Exploratory secondary analyses of a cognitive-behavioral intervention for knee osteoarthritis demonstrate reduction in biomarkers of adipocyte inflammation.

OBJECTIVE: To investigate the effects of pain coping skills training (PCST) and a lifestyle behavioral weight management (BWM) program on inflammatory markers and biomarker associations with pain and function in the OA LIFE study. METHOD: Serum samples were available from a subset (N = 169) of the overweight or obese knee OA participants in the OA LIFE study that evaluated: PCST, BWM, combined PCST + BWM, or standard care (SC). Inflammatory markers (hsCRP, IL-1ra, IL-1ß, IL-6, IL-8, TNF-α, TNFRI, TNFRII, and hyaluronic acid (HA)), and adipokines (leptin and adiponectin) were measured before and after the 24-week treatment period. Biomarkers were assessed for effects of treatment and for associations with change in weight, pain and disability (unadjusted and adjusted for age, race, sex, baseline body mass index (BMI), and baseline biomarker concentration). RESULTS: PCST + BWM was associated with significant reductions in hsCRP (P = 0.0014), IL-6 (P = 0.0075), and leptin (P = 0.0001). After adjustment, there was a significant effect of PCST + BWM on changes in leptin (b = -0.19, P = 0.01) and IL-6 (b = -0.25, P = 0.02) relative to SC. Reductions in leptin and IL-6 were significantly correlated with reductions in weight, BMI and Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain; reductions in IL-6 were correlated with improvements in WOMAC and Arthritis Impact Measurement Scales (AIMS) physical function. By mediation analyses, weight loss was responsible for 54% of the change in IL-6 and all of the change in leptin. CONCLUSIONS: OA-related inflammatory markers were reduced by a 24-week combined PCST + BWM intervention. This suggests that the inflammatory state can be successfully modified in the context of a readily instituted clinical intervention with a positive clinical outcome.

The development and assessment of the Worry About Pain Questionnaire.

BACKGROUND: Worry can be conceptualized as a cognitive-affective automatic process initiated in order to address uncertainty and potential personal inadequacies that could result in negative outcomes. The purpose of the current study was to develop a measure of pain-specific worry - the Worry About Pain Questionnaire (WAPQ). METHOD: In study 1, responses of 335 pain-free participants were used to complete an item analysis and exploratory factors analysis to develop and assess the internal structure of the WAPQ. Study 2 included 224 pain-free participants who completed the WAPQ in order to confirm its factor structure, and to examine its relation to the experience of acute experimental pain. In study 3, 137 individuals with persistent pain were asked to complete the WAPQ as well as measures of pain and depressive symptoms. RESULTS: The resulting 15-item measure assesses uncertainties and potential negative outcomes related to the experience of pain. The results of the exploratory and confirmatory factor analyses showed a two-factor structure. Across all studies, the WAPQ was found to be related to measures of pain in clinical and non-clinical samples, acute experimental pain stimuli, as well as pain anxiety, pain catastrophizing, fear of pain, rumination and depressive symptomatology. CONCLUSIONS: The results suggest that the WAPQ is a reliable and valid measure for the assessment of worry about pain that can be used to understand how pain-specific worries are related to the experience and impact of pain across different populations. SIGNIFICANCE: Worry has been assessed in pain populations using measures that assess worry in general. The current study shows a relationship between pain-specific worry and the experience of pain. Further, worry about pain is related to but not synonymous with pain catastrophizing.

Pain coping strategies and coping efficacy in rheumatoid arthritis: a daily process analysis.

Data from daily diaries were used to analyze pain coping processes in rheumatoid arthritis patients. For 30 consecutive days, 53 individuals described the pain coping strategies they used that day and rated the efficacy of their coping, joint pain, and positive and negative mood. Relations among variables were examined across-persons and within-persons over time. At the across-persons level of analysis, (i) daily coping efficacy was unrelated to pain coping or pain intensity, and (ii) the more frequent daily use of a wide variety of pain coping strategies was correlated with greater pain. Within-person analyses provided unique information about the relations among coping, pain, and mood not apparent in the across-persons results. Specifically, these analyses showed that increases in daily coping efficacy were not only related to decreases in pain, but also to decreases in negative mood and increases in positive mood. Time-lagged effects of coping and coping efficacy were also found. Individuals who reported high levels of coping efficacy on one day had lower levels of pain on the subsequent day. The daily use of pain reduction efforts and relaxation strategies also contributed to an improvement in next-day pain and an enhancement of positive mood. The implications of these findings for the assessment of pain and coping in rheumatoid arthritis patients are discussed.

The relationship of arthritis self-efficacy to daily pain, daily mood, and daily pain coping in rheumatoid arthritis patients.

