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Objective: To determine how serologic responses to coronavirus disease 2019 (COVID-19) vaccination and infection in immune-mediated inflammatory disease (IMID) are affected by time since last vaccination and other factors., Methods: Post-COVID-19 vaccination, data, and dried blood spots or sera were collected from adults with rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and spondylarthritis, and psoriasis and psoriatic arthritis. The first sample was collected at enrollment, then at 2 to 4 weeks and 3, 6, and 12 months after the latest vaccine dose. Multivariate generalized estimating equation regressions (including medications, demographics, and vaccination history) evaluated serologic response, based on log-transformed anti-receptor-binding domain (RBD) IgG titers; we also measured antinucleocapsid (anti-N) IgG., Results: Positive associations for log-transformed anti-RBD titers were seen with female sex, number of doses, and self-reported COVID-19 infections in 2021 to 2023. Negative associations were seen with prednisone, anti-tumor necrosis factor agents, and rituximab. Over the 2021-2023 period, most (94%) of anti-N positivity was associated with a self-reported infection in the 3 months prior to testing. From March 2021 to February 2022, anti-N positivity was present in 5% to 15% of samples and was highest in the post-Omicron era, with antinucleocapsid positivity trending to 30% to 35% or higher as of March 2023. Anti-N positivity in IMID remained lower than Canada's general population seroprevalence (> 50% in 2022 and > 75% in 2023). Time since last vaccination was negatively associated with log-transformed anti-RBD titers, particularly after 210 days., Conclusion: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when > 6 months has elapsed since last COVID-19 vaccination/infection., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: To understand how people with chronic immune-mediated inflammatory diseases (IMIDs) trade off the benefits and risks of coronavirus disease 2019 (COVID-19) vaccine options., Methods: We conducted an online discrete-choice experiment in people with IMIDs to quantify the relative importance (RI) of attributes relevant to COVID-19 vaccination. Participants were recruited between May and August 2021 through patient groups and clinics in Canada, and completed 10 choices where they selected 1 of 2 hypothetical vaccine options or no vaccine. The RI of each attribute was estimated and heterogeneity was explored through latent class analysis., Results: The survey was completed by 551 people (89% female, mean age 46 yrs) with a range of IMIDs (inflammatory bowel disease [48%], rheumatoid arthritis [38%], systemic lupus erythematosus [16%]). Most had received 1 (94%) or 2 (64%) COVID-19 vaccinations. Across the ranges of levels considered, vaccine effectiveness was most important (RI = 66%), followed by disease flare (21%), rare but serious risks (9%), and number/timing of injections (4%). Patients would accept a risk of disease flare requiring a treatment change of ≤ 8.8% for a vaccine with a small absolute increase in effectiveness (10%). Of the 3 latent classes, the group with the greatest aversion to disease flare were more likely to be male and have lower incomes, but this group still valued effectiveness higher than other attributes., Conclusion: Patients perceived the benefits of COVID-19 vaccination to outweigh rare serious risks and disease flare. This supports COVID-19 vaccine strategies that maximize effectiveness, while recognizing the heterogeneity in preferences that exists., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes., Methods: We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively., Results: Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01)., Conclusion: The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.

Objective: Persistent systemic lupus erythematosus (SLE) disease activity is associated with increased morbidity and mortality. In a multicenter cohort of patients with prevalent SLE, we described persistence, patterns, and predictors of change in disease activity over time., Methods: Based on SLE Disease Activity Index (SLEDAI)-2K scores at cohort entry, patients were classified into 4 groups: low (score < 4; LOW), moderate (4 to < 6; MOD), moderately high (6 to ≤ 10; MHIGH), and very high (> 10; VHIGH). Multivariable linear and longitudinal mixed linear regression models were used to identify predictors of change over time in SLEDAI-2K., Results: There were 2019 participants, with declining followup data over 5 years (1326, 580, 274, 186, and 148 patients, respectively). At cohort entry, mean (± SD) age was 42 (± 17) years, disease duration 11 (± 10) years, and 90% were female. The 4 groups included 44% LOW (n = 891), 20% MOD (n = 400), 22% MHIGH (n = 442), and 14% VHIGH (n = 286); therefore, 36% had clinically important SLE activity. The proportion of patients in the LOW group at entry who moved to a higher activity level varied from 30% (167/557) at 1 year, to 49% (41/83) at 3 years, and 54% (30/56) at 5 years. Among 181 patients with MOD to VHIGH entry activity and 3 years of followup, 116 (64.1%) remained active. In all analyses, only higher SLEDAI-2K at cohort entry remained a significant predictor of higher SLEDAI-2K in subsequent years., Conclusion: Higher SLEDAI-2K at study entry was the single major independent predictor of higher SLEDAI-2K over time, reflecting frequent persistence of active disease, even in patients with longstanding disease. This highlights gaps in the optimal treatment of SLE.

Objective: To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada., Methods: Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online., Results: There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination., Conclusion: These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.

Objective: To evaluate the diagnosis, monitoring, and treatment of systemic lupus erythematosus (SLE) in Canada., Methods: A 63-question electronic survey was developed with the Canadian Rheumatology Association and others. Descriptive analyses of responses were performed., Results: Survey respondents (n = 175) reported varying practices in the diagnosis, monitoring, and treatment of SLE. Performance of laboratory investigations for diagnosis and monitoring varied, with 78% of responders performing them at least every 6 months. Validated measures of SLE disease activity and damage were not commonly used. Most common first-line agents besides steroids for induction therapy for class III or IV lupus nephritis included intravenous cyclophosphamide and mycophenolate mofetil. Antimalarial use was common, with 96% of respondents using these in active skin disease. Over 60% of respondents indicated that 80-100% of their patients were taking antimalarials, while another 25% indicated they used these drugs in up to 80% of their patients. There were 71% of responders who reported completing frequent (6-12 mos) ophthalmology screening in patients taking antimalarials. Biologics were infrequently used. Responders were more likely to stop azathioprine and chloroquine than hydroxychloroquine in pregnant patients with SLE. Other aspects of routine care including vaccination and cardiovascular risk management varied considerably. The majority (80%) agreed that a dedicated multidisciplinary care team would improve SLE care., Conclusion: Considerable practice variation in SLE management was noted. This may help inform future recommendations for the diagnosis, monitoring, and treatment of SLE in Canada.

Objective: To assess lung cancer risk in systemic lupus erythematosus (SLE), relative to demographics, drug exposures, smoking, and disease activity., Methods: We analyzed data from 14 SLE cohorts. We calculated adjusted HR estimates for lung cancer in SLE, relative to demographics, smoking, time-dependent medication exposures, and cumulative disease activity [mean adjusted SLE Disease Activity Index (SLEDAI) scores]. This project was approved by the ethics boards of all participating institutions, including the Institutional Review Board of the McGill University Health Centre. The ethics approval number for the Cancer Risk study is GEN-06-031., Results: Within these 14 SLE cohorts, 49 incident lung cancers occurred. Among lung cancer cases, 59.0% were in the highest SLEDAI quartile at baseline versus 40.8% of lung cancer-free SLE controls. The vast majority (84.2%) of SLE lung cancer cases were ever-smokers at baseline, versus 40.1% of those without lung cancer. In adjusted models, the principal factors associated with lung cancer were ever smoking (at cohort entry) and current age. Estimated adjusted effects of all drugs were relatively imprecise, but did not point toward any drug exposures as strong lung cancer risk factors., Conclusion: We saw no clear evidence for drugs as a trigger for lung cancer risk in SLE, although drug risk estimates were relatively imprecise. Smoking may be the most significant modifiable lung cancer risk factor in SLE.

