Factors associated with first thrombosis in patients presenting with obstetric antiphospholipid syndrome (APS) in the APS Alliance for Clinical Trials and International Networking Clinical Database and Repository: a retrospective study.

OBJECTIVE: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. DESIGN: Retrospective study. SETTING: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk factors for thrombosis and aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089]. CONCLUSION: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. TWEETABLE ABSTRACT: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.

Breast cancer in systemic lupus erythematosus (SLE): receptor status and treatment.

Objective There is a decreased risk of breast cancer in systemic lupus erythematosus (SLE) versus the general population; little is known regarding the receptor status of breast cancers in SLE, or treatment. Methods Breast cancer cases occurring after SLE diagnosis were ascertained through linkage with tumor registries. We determined breast cancer positivity for estrogen receptors (ER), progesterone receptors (PR), and/or Human Epidermal Growth Factor Receptor 2 (HER2), as well as cancer treatment. Results We obtained information on ER, PR, and/or HER2 status for 63 SLE patients with breast cancer. Fifty-three had information on ER and/or PR status; 36 of these (69%) were ER positive. Thirty-six of the 63 had information on HER2 status; of these, 26 had complete information on all three receptors. Twenty-one of these 26 (81%) were HER2 negative; seven of 26(27%) were triple negative. All but one patient underwent surgery; 11.5% received both non-tamoxifen chemotherapy and radiotherapy, 16.4% radiotherapy without non-tamoxifen chemotherapy, and 14.7% received non-tamoxifen chemotherapy without radiotherapy. Conclusion ER positivity was similar to historical general population figures, with a trend toward a higher proportion of triple-negative breast cancers in SLE (possibly reflecting the relatively young age of our SLE patients).

Breast cancer in systemic lupus.

Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug exposures over time. In univariate and multivariate models, the principal factor associated with breast cancers was older age at cohort entry. Conclusions There was little evidence that breast cancer risk in this SLE sample was strongly driven by any of the clinical factors that we studied. Further search for factors that determine the lower risk of breast cancer in SLE may be warranted.

The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients.

Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression. The frequency of anti-DFS70 was 7.1% (95% CI: 5.7-8.8%), while only 1.1% (95% CI: 0.6-1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti-ß2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI: 0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence of anti-DFS70 was higher than the range previously published for adult SLE (7.1 versus 0-2.8%) and was associated with musculoskeletal activity and anti-ß2 glycoprotein 1 autoantibodies. However, 'monospecific' anti-DFS70 autoantibodies were rare (1.1%) and therefore may be helpful to discriminate between ANA-positive healthy individuals and SLE.

Anti-C1q antibodies in systemic lupus erythematosus.

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

The needs of persons with lupus and health care providers: a qualitative study aimed toward the development of the Lupus Interactive Navigator™.

OBJECTIVE: Systemic lupus erythematosus is an inflammatory autoimmune disease associated with high morbidity and unacceptable mortality. A major challenge for persons with lupus is coping with their illness and complex care. Our objective was to identify the informational and resource needs of persons with lupus, rheumatologists, and allied health professionals treating lupus. Our findings will be applied toward the development of an innovative web-based technology, the Lupus Interactive Navigator (LIN™), to facilitate and support engagement and self-management for persons with lupus. METHODS: Eight focus groups were conducted: four groups of persons with lupus (n=29), three groups of rheumatologists (n=20), and one group of allied health professionals (n=8). The groups were held in British Columbia, Ontario, and Quebec. All sessions were audio-recorded and transcribed verbatim. Qualitative analysis was performed using grounded theory. The transcripts were reviewed independently and coded by the moderator and co-moderator using 1) qualitative data analysis software developed by Provalis Research, Montreal, Canada, and 2) manual coding. RESULTS: Four main themes emerged: 1) specific information and resource needs; 2) barriers to engagement in health care; 3) facilitators of engagement in health care; and 4) tools identified as helpful for the self-management of lupus. CONCLUSION: These findings will help guide the scope of LIN™ with relevant information topics and specific tools that will be most helpful to the diverse needs of persons with lupus and their health care providers.

Breast cancer in systemic lupus erythematosus.

