Displaying publications 61 - 80 of 177 in total

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  1. Abdul Muizz AM, Mohd Shahrir MS, Sazliyana S, Oteh M, Shamsul AS, Hussein H
    Int J Rheum Dis, 2011 Feb;14(1):18-30.
    PMID: 21303478 DOI: 10.1111/j.1756-185X.2010.01593.x
    AIMS: The aim of this study was to evaluate the left ventricular (LV) diastolic dysfunction in rheumatoid arthritis (RA) patients without clinically evident cardiovascular manifestations and to estimate whether there is any correlation between RA disease severity and disability and LV diastolic dysfunction.
    METHODS: The study was a cross-sectional study involving 53 patients (47 female and 6 male) with RA without clinically evident heart disease and 53 healthy subjects (47 female and 6 male) who served as a control group. Both groups were matched for age and sex. Echocardiographic and Doppler studies were conducted in all patients with RA and control subjects.
    RESULTS: Of 17 cardiac parameters assessed, only two were abnormal. None of the specific cardiac diastolic dysfunction parameters were significantly different in RA patients compared to the control group. There was no significant correlation between diastolic function values in RA patients and value of Disease Activity Score 28 (DAS-28) and value of Health Assessment Questionnaires Disability Index (HAQDI). Atrial (A) wave velocity was greater in RA patients compared to the control group (0.71 [0.58-0.83] vs. 0.61 [0.51-0.71]; P < 0.04). However, interventricular relaxation time (IVRT) ([73.08 ± 9.92 vs. 70.74 ± 9.02], P = 0.207), lower E/A ratio (1.27 [1.02-1.56] vs. 1.42 [1.20-1.68], P = 0.102), diastolic dysfunction parameters according to Redfield Classification (25 [47.2%] vs. 27 [50.9%] P = 0.56), diastolic dysfunction using E/A (P = 0.321) and tissue doppler imaging (E/E') (P = 0.148) were not different.
    CONCLUSION: Prevalence of diastolic dysfunction in the rheumatoid arthritis group (47.2%) was not different from controls (50.9%). LV diastolic function had no significant correlation with RA disease severity and duration of disease.
    Matched MeSH terms: Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/epidemiology; Arthritis, Rheumatoid/physiopathology*
  2. Rajalingam S, Sakthiswary R, Hussein H
    Arch Rheumatol, 2017 Mar;32(1):15-20.
    PMID: 30375543 DOI: 10.5606/ArchRheumatol.2017.5960
    Objectives: This study aims to determine the predictors of poor sleep quality in rheumatoid arthritis (RA).

    Patients and methods: This was a monocentric, cross sectional, case-control study which was conducted at the Putrajaya Hospital, Malaysia. We recruited 46 patients with RA (3 males; 43 females; mean age 48.15±14.96) and 46 age and sex-matched healthy controls (3 males; 43 females; mean age 47.11±12.22). RA patients were assessed for their disease activity based on disease activity score in 28 joints, disease damage based on radiographic erosions, and functional status based on Health Assessment Questionnaire Disability Index. The Pittsburgh Sleep Quality Index (PSQI) scores were determined by interviewing all the subjects. Subjects with RA were further subdivided based on their PSQI scores as "good sleepers" with PSQI scores of <5 and "poor sleepers" with PSQI scores of ≥5.

    Results: The percentage of poor sleepers was significantly higher among RA patients (47.83% versus 9.57%). Median scores of 5 out of 7 components of the PSQI were higher among RA patients compared to controls. Among poor sleepers with RA, a significantly higher proportion tested positive for anti-citrullinated cyclic peptide autoantibodies (p=0.037). Besides, poor sleepers had significantly higher median Health Assessment Questionnaire Disability Index (p=0.017) than good sleepers. However, both Health Assessment Questionnaire Disability Index (p=0.968) and anti-citrullinated cyclic peptide (p=0.431) were insignificant when entered in the equation of a logistic regression model.

