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23049851 Potential of ayurgenomics approach in complex trait research: leads from a pilot study on 2012 BACKGROUND: Inconsistent results across association studies including Genome-wide association, have posed a major challenge in complex disease genetics. Of the several factors which contribute to this, phenotypic heterogeneity is a serious limitation encountered in modern medicine. On the other hand, Ayurveda, a holistic Indian traditional system of medicine, enables subgrouping of individuals into three major categories namely Vata, Pitta and Kapha, based on their physical and mental constitution, referred to as Prakriti. We hypothesised that conditioning association studies on prior risk, predictable in Ayurveda, will uncover much more variance and potentially open up more predictive health. OBJECTIVES AND METHODS: Identification of genetic susceptibility markers by combining the prakriti based subgrouping of individuals with genetic analysis tools was attempted in a Rheumatoid arthritis (RA) cohort. Association of 21 markers from commonly implicated inflammatory and oxidative stress pathways was tested using a case-control approach in a total cohort comprising 325 cases and 356 controls and in the three subgroups separately. We also tested few postulates of Ayurveda on the disease characteristics in different prakriti groups using clinico-genetic data. RESULTS: Inflammatory genes like IL1β (C-C-C haplotype, p=0.0005, OR=3.09) and CD40 (rs4810485 allelic, p=0.04, OR=2.27) seem to be the determinants in Vata subgroup whereas oxidative stress pathway genes are observed in Pitta (SOD3 rs699473, p=0.004, OR=1.83; rs2536512 p=0.005; OR=1.88 and PON1 rs662, p=0.04, OR=1.53) and Kapha (SOD3 rs2536512, genotypic, p=0.02, OR=2.39) subgroups. Fixed effect analysis of the associated markers from CD40, SOD3 and TNFα with genotype X prakriti interaction terms suggests heterogeneity of effects within the subgroups. Further, disease characteristics such as severity was most pronounced in Vata group. CONCLUSIONS: This exploratory study suggests discrete causal pathways for RA etiology in prakriti based subgroups, thereby, validating concepts of prakriti and personalized medicine in Ayurveda. Ayurgenomics approach holds promise for biomarker discovery in complex diseases.
21807795 Examining the similarities and differences of OMERACT core sets using the ICF: first step 2011 Aug To contribute to the discussion on a common approach for domain selection in the Outcomes in Rheumatology Clinical Trials (OMERACT) process. First, this article reports on the consistency in the selection and names of the domains of the current OMERACT core set, and next on the comparability of the specifications of concepts that are relevant within the domains. For this purpose, a convenience sample of 4 OMERACT core sets was used: rheumatoid arthritis (RA), psoriatic arthritis (PsA), longitudinal observational studies (LOS) in rheumatology, and ankylosing spondylitis (AS). Domains from the different core sets were compared directly. To be able to compare the specific content of the domains, the concepts contained in the questionnaires that were considered or proposed to measure the domains were identified and linked to the category of the International Classification of Functioning, Disability, and Health (ICF) that best fit that construct. Large differences in the domains, and lack of domain definitions, were noted among the 4 OMERACT core sets. When comparing the concepts in the questionnaires that represent the domains, core sets differed also in the number and type of constructs that were addressed within each of the domains. Especially for the specification of the concepts within the domains Discomfort and Disability, the ICF proved to be useful as external reference to classify the different constructs. Our exercise suggests that the OMERACT process could benefit from a standardized approach to select, define, and specify domains, and demonstrated that the ICF is useful for further classification of the more specific concepts of "what to measure" within the domains. A clear definition and classification of domains and their specification can be useful as a starting point to build a pool of items that could then be used to develop new instruments to assess functioning and health for rheumatological conditions.