OBJECTIVE: Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries. METHODS: Information on age, SLE duration, cancer date, and histology was available. We analyzed information on histological type and performed multivariate logistic regression analyses of histological types according to age, SLE duration, and calendar year. RESULTS: We studied 180 breast cancers in the SLE cohort. Of the 155 cases with histology information, 11 were referred to simply as 'carcinoma not otherwise specified'. In the remaining 144 breast cancers, the most common histological type was ductal carcinoma (n = 95; 66%) followed by lobular adenocarcinoma (n = 11; 8%), 15 cancers were of mixed histology, and the remaining ones were special types. In our regression analyses, the independent risk factors for lobular versus ductal carcinoma was age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01-1.14] and for the 'special' subtypes it was age (OR 1.06, 95% CI 1.01-1.10) and SLE duration (OR 1.05, 95% CI 1.00-1.11). CONCLUSIONS: Generally, up to 80% of breast cancers are ductal carcinomas. Though our results are not definitive, in the breast cancers that occur in SLE, there may be a slight decrease in the ductal histological type. In our analyses, age and SLE duration were independent predictors of histological status.

Designing an intervention for women with systemic lupus erythematosus from medically underserved areas to improve care: a qualitative study.

OBJECTIVE: Systemic lupus erythematosus (lupus) disproportionately affects women, racial/ethnic minorities and low-income populations. We held focus groups for women from medically underserved communities to discuss interventions to improve care. METHODS: From our Lupus Registry, we invited 282 women, ≥18 years, residing in urban, medically underserved areas. Hospital-based clinics and support groups also recruited participants. Women were randomly assigned to three focus groups. Seventy-five-minute sessions were recorded, transcribed and coded thematically using interpretative phenomenologic analysis and single counting methods. We categorized interventions by benefits, limitations, target populations and implementation questions. RESULTS: Twenty-nine women with lupus participated in three focus groups, (n = 9, 9, 11). 80% were African American and 83% were from medically underserved zip codes. Themes included the desire for lupus education, isolation at the time of diagnosis, emotional and physical barriers to care, and the need for assistance navigating the healthcare system. Twenty of 29 participants (69%) favored a peer support intervention; 17 (59%) also supported a lupus health passport. Newly diagnosed women were optimal intervention targets. Improvements in quality of life and mental health were proposed outcome measures. CONCLUSION: Women with lupus from medically underserved areas have unique needs best addressed with an intervention designed through collaboration between community members and researchers.

The frequency of and associations with hospitalization secondary to lupus flares from the 1000 Faces of Lupus Canadian cohort.

OBJECTIVES: Hospitalization is a major factor in health care costs and a surrogate for worse outcomes in chronic disease. The aim of this study was to determine the frequency of hospitalization secondary to lupus flare, the causes of hospitalization, and to determine risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). METHODS: Data were collected as part of the 1000 Canadian Faces of Lupus, a prospective cohort study, where annual major lupus flares including hospitalizations were recorded over a 3-year period. RESULTS: Of 665 patients with available hospitalization histories, 68 reported hospitalization related to a SLE flare over 3 years of follow-up. The average annual hospitalization rate was 7.6% (range 6.6-8.9%). The most common reasons for hospitalization were: hematologic (22.1%), serositis (20.6%), musculoskeletal (MSK) (16.2%), and renal (14.7%). Univariate risk factors for lupus hospitalization included (OR [95% CI]; p < 0.05): juvenile-onset lupus (2.2 [1.1-4.7]), number of ACR SLE criteria (1.4 [1.1-1.7], baseline body mass index (BMI) (1.1 [1.0-1.1]), psychosis (3.4 [1.2-9.9]), aboriginal race (3.2 [1.5-6.7]), anti-Smith (2.6 [1.2-5.4]), erythrocyte sedimentation rate >25 mm/hr (1.9 [1.1-3.4]), proteinuria >0.5 g/d (4.2 [1.9-9.3], and SLAM-2 score (1.1 [1.0-1.2]). After multivariate regression only BMI, number of ACR criteria, and psychosis were associated with hospitalization for lupus flare. CONCLUSIONS: The mean annual rate of hospitalization attributed to lupus was lower than expected. Hematologic, serositis, MSK and renal were the most common reasons. In a regression model elevated BMI, more ACR criteria and psychosis were associated with hospitalization.

Measurement of separate cosmic-ray electron and positron spectra with the fermi large area telescope.

We measured separate cosmic-ray electron and positron spectra with the Fermi Large Area Telescope. Because the instrument does not have an onboard magnet, we distinguish the two species by exploiting Earth's shadow, which is offset in opposite directions for opposite charges due to Earth's magnetic field. We estimate and subtract the cosmic-ray proton background using two different methods that produce consistent results. We report the electron-only spectrum, the positron-only spectrum, and the positron fraction between 20 and 200 GeV. We confirm that the fraction rises with energy in the 20-100 GeV range. The three new spectral points between 100 and 200 GeV are consistent with a fraction that is continuing to rise with energy.