Objective: In our region in Quebec, Canada, access to rheumatologists is very limited. Sharing followup of stable patients with their primary care physicians (PCP) could increase access to rheumatologists. In our study, we assessed the feasibility and potential benefits of sharing followup of inflammatory arthritis (IA) patients with their PCP., Methods: We reviewed the clinical records of 300 patients with peripheral arthritis who presented at our rheumatology outpatient clinic between July and October 2015. We distributed questionnaires to their treating rheumatologist, asking whether a PCP could participate in the followup of the patient and whether there were any factors that would prevent shared followup. We also distributed questionnaires to PCP to assess their level of comfort in participating in the followup care of patients with arthritis., Results: Chart review was completed on 300 patients. There was no treatment modification in 49% of the cases, and 38% of the visits were deemed unnecessary by the attending rheumatologist. We found that 74% of PCP were very interested in sharing the arthritis followup care of their patients. According to PCP, the main barriers to shared followup were treatment with biological agents, active disease, and need for infiltrations. Main organizational barriers were the lack of rheumatologist availability to see patients urgently (46%) and the lack of clear guidelines for the management of IA (58%)., Conclusion: Up to 38% of peripheral IA visits to a rheumatologist could have been prevented and done by a PCP. In our department, this represented up to 19 followup visits per week that could have been avoided by involving a PCP.

Objective: Microparticles (MP) are small extracellular vesicles present in body fluids. MP originate from different cellular lineages, principally from platelets in blood, and may expose phosphatidylserine (PS). In systemic lupus erythematosus (SLE), MP harbor immunoglobulin G (IgG), thereby forming MP-containing immune complexes (mpIC). We aimed to verify an association between SLE disease activity, damage, and surrogate markers of atherosclerosis and MP harboring IgG, taking into account the platelet origin and PS exposure of MP., Methods: MP expressing surface IgG, platelet antigen (CD41+), and PS were quantified using flow cytometry in plasma of 191 women with SLE. Carotid ultrasounds (US) were available in 113 patients. Spearman correlation analysis was used to analyze whether levels of MP were associated with the following outcomes: SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and carotid US plaques and intima-media thickness (CIMT) as surrogates for vascular damage., Results: We found CD41+ MP harboring IgG present in SLE. A positive correlation was found between SLEDAI-2K and levels of CD41+ MP harboring IgG and exposing (p = 0.027) and non-exposing PS (p = 0.001). Conversely, SDI (p = 0.024) and CIMT (p = 0.016) correlated with concentrations of CD41- MP harboring IgG and exposing PS. Associations were independent of low-density lipoprotein cholesterol level, body mass index, and antimalarial drug use., Conclusion: Different subtypes of mpIC are produced in SLE and are associated with distinct clinical characteristics such as disease activity and vascular damage. The assessment of MP subtypes might serve for the design of predictive markers of disease activity and vascular damage in patients.

Objective: Disease-modifying antirheumatic drugs (DMARD) have the greatest effect when initiated early. We evaluated the influence of early exposure to DMARD on time to joint replacement surgery among patients with incident rheumatoid arthritis (RA)., Method: Using a common protocol, we undertook 2 independent population-based cohort studies of patients with incident RA aged 66 years or older in Ontario (ON) and Quebec (QC) covering the period 2000-2013. We used Cox proportional hazards regression with time-dependent variables measuring duration of drug use in the first year, separately for methotrexate (MTX) and other DMARD, adjusting for baseline demographics, clinical factors, and other potentially confounding drug exposures. Our outcome measure was any joint replacement derived from standardized procedure codes. Adjusted HR and 95% CI were estimated., Results: Among 20,918 ON and 6754 QC patients with RA followed for a median of 4.5 years, 2201 and 494 patients underwent joint replacement surgery for crude event rates of 2.0 and 1.4 per 100 person-years, respectively. Greater cumulative exposure to MTX (HR 0.97, 95% CI 0.95-0.98) and other DMARD (HR 0.98, 95% CI 0.97-0.99) in the first year after diagnosis was associated with longer times to joint replacement in ON, corresponding to a 2-3% decrease in the hazard of surgery with each additional month of early use. Similar results were observed in QC., Conclusion: Greater duration of exposure to DMARD soon after RA diagnosis was associated with delays to joint replacement surgery in both provinces. Early intensive treatment of RA may ultimately reduce demand for joint replacement surgery.

Objective: To examine perceived independence, overprotection, and support, and their association with the employment participation of young adults with rheumatic disease., Methods: One hundred and forty-three young adults, ages 18 to 30 years, with systemic lupus erythematosus (54.5%) and juvenile arthritis (45.5%) completed a 30-min online questionnaire of their work and education experiences. Information collected was demographic, health (e.g., pain, fatigue, disease activity), work context (e.g., career satisfaction, helpfulness of job accommodation/benefits, and workplace activity limitations), and psychosocial (e.g., independence, social support, and overprotection). Log-Poisson regression analysis examined factors associated with employment status., Results: Over half of respondents were employed (59%) and 26% were enrolled in school. Respondents reported moderate to high perceptions of independence and social support. However, 27% reported that "quite a bit" to "a great deal" of overprotection characterized their relationships with those closest to them. At the bivariate level, employed participants and those indicating greater perceived independence reported greater social support and less overprotection. Multivariable analysis revealed that being employed was associated with older age, more job accommodations/benefits perceived as being helpful, and greater perceived independence., Conclusion: This is one of the first studies examining the employment of young adults with rheumatic diseases. Findings highlight the importance of psychosocial perceptions such as independence and overprotection, in addition to support related to working. Additional research is needed to better understand the role of those close to young adults with rheumatic diseases in supporting independence and encouraging employment.

Objective: To determine the frequency of each American College of Rheumatology (ACR) criterion met at time of enrollment, and the increase in each of the criteria over 5 years., Methods: In 2000 the Systemic Lupus International Collaborating Clinics (SLICC) recruited an international inception cohort of patients with systemic lupus erythematosus (SLE; ≥ 4 ACR criteria) who were followed at yearly intervals according to a standard protocol. Descriptive statistics were used to assess the total and cumulative number of ACR criteria met at each visit. Regression models were done to compare the increase of individual and cumulative criteria as a function of race/ethnicity group, and sex., Results: In all, 768 patients have been followed for a minimum of 5 years. Overall, 59.1% of the patients had an increase in the number of ACR criteria they met over the 5-year period. The mean number of ACR criteria met at enrollment was 5.04 ± 1.13 and at year 5 was 6.03 ± 1.42. At enrollment, nonwhite patients had a higher number of ACR criteria (5.19 ± 1.23) than white patients. The total number of criteria increased in both white and nonwhite ethnicities, but increased more among whites. Males had a slightly lower number of criteria at enrollment compared to females and males accrued fewer criteria at 5 years., Conclusion: In this international inception cohort of SLE patients with at least 4 ACR criteria at entry, there was an accumulation of ACR criteria over the following 5 years. The distribution of criteria both at inception and over 5 years is affected by sex and ethnicity.

Objective: To estimate systemic autoimmune rheumatic disease (SARD) prevalence across 7 Canadian provinces using population-based administrative data evaluating both regional variations and the effects of age and sex., Methods: Using provincial physician billing and hospitalization data, cases of SARD (systemic lupus erythematosus, scleroderma, primary Sjögren syndrome, polymyositis/dermatomyositis) were ascertained. Three case definitions (rheumatology billing, 2-code physician billing, and hospital diagnosis) were combined to derive a SARD prevalence estimate for each province, categorized by age, sex, and rural/urban status. A hierarchical Bayesian latent class regression model was fit to account for the imperfect sensitivity and specificity of each case definition. The model also provided sensitivity estimates of different case definition approaches., Results: Prevalence estimates for overall SARD ranged between 2 and 5 cases per 1000 residents across provinces. Similar demographic trends were evident across provinces, with greater prevalence in women and in persons over 45 years old. SARD prevalence in women over 45 was close to 1%. Overall sensitivity was poor, but estimates for each of the 3 case definitions improved within older populations and were slightly higher for men compared to women., Conclusion: Our results are consistent with previous estimates and other North American findings, and provide results from coast to coast, as well as useful information about the degree of regional and demographic variations that can be seen within a single country. Our work demonstrates the usefulness of using multiple data sources, adjusting for the error in each, and providing estimates of the sensitivity of different case definition approaches.

