Rheumatoid Arthritis: Edmonton

Katz SJ, Russell AS. · University of Alberta Hospital, Edmonton, Alberta, Canada. · Nat Clin Pract Rheumatol. · Pubmed #18431370 No free full text.

Abstract: Glucocorticoids have good efficacy as anti-inflammatory agents but are associated with adverse effects. Buttgereit et al. have compared the efficacy of modified-release prednisone with that of standard, immediate-release prednisone for the treatment of rheumatoid arthritis. The modified-release tablets are designed to liberate the glucocorticoid approximately 4 h after ingestion, and can be taken at bedtime so that the prednisone release coincides with peaks in endogenous cortisol levels and symptoms of disease in the early hours of the morning. The authors of this study hypothesized that the modified release would improve the benefit-risk ratio of this glucocorticoid. The 12-week, multicenter, double-blind, randomized controlled trial included 251 patients who completed the study. In patients with active rheumatoid arthritis, prescription of the modified-release tablet for night-time ingestion resulted in a mean 29.2 min shorter duration of morning stiffness than in patients who received standard immediate-release prednisone tablets in the morning, and a total 44.0 min reduction in morning-stiffness duration at 12 weeks compared with baseline. The safety profiles of the modified-release and immediate-release forms of prednisone were similar.

Powell A, Davis P, Jones N, Russell AS. · University of Alberta, Edmonton, Alberta, Canada. · J Rheumatol. · Pubmed #18412310 No free full text.

Abstract: OBJECTIVE: To determine the prevalence of palindromic rheumatism (PR) compared to new-onset rheumatoid arthritis (RA). METHODS: We reviewed 145 patients that had been newly diagnosed by a rheumatologist with either RA or PR between May 2004 and May 2006. RESULTS: Of these 145 patients, 51 were diagnosed with PR and 94 with RA. There was a similar female predominance with both conditions. The average age at diagnosis of PR was 49 years as compared to 56 years for RA. CONCLUSION: Palindromic rheumatism occurs more frequently than previously recognized.

Harirforoosh S, Jamali F. · Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8. · J Appl Toxicol. · Pubmed #18344196 No free full text.

Abstract: Chronic arthritis adversely affects glomerular function and nonsteroidal anti-inflammatory drugs (NSAIDs) reduce electrolyte urinary excretion. In addition, both acute and chronic inflammations may alter clearance of drugs. We studied (a) the effects of inflammation on the renal function and pharmacokinetics of rofecoxib and meloxicam; (b) whether inflammation could exacerbate reduced electrolytes excretion changes observed with NSAIDs; and (c) the influence of inflammation on distribution of these drugs into the kidney. Single oral doses of rofecoxib (10 mg kg(-1)), meloxicam (3 mg kg(-1)) or placebo were administered to normal or pre-adjuvant arthritic rats. Blood and urine samples were collected for the measurement of plasma nitrite, BUN and creatinine. The urinary excretion of sodium and potassium was also determined. Nitrite, BUN and plasma creatinine were increased starting on day 9 in the groups with inflammation. Sodium and potassium excretion rates were not affected by inflammation. Meloxicam did not alter the electrolyte excretion in any of the groups. Rofecoxib significantly decreased sodium and potassium excretion in normal rats and potassium excretion in inflamed rats. Inflammation significantly increased plasma concentrations of rofecoxib, but not meloxicam. The ratios of the kidney:plasma concentrations were not significantly altered by inflammation following either drug. Inflammation altered kidney function, demonstrated by increases in BUN and plasma creatinine. However, it did not influence the urinary electrolytes excretion. Since we have observed similar patterns of the effect of NSAIDs on kidney under healthy and inflammatory conditions, one may conclude that inflammation does not exacerbate the adverse effect.

Allen M, Oberle K, Grace M, Russell A, Adewale AJ. · University of Alberta, Edmonton, Alberta, Canada. · Biol Res Nurs. · Pubmed #18077778 No free full text.

