Background. Ankylosing spondylitis (AS) is a chronic, progressive inflammatory rheumatic disease that leads to structural damage, functional impairment, and decrease in the quality of life. Red cell distribution width (RDW) is a part of the complete blood count (CBC) and estimates erythrocyte variability.Objective. To analyse RDW in patients with AS and to evaluate the relationships with acute phase reactants (APRs) and disease activity index.Patients and Methods. A total of 100 patients with AS (78 males and 22 females) were diagnosed according to the modified New York classification criteria for AS and 146 (99 males: 47 females) healthy individuals matched in age and sex as controls enrolled in the study. Demographic data, disease activity scores using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), medical history, C-reactive protein (CRP), erythrocytes sedimentation rate (ESR), and complete blood count (CBC) were measured.Results. The mean age for patients and controls was 38.0 ± 9.0 and 35.8 ± 9.0 years, respectively (p=0.057). RDW was significantly higher in patients with AS compared with controls (14.133 ± 1.613 versus 12.299 ± 1.031, p < 0.001). There was a direct correlation of RDW with both ESR and CRP (P < 0.001); RDW had r=0.38 for C-reactive protein (CRP) and r=0.413 for ESR. Also BASDAI was directly correlated with RDW (r=0.326 p<0.001). RDW was a valid measure to differentiate between patients with AS and controls (AUC=0,84, p<0.001) and at optimum cut-off value>13% has highest accuracy (78.9%) with very good sensitivity test (81%) and NPV (85.6%) as well as good specificity (77.4%) and PPV (71.1%).Conclusion. RDW was higher in AS patients compared with controls and was directly correlated with ESR, CRP, and BASDAI. RDW was a valid simple measure with good accuracy to differentiate between patients with AS and controls.
Objective . This study estimated the excess clinical, humanistic, and economic burden associated with depression among working-age adults with Rheumatoid Arthritis (RA). Methods . A retrospective cross-sectional study was conducted among working-age (18 to 64 years) RA patients with depression (N=647) and without depression (N=2,015) using data from the nationally representative Medical Expenditure Panel Survey for the years 2009, 2011, 2013, and 2015. Results . Overall, 25.8% had depression. In adjusted analyses, adults with RA and depression compared to those without depression were significantly more likely to have pain interference with normal work (severe pain: AOR = 2.22; 95% CI = 1.55, 3.18), functional limitations (AOR = 2.17; 95% CI = 1.61, 2.94), and lower mental health HRQoL scores. Adults with RA and depression had significantly higher annual healthcare expenditures ($14,752 versus 10,541, p<.001) and out-of-pocket spending burden. Adults with RA and depression were more likely to be unemployed and among employed adults, those with depression had a significantly higher number of missed work days annually and higher lost annual wages due to missed work days. Conclusions . This study highlights the importance of effectively managing depression in routine clinical practice of RA patients to reduce pain and functional limitations, improve quality of life, and lower direct and indirect healthcare costs.
Background . Juvenile idiopathic arthritis (JIA) is the most common form of rheumatic disease in childhood and adolescents, affecting between 16 and 150 per 100,000 young persons below the age of 16. The lower limb is commonly affected in JIA, with joint swelling and tenderness often observed as a result of active synovitis. Objective . The objective of this scoping review is to identify the existence of physical examination (PE) tools to identify and record swollen and tender lower limb joints in children with JIA. Methods . Two reviewers individually screened the eligibility of titles and abstracts retrieved from the following online databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL. Studies that proposed and validated a comprehensive lower limb PE tool were included in this scoping review. Results . After removal of duplicates, 1232 citations were retrieved, in which twelve were identified as potentially eligible. No studies met the set criteria for inclusion. Conclusion . Further research is needed in developing and validating specific PE tools for clinicians such as podiatrists and other allied health professionals involved in the management of pathological lower limb joints in children diagnosed with JIA. These lower limb PE tools may be useful in conjunction with existing disease activity scores to optimise screening of the lower extremity and monitoring the efficacy of targeted interventions.