23271131 Polymorphism in vitamin D receptor and osteoprotegerin genes in Egyptian rheumatoid arthri 2013 May 1α,25-Dihydroxyvitamin D3 upregulates the expression of the receptor activator of nuclear factor kB ligand (RANKL), and downregulates osteoprotegerin (OPG) expression. We tested the effects of polymorphisms in the vitamin D receptor gene (VDR), and OPG gene in rheumatoid arthritis (RA) patients and healthy controls and their relationship to bone mineral density (BMD) and development of osteoporosis. Three hundred and fifty women were evaluated, 200 women having RA and 150 healthy control. The subjects were genotyped for polymorphism at BsmI in VDR and A163G in OPG genes by polymerase chain reaction followed by restriction fragment length polymorphism analysis. BMD was also measured. In A163G, the G allele increased the risk for RA and for the development of osteoporosis. We found a significant association between lower hip (BMD-h) and genotype variants of VDR (BsmI) and OPG A163G in RA patients with osteoporosis. Our results suggested that OPG A163G polymorphism was associated with RA susceptibility and with the development of osteoporosis in these patients. Also, VDR and OPG genes are important candidates for osteoporosis in RA patients.
20959355 Obesity in rheumatoid arthritis. 2011 Mar Obesity is a major threat for public health and its study has attracted significant attention in the general population, predominantly due to its association with significant metabolic and cardiovascular complications. In RA research, BMI is frequently reported as a demographical variable, but obesity, as such, has received little interest. This is surprising, in view of the clear associations of obesity with other arthritides, particularly OA, but also in view of the now-clear association of RA with increased cardiovascular morbidity and mortality. In this review, we summarize the studies that have looked into obesity in the RA population, evaluate their findings, identify knowledge gaps and propose directions for future research. We also pose a question of high clinical and research significance: is the use of BMI still a valid way of assessing obesity in RA?
21560256 Disease-related differential item functioning in the work instability scale for rheumatoid 2011 Aug OBJECTIVE: The 23-item Work Instability Scale for Rheumatoid Arthritis (RA-WIS) is a promising measure to assess risk for future work disability. Validated in both rheumatoid arthritis (RA) and osteoarthritis (OA), it has high potential for cross-disease applications. Our objective was to examine disease-related differential item functioning (DIF) in the RA-WIS. METHODS: Workers with RA (n = 120) or OA (n = 130) were recruited from 3 sites and completed a questionnaire consisting of demographic and health- and work-related variables, including the RA-WIS (range 0-23, where 23 = highest work instability). Multiple DIF detection methods were applied for comparability: 1) Mantel-Haenszel and Breslow-Day procedures, 2) hierarchical 3-step sequential logistic regression procedure, and 3) a 1-parameter item response theory approach (Rasch analysis). Both tests of significance (chi-square and F tests) and effect size statistics (Δ(MH) , ΔR(2) ) were assessed to confirm items demonstrating uniform or nonuniform DIF. A 2-step purification procedure was applied to establish a DIF-free conditioning variable (total RA-WIS score) for DIF analyses. The resultant impact of disease-related DIF at the scale level was also evaluated. RESULTS: All 3 DIF detection methods converged to reveal 3 RA-WIS items as having significant disease-related uniform DIF. Two items ("difficulty opening doors" and "pressure on hand") were more likely affirmed in RA, while 1 item ("very stiff") was more likely affirmed in OA. Overall, only a marginal impact at the scale level was found due to a small proportion of scale items exhibiting DIF and the bidirectional nature of DIF effects. CONCLUSION: RA-WIS scores can be directly compared between RA and OA without significant concerns for DIF-related measurement bias.
20734214 Patterns of background factors related to early RA patients' conceptions of the cause of t 2011 Mar The aim of the present study was to identify patterns of background factors related to the early RA patients' conceptions of the cause of the disease. Conceptions from a qualitative study formed the basis for the stratification of 785 patients from the Swedish EIRA study answering a question about their own thoughts about the cause to RA. Logistic regression analyses were used to explore the associations between patients' conceptions and relevant background factors: sex, age, civil status, educational level, anti-cyclic citrullinated peptide antibody (anti-CCP) and smoking habits. The results were presented as odds ratios (OR) with 95% confidence intervals (CI). A conception of family-related strain was strongly associated with being young (OR 0.50; 95% CI 0.33-0.78 for age 58-70 vs. 17-46), female (OR 0.38; 95% CI 0.25-0.60 for male vs. female) and having a high level of education (OR 2.15; 95% CI 1.54-3.01 for university degree vs. no degree). A conception of being exposed to climate changes was associated with being male (OR 1.99; 95% CI 1.24-3.22 for male vs. female), having a low level of education (OR 0.33; 95% CI 0.18-0.58 for university degree vs. no degree) and positive Anti-CCP (OR 1.72; 95% CI 1.03-2.87 for positive vs. negative Anti-CCP). Linking patients' conceptions of the cause of their RA to background factors potentially could create new opportunities for understanding the complexity of the aetiology in RA. Furthermore, this information is important and relevant in the care of patients with early RA.
