Example Of Rheumatoid Arthritis Research Articles

Can the General Public Be a Proxy for an "At-Risk" Group in a Patient Preference Study? A Disease Prevention Example in Rheumatoid Arthritis.

When selecting samples for patient preference studies, it may be difficult or impractical to recruit participants who are eligible for a particular treatment decision. However, a general public sample may not be an appropriate proxy. This study compares preferences for rheumatoid arthritis (RA) preventive treatments between members of the general public and first-degree relatives (FDRs) of confirmed RA patients to assess whether a sample of the general public can be used as a proxy for FDRs. Participants were asked to imagine they were experiencing arthralgia and had screening tests indicating a 60% chance of developing RA within 2 yrs. Using a discrete choice experiment, participants were offered a series of choices between no treatment and 2 unlabeled hypothetical treatments to reduce the risk of RA. To assess data quality, time to complete survey sections and comprehension questions were assessed. A random parameter logit model was used to obtain attribute-level estimates, which were used to calculate relative importance, maximum acceptable risk (MAR), and market shares of hypothetical preventive treatments. The FDR sample (n = 298) spent more time completing the survey and performed better on comprehension questions compared with the general public sample (n = 982). The relative importance ranking was similar between the general public and FDR participant samples; however, other relative preference measures involving weights including MARs and market share differed between groups, with FDRs having numerically higher MARs. In the context of RA prevention, the general public (average risk) may be a reasonable proxy for a more at-risk sample (FDRs) for overall relative importance ranking but not weights. The rationale for a proxy sample should be clearly justified. Participants from the general public were compared to first-degree relatives on their preferences for rheumatoid arthritis (RA) preventive treatments using a discrete choice experiment.Preferences were similar between groups in terms of the most important and least important attributes of preventive treatments, with effectiveness being the most important attribute. However, relative weights differed.Attention to the survey and predicted market shares of hypothetical RA preventive treatments differed between the general public and first-degree relatives.The general public may be a reasonable proxy for an at-risk group for patient preferences ranks but not weights in the disease prevention context; however, care should be taken in sample selection for patient preference studies when choosing nonpatients.

Reactivation of latent tuberculosis with TNF inhibitors: critical role of the beta 2 chain of the IL-12 receptor.

Tumor necrosis factor (TNF) inhibitors have improved a lot the treatment of numerous diseases, with the well-known example of rheumatoid arthritis (RA). In the early 2000s, postmarketing data quickly revealed an alarming number of severe tuberculosis (TB) under such treatment. These findings were consistent with previous results in mice where TNF is essential for lymph node formation and granuloma organization. The effects of TNF inhibition on RA synovium structure are very similar to those on granuloma, with changes in cellular interactions, cytokine, and chemokine production. In addition to the role of TNF in granuloma, the interleukin (IL)-12/interferon (IFN)-γ pathway is required for an efficient host defense against TB. Primary and secondary immunodeficiencies affecting this pathway lead to severe bacillus Calmette-Guérin (BCG) reaction or full TB. Any chronic inflammation as in RA induces a systemic Th1 defect that predisposes to TB through specific downregulation of the IL-12Rß2 chain. When TNF inhibitors are initiated, this transiently increases this risk of TB, through effects on cellular interactions in a latent TB granuloma. At a later stage, when a better control disease activity is obtained, the risk of TB is reduced but not abrogated. Given the clear benefit from TNF inhibition, latent TB infection screening at baseline is essential for an optimal safety.

Deciphering Potential Correlations between New Biomarkers and Pattern Classification in Chinese Medicine by Bioinformatics: Two Examples of Rheumatoid Arthritis.

Biological complexity and the need for personalized medicine means that biomarker development has become increasingly challenging. Thus, new paradigms for research need to be created that bring together a different classifier of individuals. One potential solution is collaboration between biomarker development and Chinese medicine pattern classification. In this article, two examples of rheumatoid arthritis are discussed, including a new biomarker candidate casein kinase 2 interacting protein 1 (CKIP-1) and a micro RNA 214. The authors obtained a "snapshot" of pattern classification with disease in biomarker identification. Bioinformatics analyses revealed underlying biological functions of two biomarker candidates, in varying degrees, are correlated with Chinese medicine pattern of rheumatoid arthritis. The authors' initial attempt can provide a new window for studying the win-win potential correlation between the biomarkers and pattern classification in Chinese medicine.

