Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts.

OBJECTIVES: To assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure. DESIGN: Multicentre prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN). SETTING: Secondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland. PARTICIPANTS: Patients with new diagnosis of RA, n=2701. Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3-6 months, at 12 months and annually thereafter. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA-specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis. RESULTS: Of 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any conventional synthetic disease-modifying antirheumatic drug treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and a non-significant trend for delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and longer time to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit. CONCLUSIONS: MTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary, evidence suggested that MTX may delay the onset of ILD.

Malignancy in scleroderma patients from south west England: a population-based cohort study.

The pathophysiological relationship between scleroderma and malignancy remains poorly understood. Although some previous studies have demonstrated an increased malignancy risk in patients with scleroderma, others have been inconclusive. We aimed to determine if patients with scleroderma had an increased risk of malignancy compared to an age- and sex-matched local South West England population, and if there were any important differences between scleroderma patients with and without malignancy. Methods of this study are as follows. Notes were obtained on all local scleroderma patients (n = 68) locally, and those diagnosed with malignancy verified by contacting each patient's general practitioner. Expected malignancy figures were obtained from age- and sex-stratified regional prevalence data provided by the South West Cancer Intelligence Service registry. Among the patients, 22.1% with scleroderma were identified with concurrent malignancy. Affected sites were of the breast (n = 5), haematological system (n = 5), skin (n = 4), and unknown primary (n = 1). Overall, malignancy risk was found to be increased in scleroderma (RR = 3.15, 95% CI 1.77-5.20, p = 0.01). In particular, this risk was the highest for haematological malignancies (RR = 18.5, 95% CI 6-43, p = 0.03), especially for non-Hodgkin's lymphoma (RR = 25.8, 95% CI 5-75, p = 0.10). The majority of patients (86.7%) developed malignancy after the onset of scleroderma (mean = 6.9 years). Age of >70 and patients with limited scleroderma were significant risk factors for a patient with scleroderma to have a concurrent malignancy; however, no increased risk was found in patients with any particular pattern of organ involvement, cytotoxic usage or serology. To conclude, in this small patient cohort, we have found that scleroderma is associated with an increased risk of malignancy. This risk is statistically significant in patients with limited scleroderma. Patients who are elderly and those with limited disease should be closely scrutinized at follow-up appointments.

Magnetic resonance imaging measurement of knee cartilage volume in a multicentre study.

OBJECTIVE: To investigate the variability between different high-field scanners in magnetic resonance imaging (MRI) measurement of knee cartilage volume in healthy female volunteers. METHODS: Five volunteers had both knees scanned using three different MRI scanners. Cartilage volume in each compartment was measured from the images by image segmentation. The data were analysed using analysis of variance models. RESULTS: The mean total cartilage volume of the 10 knees scanned at three different centres was 16.15, 16.40 and 15.63 ml for the Siemens, GE and Philips scanners respectively. Small systematic differences were seen in the total knee cartilage volume results. CONCLUSIONS: Although there were small systematic differences in knee cartilage volume, the three MRI scanners gave broadly similar results.

Mind-body therapies for the treatment of fibromyalgia. A systematic review.

OBJECTIVE: To assess the effectiveness of mind-body therapy (MBT) for fibromyalgia syndrome (FM) by systematically reviewing randomized/quasirandomized controlled trials using methods recommended by the Cochrane Collaboration. METHODS: Nine electronic databases, 69 conference proceedings, and several citation lists were searched for relevant trials in any language. Eligible trials were scored for methodological quality using a validated instrument. Information on major outcomes was extracted. Insufficient data reporting prevented statistical pooling, therefore a best-evidence synthesis was performed. RESULTS: Thirteen trials involving 802 subjects were included. Seven trials received a high methodological score. Compared to waiting list/treatment as usual, there is strong evidence that MBT is more effective for self-efficacy, limited evidence for quality of life, inconclusive evidence for all other outcomes. There is limited evidence that MBT is more effective than placebo (for pain and global improvement); inconclusive evidence that MBT is more effective than physiotherapy, psychotherapy, or education/attention control for all outcomes; strong evidence that moderate/high intensity exercise is more effective than MBT (for pain and function). There is moderate evidence that MBT plus exercise (MBT+E) is more effective than waiting list/treatment as usual (for self-efficacy and quality of life); limited evidence that MBT+E is more effective than education/attention control; inconclusive for other outcomes. There is inconclusive evidence for MBT+E vs other active treatments for all outcomes. Longterm within-groups results show greatest benefit for MBT+E. CONCLUSION: MBT is more effective for some clinical outcomes compared to waiting list/treatment as usual or placebo. Compared to active treatments, results are largely inconclusive, except for moderate/high intensity exercise, where results favor the latter. Further research needs to focus on the synergistic effects of MBT plus exercise and/or plus antidepressants.