Objective: To assess whether hydroxychloroquine (HCQ) prevents early damage in patients with systemic lupus erythematosus (SLE)., Methods: We updated an existing systematic review of literature on clinical effects of HCQ in patients with SLE. We conducted a nested case-control study embedded in an inception cohort of patients with SLE. Systemic Lupus International Collaborating Clinics Damage Index (SDI) at 3 years was considered as our primary outcome. Patients with SDI > 0 at 3 years were considered cases and patients with SDI = 0 were controls. Cases and controls were first compared by univariate analysis. Then conditional logistic regression models adjusting for potential confounders were done to study the effect of HCQ on damage accrual., Results: Included in the analysis were 481 patients who had 3 or more years of followup. Out of this cohort, we could match 151 cases with 151 controls. Univariate analysis identified age, the use of any immunosuppressive drugs, HCQ, and cumulative dose of steroids as significant covariates associated with damage accrual. In multivariate analysis, the use of HCQ remained significantly associated with less damage (OR 0.34, 95% CI 0.132-0.867), while age (OR 1.05, 95% CI 1.027-1.078) and a variable combining SLE activity and steroid dose (OR 1.73, 95% CI 1.306-2.295) were associated with damage at 3 years., Conclusion: We demonstrated that HCQ use was associated with less damage at 3 years after diagnosis of SLE when attention was given and adjustment done for disease activity and steroid dose, duration of disease, and calendar year of diagnosis.

Objective: Women with systemic lupus erythematosus (SLE) are at risk of osteoporosis (OP) and fractures because of SLE or its treatments. We aimed to determine in women with SLE (1) the prevalence of low bone mass (LBM) in those < 50 years of age and OP in those > 50 years of age; (2) the 10-year absolute fracture risk in those > 40 years of age using the Canadian Fracture Risk Assessment Tool (FRAX); (3) bone quality using hip structural analysis (HSA); and (4) the associations between HSA and age, SLE duration, and corticosteroid exposure., Methods: Women without prior OP fractures were eligible. Bone mineral densities at the hip, spine, and femoral neck were determined using dual-energy x-ray absorptiometry. OP was determined using World Health Organization definitions for participants aged ≥ 50 years (32.8%), and LBM was defined as Z-scores ≤ -2.0 for those aged < 50 years. For those aged ≥ 40 years (63.5%), the 10-year probabilities of a major fracture (FRAX-Major) and hip fracture (FRAX-Hip) were calculated. FRAX-Major ≥ 20% or Hip ≥ 3% was considered high risk. HSA was done in a subgroup (n = 81) of patients., Results: The study group was 271 women. Mean (SD) age was 43.8 (13.1) years and SLE duration was 11.6 (10.4) years. OP was diagnosed in 14.6% and LBM in 8.8%. FRAX-Major ≥ 20% was seen in 9 patients (5.3%), of whom 6 were taking OP medications. FRAX-Hip ≥ 3% occurred in 16 patients (9.4%), of whom 9 were taking OP medications. Buckling ratio at the left hip narrow neck was positively correlated with FRAX-Major, FRAX-Hip, SLE duration, and duration of corticosteroid use., Conclusion: LBM is prevalent in women with SLE who are < 50 years of age. FRAX may identify those at higher risk of fractures while HSA can assess bone structure noninvasively.

Objective: To produce evidence on the longitudinal evolution of risk factors for coronary heart disease (CHD) in patients with systemic lupus erythematosus (SLE)., Methods: Based on data for 115 patients from the Montreal General Hospital Lupus Clinic (1971-2003) and for 4367 control subjects from the Framingham Offspring Study (1971-1994), we investigated the temporal evolution of total serum cholesterol, systolic blood pressure (SBP), body mass index (BMI), blood glucose, and estimated risk for CHD (reflecting the balance of changes in different risk factors). In analyses limited to patients with SLE, we assessed the effect of SLE duration on each risk factor, adjusting for age, calendar time, sex, baseline level of the risk factor, and medication use. Next, we assessed how the adjusted difference in the values of the risk factors between SLE and controls changes over time., Results: Among patients with SLE, longer disease duration was independently associated with higher SBP and blood glucose levels. Compared with controls, these patients appeared to have accelerated rates of increase in total cholesterol, blood glucose, and overall estimated CHD risk. The rate of increase in BMI was lower in patients with SLE than in controls., Conclusion: Elevated CHD risk in patients with SLE appears to be at least partially mediated by accelerated increases in some CHD risk factors, longitudinal trajectories of which increasingly diverge over time from those of population controls.

Objective: To determine the prevalence of abnormal liver enzymes in patients with systemic lupus erythematosus (SLE) and whether further investigations were done, and the differences in SLE-related and/or metabolic factors in patients with and without liver biochemical abnormalities., Method: Patients from the University of Toronto Lupus Clinic who met at least 4 of the American College of Rheumatology classification criteria for SLE and had 1.5 times the upper limit for aspartate transaminase or alanine transaminase on 2 consecutive visits within a 2-year period were matched with controls for age, sex, and SLE duration. Demographic, clinical, and laboratory data were extracted at the time of the first appearance of liver enzyme abnormality for the cases and at the reference point for the controls., Results: From the 1533 patients reviewed, 134 (8.7%) met the inclusion criteria. Thirty of these patients were evaluated by a hepatologist, 75 had imaging studies (41 were done specifically for liver investigation), and 13 had liver biopsies. Results based on these investigations showed 31 fatty livers, 35 cases of drug-induced hepatotoxicity, 10 autoimmune etiologies, and 3 cases of viral hepatitis. Compared to controls, cases were higher in body mass index, anti-dsDNA antibody, prevalence of hypertension, antiphospholipid syndrome, and use of immunosuppressive medication, especially azathioprine and methotrexate; they were lower in IgM., Conclusion: Metabolic abnormalities such as obesity and hypertension and hepatotoxic effects of medication used to treat SLE may contribute more than SLE-related factors to liver biochemical abnormalities in patients with SLE.

Objective: To compare health-related quality of life (HRQOL) of patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) with and without previous thrombovascular events (TE)., Methods: The Medical Outcomes Study Short-Form 36 (SF-36) was used to assess HRQOL in 5 patient groups: (1) primary APS (PAPS; n = 35); (2) APS associated to SLE (SAPS; n = 37); (3) SLE+TE without persistent positive antiphospholipid antibody (SLE+TE-aPL; n = 75); (4) SLE-TE+aPL (n = 71); and (5) SLE-TE-aPL (n = 608)., Results: The data on both mental component summary and physical component summary (PCS) scores showed an impaired quality of life in all patient groups. Patients in the SLE+TE-aPL group had a lower PCS score compared to patients in the SLE-TE+aPL group., Conclusion: The combination of SLE and TE has a more negative influence on reported HRQOL, compared to having SLE or APS alone.

Objective: To test the interrater and intrarater reliability of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Responder Index (SRI-50), an index designed to measure ≥ 50% improvement in disease activity between visits in patients with systemic lupus erythematosus., Methods: This was a multicenter, cross-sectional study with raters from Canada, the United Kingdom, and Argentina. Patient profile scenarios were derived from real adult patients. Ten rheumatologists from university and community hospitals and postdoctoral rheumatology fellows participated. An SRI-50 data retrieval form was used. Each rheumatologist scored SLEDAI-2K at the baseline visit and SRI-50 on followup visit, for the same patients, on 2 occasions 2 weeks apart. Physician global assessment (PGA) was determined on a numerical scale at baseline visit and a Likert scale on followup visit. Interrater and intrarater reliability was assessed using intraclass correlation coefficient (ICC) and kappa statistics whenever applicable., Results: Forty patient profiles were created. The ICC performed on 80 patient profiles for interrater ranged from 1.00 for SLEDAI-2K and SRI-50 to 0.96 for PGA. The intrarater ICC for SLEDAI-2K, SRI-50, and PGA scores ranged from 1.00 to 0.86. Substantial agreement was determined for the interrater Likert scale, with a kappa statistic of 0.57., Conclusion: The SRI-50 is reliable to assess ≥ 50% improvement in lupus disease activity. Use of the SRI-50 data retrieval form is essential to ensure optimal performance of the SRI-50. SRI-50 can be used by both rheumatologists and trainees and performs equally well in trained as well as untrained rheumatologists.

