OBJECTIVE:To determine the validity, reliability, and feasibility of durometer measurements of skin hardness as an outcome measure in clinical trials of scleroderma.METHODS:Skin hardness was measured during a multicenter treatment trial for scleroderma using handheld digital durometers with a continuous scale. Skin thickness was measured by modified Rodnan skin score (MRSS). Other outcome data collected included the Scleroderma Health Assessment Questionnaire. In a reliability exercise in advance of the trial, 9 investigators examined the same 5 scleroderma patients by MRSS and durometry.RESULTS:Forty-three patients with early diffuse cutaneous systemic sclerosis were studied at 11 international centers (mean age 49 years [range 24-76], median disease duration 6.4 months [range 0.3-23], and median baseline MRSS 22 [range 11-38]). The reliability of durometer measurements was excellent, with high interobserver intraclass correlation coefficients (ICCs) (0.82-0.92), and each result was greater than the corresponding skin site ICCs for MRSS (0.54-0.85). Baseline durometer scores correlated well with MRSS (r = 0.69, P < 0.0001), patient self-assessments of skin disease (r = 0.69, P < 0.0001), and Health Assessment Questionnaire (HAQ) disability scores (r = 0.34, P = 0.03). Change in durometer scores correlated with change in MRSS (r = 0.70, P < 0.0001), change in patient self-assessments of skin disease (r = 0.52, P = 0.003), and change in HAQ disability scores (r = 0.42, P = 0.017). The effect size was greater for durometry than for MRSS or patient self-assessment.CONCLUSION:Durometer measurements of skin hardness in patients with scleroderma are reliable, simple, accurate, demonstrate good sensitivity to change compared with traditional skin scoring, and reflect patients' self-assessments of their disease. Durometer measurements are valid, objective, and scalable, and should be considered for use as a complementary outcome measure to skin scoring in clinical trials of scleroderma.

Few randomized controlled trials (RCT) have shown a demonstrable treatment effect in systemic sclerosis (SSc), making it difficult to evaluate outcome measures in this disease indication. Results from recent RCT, including those evaluating cyclophosphamide for SSc interstitial lung disease and endothelin receptor antagonists for pulmonary hypertension, have allowed analysis of certain organ-specific endpoints using the OMERACT filter. An earlier metaanalysis established that skin score, measures of Raynaud's, pulmonary function tests, blood pressure, pain, Health Assessment Questionnaire, and Medical Outcomes Survey Short-Form 36 are validated outcome measures in SSc. At OMERACT 8, data regarding validation of high-resolution computed tomography of the lungs, 6-minute walk test, and patient reported outcomes in SSc were presented. A Delphi exercise to develop consensus regarding a combined set of noninvasive measures for pulmonary arterial hypertension (PAH) is under way. Given the protean nature of this illness and its multiorgan system involvement, a composite responder index may be preferable. Another Delphi exercise is designed to develop consensus regarding a combined SSc response index to be validated in future RCT.

Objectives: Different pain thresholds were investigated, using the WOMAC Pain Scale (WOMAC-P) to determine if they could differentiate between treatment groups (hylan G-F 20 vs. appropriate care) at low and very low levels of state attainment in patients with knee osteoarthritis (OA). A method, termed the BLISS (Bellamy et a]. Low Intensity Symptom State-attainment) Index, for analyzing OA knee clinical trials data, was proposed.Study Design and Setting: Five analyses were performed: time to first BLISS day, BLISS days over 12 months, patients with a BLISS response at month 12, patients with a BLISS response at any time, and number of BLISS periods over 12 months. For each analysis, five levels of WOMAC-P were examined: <= 5 normalized units (NU), <= 10, <= 15, <= 20, and <= 25 (higher = more pain).Results: More patients in the hylan G-F 20 group achieved BLISS states in all five analyses. These differences were statistically significant for all pain threshold levels except <= 5 NU.Conclusion: Five methods of measuring BLISS attainment using four prespecified threshold levels of pain were able to statistically discriminate between treatment groups. This method may potentially provide an approach, to defining which patients not only improve but also achieve a good state of health, at low and very low levels of pain intensity. BLISS-10 is a therapeutically attainable very low symptom state at which clinically important, statistically significant between-group differences are detectable, and therefore may provide a benchmark against which therapeutic interventions can be assessed. However, the value to patients, of this and other low and very low intensity pain states, requires further elaboration. (c) 2007 Elsevier Inc. All rights reserved.