Abstract: This article examines the effects of elk velvet antler on joint pain and swelling, patient/physician global assessment of disease activity, functional ability, quality of life, blood levels of C-reactive protein, and adverse events in persons with stage 2 to 3 rheumatoid arthritis experiencing residual symptoms after standard treatment. Patients (N=168) were enrolled in a 6-month randomized, triple-blind, placebo-controlled clinical trial. Instruments included the Arthritis Impact Measurement Scale, the Health Assessment Questionnaire, tender and swollen joint counts, and 100 mm-length visual analogue scales, along with blood tests. There were no significant differences between groups on any measures. The pattern of change of the measures across time points was essentially the same for both groups. Although some patients reported clinical improvements in their symptoms, there were no statistically significant differences between groups. Overall, elk velvet antler does not effectively manage residual symptoms in patients with rheumatoid arthritis.

Maksymowych WP, Landewé R, Conner-Spady B, Dougados M, Mielants H, van der Tempel H, Poole AR, Wang N, van der Heijde D. · University of Alberta, Edmonton, Alberta, Canada. · Arthritis Rheum. · Pubmed #17530713 links to  free full text

Abstract: OBJECTIVE: In prospective studies, only baseline radiographic damage has been identified as an independent predictor of radiographic progression in ankylosing spondylitis (AS). Several biomarkers have been identified as independent predictors of radiographic progression in rheumatoid arthritis, however, and these may be of use in AS. This study was undertaken to analyze serologic biomarkers as predictors of radiographic progression in AS. METHODS: We measured a panel of biomarkers reflecting cartilage turnover and osteoclasis. These biomarkers were cartilage oligomeric matrix protein, human cartilage gp-39 (YKL-40), type II collagen epitopes detected by the C2C and C1,2C degradation assays and the CPII synthesis assay, aggrecan 846 epitope, osteoprotegerin, and matrix metalloproteinase 3 (MMP-3). The analysis was performed in a cohort of AS patients from the Netherlands, Belgium, and France enrolled in a longitudinal study, the Outcome Assessments in Ankylosing Spondylitis International Study. We examined 2-year radiographic progression data scored using the modified Stoke AS Spine Score (mSASSS). RESULTS: Complete data were available on 97 patients. Only the biomarkers YKL-40 and MMP-3 showed weak to moderate univariate correlation with 2-year progression. After adjustment for sex, age, disease duration, C-reactive protein level, and baseline mSASSS, only MMP-3 was significantly associated with 2-year progression (beta = 0.29, P = 0.004). Logistic regression analysis revealed MMP-3 (cutoff 68 ng/ml; odds ratio 9.4 [95% confidence interval 1.6-56]) and baseline mSASSS (cutoff 10 mSASSS units; odds ratio 18.6 [95% confidence interval 2.5-138]) as the only independent predictors of 2-year progression (cutoff 3 mSASSS units; model R(2) = 50%). MMP-3 was primarily contributory in patients who already had substantial baseline damage (>10 mSASSS units). CONCLUSION: These results indicate that MMP-3 is a significant independent predictor of radiographic progression in patients with AS, particularly in those with preexisting radiographic damage.

Maksymowych WP, Landewe R, Boers M, Garnero P, Geusens P, El-Gabalawy H, Heinegard D, Kraus VB, Krause V, Lohmander S, Matyas J, Saxne T, van der Heijde D. · Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. · J Rheumatol. · Pubmed #17343311 No free full text.

Abstract: OBJECTIVE: Recent work has shown that several soluble biomarkers, detectable in peripheral blood, synovial fluid, and/or urine, reflect remodeling of joint tissues and may therefore constitute outcome measures that reflect joint damage. Consequently, it is now desirable to begin the process of developing criteria for validation of a soluble biomarker as an outcome measure reflecting structural damage progression in trials of disease-modifying therapies for rheumatoid arthritis (RA) and spondyloarthritis (SpA). Our objective was to develop validation criteria for a soluble biomarker to be regarded as a valid biomarker reflecting radiological endpoints in RA and SpA clinical trials. METHODS: A special interest group was established comprising investigators with expertise in soluble biomarker assay development as well as in outcomes research. This project was initiated by means of a Delphi consensus exercise. A list of draft criteria was first generated following a review of a US National Institutes of Health (NIH) 2000 white paper (available at: http://www.niams.nih.gov/ne/oi/ oabiomarwhipap.htm) that focused on biomarkers in OA, and these were organized under subject headings relevant to the OMERACT filter: truth, discrimination, and feasibility. Additional criteria were solicited from the working group. This was followed by 3 rounds of voting. RESULTS: A list of 31 criteria was generated prior to voting. The first 2 rounds of voting resulted in cumulative agreement that 19 criteria be retained and 4 discarded, while discrepancies were recorded for 8 criteria. In the third round of voting, cumulative agreement was achieved to retain 5 of the 8 discrepant criteria, so that the final list included 24 criteria. CONCLUSION: A draft set of criteria for validation of a soluble biomarker to be regarded as reflecting radiological damage endpoints in clinical trials has been proposed on the basis of consensus.

