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Objective.To examine changes in prescribing patterns, especially the use of corticosteroids (CS), in patients with rheumatoid arthritis (RA) over 2 decades.Methods.This was a secondary analysis of health administrative data using a previously validated dataset and case definition for RA. Cases were matched 1:4 by age and sex to controls within a population of approximately 1 million inhabitants with access to universal health care. Longitudinal data for incident and prevalent RA cases were studied between 1997 and 2017.Results.There were 8240 RA cases (all ≥ 65 yrs) with a mean (SD) age 72.2 (7.5) years and 70.6% were female. Over 20 years, annual utilization of coxibs in prevalent RA cases fell with a concomitant increase in disease-modifying antirheumatic drugs (DMARDs) and biologics. Over the same period, CS use was largely unchanged. Approximately one-third of patients had at least 1 annual prescription for CS, most frequently prednisone. The mean annual dose showed a modest reduction and the duration of utilization in each year shortened. Rheumatologists prescribed CS less frequently and in lower doses than other physician groups. For incident RA cases, there was a significant fall in annual prescribed dose of prednisone by rheumatologists over time.Conclusion.In older adults with RA, the utilization of DMARDs and biologics has increased over the past 20 years. However, the use of CS has persisted. Renewed efforts are required to minimize their use in the long-term pharmacological management of RA.

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.To determine total physician encounters, emergency room (ER) visits, and hospitalizations in an incident cohort of rheumatoid arthritis (RA) cases and matched control patients over 13 years.Methods.A retrospective cohort study was performed using administrative healthcare data from about 1 million people with access to universal healthcare. Using the International Classification of Diseases, 9th ed (ICD-9) and ICD-10 diagnostic codes, 7 RA case definitions were used. Each case was matched by age and sex to 4 randomly selected controls. Data included physician billings, ER visits, and hospital discharges over 13 years.Results.The number of incident RA cases varied from 3497 to 27,694, depending on the case definition. The mean age varied from 54.3 to 65.0 years, and the proportion of women from 67.8% to 71.3%. The number of physician encounters by patients with RA was significantly higher than by controls. It was highest in the index year and declined promptly thereafter for all case definitions and by 12.2%–46.8% after 10 years. Encounters with subspecialty physicians fell by 61% (rheumatologists) and 34% (internal medicine). In contrast, clinical encounters with family physicians and other physicians fell by only 9%. Visits to the ER and hospital admissions were also significantly higher in RA cases, particularly early in the disease, and fell significantly over the followup.Conclusion.In patients with RA, healthcare use is highest in the first year following the diagnosis, which is also the time of maximal involvement by rheumatologists. Use declines over time, and encounters with patients’ family physicians predominate over other physician groups.

The 70th Annual Meeting of The Canadian Rheumatology Association (CRA) was held at the Fairmont Chateau Frontenac, Quebec City, Quebec, Canada, February 4–7, 2015. The program consisted of presentations covering original research, symposia, awards, and lectures. Highlights of the meeting include 2015 Award Winners: Distinguished Rheumatologist Award: Carter Thorne; Distinguished Investigator Award: Hani El-Gabalawy; Teacher-Educator Award: Andrew E. Thompson; Young Investigator Award: Sindhu Johnson; Summer Studentship Mentor Award: Lori Albert; Innovation in Education Award: Henry Averns; Best Abstract for Basic Science Research by a Trainee: Sina Rusta-Sallehy; Best Abstract for Research by an Undergraduate Student: Tristan Kerr; Best Abstract for Research by a Rheumatology Resident: Claire Barber; Best Poster by a Medical Student: Dennis Wong; Best Poster by a Post-Graduate Resident: Zainab Alabdurubalnabi; CRA/ARF Best Epidemiology/Health Services Research Award: Evelyn Vinet; CRA/ARF Best Clinical Research Award: Glen Hazelwood; CRA/ARF Best Basic Science Research Award: Carolina Landolt-Marticorena; Ian Watson Award for Best Abstract for SLE Research by a Trainee: Ripneet Puar; Phil Rosen Award for Best Abstract for Clinical or Epidemiology Research by a Trainee: Liam O’Neil. Lectures and more: The 2015 Dunlop Dottridge Lecture: HLA-B27, the Microbiome, and the Pathogenesis of Spondyloarthritis, by James Rosenbaum; Preventing Rheumatoid Arthritis: What We’ll Need to Know Before We Start Navigating this Uncharted Territory, by Distinguished Investigator Awardee Hani El-Gabalawy; and the 2015 State of the Art Lectures: A Genomic Approach to Understanding Rheumatic Disease, by Dr. Virginia Pascual, and Modifiable Risk Factors in RA: You Can Lead a Horse to Water but …, by Michael Vallis. The Great Debate: Treat Pre-RA vs Not Treat Pre-RA. Arguing for: Volodko Bakowsky and Derek Haaland; Against: Hani El-Gabalawy and Rob McDougall. The contributions presented at the meeting are reflected in the abstracts, which we are pleased to publish in this issue.