A 68-year-old man noted a rash followed by periorbital swelling and muscular weakness. Several months before his hospital admission, he had had involuntary weight loss, and his physician had noted anemia. The results of an evaluation for gastrointestinal cancer were negative. Abdominal computed tomography disclosed a mass involving the spleen and retroperitoneum. A diagnostic procedure was performed.

A 68-year-old man noted a rash followed by periorbital swelling and muscular weakness. Several months before his hospital admission, he had had involuntary weight loss, and his physician had noted anemia. The results of an evaluation for gastrointestinal cancer were negative. Abdominal computed tomography disclosed a mass involving the spleen and retroperitoneum. A diagnostic procedure was performed.

Despite their propensity to cause toxicity, nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely prescribed for older patients for painful musculoskeletal conditions, many of which are noninflammatory in nature. In some settings, simple analgesia with paracetamol (acetaminophen) or tramadol may be just as effective as NSAIDs.The benefits of therapy with NSAIDs must be weighed against their potential risks. With the anticipated growth of the elderly population, the economic implications of NSAID use in older patients are staggering. Estimates of the total cost of prescribing NSAIDs to the elderly must include the additional costs of gastroprotective agents, prophylaxis, laboratory monitoring, physician evaluations and interventions for adverse effects.Misoprostol may be cost effective as primary prophylaxis of NSAID-induced ulcer disease in some elderly patients. NSAIDs may reduce disability and improve quality of life, thereby offsetting their costs. To date, the direct, indirect and intangible cost of NSAIDs and cost offsets have not been systematically evaluated in the elderly. At this juncture, NSAIDs may be used judiciously in older patients, and misoprostol should be considered in high risk patients. Further studies to assess the economics of NSAIDs In the elderly population are warranted.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed frequently for patients with painful musculoskeletal conditions: Each year, physicians write approximately 60 million NSAID prescriptions. Because of the magnitude of patient exposure, gastrointestinal and other side effects of NSAIDs are a significant clinical concern. The mechanism of action of NSAIDs is inhibition of cyclooxygenase with secondary inhibition of proinflammatory prostaglandins. This mechanism also accounts for gastrointestinal toxic side effects of NSAIDs. Two forms of cyclooxygenase, cox-1 and cox-2, appear to be differentially inhibited by NSAIDs. Because cox-1 is responsible for maintaining normal physiologic function in gastric mucosa and other tissue, "ideal" NSAIDs would suppress only cox-2. The design of future NSAIDs-related peptic ulceration is characterized by its location in the gastric antrum, asymptomatic nature, and ability to develop through both topical and systemic effects of NSAIDs. Major risk factors for patients with rheumatoid arthritis include age >60 years, magnitude of disability, concomitant use of corticosteroids, larger doses/longer duration of NSAID treatment, and a history of peptic ulcer disease. A prophylactic strategy includes the identification of high-risk patients and, if NSAIDs must be used, the addition of misoprostol.

OBJECTIVE:To determine the effects of drug therapy (methotrexate [MTX] versus auranofin [AUR]) on radiographic progression in patients with active rheumatoid arthritis (RA).METHODS:We conducted a 9-month randomized, multicenter, double-blind trial comparing MTX and AUR. Standardized radiographs of the hands and wrists were obtained at baseline and at completion of the study. Four experienced bone radiologists graded the radiographs for erosions, joint space narrowing, erosion healing, and reparative bone formation.RESULTS:Two hundred eighty-one patients were enrolled in the study. Radiographs were available on 167 of the 183 who completed the trial. After 9 months of therapy, there was a significantly greater worsening of the erosion score in the AUR group (mean +/- SEM change of 1.67 +/- 0.4) compared with the change in the MTX group (0.60 +/- 0.3) (P = 0.040). There was also a significantly greater worsening of the joint space narrowing score in the AUR group compared with the MTX group (1.36 +/- 0.3 versus 0.42 +/- 0.2) (P = 0.007). There was no difference demonstrated between groups in healing of erosions or in reparative bone formation.CONCLUSION:The rate of radiographic progression in patients with RA, as measured by erosion score and joint space narrowing score, was demonstrated to be lower in those treated with MTX, as compared with AUR, over a 36-week period.

