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ID PMID Title PublicationDate abstract
22035388 Differences in treat-to-target in patients with rheumatoid arthritis versus hypertension a 2011 "Treat-to-target" of rheumatoid arthritis (RA) is similar in many respects to hypertension and diabetes. All three diseases involve a dysregulation of normal physiologic functions, which results in long-term organ damage if not treated. "Treat-to-target" strategies, based on values of specific quantitative measures, lead to improved outcomes, including longer survival. However, RA differs from hypertension and diabetes in at least five important respects: 1. the absence of a single "gold standard" measure in RA for all individual patients necessitates indices; 2. the rarity of acute emergency situations in RA leads to underestimation of its natural history, which includes increased mortality rates similar to hypertension and diabetes; 3. the patient with hypertension or diabetes goes to the doctor to learn how she or he is doing, based on a "gold standard" quantitative measure, while the patient with RA goes to the doctor to tell the doctor how she or he is doing; 4. the history and physical examination in hypertension or diabetes may be recorded as narrative, nonquantitative information, as a vital sign or laboratory test provides the crucial information for clinical care but should be recorded as quantitative, standardized "scientific" data on patient questionnaires and formal joint counts because of their importance in RA; and 5. patient mood or distress may impact directly RA indices used as quantitative measures in a "treat-to-target" strategy, which is not seen in hypertension or diabetes. These matters may be addressed through three global scales completed by health professionals concerning inflammation, damage, or neither inflammation nor damage as a basis for symptoms.
21073447 Lack of association between ADIPOQ rs266729 and ADIPOQ rs1501299 polymorphisms and cardiov 2011 Jan To assess the potential association between ADIPOQ rs266729 and rs1501299 gene polymorphisms, either isolated or in combination, and cardiovascular disease in patients with rheumatoid arthritis (RA), 674 patients seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos, Madrid, Spain, were analyzed. Genotyping was performed using predesigned TaqMan assays (Applied Biosystems, Foster City, CA). Carotid intima-media thickness, flow-mediated endothelium-dependent and endothelium-independent post-nitroglycerin vasodilatation, which are used as surrogate markers of subclinical atherosclerosis, were measured in a subsample. No significant differences in the genotype, allele or allele combination frequencies of both polymorphisms were found between RA patients with or without cardiovascular events or subclinical atherosclerosis. Therefore, ADIPOQ rs266729 and rs1501299 polymorphisms do not seem to be associated with cardiovascular disease in RA.
22806987 The effectiveness of hydrotherapy in the management of rheumatoid arthritis: a systematic 2013 Mar BACKGROUND: Hydrotherapy is frequently indicated for the rehabilitation of patients with rheumatoid arthritis (RA); nevertheless, there has been inadequate appraisal of its effectiveness. The potential benefits of hydrotherapy for patients with RA are to improve and/or maintain functional ability and quality of life. OBJECTIVES: The aim of this systematic review was to evaluate the effectiveness of hydrotherapy in the management of patients with RA. METHOD: AMED, CINAHL, EMBASE, MEDLINE, PubMed, Science Direct and Web of Science were searched between 1988 and May 2011. Keywords used were rheumatoid arthritis, hydrotherapy, aquatic physiotherapy, aqua therapy and water therapy. Searches were supplemented with hand searches of references of selected articles. Randomized controlled trials were assessed for their methodological quality using the Physiotherapy Evidence Database (PEDro) scale. This scale ranks the methodological quality of a study scoring 7 out of 10 as 'high quality', 5-6 as 'moderate quality' and less than 4 as 'poor quality'. RESULTS: Initially, 197 studies were identified. Six studies met the inclusion criteria for further analysis. The average methodological quality for all studies was 6.8 using the PEDro scale. Most of the studies reported favourable outcomes for a hydrotherapy intervention compared with no treatment or other interventions for patients with RA. Improvement was particularly noted in reducing pain, joint tenderness, mood and tension symptoms, and increasing grip strength and patient satisfaction with hydrotherapy treatment in the short term. CONCLUSIONS: There is some evidence to suggest that hydrotherapy has a positive role in reducing pain and improving the health status of patients with RA compared with no or other interventions in the short term. However, the long-term benefit is unknown. Further studies are needed.