    Conclusion: The findings of this study demonstrate a link between functional disability, anti-citrullinated cyclic peptide antibodies, and sleep quality in RA.
    Matched MeSH terms: Arthritis, Rheumatoid
  3. Sakthiswary R, Syahrul Sazliyana S, Mohd Shahrir MS, Shahril NS, Hussein H
    EXCLI J, 2012;11:142-9.
    PMID: 27385955
    Tumor necrosis factor alpha (TNFα) is a multifunctional cytokine which plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Apart from its well recognized proinflammatory properties, it is known to interfere with lipid metabolism and erythropoiesis. We evaluated the effects of adalimumab on hematologic, lipid and inflammatory parameters using data from patients on adalimumab 40 mg fortnightly from 2 centers in Malaysia. Mean changes in laboratory values from baseline to Weeks 4, 12 and 24 were compared using paired T test and Wilcoxon signed-rank test. We studied 18 patients with RA who were on adalimumab 40 mg fortnightly. The inflammatory markers i.e. erythrocyte sedimentation rate and C reactive protein showed significant changes as early as at week 4 compared to baseline with p values of 0.003 and 0.005, respectively. From a baseline of high disease activity with a mean Disease Activity Score using 28 joint counts (DAS 28) of 5.3, there was a steady improvement in the disease activity and remission was achieved at week 24 with a DAS 28 of 2.4. The hemoglobin level improved at week 12 (p=0.013) and this was sustained till week 24. As opposed to previous studies, the LDL level significantly decreased at week 12 (p=0.015) and this change persisted till week 24 (p=0.001). The total cholesterol showed a similar pattern as the LDL. The pharmacodynamics of adalimumab therapy in rheumatoid arthritis extend beyond the joints with favorable effects on haemoglobin and lipid profile.

    Study site: Putrajaya Hospital and Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Arthritis, Rheumatoid
  4. Wong SK, Chin KY, Ima-Nirwana S
    Phytomedicine, 2020 Jul 15;73:152892.
    PMID: 30902523 DOI: 10.1016/j.phymed.2019.152892
    BACKGROUND: Musculoskeletal disorders are a group of disorders that affect the joints, bones, and muscles, causing long-term disability. Berberine, an isoquinoline alkaloid, has been previously established to exhibit beneficial properties in preventing various diseases, including musculoskeletal disorders.

    PURPOSE: This review article aims to recapitulate the therapeutic potential of berberine and its mechanism of action in treating musculoskeletal disorders.

    METHODS: A wide range of literature illustrating the effects of berberine in ameliorating musculoskeletal disorders was retrieved from online electronic databases (PubMed and Medline) and reviewed.

    RESULTS: Berberine may potentially retard the progression of osteoporosis, osteoarthritis and rheumatoid arthritis. Limited studies reported the effects of berberine in suppressing the proliferation of osteosarcoma cells. These beneficial properties of berberine are mediated in part through its ability to target multiple signaling pathways, including PKA, p38 MAPK, Wnt/β-catenin, AMPK, RANK/RANKL/OPG, PI3K/Akt, NFAT, NF-κB, Hedgehog, and oxidative stress signaling. In addition, berberine exhibited anti-apoptotic, anti-inflammatory, and immunosuppressive properties.

    CONCLUSION: The current evidence indicates that berberine may be effective in preventing musculoskeletal disorders. However, findings from in vitro and in vivo investigations await further validation from human clinical trial.