Klein D, MacDonald A, Drummond N, Cave A. · Continuous Professional Learning, Faculty of Medicine and Dentistry, 2J3 Walter Mackenzie Centre Edmonton, Alberta T6G 2R7 Canada. · Fam Pract. · Pubmed #17035286 links to  free full text

Abstract: INTRODUCTION: Cyclo-oxygenase-2 inhibiting (COXIB) anti-inflammatories have been the drug class prescribed for a large number of cases of musculoskeletal (MSK) disorders in Canada over the past 5 years. The Alberta Improvements for MSK Disorders (AIMS) initiative sought to better understand the COXIB prescribing situation by funding several studies. The objective of this qualitative study was to determine the factors underlying primary care physicians' medication prescribing behaviour during an office visit for an MSK disorder, with particular emphasis on the prescribing of COXIBs. METHODS: The target respondents were Alberta primary care physicians chosen from a stratified random sample to meet a wide range of characteristics. Individual, semi-structured interviews were used to assess decision pathways in four real cases chosen by the physician. A total of 19 interviews were conducted and analysed using an analytic inductive approach. RESULTS: Factors judged as being important to decision pathways in relation to COXIB prescribing for MSK disease included safety, patient characteristics, affordability to patients, availability of samples, drug company marketing practices, habit formation, time contstraints, previous clinical experience of doctors and/or patient with certain drugs and doctors' perception of absolute versus relative risk. Interpretation. Most physicians preferentially prescribed COXIBs subsequent to a complicated, multifactorial, but essentially patient-centred, decision-making process.

Russell AS, Wallenstein GV, Li T, Martin MC, Maclean R, Blaisdell B, Gajria K, Cole JC, Becker JC, Emery P. · 562 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, T6G 2S2 Canada. · Ann Rheum Dis. · Pubmed #16984942 No free full text.

Abstract: OBJECTIVE: To examine the impact of added abatacept treatment on health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX). METHODS: The impact of abatacept treatment on HRQoL was examined in a longitudinal, randomised double blind, placebo controlled clinical trial. Effects of treatment on HRQoL were examined using repeated measures analysis of covariance and comparing rates of change in HRQoL across treatment groups. The relationship between American College of Rheumatology (ACR) clinical markers and disease duration with changes in HRQoL indicators was also examined. Finally, a responder analysis was used to examine the percentage of patients who improved by 0.5 SD in 12 months or who reached the normative levels seen in the US general population. RESULTS: Statistically significant improvements in the abatacept group relative to controls were observed across a range of HRQoL measures, including physical function, fatigue, all eight domains of the SF-36, and the physical and mental component summaries (PCS and MCS). Improvements were seen as early as day 29 for fatigue and for five out of eight SF-36 domains. By day 169, all HRQoL measures were significantly better with abatacept than with placebo. HRQoL gains were associated with greater ACR clinical improvement, and the effects were consistent for patients with different disease duration. A significantly greater percentage of patients treated with abatacept reached normative levels of PCS, MCS, physical functioning, and fatigue compared with patients treated with MTX alone. CONCLUSION: Combined abatacept and MTX treatment produces significant improvements across a wide range of HRQoL domains in patients with RA.

Russell AS, Devani A, Maksymowych WP. · Department of Medicine, Division of Rheumatology, University of Alberta, Edmonton, Alberta, Canada. · J Rheumatol. · Pubmed #16724377 No free full text.

Abstract: OBJECTIVE: To determine whether the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies at presentation is of prognostic value in patients with palindromic arthritis. METHODS: Stored sera, taken around the time of presentation from patients with palindromic arthritis, where available, were assessed for anti-CCP antibodies, and results were correlated with subsequent clinical outcome. RESULTS:Twenty-nine of 61 patients had progressed to rheumatoid arthritis after a mean followup of 5.4 years; 83% of these had had anti-CCP antibodies in their baseline sera. CONCLUSION: The sensitivity/specificity and likelihood ratios for CCP antibodies were better than rheumatoid factor in predicting outcome.

