Ottawa panel evidence-based clinical practice guidelines for therapeutic exercises in the management of rheumatoid arthritis in adults.

Introduction

Rheumatoid arthritis (RA) is a systemic inflammatory disease that produces a progressive degeneration of the musculoskeletal system. (1) One of the most prevalent chronic conditions, RA is found in approximately 1% of the adult population in the United States. (2-6) In adults, RA is more common among women than men by a ratio of 5:1 (6) and is most prevalent among those aged 40 to 60 years. Rheumatoid arthritis is a highly disabling disease associated with high morbidity. Even with appropriate drug therapy, up to 7% of patients are disabled to some extent 5 years after disease onset and 50% are too disabled to work 10 years after onset. (7) Consequently, RA results in considerable direct costs, such as health care expenses, and indirect costs, such as loss of productivity due to morbidity and decreased life expectancy (1); these combined costs are estimated at 1% of the US gross national product. (8) Impairments, disabilities, and handicaps associated with RA can be devastating, leading to pain, activity restriction, and diminished quality of life, while placing a strain on the health care system and society. (1)

Substantial progress has been made in the medical management of RA over the last decade, but rehabilitation specialists still must provide efficient and effective interventions for their patients. The development of evidence-based clinical practice guidelines (EBCPGs) for rehabilitation of adults with RA will help patients and clinicians choose effective interventions, which is important because the efficacy of rehabilitation interventions in RA management has a direct bearing on the combined costs of the disease. (6) According to Woolf, EBCPGs are "the official statements or policies of major organizations and agencies on the proper indications for performing a procedure or treatment or the proper management for specific clinical problems." (9(p1812)) The appropriate use of such statements to direct practice has been proven beneficial to the rehabilitation process and patient health outcomes. (10)

The Ottawa Panel was convened to evaluate the evidence for the effectiveness of 10 physical rehabilitation interventions for RA. Physical rehabilitation is a combination of therapeutic exercises, manual therapies, modalities, application of adaptive equipment, education, and re-education for the management of activities of daily living (ADL). The interventions examined by the Ottawa Panel were as follows: (1) acupuncture; (2) assistive devices; (3) bed rest; (4) conservation of energy; (5) electrotherapy, including electrical stimulation, low-level laser therapy, transcutaneous electrical nerve stimulation, and therapeutic ultrasound; (6) manual therapy; (7) patient education; (8) splinting and orthotics; (9) therapeutic exercises, with an emphasis on the intensity of the exercise program; and (10) thermotherapy, including heat therapy, cryotherapy, and balneotherapy. This article discusses only the evidence related to therapeutic exercises--including specific strengthening exercises and whole-body exercises (eg, general fitness and aerobic conditioning)--and manual therapy.

The target users of these EBCPGs for therapeutic exercises and manual therapy are physical therapists, occupational therapists, physiatrists, orthopedic surgeons, rheumatologists, family physicians, acupuncturists, and patients. The aim of developing the guidelines discussed in this article was to promote the appropriate use of therapeutic exercises and manual therapy in the management of RA.

Methods

The development process of these EBCPGs was similar to that of the Philadelphia Panel, except that a different target population was used. (11) Briefly, the Ottawa Methods Group (OMG), a group of 9 methodologists with experience in developing EBCPGs, asked professional associations interested in the care of people with RA for suggestions of individuals with both clinical expertise in the management of the disease and familiarity with EBCPGs. From among the suggestions given, the OMG chose 9 experts to serve as panel members. These experts in RA were a rheumatologist, a physiatrist, a physician with experience in evidence-based medicine, a family physician, 3 physical therapists (including one who practiced acupuncture and one involved in clinical research), an occupational therapist, and a patient with RA. The Ottawa Panel consisted of these 9 experts and all members of the OMG.

One OMG member assembled a research and support staff with expertise in meta-analyses, rheumatology rehabilitation interventions, research methods, or the development and assessment of EBCPGs. The OMG then established a priori a set of inclusion criteria for the study designs, subject samples, interventions, and outcomes to allow the research staff to select the most relevant material as evidence of the effectiveness of therapeutic exercise and manual therapy. The OMG also reviewed the inclusion criteria to ensure that the approach to the study selection was reproducible and systematic. This a priori protocol guided separate systematic reviews of the literature for each intervention.

The research staff reviewed articles and created evidence tables for them (see "Clinical Practice Guidelines"), which the 9 clinical experts received in preparation for their meeting with the OMG. These tables were used as the basis for making the recommendations.

Target Population

Included were studies with samples of adult patients (>18 years of age) with a diagnosis of RA according to the 1987 American Rheumatism Association (ARA) criteria. (12) A patient was said to have RA if he or she satisfied at least 4 of the following 7 ARA criteria: (1) morning stiffness, (2) arthritis of 3 or more joints, (3) arthritis of the hand joints, (4) symmetric arthritis, (5) rheumatoid nodules, (6) serum rheumatoid factor, or (7) radiologic changes. (12) Studies with patients with RA affecting peripheral joints were eligible. Studies with patients with both chronic and acute RA were included in our analysis because patients with both types of RA were included in the different clinical trials studied, sometimes in the same trial. Where possible, however, the recommendations clearly indicate whether the intervention is appropriate for chronic or acute conditions. The recommendations also include classification of functional capacity in patients with RA described as: (I) complete functional capacity with ability to carry out all usual duties without handicaps, (II) functional capacity adequate to conduct normal activities despite the handicap of discomfort or limited mobility of one or more joints, (III) functional capacity adequate to perform only a few or none of the duties of usual occupation or of self-care, or (IV) largely or wholly incapacitated, with the patient bedridden or wheelchair-bound, permitting little or no self-care. (6) When the recommendations do not indicate disease severity or functional severity, it is because the trial on which the recommendation was based did not mention severity (Appendix 1).

Studies of patients with RA who had back or neck problems were excluded because of the numerous and varied associated signs and symptoms. Another reason for not considering spine disorders for this article is that Philadelphia Panel guidelines developed by the same methodologists were recently published for back and neck pain. (11) Studies of patients who had recently had surgery also were excluded. Further exclusion criteria included studies with patients who had one of the following conditions: (1) other rheumatologic or musculoskeletal problems, such as tendinitis, bursitis, or fractures; (2) major medical problems that could interfere with the rehabilitation process or incapacitate functional status; or (3) psychiatric conditions. Studies of subjects without known pathology or impairments also were excluded. The majority of studies included patients with RA at chronic stages (> 12 years' duration).

If the study sample contained individuals with mixed arthritic conditions, the study was excluded unless those conditions involved RA and osteoarthritis (OA), in which case the study was included only if the proportion of patients with RA was at least 75%. For further inclusion and exclusion criteria, see Table 1.

Literature Search

The library scientist developed a structured literature search based on the sensitive search strategy for randomized controlled trials (RCTs)--a strategy recommended by The Cochrane Collaboration (13)--and modifications proposed by Haynes et al (14) to that strategy. The Cochrane Collaboration method minimizes bias through a systematic approach to the literature search, study selection, and data extraction and synthesis. The search was organized around the condition and interventions rather than the outcomes because it was an a priori search. Thus, we had no control over the outcomes the authors decided to measure (see Appendix 2 for an example of the search strategy).

The library scientist expanded the search strategy to identify case-control, cohort, and nonrandomized studies and conducted the search in the electronic databases of MEDLINE, EMBASE, Current Contents, the Cumulative Index to Nursing and Allied Health (CINAHL), and the Cochrane Controlled Trials Register up to December 2002. She also searched the registries of the Cochrane Field of Rehabilitation and Related Therapies, the Cochrane Musculoskeletal Group, the Physiotherapy Evidence Database (PEDro), and the University of Ottawa EBCPGs Web site. Finally, she searched the reference lists of all of the included trials for relevant studies and contacted content experts for additional studies.

In the first round of study inclusion or exclusion, 2 independent reviewers, trained and experienced occupational therapist or physical therapist students, appraised the titles and abstracts of the literature search, using a checklist with the a priori--defined selection criteria (Tab. 1). More junior students were paired with fourth-year occupational therapist or physical therapist students who were experienced with the Philadelphia Panel (11) methodology. Each pair of reviewers was assigned to a specific intervention. Within each pair of reviewers, individuals independently read the title and abstract of each article and created an individual list of all of the articles of the database with a reason for including or excluding each article. If the reviewers were uncertain about a particular article after having read the abstract, they ordered the article and read it in full before making a determination. Before deciding whether to include or exclude the article, a comparison of their individual lists was performed. A senior reviewer who is a methodologist and a clinical expert in arthritis (LB) checked the 2 independent lists of articles and the reason for inclusion or exclusion to determine potential inconsistencies. Eleven percent of the abstracts reviewed needed the consultation of the senior reviewer. For the second round of inclusion and exclusion, the pairs of reviewers retrieved articles selected for inclusion from the first round and independently assessed the full articles for inclusion or exclusion in the study. Using predetermined extraction forms, the pairs of reviewers independently extracted data from included articles on the population characteristics, details of the interventions, trial design, allocation concealment, and outcomes. The pairs of reviewers assessed methodological quality using the Jadad scale, a 5-point scale with reported reliability, and validity that assigns 2 points each for randomization and double blinding and 1 point for description of withdrawals. (15,16) The reviewers resolved differences in data extraction and quality assessment through consensus with the senior reviewer. This consensus served to support the reliability of data obtained with the article selection process.

Study Inclusion/Exclusion Criteria

The inclusion/exclusion criteria were based on previous criteria used by the Philadelphia Panel. This list of criteria, which had been created for multiple diagnoses, including back and neck pain, was adapted and approved by the OMG for use with RA (Tab. 1).

All original comparative controlled studies that evaluated the specific intervention in a sample of patients with RA were included: RCTs, controlled clinical trials (CCTs), cohort studies, and case-control studies. (Controlled clinical trials are the same as RCTs except that, according to the Jadad scale, CCTs are either not randomized or poorly randomized.) Crossover studies were included, and, to avoid potential confounders, the data from only the first part of the study (before crossing) were analyzed. (Data from the first part are more specific than data from the second part because once the study patients change from the intervention group to the placebo group, the outcome could be due to either the intervention or the placebo. Thus, such results are not useful for measuring the special effect of each intervention.)

Uncontrolled cohort studies (studies with no comparison group) and case series were excluded, as were eligible studies with greater than 20% dropout rates or a sample size of less than 5 patients per group. Abstracts were excluded because none of the abstracts found had sufficient data for analysis and the full studies of the abstracts could not be obtained from the authors. Trials published in languages other than French and English were not analyzed because of the time and cost involved in translation. Head-to-head studies (that is, the comparison of 2 active interventions, such as therapeutic exercises versus transcutaneous electrical nerve stimulation) were generally excluded in these recommendations. Because we were interested in making a recommendation specifically about therapeutic exercise or manual therapy, we rejected head-to-head studies. At the meeting, the Ottawa Panel recommended that a direct comparison of the intervention with either placebo or control was more valid for measuring the specific effect of the intervention. We did include, however, studies with head-to-head comparisons of high- versus low-intensity exercise as highly relevant for rheumatology practice in rehabilitation, especially in the presence of an inflammatory disease such as RA, where the dosage and intensity of therapy could make a difference in pain tolerance and joint damage. For further exclusion criteria, see Table 1.