    Matched MeSH terms: Arthritis, Rheumatoid/prevention & control
  5. Ruszymah Idrus, Nur Qisya Afifah Veronica Sainik, Ayu Suraya Ansari, Rabiatul Adawiyah Razali, Abid Nordin, Aminuddin Saim, et al.
    Sains Malaysiana, 2018;47:2741-2755.
    Ficus carica, a native plant to the Middle East and Western Asia, is of high value in folk medicine. The therapeutic potential
    of Ficus carica has led to the extensive studies in recent years, focusing on evaluating and validating its pharmacological
    effect. The present systematic review summarizes the effectiveness of Ficus carica on promoting bone health focusing on
    osteoporosis and rheumatoid arthritis via mineral contents and RANKL pathway. The search was done with Medline via
    Ebscohost, Scopus and Google Scholar databases to obtain relevant articles published between 1946 and December
    2016. The main inclusion criteria were research articles published in English that reported effect of Ficus carica on
    bone health. The literature search returned 716 potentially relevant articles, whereby 5 met the inclusion criteria. This
    systematic review concludes Ficus carica plays an important role in the promotion of bone health and can be a potential
    pharmaceutical product in the future.
    Matched MeSH terms: Arthritis, Rheumatoid
  6. Kotyla PJ, Engelmann M, Giemza-Stokłosa J, Wnuk B, Islam MA
    Int J Mol Sci, 2021 Feb 28;22(5).
    PMID: 33671049 DOI: 10.3390/ijms22052449
    Recent advances in immunology enabled the characterization of several signal transmitting pathways responsible for proper cytokine and chemokine signaling. Among them, Janus kinases (JAKs) are essential components of receptor activation systems. The discovery of JAK kinases enabled the synthesis of JAK kinase inhibitors (JAKi or Jakinibs), which have proven to be efficacious in the treatment of hematologic malignancies and several rheumatological disorders and continue to be investigated in many clinical indications. Blocking multiple cytokines belonging to several cytokine families with a single small molecule may, however, create a potential risk for the patients. Recently, a higher risk of thromboembolic complications, namely, deep vein thrombosis and pulmonary embolism, has been recognized as the main concern during treatment with Jakinibs. At present, it is not entirely clear whether this increased risk is related to direct cytokine blockade, the presence of concomitant diseases in treated patients or other unknown circumstances that work together to increase the risk of this side effect. In this review, we discuss data on the risk of thromboembolic side effects, with special emphasis on the mechanism that may be responsible for this increased risk. Many indirect data indicate that higher thromboembolic risk may be related to the specificity of JAK inhibitor action, such that preferentially blocking one signaling pathway upsets the balance between pro and anti-thrombotic activities.
    Matched MeSH terms: Arthritis, Rheumatoid/drug therapy*; Arthritis, Rheumatoid/enzymology
  7. Khir NAM, Noh ASM, Shafin N, Ismail CAN
    Purinergic Signal, 2021 Jun;17(2):201-213.
    PMID: 33594635 DOI: 10.1007/s11302-021-09764-z
    Pain is the most common symptom reported by patients with rheumatoid arthritis (RA) even after the resolution of chronic joint inflammation. It is believed that RA-associated pain is not solely due to inflammation, but could also be attributed to aberrant modifications to the central nervous system. The P2X4 receptor (P2X4R) is an ATP-activated purinergic receptor that plays a significant role in the transmission of information in the nervous system and pain. The involvement of P2X4R during the pathogenesis of chronic inflammatory pain and neuropathic pain is well-established. The attenuation of this receptor alleviates disease pathogenesis and related symptoms, including hyperalgesia and allodynia. Although some studies have revealed the contribution of P2X4R in promoting joint inflammation in RA, how it implicates pain associated with RA at peripheral and central nervous systems is still lacking. In this review, the possible contributions of P2X4R in the nervous system and how it implicates pain transmission and responses were examined.
    Matched MeSH terms: Arthritis, Rheumatoid/complications*; Arthritis, Rheumatoid/genetics*
  8. Noh ASM, Chuan TD, Khir NAM, Zin AAM, Ghazali AK, Long I, et al.
    PLoS One, 2021;16(12):e0260423.
    PMID: 34879087 DOI: 10.1371/journal.pone.0260423
    Complete Freund's adjuvant (CFA) has been used to develop the arthritic or inflammatory condition in the animal, but there is a lack of information concerning high CFA doses on nociceptive behaviour and inflammatory parameters. This study aimed to compare the effects of different high doses of CFA in rat to closely mimic nociceptive and inflammatory parameters of rheumatoid arthritis (RA) in humans. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6): Control (C), CFA-induced polyarthritic groups at 5.0 mg/mL (CFA 5.0), 7.5 mg/mL (CFA 7.5) and 10.0mg/mL (CFA 10.0). The rats' right hindpaw was inoculated with CFA intradermally and developed into a polyarthritic state within 20 days. Nociceptive behavioural assessments, including von Frey and hot plate tests and spontaneous activities, were conducted on day 0, 7, 15 and 20. Bilateral ankle joints diameter and circumference, full blood count, joints and paw histological examinations were also conducted throughout the study period. Based on the results, CFA 5.0 and CFA 7.5 groups showed a significant increase in spontaneous activities and development of thermal hyperalgesia but no change in body weight and food intake, no development of tactile allodynia and haematological indices, and no significant morphological changes of joints histology. Meanwhile, CFA 10.0 group demonstrated significant and constant changes in all nociceptive and inflammatory parameters investigated. In conclusion, CFA at the dose of 10mg/mL has the most potential and reliable dosage to develop polyarthritis in a rat model to mimic RA condition in humans.
    Matched MeSH terms: Arthritis, Rheumatoid/chemically induced; Arthritis, Rheumatoid/physiopathology*
  9. Park YG, Choi J, Song I, Park SY, Seol JW, Jackson CJ
    Sains Malaysiana, 2017;46:1895-1902.
    Rheumatoid arthritis (RA) is a chronic disease characterized by inflammation of the joints and their lining or synovium. Previous studies showed that the synovium in RA patients is more hypoxic than normal synovium. Activated protein C (APC) has anticoagulant and anti-inflammatory effects and is highly expressed in the joints of RA patients. We examined the effect of APC on RA and normal synovial fibroblasts under hypoxic conditions. Human synovial fibroblasts were isolated from the synovial tissues of RA patients and normal controls and cells were exposed to recombinant APC under normoxic (21% oxygen) or hypoxic (1% oxygen) conditions. Cell proliferation was measured using MTT assays. Cell lysates and conditioned media were collected and assayed for matrix metalloproteinase (MMP)-2, MMP-9 and p38 using zymography and western blots. Proliferation of both normal and RA synovial fibroblasts dose-dependently increased after APC treatment in normoxic conditions. Under hypoxia, APC enhanced RA cell proliferation but had no effect on normal fibroblasts. MMP-2 production and activation were significantly augmented by APC in both cell types under normoxia and hypoxia conditions. However, activated MMP-2 was more reduced in cells under hypoxia than normoxia. APC substantially reduced the phosphorylation of p38 in normal and RA synovial fibroblasts under hypoxia. No difference in p38 phosphorylation was observed under normoxia. The receptor for APC, endothelial protein C receptor (EPCR), was elevated in normal fibroblasts under hypoxic conditions whereas in RA cells, EPCR was highly expressed under both normoxic and hypoxic conditions. We found that hypoxia enhanced the effect of APC on RA synovial fibroblasts through activation of MMP2 and inhibition of p38 phosphorylation. Our results suggested that APC may suppress joint destruction and progression of inflammation in a hypoxic RA environment.
    Matched MeSH terms: Arthritis, Rheumatoid
  10. Wan SA, Teh CL, Cheong YK, Jobli AT
    Med J Malaysia, 2020 03;75(2):141-145.
    PMID: 32281595
    INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disorder characterised by symmetrical polyarthritis which leads to damage of joints if untreated. Early diagnosis and treatment of RA to achieve tight control of the disease will improve outcome and prevent disability.