Osteoarthritis pain and its treatment.

Pain is the most important symptom of osteoarthritis (OA) and the reason why individuals seek medical treatment. The anatomic cause is unclear and is likely to vary between individuals. Recent work confirms the heterogeneity of pain in OA with differences in severity, location, precipitating and relieving factors, and response to intra-articular anesthetic. Nonpharmacologic treatment of OA is important and evidence is now accumulating for interventions such as aerobic exercise, quadriceps exercises, footwear modification, education, and social support. Analgesia remains the first choice drug therapy: compounds more potent than acetaminophen are now available and effective. New cyclooxygenase-2 (COX-2) inhibitors may have a role in subjects for whom simple analgesia is inadequate. Glucosamine is a simple, safe product that appears to have a weak pain-relieving effect, and intra-articular hyaluronate injections may also have a limited role. Recent community studies confirm the benefit of joint replacement in OA, though a number of questions remain about the timing, indications, and alternatives to surgery.

Factors associated with functional impairment in symptomatic knee osteoarthritis.

OBJECTIVES: Knee osteoarthritis (OA) is a major cause of disability, particularly in the elderly. The factors determining disability remain unclear. The aim of this study was to assess the impact of clinical and psychosocial variables on function in knee OA and to develop models to account for observed variance in self-reported disability. METHODS: The subjects (n = 69) were hospital out-patients. Self-reported disability was measured by the Western Ontario and McMaster Universities (WOMAC) OA index. Pain was measured by the WOMAC and the McGill pain questionnaire. Depression, anxiety, helplessness, self-efficacy, fatigue and quality of life were measured by standard instruments. A detailed knee examination, including pain threshold by dolorimetry, was performed. Radiographs were scored for individual features. RESULTS: Pain severity, obesity and helplessness were the most important determinants of disability: a model including these variables accounted for 59.9% variance in WOMAC disability. Anxiety remained associated with disability in some models. Disability was unrelated to radiographic change. CONCLUSIONS: Function in symptomatic knee OA is determined more by pain and obesity than by structural change, at least as seen on plain X-ray. Our study provides further support for interventions targeting anxiety and helplessness in knee OA.

Sustained improvement produced by nonpharmacologic intervention in fibromyalgia: results of a pilot study.

OBJECTIVE: The aim of this pilot study was to examine the practicality of delivering a package of nonpharmacologic, behavioral-based treatment, previously found to be effective in chronic back pain, to patients with fibromyalgia (FM) and to assess the efficacy of the intervention using a range of outcome measures up to 4 months posttreatment. METHODS: Participants with FM (n = 28) formed a single group for 8 sessions at weekly intervals. Each session comprised an education/cognitive-behavioral component, formal relaxation/meditation training, and instruction in a Chinese movement therapy (Qi Gong). RESULTS: Twenty of 28 subjects completed at least 5 of the 8 sessions. Significant improvement was seen in the Fibromyalgia Impact Questionnaire and a range of other outcome measures including tender points and pain threshold. Improvement was sustained 4 months after the end of the intervention. CONCLUSION: A simple behavioral intervention using large groups can be administered to subjects with FM and appears to produce sustained benefit in a range of outcomes. Controlled trials are currently being planned.