There is an increasing awareness in the medical community that psychosocial variables such as beliefs in self-efficacy are important determinants of treatment outcome. However, before measures of self-efficacy are widely incorporated into clinical practice, there needs to be a better understanding of how they relate to daily pain, mood and coping. In the present study 128 rheumatoid arthritis patients completed diaries for 30 days in which they provided daily ratings of joint pain, negative and positive mood, the use of pain coping strategies, and coping efficacy. The patients then participated in an evaluation session during which measures of self-efficacy (the Arthritis Self Efficacy Scale (ASES)), demographic variables, and medical status were collected. A series of hierarchical regression analyses was conducted to determine the degree to which self-efficacy measures collected at the time of the evaluation session were related to daily diary measures collected during the 30 preceding days. The results revealed that self-efficacy was significantly related to daily ratings of pain, mood, coping and coping efficacy. Interestingly, the findings regarding self-efficacy were obtained even after taking into account the effects of important demographic and medical status variables. Taken together, these results suggest that self-efficacy ratings collected from arthritis patients at the time of an evaluation session may well be related to recent experiences of daily pain and mood, as well as the daily use and perceived effectiveness of pain coping strategies.

Methotrexate-associated hepatotoxicity: retrospective analysis of 210 patients with rheumatoid arthritis.

PURPOSE: Beginning in the 1980s, methotrexate has been used successfully to treat rheumatoid arthritis. The magnitude and severity of short- and long-term methotrexate toxicity, however, have not been adequately investigated. Our study was performed to determine the prevalence of hepatotoxicity in patients with rheumatoid arthritis receiving long-term methotrexate therapy. PATIENTS AND METHODS: We conducted a retrospective, computer-assisted review of all Duke University Medical Center patients undergoing liver biopsy for methotrexate monitoring from January 1979 to January 1988. A total of 538 biopsies were performed in 399 patients, 259 of whom had inflammatory arthritis (210 with rheumatoid arthritis, 47 with psoriatic arthritis, and two with seronegative spondyloarthropathy). RESULTS: No evidence of cirrhosis was defined in the cohort with rheumatoid arthritis; however, six patients with rheumatoid arthritis had histologic changes of fibrotic liver disease (prevalence of 2.9 percent in the group with rheumatoid arthritis) while taking methotrexate. Five of the six patients were obese and three had glucose intolerance or overt diabetes mellitus, and one person admitted to alcohol usage. Only one patient with fibrotic liver disease had elevated liver function test results, and no person showed a declining serum albumin level at the time of biopsy. Sixty-one patients with rheumatoid arthritis underwent multiple samplings (44 with two, 13 with three, and four with four biopsies). Fourteen of these patients showed progressive hepatic disease, whereas four patients improved. CONCLUSION: Although the prevalence of methotrexate hepatotoxicity in this large cohort of patients with rheumatoid arthritis was low, a small but definite risk of hepatic fibrosis, not predictable by laboratory screening, still exists.

Musculoskeletal syndromes associated with malignancy.

Evidence has been presented supporting a causal relationship between malignancies and musculoskeletal syndromes. This discussion has dealt primarily with lesser known relationships, more common associations such as hypertrophic osteoarthropathy and dermatomyositis being reviewed elsewhere. The ones discussed herein closely mimic primary connective tissue diseases and offer an insight into the study of the pathogenesis of these primary diseases. In view of the natural history of malignant disease, the hope for such patients arises from the physicians early diagnosis and treatment of the underlying malignancy. Early diagnosis and treatment may in turn be entirely dependent on the physician's awareness of a musculoskeletal syndrome being the presenting feature of an otherwise occult neoplasm. Several connective tissue syndromes appear to predispose to the development of malignancy, and increasing evidence suggests that this development of malignancy may be further enhanced by immunosuppressive therapy.

Self-efficacy for arthritis pain: relationship to perception of thermal laboratory pain stimuli.

OBJECTIVE: To examine how self-efficacy for arthritis pain relates to the perception of controlled laboratory pain stimuli. METHODS: Forty patients with osteoarthritis completed self-report measures of self-efficacy for arthritis pain. They then participated in a single experimental session in which measures of thermal pain threshold and tolerance were collected, as well as measures of the perceived intensity and unpleasantness of a range of thermal pain stimuli. RESULTS: Correlational analyses revealed that patients reporting high self-efficacy for arthritis pain rated the thermal pain stimuli as less unpleasant than those reporting low self-efficacy. When subjects scoring very high and very low in self-efficacy were compared, it was found that subjects scoring high on self-efficacy for arthritis pain had significantly higher pain thresholds and pain tolerance than those scoring low on self-efficacy. CONCLUSIONS: These results indicate that self-efficacy for arthritis pain is related to judgments of thermal pain stimuli. Implications for the understanding of arthritis pain and for future laboratory research are discussed.