Objective: To examine the relationship between interferon-α (IFN-α) and dysregulation of B cell activation factor (BAFF) and specific B cell phenotypes in systemic lupus erythematosus (SLE)., Methods: Four-color flow cytometry was used to examine the peripheral B cell populations in patients with SLE. RNA was isolated from the peripheral blood of 87 patients and BAFF expression was determined by quantitative polymerase chain reaction (PCR) and normalized to GAPDH. The expression levels of 5 IFN-responsive genes (LY6E, OAS1, IFIT1, ISG15, and MX1) were determined by quantitative PCR and totaled to generate a global IFN score. The correlations were examined between peripheral B cell populations (including transitional, pregerminal, plasmablasts, and memory) and the expression of BAFF and the global IFN score., Results: Examination of the peripheral B cell populations in SLE demonstrated a relative expansion of the transitional B cell and plasmablast compartment and a reduction in the memory B cell population. Expressions of BAFF and global IFN score were elevated in patients with SLE compared to healthy controls. A strong positive correlation was noted between BAFF expression and the relative proportion of late transitional (T2) B cells. The proportions of more mature B cell phenotypes did not correlate with BAFF expression. The global IFN score was strongly associated with the level of BAFF expression and moderately correlated with the proportion of late transitional B cells., Conclusion: The findings suggest that elevated BAFF expression supports expansion of the T2 B cell compartment and contributes to a breach in tolerance in patients with SLE.

Objective: To compare the healthcare cost and loss of productivity in patients with systemic lupus erythematosus (SLE) with (LN) and without lupus nephritis (lupus nephritis-negative, LNN)., Method: Patients were classified into those with active (ALN and ALNN) and inactive disease (ILN and ILNN). Patients reported on visits to healthcare professionals and use of diagnostic tests, medications, assistive devices, alternative treatments, hospital emergency visits, surgical procedures, and hospitalizations as well as loss of productivity in the 4 weeks preceding enrollment., Results: Enrollment was 141 patients, 79 with LN and 62 LNN. Patients with LN were more likely to visit rheumatologists and nephrologists, undergo diagnostic tests, and had higher costs for medications than patients who were LNN. The annual healthcare cost averaged $CAN 12,597 ± 9946 for patients with LN and $10,585 ± 13,149 for patients who were LNN, a difference of $2012 (95% CI -$2075, $6100). Patients with ALN had more diagnostic tests and surgical procedures, contributing to a significantly higher annual direct cost ($14,224 ± 10,265) compared to patients with ILN ($9142 ± 8419) and a difference of $5082 (95% CI $591, $9573). The healthcare cost was not different between patients with ALNN and patients with ILNN. In patients with LN and patients who were LNN, < 50% were employed and on average missed 6.5-9 days of work per month. The loss of productivity was significantly higher for caregivers of patients with LN than caregivers of patients who were LNN., Conclusion: Healthcare cost and loss of productivity were similar between patients with LN and patients who were LNN; the loss of productivity for caregivers is higher for patients with LN; and the healthcare cost is greater in ALN than in ILN.

Objective: To evaluate factors affecting therapeutic approaches used in clinical practice for the management of systemic lupus erythematosus (SLE), in a multicenter cohort., Methods: We combined data from 10 clinical adult SLE cohort registries in Canada. We used multivariate generalized estimating equation methods to model dichotomized outcomes, running separate regressions where the outcome was current exposure of the patient to specific medications. Potential predictors of medication use included demographic (baseline age, sex, residence, race/ethnicity) and clinical factors (disease duration, time-dependent damage index scores, and adjusted mean SLE Disease Activity Index-2K scores). The models also adjusted for clustering by center., Results: Higher disease activity and damage scores were each independent predictors of exposure to nonsteroid immunosuppressive agents, and for exposure to prednisone. This was not definitely demonstrated for antimalarial agents. Older age at diagnosis was independently and inversely associated with exposure to any of the agents studied (immunosuppressive agents, prednisone, and antimalarial agents). An additional independent predictor of prednisone exposure was black race/ethnicity (adjusted RR 1.46, 95% CI 1.18, 1.81). For immunosuppressive exposure, an additional independent predictor was race/ethnicity, with greater exposure among Asians (RR 1.39, 95% CI 1.02, 1.89) and persons identifying themselves as First Nations/Inuit (2.09, 95% CI 1.43, 3.04) than among whites. All of these findings were reproduced when adjustment for disease activity was limited to renal involvement., Conclusion: Ours is the first portrayal of determinants of clinical practice patterns in SLE, and offers interesting real-world insights. Further work, including efforts to determine how differing clinical approaches may influence outcome, is in progress.

Objective: To determine whether serum albumin reflects disease activity in patients with systemic lupus erythematosus (SLE) with and without nephritis (LN, LNN), and whether serum albumin could be a surrogate marker of SLE disease activity overall. There is currently no clinical "gold standard" in the assessment of disease activity in SLE., Methods: Patients with >or= 3 clinic visits within a maximum followup period of 10 years were selected from the University of Toronto Lupus Clinic database. Subjects were divided into 3 groups: LN-B, those with nephritis defined by histological findings on renal biopsies; LN-L, those with nephritis defined by laboratory abnormalities in the absence of biopsy; and LNN, those without nephritis. In a subanalysis, the renal groups were further stratified by proteinuria status. The associations of SLE-Disease Activity Index (SLEDAI-2K) with serum albumin and dsDNA were examined using the mixed model regression analysis., Results: A total of 1078 patients were studied: 89.1% female, 71.5% white, mean age 33.6 (SD 12.6) years, and with median baseline SLEDAI-2K of 8. Serum albumin was more significantly associated with SLEDAI in LN-B and LN-L. The association was also present but weaker in the LNN group. In all LN, the associations between serum albumin and SLEDAI-2K were stronger in those with proteinuria., Conclusion: In patients with SLE, higher SLEDAI was associated with lower serum albumin levels.

Objective: To investigate the expression of tumor necrosis factor receptors (TNFR1 and TNFR2) and adapter proteins (TRADD, RIP, and TRAF2) in peripheral blood mononuclear cell (PBMC) subsets from patients with systemic lupus erythematosus (SLE)., Methods: PBMC were isolated from 45 SLE patients and 25 controls, and stained with labeled antibodies that enabled identification of various T cell, B cell, and monocyte subpopulations. Expression of TNF-related signaling molecules was measured by staining with labeled antibodies either directly or following fixation and permeabilization. Apoptosis was quantified using an anti-active caspase 3 antibody. RNA expression of TNF-related signaling molecules was assessed by quantitative RT-PCR and serum levels of TNF-alpha by ELISA., Results: SLE patients had increased levels of TNFR1, TNFR2, and TRAF2, together with decreased levels of RIP, on various B, CD4+ T, and CD8+ T cell subsets as compared to controls. This altered expression was seen in both naive and memory subpopulations, and reflected altered staining of the whole population rather than a subset of cells that were activated. The levels of these molecules were not significantly correlated with serum TNF-alpha levels or their RNA expression in whole peripheral blood. TNFR1 and TNFR2 expression was negatively correlated with disease activity. There was no association between the proportion of apoptotic cells in any of the subpopulations and serum TNF-alpha levels or expression of TNF-related signaling molecules., Conclusion: Patients with SLE had altered expression of TNF-related signaling molecules, suggesting that there may be an imbalance in TNF-alpha signaling favoring cellular activation as opposed to proapoptotic pathways.

Objective: Pleuritis is a common manifestation and independent predictor of mortality in systemic lupus erythematosus (SLE). We examined the prevalence of pleuritis and factors associated with pleuritis in a multicenter Canadian SLE cohort., Methods: We studied consecutive adults satisfying the American College of Rheumatology (ACR) classification criteria for SLE who had a completed Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) score, at least 1 evaluable extractable nuclear antigen assay, and either a SLE Disease Activity Index (SLEDAI) or a SLE Activity Measure score. Pleuritis was defined as having pleuritis by satisfying the ACR criteria or the SLEDAI. Factors related to pleuritis were examined using univariate and multivariate logistic regression., Results: In our cohort of 876 patients, 91% were women, 65% Caucasian, mean age (+/- SD) was 46.8 +/- 13.5 years, and disease duration at study entry was 12.1 +/- 9.9 years; the prevalence of pleuritis was 34% (n = 296). Notably, greater disease duration (p = 0.002), higher SDI score (p

Objective: Associations between the use of micronutrient supplements (MS) and disease activity, quality of life (QOL), and healthcare resource utilization were studied in a Canadian population of patients with systemic lupus erythematosus (SLE)., Methods: QOL was assessed by the Medical Outcomes Study 36-item Short Form. Healthcare resource utilization and disease activity/damage were determined., Results: Of the 259 subjects studied, 53% were MS users and 34% used only calcium/vitamin D. MS users had a higher Systemic Lupus International Collaborating Clinics score and utilized more healthcare resources. Disease activity and QOL were similar between MS users and nonusers., Conclusion: MS are frequently used by patients with SLE and are not associated with concomitant benefit on QOL. MS users utilized more healthcare resources.