22388357 The use of kinesiology taping method in patients with rheumatoid hand--pilot study. 2012 Jan BACKGROUND: Rheumatoid arthritis (RA) most frequently affects smaller joints in the hands and feet. Among the most common deformations resulting from the progression of the disease are ulnar deviation, Boutonniere deformity, swan neck deformity, contractures and limited range of movement in the hand and wrist joints, muscular atrophy of long and short muscles. The topic of this article is the influence of using Kinesiology Taping method on the functioning of the hand of the patient suffering from rheumatoid arthritis. MATERIAL AND METHODS: The research involved 20 patients suffering from rheumatoid arthritis (16 women, 4 men), treated in the Hospital in Kup. Average age of patients was 62.2. Research subjects, apart from pharmacological treatment in the hospital ward, received standard physiotherapy. In case of 10 patients additional K-Active Tape applications were used to correct ulnar positioning of the hand and improve hand functioning. Prior to physiotherapy, all patients were given a hand functioning test and a dynamometer measurement was made. The tests were repeated after the 2-week rehabilitation process has been completed. The results were subjected to statistical analysis with the use of the Wilcoxon test and the U Mann-Whitney test. The assessment of the correlation between analysed parameters was made with the use of linear correlation test. RESULT: In the group where Kinesiology Tape applications were used, hand muscle strength increased significantly (p<0.05) in comparison with the group treated with standard physiotherapy. Hand muscle strength increase correlated with the tempo of carrying out the hand functioning test (r>0.8). CONCLUSION: Results suggest Kinesiology Taping method useful for physiotherapy of rheumatoid hand.
21226666 Critical determinants of cardiovascular risk in rheumatoid arthritis. 2011 Rheumatoid arthritis (RA), a prototypical immune-mediated inflammatory disease, is characterized by increased cardiovascular morbidity and mortality, independent from the established cardiovascular risk factors. The chronic inflammatory state, a hallmark of RA, is considered to be a driving force for accelerated atherogenesis. Concurrent conditions that expedite the atherosclerotic process in RA involve endothelial dysfunction, dyslipidemia and procoagulant changes. These facilitating states can be reversed by retraction of the systemic inflammatory activity. Consequently, aggressive control of disease activity has been suggested to be instrumental for cardiovascular risk reduction. In the present review, we focus on these critical determinant that promote premature atherosclerosis in RA.
22798268 Rheumatoid arthritis-associated polymorphisms at 6q23 are associated with radiological dam 2012 Sep OBJECTIVE: Recent studies have identified 6q23 as an important susceptibility locus for rheumatoid arthritis (RA), with risk alleles at 3 single-nucleotide polymorphisms combining to give an effect size greater than that of these markers individually. We investigated whether these polymorphisms are also associated with disease severity measured by radiological damage. METHODS: We studied 927 patients from a cross-sectional RA cohort. Median Larsen scores (LS) read from radiographs taken at study entry were compared by genotype at rs6920220, rs13207033, and rs5029937 according to a dominant model using negative binomial regression with stratification for autoantibody status. RESULTS: Median LS was associated with genotype at rs6920220 [LS 31 GG vs 36 GA/AA (p=0.02) in cyclic citrullinated peptide+ (CCP) RA] and rs13020220 [LS 37 GG vs 29 GA/AA (p=0.02) in CCP+ RA] only in autoantibody-positive RA, with no association at rs5029937. Association was stronger for these markers in combination [LS 28 vs 42 for lowest vs highest risk genotype combination in rheumatoid factor positivity (p=0.007), LS 28 vs 37 for anti-CCP+ (p=0.01)]. CONCLUSION: Established RA risk markers at 6q23 are associated also with radiographic severity in autoantibody-positive RA; as for susceptibility, the association for these markers in combination is stronger than that for markers alone.