Medical arthroscopy: A tool for diagnosis and research in rheumatology.

Arthroscopy is an important diagnostic procedure which can be used in rheumatology practice to provide direct visualization of the joint cavity, permitting macroscopic evaluation of the synovium, sampling for histopathologic and microbiologic examination and the potential therapeutic benefit of lavage. The term 'medical arthroscopy' is used here to refer to arthroscopy performed by rheumatologists for these purposes. This term differentiates arthroscopy performed by orthopedic surgeons for structural interventions such as meniscal debridement and ligament repair. Medical arthroscopy finds a place in rheumatology as an aid to diagnosis, to confirm the presence of synovitis when not expected, to provide histologic or microbiologic diagnosis, and potential stratification for therapy, for example in rheumatoid arthritis, as well as a range of other research purposes. It is performed with local anesthetic using a small bore arthroscope, most usually inserted into the knee, although the wrist and metacarpophalangeal joints may also be inspected in this way. In experienced hands it is well tolerated, safe and complications are comparable to those reported by orthopedic surgeons.

The Detection of Rheumatic Disease through Hospital Diagnoses with Examples of Rheumatoid Arthritis and Giant Cell Arteritis: What Are We Missing?

We examined hospitalizations for patients with known rheumatoid arthritis (RA) or giant cell arteritis (GCA) to evaluate whether hospitalization-related diagnoses accurately identified patients with rheumatologic diseases. Diagnosis codes for hospitalizations in 1996-2012 among previously identified population-based cohorts of patients with RA or GCA were examined for RA or GCA mentions. RA or GCA mention occurred in only 55% of 2407 hospitalizations among patients with RA and 31% of 502 hospitalizations among patients with GCA. RA or GCA was mentioned more often in recent years, younger patients, and rheumatic medication users. Coding for RA or GCA during hospitalizations was often missed. Research using hospital diagnoses alone could be biased.

From the era of genome analysis to the era of genomic drug discovery: a pioneering example of rheumatoid arthritis.

Although we have obtained comprehensive catalogs of genetic risk loci that are linked to human diseases, little is known regarding how to devise a systematic strategy to integrate genetic study results with diverse biological resources. Such strategies will be crucial for providing novel insights into disease biology and for aiding drug discovery as an ultimate goal. Here we describe the current progress in this field using a pioneering example of large-scale genetic association studies on rheumatoid arthritis (RA), an autoimmune disease characterized by inflammation and destruction of joints. Through functional and bioinformatic annotations of risk single nucleotide polymorphisms (SNPs) and genes from >100 RA risk loci identified by genome-wide association study (GWAS) meta-analysis, we found novel biological insights into RA pathogenicity. Further, by integrating RA genetic findings with the complete catalog of approved drugs for RA and other diseases, we provide empirical data to indicate that human genetic-based approaches may be useful for supporting 'genetics-driven genomic drug discovery' efforts in complex human traits and suggest that further development of integrative approaches should be undertaken.

AB0052 Human Complement Components C4B and C4A Subisotypes Patterns: Resistant Visible Biomarkers of the System Infectious and Rheumatologic Diseases

BackgroundIsotypes C4A and C4B of human complement component C4 are innate immunity factors. We found that gel electrophoresis of patient sera in the new diagnostic area of C4 complexes/aggregates (pI...