Chung CP, Russell AS, Segami MI, Ugarte CA. · Division of Rheumatology, University of Alberta, Edmonton, Alberta, Canada. · Rheumatol Int. · Pubmed #14628151 No free full text.

Abstract: OBJECTIVE: The aim of this study was to determine the difference between bone mineral density (BMD) of rheumatoid arthritis (RA) patients on low-dose prednisone and matched RA patients without prior systemic corticosteroid therapy. METHODS: Ninety patients attending our clinics and receiving 10 mg/day of prednisone or less for at least the previous 3 consecutive months were studied. The control group comprised 90 selected RA patients without corticosteroid therapy matched for age, race, gender, disease duration, use of methotrexate, postmenopause, and Health Assessment Questionnaire score. The BMD was measured using dual X-ray absorptiometry. RESULTS: Patients on prednisone had lower BMD than controls (0.94 +/- 0.17 vs 0.96 +/- 0.17 for L2-4 and 0.73 +/- 0.14 vs 0.76 +/- 0.16 for femoral neck), but these differences were not statistically significant (P > 0.05). In post hoc analysis, postmenopausal women on prednisone had more bone loss in femoral neck than controls (0.68 +/- 0.13 vs 0.74 +/- 0.15). CONCLUSION: Bone mineral density was not significantly reduced by low-dose prednisone in this diverse group of RA patients. A reduction in hip BMD was seen in postmenopausal women on prednisone.

Sattari S, Dryden WF, Eliot LA, Jamali F. · Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8. · Br J Pharmacol. · Pubmed #12839868 links to  free full text

Abstract: 1. Rheumatoid arthritis reduces verapamil oral clearance thereby increases plasma concentration of the drug. This coincides with reduced drug effects through an unknown mechanism. 2. The effect of interferon-induced acute inflammation on the pharmacokinetics and electrocardiogram of verapamil (20 mg kg(-1), p.o.) and nifedipine (0.1 mg kg(-1), i.v.) was studied in Sprague-Dawley rats. 3. The effect of both acute and chronic inflammation on radioligand binding to cardiac L-type calcium channels was also investigated. 4. Acute inflammation resulted in increased plasma concentration of verapamil but had no effect on that of nifedipine. Verapamil binding to plasma proteins was unaffected. 5. As has been reported for humans, the increased verapamil concentration coincided with a reduction in the degree to which PR interval is prolonged by the drug. The effect of nifedipine on PR interval was also reduced by inflammation. 6. Maximum binding of (3)H-nitrendipine to cardiac cell membrane was significantly reduced from 63.2+/-2.5 fmol mg(-1) protein in controls to 46.4+/-2.0 in acute inflammation and from 66.8+/-2.2 fmol mg(-1) protein in controls to 42.2+/-2.0 in chronic inflammation. 7. Incubation of the normal cardiac cell membranes with 100 and 1000 pg ml(-1) of rat tissue necrosis factor-alpha did not influence the binding indices to the calcium channels. 8. Our data suggest that the reduced calcium channel responsiveness is because of altered binding to channels.

Russell AS, Conner-Spady B, Mintz A, Maksymowych WP. · Rheumatic Disease Unit, University of Alberta, Edmonton, Alberta Canada. · J Rheumatol. · Pubmed #12734886 No free full text.

Abstract: OBJECTIVE: We used a variety of health status measures in 2 groups of patients with rheumatoid arthritis (RA) to assess both the smallest distinguishable difference and the relative responsiveness to change of these measures, when used in clinical practice. METHODS: Two groups of patients were studied. Group 1: 24 patients with stable RA tested on 2 occasions; Group 2: 60 patients receiving methotrexate tested before and 14 weeks after treatment with infliximab. Assessments were made with self-completed questionnaires: the modified Health Assessment Questionnaire, Medical Outcomes Study Short Form-36 [SF-36 (SF-6D)], EuroQol, and, in some, the standard gamble. Group 2 also had joint counts, and measures of erythrocyte sedimentation rate, C-reactive protein, and hemoglobin. RESULTS: The limits-of-agreement (Bland-Altman) approach had greater confidence intervals (CI) than did CI based on +/- 2 standard errors of the measurement. Improvement with infliximab could be determined with all measures, however, but the standard gamble seemed least responsive to change. CONCLUSION: The various measures had different degrees of responsiveness, but with all it was possible to show improvement in Group 2 compared to Group 1. There was a closer association of the patient centered measures of improvement with changes in pain score than with joint counts.