23182162 Niki de Saint Phalle's lifelong dialogue between art and diseases: psychological trauma of 2013 May The French artist Niki de Saint Phalle (1930-2002) is one of the most famous female painter and sculptor of the 20th century. Her eventful live was full of emotional and physical burdens such as abuse by the father as a adolescent, early separation from family, nervous collapse, turbulent relationship with the artist Jean Tinguely, and last not least serious diseases. The psychological trauma of sexual abuse together with a "nervous breakdown" years later was the start of a life as an artist and is also a key to her art of the early years. She was affected from rheumatoid arthritis (RA) and was treated over 20 years with prednisolone and antimalarials leading to a good functional outcome and limited erosions of the wrist joint. Additionally, she had lifelong pulmonary disorders finally leading to death, which she attributed to polyester, the material used for her sculptures. An analysis of medical documents collected by her and provided by treating physicians gives another surprising explanation: selective IgA deficiency with multiple recurrent respiratory infections, asthma, milk intolerance, autoimmune thyroiditis, and RA compatible with hypogammaglobulinemia. Very unique in case of Niki de Saint Phalle is that IgA deficiency was transient. Nevertheless, it may be possible that the occupational exposure with art materials (polystyrene, polyester) has contributed in part or temporarily to her health problems. Altogether, her enormous artistic productivity represents an outstanding example of creative coping with RA and other lifelong health problems.
22070089 Small molecular therapies for rheumatoid arthritis: where do we stand? 2012 Jan INTRODUCTION: Early aggressive treatment and utilization of targeted biological therapies for rheumatoid arthritis (RA) has dramatically improved patient outcomes. Even with this approach up to 50% of patients fail to achieve a significant clinical response and these therapies require subcutaneous injection or intravenous administration and are costly. Development of small molecules that can be administered orally has progressed and several are under investigation as potential treatments for RA. This manuscript will update the status of the small molecules under development. AREAS COVERED: This review summarizes the newer molecular protein kinase targets involved in signal transduction of inflammatory mediators and the development of inhibitors to these kinases. Additionally, the results of clinical trials evaluating these therapies will be reviewed. EXPERT OPINION: Based on the results of randomized clinical trials there is significant likelihood that a small molecular therapy to kinases involved in proinflammatory cytokine production will soon be available in the clinic. The benefit/risk profile is presently being determined in multiple late phase clinical trials.
22578877 Quantification of synovitis in the cranio-cervical region: dynamic contrast enhanced and d 2012 Nov OBJECTIVE: To test the feasibility of dynamic contrast enhanced (DCEI) and diffusion weighted (DWI) magnetic resonance imaging (MRI) for quantifying synovitis of the cranio-cervical (C-C) region in patients with early rheumatoid arthritis (RA) and neck pain at the beginning and at a six month follow up. METHODS: 27 patients with duration of RA of less than 24 months and neck pain were studied with standard qualitative MRI evaluation and two quantitative MRI methods (DCEI and DWI) at the level of atlantoaxial joints. Rate of early enhancement (REE), enhancement gradient (Genh) and apparent diffusion coefficient (ADC) were extracted from DCEI and DWI data. MRI was coupled with clinical assessment and radiographic imaging. RESULTS: Using standard qualitative MRI evaluation, unequivocal active synovitis (grade 2 or 3 contrast enhancement) was proved in 16 (59%) patients at baseline and 14 (54%) at follow up. DCEI and DWI measurements confirmed active synovitis in 25 (93%) patients at baseline and 24 (92%) at follow up. Average REE, Genh and ADC values decreased during follow up, however the difference was not statistically significant (p>0.05). Both qualitative and quantitative MRI methods confirmed active inflammatory disease in the C-C region following therapy although all clinical criteria showed signs of improvement of the peripheral disease. CONCLUSIONS: The study proved the feasibility of DCEI and DWI MRI for quantifying synovitis of the C-C region in patients with early RA and neck pain. Both techniques can be used as additional method for evaluation of synovitis of the C-C region in RA.
