'Choosing shoes': a preliminary study into the challenges facing clinicians in assessing footwear for rheumatoid patients

Background: Footwear has been accepted as a therapeutic intervention for the foot affected by rheumatoid arthritis (RA). Evidence relating to the objective assessment of footwear in patients with RA is limited. The aims of this study were to identify current footwear styles, footwear characteristics, and factors that influence footwear choice experienced by patients with RA. Methods: Eighty patients with RA were recruited from rheumatology clinics during the summer months. Clinical characteristics, global function, and foot impairment and disability measures were recorded. Current footwear, footwear characteristics and the factors associated with choice of footwear were identified. Suitability of footwear was recorded using pre-determined criteria for assessing footwear type, based on a previous study of foot pain. Results: The patients had longstanding RA with moderate-to severe disability and impairment. The foot and ankle assessment demonstrated a low-arch profile with both forefoot and rearfoot structural deformities. Over 50% of shoes worn by patients were opentype footwear. More than 70% of patients’ footwear was defined as being poor. Poor footwear characteristics such as heel rigidity and sole hardness were observed. Patients reported comfort (17%) and fit (14%) as important factors in choosing their own footwear. Only five percent (5%) of patients wore therapeutic footwear. Conclusions: The majority of patients with RA wear footwear that has been previously described as poor. Future work needs to aim to define and justify the specific features of footwear that may be of benefit to foot health for people with RA

Prevalence of amyloid deposition in long standing rheumatoid arthritis in Iranian patients by abdominal subcutaneous fat biopsy and assessment of clinical and laboratory characteristics

BACKGROUND: The study was aimed at determining the prevalence of secondary amyloidosis in a group of Iranian patients with Rheumatoid Arthritis (RA), and the assessment of its correlation with the clinical and laboratory findings and data. METHOD: A total number of 220 patients (167 female and 53 male) with a minimum five-year history of RA were selected. Congo red staining method was used for staining the specimens obtained by abdominal subcutaneous fat biopsy (ASFB) method. All of the specimens were examined for apple-green birefringence under polarized light microscope. Clinical and laboratory characteristics of the patients were assessed. Chi-square test and unpaired student's t-test were run for intergroup comparisons. RESULTS: Amyloid deposition test yielded positive results in 15 out of the 220 cases (6.8%) examined by the ASFB technique. Thirteen patients were found to have minimal amyloid deposits. Of all the clinically significant cases, 8 (53%) presented with proteinuria, and 7 cases (46.6%) had severe constipation. CONCLUSION: The prevalence of fat amyloid deposits in Iranian patients with RA is low. In up to half of the study group the deposits were subclinical. Follow up studies are required to determine whether this subclinical amyloidosis can develop into full-blown clinically significant amyloidosis

Women’s experiences of wearing therapeutic footwear in three European countries

Background: Therapeutic footwear is recommended for those people with severe foot problems associated with rheumatoid arthritis (RA). However, it is known that many do not wear them. Although previous European studies have recommended service and footwear design improvements, it is not known if services have improved or if this footwear meets the personal needs of people with RA. As an earlier study found that this footwear has more impact on women than males, this study explores women’s experiences of the process of being provided with it and wearing it. No previous work has compared women’s experiences of this footwear in different countries, therefore this study aimed to explore the potential differences between the UK, the Netherlands and Spain. Method: Women with RA and experience of wearing therapeutic footwear were purposively recruited. Ten women with RA were interviewed in each of the three countries. An interpretive phenomenological approach (IPA) was adopted during data collection and analysis. Conversational style interviews were used to collect the data. Results: Six themes were identified: feet being visibly different because of RA; the referring practitioners’ approach to the patient; the dispensing practitioners’ approach to the patient; the footwear being visible as different to others; footwear influencing social participation; and the women’s wishes for improved footwear services. Despite their nationality, these women revealed that therapeutic footwear invokes emotions of sadness, shame and anger and that it is often the final and symbolic marker of the effects of RA on self perception and their changed lives. This results in severe restriction of important activities, particularly those involving social participation. However, where a patient focussed approach was used, particularly by the practitioners in Spain and the Netherlands, the acceptance of this footwear was much more evident and there was less wastage as a result of the footwear being prescribed and then not worn. In the UK, the women were more likely to passively accept the footwear with the only choice being to reject it once it had been provided. All the women were vocal about what would improve their experiences and this centred on the consultation with both the referring practitioner and the practitioner that provides the footwear. Conclusion: This unique study, carried out in three countries has revealed emotive and personal accounts of what it is like to have an item of clothing replaced with an ‘intervention’. The participant’s experience of their consultations with practitioners has revealed the tension between the practitioners’ requirements and the women’s ‘social’ needs. Practitioners need greater understanding of the social and emotional consequences of using therapeutic footwear as an intervention

