this prevalent disease.

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The strengths of this trial include the full factorial design, the duration of the intervention, and the collection of both self-reported and physical performance measurements. The study is limited in that there is little mechanistic data being collected. The lack of body composition does not allow us to ascertain whether the weight loss was from changes in body fat, lean body mass (i.e., muscle), or a combination of both.

Acknowledgments This project is being funded by the Claude D. Pepper Older Americans (Grant 5P60AG10484-00) and the General Clinical Research Center (Grant M01-RR07122). The investigators would also like to acknowledge the other investigators and personnel involved in the development and operation of the study.

References [1] Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998;41:778–799. [2] Centers for Disease Control and Prevention. Prevalence of disabilities and associated health conditions among adults—United States, 1999. Morbidity and Mortality Weekly Reports 2001;50:120–125. [3] Centers for Disease Control and Prevention. Prevalence of arthritis—United States, 1997. Morbidity and Mortality Weekly Reports 2001;50:334–336. [4] Davis MA, Ettinger WH, Neuhaus JM. The role of metabolic factors and blood pressure in the association of obesity with osteoarthritis of the knee. J Rheumatol 1988;15:1827–1832. [5] Felson DT, Naimark A, Anderson J, et al. The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum 1987;30:914–918. [6] Davis MA. Epidemiology of osteoarthritis. Clin Geriatr Med 1988;4:241–255. [7] Ettinger WH, Davis MA, Neuhaus JM, Mallon KP. Long-term physical functioning in persons with knee osteoarthritis from NHANES.I: Effects of comorbid medical conditions. J Clin Epidemiol 1994;47:809–815. [8] Guccione AA, Felson DT, Anderson JJ. Defining arthritis and measuring functional status in elders: methodological issues in the study of disease and physical disability. Am J Public Health 1990;80:945–949. [9] Verbrugge LM, Gates DM, Ike RW. Risk factors for disability among U.S. adults with arthritis. J Clin Epidemiol 1991;44:167–182. [10] Felson DT, Zhang Y, Anthony JM, Naimark A, Anderson JJ. Weight loss reduces the risk for symptomatic knee osteoarthritis in women. The Framingham Study. Ann Intern Med 1992;116:535–539. [11] Oliveria SA, Felson DT, Cirillo PA, Reed JI, Walker AM. Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee. Epidemiology 1999;10:161–166. [12] Sturmer T, Gunther KP, Brenner H. Obesity, overweight and patterns of osteoarthritis: the Ulm Osteoarthritis Study. J Clin Epidemiol 2000;53:307–313. [13] Gelber AC, Hochberg MC, Mead LA, et al. Body mass index in young men and the risk of subsequent knee and hip osteoarthritis. Am J Med 1999;107:542–548. [14] Ettinger WH Jr, Burns R, Messier SP, et al. A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. The Fitness Arthritis and Seniors Trial (FAST). JAMA 1997;277:25–31. [15] Radin EL, Burr DB, Caterson B, et al. Mechanical determinants of osteoarthrosis. Semin Arthritis Rheum 1991;21(Suppl 2):12–21. [16] Howell DS, Treadwell BV, Troiano RP. Etiopathogenesis of osteoarthritis. In: Moskowitz RM, Howell DM, Goldberg VM, Mankin HJ, editors. Osteoarthritis: diagnosis and management. Philadelphia: W.B. Saunders Company, 1992. p. 233–254.