22283877 Differences between questionnaire- and interview-based measures of activities of daily liv 2012 Mar OBJECTIVES: Although self-report based on questionnaire is the common method to obtain information about activities of daily living (ADL) ability in rheumatic diseases, little is known about the relationship between measures of ADL ability based on questionnaire, interview, and observation. The present study examined whether measures of self-reported ADL ability based on questionnaire and interview yielded different results, determined whether the magnitude of the difference varied among women with rheumatoid arthritis (RA), knee osteoarthritis (OA), and fibromyalgia (FM), and investigated the relationships between self-reported and observed ADL ability. METHOD: The 47 ADL tasks of the ADL taxonomy were used to evaluate self-reported ADL ability based on questionnaire (ADL-Q) and interview (ADL-I), and the Assessment of Motor and Process Skills (AMPS) was used to obtain measures of observed ADL ability. RESULTS: Participants across diagnostic groups reported significantly more ADL ability based on the ADL-Q than on the ADL-I. Moderate correlations were found between the ADL-Q and ADL-I ability measures. Although low to moderate correlations were seen between measures based on the AMPS ADL motor scale and the ADL-Q and ADL-I, respectively, correlations between measures based on AMPS ADL process scale and ADL-Q and ADL-I were generally low. Overall, there was no difference in how the measures based on the two modes of self-report related to the observed ADL ability measures. CONCLUSION: Measures of self-reported ADL ability based on either questionnaire or interview have limited relationship to each other or to observed performance of ADL tasks.
21922190 Discovery of serum protein biomarkers in rheumatoid arthritis using MALDI-TOF-MS combined 2012 Sep The aim of this study was to discover potential biomarkers for rheumatoid arthritis (RA) using Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry combined with magnetic beads. Proteomic fingerprint technology combining magnetic beads with MALDI-TOF-MS was used to profile and compare the proteomes in serum samples from 60 patients with RA, 35 patients with osteoarthritis and 36 healthy controls. The proteomic pattern associated with RA was identified by Biomarker Patterns Software. Model of biomarkers was constructed and evaluated through the Biomarker Patterns Software. A total of 33 discriminative peaks were identified to be related with RA, in which the 5 peaks with the mass-charge ratio (m/z) peaks at 15,715.5, 7,771.4, 8,959.4, 8,469.8 and 8,710.8 Da were used to construct a model for the diagnosis of RA by pattern recognition software. The blind testing data indicated a sensitivity of 86.7% and a specificity of 90.0% in RA diagnosis. These results demonstrated that potential protein biomarkers for RA could be discovered in serum by MALDI-TOF-MS combined with WCX magnetic beads. The diagnosis mode tree based on the five candidate biomarkers could provide a powerful and reliable diagnostic method for RA with high sensitivity and specificity.
21077800 Gustatory and olfactory function in rheumatoid arthritis. 2011 May OBJECTIVES: To evaluate the gustatory and olfactory functions of patients with rheumatoid arthritis (RA) compared to sex- and age-matched healthy subjects and to investigate a potential relationship between disease activity [using the 28-joint Disease Activity Score (DAS28)] and chemosensory capacity. Furthermore, to dissect possible impacts of standard anti-inflammatory medications on the gustatory and olfactory functions. METHODS: Patients with established RA underwent standardized assessment of their gustatory and olfactory functions. The patients were also examined for their disease activity, had their specific blood-test results analysed, and were asked to answer a standardized questionnaire about their quality of life, the negative effects of their disease, and about comorbidities. RESULTS: A total of 101 RA patients (75 women, 26 men, mean age: 57.9 ± 13.8 and 64.2 ± 10.9 years, respectively) were analysed. In relation to age- and sex-related subjects, both female and male RA patients had a significantly decreased taste score (p < 0.001) and also a significantly decreased olfactory score (p < 0.05), indicating that a substantial number of patients suffer from hypogeusia or hyposmia. This abnormality did not correlate with disease activity, the duration of the disease, disease-modifying anti-rheumatic drug (DMARD) or tumour necrosis factor (TNF) inhibitor use, and the loss of the chemosensory functions, together indicating that hypogeusia and hyposmia are frequent clinical manifestations in RA patients independent of the inflammatory activity of their disease. CONCLUSION: The results indicate that there is a significant decrease in the olfactory and gustatory function in RA patients compared to those of healthy controls, which can seriously and substantially affect the quality of the patients' life.