The relationship of anxiety and depression with self-reported knee pain in the community: data from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To investigate the relationship between anxiety and depression and reporting of knee pain in the community. METHODS: Subjects (n = 374) were community volunteers aged 40 years and above who are participants in the Baltimore Longitudinal Study of Aging, a prospective multidisciplinary research study of normative aging. Knee pain was defined by the First National Health and Nutrition Examination Survey question "have you ever had pain in or around your knee on most days for at least one month?"; anxiety and depression were measured by the relevant subscales of the Arthritis Impact Measurement Scales questionnaire. All subjects had standing anteroposterior radiographs, read for Kellgren and Lawrence (K + L) grade. RESULTS: After adjustment for age, women reporting "ever" knee pain had significantly higher anxiety scores than those reporting "never" pain (3.06 +/- 0.26 versus 2.35 +/- 0.17; P = 0.025). Pain reporting was related neither to anxiety scores in men, nor to depression in either sex. Analysis stratified by radiographic severity, adjusted for age and gender, showed that differences in anxiety were confined to those reporting knee pain in the absence of radiographic change (i.e., K + L grade 0). CONCLUSIONS: In the community, women reporting knee pain in the absence of radiographic osteoarthritis have higher anxiety scores than those without pain. Depression was not significantly related to knee pain in this population. Psychosocial factors may explain some of the discrepancy between reported knee pain and structural change as seen on x-ray.

Intra-articular corticosteroid treatment in osteoarthritis.

Intra-articular corticosteroids remain widely used for symptomatic treatment of peripheral joint osteoarthritis (OA). Several studies in knee OA have indicated a significant benefit compared with placebo, although the effect appears to last for only 1 to 3 weeks. Two placebo-controlled studies have confirmed these findings. A further uncontrolled study has examined the effect of intra-articular corticosteroid at the hip. Attention is increasingly focused on a possible disease-modifying role for steroids in OA. Although a beneficial effect can be demonstrated in some animal models, caution should be exercised when extrapolating to human cartilage. Osteoarthritis is increasingly viewed as a phasic condition in which organ damage occurs intermittently. An ability to detect these phases of increased disease activity, perhaps with new imaging or biochemical techniques, could lead to a more rational approach to the use of intra-articular steroids in OA.

Determinants of pain severity in knee osteoarthritis: effect of demographic and psychosocial variables using 3 pain measures.

OBJECTIVES: Why some patients with knee osteoarthritis (OA) report greater pain severity than others is unclear. We examined the demographic variables, psychosocial variables, and physical findings that predict severity of pain in patients with symptomatic knee OA comparing 3 different pain scales. METHODS: Pain severity was measured in 68 outpatients with knee OA using the WOMAC OA Index, the McGill Pain Questionnaire (MPQ), and a 0-100 visual analog scale (VAS). Depression, anxiety, fatigue, helplessness, self-efficacy, and quality of life were measured using standard instruments. Pain threshold was measured by dolorimetry and a standard knee examination performed. Radiographs were viewed when available. RESULTS: Significant correlations (r = 0.39-0.61) were found between pain measures. In unadjusted analysis, BMI and helplessness correlated with all 3 scales; race, education, female sex, and osteophyte score also correlated with at least one instrument. Depression, anxiety, and fatigue correlated only with the MPQ. Age, duration, and quality of life were not related to pain severity. After adjusted analysis the following variables remained: education, helplessness, and osteophyte score (WOMAC); BMI and helplessness (MPQ); duration, education, helplessness, and osteophyte score (VAS). "Sitting pain" and "night pain" had different associations from pain on walking, standing, or using stairs. CONCLUSION: Different pain scales measure different facets of the pain experience in knee OA and cannot be used interchangeably. The WOMAC pain scale has advantages over other instruments. Helplessness, education, and BMI appear to be important, potentially treatable, factors in determining self-reported pain severity in knee OA: other associations vary with both the pain scale used and the situation in which pain occurs, supporting the hypothesis that pain in knee OA is heterogeneous.

Are psychosocial factors related to response to acupuncture among patients with knee osteoarthritis?