Maksymowych WP, Suarez-Almazor ME, Buenviaje H, Cooper BL, Degeus C, Thompson M, Russell AS. · Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. · J Rheumatol. · Pubmed #12415587 No free full text.

Abstract: OBJECTIVE: Palindromic rheumatism (PR) is an episodic arthropathy that may precede typical rheumatoid arthritis (RA), although pathogenetic relationships between these disorders remain unclear. The predictive value for those immunogenetic risk factors implicated in RA for disease progression in PR remains to be established. A previous retrospective analysis from our group has implicated rheumatoid factor in disease progression. Our objective was to determine the contribution of HLA and cytokine gene polymorphisms implicated in RA to predisposition to PR and to progression of PR to chronic joint inflammation. METHODS: We studied 147 patients with PR seen in a tertiary referral center; 87 were selected retrospectively from the period 1986-96 using a structured selection process and 60 were selected prospectively in the period 1997-2001. Comparison groups included 149 patients with RA and 149 ethnically matched controls. Typing for HLA-DRB1 alleles and HLA-DRB1-04 subtypes was performed following polymerase chain reaction (PCR) amplification using sequence-specific primers (SSP). Cytokine genotypes were ascertained following PCR-SSP with and without digestion with restriction enzymes. Time-adjusted survival analysis (Kaplan-Meier) and multivariate logistic regression were used to assess the independent contribution of immunogenetic markers in assessing progression of PR to chronic joint inflammation. RESULTS: Thirty-one percent of patients progressed to connective tissue disease after a mean of 10.6 (retrospective group) and 3.9 (prospective group) years. A significantly increased prevalence of the shared epitope (SE) allele was noted in patients with PR (65%) versus controls (39%) (OR 2.9, 95% CI 1.8-4.6, p < 0.001). This primarily reflected increased prevalence of the DRB1-0401 and 0404 and not DRB1-01 alleles. A weak contribution to disease susceptibility was also noted with carriage of the IL4 promoter -590T (OR 1.8, 95% CI 1.1-3.0, p = 0.02) and IL4 intron 3 RP1 (OR 1.7, 95% CI 1.1-2.9, p = 0.03) alleles. The TNFa +489A allele was associated with RA (OR = 2.7, 95% CI 1.5-5.1, p = 0.001) in both SE+ and SE- patients, but not with PR. Time-adjusted and multivariate Cox regression analysis revealed that only homozygosity for SE alleles was a significant independent risk factor for disease progression to chronicity in PR (hazard ratio 2.9, 95% CI 1.2-6.9, p = 0.02). However, none of 8 patients homozygous for SE- DRB1 XP4n alleles developed chronic disease after 10 years of followup (p = 0.07). CONCLUSION: The immunogenetic risk profile for PR resembles that for RA, indicating that PR is likely not an independent entity. A significant gene dose effect for SE alleles is operative in determining risk for progression from PR to RA.

Maksymowych WP, Jhangri GS, Aspeslet L, Abel MD, Trepanier DJ, Naicker S, Freitag DG, Cooper BL, Foster RT, Yatscoff RW. · Department of Medicine, University of Alberta, Edmonton, Canada. · J Rheumatol. · Pubmed #12180723 No free full text.

