Effect of menopause on the modified Rodnan skin score in systemic sclerosis

INTRODUCTION: We aimed to evaluate the effect of menopause on skin thickening, as measured by the modified Rodnan skin score (mRSS), in women with systemic sclerosis (SSc). METHODS: We identified women with either limited or diffuse SSc, aged ≥ 18 years, enrolled within the Canadian Scleroderma Research Group (CSRG) cohort, between 2004 and 2011. As part of the CSRG cohort, subjects undergo annual assessments with standardized questionnaires and physical examinations. We performed multivariate regression analyses using generalized estimating equation (GEE) to determine the effect of menopause on the mRSS, adjusting for relevant covariates including notably age, follow-up time, and disease duration. RESULTS: We identified 1070 women with SSc, contributing a total of 3546 observations over the study period. Of these women, at baseline, 65% had limited disease and 35% diffuse disease. In multivariate analyses, we observed a substantial effect of postmenopausal status on the mean mRSS in women with diffuse disease subtype [−2.62 units, 95% confidence interval (CI) -4.44, −0.80] and significant interaction between menopausal status and disease subtype (2.04 units, 95% CI 0.20, 3.88). The effect of postmenopausal status on the mean mRSS was smaller in women with limited SSc (−0.58, 95% CI −1.50, 0.34). CONCLUSIONS: Our results suggest that menopause has a substantial effect on skin thickening in diffuse SSc, with postmenopausal status being associated with a lower mean mRSS compared to premenopausal status

The X-ray source content of the XMM-Newton Galactic plane survey

We report the results of an optical campaign carried out by the XMM-Newton Survey Science Centre with the specific goal of identifying the brightest X-ray sources in the XMM-Newton Galactic plane survey. In addition to photometric and spectroscopic observations obtained at the ESO-VLT and ESO-3.6 m, we used cross-correlations with the 2XMMi, USNO-B1.0, MASS, and GLIMPSE catalogues to advance the identification process. Active coronae account for 16 of the 30 positively or tentatively identified X-ray sources and exhibit the softest X-ray spectra. Many of the identified hard X-ray sources are associated with massive stars, possible members of binary systems and emitting at intermediate X-ray luminosities of 1032−34 erg s−1. Among these are (i) a very absorbed, likely hyper-luminous star with X-ray/optical spectra and luminosities comparable to those of η Carina; (ii) a new X-rayselected WN8 Wolf-Rayet star in which most of the X-ray emission probably arises from wind collision in a binary; (iii) a new Be/X-ray star belonging to the growing class of γ-Cas analogues; and (iv) a possible supergiant X-ray binary of the kind discovered recently by INTEGRAL. One of the sources, XGPS-25, has a counterpart of moderate optical luminosity that exhibits HeII λ4686 and Bowen CIII-NIII emission lines, suggesting that this may be a quiescent or X-ray shielded low mass X-ray binary, although its X-ray properties might also be consistent with a rare kind of cataclysmic variable (CV). We also report the discovery of three new CVs, one of which is a likely magnetic system displaying strong X-ray variability. The soft (0.4–2.0 keV) band log N(>S )−log S curve is completely dominated by active stars in the flux range of 1 × 10−13 to 1 × 10−14 erg cm−2 s−1. Several active coronae are also detected above 2 keV suggesting that the population of RS CVn binaries contributes significantly to the hard X-ray source population. In total, we are able to identify a large fraction of the hard (2–10 keV) X-ray sources in the flux range of 1 × 10−12 to 1 × 10−13 erg cm−2 s−1 with Galactic objects at a rate consistent with what is expected for the Galactic contribution alone.We thank an anonymous referee for useful comments which helped to improve the quality of this paper. We are grateful to O. Herent for carrying out some of the observations presented in this work. This work has been supported in part by the DLR (Deutsches Zentrum für Luftund Raumfahrt) under grants 50 OX 0201 and 50 OX 0801. I.N. is supported by the Spanish Ministerio de Ciencia e Innovación under grants AYA2008-06166-C03-03 and CSD2006-70. This publication makes use of data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation. The DENIS project has been partly funded by the SCIENCE and the HCM plans of the European Commission under grants CT920791 and CT940627. It is supported by INSU, MEN and CNRS in France, by the State of Baden-Württemberg in Germany, by DGICYT in Spain, by CNR in Italy, by FFwFBWF in Austria, by FAPESP in Brazil, by OTKA grants F-4239 and F-013990 in Hungary, and by the ESO C&EE grant A-04-046. Jean Claude Renault from IAP was the Project manager. Observations were carried out thanks to the contribution of numerous students and young scientists from all involved institutes, under the supervision of P. Fouqué, survey astronomer resident in Chile. The WHT is operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias. The observation presented here was taken as part of the ING service programme (proposal SW2005A06). This research has made use of Aladin, of the VizieR catalogue access tool and of Simbad at CDS, Strasbourg, France

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ABSTRACT. 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. KaplanMeier 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 there

Reduced proportions of natural killer T cells are present in the relatives of lupus patients and are associated with autoimmunity

Abstract Introduction Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives. Methods Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry. Results We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait. Conclusions The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity

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ABSTRACT. 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 (SL

The Use of Micronutrient Supplements Is Not Associated with Better Quality of Life and Disease Activity in Canadian Patients with Systemic Lupus Erythematosus

ABSTRACT. 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

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL

CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update

Objective In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aimed to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence. Methods A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014-September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a two-step modified Delphi procedure to reach >80% consensus on the inclusion, wording and grading of each new and revised recommendation. Results Eleven new and 16 revised recommendations were created, and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary appendix for practical use was revised to reflect the updated recommendations. Conclusion The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701