Medicina (B Aires) 2006; 66(2): 147-9 (Read article online)

Cavallasca JA, Malah VA, Fernandez DE, Carbia SG, Nasswetter GG

Pachydermoperiostosis or primary hypertrophic osteoarthropathy is a rare disease characterized by cutaneous and osteoarthicular involvement. We describe two patients with finger clubbing, watch crystal nails, bones thickenings, arthritis and different grades of skin affection, without other clinical manifestations. Both did not know of having relatives with the same alterations. Radiological studies of the affected areas showed periostosis. Because of normal laboratory results and chest radiography plus the absence of other underlying causes, diagnosis of primary hypertrophic osteoarthropathy was made.

Pharmacotherapy 2006 Jun; 26(6): 868-71 (Read article online)

Chonlahan J, Halloran MA, Hammonds A

A 61-year-old Caucasian woman receiving long-term anticoagulation with warfarin for recurrent thromboembolism and atrial fibrillation was found to have an elevated international normalized ratio (INR) after she started leflunomide therapy for rheumatoid arthritis. Her INR had been stable for 4 months before this event. The patient required an overall decrease of 22% in her weekly warfarin dose to maintain a therapeutic INR within the goal range of 2.0-3.0 after adding leflunomide therapy. A comprehensive PubMed/MEDLINE search was conducted to identify literature addressing the potential interaction between warfarin and leflunomide. Evidence describing the interaction and its potential mechanism was limited to one published case report and to in vitro data, respectively. Our case report provides additional support that such an interaction exists and that it was at least partly responsible for the subsequent increase in the patient's INR. Therefore, continued evaluation and documentation of this potential drug interaction is imperative. To reduce the risk of adverse effects related to excessive anticoagulation with the start of leflunomide in patients taking warfarin, clinicians should increase their frequency of INR monitoring and adjust the warfarin dosage accordingly to maintain therapeutic anticoagulation.

Rheum Dis Clin North Am 2006 May; 32(2): 255-273 (Read article online)

Choi H

Gout is an inflammatory arthritis mediated by the crystallization of uric acid within the joints and often is associated with hyperuricemia. Data suggest that the overall disease burden of gout remains substantial and may be increasing. Identifying and characterizing modifiable risk factors for gout is a major step in preventing and managing this painful condition. As more scientific data on the risk factors and comorbidities of gout become available, their integration into gout prevention and care strategies may become essential. This article reviews the relevant epidemiologic data, with a focus on recent progress and data on other crystal arthropathies.

J Hand Surg [Br] 2006 May 19; (Read article online)

Abe Y, Katsube K, Tsue K, Doi K, Hattori Y

To clarify the pathology of radial-sided wrist pain with inconclusive X-ray and MRI findings, we performed arthroscopic examinations of 11 wrists in 10 patients. Physical examination and various image investigations could not identify the cause of the pain. Arthroscopy revealed partial to complete tears of the scapho-lunate interosseous ligament and synovitis and/or chondral bone defects at the scaphotrapezio-trapezoidal joint in all 11 wrists. Surgical procedures consisted of eight simple synovectomies, two ligament reconstructions and one percutaneous pinning. Pain relief was achieved in 10 wrists. One wrist which had a simple synovectomy did not recover, so underwent secondary scapho-trapezio-trapezoidal fusion. In conclusion, we found that various degrees of scapholunate interosseous ligament tear and scapho-trapezio-trapezoidal joint osteoarthritis were the main causes of radial-sided wrist pain with inconclusive X-ray and simple MRI findings.

CMAJ 2006 May 23; 174(11): 1589-94 (Read article online)

Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E

BACKGROUND: Chronic noncancer pain (CNCP) is a major health problem, for which opioids provide one treatment option. However, evidence is needed about side effects, efficacy, and risk of misuse or addiction. METHODS: This meta-analysis was carried out with these objectives: to compare the efficacy of opioids for CNCP with other drugs and placebo; to identify types of CNCP that respond better to opioids; and to determine the most common side effects of opioids. We searched MEDLINE, EMBASE, CENTRAL (up to May 2005) and reference lists for randomized controlled trials of any opioid administered by oral or transdermal routes or rectal suppositories for CNCP (defined as pain for longer than 6 mo). Extracted outcomes included pain, function or side effects. Methodological quality was assessed with the Jadad instrument; analyses were conducted with Revman 4.2.7. RESULTS: Included were 41 randomized trials involving 6019 patients: 80% of the patients had nociceptive pain (osteoarthritis, rheumatoid arthritis or back pain); 12%, neuropathic pain (postherpetic neuralgia, diabetic neuropathy or phantom limb pain); 7%, fibromyalgia; and 1%, mixed pain. The methodological quality of 87% of the studies was high. The opioids studied were classified as weak (tramadol, propoxyphene, codeine) or strong (morphine, oxycodone). Average duration of treatment was 5 (range 1-16) weeks. Dropout rates averaged 33% in the opioid groups and 38% in the placebo groups. Opioids were more effective than placebo for both pain and functional outcomes in patients with nociceptive or neuropathic pain or fibromyalgia. Strong, but not weak, opioids were significantly superior to naproxen and nortriptyline, and only for pain relief. Among the side effects of opioids, only constipation and nausea were clinically and statistically significant. INTERPRETATION: Weak and strong opioids outperformed placebo for pain and function in all types of CNCP. Other drugs produced better functional outcomes than opioids, whereas for pain relief they were outperformed only by strong opioids. Despite the relative shortness of the trials, more than one-third of the participants abandoned treatment.

Biochem Biophys Res Commun 2006 May 15; (Read article online)

Kim JK, Oh SM, Kwon HS, Oh YS, Lim SS, Shin HK

Licorice, the roots of Glycyrrhiza inflata, is used by practitioners of alternative medicine to treat individuals with gastric or duodenal ulcers, bronchitis, cough, arthritis, adrenal insufficiency, and allergies. We investigated the anti-inflammatory properties of 4 licorice extracts: extracts of roasted licorice obtained by ethanol (rLE) or water extraction (rLW) and extracts of raw licorice obtained by ethanol (LE) or water extraction (LW). rLE demonstrated strong anti-inflammatory activity through its ability to reduce nitric oxide and prostaglandin E(2) production in the LPS-stimulated mouse macrophage cell, RAW264.7. It also inhibited the production of pro-inflammatory cytokines and CD14 expression on the LPS-stimulated RAW264.7 cells. Further study indicated that LPS-induced degradation and phosphorylation of Ikappa-Balpha, along with DNA-binding of NF-kappaB, was significantly inhibited by rLE exposure in RAW264.7 cells. In the murine model, we found that in vivo exposure to rLE-induced an increase in the survival rate, reduced plasma levels of TNF-alpha and IL-6, and increased IL-10 production in LPS-treated mice. Collectively, these data suggest that the use of rLE may be a useful therapeutic approach to various inflammatory diseases.

Ann Nucl Med 2006 Apr; 20(3): 183-8 (Read article online)

Gedik GK, UÄŸur O, Atilla B, Pekmezci M, Yildirim M, Seven B, VaroÄŸlu E

OBJECTIVES: Radionuclide synovectomy is a reliable therapy in patients with chronic synovitis. However, radiation doses delivered to non-target organ systems due to leakage of radioactive material from the articular cavity are an important disadvantage of this procedure. In this study we compared extraarticular leakage values of the 3 commonly used radiopharmaceuticals; 90Y-citrate, 90Y-silicate and 186Re-sulfide colloid. MATERIALS AND METHODS: Thirty-five patients with persistent synovitis were enrolled in the study. Twenty-two hemophilic, 8 rheumatoid arthritis and 5 patients with pigmented villonodular synovitis were studied. 90Y labeled silicate and citrate were used for knee joints and 186Re-sulfide for intermediate sized joints. Radiocolloid leakage values were evaluated using a gamma camera with 20% window centered over the bremsstrahlung photopeak of 90Y and a respective window over the 137 keV photopeak of 186Re. Regions of interest were drawn over the injection site, the regional lymph nodes and the background areas. Leakage of radiocolloid was calculated by dividing the counts/pixel in the regional lymph node area to the counts/pixel in the injection site. RESULTS: No visible leakage was observed. The median leakage values calculated for 90Y-citrate, 90Y-silicate and 186Re-sulfide were found as 1.9%, 2.4% and 2.7%, respectively. The difference between the variability of leakage values was not statistically significant (p > 0.05). CONCLUSION: There was no significant difference in terms of extraarticular leakage between 9Y-citrate, 9Y-silicate and 186Re-sulfide radiocolloids.