Rehabilitation Interventions Related to Therapeutic Exercises and Manual Therapy

Rehabilitation interventions related to therapeutic exercises were identified as specific functional strengthening exercises, whole-body functional strengthening exercises, and physical activity. Strengthening exercises were defined as isometric, concentric, eccentric, and isokinetic resistance exercises. Specific functional strengthening exercises were defined as strengthening exercises applied to muscles crossing one specific joint or within one specific body part, such as the hand, shoulder, or knee. Whole-body functional strengthening exercises were defined as general strengthening exercises applied to muscles crossing many joints or within large body parts involving several joints such as the lower extremity. Physical activity was defined as a combination of strengthening and aerobic exercises (ie, therapeutic exercise and activities to increase endurance). Manual therapy was defined as passive physiologic and accessory joint movements, muscle stretching, and soil tissue mobilization applied to a specific joint. Definitions provided in this article were written according to the description of therapeutic exercises program in the primary trials included in this review (Appendix 1).

Acceptable comparators were placebo, untreated, or use of educational pamphlets or written instructions for self-management. Concurrent therapies (such as electro-analgesia and medication) were accepted only if provided to both the experimental and control groups. Studies with designs where patients were their own controls, were excluded. No limitations based on methodological quality were imposed a priori; however, the quality of the comparative controlled studies was considered when grading the recommendations resulting from our analysis.

Outcomes

The primary endpoints for measurement of effectiveness were the validated and reliable outcome measures recommended by the conference on Outcome Measures for Rheumatoid Arthritis Clinical Trials (OMERACT) (17) and by the theoretical framework for rehabilitation application. (18) The outcomes were selected according to the Philadelphia Panel recommendations and were based on the new proposal of the Canadian Society for the International Classification of Impairments, Disabilities, and Handicaps, (19) which involved the concepts of organic systems and impairment, abilities and disabilities, and life habits and handicap situation. The a priori outcomes were classified according to these concepts:

(1) organic systems and impairment: number of inflamed joints, number of acute phase reactants (eg, erythrocyte sedimentation rate, which is "a test that measures the rate at which red blood cells settle through a column of liquid" (20)), radiological damage, and side effects;

(2) abilities and disabilities: pain reduction, muscle force, range of motion (ROM), postural stares, and duration of morning stiffness; and

(3) life habits and handicap situation: global physician assessment, global patient assessment, gait stares, walking speed, walking distance, cadence, stride length, functional stares, patient adherence, patient satisfaction, length of stay, discharge disposition, quality of life, and return to work.

Studies were included if any one of the aforementioned outcomes was measured. A positive recommendation was made only if a specific intervention was effective for an outcome as measured with a validated scale. (17,18) The Ottawa Panel determined if the measurement was valid, a decision that was based on the existing literature, the outcome measure from OMERACT, (17) and McDowell and Newell's research. (21) Psychological outcomes such as depression were excluded. For more details, see the list of inclusion/exclusion criteria (Tab. 1).

The inclusion or exclusion of the report was determined by panel consensus. However, as many articles as possible were included to increase the statistical power of the final results. Each result comprised pooled data from studies measuring the same intervention and the same outcome over a similar time period.

Statistical Analysis

Data were analyzed using Review Manager software. (22) Continuous data, "data with a potentially infinite number of possible values along a continuum," (23) were analyzed using the weighted mean differences (WMDs) between the intervention and control groups at the end of the study, where the weight is the inverse of the variance. A WMD is "a method of meta-analysis used to combine measures on continuous scales (such as weight), where the mean, standard deviation, and sample size in each group are known." (23) Dichotomous data, or data with only 2 classifications, (23) were analyzed using relative risks. According to Cochrane, the relative risk is "the ratio of risk in the intervention group to the risk in the control group. The risk (proportion, probability, or rate) is the ratio of people with an event in a group to the total in the group." (23)

Heterogeneity (ie, variability or difference between studies (23)) was tested using the chi-square statistic. We tested data heterogeneity among the results of different included studies to make sure that only homogeneous data were pooled together. When heterogeneity was not significant, fixed-effect models were used. A fixed-effect model is a statistical model that stipulates that the units under analysis (eg, participants in a recta-analysis study) are the ones of interest and thus constitute the entire population of units. (23) Fixed-effect models were used to generalize data across the included studies. Random-effects models include both within-study sampling error (variance) and between-studies variation in the assessment of the uncertainty (confidence interval) of a recta-analysis' results (23) and are more severe than fixed-effect models. Such random-effects models were used when heterogeneity was significant. All figures were created using Cochrane Collaboration methodology (22) (www.cochrane.org). The square in Figure 1 illustrates the WMD between the 2 groups when comparing them for a specific outcome of interest. The horizontal line represents the standard deviation of the WMD. If the standard deviation line touches the central vertical line of the graph, the confidence interval is 0 and the difference between the 2 groups is not statistically significant. For example, functional stares, pain relief, or ROM in flexion for the group receiving shoulder strengthening exercises are not statistically different from those of the control group.

[FIGURE 1 OMITTED]

Based on previous studies in the musculoskeletal domain (24) and on consensus, (11) clinical improvement for all interventions studied by the Ottawa Panel was defined as 15% improvement relative to a control. This figure can be justified because it was developed by the Philadelphia Panel, whose members are experts in musculoskeletal practice, and confirmed by another panel (the Ottawa Panel) whose members included specialists in rheumatology and an expert biostatistician.

To determine clinical improvement, the absolute benefit and relative difference in the change from baseline were calculated. Absolute benefit was calculated as the improvement in the treatment group less the improvement in the control group, maintaining the original units of measurement. Relative difference was calculated as the absolute benefit divided by the baseline mean (weighted for the intervention and control groups). For dichotomous data, the relative percentage of improvement was calculated as the difference in the percentage of improvement between the intervention and control groups. (11)

The recommendations were graded by their level (I for RCTs, II for nonrandomized studies) and strength (A, B, C+, C, or D) of evidence. Evidence from one or more RCTs of a statistically significant, clinically important benefit (>15%) was necessary for a grade A recommendation. A grade B recommendation was given to a statistically significant, clinically important benefit (> 15%) if the evidence was from observational studies or CCTs. Evidence of clinical importance (>15%) but not statistical significance earned a grade C+ recommendation. A grade C recommendation was given to those interventions where an appropriate outcome was measured in a study that met the inclusion criteria but no clinically important difference and no statistical significance were shown. Evidence from one or more RCTs of a statistically significant, benefit favoring the control group (<0%: favors controls) resulted in a grade D recommendation. Details on this grading system were published in the Philadelphia Panel methodology article. (11)

Scales demonstrated to be valid and responsive to change are required to support a positive recommendation (A or B). Outcomes not supported in the scientific literature by an existing validation study but providing useful information in studies--such as morning stiffness duration and palm-to-pulp measurement of finger joint ROM--are insufficient to warrant a grade A or B recommendation. (17,18,25,26)

Reviewing the Guidelines

The guidelines were sent to the external experts for review. To judge clinical usefulness, the 20 positive recommendations also were sent to 5 practitioners for feedback. Practitioners were selected from clinical settings in the Ottawa and Toronto regions and were a physical therapist, an occupational therapist, a physiatrist, a family physician, and a rheumatologist, all of whom were currently working with patients with RA. Practitioners were asked 4 questions for each guideline: whether the recommendation was clear, whether the practitioners agreed with the recommendation, whether they felt that the literature search on therapeutic exercises and intensity of rehabilitation was relevant and complete, and whether the results of the trials in the guidelines were interpreted according to the practitioners' understanding of the data. Results of this survey are shown in the "Results" section.

Results

Literature Search

The literature search identified 2,280 potential articles on therapeutic exercises for several rheumatic conditions. Ninety of these articles were initially considered potentially relevant based on the selection criteria checklist for RA only. Sixteen of these articles relating to therapeutic exercises met the selection criteria and were included. (27-43) One of the 16 studies had a follow-up study, so we have counted these 2 studies as one (Tab. 2, Appendix 1). The other 74 trials (44-117) were excluded from the final selection for various reasons (Tab. 3). For manual therapy, 862 articles were identified. Four of those articles were initially considered potentially relevant, but none were ultimately included (118-121) (Tab. 4).

Therapeutic Exercises

The clinical practice guidelines tier therapeutic exercises are shown in Appendix 3.

Summary of trials. Sixteen trials (n=661 patients) evaluated different types of therapeutic exercises for RA affecting joints of the upper and lower extremities. All trials compared these exercises with a control, but the trials examined different kinds of exercise: (1) shoulder functional strengthening (n=28), (35) (2) hand functional strengthening (n=41), (32) (3) knee functional strengthening (n=35), (36) (4) whole-body functional strengthening (n=312), (28-31,33,38-41,43) (5) whole-body, low-intensity functional strengthening (group) that directly compared exercises with a home instruction program (n=100), (42) (6) physical activity compared with bed rest (n=145), (27,31,37) (7) whole-body, low-intensity (individualized) exercises versus written instructions received by a control group for a home exercise program (n=100), (42) (8) whole-body, high-intensity (group) exercises versus written instruction for a home exercise program (n=100), (42) and (9) whole-body, low-intensity (group) versus whole-body, high-intensity (group) exercises (n=100). (42) Six included trials were RCTs, (30,36,37,41-43) and 11 trials were CCTs (27-29,31-35,38-40) (Appendix 1). We used the Jadad scale to decide whether a study was an RCT or a CCT. (11)

In all trials, 2 main types of therapeutic exercises were prescribed: (1) muscle-specific functional strengthening exercises that included isometric, concentric, eccentric, and isokinetic resistance exercises and (2) whole-body functional strengthening programs that included general fitness and aerobic conditioning. The programs' durations ranged from 1 week to 6 months, the treatment schedule varied from 1 to 14 times a week, and the length of each exercise session ranged from 30 minutes to 1 hour (Appendix 1). Therapeutic exercises varied also in their extent of supervision (ie, supervised versus not supervised, group versus individual) and in their level of intensity (ie, low versus high).

Efficacy. Appendix 1 includes information on the intensity, frequency, and total duration of the exercises, which varied from study to study.

For shoulder functional strengthening versus control (one CCT, n=28), (35) no statistically significant difference or clinically important benefit was observed at 2 months for relieving pain or improving ADL and ROM in patients with chronic RA, functional class I or II, and shoulder pain (Fig. 1). No other outcomes were reported.

Hand functional strengthening versus control (one CCT, n=41) (32) showed no clinically important benefit for patients with chronic RA, functional class II or III, in improving ROM of the proximal interphalangeal (PIP) joint (results not shown) and grip force at 12 weeks (Fig. 2). However, hand functional strengthening did show a statistically significant difference (WMD= -3.10[degrees], 95% conference interval [CI]=-5.93[degrees] to -0.27[degrees]) with no clinically important benefit for PIP joint extension at 12 weeks only (Fig. 2).

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A clinically important benefit (41% relative difference) was shown in knee functional strengthening versus control (one RCT, n=35) (36) for pain in patients who had seropositive or seronegative inflammatory RA and required long-term medication at 6 weeks (Tab. 5). No clinically important benefit was shown tar function; no statistically significant difference was observed in any outcome measured after 6 weeks (Fig. 3).

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For whole-body functional strengthening programs versus control (3 RCTs and 6 CCTs, n=312), (28-31,33,38-40,43) clinically important benefits were observed for swollen joints at 2 months (29% relative difference on the Lansbury's joint index), (39) number of sick leaves after 8 years (43%), (39) and quadriceps femoris muscle torque after 8 years (26%) (39) (Tabs. 6 and 7, Figs. 4a-c) in studies with patients who had RA of functional class I, II, or III. Quadriceps femoris muscle torque (WMD=5.20 N x m, 95% CI=1.29-9.11 N x m) and length of sick leave (relative risk=-0.44 day, 95% CI=0.24-0.81 day) after 8 years obtained statistically significant values (Figs. 4b-c). No clinically or statistically significant benefit was found for any of the other outcomes measured (Tab. 6, Figs. 4a-c).