Objective: To describe disease expression and damage accrual in systemic lupus erythematosus (SLE), and determine the influence of ethnicity and socioeconomic factors on damage accrual in a large multiethnic Canadian cohort., Methods: Adults with SLE were enrolled in a multicenter cohort. Data on sociodemographic factors, diagnostic criteria, disease activity, autoantibodies, treatment, and damage were collected using standardized tools, and results were compared across ethnic groups. We analyzed baseline data, testing for differences in sociodemographic and clinical factors, between the different ethnic groups, in univariate analyses; significant variables from univariate analyses were included in multivariate regression models examining for differences between ethnic groups, related to damage scores., Results: We studied 1416 patients, including 826 Caucasians, 249 Asians, 122 Afro-Caribbeans, and 73 Aboriginals. Although the overall number of American College of Rheumatology criteria in different ethnic groups was similar, there were differences in individual manifestations and autoantibody profiles. Asian and Afro-Caribbean patients had more frequent renal involvement and more exposure to immunosuppressives. Aboriginal patients had high frequencies of antiphospholipid antibodies and high rates of comorbidity, but disease manifestations similar to Caucasians. Asian patients had the youngest age at onset and the lowest damage scores. Aboriginals had the least education and lowest incomes. The final regression model (R2=0.27) for higher damage score included older age, longer disease duration, low income, prednisone treatment, higher disease activity, and cyclophosphamide treatment., Conclusion: There are differences in lupus phenotypes between ethnic populations. Although ethnicity was not found to be a significant independent predictor of damage accrual, low income was.

Objective: To determine the prevalence and confirmation rate of autoimmune diseases reported by relatives of patients with lupus and controls., Methods: Medical histories were obtained by self-report from 626 first-degree relatives of lupus patients and 267 population controls., Results: Of 178 reports of an autoimmune disease, 44% were confirmed by medical records; excluding those whose medical records were unavailable, the confirmation rate was 76%. The prevalence of at least one confirmed autoimmune disease was 12% in lupus relatives and 2% in controls., Conclusion: Methods to improve the reliability of self-reported autoimmune disease history could enhance population and clinic-based research.

Objective: We describe the pattern of incidence of thrombovascular events after diagnosis of systemic lupus erythematosus (SLE) in a cohort of lupus patients., Methods: Descriptive study of prospectively collected data using incidence rates of thrombovascular events and 95% confidence intervals (CI) calculated for predetermined periods of observation. Kaplan-Meier survival curves were plotted to estimate thrombovascular event-free survival., Results: Among 426 individuals, person-years contributed were as follows: 399 persons and 4356.0 person-years for all events; 417 persons and 4691.9 person-years for arterial events; and 408 persons and 4846.6 person-years for venous events. The incidence of thrombovascular events was highest during the first year after SLE diagnosis (4.00, 95% CI 2.24-6.59) and after 20 years (ranging from 3.32, 95% CI 1.52-6.30, to 4.99, 95% CI 0.60-18.01), and was lowest between 1 and 5 years after SLE diagnosis (1.00, 95% CI 0.53-1.72). A similar pattern was observed for arterial events, while venous events showed a higher incidence rate only in the first 30 days after SLE diagnosis (12.06, 95% CI 3.29-30.87) and remained low afterwards. The probabilities of remaining event-free at 5, 10, and 15 years were as follows: 0.92, 0.85, and 0.78, respectively, for all thrombovascular events; 0.95, 0.88, and 0.82, respectively, for arterial events; and 0.98, 0.95, and 0.94, respectively, for venous events., Conclusion: Thrombovascular events occur throughout the course of lupus, with the highest risk of arterial or venous events in the first year after diagnosis, and the pattern of occurrence varying thereafter.

Objective: A willingness-to-pay (WTP) survey measures the value of a given intervention in money terms. We examined the WTP of Canadian patients with rheumatoid arthritis (RA) for a hypothetical cure for RA under private and public scenarios. The validity of the survey was explored by studying the association between WTP and variables thought to be associated with WTP and randomly-varied variables of the survey materials., Methods: A telephone survey was carried out in a sample of 121 patients with RA from 5 rheumatologists affiliated with the McGill University Health Centre. In advance, patients had been sent a 4-page brochure providing a comprehensive description of the disease (including photos or no photos). The hypothetical cure for RA was presented through 2 scenarios: a private insurance implying an annual premium and a public coverage requiring additional income taxes. The survey included questions related to their WTP, socioeconomic status (ability to pay), general health, opinion about the performance of the healthcare system, and their opinion about the difficulty of the survey. For elicitation of WTP, patients were randomized to one of 3 payment cards. Mailed questionnaires concerning RA health status were also completed. A series of univariate comparisons and multivariate ordered logit regressions were carried out to examine the association of WTP and patient and study variables., Results: Patients were willing to pay annually significantly more for the private program (mean 1190 Canadian dollars) than for the public program (mean 502 Canadian dollars). Annual WTP was associated with age, household income, site of care (private program), private health insurance, opinion about the performance of the public healthcare system (public program), and presence of brochure photos. The payment card did not affect WTP for either program., Conclusion: The WTP survey was well understood and accepted by the patients with RA. Although measures of RA-specific health status (e.g., Health Assessment Questionnaire) were not found to be associated with WTP, many variables thought to be associated with WTP were found to be related in the expected directions. Since WTP for the private program was higher than that for the public program, our study design did not fully capture altruistic valuations of RA patients. Thus, our estimates represent a lower bound on patients' WTP for an RA cure.

Objective: To explore the effect of multiple prothrombotic risk factors in individuals with anticardiolipin antibodies (aCL), we evaluated immunologic, coagulation, and genetic prothrombotic abnormalities in a cohort of individuals with different aCL titers., Methods: We recruited 87 individuals into 4 categories (normal, low, intermediate, or high) based on their baseline IgG aCL (aCL-IgG) titers. We measured at followup: repeat aCL-IgG, IgM aCL (aCL-IgM), antibodies to beta2-glycoprotein I (anti-beta2-GPI), lupus anticoagulant (LAC) antibodies, protein C, protein S, activated protein C resistance, factor V506 Leiden mutation, methyl tetrahydrofolate reductase (MTHFR) C677T genotype, and prothrombin 20210A gene mutation. Thrombotic events were confirmed., Results: At recruitment, 20 individuals were negative for aCL-IgG and 67 were positive (22 low, 20 intermediate, and 25 high titer). Twenty of the 87 participants had experienced a previous thrombotic event: 4 in the aCL-IgG negative group and 16 in the aCL-IgG positive group. Among the 87 individuals, the number of those with concomitant prothrombotic risk factors was as follows: 5 had no other prothrombotic risk factors, 32 had 1 risk factor, 24 had 2 risk factors, 10 had 3 risk factors, 10 had 4 risk factors, and 6 had 5 risk factors. Thrombotic events were observed in 20%, 13%, 33%, 10%, 30%, and 50% of these groups, respectively, and the odds ratio associated with a previous thrombotic event was 1.46 per each additional prothrombotic risk factor (95% confidence interval: 1.003-2.134)., Conclusion: In individuals with positive aCL-IgG, we observed an association between the number of prothrombotic risk factors and history of thrombotic events.