Clin Chim Acta 2006 Apr 7; (Read article online)

Lemarechal H, Allanore Y, Chenevier-Gobeaux C, Kahan A, Ekindjian OG, Borderie D

OBJECTIVE: To examine protein oxidation in rheumatoid arthritis (RA) and evaluate its evolution after infliximab therapy in a subgroup of patients. METHODS: Seventy-one consecutive patients with RA were included. Among them, 30 patients refractory to conventional therapy were treated with infliximab. Serum markers of oxidative stress were determined at baseline and before the infusions of infliximab at weeks 6 and 30. Baseline values were compared with those in 30 healthy volunteers. RESULTS: Mean levels of serum carbonyl groups were significantly higher in RA patients than in controls (1.29+/-0.76 versus 0.58+/-0.39nmol/mg of protein, p<0.0001), whereas thiol levels were found to be lower (238.3+/-61.6 versus 316.5+/-54.8mumol/L, p<0.0001). Thiol levels inversely correlated with the disease activity score (r=-0.42, p=0.004), and with CRP values (r=-0.45, p=0.001). Immunoblots showed that albumin and heavy chain immunoglobulin were oxidized more markedly than in healthy volunteers. Significantly lower levels of thiol groups were detected in patients with refractory RA disease (208.9+/-66.8 versus 264.2+/-43.0 mumol/L, p<0.0004) but concentrations of carbonyl groups were similar. Short-term treatment with infliximab significantly decreased carbonyl groups (0.97+/-0.47 nmol/mg protein, p=0.02) and increased thiol (231.2+/-48.7 mumol/L, p=0.02) levels. CONCLUSION: Our results highlight free radical protein damage in RA and a link with inflammation, as underlined by the beneficial effects of infliximab.

Biochem J 2006 May 23; (Read article online)

Lin M, Rose-John S, Grötzinger J, Conrad U, Scheller J

In murine models of Crohn's disease, rheumatoid arthritis and colon cancer, interleukin (IL)-6 signalling via the soluble IL-6 receptor (sIL-6R, termed IL-6 trans-signalling) has been shown to promote the pathology associated with these conditions. These detrimental activities can however be selectively blocked by soluble forms of the gp130 receptor. Although soluble gp130 (sgp130) therefore represents a viable therapeutic modality for the treatment of these conditions, the mass manufacture of such biologics is often expensive. The advent of molecular farming has however provided an extremely cost effective strategy for the engineering of recombinant proteins. Here we describe the expression and production of a biologically active sgp130 variant which is expressed in transgenic tobacco plants as an elastin-like pentapeptide (ELP) fusion protein (mini-gp130-ELP). Mini-gp130-ELP consists of the first three domains of gp130 (Ig-like domain and cytokine binding module) fused to 100 repeats of ELP. Expression of mini-gp130-ELP did not affect the growth rate or morphology of the transgenic plants, and purification was achieved using inverse transition cycling. This approach led to an overall yield of 141 microg of purified protein per gram of fresh leaf weight. The purified mini-gp130-ELP specifically inhibited sIL-6R-mediated trans-signalling as measured by binding to the IL-6/sIL-6R complex and through its ability to block sIL-6R-mediated activation of STAT3 phosphorylation and proliferation in human hepatoma cells and murine pre-B-cells. Consequently, this study validates the potential application of molecular farming in transgenic tobacco plants as a strategy for the expression and purification of therapeutically advantageous biologics such as sgp130.

Virology 2006 May 20; (Read article online)

Murphy BG, Hötzel I, Jasmer DP, Davis WC, Knowles D

Caprine arthritis encephalitis virus transcription is under the control of the viral promoter within the long terminal repeat. Previous studies with the closely related maedi visna lentivirus have indicated that viral transcription is dependent upon the AP-1 transcription factor. Other studies have indicated a potential role for the cytokines TNFalpha and GM-CSF in CAEV pathogenesis by increasing viral loads in infected tissues. The hypotheses that AP-1 transcription factors are necessary for transcriptional activation of the CAEV promoter and that CAEV transcriptional activation results from treatment with the cytokines GM-CSF and TNFalpha were tested with a stably transduced U937 cell line. Here, we found that TNFalpha and GM-CSF activated CAEV transcription in U937 cells. However, this activation effect was not blocked by SP600125, an inhibitor of Jun N-terminal kinase. SP600125 effectively prevented Jun phosphorylation in cells subsequently treated with cytokines. The cytokines TNFalpha and GM-CSF therefore activate CAEV transcription, and this effect occurs independently of AP-1. A set of progressive deletion mutants was utilized to show that TNFalpha-induced expression depends on an element or elements within the U3 70-bp repeat.

