Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland

<div><p> BACKGROUND Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. OBJECTIVES We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. METHODS We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. FINDINGS Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI) = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3%) patient, of whom 244 (27.0%; 95% CI = 24.2-30.0%) were positive. Eight (28.6%; 95% CI = 15.3-47.1%) of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000) or with Chagasic cardiomyopathy (p = 0.729). Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. CONCLUSIONS Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection.</p></div

Combining individual patient data from randomized and non-randomized studies to predict real-world effectiveness of interventions

Meta-analysis of randomized controlled trials is generally considered the most reliable source of estimates of relative treatment effects. However, in the last few years, there has been interest in using non-randomized studies to complement evidence from randomized controlled trials. Several meta-analytical models have been proposed to this end. Such models mainly focussed on estimating the average relative effects of interventions. In real-life clinical practice, when deciding on how to treat a patient, it might be of great interest to have personalized predictions of absolute outcomes under several available treatment options. This paper describes a general framework for developing models that combine individual patient data from randomized controlled trials and non-randomized study when aiming to predict outcomes for a set of competing medical interventions applied in real-world clinical settings. We also discuss methods for measuring the models’ performance to identify the optimal model to use in each setting. We focus on the case of continuous outcomes and illustrate our methods using a data set from rheumatoid arthritis, comprising patient-level data from three randomized controlled trials and two registries from Switzerland and Britain

Image_2_Characterization of serum biomarkers and antibody responses against Prevotella spp. in preclinical and new-onset phase of rheumatic diseases.jpg

IntroductionThe characterization of the influence of the microbiota on the development and drug responses during rheumatic diseases has intensified in recent years. The role of specific bacteria during disease development has become a central research question. Notably, several lines of evidence point to distinct microbes, e.g., Prevotella copri (P. copri) being targeted by antibodies in clinical phases of rheumatic diseases.MethodsIn the present study, we compiled a broad collection of human serum samples from individuals at risk of developing RA, chronic RA patients as well as patients with new-onset of rheumatic diseases. We evaluated the presence of inflammatory biomarkers in our serum collection as well as serum antibody responses against novel, genetically distinct isolates of P. copri and several oral pathobionts.ResultsOur analysis revealed the presence of increased levels of inflammatory markers already in pre-clinical and new onset rheumatoid arthritis. However, antibody reactivity against the microbes did not differ between patient groups. Yet, we observed high variability between the different P. copri strains. We found total serum IgG levels to slightly correlate with IgG antibody responses against P. copri, but no relation between the latter and presence or prevalence of P. copri in the intestine.DiscussionIn conclusion, our work underlined the importance of strain-level characterization and its consideration during further investigations of host-microbiota interactions and the development of microbiome-based therapeutic approaches for treating rheumatic diseases.</p

DS_10.1177_0272989X18775975 – Supplemental material for Prediction of Real-World Drug Effectiveness Prelaunch: Case Study in Rheumatoid Arthritis

<p>Supplemental material, DS_10.1177_0272989X18775975 for Prediction of Real-World Drug Effectiveness Prelaunch: Case Study in Rheumatoid Arthritis by Eva-Maria Didden, Yann Ruffieux, Noemi Hummel, Orestis Efthimiou, Stephan Reichenbach, Sandro Gsteiger, Axel Finckh, Christine Fletcher, Georgia Salanti and Matthias Egger in Medical Decision Making</p

Synovial fluid concentrations of IL-17 and IL-6 in patients following stratification by hip or knee OA.

<p>Error bars show median ± 95% confidence intervals, *p<0.05, **p<0.01, **p<0.001, ND = not detectable.</p

Correlation between synovial fluid and serum IL-17 concentrations in patients with detectable IL-17 in synovial fluid.

<p>Correlation between synovial fluid and serum IL-17 concentrations in patients with detectable IL-17 in synovial fluid.</p

Synovial fluid IL-17 levels in relation to baseline and clinical characteristics and patient-reported outcome measures.

<p>Synovial fluid IL-17 levels in relation to baseline and clinical characteristics and patient-reported outcome measures.</p

Synovial fluid IL-17 levels in relation to synovial fluid and serum adipokines and cytokines.

<p>Synovial fluid IL-17 levels in relation to synovial fluid and serum adipokines and cytokines.</p

Synovial fluid IL-17 levels in relation to radiographic characteristics.

<p>Synovial fluid IL-17 levels in relation to radiographic characteristics.</p

Correlation between synovial fluid and serum IL-17 and the concentrations of adipokines and cytokines that show significant elevation in the cohort of patients with detectable synovial fluid IL-17.

<p>Correlation between synovial fluid and serum IL-17 and the concentrations of adipokines and cytokines that show significant elevation in the cohort of patients with detectable synovial fluid IL-17.</p