21181221 Observational studies: a valuable source for data on the true value of RA therapies. 2011 Mar The validity of observational studies is sometimes questioned because of the limitations of non-randomly assigned controls, various biases such as channeling bias, confounding by indication, and other pitfalls. Yet, (post-marketing) observational data can provide important information regarding not only drug safety but also the effectiveness and appropriate use of agents in the real world, outside of clinical trials. Observational studies also provide data regarding the wider value of these agents in terms of, for example, reducing the need for surgical procedures, reducing absenteeism and increasing productivity. Importantly, data from some observational registry studies have subsequently been confirmed by clinical trials, supporting the overall validity of the registry-based approach. Observational studies also allow measures such as health assessment questionnaire scores, disease activity scores, and glucocorticoid use over time to be monitored for longer periods. Furthermore, observational data in real, less strictly selected patients without the constraints of formal study populations may produce findings not observed in clinical trials but that warrant further investigation in a controlled trial environment. For example, recent data from the Stockholm tumor necrosis factor follow-up registry in Sweden showed increases in the time people worked after initiation of biologics that, surprisingly, continued into the fourth and fifth years of treatment--a finding not observed with standardized outcomes. Observational studies are truly an underappreciated and valuable source of data on the real value of anti-rheumatic therapies, and these data are essential for making sound decisions regarding coverage and reimbursement.
22562973 Clinical, functional and radiographic consequences of achieving stable low disease activit 2013 Jan OBJECTIVE: To assess the efficacy and safety of adalimumab plus methotrexate (ADA+MTX) compared with methotrexate monotherapy in achieving stable low disease activity (LDA; disease activity score (DAS28(CRP)) <3.2 at weeks 22 and 26) and clinical, radiographic and functional outcomes in methotrexate-naive patients with early rheumatoid arthritis (RA). METHODS: 1032 patients with active RA were randomly assigned 1:1 to ADA+MTX or placebo plus methotrexate (PBO+MTX) for 26 weeks. Treatment modifications were to be made in a subsequent study period based on the achievement of DAS28(CRP) <3.2 at weeks 22 and 26. Post-hoc analyses compared patients achieving stable remission using DAS28 and 2010 ACR/EULAR criteria with those achieving LDA but not remission. RESULTS: Among patients completing 6 months, 44% (207/466) ADA+MTX versus 24% (112/460) PBO+MTX patients achieved stable LDA at weeks 22 and 26 (p<0.001). Combination therapy was statistically superior to methotrexate in obtaining higher ACR20/50/70 responses, more clinical remissions, greater mean reductions in DAS28(CRP), no radiographic progression, and normal functional status at week 26 (p<0.001 for all). The only factor predicting stable LDA was disease activity at week 12. Patients achieving ACR/EULAR remission, particularly in the PBO+MTX group, had some advantage in radiographic outcomes compared with patients who only achieved LDA (but not remission). The overall frequency of adverse events was comparable between groups. There were more serious infections and deaths in the ADA+MTX group, with a possible age effect. CONCLUSIONS: Treatment with ADA+MTX was significantly superior to methotrexate alone with respect to clinical, radiographic and functional outcomes in patients with early active RA. Before initiating treatment with adalimumab, individual patient evaluation of the benefit/risk ratio should be carefully considered.