Objective.Large vessel uptake on positron emission tomography/computerized tomography (PET/CT) supports the diagnosis of giant cell arteritis (GCA). Its value, however, in patients without arteritis on temporal artery biopsy and in those receiving glucocorticoids remains unknown. We compared PET/CT results in GCA patients with positive (TAB+) and negative temporal artery biopsies (TAB−), and controls.Methods.Patients with new clinically diagnosed GCA starting treatment with glucocorticoids underwent temporal artery biopsy and PET/CT. Using a visual semiquantitative approach, 18F-fluorodeoxyglucose (FDG) uptake was scored in 8 vascular territories and summed overall to give a total score in patients and matched controls.Results.Twenty-eight patients with GCA and 28 controls were enrolled. Eighteen patients with GCA were TAB+. Mean PET/CT scores after an average of 11.9 days of prednisone were higher in patients with GCA compared to controls, for both total uptake (10.34 ± 2.72 vs 7.73 ± 2.56; p = 0.001), and in 6 of 8 specific vascular territories. PET/CT scores were similar between TAB+ and TAB− patients with GCA. The optimal cutoff for distinguishing GCA cases from controls was a total PET/CT score of ≥ 9, with an area under the receiver-operating characteristic curve of 0.75, sensitivity 71.4%, and specificity 64.3%. Among patients with GCA, these measures correlated with greater total PET/CT scores: systemic symptoms (p = 0.015), lower hemoglobin (p = 0.009), and higher platelet count (p = 0.008).Conclusion.Vascular FDG uptake scores were increased in most patients with GCA despite exposure to prednisone; however, the sensitivity and specificity of PET/CT in this setting were lower than those previously reported.

Objective.To describe the development of the Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 (S2K RI-50) Website (www.s2k-ri-50.com) and to assess satisfaction with its training and examination modules among rheumatologists and rheumatology fellows.Methods.The development of the Website occurred in 3 phases. The first was a deployment phase that consisted of preparing the site map along with its content. The content included the S2K RI-50 training manual, the tests and corresponding question bank, and the online adaptive training module, along with the extensive site testing. The second phase included the participation of rheumatologists and trainees who completed the Website modules. The third was a quality assurance phase in which an online survey was developed to determine the satisfaction level of its users. Further modifications were implemented per participants’ recommendations.Results.The site has been online since it was registered in September 2010. Fourteen rheumatologists and rheumatology trainees from different centers reviewed and completed the material contained in the Website. The survey revealed acceptance among rheumatologists for the Website’s content, design, and presentation. The Website was rated as user-friendly and useful in familiarizing investigators with the S2K RI-50. After completion of the training and examination modules, participants reported a suitable level of preparation to implement the S2K RI-50 in clinical trials and research settings in a timely manner.Conclusion.The Website includes training and examination modules that familiarize rheumatologists with the S2K RI-50 and assesses their competence to use the index. This prepares them for the use of the S2K RI-50 in clinical trials and research settings.