CONTEXT: Acupuncture has been found to be beneficial in the treatment of patients with knee osteoarthritis. However, response among such patients is highly variable. Identification of subjects with greater response would facilitate a more rational use of acupuncture. OBJECTIVE: To examine the relationship between demographic and psychosocial variables and response to acupuncture as defined by reduction in pain and disability at the end of an 8-week course of treatment. DESIGN: Retrospective study. SETTING: Outpatients attending rheumatologists or primary care physicians. PATIENTS: 37 patients with symptomatic knee osteoarthritis who had previously participated in a controlled trial using acupuncture were recalled for an interview approximately 1 year later. INTERVENTION: Structured interview, questionnaire completion, and an examination. MAIN OUTCOME MEASURES: Depression, anxiety, helplessness, self-efficacy, and fatigue were measured by standard instruments. Knee examination and assessment of pain threshold were measured by dolorimetry. RESULTS: Response at 8 weeks was significantly related to duration of symptoms. A statistically nonsignificant trend was found for older and more educated subjects to have a better response; anxiety and fatigue were found to be inversely related to response (also statistically nonsignificant). Subjects with localized medial pain had significantly better response in terms of pain and disability than did subjects with generalized knee pain. CONCLUSION: Other than a weak relationship with anxiety (at 8 weeks only), no evidence of a link between psychosocial variables and response to acupuncture was found. Prospective studies are needed to confirm these results.

A pilot study of cognitive behavioral therapy in fibromyalgia.

BACKGROUND: Fibromyalgia is a syndrome characterized by widespread musculoskeletal pain and multiple tender points as well as high levels of self-reported disability and poor quality of life. OBJECTIVES: In this pilot study, a mind-body approach (cognitive-behavioral therapy) was tested that has been successful in treating chronic back pain patients to determine whether it would improve function, decrease perceived pain, and improve mood state for fibromyalgia patients. PARTICIPANTS: 28 patients recruited from the greater Baltimore area. INTERVENTION: Eight weekly sessions, 2 1/2 hours each, with three components: an educational component focusing on the mind-body connection, a portion focusing on relaxation response mechanisms (primarily mindfulness meditation techniques), and a qigong movement therapy session. MAIN OUTCOME MEASURES: Data collection instruments were the Fibromyalgia Impact Questionnaire, the Health Assessment Questionnaire, the Beck Depression Inventory, the Coping Strategies Questionnaire, the helplessness subscale of the Arthritis Attitudes Index, the Medical Outcomes Study Short Form General Health Survey, and a double-anchored 100-mm visual analog scale to assess sleep. RESULTS: Twenty patients completed the study. Standard outcome measures showed significant reduction in pain, fatigue, and sleeplessness; and improved function, mood state, and general health following an 8-week intervention. CONCLUSION: A mind-body intervention including patient education, meditation techniques, and movement therapy appears to be an effective adjunctive therapy for patients with fibromyalgia.

Management of osteoarthritis in older adults.

Management of osteoarthritis (OA) is directed primarily towards relief of pain and functional limitation. This article discusses a range of nonpharmacologic modalities, including education, social support, weight reduction, and exercise. Drug treatment should begin with adequate doses of acetaminophen. Guidelines for appropriate use of NSAIDs also are suggested in this article. Intraarticular steroids help a proportion of patients, particularly those with OA of the knee or thumb base; the role of intraarticular therapies remains uncertain. Surgery (total joint replacement) remains an excellent treatment for patients in whom medical treatment has failed to provide adequate symptom relief. Future developments are likely to include earlier intervention using drugs with the potential to modify the course of the disease.

The relationship between psychosocial variables and pain reporting in osteoarthritis of the knee.