Multivariate meta‐analysis of mixed outcomes: a Bayesian approach

Multivariate random effects meta-analysis (MRMA) is an appropriate way for synthesizing data from studies reporting multiple correlated outcomes. In a Bayesian framework, it has great potential for integrating evidence from a variety of sources. In this paper, we propose a Bayesian model for MRMA of mixed outcomes, which extends previously developed bivariate models to the trivariate case and also allows for combination of multiple outcomes that are both continuous and binary. We have constructed informative prior distributions for the correlations by using external evidence. Prior distributions for the within-study correlations were constructed by employing external individual patent data and using a double bootstrap method to obtain the correlations between mixed outcomes. The between-study model of MRMA was parameterized in the form of a product of a series of univariate conditional normal distributions. This allowed us to place explicit prior distributions on the between-study correlations, which were constructed using external summary data. Traditionally, independent ‘vague’ prior distributions are placed on all parameters of the model. In contrast to this approach, we constructed prior distributions for the between-study model parameters in a way that takes into account the inter-relationship between them. This is a flexible method that can be extended to incorporate mixed outcomes other than continuous and binary and beyond the trivariate case. We have applied this model to a motivating example in rheumatoid arthritis with the aim of incorporating all available evidence in the synthesis and potentially reducing uncertainty around the estimate of interest. © 2013 The Authors. Statistics inMedicine Published by John Wiley & Sons, Ltd.

PMS18 Importance of COI Studies in the Health Care-Related Decision-Making Process Through the Example of Rheumatoid Arthritis

PMS18 Importance of COI Studies in the Health Care-Related Decision-Making Process Through the Example of Rheumatoid Arthritis

Taurine and inflammatory diseases

Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in humans and plays an important role in several essential biological processes such as bile acid conjugation, maintenance of calcium homeostasis, osmoregulation and membrane stabilization. Moreover, attenuation of apoptosis and its antioxidant activity seem to be crucial for the cytoprotective effects of taurine. Although these properties are not tissue specific, taurine reaches particularly high concentrations in tissues exposed to elevated levels of oxidants (e.g., inflammatory cells). It suggests that taurine may play an important role in inflammation associated with oxidative stress. Indeed, at the site of inflammation, taurine is known to react with and detoxify hypochlorous acid generated by the neutrophil myeloperoxidase (MPO)–halide system. This reaction results in the formation of less toxic taurine chloramine (TauCl). Both haloamines, TauCl and taurine bromamine (TauBr), the product of taurine reaction with hypobromous acid (HOBr), exert antimicrobial and anti-inflammatory properties. In contrast to a well-documented regulatory role of taurine and taurine haloamines (TauCl, TauBr) in acute inflammation, their role in the pathogenesis of inflammatory diseases is not clear. This review summarizes our current knowledge concerning the role of taurine, TauCl and TauBr in the pathogenesis of inflammatory diseases initiated or propagated by MPO-derived oxidants. The aim of this paper is to show links between inflammation, neutrophils, MPO, oxidative stress and taurine. We will discuss the possible contribution of taurine and taurine haloamines to the pathogenesis of inflammatory diseases, especially in the best studied example of rheumatoid arthritis.

On the origins of complex immune-mediated disease: the example of rheumatoid arthritis

This essay discusses strategies for understanding the origins and outcomes of complex chronic inflammatory diseases using genetic and environmental determinants as tools for new definitions of disease subsets. Rheumatoid arthritis has been chosen as the prototype to illustrate these general concepts. Through recent data on two different disease subsets, it has been possible to devise a new molecular model for disease development by incorporating multiple genes and environmental agents which generate immune reactions that may eventually cause disease. These kinds of studies, aiming to integrate genetic epidemiology and molecular immunology, require close proximity between institutions for molecular medicine, clinical departments able to provide follow-up, careful surveillance of large patient groups and collaboration with experts in epidemiology and biostatistics.

3590: Role of ultrasound in the evaluation of arthritis: A pictorial review

Our purpose is to illustrate the potential role of ultrasound (US) in the evaluation of sero-positive and sero-negative arthritis, as well as osteoarthritis. Anatomy and methods of optimizing technical factors will be reviewed. Examples of the diagnostic capabilities of US in the evaluation of synovitis, joint effusions, erosions, bursal and tendon diseases, enthesitis and osteophytosis will be presented. The role of color and power Doppler will be demonstrated. Specific examples of rheumatoid arthritis, psoriatic arthritis, crystal deposition disease, and osteoarthritis will be provided. Our clinical experience using US for diagnostic and therapeutic interventions, including joint aspiration and injection, synovial biopsy and needle therapy will be discussed. Advantages, safety issues and limitations of US, as well as pearls and pitfalls will be discussed. In our experience, US is valuable in diagnosing early arthritis, and has an important role in guiding both diagnostic and therapeutic interventions and assessing response to treatment. Our purpose is to illustrate the potential role of ultrasound (US) in the evaluation of sero-positive and sero-negative arthritis, as well as osteoarthritis. Anatomy and methods of optimizing technical factors will be reviewed. Examples of the diagnostic capabilities of US in the evaluation of synovitis, joint effusions, erosions, bursal and tendon diseases, enthesitis and osteophytosis will be presented. The role of color and power Doppler will be demonstrated. Specific examples of rheumatoid arthritis, psoriatic arthritis, crystal deposition disease, and osteoarthritis will be provided. Our clinical experience using US for diagnostic and therapeutic interventions, including joint aspiration and injection, synovial biopsy and needle therapy will be discussed. Advantages, safety issues and limitations of US, as well as pearls and pitfalls will be discussed. In our experience, US is valuable in diagnosing early arthritis, and has an important role in guiding both diagnostic and therapeutic interventions and assessing response to treatment.