21446207 [Anticitrullin antibodies--modern markers of rheumatoid arthritis]. 2011 Modern diagnosis of rheumatoid arthritis (RA) is based on the ARA criteria with seropositivity detection by the rheumatoid factor (RF). In a clinically evident stage of the disease this factor is highly sensitive and specific (about 90%), but in early RA efficacy of this diagnosis is considerably less. RF-IgM phenotype has limitation: frequent detection of this factor in the absence of RA and unstability of RF-IgM phenotype. Therefore, it is necessary to search for new serological criteria of RA diagnosis at early stage of the disease. Proteins containing citrullin appear only in the course of posttranslation modification of arginin residues. This fact gave rise to an original, available for clinical practice method of enzyme immunoassay for detection of antibodies to cyclic citrullinized (ACCP)--filaggrin derivative with synthetic cyclic citrullinized peptide serves as antigenic substance. According to the results of different studies, ACCP specificity in early RA diagnosis is more than 80%, combination of ACCP with ESR, RF-IgM, CRP, morning stiffness--more than 90%. As specificity of combination of these autoantibodies is almost 100%, their simultaneous determination is indicated in patients with undifferentiated arthritis for specification of the diagnosis. ACCP and antibodies to modified citrullinized vimentin (AMCV) significantly correlate with RA activity, are prognostic factors of rapidly progressive course and can be used for the disease prognosis at its early stage. Present-day data on comparative specificity and sensitivity of ACCP and AMCV are not certain and need further study.
21639951 Negative regulation of NF-κB and its involvement in rheumatoid arthritis. 2011 May 31 The transcription factor NF-κB plays crucial roles in the regulation of inflammation and immune responses, and inappropriate NF-κB activity has been linked with many autoimmune and inflammatory diseases, including rheumatoid arthritis. Cells employ a multilayered control system to keep NF-κB signalling in check, including a repertoire of negative feedback regulators ensuring termination of NF-κB responses. Here we will review various negative regulatory mechanisms that have evolved to control NF-κB signalling and which have been implicated in the pathogenesis of rheumatoid arthritis.
22589253 Autofeedback from ultrasound images provides rapid improvement in palpation skills for ide 2012 Jun OBJECTIVE: Joint swelling, an important factor in the classification criteria and disease activity assessment in rheumatoid arthritis (RA), renders joint palpation a necessary skill for physicians. Ultrasound (US) examination that visualizes soft tissue abnormalities is now used to assess musculoskeletal disease. We assessed the usefulness of US assessments in enhancing physical joint examination skills. METHODS: We examined 1944 joints (bilateral shoulder, elbow, wrist, metacarpophalangeal joints 1-5, and knee joints) in 108 patients with RA during April-July 2011. We first physically examined and confirmed joint swelling; subsequently, the same rheumatologist conducted US examinations and multiple assessors graded the joint swelling. When the 2 results differed, we received autofeedback from the US results to improve the physical examination skills. RESULTS: The sensitivities and specificities of physical examination for US-detected swollen joint, the correlation coefficient (CC) of the swollen joint counts, and the concordance rate in each patient for joint swelling sites and power Doppler (PD)-positive sites with the κ coefficients between the physical and US examinations were compared over time. We found that the sensitivity of physical examination increased by 42 percentage points (pp), while the specificity decreased by 18 pp. The average CC in June-July was greater than that in April-May. The percentage of κ coefficients > 0.8 increased from 8.8% to 17% for joint swelling and from 8.3% to 14% for PD-positive sites. CONCLUSION: Our results suggest that autofeedback from US assessment provides quick improvement in palpation skills for identifying joint swelling in patients with RA.