Forefoot pathology in rheumatoid arthritis identified with ultrasound may not localise to areas of highest pressure: cohort observations at baseline and twelve months

BackgroundPlantar pressures are commonly used as clinical measures, especially to determine optimum foot orthotic design. In rheumatoid arthritis (RA) high plantar foot pressures have been linked to metatarsophalangeal (MTP) joint radiological erosion scores. However, the sensitivity of foot pressure measurement to soft tissue pathology within the foot is unknown. The aim of this study was to observe plantar foot pressures and forefoot soft tissue pathology in patients who have RA.Methods A total of 114 patients with established RA (1987 ACR criteria) and 50 healthy volunteers were assessed at baseline. All RA participants returned for reassessment at twelve months. Interface foot-shoe plantar pressures were recorded using an F-Scan® system. The presence of forefoot soft tissue pathology was assessed using a DIASUS musculoskeletal ultrasound (US) system. Chi-square analyses and independent t-tests were used to determine statistical differences between baseline and twelve months. Pearson’s correlation coefficient was used to determine interrelationships between soft tissue pathology and foot pressures.ResultsAt baseline, RA patients had a significantly higher peak foot pressures compared to healthy participants and peak pressures were located in the medial aspect of the forefoot in both groups. In contrast, RA participants had US detectable soft tissue pathology in the lateral aspect of the forefoot. Analysis of person specific data suggests that there are considerable variations over time with more than half the RA cohort having unstable presence of US detectable forefoot soft tissue pathology. Findings also indicated that, over time, changes in US detectable soft tissue pathology are out of phase with changes in foot-shoe interface pressures both temporally and spatially.Conclusions We found that US detectable forefoot soft tissue pathology may be unrelated to peak forefoot pressures and suggest that patients with RA may biomechanically adapt to soft tissue forefoot pathology. In addition, we have observed that, in patients with RA, interface foot-shoe pressures and the presence of US detectable forefoot pathology may vary substantially over time. This has implications for clinical strategies that aim to offload peak plantar pressures

Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

Safety and effectiveness of adalimumab in a clinical setting that reflects Canadian standard of care for the treatment of rheumatoid arthritis (RA): Results from the CanACT study

<p>Abstract</p> <p>Background</p> <p>This multicenter, open-label, prospective, single cohort study evaluated the effectiveness and safety of adalimumab in a clinical setting reflecting the Canadian standard of care for the treatment of patients with rheumatoid arthritis (RA).</p> <p>Methods</p> <p>Patients ≥ 18 years of age with a history of active RA ≥ 3 months and fulfilling Canadian requirements for biological therapy received adalimumab 40 mg subcutaneously every other week for 12 weeks. Pre-study DMARD treatment regimens, corticosteroids, or NSAIDs were allowed throughout the study. The primary effectiveness outcome measure was the mean change in 28-joint disease activity score (DAS28) from baseline to Week 12. Secondary measures included the proportion of patients achieving joint remission (DAS28 < 2.6) and low-disease activity (DAS28 < 3.2) at Week 12, and European League Against Rheumatism (EULAR: moderate and good) and American College of Rheumatology (ACR: ACR20, 50, and 70) responses, as well as responses in ACR core components at Weeks 4, 8, and 12. Subgroup analysis included a comparison of patients naïve to biological DMARD (BDMARD) therapy versus BDMARD-experienced patients. Safety was assessed in terms of adverse and serious adverse events.</p> <p>Results</p> <p>A total of 879 patients (mean disease duration > 12 years) were enrolled; 772 (87.9%) completed the 12-week period. Adalimumab treatment was associated with rapid and sustained improvements in the signs and symptoms of RA. Significant improvements in mean DAS28 score were observed as early as Week 4. After 12 weeks of adalimumab treatment, 15.3% and 28.9% of patients achieved clinical remission and low-disease activity, respectively. Similarly, significant improvements in ACR core components were observed as early as Week 4, with continued improvements occurring through 12 weeks. Patients naïve to BDMARD therapy demonstrated numerically greater clinical responses when compared with patients who had experienced prior BDMARD therapy, although both subgroups were associated with significant improvements from baseline. The rates and types of adverse events, as well as the results of laboratory measures, demonstrated that adalimumab was generally safe and well-tolerated.</p> <p>Conclusions</p> <p>This study demonstrated that, under conditions reflective of the normal clinical practice in Canada, adalimumab is an effective and safe treatment for patients with RA.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00649545">NCT00649545</a>.</p

A Model for the Detection of Moving Targets in Visual Clutter Inspired by Insect Physiology