G.D. Miller et al./Controlled Clinical Trials 24 (2003) 462–480

479

[17] Messier SP, Ettinger WH, Doyle TE. Obesity: effects of gait in an osteoarthritic population. Journal Applied Biomechanics 1996;12:161–172. [18] Toda Y, Toda T, Takemura S, et al. Change in body fat, but not body weight or metabolic correlates of obesity, is related to symptomatic relief of obese patients with knee osteoarthritis after a weight control program. J Rheumatol 1998;25:2181–2186. [19] Deyle GD, Henderson NE, Matekel RL, et al. Effectiveness of manual physical therapy and exercise in osteoarthritis of the knee. A randomized, controlled trial. Ann Intern Med 2000;132:173–181. [20] Peterson MG, Kovar-Toledano PA, Otis JC, et al. Effect of a walking program on gait characteristics in patients with osteoarthritis. Arthritis Care Res 1993;6:11–16. [21] Schilke JM, Johnson GO, Housh TJ, O’Dell JR. Effects of muscle-strength training on the functional status of patients with osteoarthritis of the knee joint. Nurs Res 1996;45:68–72. [22] van Baar ME, Dekker J, Oostendorp RA, et al. The effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a randomized clinical trial. J Rheumatol 1998;25:2432–2439. [23] Mangione KK, McCully K, Gloviak A, et al. The effects of high-intensity and low-intensity cycle ergometry in older adults with knee osteoarthritis. J Gerontol A Biol Sci Med Sci 1999;54:M184–M190. [24] O’Reilly SC, Muir KR, Doherty M. Effectiveness of home exercise on pain and disability from osteoarthritis of the knee: a randomised controlled trial. Ann Rheum Dis 1999;58:15–19. [25] Hochberg MC, Altman RD, Brandt KD, et al. Guidelines for the medical management of osteoarthritis. Part II. Osteoarthritis of the knee. American College of Rheumatology. Arthritis Rheum 1995;38:1541–1546. [26] Meichenbaum D, Turk DC. Facilitating treatment adherence: a practitioner’s guidebook. New York: Plenum Press, 1987. [27] Rejeski WJ, Brawley LR, Ettinger W, Morgan T, Thompson C. Compliance to exercise therapy in older participants with knee osteoarthritis: implications for treating disability. Med Sci Sports Exerc 1997;29:977–985. [28] Cartwright DC, Zander A. Group dynamics: research and theory. New York: Harper & Row, 1953. [29] Bandura A. Social foundations of thought and action: a social cognitive theory. Englewood Cliffs, NJ: Prentice Hall, 1986. [30] Whelton PK, Appel LJ, Espeland MA, et al. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE Collaborative Research Group. JAMA 1998;279:839–846. [31] Coons SJ, Rao S, Keininger DL, Hays RD. A comparative review of generic quality-of-life instruments. Pharmacoeconomics 2000;17:13–35. [32] Sherbourne CD, Stewart AL. The MOS social support survey. Soc Sci Med 1991;32:705–714. [33] Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15:1833–1840. [34] Rejeski WJ, Ettinger WH, Shumaker S, et al. The evaluation of pain in patients with knee osteoarthritis: the knee pain scale. J Rheumatol 1995;22:1124–1129. [35] Kantz ME, Harris WJ, Levitsky K, Ware JE, Davies AR. Methods for assessing condition-specific and generic functional status outcomes after total knee replacement. Med Care 1992;30(Suppl):MS240–MS252. [36] Folstein MF, Folstein SE, McHugh PR. “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198. [37] Myers JK, Weissman MM. Use of a self-report symptom scale to detect depression in a community sample. Am J Psychiatry 1980;137:1081–1084. [38] Reboussin BA, Rejeski WJ, Martin KA, et al. Correlates of satisfaction with body function and body appearance in middle- and older aged adults: The Activity Counseling Trial (ACT). Psychology and Health 2000;15:239–254. [39] Altman RD, Fries JF, Bloch DA, et al. Radiographic assessment of progression in osteoarthritis. Arthritis Rheum 1987;30:1214–1225. [40] DeVita P, Hortobagyi T. Functional knee brace alters predicted knee muscle and joint forces in persons with ACL reconstruction during walking. Journal of Applied Biomechanics 2001;17:297–311.

480

G.D. Miller et al./Controlled Clinical Trials 24 (2003) 462–480

[41] Kramer JF, Vaz MD, Hakansson D. Effect of activation force on knee extensor torques. Med Sci Sports Exerc 1991;23:231–237. [42] Ettinger WH Jr, Afable RF. Physical disability from knee osteoarthritis: the role of exercise as an intervention. Med Sci Sports Exerc 1994;26:1435–1440. [43] Kovar PA, Allegrante JP, MacKenzie CR, et al. Supervised fitness walking in patients with osteoarthritis of the knee. A randomized, controlled trial. Ann Intern Med 1992;116:529–534. [44] National Institute of Health NHLBI. Clinical guidelines on the identification, evaluation and treatment of overweight and obesity in adults—the evidence report. Obes Res 1998;6:51S–209S. [45] Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes Relat Metab Disord 1992;16: 397–415. [46] The writing group for the Activity Counseling Trial research group. Effects of physical activity counseling in primary care: the Activity Counseling Trial: a randomized controlled trial. JAMA 2001;286:677–687. [47] Sherwood NE, Jeffery RW. The behavioral determinants of exercise: implications for physical activity interventions. Annu Rev Nutr 2000;20:21–44. [48] Larsson UE, Mattsson E. Functional limitations linked to high body mass index, age and current pain in obese women. Int J Obes Relat Metab Disord 2001;25:893–899. [49] Stafford M, Hemingway H, Marmot M. Current obesity, steady weight change and weight fluctuation as predictors of physical functioning in middle aged office workers: the Whitehall II Study. Int J Obes Relat Metab Disord 1998;22:23–31. [50] Wolk A, Rossner S. Obesity and self-perceived health in Sweden. Int J Obes Relat Metab Disord 1996; 20:369–372. [51] Jordan J, Luta G, Renner J, et al. Knee pain and knee osteoarthritis severity in self-reported task specific disability: the Johnston County Osteoarthritis Project. J Rheumatol 1997;24:1344–1349.