21947350 Compliance with treatment of rheumatoid arthritis. 2012 Oct Rheumatoid arthritis (RA) is a chronic, progressive, debilitating disease that demands continuous therapy with multiple medications. Noncompliance with disease-modifying drugs may cause disease flares, preventable functional impairment, unnecessary treatment changes, and loss of health care resources. The aim of the current study was to explore self-reported compliance with treatment and the factors contributing to this compliance using a representative sample of an RA patient population in Estonia. Two thousand patients diagnosed with RA were randomly selected from the Estonian Health Insurance Fund database. The eligible response rate of the study was 60%. Using prestructured questionnaires, the following information about the disease and treatment was evaluated: self-reported compliance with treatment, reasons for noncompliance, disease history, sociodemographic variables, health care utilization, and satisfaction with health care providers. The self-reported compliance rate was 80.3%, reflecting the percentage of patients who reported that they always took their medications exactly as described. The most often reported reasons for noncompliance were side effects and fear of side effects. Compliance was found to be the lowest in a group of younger and active patients with higher income. Higher frequency of visits to the rheumatologist, satisfaction with health care providers, and sufficient information about RA treatment correlated with better compliance.
21364350 Vitamin D, immunoregulation, and rheumatoid arthritis. 2011 Mar In addition to being important in calcium and phosphorus metabolism, bone formation, and mineralization, vitamin D also plays a part in the maintenance of immune homeostasis. Vitamin D receptors are expressed in a number of different tissues, including, and perhaps most notably, on immune cells. The presence or absence of activated vitamin D has a number of effects on in vitro immune cell function. This review describes the possible immunoregulatory role of vitamin D in rheumatoid arthritis with clinical and animal studies.
21965644 Validating the 28-tender joint count using item response theory. 2011 Dec OBJECTIVE: To examine the construct validity of the 28-tender joint count (TJC-28) using item response theory (IRT)-based methods. METHODS: A total of 457 patients with early stage rheumatoid arthritis (RA) were included. Internal construct validity of the TJC-28 was evaluated by determining whether the TJC-28 fit a 2-measure logistic IRT model. As well, we tested whether the discrimination and difficulty parameters of the joints properly reflected the known left-right symmetry of joint involvement. External validity was evaluated by correlations with other established measures of disease activity, including pain, disability, general health, erythrocyte sedimentation rate (ESR), and the 28-swollen joint count. RESULTS: The TJC-28 showed a good fit with the 2-parameter logistic model, with no relevant differential item functioning across sex, age, and time and with excellent reliability. The 28 joints covered a reasonable range of disease activity, even though they were mainly targeted at patients with moderate or high disease activity levels. The joint parameters reflected the left-right symmetry of joint involvement for all pairs of joints except one. All disease activity measures, except ESR, were significantly correlated with the TJC-28. Most correlations were of the expected magnitude. CONCLUSION: The TJC-28 showed good internal and acceptable external construct validity for patients with early-stage RA. The IRT analyses did point to some potential limitations of the instrument, a major problem being its limited measurement range. Future research should examine whether instrument modifications might lead to a more robust assessment of disease activity in patients with RA.
22172039 Measuring intranodal pressure and lymph viscosity to elucidate mechanisms of arthritic fla 2011 Dec Rheumatoid arthritis (RA) is a chronic autoimmune disease with episodic flares in affected joints; the etiology of RA is largely unknown. Recent studies in mice demonstrated that alterations in lymphatics from affected joints precede flares. Thus, we aimed to develop novel methods for measuring lymph node pressure and lymph viscosity in limbs of mice. Pressure measurements were performed by inserting a glass micropipette connected to a pressure transducer into popliteal lymph nodes (PLN) or axillary lymph nodes (ALN) of mice; subsequently, we determined that the lymphatic pressures of water were 9 and 12 cm, respectively. We are also developing methods for measuring lymph viscosity in lymphatic vessels afferent to PLN, which can be measured by multiphoton fluorescence recovery after photobleaching (MP-FRAP) of fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) injected into the hind footpad. These results demonstrate the potential of lymph node pressure and lymph viscosity measurements, and future studies to test these outcomes as biomarkers of arthritic flare are warranted.