22072013 Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogen 2012 Jan OBJECTIVES: To examine how rituximab may result in the inhibition of joint destruction in rheumatoid arthritis (RA) patients. METHODS: Twenty-eight patients with active RA were treated with rituximab. Radiographs of hands and feet before and 1 year after therapy were assessed using the Sharp-van der Heijde score (SHS). Expression of bone destruction markers was evaluated by immunohistochemistry and immunofluorescence of synovial biopsies obtained before and 16 weeks after the initiation of treatment. Serum levels of osteoprotegerin, receptor activator of nuclear factor κB ligand (RANKL), osteocalcin and cross-linked N-telopeptides of type I collagen (NTx) were measured by ELISA before and 16 weeks post-treatment. RESULTS: After 1 year, the mean (SD) change in total SHS was 1.4 (10.0). Sixteen weeks after treatment there was a decrease of 99% in receptor activator of nuclear factor κB-positive osteoclast precursors (p=0.02) and a decrease of 37% (p=0.016) in RANKL expression in the synovium and a trend towards reduced synovial osteoprotegerin expression (25%, p=0.07). In serum, both osteoprotegerin (20%, p=0.001) and RANKL (40%, p<0.0001) levels were significantly reduced 16 weeks after treatment, but the osteoprotegerin/RANKL ratio increased (157%, p=0.006). A trend was found towards an increase of osteocalcin levels (p=0.053), while NTx concentrations did not change. CONCLUSIONS: Rituximab treatment is associated with a decrease in synovial osteoclast precursors and RANKL expression and an increase in the osteoprotegerin/RANKL ratio in serum. These observations may partly explain the protective effect of rituximab on the progression of joint destruction in RA.
22826971 [Possible association of gynecological cancer and rheumatoid arthritis]. 2012 Jun BACKGROUND: The association between rheumatoid arthritis and cancer is controversial. Previous studies have shown a correlation between rheumatoid arthritis and the development of lymphoma. OBJECTIVE: Describe a case of rheumatoid arthritis and associated breast cancer plus the identification of the clinical features of a set of cases in which arthritis and cancer go along. MATERIAL AND METHOD: This is a retrospective clinical series study. A database of Hospital General ISSSTECALI of Mexicali, Mexico, containing information on patients suffering from both rheumatoid arthritis and cancer until 2012 was checked. The medical files confirmed the diagnoses. The data available included age, date of arthritis diagnosis, date of cancer diagnosis, related conditions, results of serological tests, type of cancer, treatments used and follow-up information. RESULTS: Fifteen cases of women suffering from both rheumatoid arthritis and cancer were identified on the database of the Hospital General ISSSTECALI in Mexicali. The case described here is the number four on that list. The average age was 54 years and the average time between arthritis and cancer diagnoses was four years. Ten patients were administered methotrexate. Nine patients (60%) suffered from breast cancer and six more from cervical cancer. Three patients suffered from cervical dysplasia. CONCLUSIONS: These cases emphasize the need of strict follow-up on patients suffering from inflammatory rheumatoid condition. If cancer follows chronic inflammation, immunosuppression, or it is pure coincidence, is still a matter of debate.
23183089 Therapeutic effects of total alkaloids of Tripterygium wilfordii Hook f. on collagen-induc 2013 Feb 13 ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii Hook f. is one of Traditional Chinese Medicines which is commonly used to treat rheumatoid arthritis (RA). The total alkaloids were the main constituent part of Tripterygium wilfordii Hook f. It has a great significance to study the effects of the total alkaloids of Tripterygium wilfordii Hook f. (ATW) on RA. AIM OF THE STUDY: This paper aims at investigating the therapeutic effect of ATW on RA and its possible mechanism, and providing a theoretical and experimental basis for the clinical use of ATW. MATERIALS AND METHODS: The model of wistar rats of type II collagen-induced arthritis (CIA) was made, and the rats were perfused a stomach with ATW for 4 weeks continuously. Then the levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-, in the serum of CIA rats were detected by enzyme linked immunosorbent assay (ELISA), and the joint pathological section of CIA rats was observed by hematoxylin and eosin (HE) staining method and the expression of IL-6, IL-8, nuclear factor kappa B (NF-κB), TNF-α were measure by immunohistochemistry staining method. RESULTS: Compared with model group, ATW could significantly reduce paw swelling and suppresse articular cartilage degenerated. The results also found that there was significant reduction levels of IL-6, IL-8 and TNF-α in serum of CIA rats treated with ATW and ATW inhibited the expression of IL-6, IL-8, NF-κB, TNF-α in synovial tissue. CONCLUSION: ATW not only could inhibit the symptom of CIA rats significantly but also could inhibit the production of IL-6, IL-8, TNF-α in serum and the expression of IL-6, IL-8, NF-κB and TNF-α in synovial tissue targeting the inflammatory. ATW would be a drug as a novel botanical drug for the treatment of RA.