    OBJECTIVE: We aimed to examine the delays in the diagnosis of RA in patients presenting to the Rheumatology Unit, Sarawak General Hospital (SGH).

    METHODS: Data on demographics and various delays were collected from the medical records from January 2015 until March 2018. Patient delay is defined as from the time onset of symptom to the first primary care presentation. Primary care delay is defined as from the first primary care presentation to referral to rheumatology. Rheumatology delay is defined as from rheumatology referral to appointment at the rheumatology clinic. Disease modifying anti-rheumatic drugs (DMARDS) delay is defined as from the rheumatology clinic appointment to starting DMARDS. Total delay is from symptom onset to starting DMARDS.

    RESULTS: There were 84 new patients diagnosed with rheumatoid arthritis, out of which 66 were females (78.6%). The mean age was 54.1±12.0 years. Only 19 patients (22.6%) were treated with DMARDS within 12 weeks of symptom onset. The median time for patient delay was four weeks (Interquartile range (IQR) 2-20 weeks), while the median time primary care delay was 11 weeks (IQR 4-24 weeks). The median time for rheumatology delay was zero weeks (IQR 0- 1 week) and the DMARDS delay was zero week (IQR 0). The median time from symptom onset to DMARDS initiation was 23.5 weeks (IQR 13.25-51 weeks).