21906442 [Combination of AD5-10 and epirubicin in treating rheumatoid arthritis]. 2011 Aug OBJECTIVE: To investigate the mechanism of anti-death receptor 5-10 (AD5-10) combined with epirubicin in treating rheumatoid arthritis (RA). METHODS: We detected the cell viability of the fibroblast-like synoviocytes (FLS) from RA patients with MTT. The expression level of apoptosis signaling pathways protein, p53, and p21 were evaluated with Western blot. RESULTS: We found that epirubicin, at different doses, could enhance the effect of AD5-10 on FLS, promoting the apoptosis of FLS. The expression levels of caspase-3, -8, -9, c-FLIP, Bcl-2, p53, and p21 in the FLS changed after epirubicin treatment. CONCLUSION: Epirubicin may coordinate with AD5-10 in inducing FLS apoptosis through affecting the levels of p53, p21, c-FLIP, and Bcl-2.
21833526 A Tunisian case-control association study of a 6q polymorphism in rheumatoid arthritis. 2012 Jun Rheumatoid arthritis (RA), the most common autoimmune inflammatory disease of the joints, is a multifactorial disease, involving both genetic and environmental risk factors. TNFAIP3 (tumor necrosis factor, alpha-induced protein 3) gene located in a region of genetic susceptibility in RA is an attractive candidate to be involved in autoimmunity disorders. Our aim was to test the single nucleotide polymorphism rs6920220 located near TNFAIP3 in a case-control study in Tunisian population. The rare allele rs6920220-A was reported to have a risk effect on RA in several genome-wide association studies. Our results revealed a trend of an association of rs6920220-A allele with RA and genotypes containing this allele were in a higher proportion in RA patients than in matched controls. These findings have to be confirmed by a replication in largest RA and control groups of the same ethnic origin. TNFAIP3 gene may have a key role in autoimmunity through its action as a negative regulator of the NF-κB pathway. Further functional investigations are required to understand the mechanism by which this gene is involved in the RA pathogenesis.
22004226 Quantitative measurement of serum hyaluronic acid molecular weight in rheumatoid arthritis 2011 Oct AIM: Hyaluronic acid (HA) is a glycosaminoglycan and is essential for protecting the cartilage surface by its physical property. It is known that serum HA concentration in rheumatoid arthritis (RA) patients is higher than in healthy volunteer. However, molecular weight (MW) of serum HA in RA patients is not clear, since it needs a large sample volume to assay serum HA MW. The aim of this study is to establish the method for measuring serum HA MW in small sample sizes and to assess the association between serum HA MW and hyaluronidase (HAase) activity. METHODS: MW of serum HA in RA patients was measured using high-performance liquid chromatography and HA-binding protein. Additionally, the correlation between serum HA and HAase activity was examined using zymographic measurements. RESULTS: Serum HA MW peaked at 1-2 × 10(5) Da in all cases. However, in certain cases two peaks were observed, one each at low (1-2 × 10(5) Da) and high (8-14 × 10(5) Da) MW. HAase activity was lower in cases exhibiting this two-peaked serum HA MW pattern than in those cases with only a single peak. CONCLUSION: The novel method developed for this study permits accurate measurement of serum HA MW. The correlation observed between serum HA MW and HAase activity suggests that serum HA MW may reflect the condition of subjects' joints.
21441551 Levels of plasma fibrinogen are elevated in well-controlled rheumatoid arthritis. 2011 Aug OBJECTIVE: Patients with RA have systemic inflammation and increased risk of cardiovascular (CV) events, including thrombosis. Levels of fibrinogen, a pro-thrombotic protein with predictive value for CV disease (CVD), are elevated during systemic inflammation. We compared circulating fibrinogen levels in patients with RA with healthy controls and evaluated the relationship with measures of disease activity. METHODS: Patients with RA and controls were recruited at the University of California, San Francisco (UCSF). Disease activity was evaluated using standard composite indices. Fibrinogen, ESR, serum CRP, acute-phase serum amyloid A and levels of selected cytokines were quantified. RESULTS: A total of 105 RA patients and 62 controls were studied. Among patients with RA, disease activity ranged from quiescent to highly active disease. Circulating fibrinogen levels were significantly higher in RA than in controls [median (interquartile range) 466 (391-575) vs 367 (309-419) mg/dl, respectively, P < 0.0001]. This difference remained highly statistically significant after adjustment for demographic variables and BMI. Although fibrinogen correlated significantly with clinical measures of disease activity, significantly elevated levels were observed at low levels of activity, even in RA patients with no detectable swollen or tender joints. In multivariable models, ~ 80% of the increased fibrinogen in RA was accounted for by increases in CRP and ESR. CONCLUSION: Circulating levels of fibrinogen are elevated in RA and correlated with markers of inflammation, but only modestly correlate with clinical assessments of disease activity. Even RA patients with excellent clinical disease control exhibit elevated levels compared with controls.