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No clinically important benefit was calculated for global patient (patient's assessment of overall disease activity or impairment) at 3 and 6 months, function measured by the Health Assessment Questionnaire (HAQ) at 3 and 6 months, pain measured on a visual analog scale (VAS) at 3 and 6 months, or number of swollen joints at 3 and 6 months in patients with RA, chronic stage (Tab. 8, Fig. 5) for whole-body, low-intensity functional strengthening exercise programs in supervised groups versus instructions for a home-based program (one RCT, n=100). (42)

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For physical activity compared with bed rest (considered by the panel to be a control), one RCT (37) demonstrated a significant difference favoring physical activity (WMD=8.15, 95% CI=4.25-12.05) for improving grip force (17% relative difference) at 3 months in patients with chronic RA (Tab. 9, Fig. 6a). Results for pain relief, traction, ROM, and tender or swollen joints or time to walk 15.24 m (50 ft) favored the group receiving bed rest in the same RCT (37) and in 2 CCTs (27,34) featuring the same type of patients (n=145) (Tabs. 9 and 10, Figs. 6a-b).

[FIGURE 6 OMITTED]

For low-intensity, whole-body functional exercises (individualized) versus a control group whose participants received instruction in a home-based program (one RCT, n=100), (42) statistically significant differences and clinically important benefits were obtained for change in function at 12 weeks (function-statistically significant at 12 weeks) (30% relative difference; WMD=-0.19, 95% CI=-0.36 to -0.02 [12 weeks]; WMD=-0.08, 95% CI=-0.36 to 0.2 [24 weeks]). Clinically important benefits were obtained for pain relief at 12 weeks (40% relative difference) (Tab. 11, Figs. 7a-b). However, no clinically important effects were observed for change in tender joints, change in muscle force, change in swollen joints, or change in joint mobility at 3 and 6 months (Tab. 11, Figs. 7a-b). Patients had RA in a chronic stage.

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Whole-body, high-intensity exercises (group) versus control as described above (one RCT, n=100) (42) demonstrated no clinically important benefit for pain relief, muscle force, swollen/tender joints, joint mobility, or improvement in traction (HAQ) at 3 and 6 months in patients with chronic RA (Tab. 12, Figs. 8a-b).

[FIGURE 8 OMITTED]

In the same RCT (n=100), (42) low-intensity supervised exercises (group) were compared with high-intensity exercises (group) and showed statistically significant differences and clinically important benefits for pain relief at 24 weeks (21% relative difference; WMD= 1.30 cm on a 10-cm VAS, 95% CI=0.20-2.40 cm). Function only showed clinically important benefits at 12 weeks (HAQ: 21% relative difference; WMD=0, 95% CI=-0.21 to 0.21). No clinically important effects were shown for muscle force, swollen/tender.joints, or joint mobility at 3 and 6 months for patients with RA in a chronic stage (Tab. 13, Figs. 9a-b).

[FIGURE 9 OMITTED]

Strength of published evidence compared with other guidelines. Good evidence (level I, RCT) exists that therapeutic exercises, including functional strengthening and low- or high-intensity exercises, relieve pain and improve overall function in patients with RA. The strength of evidence has been graded by the Ontario Program for Optimal Therapeutics, (122) which reported good-quality evidence related to therapeutic exercises (see Appendixes 4 and 5 for previous clinical practice guidelines on therapeutic exercises for RA and for shoulder pain). (123-127)

Clinical recommendations compared with other guidelines. The Ottawa Panel concluded that good evidence exists (grade A for pain, function, and grip force; grade B for sick leave and lower-limb muscle force; grade C+ for swollen joints) that therapeutic exercises similar to those mentioned above, including functional strengthening and low- or high-intensity exercises, should be included as an intervention for patients with RA. Therapeutic exercises reduce pain while improving periarticular muscle force, aerobic capacity, and joint mobility (Appendix 4). This recommendation is in concordance with all other existing guidelines (122-125) and with 2 protocols). (128,129)

Practitioners' response to Ottawa Panel guidelines. All practitioners surveyed agreed with the recommendations for therapeutic exercises. Two practitioners found the recommendations clear, while one practitioner was confused as to which intervention was effective. The Ottawa Panel responded that interventions with grades A, B, and C+ are effective depending on the specific outcome, and the summaries of the guidelines (see "Clinical Practice Guidelines") were rewritten to clarify this issue. The decision aid available on the University of Ottawa Web site (see below for more details) contributes to the clarity of the clinical application of the individual guideline.

Manual Therapy

Evidence with acceptable research design, interventions, group comparisons, or outcomes could not be identified to guide the development of recommendations for manual therapy. To our knowledge, no EBCPGs exist on manual therapy for RA conditions.

Discussion

From this extensive systematic review, numerous EBCPGs (6 with grade A, B, and C+ recommendations) have been developed for therapeutic exercises for RA, including strengthening exercises and whole-body exercises, with an emphasis on intensity of the exercise program. One or more CCTs have shown that these interventions provide clinically important benefits. More evidence, however, is needed to determine the efficacy of therapeutic exercises and manual therapy in the management of RA (9 primary grade C recommendations for therapeutic exercises and one "insufficient data" for manual therapy). Although no harmful side effects were reported in the original studies, the results of our review seem to suggest some potentially negative effects of intervention. For example, physical activity as compared with bedrest may have negative effects on outcomes such as pain, function, ROM, number of tender or swollen joints, and time to walk 15.24 m (50 ft). The effects of high-intensity exercise on pain also raise concern.

However, as with all such reviews, this review has its limitations. The effectiveness of conservative management of patients with RA is a complex issue, (7) and rehabilitation specialists often use concomitant interventions in their daily practice. (130) For example, interventions such as cryotherapy, wax bath, and electrotherapy are used for pain relief or as treatment preparation before exercise intervention. The use of a single intervention does not reflect the complexity of the global approach adopted by rehabilitation specialists in real-life clinical situations.

Furthermore, the efficacy of therapeutic exercises for RA is thought to be influenced by a number of factors, (7) including biological, psychosocial, and environmental health indicators, (7,131) Therefore, a multidimensional clinical evaluation is recommended in arthritis management. (122,132) However, it was not possible to examine the effect of possible concurrent therapies such as medication intake and thermotherapy on the effectiveness of the interventions examined. (133)

The Ottawa Panel EBCPGs for the management of RA generally concur with previous and relatively recent EBCPGs for RA, (122-125) shown in Appendix 4, and with 2 protocols, (128,129) The Philadelphia Panel EBCPGs, on whose methodology those of the Ottawa Panel were based, were developed based on a systematic grading of the evidence determined by an expert panel. In both cases, the evidence was derived from new systematic reviews and meta-analyses conducted by the OMG using The Cochrane Collaboration methodology. The Ottawa Panel comprised several practitioners who verified the guidelines' applicability and ease of use for practicing clinicians. This additional procedure provides credibility for rehabilitation specialists who intend to use these EBCPGs in their daily practice.

The EBCPGs developed by the Ottawa Panel have some potential limitations due to methodological weaknesses. Although the included trials were selected based on well-established inclusion and exclusion criteria, selection was performed by occupational therapist and physical therapist students. Potential omission of studies due to reviewer inexperience could have led to selection bias. Consultation with a third reviewer (LB) and the use of the panel of senior clinical experts may have compensated in part for this potential methodological flaw. The EBCPGs also are limited by the inclusion and exclusion criteria for the included studies. For example, some reports of RCTs (31-33,36,37,40,41) did not specify if the study sample included individuals in acute or chronic stages of RA. Additionally, some studies lacked details about the specific characteristics of the exercise intervention such as intensity. This lack of specificity (18) could be problematic for future clinical implementation of the guidelines, especially for the whole-body functional strengthening recommendation.

The OMG, however, made sure that the development of the draft EBCPGs prepared for the expert members was in concordance with Appraisal of Guidelines Research and Evaluation (AGREE) criteria. (134) Using AGREE (www.agreecollaboration.org), 2 trained physical therapists assessed the Ottawa Panel EBCPGs for RA. This tool consists of 6 dimensions measured on a 4-point scale, where 1 represents "strongly agree" and 4 represents "strongly disagree." The dimensions are: (1) purpose, defined as overall objectives that described the potential impact of a guideline on society and populations of patients; (2) stakeholder involvement, defined as the extent to which the guideline represents the views of its targed users; (3) rigor of development, which deals with the process used to gather and synthesize the evidence and with the methods to formulate the recommendations and to update them; (4) clarity and presentation, which refers to the language and format of the guideline; (5) applicability, which relates to the likely organizational, behavioral, and cost implications of applying the guideline; and (6) editorial independence, which refers to the independence of the recommendations and acknowledgment of possible conflict of interest from the guideline development group. The EBCPGs obtained a very, high score for dimensions 1 (purpose), 2 (stakeholder involvement), 4 (clarity), and 6 (editorial independence), with lower scores for dimensions 3 (rigor of development) and 5 (applicability). On the University of Ottawa School of Rehabilitation Sciences Web page (http://www.health.uottawa.ca/EBCpg/english/main.htm) precise results are currently available, and decision aids with detailed clinical application will soon be available. The rigor of development was low because of poor reporting of side effects and risks, which were not reported in the primary trials and therefore not included in the EBCPGs. The applicability was low, particularly in identifying potential organizational barriers, cost implications, and methods of applying and monitoring the guidelines. After publication, the Ottawa Panel is planning to implement these guidelines in the Arthritis Rehabilitation and Education Program of The Arthritis Society of Ontario.

Therapeutic Exercises

The Ottawa Panel concluded that therapeutic exercises, including specific functional strengthening and whole-body functional strengthening, are a beneficial intervention for patients with RA. The benefit may vary, however, according to disease acuity and the time frame during which the outcomes are measured. Clinical benefits are recognized for pain relief, upper-limb (grip) and lower-limb force, and functional status. Other benefits include improved overall function and, of particular importance due to its socioeconomic impact, decreased number of sick leaves. In the presence of an inflammatory disease such as RA, a low-intensity exercise program favors the reduction of pain and an improved functional status as compared with a high-intensity program, which may exacerbate the inflammatory process and the risk of damage to the affected joints. This evidence was not reproduced in noninflammatory diseases such as OA. (135) Physiological changes in plasma opioid concentrations support the reduction of pain observed in patients with RA alter exercise). (136-138)

The recommendation for therapeutic exercises is in concordance with all existing guidelines (122-125) and 2 protocols. (128,129) To our knowledge, all systematic reviews (112) and all existing descriptive literature (16,99,133,139-142) support this recommendation. Some subtle variation exists, though, depending on the outcome studied.

Although the Ottawa Panel EBCPGs are based mainly on RCTs, further research investigating the efficacy of therapeutic exercises for patients with RA requires trials of higher methodological quality. Indeed, a large number of studies failed to meet the inclusion criteria. The overall methodological quality of the included studies underlying the EBCPGs was relatively weak (15) due to the difficulty in masking patients and evaluators for this kind of intervention. This methodolological weakness observed in the included RCTs may have caused an overestimation of effect. The impossibility of truly masking patients is a common problem in trials of rehabilitation interventions. (143) Additionally, although we found many RCTs on therapeutic exercises for RA, the authors did not always report the characteristics of the intervention, the characteristics of the sample, and the stage of the disease in a standardized way. Some outcomes studied in the primary trials may not be clinically plausible. For example, it is unclear how therapeutic exercise alone could lead to improvement in joint swelling. To improve methodological quality, future RCTs should use the Morin Theoretical Framework (18) and the CONSORT Model (144) to report not only the characteristics of clinical application, of the sample, and of the disease, but also of the dropouts, the method of randomization, and the use of validated measurements.

