Systemic autoimmune rheumatic disease prevalence in Canada: updated analyses across 7 provinces.

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.

Lymphoma risk in systemic lupus: effects of disease activity versus treatment.

OBJECTIVE: To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). METHODS: We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. RESULTS: We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. CONCLUSIONS: In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.

Historical perspectives on the discovery and elucidation of autoantibodies to centromere proteins (CENP) and the emerging importance of antibodies to CENP-F.

Autoantibodies to the centromere proteins (CENP), which are major constituents of the primary constriction of metaphase chromosomes, were first described in 1980. In those seminal publications and 30 years of research that have followed, a number of CENP have been identified as autoantibody targets in human diseases. Historically, autoantibodies directed to CENP-A, -B and -C have been considered relatively specific biomarkers for limited cutaneous systemic sclerosis (lcSSc) or the calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome. These autoantibodies, found in up to 40% of SSc sera, can be identified by indirect immunofluorescence (IIF) on a variety of tissue culture cell lines as a discrete speckled staining pattern of both interphase nuclei and metaphase chromatin. Early in the investigation of anti-CENP, it became apparent that some autoantibodies had a similar IIF pattern wherein as cells entered into the cell cycle, speckled staining of the metaphase chromatin could be observed but, unlike conventional CENP staining, interphase nuclei were not stained. Subsequent studies identified one of the targets of these autoantibodies to be CENP-F, a kinesin binding protein essential for completion of the cell cycle. Early clinical studies found that, unlike antibodies to the earlier described CENP, lcSSc rarely expressed anti-CENP-F and approximately 50% of these patients had a malignancy. This review provides a historical perspective of CENP autoantibodies and focuses on an update of the information on CENP-F and their clinical associations.

Effects of an enhanced secondary prevention program for patients with heart disease: a prospective randomized trial.

BACKGROUND: Secondary prevention medications in cardiac patients improve outcomes. However, prescription rates for these drugs and long-term adherence are suboptimal. OBJECTIVE: To determine whether an enhanced secondary prevention program improves outcomes. METHODS: Hospitalized patients with indications for secondary prevention medications were randomly assigned to either usual care or an intervention arm, in which an intensive program was used to optimize prescription rates and long-term adherence. Follow-up was 19 months. RESULTS: A total of 2643 patients were randomly assigned in the study; 1342 patients were assigned to usual care and 1301 patients were assigned to the intervention arm. Prescription rates were near optimal except for lipid-lowering medications. Rehospitalization rates per 100 patients were 136.2 and 132.6 over 19 months in the usual care and intervention groups, respectively (P=0.59). Total days in hospital per patient were similar (10.9 days in the usual care group versus 10.2 days in the intervention group; P not significant). Crude mortality was 6.2% and 5.5% in the usual care and intervention groups, respectively, with no significant difference (P=0.15) in overall survival. Post hoc analysis suggested that after the study team became experienced, days in hospital per patient were reduced by the program (11.1+/-0.91 and 8.9+/-0.61 in the usual care and intervention groups, respectively; P<0.05). CONCLUSIONS: The intervention program failed to improve outcomes in the present study. One explanation for these results is the near optimal physician compliance with guidelines in both groups. It is also possible that a substantial learning curve for the staff was involved, as suggested by the reduction in total days in hospital in the intervention patients during the second part of the study.

The development of systemic sclerosis classification criteria.

Systemic sclerosis (SSc) is a rare connective tissue disorder whose aetiology remains obscure, although environmental and genetic influences are likely to play a role. Disease registries have contributed to enhancing our understanding of this debilitating illness, but without sensitive, specific, and extensively validated classification criteria, accurate comparison between registries and the identification of patients suitable for clinical trials can be problematic. The American College of Rheumatology (ACR) criteria, published in 1980, have become outdated as our understanding of disease specific autoantibodies and nailfold capillaroscopy has improved. In addition, the sensitivity of the ACR criteria is low with respect to limited SSc. Although subsequent classification systems have been proposed, none has gained universal approval. The two- versus three-subset disease model remains a point of debate. Newly derived criteria are likely to draw upon the older classification systems as well as incorporating up-to-date diagnostic techniques and biomarkers. Validation will be critical before their use becomes widespread.

Group psychotherapy reduces illness intrusiveness in systemic lupus erythematosus.

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.

Internet hand x-rays: A comparison of joint space narrowing and erosion scores (Sharp/Genant) of plain versus digitized x-rays in rheumatoid arthritis patients.

BACKGROUND: The objective of the study is to examine the reliability of erosion and joint space narrowing scores derived from hand x-rays posted on the Internet compared to scores derived from original plain x-rays. METHODS: Left and right x-rays of the hands of 36 patients were first digitized and then posted in standard fashion to a secure Internet website. Both the plain and Internet x-rays were scored for erosions and joint space narrowing using the Sharp/Genant method. All scoring was completed in a blind and randomized manner. Agreement between plain and Internet x-ray scores was calculated using Lin's concordance correlations and Bland-Altman graphical representation. RESULTS: Erosion scores for plain x-rays showed almost perfect concordance with x-rays read on the Internet (concordance 0.887). However, joint space narrowing scores were only "fair" (concordance 0.365). Global scores demonstrated substantial concordance between plain and Internet readings (concordance 0.769). Hand x-rays with less disease involvement showed a tendency to be scored higher on the Internet versions than those with greater disease involvement. This was primarily evident in the joint space narrowing scores. CONCLUSIONS: The Internet represents a valid medium for displaying and scoring hand x-rays of patients with RA. Higher scores from the Internet version may be related to better viewing conditions on the computer screen relative to the plain x-ray viewing, which did not include magnifying lens or bright light. The capability to view high quality x-rays on the Internet has the potential to facilitate information sharing, education, and encourage collaborative studies.