Systematic reviews of self-management programs for osteoarthritis suggest minimal evidence of benefit and indicate substantial heterogeneity in interventions. The purpose of this scoping review was to describe the nature of self-management interventions provided to patients with osteoarthritis focusing on the inclusion and type of education and social support components. We searched PsycINFO, EMBASE, MEDLINE, and Cochrane Library databases from 1990 to 2016 to identify studies addressing community-based management strategies for osteoarthritis that included aspects of disease-specific education and ongoing social support. Results are presented as a narrative synthesis to facilitate integration of diverse evidence. Data were extracted from 23 studies that met our inclusion and exclusion criteria, describing complex, multicomponent interventions for osteoarthritis. All studies included education components, and 18 of these were osteoarthritis-specific. Social support was most often offered through peers and health care professionals, but also through exercise trainers/instructors and researchers, and lasted between 5 and 52 weeks. We charted positive social interaction offered by peers in group settings and emotional/informational support offered by health care professionals. Overall, descriptions of self-management provided limited documentation of the rationale or content of the programs. This suggests that more precise definitions of the theoretical underpinnings, components, and mechanisms would be useful for greater insight into best practices for osteoarthritis self-management programs.
A biosimilar is a biologic product that is highly similar to a licensed biologic (“originator”) such that there are no clinically meaningful differences in safety, purity, or potency between the biosimilar and the originator. As patent protection and data exclusivity for the biologic rituximab expire, several potential biosimilars to rituximab are in development, which could soon lead to the availability of numerous rituximab biosimilars. Biosimilars are evaluated using thorough and rigorous analyses of the potential biosimilar versus the originator biological to confirm similar structure, function, and clinical efficacy as well as safety. Approval of a biosimilar is based upon the totality of the evidence demonstrating similarity to the originator. An understanding of the process of the interchangeable designation of a biosimilar is important in the context of patient outcomes. We conducted an analysis of the properties and benefits of rituximab in the treatment of inflammatory diseases, the development and approval of biosimilars, and the potential benefits of rituximab biosimilars. PubMed and ClinicalTrials.gov databases were searched for “biosimilar” and “rituximab” and regulatory and pharmaceutical company web pages were screened regarding biosimilars in development and specific guidelines developed for the approval of biosimilars. The results indicate that, at present, six rituximab biosimilar candidates are undergoing comparative clinical development, and two were recently approved in the European Union. Our analysis indicates rituximab biosimilars are expected to have a continuing role in treating inflammatory conditions such as rheumatoid arthritis.
Physical inactivity is important to address, and an objective way of measuring inactivity is by accelerometry. The objective of this study was to determine the reliability and construct validity of the SENS motion system to record physical activity and inactivity in patients with knee osteoarthritis. Participants with an age > 40 years and an average weekly pain above 0 on a numeric rating scale (0 = no pain, 10 = worst pain) were included. Participants had a total of two study visits and at each visit participants completed a standardized activity. Data from 24 participants were analysed. A mean agreement of 99% (SD 3%) for sedentary behaviour and a mean agreement of 97% (SD 9%) for active behaviour were found. The agreement for “walking” was 28% (SD 18%). Mean agreement between recordings on the two visits was 96% (SD 8%) for sedentary behaviour and 99% (SD 1%) for active behaviour. The SENS motion activity measurement system can be regarded as a reliable and valid device for measuring sedentary behaviour in patients with knee OA, whereas detection of walking is not reliable and would require further work.
Objective. Interprofessional collaboration is a crucial component of care for children with rheumatic disease. Interprofessional care, when delivered appropriately, prevents disability and improves long-term prognosis in this vulnerable group. Methods. The aim of this survey was to explore allied health professionals' and nurses' confidence in treating paediatric rheumatology patients. Results. Overall, 117 participants were recruited, 77.9% of participants reported being "not confident at all," "not confident," or "neutral" in treating children with rheumatic diseases (RD) despite 65.1% of participants reporting having treated >1 paediatric rheumatology case in the past month. Furthermore, 67.2% of participants felt their undergraduate education in paediatric rheumatology was inadequate. "Journals" or "texts books" were used by 49.3% of participants as their primary source of continuing professional development (CPD) and 39.3% of participants indicated that they did not undertake any CPD related to paediatric rheumatology. Small group and online education were perceived to be potentially of "great benefit" for CPD. Conclusion. This paper highlights allied health professionals' and nurses' perceived inadequacy of their undergraduate education in paediatric RD and their low confidence in recognising and treating RD. Undergraduate and postgraduate education opportunities focusing on inter-professional collaboration should be developed to address this workforce deficiency.