Investigators in future studies examining the benefits of therapeutic exercises in the management of patients with RA will need to be more explicit in specifying the characteristics of the implemented exercises and program, including aquatics programs (38,106,107); the intensity of the exercise; and the progression. In addition, to provide a more judicious evaluation of the benefits, patient-specific information concerning physical impairment, functional goals, and standardized outcome measures (17) must be provided. (140)

Manual Therapy

No studies of manual therapy with acceptable research designs were identified.

Implications for Practice

The Ottawa Panel found evidence to recommend and support the use of therapeutic exercises, especially knee functional strengthening, whole-body functional strengthening, general physical activity, and whole-body, low-intensity exercises, for the management of RA. Conversely, evidence is lacking at present as to whether the use of shoulder and hand strengthening exercises and whole-body, high-intensity exercises or manual therapy should be included or excluded in the daily practice of physical rehabilitation for RA management. It is important to note that the recommendations outlined here are limited by methodological considerations such as the quality of studies in the literature, including the generally poorly reported descriptions of therapeutic exercise programs, and the outcomes in those studies.

Appendix 1.
Description of Included Trials (a)

Author/         Sample
Year            Size        Population Details

Alexander       CCT         Inclusion criteria: patients
  et al,        Total: 75     with one of the
  (27) 1983                   following: (1) active
                              synovitis or (2) RA of
                              sufficient severity to
                              require bed rest
                            Gr1: 25F/11M
                            Gr2: 27F/12M

Ekblom et al,   CCT         Inclusion criteria: patients
  (28) 1975     Total: 34     with nonacute stage of
                Gr1: 23       RA and second or third
                Gr2: 11       degree of RA

Ekblom et al,   CCT         Inclusion criteria: patients
  (29) 1975     Total: 30     with nonacute stage of
                Gr1: 6        RA and second or third
                Gr2: 12       degree of RA
                Gr3: 5
                Gr4: 3
                Gr5: 4

Hakkinen and    RCT         Inclusion criteria: patients
  Hakkinen,     Total: 39     with recent-onset RA
  (30) 1994     Gr1: 22
                Gr2: 17

Harkcom et al,  CCT         Inclusion criteria: patients
  (31) 1985     Total: 17     with RA according to
                Gr1: 4        ARA criteria, functional
                Gr2: 3        class II RA, and no
                Gr3: 4        acute flares of joint
                Gr4: 6        symptoms at the time of
                              entry or during the study

Hoening et al,  CT          Inclusion criteria: patients
  (32) 1993     Total: 41     meeting ARA criteria,
                Gr1: 11       functional class II or III
                Gr2: 9
                Gr3: 10
                Gr4: 11

Kirsteins       CCT         Inclusion criteria: patients
  et al,        Study 1:42    with ARA functional
  (33) 1991     Study 2: 21   class II or III RA who
                              were selected from the
                              private practices of
                              3 rheumatologists

Lee et al,      CCT         Inclusion criteria: patients
  (34) 1974     Total: 30     with active disease,
                G1: 16        severe pain, swelling
                Gr2: 14       and tenderness in
                              multiple joints, and
                              augmentation of
                              erythrocyte
                              sedimentation rate
                            Gr1: 13F/3M
                            Gr2: 12F/2M

Monnerkorpi     CCT         Inclusion criteria: patients
  and           Total: 28     with RA and shoulder
  Bjelle, (35)  Gr1: 14       pain who met the
  1994          Gr2: 14       criteria of ARA
                              functional class I or II
                            Gr1: 0M/14F
                            Gr2: 0M/14F

McMeeken        RCT         Inclusion criteria: patients
  et al,        Total: 35     with positive
  (36) 1999     Gr1: 17       inflammatory RA
                Gr2: 18       according to the ARA
                              and with joint disease
                              requiring long-term
                              medication who took
                              >10 s to perform the
                              TUG
                            Gr1: 2M/15F
                            Gr2: 4M/14F

Mills et al,    RCT         Inclusion criteria: patients
  (37) 1971     Total: 40     with definite or classic
                G1: 18        RA, subcutaneous
                Gr2: 22       nodules, positive
                              rheumatoid factor,
                              soft tissue swelling,
                              fatigability, and
                              weight loss

Minor and       CCT         Inclusion criteria: patients
  Hewett,       Total: 32     with the intention to
  (38) 1995     Gr1: 15       exercise in a group
                Gr2: 17       setting and no pre-
                              existing medical
                              condition that would
                              preclude moderate
                              exercises
                            Gr1: 0M/15F
                            Gr2: 0M/17F

Nordemar        CCT         Inclusion criteria: patients
  et al,        Total: 46     with RA according to
  (39) 1981     Gr1: 23       the ARA criteria,
                Gr2: 23       moderate disease
                              activity, and functional
                              stage I, II, or III RA
                            Gr1: 4M/19F
                            Gr2: 4M/19F

Noreau          CCT         Inclusion criteria: patients
  et al,        Total: 29     with confirmed
  (40) 1995     Gr1: 19       diagnosis of RA of
                Gr2: 10       functional class I or II
                              and no acute joint
                              symptoms who were
                              free of unstable
                              cardiovascular disease
                              and able to perform a
                              graded exercise test on
                              a bicycle ergometer
                            Gr1: 7M/17F
                            Gr2: 2M/18F

Rintala et al,  RCT         Inclusion criteria: patients
  (41) 1996     Total: 34     with definite diagnosis
                Gr1: 18       of RA (functional class I
                Gr2: 16       or II) with disease
                              duration >6 mo who
                              had not had an
                              operation in the last
                              6 mo, had no other
                              serious disease, and
                              were medically stable
                            Gr1: 3M/15F
                            Gr2: 2M/14F

van den Ende    RCT         Inclusion criteria: patients
  et al, (42)   Total: 100    with RA (ACR criteria)
  1996          Gr1: 25       whose symptoms had
                Gr2: 25       been stabilized with
                Gr3: 25       medication for 3 mo,
                Gr4: 25       who were between 20
                              and 70 y of age, and
                              who were able to cycle
                              on a home trainer
                            Gr1: 12M/13F
                            Gr2: 9M/16F
                            Gr3: 9M/16F
                            Gr4: 7M/18F

Van Deusen      RCT         Inclusion criteria:
  and           Total: 39     ambulatory adult
  Harlowe,      Gr1: 22       patients with RA,
  (43) 1987     Gr2: 17       medical
                              recommendations for
                              home rest and exercise
                              use, and no prior ROM
                              dance experience
                            Ratio: Gr1 and Gr2
                            32M/7F

Author/
Year             Time Since Onset       Age (y)

Alexander        Gr1: [bar.X]=8 y,      Gr1: [bar.X]=53,
  et al,           range=0.25-37 y        range=20-75
  (27) 1983      Gr2: [bar.X]=6.5 y,    Gr2: [bar.X]=57,
                   range=0.25-20 y        range=32-75

Ekblom et al,    Gr1 and Gr2: [bar.X]=  Gr1 and Gr2:
  (28) 1975        N/A, range=            range=38-63
                   3-18 y

Ekblom et al,    Range=3-18 y           [bar.X]=56, SD=6.25
  (29) 1975

Hakkinen and     Gr1: [bar.X]=0.88 y,   Gr1: [bar.X]=41.6,
  Hakkinen,        SD=0.79 y              SD=9.9
  (30) 1994      Gr2: [bar.X]=1.54 y,   Gr2: [bar.X]=45.7,
                   SD=2 y                 SD=10.6

Harkcom et al,   Gr1: [bar.X]=12.2 y,   Gr1: [bar.X]=51.5,
  (30) 1985        SD=8.7 y               SD=3.1
                 Gr2: [bar.X]=10.6 y,   Gr2: [bar.X]=47.3,
                   SD=5.4 y               SD=14.5
                 Gr3: [bar.X]=5.6 y,    Gr3: [bar.X]=44,
                   SD=3.7 y               SD=18.3
                 Gr4: [bar.X]=8.8 y,    Gr4: [bar.X]=45.1,
                   SD=10.1 y              SD=19.3

Hoening et al,   [bar.X]=9.8 y, SD=N/A  [bar.X]=57, SD=N/A
  (32) 1993

Kirsteins        N/A                    Study 1: [bar.X]=N/A,
  et al,                                  range=37-70
  (33) 1991                             Study 2: [bar.X]=N/A,
                                          range=38-72

Lee et al,       Gr1: [bar.X]=4.4 y,    Gr1: [bar.X]=53.2,
  (34) 1974        SD=0.08 y              SD=8.40
                 Gr2: [bar.X]=9.5 y,    Gr2: [bar.X]=56.1,
                   SD=2.2 y               SD=8.61

Monnerkorpi      Gr1: [bar.X]=5.4 y,    Gr1: [bar.X]=54.7,
  and              SD=2 y                 SD=7
  Bjelle, (35)   Gr2: [bar.X]=5.2 y,    Gr2:[bar.X]=50.1,
  1994             SD=2 y                 SD=10.3

McMeeken         Gr1: N/A               Gr1: [bar.X]=51.4,
  et al,         Gr2: N/A                 SD=11.1
  (36) 1999                             Gr2: [bar.X]=49.7,
                                          SD=51.3

Mills et al,     Gr1 and Gr2:           Gr1: [bar.X]=53.1,
  (37) 1971        range=2-10 y           range=19-76
                                        Gr2: [bar.X]=53.6,
                                          range=21-78

Minor and        Gr1: [bar.X]=5.8 y,    Gr1: [bar.X]=46.0,
  Hewett,          SD=7.6 y               SD=13.1
  (38) 1995      Gr2: [bar.X]=10.4 y,   Gr2: [bar.X]=54.8,
                   SD=9.1 y               SD=8.4

Nordemar         Gr1: [bar.X]=16 y,     Gr1: [bar.X]=56,
  et al,           SD=7 y                 SD=9
  (39) 1981      Gr2: [bar.X]=14 y,     Gr2: [bar.X]=58,
                   SD=7 y                 SD=10

Noreau           Gr1: [bar.X]=8.1 y,    Gr1: [bar.X]=49.3,
  et al,           SD=8.2 y               SD=13
  (40) 1995      Gr2: [bar.X]=11.0 y,   Gr2: [bar.X]=49.4,
                   SD=5.1 y               SD=12

Rintala et al,   N/A                    N/A
  (41) 1996

van den Ende     Gr1: [bar.X]=11.5 y,   Gr1: [bar.X]=51.1,
  et al, (42)      SD=8.4y                SD=9.5
  1996           Gr2: [bar.X]=8.4 y,    Gr2: [bar.X]=47.7,
                   SD=5.8                 SD=13.6
                 Gr3: [bar.X]=8.6 y,    Gr3: [bar.X]=53.1,
                   SD=7.1 y               SD=12.1
                 Gr4: [bar.X]=11.2 y,   Gr4: [bar.X]=56.1 ,
                   SD=9.8                 SD=10.9

Van Deusen       [bar.X]=10.92 y,       [bar.X]=55.91,
  and              SD=2.17 y              SD=2.6
  Harlowe,
  (43) 1987

Author/
Year             Intervention

Alexander        Gr1: 1 wk of bed rest
  et al,         Gr2: planned activity for 1 wk
  (27) 1983        followed by bed rest for
                   1 wk

Ekblom et al,    Gr1: muscle force training,
  (28) 1975        joint mobility training, and
                   bicycle training
                 Gr2: no exercises (control
                   group)

Ekblom et al,    Gr1: physical training (muscle
  (29) 1975        force training, joint mobility
                   training, and bicycle
                   training) 4 times a week for
                   the last 6 mo
                 Gr2: physical training twice a
                   week
                 Gr3: stopped training or
                   trained infrequently
                 Gr4 (control): started to train
                   after the experimentation
                 Gr5 (control): did not train