Abstract: OBJECTIVE: To examine the efficacy and toxicity of ISA(TX)247, a novel calcineurin inhibitor, in comparison to cyclosporine (cyclosporin A, CSA) and placebo in established collagen induced arthritis. ISA(TX)247 has up to 3-fold greater potency than CSA in an in vitro whole blood calcineurin inhibition assay and in in vivo solid organ and cell transplantation models. Phase I clinical trials show no discernible nephrotoxicity. METHODS: Type II collagen immunized DBA/Lac J mice with established arthritis were randomized to treatment with ISA(TX)247 (125/250/500 microg/mouse), CSA (250/500 microg/mouse), or drug vehicle, by daily intraperitoneal injection for 10 days from the onset of clinical arthritis. RESULTS: A significant dose dependent reduction in clinical severity was observed in ISA(TX)247 treated but not in CSA treated animals 10 days after the onset of established arthritis, and when examined by area under the curve analysis during the treatment period. Significant improvement in paw swelling (p < 0.001), synovial histology (p < 0.001), and articular cartilage damage scores (p = 0.002) was also noted in ISA(TX)247 treated animals, even in the 125 pg dose group (p = 0.03 for paw swelling and synovial histology). By comparison, CSA had no significant effect on either synovial inflammation or articular cartilage damage. ISA(TX)247 (500 microg dose group) was the only treatment to significantly decrease the development of proximal interphalangeal joint erosions (p < 0.05). A significant reduction in Type II collagen antibody titer was noted in ISA(TX)247 animals in both 250 microg (p = 0.02) and 500 microg (p = 0.004) dosage groups, but only in the 500 microg group for CSA (p = 0.004). Treatment was well tolerated, with no significant toxicity in ISA(TX)247 groups. CONCLUSION: ISA(TX)247 demonstrates efficacy and safety in the treatment of established collagen induced arthritis. Together with its improved potency and nephrotoxicity profile in comparison to CSA, this agent warrants further clinical investigation in autoimmune disease. Phase II studies in rheumatoid arthritis have been initiated.

Yacyshyn BR, Crooke ST. · Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada. · Dis Colon Rectum. · Pubmed #11584192 No free full text.

Abstract: Since the identification of the double-stranded DNA helix by Watson and Crick in 1953, the knowledge of nucleotide structure and function has been an important potential tool in the study and therapy of disease. There is recent clinical evidence that antisense oligonucleotides may be important therapeutic compounds in the clinical therapy of a range of diseases, including infection (viruses and bacteria), oncology, and inflammation. Our laboratory-based understanding of antisense oligonucleotide activity has provided a foundation for their use in several human diseases. Potentially relevant applications include inflammatory bowel disease therapy, psoriasis, transplantation, rheumatoid arthritis, cytomegalovirus retinitis, hepatitis C, and solid tumor therapy. Here we will outline these applications as well as our ongoing clinical trials for Crohn's disease.

Gervais RO, Russell AS, Green P, Allen LM, Ferrari R, Pieschl SD. · Department of Rheumatic Diseases, University of Alberta, Canada. · J Rheumatol. · Pubmed #11508597 No free full text.

Abstract: OBJECTIVE: To examine whether symptom exaggeration is a factor in complaints of cognitive dysfunction using 2 new validated instruments in patients with fibromyalgia (FM). METHODS: Ninety-six patients with FM and 16 patients with rheumatoid arthritis (RA) were administered 2 effort or symptom validity tests designed to detect exaggerated memory complaints as part of a battery of psychological tests and self-report questionnaires. RESULTS: A large percentage of patients with FM who were on or seeking disability benefits failed the effort tests. Only 2 patients with FM who were working and/or not claiming disability benefits and no patient with RA scored below the cutoffs for exaggeration of memory difficulties. CONCLUSION: This study illustrates the importance of assessing for exaggeration of cognitive symptoms and biased responding in patients with FM presenting for disability related evaluations.

Russell AS, Morrison RT. · Heritage Medical Research Centre, University of Alberta, Edmonton, Canada. · Scand J Rheumatol. · Pubmed #11252690 No free full text.

Abstract: BACKGROUND: The study was done to determine whether the new SCORE (Simple Calculated Osteoporosis Risk Estimation) index might reduce the utilization of bone mineral density (BMD) measurement. METHODS: 989 consecutive patients who were referred by a range of physicians for BMD assessments at one of two clinics had a SCORE index constructed. Approximately 95% of the subjects were Caucasian. The index is based on only 6 factors: age, previous fractures, rheumatoid arthritis, estrogen use, weight, and race. RESULTS: All but 1 (0.1%) of those with a femoral neck BMD T-score of < -2.5 had an abnormal SCORE index. However, its specificity was relatively low, since two thirds of those individuals also with an abnormal index had a T-score of > -2.5. One percent false negatives were also seen in the lumbar spine. CONCLUSION: The SCORE index correctly predicted those individuals who did not have an osteoporotic T-score. It was of the most value in the < 60 age group. DISCUSSION: The precise role of BMD measurement in the assessment and management of individuals possibly at risk for osteoporosis remains controversial. Our results suggest that the prior use of the SCORE index by the referring physicians to screen the patients sent for BMD measurement would have allowed them to exclude over 20% of the patients referred for assessment, and therefore reduce the need and cost of BMD measurement. The proportion of individuals who had a normal SCORE index, and would have been screened out, was 43% in the under 60 year age group, but in the 65 and over age group it provided no additional information to help with, for example, the National Osteoporosis Foundation (NOF) guidelines.