Objective.Antinuclear antibodies (ANA) are a serological hallmark of systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE). While a number of ANA patterns detected by indirect immunofluorescence (IIF) have diagnostic significance, autoantibodies producing the dense fine speckled (DFS) pattern have been reported to be more prevalent in healthy individuals than in SARD.Methods.Sequential samples submitted for ANA testing were screened for anti-DFS antibodies by IIF (n = 3263). Samples with the DFS pattern were tested for anti-DFS70/lens epithelium–derived growth factor (LEDGF) antibodies by ELISA and by a novel chemiluminescence assay (CIA, Quanta Flash DFS70). Sera from patients with various diseases and healthy individuals were tested for anti-DFS70/LEDGF antibodies by CIA. A cohort of 251 patients with SLE was used to analyze serological and clinical associations of anti-DFS70 antibodies.Results.The frequency of anti-DFS antibodies by IIF was 1.62%. The prevalence of anti-DFS70/LEDGF antibodies as detected by CIA in the different cohorts was 8.9% in healthy individuals, 2.8% in SLE, 2.6% in rheumatoid arthritis, 4.0% in asthma, 5.0% in interstitial cystitis, 1.7% in Graves’ disease, and 6.0% in Hashimoto’s thyroiditis. Of note, the prevalence of anti-DFS70/LEDGF antibodies was significantly higher in healthy individuals compared to patients with SARD (p = 0.00085). In SLE results, anti-DFS70/LEDGF antibodies were not significantly associated with clinical features or other autoantibodies typically found in SLE. Only 1/7 SLE sera showed anti-DFS70/LEDGF, but no other autoantibody reactivity.Conclusion.“Monospecific” anti-DFS70/LEDGF antibodies may represent a biomarker for differentiating SARD from non-SARD individuals, but there is a need for a reliable assay to ensure reactivity to DFS70.

Objective.To determine if a hospital rheumatology consultation service improves diagnostic accuracy and adherence to treatment recommendations for gout.Methods.This was a retrospective, single-center, case-control study of consecutive hospitalized patients with gout. Demographic, diagnostic, and treatment variables were compared in patients with and without a rheumatology consultation (controls). American College of Rheumatology (ACR) preliminary criteria for the classification of acute gout and the European League Against Rheumatism (EULAR) recommendations were used to determine diagnostic accuracy. Adherence to EULAR drug management recommendations and Quality Indicators for treatment were compared between groups.Results.In total, 138 patients were studied. The mean (SD) age was 71.3 (13.4) years and 70% were men. Forty-eight (35%) patients had gout on admission, 90 (65%) during their hospital stay, and 8 (6%) had multiple attacks. A total of 79 (57%) patients had a rheumatology consultation. These patients had more joints involved (p < 0.001), more frequent synovial fluid analysis (p < 0.001), and fulfilled ACR classification criteria more frequently than those who did not have a rheumatology consultation (65% vs 37%; p = 0.002). Intraarticular corticosteroid use was more common (44% vs 12%; p < 0.001) in patients who were seen by rheumatology. In contrast, colchicine was used more frequently in controls (63% vs 40%; p = 0.006). Patients seen by rheumatology were more likely to use nonsteroidal antiinflammatory drugs or colchicine for gout prophylaxis while titrating allopurinol to target (p = 0.033).Conclusion.A rheumatology consultation service for hospitalized patients with gout significantly improved the diagnostic accuracy and adherence to established guidelines for short and longterm treatment.

Objective.To describe organ damage accrual, predictors of damage progression, and effect on health-related quality of life (HRQOL) in patients with systemic lupus erythematosus (SLE).Methods.A longitudinal database of patients who met the American College of Rheumatology (ACR) classification criteria for SLE was used. Annual assessments included the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) and the Medical Outcomes Study Short Form-36 (SF-36). The prognostic significance of demographic, disease-related, and treatment-related factors on damage progression was examined using multivariable Cox regression. The effect of changes in SDI scores on HRQOL, measured using the SF-36 summary and subscale scores, was assessed using linear mixed-effects modeling.Results.There were 273 patients with SLE studied over a mean (SD) duration of followup of 7.3 (4.3) years. During followup, 126 (46.2%) had an increase in SDI scores. Patients with preexisting damage at baseline were more likely to have earlier damage progression (HR 2.09, 95% CI 1.44–3.01). Older age, ≥ 8 ACR classification criteria, immunosuppressive drugs, cigarette smoking, and higher mean serum C-reactive protein levels were associated with an earlier increase in SDI scores in multivariable analysis. In general, changes in SDI scores were associated with initial declines in SF-36 scores at the time that damage occurred, with subsequent change comparable to that seen in patients without damage progression.Conclusion.This study identified multiple risk factors, some modifiable, associated with damage progression in patients with SLE. The negative effect on HRQOL emphasizes the need for treatment strategies to reduce the risk of organ damage over time.

