EULAR Sjogren's syndrome disease activity index (ESSDAI):a user guide

The EULAR Sj\uf6gren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS

A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren's syndrome

BACKGROUND. Primary Sjögren's syndrome (pSS) is characterized by B cell hyperactivity and elevated B-lymphocyte stimulator (BLyS). Anti-BLyS treatment (e.g., belimumab) increases peripheral memory B cells; decreases naive, activated, and plasma B cell subsets; and increases stringency on B cell selection during reconstitution. Anti-CD20 therapeutics (e.g., rituximab) bind and deplete CD20-expressing B cells in circulation but are less effective in depleting tissue-resident CD20+ B cells. Combined, these 2 mechanisms may achieve synergistic effects. METHODS. This 68-week, phase II, double-blind study (GSK study 201842) randomized 86 adult patients with active pSS to 1 of 4 arms: placebo, s.c. belimumab, i.v. rituximab, or sequential belimumab + rituximab. RESULTS. Overall, 60 patients completed treatment and follow-up until week 68. The incidence of adverse events (AEs) and drug-related AEs was similar across groups. Infections/infestations were the most common AEs, and no serious infections of special interest occurred. Near-complete depletion of minor salivary gland CD20+ B cells and a greater and more sustained depletion of peripheral CD19+ B cells were observed with belimumab + rituximab versus monotherapies. With belimumab + rituximab, reconstitution of peripheral B cells occurred, but it was delayed compared with rituximab. At week 68, mean (± standard error) total EULAR Sjögren's syndrome disease activity index scores decreased from 11.0 (1.17) at baseline to 5.0 (1.27) for belimumab + rituximab and 10.4 (1.36) to 8.6 (1.57) for placebo. CONCLUSION. The safety profile of belimumab + rituximab in pSS was consistent with the monotherapies. Belimumab + rituximab induced enhanced salivary gland B cell depletion relative to the monotherapies, potentially leading to improved clinical outcomes

A multiplicative hazard regression model to assess the risk of disease transmission at hospital during community epidemics

<p>Abstract</p> <p>Background</p> <p>During community epidemics, infections may be imported within hospital and transmitted to hospitalized patients. Hospital outbreaks of communicable diseases have been increasingly reported during the last decades and have had significant consequences in terms of patient morbidity, mortality, and associated costs. Quantitative studies are thus needed to estimate the risks of communicable diseases among hospital patients, taking into account the epidemiological process outside, hospital and host-related risk factors of infection and the role of other patients and healthcare workers as sources of infection.</p> <p>Methods</p> <p>We propose a multiplicative hazard regression model to analyze the risk of acquiring a communicable disease by patients at hospital. This model derives from epidemiological data on communicable disease epidemics in the community, hospital ward, patient susceptibility to infection, and exposure of patients to infection at hospital. The model estimates the relative effect of each of these factors on a patient's risk of communicable disease.</p> <p>Results</p> <p>Using individual data on patients and health care workers in a teaching hospital during the 2004-2005 influenza season in Lyon (France), we show the ability of the model to assess the risk of influenza-like illness among hospitalized patients. The significant effects on the risk of influenza-like illness were those of old age, exposure to infectious patients or health care workers, and a stay in a medical care unit.</p> <p>Conclusions</p> <p>The proposed multiplicative hazard regression model could be an interesting epidemiological tool to quantify the risk of communicable disease at hospital during community epidemics and the uncertainty inherent in such quantification. Furthermore, key epidemiological, environmental, host, or exposure factors that influence this risk can be identified.</p

Presence of anticitrullinated protein antibodies in a large population-based cohort from the Netherlands

Objectives To determine the prevalence of anticitrullinated protein antibodies (ACPAs) and their association with known rheumatoid arthritis (RA) risk factors in the general population. Methods Lifelines is a multidisciplinary prospective population-based cohort study in the Netherlands. Cross-sectional data from 40 136 participants were used. The detection of ACPA was performed by measuring anti-CCP2 on the Phadia-250 analyser with levels >= 6.2 U/mL considered positive. An extensive questionnaire was taken on demographic and clinical information, including smoking, periodontal health and early symptoms of musculoskeletal disorders. RA was defined by a combination of self-reported RA, medication use for the indication of rheumatism and visiting a medical specialist within the last year. Results Of the total 40 136 unselected individuals, 401 (1.0%) had ACPA level >= 6.2 U/mL. ACPA positivity was significantly associated with older age, female gender, smoking, joint complaints, RA and first degree relatives with rheumatism. Of the ACPA-positive participants, 22.4% had RA (15.2% had defined RA according to our criteria and 7.2% self-reported RA only). In participants without RA, 311 (0.8%) were ACPA-positive. In the non-RA group, older age, smoking and joint complaints remained significantly more frequently present in ACPA-positive compared with ACPA-negative participants. Conclusions In this large population-based study, the prevalence of ACPA levels >= 6.2 U/mL was 1.0% for the total group and 0.8% when excluding patients with RA. Older age, smoking and joint complaints were more frequently present in ACPA-positive Lifelines participants. To our knowledge, this study is the largest study to date on ACPA positivity in the general, mostly Caucasian population

Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren's syndrome

Labial salivary gland (LSG) biopsy is used in the classification of primary Sjögren's syndrome (PSS) and in patient stratification in clinical trials. It may also function as a biomarker. The acquisition of tissue and histological interpretation is variable and needs to be standardised for use in clinical trials. A modified European League Against Rheumatism consensus guideline development strategy was used. The steering committee of the ad hoc working group identified key outstanding points of variability in LSG acquisition and analysis. A 2-day workshop was held to develop consensus where possible and identify points where further discussion/data was needed. These points were reviewed by a subgroup of experts on PSS histopathology and then circulated via an online survey to 50 stakeholder experts consisting of rheumatologists, histopathologists and oral medicine specialists, to assess level of agreement (0–10 scale) and comments. Criteria for agreement were a mean score ≥6/10 and 75% of respondents scoring ≥6/10. Thirty-nine (78%) experts responded and 16 points met criteria for agreement. These points are focused on tissue requirements, identification of the characteristic focal lymphocytic sialadenitis, calculation of the focus score, identification of germinal centres, assessment of the area of leucocyte infiltration, reporting standards and use of prestudy samples for clinical trials. We provide standardised consensus guidance for the use of labial salivary gland histopathology in the classification of PSS and in clinical trials and identify areas where further research is required to achieve evidence-based consensus

Serum and Tissue Biomarkers Associated With Composite of Relevant Endpoints for Sj\uf6gren Syndrome (CRESS) and Sj\uf6gren Tool for Assessing Response (STAR) to B Cell–Targeted Therapy in the Trial of Anti–B Cell Therapy in Patients With Primary Sj\uf6gren Syndrome (TRACTISS)

\ua9 2023 The Authors. Arthritis &amp; Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.Objective: This study aimed to identify peripheral and salivary gland (SG) biomarkers of response/resistance to B cell depletion based on the novel concise Composite of Relevant Endpoints for Sj\uf6gren Syndrome (cCRESS) and candidate Sj\uf6gren Tool for Assessing Response (STAR) composite endpoints. Methods: Longitudinal analysis of peripheral blood and SG biopsies was performed pre- and post-treatment from the Trial of Anti–B Cell Therapy in Patients With Primary Sj\uf6gren Syndrome (TRACTISS) combining flow cytometry immunophenotyping, serum cytokines, and SG bulk RNA sequencing. Results: Rituximab treatment prevented the worsening of SG inflammation observed in the placebo arm, by inhibiting the accumulation of class-switched memory B cells within the SG. Furthermore, rituximab significantly down-regulated genes involved in immune-cell recruitment, lymphoid organization alongside antigen presentation, and T cell co-stimulatory pathways. In the peripheral compartment, rituximab down-regulated immunoglobulins and auto-antibodies together with pro-inflammatory cytokines and chemokines. Interestingly, patients classified as responders according to STAR displayed significantly higher baseline levels of C-X-C motif chemokine ligand-13 (CXCL13), interleukin (IL)-22, IL-17A, IL-17F, and tumor necrosis factor-α (TNF-α), whereas a longitudinal analysis of serum T cell–related cytokines showed a selective reduction in both STAR and cCRESS responder patients. Conversely, cCRESS response was better associated with biomarkers of SG immunopathology, with cCRESS-responders showing a significant decrease in SG B cell infiltration and reduced expression of transcriptional gene modules related to T cell costimulation, complement activation, and Fcγ-receptor engagement. Finally, cCRESS and STAR response were associated with a significant improvement in SG exocrine function linked to transcriptional evidence of SG epithelial and metabolic restoration. Conclusion: Rituximab modulates both peripheral and SG inflammation, preventing the deterioration of exocrine function with functional and metabolic restoration of the glandular epithelium. Response assessed by newly developed cCRESS and STAR criteria was associated with differential modulation of peripheral and SG biomarkers, emerging as novel tools for patient stratification. (Figure presented.)

Ethnic differences in Internal Medicine referrals and diagnosis in the Netherlands

As in other Western countries, the number of immigrants in the Netherlands is growing rapidly. In 1980 non-western immigrants constituted about 3% of the population, in 1990 it was 6% and currently it is more than 10%. Nearly half of the migrant population lives in the four major cities. In the municipality of Rotterdam 34% of the inhabitants are migrants. Health policy is based on the ideal that all inhabitants should have equal access to health care and this requires an efficient planning of health care resources, like staff and required time per patient. The aim of this study is to examine ethnic differences in the use of internal medicine outpatient care, specifically to examine ethnic differences in the reason for referral and diagnosis. Methods We conducted a study with an open cohort design. We registered the ethnicity, sex, age, referral reasons, diagnosis and living area of all ne