Gesundheitsökonomie am Beispiel rheumatischer Erkrankungen

Thorough health economic research of budget-relevant diseases should be one of the major tasks in the German health care system. Up to now cost studies were only performed for special research questions and/or with very limited focuses, e.g. the patients' view. Hence, federal programmes, like competence networks for certain diseases, which were introduced by the German Ministry for Research and Education in the late 1990s, should give a broader focus on health services research. With such an approach health politicians may obtain a deeper insight into areas of the health care sector which are likely to be more efficient after reorganisation. The process of a structured analysis of certain diseases will be demonstrated using the example of rheumatoid arthritis (RA). To this end, the results of a research programme sponsored within the Competence Network for Musculoskeletal Diseases will be presented. Direct costs, indirect costs as well as values for health-related quality of life of German RA patients in routine care by generalists and specialists will be discussed.

Models of adjustment to chronic illness: Using the example of rheumatoid arthritis

There are a number of theoretical frameworks that attempt to explain how individuals may adjust to threats to health and serious physical illness. The three major paradigms that attempt to organize key components of health and adaptation to illness include the following: the biomedical model which emphasizes disease; psychological models of adaptation to illness; and biopsychosocial models with the latter two emphasizing health, functioning, and well-being. Each of these three major paradigms, including biomedical, psychosocial, and biopsychosocial frameworks, is discussed and critiqued in turn, and contributions and theoretical issues in terms of adjustment to chronic illness, particularly rheumatoid arthritis (RA), are highlighted. Furthermore, a biopsychosocial framework for conceptualizing adjustment to physical illness is proposed that incorporates elements from key existing biomedical and psychosocial models of adaptation to chronic physical health issues.

Biomolecular cytokine therapy.

As for the chronicity of inflammatory-immune diseases, the medication of them needs to be longterm and thus, quite safe with respect to side effects due to drug actions. Therapy of these diseases includes steroid and non steroid anti-inflammatories given in monotherapy or in combination with cytotoxic antimetabolites. Longterm administration of these active substances cumulate in side effects, not to speak of the probability of developing unresponsiveness to the drug in use. In principle, the earlier the intervention, the better the outcome of medication in therapy. In harmony with this principle, biopharmacology focuses on specific targets in early (acute) phase of inflammatory-immune diseases. One of these targets is the proinflammatory cascade of cytokines (IL1beta, IL6, IL8, IL12, TNFalpha). Among them, the overproduction of tumor necrosis factor (TNFalpha) is suggested to orchestrate and escalate the disease phenotype. Hence, targeting of TNFa may restrict or stop the propagation of pathological reactions. TNFalpha in its excess can be captured at transcription, translation, secretion levels as well as in the extracellular soluble form. This latter approach is supported by clinical records emphasizing the use of recombinant antibodies and soluble receptors in trapping extra amounts of TNFalpha. This review serves as an illustration for the efficacy and safety of infliximab (antibody) and etanercept (soluble receptor) in the example of rheumatoid arthritis (RA).