21330341 Societal costs of rheumatoid arthritis in Hong Kong: a prevalence-based cost-of-illness st 2011 Jul OBJECTIVE: To estimate the direct and indirect costs among a cohort of Chinese patients with RA in Hong Kong. METHODS: A cost-of-illness study using cross-sectional and retrospective data was conducted on 144 patients with RA. Costs were estimated from the societal perspective. Participants completed questionnaires regarding demographics, employment status and out-of-pocket expenses. Health resources consumption was recorded by review of medical records. Functional disability was assessed using the HAQ score. RESULTS: The cohort had a mean age of 49 years and mean disease duration of 10.8 years. Average total costs of RA were estimated at $9286 (2006 US dollars) per patient-year, >60% of which was attributable to indirect costs due to productivity losses. Patients' out-of-pocket expenses and costs of inpatient care dominated direct costs, each representing 11% of total direct costs. Younger age, poorer physical and mental health independently predicted high direct costs. Older age, lower education level and more functional disability independently predicted high indirect costs. CONCLUSION: RA is associated with both high direct and indirect costs, imposing a considerable economic burden on patients and society. The hope is that effort will be gathered not only from patients and physicians, but more importantly from government, to improve the care and treatment of patients with RA and to help reduce or avoid the considerable societal costs of RA.
22114882 Clinical pharmacology of tocilizumab for the treatment of patients with rheumatoid arthrit 2011 Sep Tocilizumab is a humanized anti-IL-6 receptor (IL-6R) monoclonal antibody for the treatment of rheumatoid arthritis (RA). A dose of 8 mg/kg produces adequate blockade of IL-6 receptors throughout a dosing interval, as confirmed by sustained high levels of tocilizumab-bound soluble IL6-R complex and normalization of C-reactive protein levels. Studies have confirmed 8 mg/kg every 4 weeks as the optimal dose and 4 mg/kg as the starting dose for the treatment of RA, with favorable efficacy and acceptable safety profiles. After 8 mg/kg, steady-state peak and trough concentrations were 183 ± 86 and 9.7 ± 11 µg/ml, respectively. Tocilizumab serum exposures increased more than proportionally to the dose increase from 2-10 mg/kg. Total clearance is concentration dependent, with non-linear receptor-mediated clearance dominant at low concentrations (<25 µg/ml). Tocilizumab exposures are not affected by common concomitant medications in RA patients, but decreased IL-6 activity resulted in increased CYP3A4 activity and hence decreased exposures of CYP3A4 substrates.
21258799 Concomitant rheumatoid arthritis and amyotrophic lateral sclerosis: report of two new case 2011 Jun To describe a rare association between rheumatoid arthritis (RA) and amyotrophic lateral sclerosis (ALS). Two new cases of patients with RA who developed amyotrophic lateral sclerosis (ALS), one receiving anti-TNFα agents, were reported. Only other five cases of this rare association have been previously described in literature. The simultaneous presence of the two diseases represents a difficult diagnostic challenge because RA may mimic some musculoskeletal symptoms of ALS. There is no evidence in favor of a common pathophysiologic mechanism, and thus the possibility of a fortuitous association must be raised. A neurotoxic side effect of various drugs for RA treatment could be considered. Casual or causal association remains a difficult choice. The possibility of a coincidental association must be raised but neurologic side effects of TNFα blockers lead to discussion.