Hakkinen and     Gr1: muscle force training
  Hakkinen,      Gr2: control group; patients
  (30) 1994        maintained their habitual
                   physical activities

Harkcom et al,   Gr1: training on ergometer
  (30) 1985        3 times a week for 12 wk,
                   15 min a session
                 Gr2: same as Gr1 but 25 min
                   a session
                 Gr3: same as Gr1 but 35 min
                   a session
                 Gr4: no exercises (control
                   group)

Hoening et al,   Gr1: ROM exercises
  (32) 1993      Gr2: resistance exercises
                 Gr3: resistance exercises and
                   ROM
                 Gr4: no exercises (control
                   group)

Kirsteins        Gr1: tai chi chuan exercises
  et al,         Gr2: continued their usual
  (33) 1991        activities but without tai
                   chi chuan exercises

Lee et al,       Gr1: bed rest, supervised
  (34) 1974        exercises (gentle, active
                   exercises performed on the
                   bed once daily) (control
                   group)
                 Gr2: free and unsupervised
                   physical activity

Monnerkorpi      Gr1: shoulder training
  and              instructions with exercises
  Bjelle, (35)   Gr2: no exercises (control
  1994             group)

McMeeken         Gr1: exercises on the
  et al,           KIN-COM (b) apparatus
  (36) 1999      Gr2: no exercises (control
                   group)

Mills et al,     Gr1: rest program (22 h of
  (37) 1971        bed rest a day for 4 wk
                   followed by 18 h of bed rest
                   a day for the next 6 wk)

Minor and        Gr1: low-impact aerobic
  Hewett,          exercises in water 3 times a
  (38) 1995        week for 12 wk
                 Gr2: no exercises (control
                   group)

Nordemar         Gr1: bicycle ergometer (at
  et al,           home and at the hospital,
  (39) 1981        plus strengthening exercises
                   for lower limbs)
                 Gr2: no exercises (control
                   group)

Noreau           Gr1: warm-up plus aerobic
  et al,           exercises
  (40) 1995      Gr2: no exercises (control
                   group)

Rintala et al,   Gr1: warm-up (12 min),
  (41) 1996        conditioning (35 min), cool-
                   down, and stretching
                 Gr2: no exercises (control
                   group)

van den Ende     Gr1: Intensive dynamic group
  et al, (42)      exercises with full weight-
  1996             bearing and stationary
                   bicycle at high intensity
                 Gr2: group ROM exercises
                   plus isometric group
                   exercises at low intensity
                 Gr3: individualized isometric
                   and ROM exercises at low
                   intensity
                 Gr4: control group, written
                   home individualized
                   instructions for isometric and
                   ROM exercises

Van Deusen       Gr1: daily ROM dance
  and              sequence, exercises, and
  Harlowe,         relaxation techniques
  (43) 1987      Gr2: control group, received a
                   brochure that explained the
                   ROM dance program, but
                   no instructions were given

Author/          Comparison             Concurrent
Year             Group                  Therapy

Alexander        Parallel group         None
  et al,           (Gr1 and
  (27) 1983        Gr2 were
                   compared
                   throughout
                   the study
                   period, no
                   crossover)

Ekblom et al,    Parallel group         None
  (28) 1975

Ekblom et al,    Parallel group         None
  (29) 1975

Hakkinen and     Parallel group         Antirheumatic
  Hakkinen,                               medication for all
  (30) 1994                               patients during study
                                          period
                                        Five patients received a
                                          small daily dose
                                          (5-7.5 mg) of
                                          glucocorticoids

Harkcom et al,   Parallel group         None
  (30) 1985

Hoening et al,   Parallel group         NSAIDs
  (32) 1993

Kirsteins        Crossover              Self-ROM exercises
  et al,           group
  (33) 1991

Lee et al,       Parallel group         100 mg indomethacin
  (34) 1974

Monnerkorpi      Crossover              None
  and              group
  Bjelle, (35)
  1994

McMeeken         Parallel group         None
  et al,
  (36) 1999

Mills et al,     Gr2: physical          N/M
  (37) 1971        therapy
                   program
                   (patients
                   were
                   permitted
                   activity as
                   desired and
                   encouraged
                   to ambulate)

Minor and        Parallel group         None
  Hewett,
  (38) 1995

Nordemar         Parallel group         Corticosteroid injections
  et al,                                  as needed
  (39) 1981

Noreau           Parallel group         Psychologist
  et al,
  (40) 1995

Rintala et al,   Parallel group         None
  (41) 1996

van den Ende     Parallel group         None
  et al, (42)
  1996

Van Deusen       Parallel group         Exercises recommended
  and                                     by a physical therapist
  Harlowe,                                (type of exercises
  (43) 1987                               N/A)

                 Session
Author/          Frequency              Follow-up    Quality
Year             and Duration           Duration     (R, B, W)

Alexander        Treatments daily       None         0, 0, 0
  et al,           for 1 wk
  (27) 1983

Ekblom et al,    Gr1: 4 times a         6 mo (see    0, 0, 0
  (28) 1975        week                   next
                 Gr2: twice a             study)
                   week
                 6 wk total

Ekblom et al,    Gr1: 4 times a         This was a   0, 0, 1
  (29) 1975        week for the           follow-up
                   last 6 mo              study
                 Gr2: Twice a             done 6
                   week                   mo after
                 Gr3 N/A                  the
                 Gr4 N/A                  previous
                 Gr5: N/A                 study
                 6 mo total

Hakkinen and     Twice a week for       None         1, 0, 1
  Hakkinen,        2 mo and 2-3
  (30) 1994        times a week
                   for the last
                   4 mo

Harkcom et al,   3 times a week         None         0, 0, 1
  (30) 1985        for 12 wk
                   (36 sessions)

Hoening et al,   Twice a day for        None         0, 0, 1
  (32) 1993        12 wk (24
                   sessions)

Kirsteins        11 wk                  None         0, 0, 1
  et al,         Gr1: once a
  (33) 1991        week for 10
                   wk
                 Gr2 and Gr4:
                   no exercises
                 Gr3: twice a
                   week for 10
                   wk (11-12
                   sessions)

Lee et al,       Treatments daily       None         0, 0, 1
  (34) 1974        for 4 weeks

Monnerkorpi      8 wk, 3 times          1 wk         0, 1, 1
  and              a week
  Bjelle, (35)
  1994

McMeeken         Every 3 d for 6        None         1, 1, 1
  et al,           wk (14
  (36) 1999        sessions)

Mills et al,     10 wk                  N/M          2, 0, 1
  (37) 1971

Minor and        3 times a week         9 mo         0, 0, 1
  Hewett,          for 12 wk (36
  (38) 1995        sessions)

Nordemar         1 h daily for 2        None         0, 0, 1
  et al,           wk (in group)
  (39) 1981        plus 30 min
                   daily (alone)

Noreau           12 wk, twice a         24           0, 0, 0
  et al,           week (24
  (40) 1995        sessions)

Rintala et al,   12 wk                  None         1, 0, 0
  (41) 1996

van den Ende     12 wk, 3-4             12 wk         1, 0, 0
  et al, (42)      times a week
  1996             (36-48
                   treatments)

Van Deusen       8 wk, 1 session        4 mo         1, 0, 1
  and              a day,
  Harlowe,         7 d a wk
  (43) 1987

(a) R=randomization: 2 points maximum (Jadad scale  (15,16));
B=blinding: 2 points maximum (Jadad scale (15,16)); W=withdrawals:
1 point maximum (Jadad scale (15,16); CCT=controlled clinical trial;
RA=rheumatoid arthritis; F=females; M=males; Gr1=group 1, Gr2=group
2, etc; N/A=not available; RCT=randomized controlled trial; ARA=
American Rheumatism Association; ROM=range of motion; N/M=not
mentioned. NSAIDs=nonsteroidal anti-inflammatory drugs; ACR=American
College of Rheumatology; TUG=Timed "Up & Go" Test.

(b) Chattecx Corp. 101 Memorial Dr, PO Box 4287, Chattanooga, TN 37405.

Appendix 2.
Literature Search Strategy (Part of a Global Search)

The literature search strategy used was as follows:

1 exp osteoarthritis/

2 osteoarthritis.tw.

3 osteoarthrosis.tw.

4 degenerative arthritis.tw.

5 exp arthritis, rheumatoid/

6 rheumatoid arthritis.tw.

7 rheumatism.tw.

8 arthritis, juvenile rheumatoid/

9 caplan's syndrome.tw.

10 felty's syndrome.tw.

11 rheumatoid.tw.

12 ankylosing spondylitis.tw.

13 arthrosis.tw.

14 sjogren$.tw.

15 or/1-14

16 heat/tu

17 (heat or hot or ice).tw.

18 cryotherapy.sh,tw.

19 (vapocoolant or phonophoresis).tw.

20 exp hyperthermia, induced/

21 (hypertherm$ or thermotherapy).tw.

22 (fluidotherapy or compression).tw.

23 15 and 22

24 clinical trial.pt.

25 randomized controlled trial.pt.

26 tu.fs.

27 dt.fs.

28 random$.tw.

29 placebo$.tw.

30 ((sing$ or doubl$ or tripl$) adj (masked or blind$)).tw

31 sham.tw.

32 or/24-31

33 23 and 32

Appendix 3. Clinical Practice Guidelines

Shoulder functional strengthening (strengthening involving movement useful in daily activities) versus control, level II (CCT, n 28) (35): grade C for ADL, pain, and ROM at 2 months (no benefit). Patients with chronic RA, functional class I or II, and shoulder pain.

Hand functional strengthening versus control, level II (CCT, n=4 1) (32): grade C for ROM and grip force at 3 months (no benefit). Patients with chronic RA, and functional class II or III.

Knee functional strengthening versus control, level I (RCT, n= 351) (36): grade A for pain at 6 weeks (clinically important benefit); grade C for function at 6 weeks (no benefit). Patients with seropositive or seronegative inflammatory RA requiring long-term medication.

Whole-body functional strengthening versus control, level II (CCT, n=312) (28-30,31,33,38-41,43): grade B for sick leave and lower-limb muscle force at 8 years (clinically important benefit); grade C+ for swollen joints at 2 months. Grade C for the following: pain at 2 months and 8 years; function at 3 and 6 months; ROM at 3, 6, and 12 months; number of inflamed joints at 2 months and 8 years; grip force at 2, 6, and 12 months; leg muscle force at 8 weeks; and walking capacity at 6 weeks and 6 months (no clinically important benefit). Patients with diagnosis of RA and functional class I, II, or III.

Whale-body, low-intensity functional strengthening exercises (group dynamic exercises) versus instructions far home, level I (RCT, n=100) (42): grade C for pain, function, swollen/tender joints, and global patient (patient's assessment of overall disease activity or improvement) (11) at 3 and 6 months (no benefit). Patients with RA (chronic stage).

Physical activity versus bed rest, level I (RCT, n= 145) (27,34,37): grade A for grip force at 3 months (clinically important benefit); grade C far pain, tender joints, function, ROM, swollen joints, and time to walk 15.24 m (50 ft) (no benefit demonstrated). Patients with RA (chronic stage).

Whole-body, low-intensity exercises (individualized) versus control (written instructions for home exercises), level I (RCT; n= 100) (42): grade A for change in function at 3 months (clinically important benefit); grade C+ for pain relief at 3 months (clinically but not statistically important benefit); grade C for changes in tender/ swollen joints, joint mobility, and muscle force at 3 and 6 months (no benefit). Patients with RA (chronic stage).