    CONCLUSION: The delays in the diagnosis of rheumatoid arthritis were mainly from the patient and primary care.

    Matched MeSH terms: Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/drug therapy*; Arthritis, Rheumatoid/epidemiology
  11. Bajuri MN, Abdul Kadir MR, Murali MR, Kamarul T
    Med Biol Eng Comput, 2013 Feb;51(1-2):175-86.
    PMID: 23124814 DOI: 10.1007/s11517-012-0982-9
    The total replacement of wrists affected by rheumatoid arthritis (RA) has had mixed outcomes in terms of failure rates. This study was therefore conducted to analyse the biomechanics of wrist arthroplasty using recently reported implants that have shown encouraging results with the aim of providing some insights for the future development of wrist implants. A model of a healthy wrist was developed using computed tomography images from a healthy volunteer. An RA model was simulated based on all ten general characteristics of the disease. The ReMotion ™ total wrist system was then modelled to simulate total wrist arthroplasty (TWA). Finite element analysis was performed with loads simulating the static hand grip action. The results show that the RA model produced distorted patterns of stress distribution with tenfold higher contact pressure than the healthy model. For the TWA model, contact pressure was found to be approximately fivefold lower than the RA model. Compared to the healthy model, significant improvements were observed for the TWA model with minor variations in the stress distribution. In conclusion, the modelled TWA reduced contact pressure between bones but did not restore the stress distribution to the normal healthy condition.
    Matched MeSH terms: Arthritis, Rheumatoid/physiopathology*; Arthritis, Rheumatoid/surgery*
  12. Bajuri MN, Kadir MR, Raman MM, Kamarul T
    Med Eng Phys, 2012 Nov;34(9):1294-302.
    PMID: 22277308 DOI: 10.1016/j.medengphy.2011.12.020
    Understanding the pathomechanics involved in rheumatoid arthritis (RA) of the wrist provides valuable information, which will invariably allow various therapeutic possibilities to be explored. The computational modelling of this disease permits the appropriate simulation to be conducted seamlessly. A study that underpins the fundamental concept that produces the biomechanical changes in a rheumatoid wrist was thus conducted through the use of finite element method. The RA model was constructed from computed tomography datasets, taking into account three major characteristics: synovial proliferation, cartilage destruction and ligamentous laxity. As control, a healthy wrist joint model was developed in parallel and compared. Cartilage was modelled based on the shape of the articulation while the ligaments were modelled with linear spring elements. A load-controlled analysis was performed simulating physiological hand grip loading conditions. The results demonstrated that the diseased model produced abnormal wrist extension and stress distribution as compared to the healthy wrist model. Due to the weakening of the ligaments, destruction of the cartilage and lower bone density, the altered biomechanical stresses were particularly evident at the radioscaphoid and capitolunate articulations which correlate to clinical findings. These results demonstrate the robust finding of the developed RA wrist model, which accurately predicted the pathological process.
    Matched MeSH terms: Arthritis, Rheumatoid; Arthritis, Rheumatoid/physiopathology*
  13. Yuslina MY, Shahnaz M, Too CL, Hussein H, Wahinuddin S, Eashwary M, et al.
    APLAR Journal of Rheumatology, 2006;9 Suppl 1:A187-A188.
    Background: Anti-cyclic citrullinated peptide autoantibodies (anti-CCP) is a new serological test for the diagnosis of rheumatoid arthritis (RA). It is an enzyme immunoassay (EIA) for the detection of antibodies directed toward citrullinated peptides. Studies show this test has an improved diagnostic value compared to rheumatoid factor (RF). Objective: To determine the sensitivity and specificity of anti-CCP in patients with rheumatoid arthritis and other rheumatic diseases. Method: 227 serum samples for rheumatology clinics (Putrajaya, Taiping, and Ipoh Hospital) were tested for the presence of anti-CCP and rheumatoid factor (RF). These included 171 patients diagnosed with RA and 56 from other rheumatic diseases. Patient demographic data, clinical diagnosis, radiographic information and other laboratory data were obtained from the patients' clinical notes. Results: Anti-CCP antibodies were detected in 76.6% (131/171) patients with RA and 17.9% (10/56) patients with other arthritis. The sensitivity and specificity of anti-CCP reactivity at the optimal cut off values were 66.1% and 87.5% respectively. The sensitivity of anti-CCP was higher than that for RF (41.8%). However, the presence of either anti-CCP or RF improved the sensitivity to 76.2%. Conclusion: The detection of anti-CCP alone maybe useful in the diagnosis of RA. However, when used concomitantly with RF, it can improve the diagnostic ability significantly.
    Matched MeSH terms: Arthritis, Rheumatoid
  14. Naqvi AA, Hassali MA, Naqvi SBS, Kachela B, Khan I
    Int J Rheum Dis, 2020 Mar;23(3):325-333.
    PMID: 31880102 DOI: 10.1111/1756-185X.13776
    OBJECTIVE: This study aimed to estimate annual direct cost attributed to rheumatoid arthritis (RA) treatment from a patient's perspective using real-world patient follow-up data from hospitals' electronic database.