Rheum Dis Clin North Am 2006 May; 32(2): 401-12 (Read article online)

Rosenthal AK

Calcium crystals are common and under-recognized participants in osteoarthritis. Excellent evidence supports two hypotheses explaining the relationship between calcium crystal deposition and osteoarthritis. There is ample support for the theory that calcium crystals cause or worsen osteoarthritis and equally compelling evidence to support the theory that osteoarthritis causes or worsens calcium crystal formation. Further research in this area will improve understanding of the pathogenesis of these conditions and should lead to the development of effective therapy for all types of degenerative arthritis.

Osteoarthritis Cartilage 2006 May 20; (Read article online)

Gold GE, Burstein D, Dardzinski B, Lang P, Boada F, Mosher T

Osteoarthritis (OA) is a leading cause of disability worldwide. Magnetic resonance imaging (MRI), with its unique ability to image and characterize soft tissue non-invasively, has proven valuable in assessing cartilage in OA. The development of new, fast imaging methods with high contrast show promise to improve the magnetic resonance (MR) evaluation of this disease. In addition to morphologic MRI methods, MRI contrast mechanisms under development may reveal detailed information about the physiology of cartilage. It is anticipated that these and other MRI techniques will play an increasingly important role in assessing the success or failure of therapies for OA. On December 5 and 6, 2002, OMERACT (Outcome Measures in Rheumatology Clinical Trials) and OARSI (Osteoarthritis Research Society International) held a workshop in Bethesda, MD aiming at providing a state-of-the-art review of imaging outcome measures for OA of the knee to help guide scientists and pharmaceutical companies in the use of MRI in multi-site studies of OA. Applications of MRI were initially reviewed by a multidisciplinary, international panel of expert scientists and physicians from academia, the pharmaceutical industry and regulatory agencies. The findings of the panel were then presented to a wider group of participants for open discussion. The following report summarizes the results of these discussions with respect to novel MRI pulse sequences for evaluating articular cartilage of the knee in OA and notes any additional advances that have been made since.

J Exp Med 2006 May 22; (Read article online)

Sawa SI, Kamimura D, Jin GH, Morikawa H, Kamon H, Nishihara M, Ishihara K, Murakami M, Hirano T

Mice homozygous for the F759 mutation in the gp130 interleukin (IL)-6 receptor subunit have enhanced gp130-mediated signal transducer and activator of transcription (STAT)3 activation and spontaneously developed a lymphocyte-mediated rheumatoid arthritis-like joint disease. Here, we show that the development of the disease is dependent on both major histocompatibility complex (MHC) II-restricted CD4(+) T cells and IL-6 family cytokines. In spite of the necessity for CD4(+) T cells, the gp130 mutation was only required in nonhemtopoietic cells for the disease. The gp130 mutation resulted in enhanced production of IL-7. Conditional knockout of STAT3 in nonlymphoid cells showed that the enhancement of IL-7 production was dependent on STAT3 activation by IL-6 family cytokines. Homeostatic proliferation of CD4(+) T cells was enhanced in gp130 mutant mice and acceleration of homeostatic proliferation enhanced the disease, whereas the inhibition of homeostatic proliferation suppressed the disease. Anti-IL-7 antibody treatment inhibited not only the enhanced homeostatic proliferation, but also the disease in gp130 mutant mice. Thus, our results show that autoimmune disease in gp130 mutant mice is caused by increased homeostatic proliferation of CD4(+) T cells, which is due to elevated production of IL-7 by nonhematopoietic cells as a result of IL-6 family cytokine-gp130-STAT3 signaling.