Whole-body, high-intensity exercises (group) versus control (written instructions far home exercises), level I (RCT, n= 100) (42): grade C for pain function, joint mobility, muscle force, and swollen/tender joints at 3 and 6 months (no benefit). Patients with RA (chronic stage).

Whole-body, low-intensity exercises (group) versus whole-body, high-intensity exercises (group), level I (RCT, n= 100) (42): grade A for pain at 6 months (clinically important benefit favoring low intensity); grade C+ for function at 3 months (clinically but not statistically important benefit); grade C far joint mobility, muscle force, and swollen/tender joints at 3 and 6 months (no benefit). Patients with RA (chronic stage).

Appendix 4.
Previous Clinical Practice Guidelines on Therapeutic
Exercises for Rheumatoid Arthritis (a)

               Quality of
               Scientific
Author         Evidence       Clinical Recommendations

ACR (123)      N/R            Exercise programs
                                recommended to maintain or
                                improve joint ROM and
                                periarticular muscle force
OPOT (122)     Good-quality   Dynamic exercise improves
                 evidence       aerobic capacity, muscle
                                force, and joint mobility
                                without adversely affecting
                                pain relief
APS (124)      Good-quality   Exercise (ROM; stretching and
                 evidence       strengthening: isometric,
                                dynamic, and resistance;
                                aerobic) and physical activity
                                are recommended for pain
                                relief
Yosuda (125)   N/R            Aquatic therapy is
                                recommended

(a) ACR=American College of Rheumetology, N/R=not reported,
ROM=range of motion, OPOT=Ontario Program for Optimal
Therapeutics, APS=American Pain Society.

Appendix 5.
Previous Clinical Practice Guidelines on Therapeutic
Exercises for Shoulder Pain (a)

                  Quality of             Clinical
Author            Scientific Evidence    Recommendations

The Philadelphia  Fair scientific        No evidence to include
  Panel (126)       evidence (level        or exclude
                    II) for therapeutic    therapeutic exercises
                    exercises for          alone for shoulder
                    nonspecific            pain
                    shoulder pain
BMJ (127)         N/R                    No evidence that
                                           therapeutic exercises
                                           combined with
                                           manual therapy are
                                           effective for shoulder
                                           pain

(a) BMJ=British Medical Journal, N/R=not reported.

Table 1.
A Priori Inclusion/Exclusion Criteria for Rheumatoid Arthritis
Project (a)

Inclusion                           Exclusion

Study Designs                       Study Designs
  * Randomized controlled trial       * Case series/case report
  * Controlled clinical trial         * Uncontrolled cohort studies
  * Cohort study                        (studies with no control group)
  * Case-control study                * Eligible studies with greater
  * Crossover studies                   than 20% drop-out rates or
  * Head-to-head comparison of          sample size of fewer than 5
    high-and low-intensity              patients per group
    exercise                          * Studies where only the abstract
                                        was available
                                      * Trials published in languages
                                        other than French or English
                                      * Data (graphic) without a mean
                                        and standard deviation
                                      * Head-
to-head studies

Population                          Population
  * Outpatients/inpatients            * RA presenting back or neck
  * RA of all human joints except       problems
    cervical, dorsal, and lumbar      * Recent surgery
    spine                             * Arthritis or rheumatic
  * Patients >18 y of age               conditions other than RA
  * Classical or definite RA          * Scoliosis
    according to the 1987 American    * Cancer (and other oncologic
    Rheumatism Association              conditions)
    criteria (12)                     * No known pathology or
  * Chronic and acute conditions        impairments
  * Mixed arthritic conditions if     * Pulmonary conditions
    involving RA and                  * Neurologic conditions
    osteoarthritis and if             * Pediatric conditions (no
    proportion of patients with         juvenile arthritis)
    RA was at least 75%               * Cardiac conditions
                                      * Dermatologic conditions
                                      * Psychiatric conditions
                                      * Multiple conditions
                                      * Major medical problems that
                                        could interfere with the
                                        rehabilitation process or
                                        incapacitate functional status

Intervention                        Intervention
  * Eligible control groups:          * Bilateral interventions
    placebo, untreated, sham, or        (if systemic effects)
    routine conventional therapy      * Multidisciplinary, functional
    such as educative pamphlets         restoration programs
  * Eligible interventions:           * Psychosociol (nonphysical)
    1. Chiropractic interventions       interventions
       (manipulation,                 * Surgery of any joint
       mobilization, manual
       therapy)
    2. Intensity of exercise
       program
    3. Therapeutic exercises
       including postsurgery and
       swimming pool exercises

Outcomes (b)                        Outcomes
  * Absenteeism, return to work       * Biochemical measures
  * Balance status                    * Postural assessment
  * Cadence                           * Physiological measures, such
  * Coordination status                 as electromyographic activity
  * Costs (economics)                   and H-reflex and
  * Discharge disposition               cardiopulmonary capacity
  * Disease activity (including         (maximal oxygen uptake)
    no. of inflamed joints)           * Psychosocial measures, such as
  * Duration of morning stiffness       depression, home and community
  * Edema                               activities, leisure, social
  * Flexibility                         roles, and sexual functions
  * Functional status, activities     * Serum markers
    of daily living (self-care
    activities)
  * Gait status
  * Girth, volume
  * Global patient assessment
  * Global physician assessment
  * Inflammation
  * Joint imaging
  * length of stay
  * Medication intake
    (if reported)
  * Muscle force and power
  * No. of acute phase reactants
    (eg, erythrocyte sedimentation
    rate)
  * No. of swollen or tender
    joints
  * Pain reduction
  * Patient adherence
  * Patient satisfaction
  * Postural Status
  * Quality of life
  * Radiological damage
  * ROM, flexibility, mobility
  * Side effects (if reported)
  * Stride length
  * Walking distance
  * Walking speed

(a) RA=rheumatoid arthritis, ROM=range of motion.

(b) Authors might have operationalized their concepts differently.
For example, range of motion can include joint mobility and proximal
interphalangeal joint extension.

Table 2.
Included Studies for Therapeutic Exercises (n=16) (a)

Study                     Study    Population
                          Design

Alexander et al (27)      CCT      Adult patients with one of the
                                    following: (1) active synovitis
                                    or (2) RA of sufficient
                                    severity to require bed rest.
                                    All patients had definite or
                                   classical RA.
Ekblom et al (28)         CCT      Chronic RA, class II or III, age
                                    38-63 y
Ekblom et al (29)         CCT      Chronic RA, class II or III, age
 (follow-up study to                38-63 y
 the previous study)
Hakkinen and              RCT      Recent onset of RA, adult
 Hakkinen (30)                      patients with mean age of 41.6
                                    y (Gr1) and 45.7 y (Gr2)
Harkcom et al (31)        CCT      RA class II, adult patients
Hoenig et al (32)         CCT      RA class II or III, adult
                                    outpatients, mean age 57
Kirsteins et al (33)      CCT      RA class II or III, age 37-72 y
Lee et al (34)            CCT      Active RA, severe pain, swelling
                                    and tenderness in multiple
                                    joints, adult patients
Mannerkorpi and           CCT      RA class I or II, adult patients
Bjelle (35)                         with mean age of 54.7 y (Gr1)
                                    and 50.1 y (Gr2)
McMeeken et al (36)       RCT      Sero+ or sero- inflammatory
                                    RA, adult patients with mean
                                    age of 51.4 y (Gr1) and
                                    49.7 y (Gr2)
Mills et al (37)          RCT      Definite or classical RA,
                                    age 19-78 y
Minor and                 CCT      RA, no pre-existing medical
Hewett (38)                         condition, adult patients with
                                    mean age of 46 y (Gr1) and
                                    54.8 y (Gr2)
Nordemar et al (39)       CCT      Classical or definite RA, stage
                                    I, II, or III, adult patients
                                    with mean age of 56 y (Gr1) and
                                    58 y (Gr2)
Noreau et al (40)         CCT      RA stage I or II, adult patients
                                    with mean age of 49.3 y (Gr1)
                                    and 49.4 y (Gr2)
Rintala et al (41)        RCT      RA class I or II, adult patients
van den Ende              RCT      Chronic RA, age 20-70 y
et al (42)
Van Deusen and            RCT      RA, adult patients with mean age
Harlowe (43)                        of 55.9 y

Study                     Outcomes

Alexander et al (27)      No. of patients improving in
                           pain, Ritchie Articular Index,
                           morning stiffness, compound
                           thermography index, and grip
                           force
Ekblom et al (28)         Walk test, up and down stairs
Ekblom et al (29)         Walk test, up and down stairs
 (follow-up study to
 the previous study)
Hakkinen and              Ritchie Articular Index, maximum
 Hakkinen (30)             isometric grip force, no. of
                           eroded or inflamed joints, HAQ,
                           pain (VAS), maximum isometric
                           force of trunk extensors and
                           flexors, disease activity score
Harkcom et al (31)        No. of inflamed joints, maximum
                           heart rate, aerobic work
                           capacity, grip force, ADL
                           functional status
Hoenig et al (32)         Grip force, proximal
                           interpholangeal joint extension
Kirsteins et al (33)      No. of swollen or inflamed
                           joints, grip force, HAQ, tender
                           joints (Ritchie Articular
                           Index)
Lee et al (34)            Pain, morning stiffness
                           severity, morning stiffness
                           duration, digital joint
                           circumference, grip force,
                           Ritchie Articular Index
Mannerkorpi and           Pain at rest, pain on motion,
Bjelle (35)                arm ADL index, flexion ROM
McMeeken et al (36)       Pain, HAQ
Mills et al (37)          Ring size, grip force, 15.24 m
                           (50 ft) walking time, ROM, no.
                           of swollen joints, no. of
                           tender joints
Minor and                 Aerobic work capacity, grip
Hewett (38)                force, shoulder flexion,
                           hands-work capacity evaluation,
                           legs-work capacity evaluation,
                           lift-work capacity evaluation
Nordemar et al (39)       Quadriceps femoris muscle
                           torque, rate of perceived
                           exertion, Lansbury's joint
                           index, no. who used sick leave
                           between 1970-1978, x-ray
                           index, walk test
Noreau et al (40)         No. of swollen joints, peak
                           extension torque of the
                           quadriceps femoris muscle
                           (force), maximum heart rate,
                           maximum aerobic power
Rintala et al (41)        Rate of perceived exertion,
                           maximal oxygen uptake, pain
                           (VAS), pain during the test
van den Ende              No. of swollen joints, 15.24 m
et al (42)                 (50 ft) walk test, disease
                           activity score, HAQ (function),
                           pain (VAS), Ritchie Articular
                           Index (tender joints), patient
                           global (patient's assessment of
                           overall disease activity or
                           improvement (11)), elbow flexion
                           and extension, palmar and
                           dorsal wrist flexion (joint
                           mobility), hip flexion (joint
                           mobility), ankle plantar
                           flexion (joint mobility),
                           muscle force
Van Deusen and            Shoulder flexion, shoulder
Harlowe (43)              external and internal rotation,
                           lower-extremity flexion, ankle
                           plantar flexion

(a) CCT = controlled clinical trial, RA = rheumatoid arthritis, RCT =
randomized controlled trial, Gr1 = group 1, Gr2 = group 2, HAQ =
Health Assessment Questionnaire, VAS = visual analog scale, ADL =
activities of daily living. ROM = range of motion.

