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      Identifying Compound Effect of Drugs on Rheumatoid Arthritis Treatment Based on the Association Rule and a Random Walking-Based Model

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          Abstract

          Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is diagnosed mainly on the basis of patient signs, symptoms, and laboratory indices. However, the exact causes of RA are unclear. Moreover, there is a lack of any method of dynamically evaluating the efficacy of the medication administered to treat RA. Here, we applied a random walk model to reveal the compatibility among the various constituents of traditional Chinese medicine and evaluate their therapeutic efficacy against RA. Drugs commonly used to treat RA were investigated using cluster analysis. The association rule analysis was applied to identify compatibilities among the constituents. A random walk model was developed to evaluate drug efficacy based on an in-house database comprising the clinical records of 9,408 RA patients. Frequently administered medicines were combined into three correlated sets. The evaluation based on the random walk method showed that the drug combination improved ESR, CRP, C3, C4, and IgA more effectively than any single drug. The present study demonstrated that the TCM constituents complement each other and various combinations of them produce different therapeutic effects on RA treatment.

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          Most cited references23

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          EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update

          To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.
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            Long-range correlations in nucleotide sequences.

            DNA sequences have been analysed using models, such as an n-step Markov chain, that incorporate the possibility of short-range nucleotide correlations. We propose here a method for studying the stochastic properties of nucleotide sequences by constructing a 1:1 map of the nucleotide sequence onto a walk, which we term a 'DNA walk'. We then use the mapping to provide a quantitative measure of the correlation between nucleotides over long distances along the DNA chain. Thus we uncover in the nucleotide sequence a remarkably long-range power law correlation that implies a new scale-invariant property of DNA. We find such long-range correlations in intron-containing genes and in nontranscribed regulatory DNA sequences, but not in complementary DNA sequences or intron-less genes.
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              The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study.

              To estimate the global burden of rheumatoid arthritis (RA), as part of the Global Burden of Disease 2010 study of 291 conditions and how the burden of RA compares with other conditions. The optimum case definition of RA for the study was the American College of Rheumatology 1987 criteria. A series of systematic reviews were conducted to gather age-sex-specific epidemiological data for RA prevalence, incidence and mortality. Cause-specific mortality data were also included. Data were entered into DisMod-MR, a tool to pool available data, making use of study-level covariates to adjust for country, region and super-region random effects to estimate prevalence for every country and over time. The epidemiological data, in addition to disability weights, were used to calculate years of life lived with disability (YLDs). YLDs were added to the years of life lost due to premature mortality to estimate the overall burden (disability-adjusted life years (DALYs)) for RA for the years 1990, 2005 and 2010. The global prevalence of RA was 0.24% (95% CI 0.23% to 0.25%), with no discernible change from 1990 to 2010. DALYs increased from 3.3 million (M) (95% CI 2.6 M to 4.1 M) in 1990 to 4.8 M (95% CI 3.7 M to 6.1 M) in 2010. This increase was due to a growth in population and increase in aging. Globally, of the 291 conditions studied, RA was ranked as the 42nd highest contributor to global disability, just below malaria and just above iodine deficiency (measured in YLDs). RA continues to cause modest global disability, with severe consequences in the individuals affected. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2020
                6 November 2020
                : 2020
                : 4031015
                Affiliations
                1Department of Clinical Data Center, The First Affiliated Hospital, Anhui University of Chinese Medicine, Hefei 230031, China
                2Department of Rheumatism Immunity, The First Affiliated Hospital, Anhui University of Chinese Medicine, Hefei 230031, China
                3Graduate Faculty, Anhui University of Chinese Medicine, Hefei 230038, China
                4School of Electrical & Informatics Engineering, Anhui University of Technology, Maanshan 243002, China
                Author notes

                Academic Editor: Fu-Ming Tsai

                Author information
                https://orcid.org/0000-0001-8754-7786
                https://orcid.org/0000-0003-3101-7553
                https://orcid.org/0000-0001-9986-4551
                https://orcid.org/0000-0001-7903-3638
                https://orcid.org/0000-0001-7855-0422
                https://orcid.org/0000-0002-9327-8583
                https://orcid.org/0000-0003-2757-8462
                https://orcid.org/0000-0002-3247-2446
                https://orcid.org/0000-0003-4945-7725
                Article
                10.1155/2020/4031015
                7665920
                33204694
                686b31f3-c3c3-42e8-9693-1bd58ad058e7
                Copyright © 2020 Yanyan Fang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 June 2020
                : 15 October 2020
                : 23 October 2020
                Funding
                Funded by: 12th Batch of “115” Innovation Team of Anhui Province
                Award ID: 1
                Funded by: Anhui Provincial Laboratory of Applied Basis and Development of Internal Medicine of Modern Traditional Chinese Medicine
                Award ID: 2016080503B041
                Funded by: Key Research and Development Plan Project of Anhui Province
                Award ID: 201904a07020004
                Funded by: National Key Innovative Talents Training Project of Traditional Chinese Medicine
                Award ID: 128
                Funded by: Anhui Famous Traditional Chinese Medicine Liu Jian Studio Construction Project
                Award ID: 11
                Funded by: Anhui Provincial Quality Engineering Teaching and Research Project
                Award ID: 2018jyxm1068
                Funded by: National Nature Fund Program
                Award ID: 81973655
                Funded by: Ministry of Science and Technology
                Award ID: 2018YFC1705204
                Funded by: Study on Individualized Treatment of Rheumatoid Arthritis with Integrated Traditional Chinese and Western Medicine Based on Clinical Big Data
                Award ID: KJ2019A0439
                Funded by: Anhui key Research and Development Program Foreign Science and Technology Cooperation Project
                Award ID: 201904b11020011
                Categories
                Research Article

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