Objective: To compare the effectiveness of tetracycline antibiotics versus control (placebo or conventional treatment) in rheumatoid arthritis (RA) for the reduction of disease activity as defined by American College of Rheumatology criteria., Methods: We searched Medline (1966-February 2002), Embase (1980-February 2002), and the Cochrane Controlled Trials Register (Issue 1, 2002 Cochrane Library). Reference lists of published trials were searched by hand for further identification of published reports and presentations at scientific meetings. Randomized controlled trials comparing tetracyclines to control (placebo or conventional disease modifying antirheumatic therapy) were selected for inclusion if at least one of the following outcomes was reported: tender joint count (TJC), swollen joint count, patient pain score by visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity, eosinophil sedimentation rate (ESR) and C-reactive protein (CRP), joint space narrowing and erosions, adverse events, and quality of life as measured by the Health Assessment Questionnaire. Subjects were required to have RA as defined by the 1987 ARA criteria., Results: Ten randomized controlled trials including 535 individuals were reviewed. Only 3 trials were considered high quality; elements of bias could not be excluded in the remainder. Tetracyclines, when administered for > or = 3 months, were associated with a significant reduction in disease activity in RA as follows: for TJC, standardized mean difference (SMD) = -0.39, 95% CI -0.74, -0.05; and for acute phase reactants, ESR, SMD = -8.96, 95% CI -14.51, -3.42. The treatment effect was more marked in the subgroup of patients with disease duration < 1 year who were seropositive. There was no absolute increased risk of adverse events associated with tetracyclines: absolute risk difference = 0.10, 95% confidence interval (CI) -0.01, 0.21. No beneficial effect was seen on radiological progression of disease: for erosions, SMD = 0.17, 95% CI -0.29, 0.64. In addition, subgroup analysis excluding trials with doxycycline showed that minocycline alone had a greater effect on reduction of disease activity: for TJC, SMD = -0.69, 95% CI -0.89, -0.49; and for ESR, SMD = -10.14, 95% CI -14.72, -5.57., Conclusion: Tetracyclines, in particular minocycline, were associated with a clinically significant improvement in disease activity in RA with no absolute increased risk of side effects. Unfortunately, the information available was inadequate to allow a detailed analysis of individual side effects in the studies. Further research is warranted to compare these agents to newer disease modifying drugs for comparable safety, efficacy, and cost-effectiveness.

Objective: We evaluated different methods for quantifying patient-physician discordance and identified factors associated with discordance in the assessment of lupus disease activity., Methods: Data from 208 female patients who had a comprehensive annual examination were extracted from the Montreal General Hospital Lupus Registry. Discordance was measured by the difference between the patient self-reported 10 cm visual analog scale (VAS) and the physician VAS for global disease activity (VASDIFF). Multiple linear regression was used to identify the correlates of discordance, e.g., SF-36TM scales, Systemic Lupus Activity Measure (SLAM) components, etc. Four regression models were estimated using: (1) all patients; (2) only patients who evaluated disease activity higher than their physician's assessment; (3) only patients who evaluated disease activity lower than their physician's assessment; and (4) all patients, with the absolute value of VASDIFF as the dependent variable., Results: Of the 208 observations, 150 (72%) of the VASDIFF scores were within +/- 2.5 cm on a 10 cm scale, indicating absence of marked discordance; 43 (20.7%) were from patients overscoring and 15 (7.2%) from patients underscoring their physician by at least 2.5 cm. Higher SF-36 role physical score, more bodily pain, and lower role emotional score in addition to the SLAM-skin component were independently associated with higher discordance. SF-36 social function and mental health scores as well as SLAM-neurological and kidney components were correlated with discordance in some subanalyses. Bodily pain was the most important variable for predicting "clinically relevant" discordance, followed by SLAM-skin and kidney components., Conclusion: Discordance between patients and physicians may result from patients scoring their disease activity based on their psychological and physical well-being, whereas physicians score disease activity based on the clinical and physical signs and symptoms of lupus.

Objective: We investigated whether brief supportive-expressive group psychotherapy might reduce illness-induced interference with valued activities and interests (i.e., illness intrusiveness) among women with systemic lupus erythematosus (SLE) in relation to 3 life domains: (1) relationships and personal development (family relationships, other social relationships, self-expression), (2) intimacy (relationship with spouse, sex life), and/or (3) instrumental life (work, finances, active recreation)., Methods: Women with SLE recruited from 9 rheumatology centers were randomly assigned to receive either usual care (n = 66) or a 12 week brief supportive-expressive group psychotherapy followed by 3 monthly booster sessions (n = 58). Standard instruments assessed disease activity and damage, illness intrusiveness, and psychological distress at 4 measurement occasions: (1) pretreatment, (2) posttreatment, (3) 6 month followup, and (4) 12 month followup., Results: Analysis of covariance, controlling for disease activity and household income, indicated that women who received brief supportive-expressive group psychotherapy experienced significant reductions in illness intrusiveness for 2 of 3 domains: (1) relationships and personal development and (2) intimacy. Benefits were evident at 6 and 12 month followups., Conclusion: Brief supportive-expressive group psychotherapy facilitates adaptation to SLE by assisting women in reducing illness-induced disruptions into important domains of life experience.

Objective: To determine (1) which organ system manifestations contribute to the overall responsiveness of the Systemic Lupus Activity Measure (SLAM, revised 1991 with minor modifications as SLAM-R) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and (2) whether responsive items differ for physicians and patients., Methods: Blinded data were obtained from repeated visits of 76 patients in the Study of Methotrexate in Lupus Erythematosus. At each visit, physicians and patients reported improvement, no change, or deterioration, and physicians then completed SLAM-R and SLEDAI. Items in SLAM-R and SLEDAI were grouped by organ system. The generalized estimating equations approach was used to measure associations between change in organ system activity and physician or patient perception of change in overall disease activity. The outcomes assessed, in separate analyses, were improvement and deterioration from the previous visit., Results: Seventy-six patients contributed a total of 471 observations. The strongest correlates of physician-reported improvement were decreased constitutional, gastrointestinal (GI), and musculoskeletal involvement (components of SLAM-R), and decreased musculoskeletal (MSK) and central nervous system involvement (SLEDAI). Improvement reported by patients was most strongly associated with decreases in erythrocyte sedimentation rate and MSK and reticuloendothelial activity (SLAM-R), and in MSK activity (SLEDAI). Increased integument and MSK subscores (SLAM-R) and serosal and MSK subscores (SLEDAI) were associated with overall deterioration reported by physicians. Patient-reported deterioration was associated with increased GI subscores (SLAM-R) and with no changes in organ system involvement in SLEDAI., Conclusion: Organ systems associated with reported change in overall SLE activity differed between SLAM-R and SLEDAI, between patients and physicians, and between each direction of change.

Objective: To determine if the prevalence of 2 prothrombotic genetic factors, factor V Leiden and prothrombin gene mutation, is increased in patients with antiphospholipid (aPL) antibodies with a history of venous/arterial thrombosis compared to patients with aPL antibodies with no history of thrombosis., Methods: One hundred fifty-seven patients with aPL antibodies were studied. The occurrence of venous and arterial thrombotic events since the time of antibody detection was determined retrospectively, using appropriate clinical and diagnostic criteria. Clinical risk factors for thrombosis were documented and included hypertension, hyperlipidemia, cigarette smoking, diabetes, positive family history, use of oral contraceptive, pregnancy, trauma, hospitalization, varicose veins, and malignancy. Genomic DNA was extracted from blood cells for determination of factor V Leiden mutation G1691 --> A and prothrombin mutation G20210 --> A by polymerase chain reaction and restriction fragment length polymorphism analysis., Results: Of 157 patients, 69 had a history of thrombosis (venous 37, arterial 32); 147 (94%) patients had anticardiolipin (aCL) antibodies; 69 (45%) had lupus anticoagulant (LAC). The prevalence of factor V Leiden in patients with thrombosis was 13% compared to 4.6% in patients without thrombosis (OR 3.11, CI 0.92-10.6). In patients with aCL antibodies, 15% of patients with arterial thrombosis had factor V mutation compared to 3.5% of patients without thrombosis (OR 4.9, CI 1.2-19.3). The prothrombin gene mutation was identified in 5 patients, none of whom had thrombosis. Stepwise logistic regression analysis indicated that LAC (p = 0.005), male sex (p = 0.04), and hypertension (p = 0.03) were the strongest risk factors for developing thrombosis and that no additional risk was conferred by factor V Leiden (p = 0.13) and prothrombin gene mutation., Conclusion: Although the prevalence of factor V Leiden is modestly increased in patients with autoimmune aPL antibodies and thrombosis, these results suggest that its detection does not significantly increase the risk of a thrombotic event, once other clinical risk factors have been considered. Prothrombin gene mutation is not associated with thrombosis in patients with aPL antibodies.