Weekly treatment with low-dose oral methotrexate (MTX) was compared with daily auranofin (AUR) treatment in a 36-week double-blind, randomized, multicenter study of 281 patients with active, adult-onset rheumatoid arthritis. Both treatment groups showed significant improvement by the usual measures of clinical efficacy. The response with MTX occurred earlier and was consistently greater than that with AUR. An intent-to-treat analysis showed significantly greater improvement (P less than 0.01) with MTX for painful and swollen joint counts and physician and patient global assessments of disease activity. Adverse reactions were reported more frequently in the AUR group, and more AUR-treated patients were withdrawn from the study because of toxicity. MTX was thus more effective and better tolerated than AUR in this study.

Weekly treatment with low-dose oral methotrexate (MTX) was compared with daily auranofin (AUR) treatment in a 36-week double-blind, randomized, multicenter study of 281 patients with active, adult-onset rheumatoid arthritis. Both treatment groups showed significant improvement by the usual measures of clinical efficacy. The response with MTX occurred earlier and was consistently greater than that with AUR. An intent-to-treat analysis showed significantly greater improvement ( P < 0.01) with MTX for painful and swollen joint counts and physician and patient global assessments of disease activity. Adverse reactions were reported more frequently in the AUR group, and more AUR-treated patients were withdrawn from the study because of toxicity. MTX was thus more effective and better tolerated than AUR in this study.

Inflammation of the iliopsoas bursa is a common manifestation of a wide array of inflammatory, degenerative, and traumatic musculoskeletal conditions. The clinical presentation of iliopsoas bursitis is variable, and includes pain, mass lesion, or compression syndromes of the inguinal compartment. Affected individuals frequently have underlying synovitis of the hip or a history of occupational or recreational injury. Early and accurate diagnosis is facilitated by appropriate radiographic studies.

Dietary marine lipids markedly reduce the severity of glomerulonephritis and its associated mortality in inbred strains of mice developing autoimmune disease, a model for human systemic lupus erythematosus. We report here the influence of varying the dose of menhaden oil and the timing of its administration on the mortality of female (NZB x NZW) F1 mice. After ingesting 25 wt% menhaden oil (MO) for periods of 1.5 weeks to 12 months, there was a stable content of tissue n-3 fatty acids, with total n-3 fatty acids of 28% and 35% in spleen and liver, respectively. The extent of protection from mortality was dependent on the dose of MO with marked protection at doses of 11 to 25%, marginal protection at 5.5% and no protection at 2.5% MO. Delay in the institution of MO until ages 5 or 7 months still resulted in large reductions of mortality. Conversely, institution of a MO diet from 6 weeks until ages 5 to 7 months followed by a change to beef tallow resulted in little protection. Serum levels of 4 cyclooxygenase products were reduced ranging from 26 to 76% in mice fed MO diets, compared to mice fed beef tallow, based on radioimmunoassay. The degree of reduction of mortality on different doses of MO was correlated best with tissue levels of C22:5, and levels of C20:5 and C22:6 were similar at high and low doses of MO, suggesting that levels of 22:5 may be related to the protective effects of marine lipids on autoimmune disease.

We undertook a retrospective analysis of 26 patients with X-linked hypophosphatemic osteomalacia (or rickets), whose ages ranged from 1 to 62 years and who were from 11 different kindreds, to determine the prevalence and clinical characteristics of a unique disorder of the entheses (tendons, ligaments, and joint capsules). We found a generalized involvement of the entheses, with exuberant calcification of tendon and ligament insertions and of joint capsules, in 69 per cent of the subjects. The prevalence and extent of disease increased with age but were not correlated with sex. Commonly affected sites included the hand and sacroiliac joints. Histologic evaluation in a selected patient revealed intratendinous lamellar bone but no inflammatory cells. Our observations indicate that this disorder is an integral part of X-linked hypophosphatemic osteomalacia and exhibits clinical, radiographic, and histologic characteristics that differentiate it from degenerative disorders of these tissues and seronegative spondyloarthropathies.

Martinez, Salutario M.D.; Apple, Jerry S. M.D; Harrelson, John M. M.D; Polisson, Richard M.D; Drezner, Marc M.D.