Spouse-assisted coping skills training in the management of osteoarthritic knee pain.

OBJECTIVE: To evaluate the effects of a spouse-assisted pain-coping skills training intervention on pain, psychological disability, physical disability, pain-coping, and pain behavior in patients with osteoarthritis (OA) of the knees. METHODS: Eighty-eight OA patients with persistent knee pain were randomly assigned to 1 of 3 conditions: 1) spouse-assisted pain-coping skills training, (spouse-assisted CST), 2) a conventional CST intervention with no spouse involvement (CST), or 3) an arthritis education-spousal support (AE-SS) control condition. All treatment was carried out in 10 weekly, 2-hour group sessions. RESULTS: Data analysis revealed that at the completion of treatment, patients in the spouse-assisted CST condition had significantly lower levels of pain, psychological disability, and pain behavior, and higher scores on measures of coping attempts, marital adjustment, and self-efficacy than patients in the AE-SS control condition. Compared to patients in the AE-SS control condition, patients who received CST without spouse involvement had significantly higher post-treatment levels of self-efficacy and marital adjustment and showed a tendency toward lower levels of pain and psychological disability and higher scores on measures of coping attempts and ratings of the perceived effectiveness of pain-coping strategies. CONCLUSION: These findings suggest that spouse-assisted CST has potential as a method for reducing pain and disability in OA patients.

Spouse-assisted coping skills training in the management of knee pain in osteoarthritis: long-term followup results.

OBJECTIVE: To evaluate the long-term effects of a spouse-assisted coping skills intervention in patients with osteoarthritis (OA) of the knees, and to evaluate how pre- to posttreatment changes in marital adjustment and self-efficacy relate to long-term improvements in pain, psychological disability, physical disability, pain coping, and pain behavior. METHODS: A followup study was conducted with 88 OA patients who had been randomly assigned to 1 of 3 treatment conditions: 1) spouse-assisted coping skills training (spouse-assisted CST), 2) a conventional CST intervention with no spouse involvement, and 3) an arthritis education-spousal support (AE-SS) control condition. To evaluate long-term outcome, comprehensive measures of self-efficacy, marital adjustment, pain, psychological disability, physical disability, pain coping, and pain behavior were collected from these individuals at 6 and 12 months posttreatment. RESULTS: Data analysis revealed that, at 6-month followup, patients in the spouse-assisted CST condition scored higher on measures of coping and self-efficacy than those in the AE-SS control group. At 6-month followup, patients who received CST without spouse involvement showed a significantly higher frequency of coping attempts and reported higher levels of marital adjustment than those in the AE-SS control group. At 12-month followup, patients in the spouse-assisted CST condition had significantly higher overall self-efficacy than those in the AE-SS control condition. In addition, patients in both the spouse-assisted CST and CST only conditions tended to show improvements in physical disability at the 12-month followup. Individual differences in outcome were noted at the 12-month followup. Patients in the spouse-assisted CST condition who reported initial (pre- to posttreatment) increases in marital adjustment had lower levels of psychological disability, physical disability, and pain behavior at 12-month followup. However, for patients in the conventional CST and AE-SS control conditions, increases in marital adjustment occurring over the initial phase of treatment were related to increases in pain and decreases in scores on the Pain Control in Rational Thinking factor of the Coping Strategies Questionnaire. Finally, patients in the spouse-assisted CST condition who showed pre- to posttreatment increases in self-efficacy were more likely to show decreases in pain, psychological disability, and physical disability at 12-month followup. CONCLUSIONS: These findings suggest that spouse-assisted CST can enhance self-efficacy and improve the coping abilities of OA patients in the long term. Individual differences in the long-term outcome of spouse-assisted CST were noted, with some patients (those showing increases in marital satisfaction and self-efficacy) showing much better outcomes than others.

Living with rheumatoid arthritis: the role of daily spirituality and daily religious and spiritual coping.