Large-vessel involvement is now well recognized in patients with giant cell arteritis (GCA). While exact numbers vary, a recent study demonstrated that up to 67.5% of patients with biopsy-proven GCA have large-vessel disease at the time of diagnosis1. On occasion, large-vessel arteritis may occur in isolation, without classical features such as headache and scalp tenderness, making a clinical diagnosis difficult2. Recognition, however, remains important, as mortality in this subset of patients is significantly increased3. While temporal artery biopsy remains the diagnostic gold standard in GCA, it may be falsely negative in 42% of patients with isolated large artery disease2. In such cases, imaging studies are necessary to confirm large-vessel vasculitis. Angiography is suboptimal because of its invasive nature, risks of contrast allergy and nephropathy, and ability to detect only late anatomical changes such as stenosis or aneurysm. Positron emission tomography/computed tomography (PET/CT) is an alternative, offering the ability to detect both structural lesions and active inflammation. When inflammatory cells become activated, they undergo a “respiratory burst” and metabolize large amounts of glucose4. (18F) fluorodeoxyglucose (FDG) PET is a nuclear medicine scan that uses a glucose analog labeled with radioactive fluorine-18, which is taken into cells through the glut-1-transporter. This tracer mimics the distribution of glucose, thereby identifying conditions with high glucose metabolism, such as malignancy, infection, and inflammation5. Current PET scans are often combined with a low-dose CT scan for enhanced anatomical localization of isotope. While used most commonly for oncologic detection and staging, PET/CT is gaining popularity for use in a number of inflammatory diseases, and has notable advantages for the diagnosis of large-vessel arteritis. PET/CT identifies active inflammation within the arterial wall, potentially leading to an earlier diagnosis of GCA. Studies of small numbers of … Address correspondence to Dr. J.G. Hanly, Division of Rheumatology, Nova Scotia Rehabilitation Centre (2nd Floor), 1341 Summer Street, Halifax, Nova Scotia B3H 4K4, Canada. E-mail: john.hanly{at}cdha.nshealth.ca

Objective.To prospectively examine neuropsychiatric (NP) events and their association with health related quality of life (HRQOL) over time in patients with systemic lupus erythematosus (SLE).Methods.In an observational cohort study from a single academic center, NP events and their attribution were identified at enrollment and at annual assessments for up to 7 years. NP events were characterized using the American College of Rheumatology case definitions; other variables were global SLE disease activity and cumulative organ damage. The outcomes of NP events were recorded and self-report HRQOL was measured with the mental (MCS) and physical (PCS) component summary scores of the Medical Outcomes Study Short Form-36.Results.There were 209 patients, 88% female and 92% Caucasian, with a mean (standard deviation) age of 43.7 (13.8) years. Followup was available in 175/209 (84%) patients. There were 299 NP events in 132/209 (63%) patients over a mean followup of 3.6 (2.5) years. Thirty-one percent of NP events in 54 patients were attributed to SLE. Multivariate analysis indicated lower MCS scores in patients with NP events compared to those without events (p < 0.001) regardless of attribution. The group means for PCS scores were significantly lower in patients with NP events (p < 0.001) regardless of attribution. There was no association between HRQOL and cumulative organ damage, nor between NP events and the progression of organ damage.Conclusion.The association of lower HRQOL with NP events over time, which is independent of progression in cumulative organ damage, emphasizes the persistent negative effect of NP events in the lives of patients with SLE.