Ashour M, Salem S, Hassaneen H, el-Gadban H, Elwan N, Awad A, Basu TK. · Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada. · Int J Food Sci Nutr. · Pubmed #10953752 No free full text.

Abstract: The aim of this study was to examine both enzymatic and non-enzymatic antioxidant status in a select group of children with juvenile rheumatoid arthritis (JRA), living in Cairo, Egypt. The plasma concentrations of albumin, ceruloplasmin, vitamin C, vitamin E as well as erythrocyte superoxide dismutase and whole blood glutathione peroxidase activities were all significantly decreased in the presence of JRA compared to those without JRA. Unlike these antioxidant factors, vitamin A and its carrier (e.g. retinol binding protein), which have very little or no antioxidant property, remained unaffected by JRA. These results suggest that the children with JRA are subject to oxidative stress.

Gonzalez-Lopez L, Gamez-Nava JI, Jhangri G, Russell AS, Suarez-Almazor ME. · Department of Public Health Sciences, University of Alberta, Edmonton, Canada. · J Rheumatol. · Pubmed #10648016 No free full text.

Abstract: OBJECTIVE: To determine whether the use of antimalarials is associated with a reduction in the risk of developing rheumatoid arthritis (RA) or other connective tissue diseases in patients with palindromic rheumatism. METHODS: We conducted a retrospective cohort study based on a review of medical records to evaluate the outcome of patients with palindromic rheumatism referred to an academic center from 1986 to 1996: 113 patients complied with the selection criteria, including diagnostic criteria for palindromic rheumatism and onset of disease since 1980. After adjusting for potential confounders, Kaplan-Meier methods and Cox regression models were used to estimate the risk of developing RA or other connective tissue disease in patients who had received antimalarials compared to those who had not. RESULTS: Age of disease onset was 40+/-12 yrs, and mean disease duration 4.8+/-4 yrs; two-thirds of the patients were female. Sixty-two (55%) patients received antimalarials, for a mean duration of therapy of 28 mo. Thirty-three (29%) patients developed RA, 3 developed systemic lupus, and 4 developed other connective tissue diseases. Twenty (32%) patients in the antimalarial group developed a secondary disease, compared to 20 (39%) who did not receive therapy. Statistically significant differences were observed comparing time to event in both groups. The estimated median time to development of a chronic disease was 162 months in treated and 56 months in untreated patients. After adjusting for other variables in the Cox regression models, significant risk reduction in the development of a secondary disease was observed for antimalarial use (hazard ratio = 0.24; 95% CI 0.09-0.61). For RA, the risk reduction was 0.19 (95% CI 0.07-0.57). We conducted a sensitivity analysis around our censoring estimates. The risk reduction remained statistically significant, with 0.36 for RA and 0.41 for RA or other connective tissue disease. CONCLUSION: Use of antimalarials in patients with palindromic rheumatism is associated with a reduction in the risk of developing subsequent RA or other connective tissue disease.

Galindo-Rodriguez G, Aviña-Zubieta JA, Russell AS, Suarez-Almazor ME. · Department of Public Health Sciences, University of Alberta, Edmonton, Canada. · J Rheumatol. · Pubmed #10555887 No free full text.

Abstract: OBJECTIVE: To evaluate the longterm effectiveness of disease modifying antirheumatic drugs (DMARD) in an inception cohort of patients with rheumatoid arthritis (RA) seen by rheumatologists. METHODS: We performed a retrospective audit of the records of patients with onset of RA between January 1985 and June 1994. Charts were reviewed from the time of diagnosis to the last consult. Survival analysis was performed using Kaplan-Meier and Cox proportional hazard regression to adjust for potential confounders. RESULTS: A total of 2296 DMARD therapies were analyzed. Roughly half were started within 2 years of disease onset. By 16 months, 50% of the DMARD therapy courses had been discontinued, and after 4.5 years 75% had been discontinued. Over all, methotrexate (MTX) had the highest probability of continuation. After roughly 3 years 50% of patients were still receiving MTX, compared to one-third of patients who received antimalarials or intramuscular gold, 30% D-penicillamine, 25% sulfasalazine, and 18% oral gold. After 6 years, when considering all DMARD together, only 20% of the therapies had not been discontinued, with no substantial differences between drugs. Toxicity from gold compounds occurred within the first 18 months of therapy and stabilized thereafter. For MTX, withdrawals due to toxicity continued throughout therapy. CONCLUSION: This is the largest observational study examining the longterm termination rates of DMARD in patients followed from the time of their initial consult. Our results confirm previous reports of short therapeutic times, even for patients treated early in the course of their disease. MTX appears to be the best drug within the first 5 years of disease. These differences, however, decrease in the longer term. It is unclear whether the results observed for MTX within the first years of therapy translate to better health status in the longer term when compared to other DMARD.