Introduction We examined racial/ethnic disparities in healthcare providers' recommendations for physical activity among individuals with arthritis and evaluated this association among groups of individuals who adhered to physical activity guidelines and those who did not. Methods With a cross-sectional design based on Behavioral Risk Factor Surveillance System, we analyzed individuals with self-reported physician-diagnosed arthritis, ≥18 years of age (n = 83,376). Outcome variable was healthcare providers' recommendations for physical activity. Race/ethnicity was categorized as African American, Hispanic, and White. Associations were examined using multivariate logistic regression. Results African Americans (Adjusted OR: 0.66; 95% CI: 0.55–0.79) and Hispanics (Adjusted OR: 0.68; 95% CI: 0.56–0.83) were less likely to receive providers' recommendations. Conclusions Although the importance of physical activity to improve health outcomes for adults with arthritis, as well as providers' influence on individuals' behavior change, is well established, providers are less likely to recommend physical activity to minorities. Further studies are required to identify the causes for this quality-of-care issue.
Hemophilic arthropathy is a progressive, disabling condition with poorly understood pathobiology. Since there is an emerging interest to study the role of intra-articular fat pad size and biology in arthritic conditions, we explored fat pad volume changes in hemophilic arthropathy and to what extent they differed from osteoarthritis. We matched a cohort of 13 adult patients with hemophilic arthropathy of the knee with age- and gender-matched cohorts without osteoarthritis ("control cohort") and with the same degree of radiographic osteoarthritis ("OA cohort") in 1 : 2 fashion. Infrapatellar fat pad (IPFP) and suprapatellar fat pad (SPFP) volumes were calculated based on magnetic resonance imaging and differences in fat pad volumes, demographics, height, weight, and osteoarthritis scores were evaluated. Fat pad volumes were positively associated with body size parameters in all three cohorts but were unaffected by the degree of osteoarthritis. While IPFP volumes did not differ between cohorts, SPFP volumes expanded disproportionally with weight in hemophilia patients. Our observations indicate that IPFPs and SPFPs behave biologically differently in response to different arthritic stimuli. The exaggerated expansion of the SPFP in hemophilia patients highlights the importance of further studying the implications of fat pad biology for progression of hemophilic arthropathy.
Large animal models of osteoarthritis are a necessary testing ground for FDA approval of human medicine applications. Sheep models have advantages over other available large animals, but development and progression of osteoarthritis in sheep is exceedingly slow, which handicaps progress in development of potential treatments. We combined oblique angle forced exercise to increase stress on the stifle, with surgical destabilization to hasten the development of osteoarthritis in ewes. Methods for early detection of clinical signs included radiography, urine, and serum biomarker assays and gait analysis and ex vivo we used microcomputed tomography and macroscopic joint analysis. Our model was able to produce clinically detectable signs of osteoarthritis in a relatively short period (14 weeks). Changes in bone were highly correlated between microcomputed tomography and radiographic analysis and changes in cartilage correlated well between urinary glycosaminoglycan levels and serum aggrecanase analyses. Exercise improved the negative effects of destabilization in bone but exacerbated the negative effects of destabilization in cartilage. These observations suggest that wemay need to consider treatments for bone and cartilage separately. These results represent an improved large animal model of osteoarthritis with rapid onset of disease and superior detection of bone and soft tissue changes.
Remission of inflammation has become an achievable goal in inflammatory or rheumatoid arthritis (RA); however, bone erosion continues in many patients. Interleukin- (IL-) 27 regulates immune and bone cell balance and also suppresses activities of several inflammatory cell types in RA. Despite its promise, challenges to clinical translation of IL-27 have been its partial effects in vivo. Due to their ability to modulate plasticity of bone and immune cell differentiation, we examined the potential for several microRNA (miR) candidates in enhancing the effects of IL-27. Using differentiation, luciferase, and real time quantitative PCR assays, we show that IL-27 promotes osteoblast differentiation, reduces expression of osteoblast inhibitory genes, and reduces osteoclast differentiation, and results suggest a potential coordination with TGFβ/BMP/SMAD and JAK/STAT pathways. We selected miRNA regulators of these and related pathways to examine whether the effects of IL-27 could be augmented for therapeutic applications. miR-29b and miR-21 augmented IL-27 proosteogenic while downregulating osteoclastogenic signals and also worked to reduce inflammatory signaling in activated macrophages, while miR-21 and miR-20b worked with IL-27 to reduce inflammatory gene expression in fibroblasts and T cells. It appears that several miRNAs can be utilized to enhance IL-27's impact on modulating osteogenesis and reducing proinflammatory signaling.