Bioorg Med Chem 2006 May 20; (Read article online)

Bikádi Z, Hazai E, Zsila F, Lockwood SF

Inhibitors for matrix metalloproteinases (MMPs) are under investigation for the treatment of various important chronic illnesses, including cancer, arthritis, and cardiovascular disease (CVD). In particular, MMP-13 is currently being probed as a potential key target in CVD and malignant disease due to its documented effects on extracellular matrix (ECM) remodeling, important in the pathophysiology of these diseases. Within the family of related mammalian MMP enzymes, MMP-13 possesses a large hydrophobic binding pocket relative to that of other MMPs. Homochiral astaxanthin (3S,3'S-AST; 3S,3'S-dihydroxy-beta,beta-carotene-4,4'-dione), an important antioxidant and anti-inflammatory xanthophyll carotenoid, is an active metabolite of several novel soft drugs in clinical development; it is also extensively used and tested as a human nutraceutical. In the current study, the prediction of the geometry and energetics of its binding to human MMP-13 was conducted with molecular modeling. The method used was found to predict the energy of binding of known ligands of MMP-13 with great precision. Blind docking using the whole protein target was then used in order to identify the possible binding site(s) of AST. AST was predicted to bind at several sites in close proximity to the active center. Subsequent analyses focused on the binding site at the atomic (i.e., amino acid sequence) level suggested that AST can bind to MMP-13 with high affinity and favorable energetics. Therefore, the modeling study predicts potential direct enzyme-inhibitory activity of AST against MMP-13, a behavior that may be exploited in mammalian systems in which pathological upregulation of MMP activity is paramount.

Pol Arch Med Wewn 2005 Sep; 114(3): 843-7 (Read article online)

Pawlik A, Czerny B, Dabrowska-Zamojcin E, Górnik W, Poziomkowska I, Gawrońska-Szklarz B, Herczyńska M

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which cytokines play an important role. The therapy of RA is associated with application of the drugs modulating the immune response via inhibiting the cytokine production. The common drugs used in RA therapy are methotrexate and prednisone. Recent investigations showed the importance of genetically determined differences in cytokine production in RA activity and therapy. The aim of the present study was to examine the influence of - 174 interleukin-6 (IL-6) promoter polymorphism on the efficacy of treatment of RA patients with methotrexate and prednisone. Polymerase chain reaction amplification was used for analysis of the polymorphism at IL-6 gene. Seventy patients with RA diagnosed according to the criteria of the American College of Rheumatology were investigated. The patients were divided into two subgroups. The first subgroup included patients who have obtained remission for at least 6 months after therapy with methotrexate and glucocorticosteroids. The second subgroup included patients with active disease despite at least 6 months of therapy with methotrexate and glucocorticosteroids. It has been shown that the incidence of remission after therapy with methotrexate and glucocorticosteroids was significantly lower in patients with GG genotype as compared with GC and CC genotypes p< 0.05. We suggest that -174 IL-6 promoter polymorphism may be a genetic risk factor determining the effectiveness of RA treatement with methotrexate and glucocorticosteroids.

Int Arch Occup Environ Health 2006 May 20; (Read article online)

de Buck PD, de Bock GH, van Dijk F, van den Hout WB, Vandenbroucke JP, Vliet Vlieland TP

Objectives: To study the occurrence and duration of sick leave as potential risk factors for permanent job loss after 24 months among 112 individuals with chronic arthritis and a disease related problem at work. Methods: Data collection was embedded in a multicentre randomised controlled trial in which the cost-effectiveness of a multidisciplinary job retention vocational rehabilitation programme for employees with chronic arthritis and a disease related problem at work was compared to usual outpatient care. Sick leave (complete or partial) was defined as absenteeism reported to the employer and permanent job loss as receiving a full work disability pension or unemployment. The association between sick leave at baseline and job loss after 24 months was investigated by multivariate logistic regression analysis, including those variables that were univariately significantly associated with job loss after 24 months. Results: At baseline, 60 of the 112 subjects (54%) were on sick leave, with a mean duration of 18.7 weeks, in half of these patients the sick leave was complete. After 24 months, 26 of the 112 patients (23%) had lost their job. The presence of complete sick leave (OR 4.74, 95% CI 1.86-12.07) and the depression score of the hospital anxiety and depression scale (OR 1.18, 95% CI 1.02-1.36) were significantly and independently associated with job loss after 2 years follow-up. Conclusion: The occurrence of complete sick leave was found to be an independent risk factor for job loss in patients with chronic arthritis who have a disease related problem at work.