Table 3.
Excluded Studies for Therapeutic Exercises (n=74) (a)

Study                          Reason for Exclusion

Ahern et al (44)               More OA than RA in the population
Andersson and Ekdahl (45)      Predictive study
Bonwell et al (46)             No standard deviation
Barroclough et al (47)         No control group
Baslund et al (48)             Physiological outcomes
Basmajian (49)                 Review
Beals et al (50)               People without known pathology or
                                limitations as a control group
Beaupre et al (51)             More OA than RA in the population
Bostrom et al (52)             Head-to-head study
Brighton et al (53)            Not the study period or the outcome
                                measurement period of interest
D'Lima et al (54)              More OA than RA in the population
Doltroy et al (55)             Systemic lupus erythematosus and RA in
                                the same population
Dellhag et al (56)             Head-to-head study
Ekblom (57)                    Review of different clinical trials
Ekblom et al (58)              Not a clinical trial, baseline
                                measurements only
Ekdahl and Broman (59)         Comparative study
Ekdahl et al (60)              Measurements given in terms of
                                differences
Hakkinen et al (61)            Head-to-head study
Hakkinen et al (62)            Head-to-head study
Hansen et al (63)              Not the study period or the outcome
                                measurement period of interest
Harris and Copp (64)           Patients were their own control
Hart et al (65)                Wrong reference
Haug and Wood (66)             Majority of patients had degenerative
                                joint disease
Helewa et al (67)              Treatment with medication
Hsieh et al (68)               Not a clinical trial
Karten et al (69)              No control group
Kelly (70)                     No statistical data
Komatireddy et al (71)         Not the study period or the outcome
                                measurement period of interest
Lee et al (72)                 Periarthritis
Lineker and Horn (73)          Review
Lineker et al (74)             No control group
London et al (75)              More OA than RA in the population
Lyngberg et al (76)            Not the study period or the outcome
                                measurement period of interest
Lyngberg et al (77)            Patients were their own control
Lyngberg et al (78)            Not the study period or the outcome
                                measurement period of interest
Machover and Sapecky (79)      No control group
Maloney et al (80)             More OA than RA in the population
McCubbin (81)                  Review
Minor (82)                     Not a clinical trial
Minor and Brown (83            More OA than RA in the population
Minor et a1 (84)               No control group
Minor et al (85)               More OA than RA in the population
Neuberger et al (86)           No control group
Nicholson et al (87)           Not found
Nitz and Luparia (88)          Not the study period or the outcome
                                measurement period of interest
Nordesjo et al (89)            People without known pathology or
                                limitations as a control group
Nordstrom et al (90)           Head-to-head study
Partridge and Duthie (91)      Not the intervention of interest, no
                                exercises involved
Perlman et al (92)             No control group
Petri et al (93)               Medication effects
Roll et al (94)                People without known pathology or
                                limitations as a control group
Raspe et al (95)               Head-to-head study
Romness and Rand (96)          More OA than RA in the population
Sanford-Smith et al (97)       Head-to-head study
Scholten et al (98)            Multidisciplinary
Semble et al (99)              Review
Simon and Blotman (100)        Not a clinical trial
Smith and Polley (101)         Review
Stenstrom (102)                Head-to-head study
Stenstrom et al (103)          Head-to-head study
Stenstrom et al (104)          Head-to-head study
Stenstrom et al (105)          Not the study period or the outcome
                                measurement period of interest
Suomi and Koceja (106)         More OA than RA in the population
Suomi and Lindauer (107)       More OA than RA in the population
Suwalska (108)                 Not a clinical trial
Tegelberg and Kopp (109)       Ankylosing spondylitis
Tegelberg and Kopp (110)       Ankylosing spondylitis
Templeton et al (111)          No control group
van den Ende et al (112)       Systematic review
van den Ende et al (113)       Head-to-head study
Van Deusen and Harlowe (114)   No numerical value available for the
                                outcome measure
Waggoner and LeLieuvre (115)   Inadequate outcome: adherence to
                                intervention; no information about
                                exercise program
Wessel (116)                   Lack of information; authors contacted
Westby et al 117)              Mixed interventions, with investigation
                                of the effects of medication, not a
                                proper control or comparison group

(a) OA = osteoarthritis, RA = rheumatoid arthritis.

Table 4.
Excluded Studies for Manual Therapy (n=4) (a)

Study                Reason for Exclusion

Deyle et al (118)    OA
Dhondt et al (119)   RCT for spinal condition with RA
Fox and Poss (120)   No statistical data available
Kouppi et al (121)   RCT for spinal condition with RA

OA = osteoarthritis, RA = rheumatoid arthritis,
RCT = randomized controlled trial.

Table 5.
Knee Functional Strengthening Versus Control (a)

Study         Intervention   Outcome           No. of       Baseline
              Group (b)                        Patients     Mean

McMeeken et   E: exercises   Pain measured     17           4.3
al (36)                      with 10-cm VAS
              C: no          Pain measured     18           4.1
              intervention   with 10-cm VAS

Study         End-of-Study   Absolute          Relative
              Mean           Benefit           Difference
                                               in Change
                                               From
                                               Baseline

McMeeken et   2.4            -1.7              -41%
al (36)
              3.9

(a) In the table, we have included only outcomes for which the
corresponding graphs do not provide adequate information. VAS = visual
analog scale (0-10, where 10 = greatest pain).

(b) E = experimental group, C = control group.

Table 6.
Whole-Body Functional Strengthening Versus Control (a)

Study            Group                      Outcome

Ekblom et        E: whole-body functional   Walk test (minutes) at
 al (29)          strengthening              6 wk
                 C: no intervention         Walk test (minutes) at
                                             6 wk
Van Deusen and   E: ROM dance               Lower-extremity flexion
 Harlowe (43)     sequence, exercises,       (degrees) at 9 mo
                  and relaxation
                  techniques
                 C: no intervention         Lower-extremity flexion
                                             (degrees] at 9 mo
Minor and        E: supervised class of     Shoulder flexion at 3 mo
 Hewitt (38)      aquatic, low-impact
                  aerobics or walking
                 C: no intervention         Shoulder flexion at 3 mo
Minor and        E: supervised class of     Shoulder flexion at 12 mo
 Hewitt (38)      aquatic, low-impact
                  aerobics or walking
                 C: no intervention         Shoulder flexion at 12 mo
Nordemar         E: training                Quadriceps femoris
et al (39)                                   muscle torque (newton-
                                             meters)
                 C: no intervention         Quadriceps femoris
                                             muscle torque (newton-
                                             meters)
Nordemar         E: training                Swollen joints: Lansbury's
et al (39)                                   joint index
                 C: no intervention         Swollen joints: Lansbury's
                                             joint index
Nordemar         E: training                Swollen joints: Lansbury's
et al (39)                                   joint index
                 C: no intervention         Swollen joints: Lansbury's
                                             joint index
Nordemar         E: training                Walk test (minutes)
et al (39)
                 C: no intervention         Walk test (minutes)

Study            Group                      No. of       Baseline
                                            Patients     Mean

Ekblom et        E: whole-body functional   23           9.36
 al (29)          strengthening
                 C: no intervention         11           9.17

Van Deusen and   E: ROM dance               17           Not available
 Harlowe (43)     sequence, exercises,
                  and relaxation
                  techniques
                 C: no intervention         16           Not available

Minor and        E: supervised class of     17           149
 Hewitt (38)      aquatic, low-impact
                  aerobics or walking
                 C: no intervention         19           140
Minor and        E: supervised class of     15           149
 Hewitt (38)      aquatic, low-impact
                  aerobics or walking
                 C: no intervention         17           140
Nordemar         E: training                23           14.50
et al (39)

                 C: no intervention         23           12.90

Nordemar         E: training                23           94
et al (39)
                 C: no intervention         23           85

Nordemar         E: training                23           6.20
et al (39)
                 C: no intervention         23           6.70

Nordemar         E: training                23           8.42
et al (39)
                 C: no intervention         23           816

Study            Group                      End-of-      Absolute
                                            Study        Benefit
                                            Mean

Ekblom et        E: whole-body functional   8.02         -1.14
 al (29)          strengthening
                 C: no intervention         8.97

Van Deusen and   E: ROM dance               487          34[degrees]
 Harlowe (43)     sequence, exercises,
                  and relaxation
                  techniques
                 C: no intervention         453

Minor and        E: supervised class of     151          -1
 Hewitt (38)      aquatic, low-impact
                  aerobics or walking
                 C: no intervention         143
Minor and        E: supervised class of     152          1
 Hewitt (38)      aquatic, low-impact
                  aerobics or walking
                 C: no intervention         142
Nordemar         E: training                16.7         3.6
et al (39)
                 C: no intervention         11.5

Nordemar         E: training                59           -26
et al (39)
                 C: no intervention         76

Nordemar         E: training                10.2         -2.9
et al (39)
                 C: no intervention         13.6

Nordemar         E: training                8.92         0.69
et al (39)
                 C: no intervention         7.97

Study            Group                      Relative
                                            Difference
                                            in Change
                                            From
                                            Baseline

Ekblom et        E: whole-body functional   -12%
 al (29)          strengthening
                 C: no intervention

Van Deusen and   E: ROM dance               Cannot
 Harlowe (43)     sequence, exercises,      calculate
                  and relaxation
                  techniques
                 C: no intervention

Minor and        E: supervised class of     -1%
 Hewitt (38)      aquatic, low-impact
                  aerobics or walking
                 C: no intervention
Minor and        E: supervised class of     1%
 Hewitt (38)      aquatic, low-impact
                  aerobics or walking
                 C: no intervention
Nordemar         E: training                26%
et al (39)
                 C: no intervention

Nordemar         E: training                -29%
et al (39)
                 C: no intervention

Nordemar         E: training                -45%
et al (39)
                 C: no intervention

Nordemar         E: training                8%
et al (39)
                 C: no intervention

(a) E = experimental group, C = control group.

Table 7.
Whole-Body Functional Strengthening Versus Control (a)

Author         Group            Outcome                 No. of Patients
                                                        Who Improved

Nordemar et    E: training      No. of patients who     8
al (39)                         used sick leave
               C: no training   No. of patients who     18
                                used sick leave

Author         Group            Total No.               Risk
                                of Patients             Occurrence

Nordemar et    E: training      23                      35%
al (39)
               C: no training   23                      78%

Author         Group            Risk
                                Difference

Nordemar et    E: training      43%
al (39)
               C: no training

(a) E = experimental group, C = control group.

Table 8.
Whole-Body Low-Intensity Functional Strengthening (Group: Dynamic
Exercises Versus Instructions for Home Exercises (a)

Study           Intervention Group     Outcome            No. of
                                                          Patients

van den Ende    E: dynamic whole-      Pain measured      25
et al (42)      body functional         with 10-cm VAS
                strengthening           at 24 wk
                C: written             Pain measured
                instructions for        with 10-cm VAS    25
                home exercises          at 24 wk

Study           Intervention Group     Baseline           End-of-
                                       Mean               Study
                                                          Mean

van den Ende    E: dynamic whole-      3.40               4.8
et al (42)      body functional
                strengthening
                C: written                                3.3
                instructions for       2.10
                home exercises

Study           Intervention Group     Absolute           Relative
                                       Benefit            Difference
                                                          in Change
                                                          From
                                                          Baseline

van den Ende    E: dynamic whole-      0.2                7%
et al (42)      body functional
                strengthening
                C: written
                instructions for
                home exercises

(a) E = experimental group, C = control group, VAS = visual analog
scale (0-10, where 10 = greatest pain).