Modulation of bovine articular chondrocyte gene expression in vitro by oxygen tension

Objective Adult articular cartilage is a physiologically hypoxic tissue with a proposed gradient of oxygen tension ranging from <10% oxygen at the cartilage surface to <1% in the deepest layers. This gradient may be disturbed during diseases of the joint, for example in rheumatoid arthritis when synovial fluid pO2falls. We investigated whether changes in oxygen tension modulate gene expression in articular chondrocytes.Design Bovine articular chondrocytes were cultured in alginate beads in medium maintained at <0.1, 5, 10 or 20% oxygen. A modified RNA arbitrarily primed polymerase chain reaction (RAP-PCR) technique was used to identify several genes whose mRNA abundance in articular chondrocytes was dependent upon oxygen tension. Northern hybridization slot blots were used to quantify changes in mRNA level relative to a housekeeping gene, β-actin.Results Genes found by RAP-PCR to undergo up-regulation in hypoxia included TIMP-1 and integrin-linked kinase. Collagen V mRNA levels were down-regulated in hypoxic chondrocytes. This led us to examine mRNA levels for various cytokines, matrix structural molecules and β1 integrin. Interleukin 1β, transforming growth factor β and connective tissue growth factor were all up-regulated by low oxygen tensions, as was β1 integrin. Collagen II (COL2A1) was down-regulated by hypoxia but aggrecan mRNA levels remained unchanged. The mRNA levels for GAPDH, the archetypal hypoxia responsive gene, were not modulated in articular chondrocytes by changes in oxygen tension.ConclusionsOxygen tension modulates the abundance of mRNAs encoding structural molecules, several cytokines, β1 integrin and integrin-linked kinase in articular chondrocytes. This may be important during disease progression. Chondrocytes are unusual in their response to hypoxia, presumably because they exist physiologically in a low oxygen environment.

Inhibition of T cell activation by MHC blockade: A possible strategy for immunointervention in autoimmune diseases

Autoimmune diseases result from the activation of self-reactive T cells induced by autoantigens or by foreign antigens cross-reactive with an autoantigen. A striking characteristic of autoimmune diseases is the increased frequency of certain HLA alleles in affected individuals. Moreover, as demonstrated for example in rheumatoid arthritis and insulin-dependent diabetes mellitus, class II alleles positively associated with autoimmune diseases share amino acid residues in the hypervariable HLA regions involved in peptide binding. Therefore, it is likely that disease-associated HLA class II molecules have the capacity to bind the autoantigen and present it to T cells, thereby inducing and maintaining, under appropriate conditions, the autoimmune disease. The data reviewed here demonstrate MHC-selective inhibition of antigen-induced T cell responses in vivo by parenterally administered soluble, MHC-binding peptide competitors, under conditions in which the competitor is not immunogenic. This suggests the feasibility of a therapeutic approach based on blockade of MHC class II molecules in the treatment of HLA-linked autoimmune diseases.

On the design of the Phase III drug trial. The example of rheumatoid arthritis.

No new drug can be marketed in the United States unless a favorable risk-benefit ratio has been demonstrated to the satisfaction of the Food and Drug Administration. Inspection of the fashion in which this is accomplished with reference to rheumatoid arthritis reveals shortcomings in form and substance. Ten issues of design are isolated and options discussed. One design suggested, as a compromise, is 2 20-center trials to supplant late Phase II and Phase III trials. At each center a single investigator evaluates at least a 10-subject, highly selected cohort over 6 months in a 2-drug or a 2-drug plus placebo double-blind format. The active drug versus active drug component of the program will be pivotal in analysis. Advantages include expedience, lower cost, effective detection of short-term stratum-specific toxicity and of investigator bias, and absence of compromise in beta error. With such data and with emphasis on the beta error, the risk-benefit judgment will be more meaningful. Formalized Phase IV monitoring is proposed to detect infrequent or delayed toxicities.

Arthritis in Flemish paintings (1400-1700).

A close examination of the hands of people depicted in paintings of the Flemish school showed that in five paintings there were figures with hand lesions resembling those of rhematoid arthritis. Although none of the deformities or swellings are indisputable examples of rheumatoid arthritis, they do at least suggest that the painters must have been confronted with rheumatoid-like lesions in their models. In two other paintings there were signs of rheumatic fever and of temporal arteritis. No arthritic lesions were found in the works of painters of the Italian Renaissance, probably because they are less detailed. The finding of rheumatoid deformities in the Flemish paintings does, however, question the general belief that rheumatoid arthritis is a condition that has arisen relatively recently.