Objectives. In this prospective study, we intend to establish the psychometric properties of ICOAP for its use in studies involving the Hellenic population. Methods. SF-36 Health Survey was used as a standard against ICOAP scores from a sample of 89 patients (mean age: 71.07, 69 females) with hip and knee OA pain who underwent 2 treatment cycles of 4 intra-articular injections of sodium hyaluronate, separated by a 12-week medication-free time interval. Both questionnaires were filled twice with no missing data during follow-up. Results. ROC analysis accomplished ICOAP's criterion-related validation. Wilcoxon Signed-Rank Test and paired samples t-test endorsed ICOAP's responsiveness along with Effect Size values, standard response mean, and Relative Efficiency. Comparisons between the areas under curves (AUC) on ROC plots established external responsiveness. Cronbach's-alpha value favored ICOAP's internal consistency. This, along with intraclass correlation, results in both advocated reliability and content validity. Interitem discrimination was demonstrated by the ease of completion of ICOAP as well as the degree of familiarity with it. These findings inaugurated construct validity in collaboration with Spearman's and One-Way ANOVA results. Conclusions. ICOAP is a valid, reliable, and responsive QoL instrument and suitable for studies of osteoarthritic joint pain in the Greek setting.
Objectives. To assess the validity, reliability, and responsiveness to change of a patient self-reported questionnaire combining the Widespread Pain Index and the Symptom Severity Score as well as construct outcome measures and comorbidities assessment in fibromyalgia patients. Methods. The PROMs-FM was conceptualized based on frameworks used by the WHO Quality of Life tool and the PROMIS. Initially, cognitive interviews were conducted to identify item pool of questions. Item selection and reduction were achieved based on patients as well as an interdisciplinary group of specialists. Rasch and internal consistency reliability analyses were implemented. The questionnaire included the modified ACR criteria main items (Symptom Severity Score and Widespread Pain Index), in addition to assessment of functional disability, quality of life (QoL), review of the systems, and comorbidities. Every patient completed HAQ and EQ-5D questionnaires. Results. A total of 146 fibromyalgia patients completed the questionnaire. The PROMs-FM questionnaire was reliable as demonstrated by a high standardized alpha (0.886-0.982). Content construct assessment of the functional disability and QoL revealed significant correlation (p < 0.01) with both HAQ and EQ-5D. Changes in functional disability and QoL showed significant (p < 0.01) variation with diseases activity status in response to therapy. There was higher prevalence of autonomic symptoms, CVS risk, sexual dysfunction, and falling. Conclusions. The developed PROMs-FM questionnaire is a reliable and valid instrument for assessment of fibromyalgia patients. A phased treatment regimen depending on the severity of FMS as well as preferences and comorbidities of the patient is the best approach to tailored patient management.
Introduction. The Infrapatellar fat pad (IPFP) represents an emerging alternative source of adipose-derived mesenchymal stem cells (ASCs). We compared the characteristics and differentiation capacity of ASCs isolated from IPFP and SC. Materials and Methods. ASCs were harvested from either IPFP or SC. IPFPs were collected from patients undergoing total knee arthroplasty (TKA), whereas subcutaneous tissues were collected from patients undergoing lipoaspiration. Immunophenotypes of surface antigens were evaluated. Their ability to form colony-forming units (CFUs) and their differentiation potential were determined. The ASCs karyotype was evaluated. Results. There was no difference in the number of CFUs and size of CFUs between IPFP and SC sources. ASCs isolated from both sources had a normal karyotype. The mesenchymal stem cells (MSCs) markers on flow cytometry was equivalent. IPFP-ASCs demonstrated significantly higher expression of SOX-9 and RUNX-2 over ASCs isolated from SC (6.19 ± 5.56-, 0.47 ± 0.62-fold; p value = 0.047, and 17.33 ± 10.80-, 1.56 ± 1.31-fold; p value = 0.030, resp.). Discussion and Conclusion. CFU assay of IPFP-ASCs and SC-ASCs harvested by lipoaspiration technique was equivalent. The expression of key chondrogenic and osteogenic genes was increased in cells isolated from IPFP. IPFP should be considered a high quality alternative source of ASCs.