Vaile JH, Mathers DM, Ramos-Remus C, Russell AS. · Department of Medicine, University of Alberta, Edmonton, Canada. · J Rheumatol. · Pubmed #10332984 No free full text.

Abstract: OBJECTIVE: To assess the sensitivity to change of general quality of life indices in patients with rheumatic diseases, we assessed the performance of 4 instruments in patients with carpal tunnel syndrome (CTS) treated with local injection of corticosteroid. METHODS: We administered visual analog scales (VAS) incorporating measures of overall well being, discomfort, frequency of symptoms, and physical activity; 2 generic instruments [the Nottingham Health Profile (NHP), the Medical Outcomes Study 36 Item Short Form (SF-36)]; and a rheumatoid arthritis-specific instrument, the modified Health Assessment Questionnaire, at baseline and one month after injection. We assessed 30 patients. RESULTS: VAS were significantly better at determining improvement than the generic instruments or the arthritis specific instrument. For the generic scales, only the pain scales of NHP and SF-36 showed moderate or greater change using standardized response means. CONCLUSION: These results suggest that standard tools may not be sufficiently sensitive to show clinically significant change in this common rheumatological problem.

Gonzalez-Lopez L, Gamez-Nava JI, Jhangri GS, Ramos-Remus C, Russell AS, Suarez-Almazor ME. · Healthcare Quality and Outcomes Research Centre, Department of Public Health Sciences, University of Alberta, Edmonton, Canada. · J Rheumatol. · Pubmed #10090159 No free full text.

Abstract: OBJECTIVE: Palindromic rheumatism is characterized by attacks of acute arthritis of short duration. In the long term, a substantial proportion of patients will develop rheumatoid arthritis (RA) or other connective tissue diseases, but the determinants of subsequent chronic disease have not been adequately established. We identify clinical prognostic factors for the development of RA and other connective tissue diseases in patients with palindromic rheumatism in a retrospective cohort study. METHODS: The medical records of 4900 patients with arthritis referred from 1986 to 1996 to 3 rheumatologists at an academic center were reviewed. One hundred sixty patients were diagnosed as having palindromic rheumatism. After review, 127 complied with diagnostic criteria for palindromic rheumatism. Disease duration was estimated as time of first attack until the last consultation, or the development of RA or other connective tissue disease. Survival analysis including Cox regression was used to identify clinical variables associated with the risk of developing RA or other connective tissue disease, adjusting for varying disease duration. RESULTS: Sixty-five percent of the patients were female. Age at onset was 40+/-12 years. Mean disease duration was 6+/-6 years, and mean followup by the rheumatologists was 40+/-45 months. Joints more frequently affected were wrist, knee, and metacarpophalangeal. Forty-three patients (34%) subsequently developed a connective tissue disease including 36 (28%) RA, 3 (2%) systemic lupus erythematosus, and 4 (3%) other connective tissue diseases. In the final Cox regression model the hazard ratio for development of a connective tissue disease in the presence of a positive rheumatoid factor (RF) was 2.9 (p = 0.002), for proximal interphalangeal (PIP) joint involvement 2.4 (p = 0.02), for wrist involvement 2.5 (p = 0.05), for female sex 2.2 (p = 0.05), and for age at onset 1.03 (per year) (p = 0.001). Female patients with positive RF and involvement of the hands had an 8-fold risk of developing disease, compared with patients with one or fewer of these features. CONCLUSION: Positive RF and early involvement of the wrist and PIP joints predict the subsequent development of RA or other connective tissue disease in patients with palindromic rheumatism, and identify a group of patients at increased risk.