The objective of this preliminary study was to evaluate more fully the role of daily spiritual experiences and daily religious/spiritual coping in the experience of individuals with pain due to rheumatoid arthritis (RA). Thirty-five individuals with RA were asked to keep a structured daily diary for 30 consecutive days. The diary included standardized measures designed to assess spiritual experiences, religious and spiritual pain coping, salience of religion in coping, religious/spiritual coping efficacy, pain, mood, and perceived social support. The participants in this study reported having spiritual experiences, such as feeling touched by the beauty of creation or feeling a desire to be closer or in union with God, on a relatively frequent basis. These participants also reported using positive religious and spiritual coping strategies much more frequently than negative religious and spiritual coping strategies. Although most of the variance in these measures was due to differences between persons, each measure also displayed a significant variability in scores from day to day. Indeed, there was just as much (or more) variability in these measures over time as there was variability in pain. Individuals who reported frequent daily spiritual experiences had higher levels of positive mood, lower levels of daily negative mood, and higher levels of each of the social support domains. Individuals who reported that religion was very salient in their coping with pain reported much higher levels of instrumental, emotional, arthritis-related, and general social support. Coping efficacy was significantly related to pain, mood, and social support in that on days that participants rated their ability to control pain and decrease pain using spiritual/religious coping methods as high, they were much less likely to have joint pain and negative mood and much more likely to have positive mood and higher levels of general social support. Taken together, these results suggest that daily spiritual experiences and daily religious/spiritual coping variables are important in understanding the experience of persons who have RA. They also suggest that newly developed daily diary methods may provide a useful methodology for studying religious and spiritual dimensions of living with arthritis.

Rheumatologic manifestations of cancer.

A variety of musculoskeletal syndromes have been described in association with malignancy. The majority of such descriptions have dealt with the connective tissue disorder as a paraneoplastic syndrome, frequently the presenting feature of an otherwise occult malignancy. This may range from the well known syndrome of HOA, heralding lung cancer, to a lesser known association of pyogenic arthritis due to an unusual enteric pathogen, signaling colon cancer. Conversely, the connective tissue disorder may precede the malignancy, and by virtue of its pathophysiology or its therapy, foster the subsequent development of cancer. Awareness of these associations may lead to earlier cancer detection, and hence, potentially more effective therapy.

Cognitive behavioral control of arthritis pain.

Cognitive-behavioral approaches appear to offer a viable alternative for the management of arthritis pain. Controlled studies have documented the efficacy of CBT protocols for managing pain in individuals having OA and RA. Preliminary studies examining the efficacy of CBT for FM patients have also yielded encouraging results. A number of clinical and research issues need attention if CBT is to be incorporated into rheumatology practice settings. These issues include identifying the most important components of CBT, developing strategies for matching CBT interventions to patients' readiness for behavior change, testing the efficacy of different therapy formats (e.g., individual versus group), broadening the scope of CBT to address issues other than pain, and insurance reimbursement.

Peripheral nerve entrapment due to steroid-induced lipomatosis of the popliteal fossa. Case report.

A case of peroneal nerve entrapment is reported in a patient with scleroderma. Compression was due to a lipoma in the popliteal fossa and resulted in increasingly severe foot-drop. Complete recovery occurred after the lipoma was resected. A brief review of peroneal nerve palsies and lipomatosis is presented.

Cyclosporin A therapy for Wegener's granulomatosis.

Five patients with active Wegener's granulomatosis were treated with the immunosuppressive agent Cyclosporin A, along with low dose prednisone. All five patients had previously taken cyclophosphamide, but further treatment with this agent was not desired, either due to patient choice, drug toxicity or malignancy. In initial doses of up to 5mg/kg/day, CyA showed efficacy but when lowered to 1-2mg/kg/day, mild disease flares occurred. CyA may provide an alternative to traditional therapy in selected patients with WG.

Aggression in dogs and associated neuropathology.

The central nervous systems of eight dogs with behavioral changes were compared. Three had pathological lesions involving the limbic system. The nervous system and, in particular, the limbic system should be examined as a possible site for lesions in dogs with a history of behavioral changes.

Renal agenesis after first trimester exposure to chlorambucil.

One of a set of twins aborted at 20 weeks' gestation had unilateral renal agenesis after exposure to chlorambucil and prednisone since conception. There are no firm clinical data suggesting that second or third trimester exposure to any of the immunosuppressive drugs is toxic to the fetus, and no absolute cause-and-effect relationship is established in this case.

Polymyositis after propylthiouracil treatment for hyperthyroidism.

An additional disorder in the spectrum of thyroid related muscle disease is presented. Hypothyroid and hyperthyroid disease are both associated with a variety of muscle abnormalities, from myalgias to myopathy. Polymyositis, however, has never been reported immediately after treatment for active hyperthyroidism. A patient is presented with typical hyperthyroidism, who developed a severe proximal muscle weakness and a raised creatine phosphokinase after treatment for hyperthyroidism with propylthiouracil (100 mg orally, three times a day). Electromyography, muscle biopsy, and the course of the patient's illness were consistent with polymyositis. Whether this represents a cause-effect association or a chance occurrence is unknown. Physician awareness of the occurrence of a variety of muscle disorders including polymyositis in thyroid disease is emphasised. A brief discussion of thyroid myopathy, thionamide drug reactions, and polymyositis is included.