Am J Chin Med 2006; 34(3): 417-426 (Read article online)

Park IB, Ahn CB, Choi BT

The aim of this study was to investigate the effects of electroacupuncture (EA) on the glycoconjugate (GC) changes in articular cartilage in the ankle of an arthritic model. Arthritis was induced by an intraplantar injection of complete Freund's adjuvant (CFA) into the hindpaw of male Sprague-Dawley rats. Bilateral EA stimulation at 2 Hz, 15 Hz and 120 Hz was applied at those acupoints corresponding to Zusanli and Sanyinjiao in man, using needles for 3-day intervals for 30 days. To determine the presence of arthritis, paw edema was measured by a water displacement plethysmometer. Edema of the hindpaw induced by CFA-injection was strongly inhibited by EA stimulation throughout the experimental period. At 30 days after CFA-injection, GC changes of articular cartilage of the ankle joint were observed using conventional and lectin histochemistry. The CFA-injected rat revealed general reduction of staining abilities and lectin affinities for GC in comparison with normal rats. Significant reductions of neutral and acidic GC were observed in interterritorial matrix and chondrocyte capsules, respectively. All lectin affinities examined except DBA were also decreased in CFA-injected rats compared to normal ones. However, EA-treated rats, showed similar staining patterns and lectin affinities for GC as to normal ones, especially neutral GC in interterritorial matrix and sWGA and RCA-1 affinities in chondrocytes. It is concluded that EA in all frequencies examined, especially 2 Hz, can attenuate inflammatory edema in CFA-injected rats through alleviation of alterations of GC components in articular cartilage.

Acta Derm Venereol 2006; 86(3): 209-214 (Read article online)

Birlea S, Birlea M, Cimponeriu D, Apostol P, Cosgarea R, Gavrila L, Tigan S, Costin G, Das PK

Vitiligo has been associated with the host's genetic profile, metabolic abnormality and immunostatus. The purpose of this study was to investigate the association of vitiligo with autoimmune diseases for 31 out of 39 subjects with vitiligo and their first-degree relatives living in a small Caucasian inbred rural community. They were compared with healthy individuals. A 2.28% prevalence of vitiligo was calculated and the presence of consanguine marriages (72.3%) was noted for this community. Our results indicate an increased prevalence of thyroidopathies, diabetes mellitus and rheumatoid arthritis in families with vitiligo. We also show that the Apa-I polymorphism of the vitamin D receptor gene is associated with vitiligo. This is the first study of its kind performed in Romania suggesting that the vitamin D receptor gene might play a role in the aetiopathogenesis of skin depigmentation.

Scand J Infect Dis 2006 May; 38(5): 396-399 (Read article online)

Bilavsky E, Yarden-Bilavsky H, Zevit N, Amir J

We present a case of primary meningococcal arthritis in an 8-month-old immunocompetent female. We also review 18 additional paediatric cases and characterize this unique form of meningococcal disease.

J Orofac Pain 2006; 20(2): 115-24 (Read article online)

Brister H, Turner JA, Aaron LA, Mancl L

AIMS: To examine the psychometric characteristics of a measure of self-efficacy for managing temporomandibular disorders (TMD) and to determine whether scores on this measure were related to pain, disability, and psychological distress in patients with chronic TMD pain. METHODS: Patients seeking treatment for chronic TMD pain (n = 156, 87% female, mean age = 37 years) completed measures assessing pain, disability, mental health, pain-coping strategies, and self-efficacy for managing their pain. RESULTS: The self-efficacy measure, which was adapted from arthritis research, demonstrated good psychometric characteristics (Cronbach's alpha = 0.91, minimal floor and ceiling effects, and validity). Greater self-efficacy was associated with significantly (P < .05) lower levels of pain, disability, and psychological distress. Self-efficacy remained significantly associated with disability and mental health measures even after controlling for demographic variables and pain intensity. In addition, patients with higher self-efficacy reported significantly (P < .05) greater use of an active, adaptive chronic pain-coping strategy (task persistence) and less use of a passive, maladaptive chronic pain-coping strategy (rest). CONCLUSION: Self-efficacy for managing pain appears to be important in the adjustment of patients with chronic TMD pain. Research is needed to determine whether treatments designed to increase self-efficacy improve TMD patient outcomes.