Objective: To evaluate the relationship between patient expectations of total joint arthroplasty (TJA) and health related quality of life plus satisfaction 6 months after surgery. Methods. This prospective cohort study included patients undergoing primary total hip (THA) and knee arthroplasty (TKA). Patients were evaluated with self-report questionnaires prior to surgery and 6 months post-surgery. Medical Outcomes Study Short Form 36 (SF-36), the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), and a satisfaction scale were used to evaluate outcomes at final followup. Multivariate regression models were used to evaluate the impact of expectations on outcomes., Results: There were 102 patients with THA and 89 with TKA. Mean age was 66 years. All patients achieved significant improvements in their WOMAC and SF-36 scores following surgery. Patient expectations regarding surgery were not associated with their age, gender, index joint of surgery, marital status, or race. Expectations were not correlated with pre-operative functional health status. Expectation of complete pain relief after surgery was an independent predictor of better physical function and improvement in level of pain at 6 months post-surgery. Expectation of low risk of complications from TJA was an independent predictor of greater satisfaction., Conclusions: Patient expectations were important independent predictors of improved functional outcomes and satisfaction following TJA. Greater understanding of the relationship between expectations and outcomes may improve the process of care and outcomes of TJA.

Objective: To portray life with lupus for women affected by this disease and to identify predictors of fatigue, a common symptom that compromises patients' quality of life., Methods: A sample of 120 female patients (mean age 42.5 yrs) with systemic lupus erythematosus (SLE) from 9 rheumatology clinics across Canada were followed prospectively for 15 months. Assessments of psychosocial functioning took place at baseline, and at 3, 9, and 15 months. Physician examinations were conducted at baseline and 15 months., Results: Significant time effects were found for: global psychological distress (p < 0.001), stress (p < 0.01), emotion-oriented coping (p < 0.001), physical health status (p < 0.001), and fatigue (p < 0.001), indicating that patients improved from baseline to 15 months. Disease activity worsened for 40.3%, improved for 50.8%, and remained the same for 8.8% of the patients from baseline to 15 months. Controlling for baseline disease activity and fatigue, and considering sleep problems, decreases in stress and depression predicted less fatigue at 15 months (p < 0.001; adjusted R2 = 0.43)., Conclusion: Despite fluctuations in disease activity, patients with SLE, as a group, cope adequately with their disease over time. There is, nonetheless, a subset of patients (about 40%) who remain distressed and who may benefit from psychosocial interventions.

Objective: The Rheumatoid Arthritis Quality of Life questionnaire (RAQoL) was developed simultaneously in the UK and the Netherlands to measure quality of life in patients with RA. We adapted and validated the RAQoL for the English-Canadian and French-Canadian languages and culture., Methods: The UK RAQoL was translated into French-Canadian by a bilingual translation panel. Separate lay panels were then used to ensure that this and the English-Canadian instruments were appropriate for use with Canadian patients. Interviews were conducted with 15 French-Canadian and 15 English-Canadian patients with RA to determine the content validity. Reliability and construct validity were established by means of test-retest mail surveys conducted with 92 French-Canadian and 87 English-Canadian RA patients. The survey consisted of the adapted RAQoL, the Health Assessment Questionnaire (HAQ), and a demographic questionnaire., Results: The RAQoL was successfully adapted for both the French and English-Canadian cultures. Field testing showed both versions to be well received by respondents. Of the French-Canadian patients included in the postal survey, 52 responded at Time 1 and 50 at Time 2. For the English-Canadian sample, 54 responded at both time points. Missing data rates for the RAQoL were low and floor and ceiling effects were minimal. Test-retest reliability was good for both versions: 0.87 for the French-Canadian and 0.95 for the English-Canadian. Alpha coefficients (0.92 for the French-Canadian, 0.93 for the English-Canadian) showed the items to be adequately interrelated and scores on the measure showed moderate to high correlations with the HAQ, confirming construct validity. Both versions of the RAQoL were also able to distinguish patient groups that differed according to perceived health status and perceived severity of RA. In addition, the French-Canadian version was able to distinguish patients who rated today as bad or very bad from those who rated today as good or very good., Conclusion: The new versions of the RAQoL were well received by both French and English speaking Canadians. The psychometric quality of the adapted questionnaires means they are suitable for inclusion in clinical trials involving patients with RA.

Objective: To evaluate the relationship between self-reported quality of life and disease activity, damage, impairment, disability, and handicap in systemic lupus erythematosus (SLE)., Methods: In this cross sectional study disease activity was measured with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus Activity Measure (SLAM), and damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). Quality of life was assessed by the Medical Outcome Survey Short Form 36 (SF-36) and the EuroQol (EQ-5D). Multiple linear regression was used to identify significant associations of patients' health status, and logistic regression was used to evaluate the relationship of each of the 5 dimensions of the EQ-5D in terms of impairment, disability, and handicap., Results: Damage was associated with the Physical Function (PF) and Social Function subscales of the SF-36. Disease activity was associated with the General Health (GH) subscale. Ability to carry out usual activities was strongly related to PF and GH as well as to global rating of the thermometer rating scale of the EQ-5D. Role Physical (RP) and Bodily Pain (BP) of the SF-36 were also associated with the EQ-5D rating scale. In addition, patients' ratings of anxiety and depression were strongly related to the Mental Health (MH) summary scale of the SF-36., Conclusion: Perceived health status of patients with lupus was associated with disease activity, damage, role physical, bodily pain, capacity for usual activity, and mobility. EQ-5D is a valid instrument for the measure of health related quality of life in SLE.

Objective: Indirect costs result from diminished productivity and are incorporated in cost-benefit analysis to guide health resource allocation. Valuing the productivity impairment of those not involved in labor market activities is controversial but important for diseases affecting predominantly women if allocation decisions are to be economically efficient and equitable. We compared indirect costs incurred by women with systemic lupus erythematosus (SLE), a prototypical women's disease, calculated under varying assumptions for the value of diminished labor market and non-labor market activity., Methods: Six hundred forty-eight female patients with SLE reported on employment status and time lost by themselves and their caregivers from labor market and non-labor market activities over a 6 month period., Results: Average annual indirect costs ranged from $1,424 to $22,604 (1997 Canadian dollars) dependent on the value assigned to labor market and non-labor market activity., Conclusion: Indirect cost estimates that fail to consider longterm labor market absenteeism and diminished non-labor market productivity and do not use gender neutral wages to value labor market activity may lead to decisions that jeopardize resources for women's diseases.

Objective: New scales for the clinical assessment of patients with systemic lupus erythematosus (SLE) are valid and reliable, and quantitate disease activity. We assessed the responsiveness to change of 2 widely used standardized multi-item lupus activity measures, the revised Systemic Lupus Activity Measure (SLAM-R) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and their ability to detect clinically relevant changes., Methods: Ninety-six (96) patients with definite SLE participated in this study. The group mean age was 45.0 (13.7) years, 91% were female, and the mean disease duration was 14.9 (7.5) years. Sociodemographic information, lupus activity (SLAM-R, SLEDAI), and damage were recorded at baseline. At each of the 5 monthly followup visits, the activity measures were repeated and a transition scale asked the physician if their patient's lupus activity had changed. Five different methods were used to compare the responsiveness of the activity measures studied: 1. the effect size; 2. the standardized response mean; 3. the control standardized response mean; 4. the area under the curve of a receiver operating characteristic (ROC) curve; and 5. a new multiple response modeling approach., Results: Both SLAM-R and SLEDAI are responsive. SLAM-R is consistently, although moderately, more responsive than SLEDAI. All 5 methods of evaluating responsiveness yielded a consistent ranking of disease activity measures., Conclusion: SLAM-R and SLEDAI are responsive measures of lupus activity. SLAM-R appears to be more responsive than SLEDAI.