Objective.To determine the incidence, healthcare utilization, and costs in older adults with gout.Methods.A 5-year retrospective case-control study of patients with incident gout and matched controls was performed. Study variables were derived from health administrative data and included patient demographics, International Classification of Diseases diagnostic codes, and healthcare cost information.Results.There were 4,071 cases and 16,281 controls, providing a 5-year incidence of gout of 4.4%. The mean (± SD) age (77 ± 7.3 and 76 ± 7.1 yrs) and the male:female ratio (1.0:1.04) were similar in both groups. Gout was diagnosed by family physicians (77%), nonrheumatology subspecialists (18%), general internists (4%), and rheumatologists (0.02%). Hospitalizations were significantly higher in cases (p < 0.001) in the year of diagnosis. Patients with gout had an average of 28.1 physician visits per year compared to 20.6 for controls (p < 0.0001). Drug utilization for the treatment (nonsteroidal antiinflammatory drugs, colchicine, corticosteroids) and prevention (allopurinol, probenecid, sulfinpyrazone) of gout was significantly higher (p < 0.0001). The average healthcare cost differential was +$134 (Cdn) per month (p < 0.001) and +$8,020 per case over 5 years. These costs were due to hospital utilization (64.4%), medications (23.1%), and physician visits (12.5%).Conclusion.Gout is associated with a high disease burden in older men and women. The cost is primarily attributable to hospitalization, probably due to the comorbidities associated with gout. As the majority of cases are managed by nonrheumatologists, it is important that guidelines for the diagnosis and treatment of gout are disseminated to and met by all physician groups.

To determine the prevalence of circulating anti-NR2 antibodies and their association with neuropsychiatric systemic lupus erythematosus (NP-SLE), particularly cognitive function, in women with SLE.Cognitive function was assessed in 65 consecutive women with SLE from a single referral center using standardized neuropsychological tests. These were selected subtests of the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, and the California Verbal Learning Test, which provided information on 8 areas of cognitive function. After a mean followup of 64 (range 52-71) months, cognitive assessments were repeated. Global and domain-specific cognitive impairment was examined using predetermined decision rules, and the change in individual tests of cognitive performance over time was also examined. Overt NP-SLE was identified by clinical assessment and classified using the American College of Rheumatology nomenclature. Circulating IgG anti-NR2 and anti-dsDNA antibodies were determined by ELISA on up to 4 occasions over the study period. A positive result was defined as at least 3 standard deviations above the mean of healthy controls.At enrollment, 15/65 (23%) patients had cognitive impairment. This fell to 7/54 (13%) at followup. In addition 15/65 (23%) patients had a history of clinically overt NP-SLE. Twenty-three of 65 (35%) patients had anti-NR2 antibodies and 48/65 (74%) had anti-dsDNA antibodies. Anti-NR2 antibodies were present in 18/48 (38%) patients with anti-DNA antibodies, and 18/23 patients (78%) with anti-NR2 antibodies also had anti-dsDNA antibodies. There was no association between global cognitive impairment, domain-specific cognitive impairment, or a history of clinically overt NP-SLE and either the presence or amount of anti-NR2 or anti-dsDNA antibodies (p0.05). When change in cognitive performance or the occurrence of new NP-SLE events over the 5-year followup period was examined, there was no significant association with persistent elevation of either antibody (p0.05). Similarly there was no association between a rise in autoantibodies over time and the development of overt NP events or cognitive decline (p0.05).These results indicate that anti-NR2 antibodies occur in 35% of women with SLE and are infrequent in the absence of detectable anti-dsDNA antibodies. Their presence in the circulation is not associated with cognitive dysfunction at a single timepoint, and an increase in or persistently elevated antibody levels are not associated with a change in cognitive performance over time. There was no association with clinically overt NP-SLE. However, as our study did not examine cerebrospinal fluid samples, these results do not exclude a potential pathogenic role in selected patients for this group of autoantibodies should they penetrate the blood-brain barrier and thereby gain direct access to neuronal tissues.