We present a computational model for target discrimination based on intracellular recordings from neurons in the fly visual system. Determining how insects detect and track small moving features, often against cluttered moving backgrounds, is an intriguing challenge, both from a physiological and a computational perspective. Previous research has characterized higher-order neurons within the fly brain, known as ‘small target motion detectors’ (STMD), that respond robustly to moving features, even when the velocity of the target is matched to the background (i.e. with no relative motion cues). We recorded from intermediate-order neurons in the fly visual system that are well suited as a component along the target detection pathway. This full-wave rectifying, transient cell (RTC) reveals independent adaptation to luminance changes of opposite signs (suggesting separate ON and OFF channels) and fast adaptive temporal mechanisms, similar to other cell types previously described. From this physiological data we have created a numerical model for target discrimination. This model includes nonlinear filtering based on the fly optics, the photoreceptors, the 1st order interneurons (Large Monopolar Cells), and the newly derived parameters for the RTC. We show that our RTC-based target detection model is well matched to properties described for the STMDs, such as contrast sensitivity, height tuning and velocity tuning. The model output shows that the spatiotemporal profile of small targets is sufficiently rare within natural scene imagery to allow our highly nonlinear ‘matched filter’ to successfully detect most targets from the background. Importantly, this model can explain this type of feature discrimination without the need for relative motion cues

Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, phase II, dose-finding study

<p>Abstract</p> <p>Background</p> <p>Canakinumab is a fully human anti-interleukin IL-1beta monoclonal antibody, being investigated for the treatment of rheumatoid arthritis (RA). This multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study investigated the efficacy and safety of canakinumab in patients with active RA despite ongoing therapy at stable doses of methotrexate.</p> <p>Methods</p> <p>Patients were randomized to receive one of four regimens, in addition to methotrexate, for 12 weeks: canakinumab 150 mg subcutaneously (SC) every 4 weeks (q4wk), canakinumab 300 mg SC (2 injections of 150 mg SC) every 2 weeks, a 600 mg intravenous loading dose of canakinumab followed by 300 mg SC every 2 weeks', or placebo SC every 2 weeks.</p> <p>Results</p> <p>Among 274 patients with evaluable efficacy data, the percentage of responders according to American College of Rheumatology 50 criteria (the primary endpoint, based on a 28-joint count) was significantly higher with canakinumab 150 mg SC q4wk than with placebo (26.5% vs. 11.4%, respectively; p = 0.028). Compared to placebo, this dosage of canakinumab was also associated with significantly more favorable responses at week 12 with respect to secondary endpoints including the Disease Activity Score 28, scores on the Health Assessment Questionnaire and Functional Assessment of Chronic Illness Therapy-Fatigue, swollen 28-joint count, and patient's and physician's global assessments of disease activity. No safety concerns were raised with canakinumab therapy, particularly with regard to infections. Few injection-site reactions occurred.</p> <p>Conclusion</p> <p>The addition of canakinumab 150 mg SC q4wk improves therapeutic responses among patients who have active RA despite stable treatment with methotrexate.</p> <p>Trial Registration</p> <p>(ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00784628">NCT00784628</a>)</p

Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression, but little interleukin-22 and interleukin-23R expression

Introduction\ud Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to systematically analyse the phenotype, cytokine profile and frequency of interleukin-17 (IL-17) producing CD4-positive T cells in mononuclear cells isolated from peripheral blood, synovial fluid and synovial tissue of RA patients with established disease, and to correlate cell frequencies with disease activity. \ud \ud Methods\ud Flow cytometry was used to analyse the phenotype and cytokine production of mononuclear cells isolated from peripheral blood (PBMC) (n = 44), synovial fluid (SFMC) (n = 14) and synovium (SVMC) (n = 10) of RA patients and PBMC of healthy controls (n = 13). \ud \ud Results\ud The frequency of IL-17-producing CD4 T cells was elevated in RA SFMC compared with RA PBMC (P = 0.04). However, the frequency of this population in RA SVMC was comparable to that in paired RA PBMC. The percentage of IL-17-producing CD4 T cells coexpressing tumor necrosis factor alpha (TNFα) was significantly increased in SFMC (P = 0.0068). The frequency of IFNγ-producing CD4 T cells was also significantly higher in SFMC than paired PBMC (P = 0.042). The majority of IL-17-producing CD4 T cells coexpressed IFNγ. IL-17-producing CD4 T cells in RA PBMC and SFMC exhibited very little IL-22 or IL-23R coexpression. \ud \ud Conclusions\ud These findings demonstrate a modest enrichment of IL-17-producing CD4 T cells in RA SFMC compared to PBMC. Th17 cells in SFMC produce more TNFα than their PBMC counterparts, but are not a significant source of IL-22 and do not express IL-23R. However, the percentage of CD4 T cells which produce IL-17 in the rheumatoid joint is low, suggesting that other cells may be alternative sources of IL-17 within the joints of RA patients. \ud \u