Psychosocial factors may explain some of the variation in pain reporting among individuals with knee OA. This has important potential implications for management; indeed, several studies (reviewed in ref. 56) have demonstrated that interventions may reduce knee pain without apparent halting or reversing of structural damage. Such interventions have included the simple provision of support by monthly telephone calls (57), self-management programs (58), and cognitive-behavioral approaches designed to teach patients ways of coping with their pain (59). These programs are even more effective if the spouse is involved (60). It should be noted that there may be a large placebo effect in these interventions, and the degree to which patients are responding simply to an interest being taken in them and their problems is unclear; at least one study has shown that formal cognitive-behavioral therapy is no better than didactic education at improving pain and function in knee OA (though both are beneficial) (61). Many studies examining the role of psychosocial factors have suffered from poor design; many, for example, fail to control for radiographic severity. Future studies should define how pain is identified (dichotomous, ever/never/current, severity), differentiate community and hospital subjects, and separate patients by type and location of OA. Studies should also control for other factors potentially associated with pain: obesity, comorbidity, muscle weakness, and aerobic fitness. Prospective studies would allow clarification of the cause and effect relationship between anxiety, depression, and pain, both in the community and in patients who have elected to seek medical help. In this way, we may increase our understanding of the complex interaction between mood, social factors, and pain reporting in knee OA and, thus, improve the effectiveness, already equivalent to many pharmacologic interventions, of treatments designed to address psychosocial factors.

Where does it hurt? Pain localization in osteoarthritis of the knee.

OBJECTIVE: To identify the most common sites of pain in symptomatic knee osteoarthritis (OA) and to investigate clinical, radiographic and psychosocial associations of pain occurring in different locations. DESIGN: Sixty-eight outpatients with knee OA were interviewed in detail about their knee pain. Location of pain was recorded on a standard drawing of the knee. Validated instruments were used to measure pain severity, function, depression, anxiety, quality of life, fatigue, helplessness, self efficacy. Pain threshold was measured by dolorimetry and a knee examination performed. Radiographs (anterioposterior and lateral) were viewed if available. RESULTS: Most (85.3%) patients reported either 'generalized' (N = 35, 51.5%) or 'medial' (N = 23, 33.8%) knee pain. There were no differences between groups in pain severity, demographic or psychosocial variables, pain threshold or radiographic location or severity. However, function was significantly worse in the 'generalized' group (WOMAC function score 48.9 +/- 20.8 vs 34.2 +/- 22.3; P = 0.01): this remained significant after adjustment for potential confounding factors. The difference in function was most marked for activities involving knee bending. Early morning stiffness was also greater in the generalized group. CONCLUSIONS: Knee pain is not the same in all individuals with knee OA, confirming the heterogeneity of the condition. Location of pain is usually either generalized or medial. Patients with these patterns do not differ in demographic, radiographic or psychosocial variables but important differences in functional ability can be detected, suggesting differences in the underlying causes of pain and disability between the two groups.

Quantitative magnetic resonance imaging of the knee: a method of measuring response to intra-articular treatments.

OBJECTIVES: To investigate the potential of quantitative magnetic resonance imaging (MRI) to differentiate between therapeutically induced changes in inflammation and synovial proliferation in rheumatoid arthritis (RA) of the knee. METHODS: MRI of the knee was performed on patients with RA before and one week after injection with corticosteroid (triamcinolone acetonide, TA group, n = 9) and before, four, and 12 weeks after injection with yttrium-90 plus TA (TA+Y group, n = 7). MRI scans were analysed by subjective visual grading by a trained observer and by computer aided quantitation for three features: synovial fluid volume, synovial pannus volume, and synovial enhancement after intravenous contrast agent. RESULTS: All TA subjects improved clinically at one week but the effects of TA+Y were more variable. TA significantly reduced synovial enhancement and effusion volume, whereas TA+Y at 12 weeks tended to increase synovial enhancement and decrease pannus volume. Quantitative MRI values agreed well with subjective assessment of scans. Comparison of calculated change on MRI scan before and immediately after aspiration with actual volume aspirated showed high correlation (r = 0.96). CONCLUSIONS: Quantitative MRI correlates with subjective visual assessment and, at least for synovial fluid, is accurate. MRI can differentiate actions of two therapeutic modalities on various pathological processes and is sensitive enough to detect change after one week. With the additional advantage of lack of observer bias, it will probably become a useful tool in the development and assessment of existing and novel treatments.