We describe a patient with Wegener's granulomatosis (WG) who developed neurological symptoms attributed to meningeal involvement. The diagnosis of WG was complicated by persistently negative antineutrophil cytoplasmic antibodies (ANCA) and lack of specificity in the histopathological findings from multiple anatomical sites. This rare neurological manifestation of WG was treated successfully with oral cyclophosphamide and the patient has continued remission for 3 years taking oral methotrexate.

The cause of neurologic (N) and psychiatric (P) syndromes in patients with systemic lupus erythematosus (SLE) is mutifactorial and includes primary immunopathogenic mechanisms, nonspecific sequelae of chronic disease, and concurrent illnesses. We compared the prevalence, diversity, and clinical significance of NP syndromes in patients with SLE and rheumatoid arthritis (RA).Fifty-three patients with SLE were matched by age and sex to 53 patients with RA attending ambulatory clinics in a single academic medical center. All fulfilled the American College of Rheumatology (ACR) classification criteria for either SLE or RA. Cumulative NP manifestations were determined using the ACR nomenclature and case definitions for 19 NP syndromes. Depression and anxiety were measured by the Hospital Anxiety and Depression Scales (HADS) and symptoms of cognitive dysfunction were assessed by the Cognitive Symptoms Inventory (CSI). Health related quality of life (HRQOL) was evaluated by the SF-36 and fatigue by a 10 point Likert scale.The patients were well matched with regard to age, sex, disease duration, and years of education. There were no significant differences in self-reported HRQOL, fatigue, anxiety, depression, and cognitive symptoms between the 2 groups. The proportion of patients with cumulative NP events was higher in RA than in SLE patients (47% vs 28%; p = 0.045), and of these the occurrence of multiple NP events in individual patients was comparable in both groups (SLE 53%; RA 48%; p = 0.75). Fifty-five percent and 66% of NP events occurred prior to the diagnosis of SLE and RA, respectively. NP events common to both SLE and RA patients were headaches, mood disorders, acute confusional states, anxiety, cerebrovascular disease, and cognitive dysfunction. Seizures and demyelinating syndrome occurred only in SLE patients, but were rare. Depression scores (HADS) were significantly higher in SLE patients with a history of cumulative NP events compared to RA patients with NP events (p = 0.02). Similarly, symptoms of cognitive dysfunction (CSI) were more common in SLE patients with a history of NP manifestations (p = 0.02). However, there were no significant differences in SF-36 subscale or fatigue scores between SLE and RA patients with cumulative NP events.NP syndromes, regardless of etiology, are common in both SLE and RA patients. SLE patients with NP syndromes report more symptoms of depression and cognitive dysfunction compared to RA patients with NP syndromes, but do not report significantly poorer HRQOL. These results emphasize the presence of non-disease-specific causes of NP manifestations in SLE patients, which should be acknowledged in future studies of pathogenesis and treatment.

To describe the range and attribution of neuropsychiatric (NP) disease in an unselected cohort of patients with systemic lupus erythematosus (SLE) and to examine the association with cumulative organ damage, medication use, and quality of life.One hundred eleven patients with SLE in a single referral center were studied. NP syndromes were defined using the American College of Rheumatology (ACR) nomenclature and case definitions. Overall disease activity was measured by the SLE Disease Activity Index (SLEDAI); cumulative organ damage was determined by the ACR/SLICC damage index; and quality of life by the SF-36.Patients' mean age was 44.7 years, 87% were female, and 92% were Caucasian. The mean (+/- SE) disease duration was 10.1 +/- 0.7 years. A total of 74 NP events were identified in 41 of 111 (37%) patients. Thirteen of the 19 ACR NP syndromes were identified and 2 or more NP manifestations occurred in 56% of patients. Central nervous system manifestations accounted for 92% of the events compared to involvement of the peripheral nervous system in 8%. Thirty-five (47%) of these events were attributed entirely to SLE, 30 (41%) were attributed exclusively to non-SLE factors, and in the remaining 9 events (12%) both SLE and non-SLE factors were felt to be contributory. Cumulative organ damage was higher in patients with NP disease, although this was not statistically significant and they were more likely to have received prednisone or immunosuppressive drugs (p0.05). Patients with NP disease reported more fatigue (p0.05) and had significantly lower scores on 7 of 8 subscales of the SF-36 (p0.05). These associations were found regardless of the attribution of NP disease. In contrast, the occurrence of renal disease in the same cohort of patients was not associated with lower SF-36 scores or fatigue.In patients with SLE, NP disease has diverse manifestations and can be attributed to lupus in roughly half of the cases. The occurrence of NP disease is associated with more frequent use of corticosteroids and immunosuppressive drugs. In contrast to other serious manifestations of SLE, such as renal disease, NP disease is associated with a significant reduction in quality of life.