22986992 Patients' access to biologics in rheumatoid arthritis: a comparison between Portugal and o 2013 Dec BACKGROUND: Despite the widespread availability of biologics across Europe, rheumatoid arthritis (RA) patients' access to these drugs differs significantly among countries. OBJECTIVES: To compare the proportion of RA patients treated with biologics across Europe and investigate the factors that most influence it, with focus on the Portuguese case, reportedly with low access rates to biologics. METHODS: The biologics' market was characterized for 15 selected European countries. Variables potentially influencing patients' access to biologics (PAB) in RA were also collected, including demographic, disease, economic, funding and biologics' market-related data. A multivariable regression model identified the factors that best explain PAB. Based on these determinants, a cluster analysis was performed to group the countries with most similar behaviour regarding PAB allowing the evaluation of Portugal's relative position among these countries. RESULTS: The regression model (R(2) = 0.953) indicated that PAB in selected countries is explained mostly by its gross domestic product (GDP) per capita, the usage of methotrexate (MTX) and the biologics' distribution channel. Current MTX usage in Portugal shows similarity with practice from UK, France, Germany or Spain 5 years before, explaining why PAB in Portugal stood at 7% in 2010, 12 percentage points below the average of selected countries. CONCLUSIONS: Variations in RA PAB were found across selected countries with Portugal showing the lowest proportion. GDP per capita, biologics distribution channel and consumption of MTX appear to be the best explanatory factors for these fluctuations in European countries.
22391858 An investigation of the correlation between blood concentration of mizoribine and its effi 2012 Nov OBJECTIVES: The efficacy of mizoribine (MZR) in treatment of rheumatoid arthritis (RA) was retrospectively investigated in terms of drug survival, improvement in Disease Activity Score-28 (DAS28)-C-reactive protein (CRP), and blood MZR concentration obtained 3 h after dosing (MZR-C3). METHODS: To compare the efficacy of MZR administered via different regimens, the subjects were divided into 2 groups: those receiving a single dose of MZR at 100-150 mg every other day (group A) and those receiving 2 or 3 divided doses of the drug on consecutive days, which is the usual dosing method of the drug (group B). RESULTS: Group A had significantly higher MZR-C3 levels compared with group B, as well as significantly greater improvement in DAS28-CRP. Moreover, drug survival was significantly longer in group A. The primary regression equation suggested that the effective blood MZR concentration in RA treatment is MZR-C3 of 1.47 µg/mL or more. CONCLUSIONS: The results of the present study indicate that it is possible to increase the efficacy of MZR in a blood concentration-dependent manner, and also to control RA over a prolonged period, using single administration of MZR on alternate days at an increased dose.
23083037 Sexual dysfunction and its determinants in Malaysian women with rheumatoid arthritis. 2012 Oct AIM: To determine the prevalence of sexual dysfunction (FSD) among women with rheumatoid arthritis attending the Rheumatology Clinic in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and Hospital Putrajaya, Malaysia, and to determine its associations with potential clinical and disease activity factors. METHOD: This was a cross-sectional study involving women with rheumatoid arthritis between the ages of 20 and 60 years. A validated Malay Version Female Sexual Function Index (MVFSFI) was administered to diagnose FSD. Sociodemographic and disease activity profiles were obtained and those who had and did not have FSD were compared. RESULTS: Among 63 respondents, 51 patients were included in the analysis for FSD. The prevalence of FSD in women with rheumatoid arthritis attending UKMMC and Hospital Putrajaya Rheumatology Clinic was 29.4%. Erythrocyte sedimentation rate (ESR) and Disease Activity Score in 28 joints (DAS28-ESR) correlates with MVFSFI score with r=-0.364 (P=0.009) and r=-0.268 (P=0.057), respectively. Sociodemographic factors that correlate with MVFSFI score were: patient's age (r=0.520, P<0.001); duration of marriage (r=-0.355, P=0.001); husband's age (r=-0.460, P=0.001); age of oldest child (r=-0.449, P=0.001); and age of youngest child (r=-0.627, P<0.001). CONCLUSION: We found in this study that the prevalence of FSD in rheumatoid arthritis in our centers was 29.4%. Age and family dynamics appear to be more important predictors compared to disease activity.