    METHODS: A prospective 1-year study was conducted in rheumatology clinics of tertiary care hospitals of Karachi, Pakistan. Cost-of-illness methodology was used and all patient data related to costs of rheumatologist visits, physical therapy sessions, medications, assistive devices and laboratory investigations were obtained directly in printed hardcopies from patient electronic databases using their medical record numbers. Transportation cost was calculated from patient-reported log books. Data were analyzed through IBM SPSS version 23. Patients were asked to sign a written consent and the study was ethically approved.

    RESULTS: The mean age of patients (N = 358) was 48 years. Most patients (73.7%) were female, married (86%) and had basic education (71.8%). Average cost of rheumatologist visits was PKR 11 510.61 (USD: 72.05) while it was PKR 66 947.37 (USD: 419.07) for physical therapy sessions. On average, medicines and medical devices costs were estimated at PKR 10 104.23 (USD: 63.25) and PKR 7848.48 (USD: 49.13) respectively. Cost attributed to diagnostic and laboratory charges was PKR 1962.12 (USD: 12.28) and travel expense was PKR 6541 (USD: 40.95). The direct expenditure associated with managing RA was PKR 37 558 (USD: 235.1). All costs were reported per annum.

    CONCLUSION: Patient with RA in Pakistan pay a considerable amount of their income for managing their condition. Most patients have no provision for insurance which is a need considering the nature of the disease and associated productivity loss that would significantly lower income as the disease progresses.

