Gene-based large scale LD-mapping of rheumatoid arthritis-associated genes

Author(s):  
Ryo Yamada ◽  
Kazuhiko Yamamoto
2017 ◽  
Vol 33 (S1) ◽  
pp. 33-34
Author(s):  
Mark Clowes

INTRODUCTION:One of the challenges of large scale Health Technology Assessment (HTA) projects is managing the large volume of studies retrieved by the requisite comprehensive literature searches. At the scoping stage of the project, a pragmatic judgement needs to be made as to how sensitive the search strategy should be in order to find all the relevant papers without returning an overwhelming volume of irrelevant studies.METHODS:For this HTA (evaluating prognostic and predictive markers in rheumatoid arthritis), the research team already had prior knowledge of several key markers of interest, but wanted to ensure that no others had been missed. Advice from practising clinicians was obtained, but for additional validation, a broad scoping search was conducted for ‘rheumatoid arthritis’ using the sensitive Haynes filters for prognostic (1) and clinical prediction (2) studies. Unsurprisingly, this initial search retrieved too many studies for them all to be admitted to the full review; but once those dealing with known markers had been removed, a sample of the remaining records was loaded into a software visualization tool (3) to display “heat maps” of frequently occurring terms and phrases.RESULTS:On this occasion, no additional markers were identified, however this provided reassurance that the advice obtained from clinicians was comprehensive, enabling the HTA team to proceed confidently with its evaluation of the selected markers.CONCLUSIONS:Visualization offers an alternative means of exploring and interrogating large text archives, and has the potential to complement the role of traditional search methods in identifying literature for systematic reviews and health technology assessments. As processing power increases and more and more full-text papers become available open access, it may provide a solution to some of the limitations associated with comprehensive searching.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Noha A. Yousri ◽  
Karim Bayoumy ◽  
Wessam Gad Elhaq ◽  
Robert P. Mohney ◽  
Samar Al Emadi ◽  
...  

2002 ◽  
Vol 30 (6) ◽  
pp. 1037-1041 ◽  
Author(s):  
R. A. G. Smith

Biological targeting is normally thought of as a process of specific direction of one molecule (the agent) to another (the target) in vivo. However, an addressive approach in which the agent is concentrated, first within the vasculature and then at a disease site containing one or more targets, may be more suitable for delivering therapeutic quantities of certain drugs. This approach has been applied to complement regulatory molecules expressed in recombinant soluble forms and attached post-translationally to highly soluble synthetic peptide derivatives comprising two addressin units, one with affinity for the membrane bilayer interior and the other for phospholipid headgroups. This combination conferred affinity for outer cell membranes in general, and areas of translocated acidic phospholipid in particular. Large increases in potency in cell-based antihaemolytic assays accompanied modification and were shown to be associated with membrane binding. Modified agents co-localized with glycosylphosphatidyl-inositol-anchored proteins in lipid rafts on cell membranes. One agent, a modified fragment of human complement receptor-1 (APT070), has been prepared on a large scale and has been shown to be an active anti-inflammatory agent when administered locally and systemically in animal models of vascular shock, rheumatoid arthritis and transplantation reperfusion injury. APT070 has been shown to be well tolerated in human subjects when given intravenously and is currently under study in rheumatoid arthritis patients to explore the therapeutic potential of localized complement inhibition in the synovial space.


2007 ◽  
Vol 1 (Suppl 1) ◽  
pp. S100 ◽  
Author(s):  
Marian L Hamshere ◽  
Ricardo Segurado ◽  
Valentina Moskvina ◽  
Ivan Nikolov ◽  
Beate Glaser ◽  
...  

2020 ◽  
Vol 7 ◽  
Author(s):  
Xiangling Ye ◽  
Zehua Chen ◽  
Zhen Shen ◽  
Guocai Chen ◽  
Xuemeng Xu

Purpose: Rheumatoid arthritis (RA) is a pervasive inflammatory autoimmune disease that seriously impairs human health and requires more effective non-pharmacologic treatment approaches. This study aims to systematically review and evaluate the efficacy of yoga for patients with RA.Methods: Medline (through PubMed), Cochrane Library, EMBASE (through SCOPUS), and Web of Science database were screened through for articles published until 20 July 2020. Randomized controlled trials (RCTs) of yoga in patients with RA were included. Outcomes measures were pain, physical function, disease activity, inflammatory cytokines, and grip strength. For each outcome, standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated.Result: Ten trials including 840 patients with RA aged 30–70 years were identified, with 86% female participants. Meta-analysis revealed a statistically significant overall effect in favor of yoga for physical function (HAQ-DI) (5 RCTs; SMD = −0.32, 95% CI −0.58 to −0.05, I2 = 15%, P = 0.02), disease activity (DAS-28) (4 RCTs; SMD = −0.38, 95% CI −0.71 to −0.06, I2 = 41%, P = 0.02) and grip strength (2 RCTs; SMD = 1.30, 95% CI 0.47–2.13, I2 = 63%, P = 0.002). No effects were found for pain, tender joints, swollen joints count or inflammatory cytokines (i.e., CRP, ESR, IL-6, and TNF-α).Summary: The findings of this meta-analysis indicate that yoga may be beneficial for improving physical function, disease activity, and grip strength in patients with RA. However, the balance of evidence showed that yoga had no significant effect in improving pain, tender joints, swollen joints count, and inflammatory cytokines in patients suffering from RA. Considering methodological limitations, small sample size, and low-quality, we draw a very cautious conclusion in the results of the estimate of the effect. High-quality and large-scale RCTs are urgently needed in the future, and the real result may be substantially different.


2019 ◽  
Vol 8 (6) ◽  
pp. 826 ◽  
Author(s):  
Marialbert Acosta-Herrera ◽  
David González-Serna ◽  
Javier Martín

During the last decade, important advances have occurred regarding understanding of the pathogenesis and treatment of rheumatoid arthritis (RA). Nevertheless, response to treatment is not universal, and choosing among different therapies is currently based on a trial and error approach. The specific patient’s genetic background influences the response to therapy for many drugs: In this sense, genomic studies on RA have produced promising insights that could help us find an effective therapy for each patient. On the other hand, despite the great knowledge generated regarding the genetics of RA, most of the investigations performed to date have focused on identifying common variants associated with RA, which cannot explain the complete heritability of the disease. In this regard, rare variants could also contribute to this missing heritability as well as act as biomarkers that help in choosing the right therapy. In the present article, different aspects of genetics in the pathogenesis and treatment of RA are reviewed, from large-scale genomic studies to specific rare variant analyses. We also discuss the shared genetic architecture existing among autoimmune diseases and its implications for RA therapy, such as drug repositioning.


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