A targeted association study in systemic lupus erythematosus identifies multiple susceptibility alleles.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Multiple genetic and environmental factors contribute to the pathogenesis of this disease. Recent genome-wide association studies have added substantially to the number of genes associated with SLE. To replicate some of these susceptibility loci, single-nucleotide polymorphisms reported to be associated to SLE were evaluated in a cohort of 245 well-phenotyped Canadian SLE trios. Our results replicate previously reported associations to alleles of interferon regulatory factor 5 (IRF5), major histocompatibility complex (MHC), tumor necrosis factor (ligand) superfamily member 4 (TNFSF4), Kell blood group complex subunit-related family member 6 (XKR6), B-cell scaffold protein with ankyrin repeats 1 (BANK1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), ubiquitin-conjugating enzyme E2L 3 (UBE2L3) and islet cell autoantigen 1 (ICA1). We also identify putative associations to cytotoxic T-lymphocyte-associated protein 4 (CTLA4), a gene associated with several autoimmune disorders, and ERBB3, a locus on 12q13 that was previously reported to be associated with type 1 diabetes. This study confirms the existence of multiple genetic risk factors for SLE, and supports the notion that some risk factors for SLE are shared with other inflammatory disorders.

An assessment of disease flare in patients with systemic lupus erythematosus: a comparison of BILAG 2004 and the flare version of SELENA.

AIMS: To compare the British Isles Lupus Assessment Group (BILAG) 2004, the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) flare index (SFI) and physician's global assessment (PGA) in assessing flares of disease activity in patients with systemic lupus erythematosus (SLE). METHODS: Sixteen patients with active SLE were assessed by a panel of 16 rheumatologists. The order in which the patients were seen was randomised using a 4×4 Latin square design. Each patient's flare status was determined at each assessment using the BILAG 2004 activity index; the SFI and a PGA. A group of five specialists designated each patient into severe, moderate, mild or no flare categories. RESULTS: The rate of complete agreement (95% CI) of the four individual examining physicians for any flare versus no flare was 81% (55% to 94%), 75% (49% to 90%) and 75% (49% to 90%) for the BILAG 2004 index, SELENA flare instrument and PGA, respectively. The overall agreement between flare defined by BILAG 2004 and the SFI was 81% and when type of flare was considered was 52%. Intraclass correlation coefficients (95% CI), as a measure of internal reliability, were 0.54 (0.32 to 0.78) for BILAG 2004 flare compared with 0.21 (0.08 to 0.48) for SELENA flare and 0.18 (0.06 to 0.45) for PGA. Severe flare was associated with good agreement between the indices but mild/moderate flare was much less consistent. CONCLUSIONS: The assessment of flare in patients with SLE is challenging. No flare and severe flare are identifiable but further work is needed to optimise the accurate 'capture' of mild and moderate flares.

SF-36 summary and subscale scores are reliable outcomes of neuropsychiatric events in systemic lupus erythematosus.

OBJECTIVE: To examine change in health-related quality of life in association with clinical outcomes of neuropsychiatric events in systemic lupus erythematosus (SLE). METHODS: An international study evaluated newly diagnosed SLE patients for neuropsychiatric events attributed to SLE and non-SLE causes. The outcome of events was determined by a physician-completed seven-point scale and compared with patient-completed Short Form 36 (SF-36) health survey questionnaires. Statistical analysis used linear mixed-effects regression models with patient-specific random effects. RESULTS: 274 patients (92% female; 68% Caucasian), from a cohort of 1400, had one or more neuropsychiatric event in which the interval between assessments was 12.3 ± 2 months. The overall difference in change between visits in mental component summary (MCS) scores of the SF-36 was significant (p<0.0001) following adjustments for gender, ethnicity, centre and previous score. A consistent improvement in neuropsychiatric status (N=295) was associated with an increase in the mean (SD) adjusted MCS score of 3.66 (0.89) in SF-36 scores. Between paired visits when the neuropsychiatric status consistently deteriorated (N=30), the adjusted MCS score decreased by 4.00 (1.96). For the physical component summary scores the corresponding changes were +1.73 (0.71) and -0.62 (1.58) (p<0.05), respectively. Changes in SF-36 subscales were in the same direction (p<0.05; with the exception of role physical). Sensitivity analyses confirmed these findings. Adjustment for age, education, medications, SLE disease activity, organ damage, disease duration, attribution and characteristics of neuropsychiatric events did not substantially alter the results. CONCLUSION: Changes in SF-36 summary and subscale scores, in particular those related to mental health, are strongly associated with the clinical outcome of neuropsychiatric events in SLE patients.

Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus.

OBJECTIVE: Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. METHODS: Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti-ß(2) glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. RESULTS: Disease duration at enrolment was 5.4 ± 4.2 months, follow-up was 3.6 ± 2.6 years. Patients were 89.1% female with mean (±SD) age 35.2 ± 13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-ß(2) glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. CONCLUSION: In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.

Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity.

Systemic lupus erythematosus (SLE) is characterized by multiple autoantibodies and complement activation. Recent studies have suggested that anti-nuclear antibody (ANA) positivity may disappear over time in some SLE patients. Anti-double-stranded DNA (dsDNA) antibody titers and complement levels may vary with time and immunosuppressive treatment, while the behavior of anti-extractable nuclear antigen (ENA) over time is less well understood. This study sought to determine the correlation between historical autoantibody tests and current testing in patients with SLE. Three hundred and two SLE patients from the ACR Reclassification of SLE (AROSE) database with both historical and current laboratory data were selected for analysis. The historical laboratory data were compared with the current autoantibody tests done at the reference laboratory and tested for agreement using percent agreement and Kappa statistic. Serologic tests included ANA, anti-dsDNA, anti-Smith, anti-ribonucleoprotein (RNP), anti-Ro, anti-La, rheumatoid factor (RF), C3 and C4. Among those historically negative for immunologic markers, a current assessment of the markers by the reference laboratory generally yielded a low percentage of additional positives (3-13%). However, 6/11 (55%) of those historically negative for ANA were positive by the reference laboratory, and the reference laboratory test also identified 20% more patients with anti-RNP and 18% more with RF. Among those historically positive for immunologic markers, the reference laboratory results were generally positive on the same laboratory test (range 57% to 97%). However, among those with a history of low C3 or C4, the current reference laboratory results indicated low C3 or C4 a low percentage of the time (18% and 39%, respectively). ANA positivity remained positive over time, in contrast to previous studies. Anti-Ro, La, RNP, Smith and anti-dsDNA antibodies had substantial agreement over time, while complement had less agreement. This variation could partially be explained by variability of the historical assays, which were done by local laboratories over varying periods of time. Variation in the results for complement, however, is more likely to be explained by response to treatment. These findings deserve consideration in the context of diagnosis and enrolment in clinical trials.

International consensus for a definition of disease flare in lupus.

The Lupus Foundation of America (LFA) convened an international working group to obtain a consensus definition of disease flare in lupus. With help from the Paediatric Rheumatology International Trials Organization (PRINTO), two web-based Delphi surveys of physicians were conducted. Subsequently, the LFA held a second consensus conference followed by a third Delphi survey to reach a community-wide agreement for flare definition. Sixty-nine of the 120 (57.5%) polled physicians responded to the first survey. Fifty-nine of the responses were available to draft 12 preliminary statements, which were circulated in the second survey. Eighty-seven of 118 (74%) physicians completed the second survey, with an agreement of 70% for 9/12 (75%) statements. During the second conference, three alternative flare definitions were consolidated and sent back to the international community. One hundred and sixteen of 146 (79.5%) responded, with agreement by 71/116 (61%) for the following definition: "A flare is a measurable increase in disease activity in one or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements. It must be considered clinically significant by the assessor and usually there would be at least consideration of a change or an increase in treatment." The LFA proposes this definition for lupus flare on the basis of its high face validity.

Surveillance of systemic autoimmune rheumatic diseases using administrative data.