    Matched MeSH terms: Arthritis, Rheumatoid/diagnosis; Arthritis, Rheumatoid/drug therapy*; Arthritis, Rheumatoid/economics*; Arthritis, Rheumatoid/epidemiology
  15. Toh BH, Sengupta S, Ang AH, White JC, Lau KS
    Ann Rheum Dis, 1973 Mar;32(2):151-6.
    PMID: 4120913 DOI: 10.1136/ard.32.2.151
    In West Malaysia RA appears to be less common than in temperate climates, but more common than in tropical Africa; furthermore, the incidence of gout and SLE is comparable. The clinical manifestations of RA are milder than those seen in more temperate climates. Subcutaneous rheumatoid nodules have not been observed. Positive serological tests for RF are significantly higher than in the general Malaysian population, but still lower than those reported for patients with RA in temperate climates. Of the three main ethnic groups, the highest incidence of positive results is found in the Chinese.
    Study site: Arthritis Clinic, University Hospital, Kuala Lumpur (University Malaya Medical Centre, UMMC, Kuala Lumpur, Malaysia)
    Matched MeSH terms: Arthritis, Rheumatoid/blood; Arthritis, Rheumatoid/immunology; Arthritis, Rheumatoid/epidemiology*
  16. Tan BE, Lim AL, Kan SL, Lim CH, Ng YF, Tng SLC, et al.
    Rheumatol Int, 2017 Jun;37(6):905-913.
    PMID: 28389855 DOI: 10.1007/s00296-017-3705-6
    To evaluate the achievement of treat-to-target (T2T) strategy in rheumatoid arthritis (RA) and identify factors associated with failed treatment target in a public rheumatology center. A cross-sectional study was conducted from June 2015 to February 2016. RA patients with disease duration greater than 2 years and under T2T for over a year were invited to the study. Demographic, clinical data, disease activity score of 28 joints (DAS28), and clinical disease activity index (CDAI) were collected in a single routine clinic visit. Treatment target was defined as DAS28 <3.2 or CDAI ≤10. Retrospective chart review was performed to determine reasons of failed treatment target. A total of 371 patients were recruited and 87.1% were female. Mean age and duration of RA were 53.5 years (SD 10.3) and 9.1 years (SD 6.6), respectively. Ethnic distribution was 49% Chinese, 27% Malay, and 24% Indian. T2T was achieved in 81.7% of the cohort. Non-Chinese ethnicity, positive rheumatoid factor, and treatment with three disease modifying anti-rheumatic drugs (DMARDs) were associated with failed treatment target. After controlling for covariates, Malay ethnicity (OR 2.96; 95% CI 1.47-5.96) and treatment with three DMARDs (OR 2.14; 95% CI 1.06-4.35) were associated with failed treatment target. There was no association between age, gender, duration of RA, BMI, smoking status, anti-citrulinated cyclic peptide, and achievement of T2T. The most common reasons of failed treatment target were inability to escalate DMARDs due to side effects (18.8%), lack of biologics fund (15.6%), and persistent disease despite optimum treatment (14.1%). T2T was successfully implemented. Malay patients need aggressive treatment adaptation to achieve optimal outcome.
    Matched MeSH terms: Arthritis, Rheumatoid/diagnosis; Arthritis, Rheumatoid/drug therapy*; Arthritis, Rheumatoid/ethnology
  17. Kuan WP, Tam LS, Wong CK, Ko FW, Li T, Zhu T, et al.
    J Rheumatol, 2010 Feb;37(2):257-64.
    PMID: 20032101 DOI: 10.3899/jrheum.090769
    OBJECTIVE:
    To assess whether serum levels of CC and CXC chemokines correlate with disease activity in patients with rheumatoid arthritis (RA), and to determine whether these effects predict clinical response.

    METHODS:
    Serum levels of the chemokines CC (CCL2, CCL5) and CXC (CXCL8, CXCL9, CXCL10) were quantified at baseline and after 12 weeks of treatment with disease-modifying antirheumatic drugs or biologic agents in 28 patients using flow cytometry. Serum from 40 healthy individuals was collected for comparison at baseline. Response to treatment was classified according to the European League Against Rheumatism (EULAR) response criteria. Remission of disease was defined as a Disease Activity Score < 2.6.

    RESULTS:
    The baseline serum concentrations of CC and CXC chemokines were significantly elevated in patients with active RA compared to healthy controls (p < 0.05) except for CCL2. Significant improvement in all disease activity measurements was observed after 12 weeks of treatment. Seventeen (60.7%) patients achieved good to moderate response based on the EULAR response criteria, and 5 (17.9%) patients achieved remission. The improvement in clinical activity in patients with RA was accompanied by a significant reduction in the serum concentration of CXCL9 and CXCL10 (p < 0.001). A significant reduction in the serum level of CXCL10 was also observed in the group that achieved EULAR response. Serum concentration of CCL5 remained significantly elevated in patients with RA (n = 5) who achieved remission compared to the healthy controls (p < 0.05).

    CONCLUSION:
    Serum concentration of CXCL9 and CXCL10 may serve as sensitive biomarkers for disease activity in patients with RA.
    Study done in Hong Kong
    Matched MeSH terms: Arthritis, Rheumatoid/blood*; Arthritis, Rheumatoid/therapy
  18. Guo J, Wu X, Too CL, Yin F, Lu X, He J, et al.
    PLoS One, 2012;7(7):e41228.
    PMID: 22829930 DOI: 10.1371/journal.pone.0041228
    OBJECTIVES: Dendritic cell immunoreceptor (DCIR) has been implicated in development of autoimmune disorders in rodent and DCIR polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA)-negative rheumatoid arthritis (RA) in Swedish Caucasians. This study was undertaken to further investigate whether DCIR polymorphisms are also risk factors for the development of RA in four Asian populations originated from China and Malaysia.