Table 9.
Bed Rest Versus Physical Activity at 10 Weeks (a)

Study      Intervention          Outcome                No. of
           Group                                        Patients

Mills et   C: bed rest           No. of swollen joints  20
al (37)    E: physical activity  No. of swollen joints  22
Mills et   C: bed rest           No. of tender joints   20
al (37)    E: physical activity  No. of tender joints   22
Mills et   C: bed rest           Grip force             20
al (37)    E: physical activity  Grip force             22
Mills et   C: bed rest           15.24-m (50-ft)        20
al (37)                          walking time
           E: physical activity  15.24-m (50-ft)        22
                                 walking time

Study      Intervention          Baseline               End-of-Study
           Group                 Mean                   Mean

Mills et   C: bed rest           24.02                  25.40
al (37)    E: physical activity  19.41                  19.34
Mills et   C: bed rest           32.45                  27.15
al (37)    E: physical activity  38.50                  33.73
Mills et   C: bed rest           91.05                  103.70
al (37)    E: physical activity  82.90                  110.33
Mills et   C: bed rest           31.91                  20.03
al (37)    E: physical activity  27.83                  19.18

Study      Intervention          Absolute               Relative
           Group                 Benefit                Difference in
                                                        Change From
Mills et   C: bed rest                                  Baseline
al (37)    E: physical activity
           C: bed rest           1.45                   7% (favors
                                                        bed rest)
Mills et   E: physical activity
al (37)    C: bed rest           -0.53                  -1% (favors
                                                        bed rest)
Mills et   E: physical activity  -14.78                 -17% (favors
al (37)    C: bed rest                                  physical
                                                        activity)
Mills et   E: physical activity  -3.23                  -11% (favors
al (37)                                                 bed rest)

(a) E = experimental group, C = control group.

Table 10.
Bed Rest Versus Physical Activity (a)

Author      Group        Outcome              No. of      Total
                                              Patients    No. of
                                              Who         Patients
                                              Improved

Alexander   C: bed rest  No. of patients who  31          36
et al (27)               improved on the
                         Ritchie Articular
                         Index
            E: physical  No. of patients who  21          39
            activity     improved on the
                         Ritchie Articular
                         Index

                                              Risk        Risk
                                              Occurrence  Difference

Alexander   C: bed rest  No. of patients who  86%         32% (favors
et al (27)               improved on the                  bed rest)
                         Ritchie Articular
                         Index
            E: physical  No. of patients who  54%
            activity     improved on the
                         Ritchie Articular
                         Index

(a) E = experimental group, C = control group.

Table 11.
Low-Intensity Exercises (Individualized) Versus Control (a)

                                                               No. of
Study         Intervention Group   Outcome                     Patients

van den Ende  E: low-intensity     Pain measured with          25
  et a1 (42)    exercise             10-cm VAS at
                                     12 wk
              C: instructions      Pain measured with          25
                for home exercise    10-cm VAS at
                                     12 wk

van den Ende  E: low-intensity     Ritchie Articular           25
  et al (42)    exercise             Index at 12 wk
              C: instructions      Ritchie Articular           25
                for home exercise    Index at 12 wk

van den Ende  E: low-intensity     Muscle force:               25
  et a1 (42)    exercise             isokinetic
                                     extension 120[degrees]/s
                                     (in newton-
                                     meters) at 12 wk
              C: instructions      Muscle force:               25
                for home exercise    isokinetic
                                     extension 120[degrees]/s
                                     (in newton-
                                     meters) at 12 wk

van den Ende  E: low-intensity     HAQ (0-3 point              25
  et al (42)    exercise             scale) at 12 wk
              C: instructions      HAQ (0-3 point              25
                for home exercise    scale) at 12 wk

                                                End-of-
                                   Baseline     Study
Study         Intervention Group   Mean         Mean

van den Ende  E: low-intensity     2.4          2.4
  et a1 (42)    exercise

              C: instructions      2.1          3
                for home exercise

van den Ende  E: low-intensity     10.7         10.2
  et al (42)    exercise
              C: instructions      12.4         12.6
                for home exercise
van den Ende  E: low-intensity     86           82
  et a1 (42)    exercise
              C: instructions      78           75
                for home exercise
van den Ende  E: low-intensity     0.72         0.67
  et al (42)    exercise
              C: instructions      0.70         0.86
                for home exercise

                                               Relative
                                               Difference
                                               in Change
                                   Absolute    From
Study         Intervention Group   Benefit     Baseline

van den Ende  E: low-intensity     -0.9        -40%
  et a1 (42)    exercise
              C: instructions
                for home exercise

van den Ende  E: low-intensity     -0.7        -1%
  et al (42)    exercise
              C: instructions
                for home exercise

van den Ende  E: low-intensity     3           4%
  et a1 (42)    exercise
              C: instructions
                for home exercise

van den Ende  E: low-intensity     -0.21       30%
  et al (42)    exercise
              C: instructions
                for home exercise

(a) E=experimental group, C=control group, VAS=visual analog scale
(0-10, where 10=greatest pain). HAQ=Health Assessment Questionnaire.

Table 12.
High-Intensity Exercises Versus Control (a)

                                                               No. of
Study         Intervention Group   Outcome                     Patients

van den Ende  E: high-intensity    Pain measured with 10-cm    25
  et al (42)    exercise             VAS at 24 wk
              C: no intervention   Pain measured with 10-cm    25
                                     VAS at 24 wk

van den Ende  E: high-intensity    Joint mobility at 24 wk     25
  et al (42)    exercise
              C: no intervention   Joint mobility at 24 wk     25

van den Ende  E: high-intensity    Muscle force: isokinetic    25
  et al (42)    exercise             extension 120[degrees]/s
                                     (in newton-meters) at
                                     12 wk
              C: no intervention   Muscle force: isokinetic    25
                                     extension 120[degrees]/s
                                     (in newton-meters) at
                                     12 wk

                                              End-of-
                                   Baseline   Study
Study         Intervention Group   Mean       Mean

van den Ende  E: high-intensity     3.4        4.8
  et al (42)    exercise
              C: no intervention    2.1        3.3

van den Ende  E: high-intensity    10.9       10.8
  et al (42)    exercise
              C: no intervention    8.6        8.9

van den Ende  E: high-intensity    81         87
  et al (42)    exercise
              C: no intervention   78         75

                                              Relative
                                              Difference
                                              in Change
                                   Absolute   From
Study         Intervention Group   Benefit    Baseline

van den Ende  E: high-intensity     0.2        7%
  et al (42)    exercise
              C: no intervention

van den Ende  E: high-intensity    -0.4       -1
  et al (42)    exercise
              C: no intervention

van den Ende  E: high-intensity     9         11%
  et al (42)    exercise
              C: no intervention

(a) E=experimental group, C=control group, VAS=visual
analog scale (0-10, where 10=greatest pain).

Table 13.
Low-Intensity Exercises (Group) Versus
High-Intensity Exercises (Group) (a)

                                                              No. of
Study         Intervention Group          Outcome             Patients

van den Ende  C: high-intensity exercise  Pain measured with  25
  et al (42)                                10-cm VAS at
                                            12 wk
              E: low-intensity exercise   Pain measured with  25
                                            10-cm VAS at
                                            12 wk

van den Ende  C: high-intensity exercise  Pain measured with  25
  et al (42)                                10-cm VAS at
                                            24 wk
              E: low-intensity exercise   Pain measured with  25
                                            10-cm VAS at
                                            24 wk

van den Ende  C: high-intensity exercise  Joint mobility at   25
  et al (42)                                24 wk
              E: low-intensity exercise   Joint mobility at   25
                                            24 wk

van den Ende  C: high-intensity exercise  HAQ (0-3 point      25
  et al (42)                                scale) at 12 wk
              E: low intensity exercise   HAQ (0-3 point      25
                                            scale) at 12 wk

                                                    End-of-
                                          Baseline  Study
Study         Intervention Group          Mean      Mean

van den Ende  C: high-intensity exercise  3.4       3.6
  et al (42)
              E: low-intensity exercise   2.4       2.4

van den Ende  C: high-intensity exercise  3.4       4.8
  et al (42)
              E: low-intensity exercise   2.4       2.3

van den Ende  C: high-intensity exercise  10.9      10.8
  et al (42)
              E: low-intensity exercise   8.9       9.5

van den Ende  C: high-intensity exercise  0.83      0.88
  et al (42)
              E: low intensity exercise   0.72      0.61

                                                    Relative
                                                    Difference
                                                    in Change
                                          Absolute  From
Study         Intervention Group          Benefit   Baseline

van den Ende  C: high-intensity exercise  0.2        7%
  et al (42)
              E: low-intensity exercise

van den Ende  C: high-intensity exercise  1.5       21% (favors low
  et al (42)                                          intensity
                                                      exercise)
              E: low-intensity exercise

van den Ende  C: high-intensity exercise  -0.7      -7%
  et al (42)
              E: low-intensity exercise

van den Ende  C: high-intensity exercise  0.16      21% (favors
  et al (42)                                          low-intensity
                                                      exercise)
              E: low intensity exercise

(a) E=experimental group, C=control group, VAS=visual analog scale
(0-10, where 10=greatest pain). HAQ=Health Assessment Questionnaire.

Ottawa Panel Members:

Ottawa Methods Group:

Lucie Brosseau, PhD, Physiotherapy Program, School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada

George A Wells, PhD, Department of Epidemiology and Community Medicine, University of Ottawa

Peter Tugwell, MD, MSc, Centre for Global Health, Institute of Population Health, Ottawa, Ontario, Canada

Mary Egan, PhD, Occupational Therapy Program, School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa

Claire-Jehanne Dubouloz, PhD, Occupational Therapy Program, School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa

Lynn Casimiro, MA, Physiotherapy Program, School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa

Vivian A Robinson, MSc, Centre for Global Health, Institute of Population Health

Lucie Pelland, PhD, Physiotherapy Program, School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa

Jessie McGowan, MLIS, Director, Medical Library, Centre for Global Health, Institute of Population Health

External Experts:

Mary, Bell, MD (Rheumatologist), Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada

Hillel M Finestone, MD (Physiatrist), Sisters of Charity of Ottawa Health Service, Ottawa, Ontario, Canada

France Legare, MD (Evidence-Based Practice in Family Medicine), University of Laval, Quebec City, Quebec, Canada

Catherine Caron, MD (Family Physician), Sisters of Charity of Ottawa Health Service

Sydney Lineker, PT, MSc, The Arthritis Society, Ontario Division, Research Co-ordinator, Toronto, Ontario, Canada

Angela Haines-Wangda, PT, MSc, Ottawa Hospital, General Campus, Ottawa, Ontario, Canada

Marion Russell-Doreleyers, PT who practices acupuncture, MSc, Canadian Physiotherapy Association and Ottawa Arthritis Rehabilitation and Education Program, Ottawa, Ontario, Canada

Martha Hall, OT, MPA, Canadian Association of Occupational Therapists and Ottawa Arthritis Rehabilitation and Education Program

Paddy Cedar, patient with rheumatoid arthritis (named with her written permission)

Assistant Manuscript Writer:

Marnie Lamb, MA, School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa

Address all correspondence and requests for reprints to: Lucie Brosseau, PhD, Physiotherapy Program, School of Rehabilitation Sciences, Faculty of Health Sciences, 451 Smyth Rd, University of Ottawa, Ottawa, Ontario, Canada KIH 8M5 ([e-mail]).

This study was financially supported by The Arthritis Society (Canada); the Ontario Ministry of Health and Long-Term Care (Canada); the Career Scientist Salary Support Program, University of Ottawa for Dr Brosseau; the University Research Chair Program tot Dr Brosseau; and the Ministry of Human Resources, Summer Students Program (Canada).

Acknowledgments: The Ottawa Panel is indebted to Ms Catherine Lamothe, Ms Shannon Rees, Ms Judith Robitaille, Ms Lucie Lavigne, Mr Shaun Cleaver, Mr Guillaume Leonard, Ms Marie-Andree Ouimet, Mr Martin Campbell, Ms Isabelle Blais, Ms Simon Barsoum, and Ms Karin Phillips for their technical support and help in data extraction.

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