Objective: Differences have been described between patient and physician assessments of well being in several chronic illnesses, and these differences may affect outcome. Disagreement may lead to dissatisfaction and to behaviors with dangerous consequences. We describe and identify predictors of patient-physician differences on ratings of disease activity in systemic lupus erythematosus (SLE)., Methods: Data collected on 154 patients included age, education, disease duration, and patient and physician global assessments of lupus activity on a 10 cm visual analog scale (VAS), the Health Assessment Questionnaire (HAQ), the Medical Outcome Study Short-Form 36 (SF-36), the Systemic Lupus Disease Activity Index (SLEDAI), the Systemic Lupus Activity Measure (SLAM-R), and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Multiple linear regression models were performed using patient VAS scores, physician VAS scores, and patient minus physician VAS scores as the dependent variables, and age, disease duration, selected SF-36 and SLAM-R subscales, and SDI as independent variables., Results: Patients were 90% female and 80% Caucasian, with a mean education of 13 +/- 2.8 years and a mean age of 43.1 +/- 13.6 years. The overall mean disease duration was 10.5 +/- 7.8 years. Physicians overscored patients by 2.5 cm in 6% of the cases and patients overscored physicians in 16% of the cases. The best multivariate model to predict overall differences included SF-36 mental health and SLAM-R kidney scores., Conclusion: Patient-physician differences may result from a divergence in focus. Patients score lupus activity based on their psychological status, while physicians rely more heavily on the physical effect of the disease.

Objective: To compare perceived health status in women with fibromyalgia (FM) and systemic lupus erythematosus (SLE) using the Medical Outcomes Study (MOS) Short Form Health Survey (SF-36); and to identify determinants of physical and mental health in each patient group., Methods: A cross sectional study of 46 women with FM (mean age 48.13 yrs, SD 9.40) and 59 women with SLE (mean age 42.36 yrs, SD 11.31). Patients with FM were recruited from a rheumatology clinic and a rheumatology practice, while patients with SLE were recruited from 4 rheumatology clinics. Clinical examination determined disease activity (by Systemic Lupus Activity Measure) in SLE and a tender point count was used for FM. Patients completed questionnaires assessing health status (SF-36), stress (Hassles), social support (Social Support Questionnaire 6), and coping (Coping Inventory for Stressful Situations)., Results: Patients with FM reported more impairment on the following SF-36 subscales: physical function (p < 0.001), role physical (p < 0.001), bodily pain (p < 0.001), and vitality (p < 0.001). Physical component summary scores were also significantly lower (p < 0.001) for the FM group. Four hierarchical regression analyses were computed to determine factors related to physical and mental health in each patient group, with the following variables in the equation: age, income, disease activity (Step 1), hassles (Step 2), emotional and task coping, and social support (Step 3). Better physical health in FM was related to higher income (R2 = 0.17, p < 0.05). In the SLE group, better physical health was associated with younger age, less disease activity, and lower hassles (R2 = 0.37, p < 0.0001). Worse mental health among women with FM was associated with more hassles, more emotional coping, and less satisfaction with social support (R2 = 0.64, p < 0.0001), while lower income, higher hassles, and more emotional coping were linked to worse mental health in SLE (R2 = 0.46, p < 0.0001)., Conclusion: Health related quality of life (HRQL) is impaired among women with FM and SLE, with FM patients reporting greater impairment along several dimensions. Enhancing the HRQL of patients with FM and SLE requires targeting specific modifiable psychosocial factors.

Objective: To determine the association of serum IgG advanced glycation endproducts (AGE) and IgM anti-IgG-AGE antibodies with clinical measurements of rheumatoid arthritis (RA) disease activity., Methods: The study group consisted of 62 patients with RA and 16 control patients with osteoarthritis. Patient derived variables included perceived disease activity (10 cm visual analog scale, VAS) and Health Assessment Questionnaire (HAQ) results. Clinical measures of RA activity consisted of tender and swollen joint counts and a physician evaluation of disease activity (by VAS) as well as history of nodules, bone erosions, Sjogren's syndrome, and vasculitis documented by chart review. Patient sera were evaluated for glucose, glycosylated hemoglobin, and presence of RF, IgG-AGE and IgM anti-IgG-AGE. The nitroblue tetrazolium colorimetric and aminophenyl boronic acid methods were used for measurement of IgG-AGE, along with an ELISA for measurement of IgM anti-IgG-AGE., Results: Significant correlations were found between the presence of IgM anti-IgG-AGE and clinical measurements of swollen joint count and physician VAS., Conclusion: IgM anti-IgG-AGE appears to be associated with clinical measurements of RA activity and represents a new marker of more active disease in RA.

Objective: To compare health care expenditure and health status for patients with systemic lupus erythematosus (SLE) between nations with distinct mechanisms for funding and delivering health care services., Methods: Seven hundred eight patients with SLE from 2 centers in each of 3 countries (Canada 229, United States 268, United Kingdom 211) underwent physician assessment of disease activity and damage and reported on physical and psychosocial well being, satisfaction, social support, and health resource utilization. To compare overall utilization, constant prices (1997 Canadian dollars) were applied across countries for each service, enabling diverse resources to be collapsed into a single expression., Results: After adjusting for important patient covariates, Canadian, compared to American and British patients, reported significantly superior health status in 3 of 8 Medical Outcome Survey Short Form-36 (SF-36) subscales, the SF-36 physical component summary score, and the visual analog scale of general health status. There was no consistent trend in patient satisfaction. Overall annual resource utilization did not vary significantly, with mean annual per patient expenditures (adjusted for demographics, disease duration, activity, damage, social support, health status, patient satisfaction, and age and sex adjusted country-specific SF-36 general population norms) totalling $4853, $5285, and $4760 for Canada, US, and the UK, respectively. However, within each resource category, differences were observed. Canadians saw more specialists than the British, the British more generalists. Canadians and Americans were more frequent users of the emergency room; Americans of laboratory/imaging procedures. Canadians had higher hospital costs than Americans., Conclusion: After adjustment, Canadian patients reported better well being than their counterparts. Despite considerable differences in the mechanisms of health care funding and service mixture, overall resource utilization did not vary significantly between the countries, although there was a trend towards more intense use of inpatient services in Canada and outpatient services in the United States.

Objective: To assess validity and reliability of 4 utility indices in patients with systemic lupus erythematosus (SLE)., Methods: Twenty-five patients with stable SLE underwent assessment of disease activity [Systemic Lupus Disease Activity Measure (SLAM-R) and SLE Disease Activity Index (SLEDAI)] and damage [Systemic Lupus Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI)] and completed a health survey [Medical Outcome Survey Short Form-36 (SF-36)] and 4 utility measures: the visual analog scale (VAS), the time trade-off (TTO), the standard gamble (SG), and the McMaster Health Utilities Index Mark 2 (HUI2). To assess validity, Pearson's correlations were calculated between the SF-36 subscales and the utility measures. To assess reliability, intraclass correlations or kappa coefficients were calculated between first and second assessments, performed from 2 to 4 weeks apart, in patients without important clinical change in disease activity., Results: Disease activity from a SLAM-R varied from 0 to 14 (median = 4) and SLEDAI from 0 to 18 (median = 0). All subscales of the SF-36 correlated well with the VAS [lowest r = 0.56, 95% confidence interval (CI) (0.17, 0.80)] and poorly with the SG [maximum r = 0.41, CI (-0.01, 0.70); minimum r = 0.10, CI (-0.32, 0.50)]. The subscales of bodily pain (r = 0.56), mental health (r = 0.45), physical functioning (r = 0.62), role-emotional (r = 0.47), social functioning (r = 0.49) and vitality (r = 0.44) correlated significantly with TTO. All subscales correlated significantly [lowest r = 0.48, CI (0.09, 0.75)] with the HUI2 index of pain. Intraclass correlations for the VAS (ICC = 0.67) and TTO (ICC = 0.60) were good. They were fair for the SG (ICC = 0.45). The kappa coefficient was poor (0.32) for the HUI attribute of pain, but varied from fair (0.46) to excellent (0.88) for the remaining attributes. Regression analysis showed that a model incorporating the SLAM-R value and SF-36 subset of mental health was a good predictor of VAS and TTO utility measures., Conclusion: The VAS, TTO, and to some extent, the HUI2, when compared with the SF-36 health survey, are valid and reliable measures to assess health related quality of life in a group of patients with SLE and may be useful for future research in this population. On the basis of these results the usefulness of the SG is questionable in these patients.