There is growing interest in developing tools and methods for the surveillance of chronic rheumatic diseases, using existing resources such as administrative health databases. To illustrate how this might work, we used population-based administrative data to estimate and compare the prevalence of systemic autoimmune rheumatic diseases (SARDs) across three Canadian provinces, assessing for regional differences and the effects of demographic factors. Cases of SARDs (systemic lupus erythematosus, scleroderma, primary Sjogren's, polymyositis/dermatomyositis) were ascertained from provincial physician billing and hospitalization data. We combined information from three case definitions, using hierarchical Bayesian latent class regression models that account for the imperfect nature of each case definition. Using methods that account for the imperfect nature of both billing and hospitalization databases, we estimated the over-all prevalence of SARDs to be approximately 2-3 cases per 1,000 residents. Stratified prevalence estimates suggested similar demographic trends across provinces (i.e. greater prevalence in females-versus-males, and in persons of older age). The prevalence in older females approached or exceeded 1 in 100, which may reflect the high burden of primary Sjogren's syndrome in this group. Adjusting for demographics, there was a greater prevalence in urban-versus-rural settings. In our work, prevalence estimates had good face validity and provided useful information about potential regional and demographic variations. Our results suggest that surveillance of some rheumatic diseases using administrative data may indeed be feasible. Our work highlights the usefulness of using multiple data sources, adjusting for the error in each.

Prospective analysis of neuropsychiatric events in an international disease inception cohort of patients with systemic lupus erythematosus.

OBJECTIVES: To determine the frequency, accrual, attribution and outcome of neuropsychiatric (NP) events and impact on quality of life over 3 years in a large inception cohort of patients with systemic lupus erythematosus (SLE). METHODS: The study was conducted by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis. NP events were identified using the American College of Rheumatology case definitions, and decision rules were derived to determine the proportion of NP disease attributable to SLE. The outcome of NP events was recorded and patient-perceived impact determined by the SF-36. RESULTS: 1206 patients (89.6% female) with a mean (+/-SD) age of 34.5+/-13.2 years were included in the study. The mean disease duration at enrollment was 5.4+/-4.2 months. Over a mean follow-up of 1.9+/-1.2 years, 486/1206 (40.3%) patients had > or =1 NP events, which were attributed to SLE in 13.0-23.6% of patients using two a priori decision rules. The frequency of individual NP events varied from 47.1% (headache) to 0% (myasthenia gravis). The outcome was significantly better for those NP events attributed to SLE, especially if they occurred within 1.5 years of the diagnosis of SLE. Patients with NP events, regardless of attribution, had significantly lower summary scores for both mental and physical health over the study. CONCLUSIONS: NP events in patients with SLE are of variable frequency, most commonly present early in the disease course and adversely impact patients' quality of life over time. Events attributed to non-SLE causes are more common than those due to SLE, although the latter have a more favourable outcome.

Fermi large area telescope search for photon lines from 30 to 200 GeV and dark matter implications.

Dark matter (DM) particle annihilation or decay can produce monochromatic gamma rays readily distinguishable from astrophysical sources. gamma-ray line limits from 30 to 200 GeV obtained from 11 months of Fermi Large Area Space Telescope data from 20-300 GeV are presented using a selection based on requirements for a gamma-ray line analysis, and integrated over most of the sky. We obtain gamma-ray line flux upper limits in the range 0.6-4.5x10{-9} cm{-2} s{-1}, and give corresponding DM annihilation cross-section and decay lifetime limits. Theoretical implications are briefly discussed.

Burden of autoantibodies and association with disease activity and damage in systemic lupus erythematosus.

OBJECTIVES: To determine whether immunological burden of autoantibodies as reflected by the number of cumulative antibodies present at inception and after 3 and 5 years is associated with or predicts subsequent disease activity and damage in lupus. METHODS: Patients with SLE followed from inception at a single centre between 1992 and 2007 were included. Twelve autoantibodies were assayed in each patient at years 1, 3 and 5 of disease. The relationship between the burden of autoantibodies and outcomes, SDI (Systemic Lupus International Collaborative Clinics Damage Index), AMS (Adjusted Mean SLEDAI-2K) and AMS excluding anti-ds DNA (AMS-DNA) was evaluated as an association and as prediction. We determined the association between autoantibody burden and outcomes at years 1, 3 and 5 and the prediction using autoantibody burden at year 1 and year 3 to predict outcomes at years 3 and 5 respectively. RESULTS: Between 1992 and 2007, 235 inception patients were identified. Of these, 223, 163 and 129 patients had 10 or more autoantibodies tested at years 1, 3 and year 5 following diagnosis respectively. There was no association between the burden at years 1, 3 and 5 and outcome measures at years 1, 3 and 5 respectively. Furthermore, burden of autoantibodies at years 1 and 3 did not predict the outcome measures at years 3 and 5 respectively. CONCLUSIONS: Immunological burden in SLE at years 1, 3 or 5 as reflected by the number of autoantibodies found, was not associated with or predictive of subsequent disease activity or damage over time.