To describe the trends in physician resources, changes in activity profiles, and the output of the postgraduate training programs in Canadian academic rheumatology centers from 1998-2002.In 1998, the Canadian Council of Academic Rheumatologists (CCAR) established a prospective database to monitor physician resources, activity profiles, and recruitment within 15 academic rheumatology units in Canada. Information was also collected on residents pursuing subspeciality training in rheumatology.Over the 5 year period there was an increase in the number of rheumatologists from 157 to 168. The majority of this increase (91%) was attributable to changes in full-time staff. The mean age of rheumatologists increased from 47.9 to 48.9 years over the same period and the ratio of male to female rheumatologists decreased incrementally from 2.5:1 to 1.9:1. The overall allocation of time for clinical care (54-53%), teaching (17-16%), research (21-23%), and administration (7%) remained stable over time. Unfilled staff positions varied between 18-25 per year and were spread between 9-12 centers. The number of trainees in adult and pediatric rheumatology fell incrementally from 38 to 22 over the first 4 years of the study, with an increase to 30 in 2002. The majority of trainees were located at 2 centers and the number of active training programs varied between 6 and 12 per year. Funding for clinical fellowship training was provided by government (27-51%), the Arthritis Society (21-33%), and alternative sources (23-40%).These results indicate that rheumatology physician resources within Canadian academic units are inadequate to fulfill responsibilities in the delivery of clinical service and academic programs. Enrollment in rheumatology training programs is falling and is insufficient to meet the present and future needs for patients with rheumatic diseases in Canada.

To examine the effect on annexin V binding to cardiolipin (CL) and in vitro thrombin generation by plasma samples from an unselected population of patients with confirmed venous thrombosis and matched controls. The prevalence of autoimmune antiphospholipid antibodies (aPL) was also determined.A total of 111 patients who presented to a single emergency room with symptoms suggestive of venous thromboembolic (VTE) disease were studied. In 34 patients the diagnosis of lower limb deep venous thrombosis (DVT) and/or pulmonary embolus (PE) was confirmed (VTE+ group). In the remaining 77 patients the diagnostic workup was negative (VTE- group). Plasma samples were collected prior to the initiation of anticoagulation and examined for IgG anticardiolipin (aCL), IgG anti-beta2-glycoprotein I (GPI), and IgG anti-prothrombin (aPT antibodies) by ELISA. In addition, the effect of individual patient and control plasma samples on annexin V binding to CL and on in vitro thrombin generation was determined by a competitive ELISA and a chromogenic assay, respectively.The prevalence and levels of IgG aCL, anti-beta2-GPI, and aPT antibodies were similar in the VTE+ and VTE- groups. However, plasma samples from the VTE+ group caused a significant inhibition of in vitro thrombin generation (mean +/- SD Z score: -0.66 +/- 0.97 vs 0.26 +/- 1.46; p0.001) and a concurrent but less impressive inhibition of annexin V binding to CL (mean +/- SD Z score: -2.53 +/- 1.44 vs -2.05 +/- 1.61; p = 0.123). Upon analyzing a panel of clinical and laboratory variables, only age and inhibition of thrombin generation were significantly associated with VTE disease.Our findings suggest that subtle abnormalities in annexin V physiology may contribute to the procoagulant state in patients with idiopathic venous thrombosis.

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.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.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.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.