    METHODS: We genotyped two DCIR SNPs rs2377422 and rs10840759 in Han Chinese population (1,193 cases, 1,278 controls), to assess their association with RA. Subsequently, rs2377422 was further genotyped in three independent cohorts of Malaysian-Chinese subjects (MY_Chinese, 254 cases, 206 controls), Malay subjects (MY_ Malay, 515 cases, 986 controls), and Malaysian-Indian subjects (MY_Indian, 378 cases, 285 controls), to seek confirmation of association in various ethnic groups. Meta-analysis was preformed to evaluate the contribution of rs2377422 polymorphisms to the development of ACPA-negative RA in distinct ethnic groups. Finally, we carried out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels.

    RESULTS: DCIR rs2377422 was found to be significantly associated with ACPA -negative RA in Han Chinese (OR 1.92, 95% CI 1.27-2.90, P=0.0020). Meta-analysis confirms DCIR rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (OR(overall) =1.17, 95% CI 1.06-1.30, P=0.003). The SNP rs2377422 polymorphism showed significant association with DCIR mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (P=0.0023, Kruskal-Wallis).

    CONCLUSIONS: Our data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA.
    Matched MeSH terms: Arthritis, Rheumatoid/genetics*
  19. Wazir NN, Moorthy V, Amalourde A, Lim HH
    J Orthop Surg (Hong Kong), 2005 Aug;13(2):203-6.
    PMID: 16131689 DOI: 10.1177/230949900501300220
    This is a case report of an extremely rare condition of atlanto-axial subluxation secondary to gouty arthritis, which mimicked rheumatoid arthritis at presentation. Gouty arthritis involving the spine is a rare condition. We highlight a case of gouty arthritis involving the atlanto-axial joint resulting in joint instability, subluxation, and neurological deficit. A 66-year-old obese woman who had a polyarticular disease for the previous 3 years presented with neck pain and progressive neurology. A 2-stage procedure was performed: posterior decompression and occipitocervical fusion followed by further anterior trans-oral decompression. However, after an initial neurological improvement, she succumbed to aspirational pneumonia and septicaemia. Atlanto-axial subluxation caused by gouty arthritis can present in the same way as rheumatoid arthritis. Therefore, the possibility of this as a differential diagnosis should be kept in mind.
    Matched MeSH terms: Arthritis, Rheumatoid/diagnosis*
  20. Meng W, Zhu Z, Jiang X, Too CL, Uebe S, Jagodic M, et al.
    Arthritis Res Ther, 2017 03 29;19(1):71.
    PMID: 28356135 DOI: 10.1186/s13075-017-1276-2
    BACKGROUND: Multiple factors, including interactions between genetic and environmental risks, are important in susceptibility to rheumatoid arthritis (RA). However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether DNA methylation can mediate the interaction between genotype and smoking in the development of anti-citrullinated peptide antibody (ACPA)-positive RA.

    METHODS: We investigated the gene-smoking interactions in DNA methylation using 393 individuals from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). The interaction between rs6933349 and smoking in the risk of developing ACPA-positive RA was further evaluated in a larger portion of the EIRA (1119 controls and 944 ACPA-positive patients with RA), and in the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) (1556 controls and 792 ACPA-positive patients with RA). Finally, mediation analysis was performed to investigate whether DNA methylation of cg21325723 mediates this gene-environment interaction on the risk of developing of ACPA-positive RA.

    RESULTS: We identified and replicated one significant gene-environment interaction between rs6933349 and smoking in DNA methylation of cg21325723. This gene-smoking interaction is a novel interaction in the risk of developing ACPA-positive in both Caucasian (multiplicative P value = 0.056; additive P value = 0.016) and Asian populations (multiplicative P value = 0.035; additive P value = 0.00027), and it is mediated through DNA methylation of cg21325723.

    CONCLUSIONS: We showed that DNA methylation of cg21325723 can mediate the gene-environment interaction between rs6933349 and smoking, impacting the risk of developing ACPA-positive RA, thus being a potential regulator that integrates both internal genetic and external environmental risk factors.
    Matched MeSH terms: Arthritis, Rheumatoid/genetics*; Arthritis, Rheumatoid/immunology
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