Aim. To assess the gastrosparing effect of amtolmetin guacyl (AMG) against other nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with osteo-/rheumatoid arthritis. Methods. A literature search was done in the electronic databases (PubMed, Google Scholar, Embase, and Scopus) with key words "amtolmetin guacyl", "amtolmetin", and "arthritis"; filters were applied to obtain publications between 01-Jan-1985 and 01-Oct-2015, which were "clinical trials" in osteo-/rheumatoid arthritis patients and in "English language." Studies were assessed using the Jadad criteria and trials with score ≥ 3 were included in the analysis to compare the safety and efficacy of AMG against other NSAIDs. Results. Search yielded 19 publications of which 3 were included for analysis. Baseline characteristics of patients were comparable between the AMG group and other NSAIDs (diclofenac, celecoxib, and piroxicam) groups in all trials. Efficacy of AMG was similar to the other NSAIDs compared in the trials. The number of adverse events (AEs) reported was similar between both the groups; however, severe AEs reported were significantly lower in the AMG group. Of note was the significant lower number of duodenal ulcers after treatment in the AMG group. Conclusions. AMG has efficacy similar to other NSAIDs and a safer gastrointestinal AE profile when compared to the other NSAIDs.
Objective. To clarify molecular mechanisms for the response to rituximab in a longitudinal study. Methods. Peripheral blood from 16 RA patients treated with rituximab for a single treatment course and 26 healthy controls, blood and knee articular cartilages from 18 patients with long-standing RA, and cartilages from 14 healthy subjects were examined. Clinical response was assessed using ESR, ACPA, CRP, RF, DAS28 levels, CD19+ B-cell counts, bone erosion, and joint space narrowing scores. Protein expression in PBMCs was quantified using ELISA. Gene expression was performed with quantitative real-time PCR. Results. A decrease (p < 0.05) in DAS28, ESR, and CRP values after rituximab treatment was associated with the downregulation of MTOR, p21, caspase 3, ULK1, TNFα, IL-1β, and cathepsin K gene expression in the peripheral blood to levels found in healthy subjects. MMP-9 expression remained significantly higher compared to controls although decreased (p < 0.05) versus baseline. A negative correlation between baseline ULK1 gene expression and the number of tender joints at the end of follow-up was observed. Conclusions. The response to rituximab was associated with decreased MTOR, p21, caspase 3, ULK1, TNFα, IL-1β, and cathepsin K gene expression compared to healthy subjects. Residual increased expression in MMP-9, IFNα, and COX2 might account for remaining inflammation and pain. High baseline ULK1 gene expression indicates a good response in respect to pain.
Imaging used for the evaluation of knee pain has historically included weight-bearing anteroposterior (AP), lateral, and sunrise radiographs. We wished to evaluate the utility of adding the weight-bearing (WB) posteroanterior (PA) view of the knee in flexion. We hypothesize that (1) the WB tunnel view can detect radiographic osteoarthritis (OA) not visualized on the WB AP, (2) the combination of the AP and tunnel view increases the radiographic detection of OA, and (3) this may provide additional information to the clinician evaluating knee pain. We retrospectively reviewed the WB AP and tunnel view radiographs of 100 knees (74 patients) presenting with knee pain and analyzed for evidence of arthritis. The combination of the WB tunnel view and WB AP significantly increased the detection of joint space narrowing in the lateral (p < 0.001) and medial (p = 0.006) compartments over the AP view alone. The combined views significantly improved the identification of medial subchondral cysts (p = 0.022), sclerosis of the lateral tibial plateau (p = 0.041), and moderate-to-large osteophytes in the medial compartment (p = 0.012), intercondylar notch (p < 0.001), and tibial spine (p < 0.001). The WB tunnel view is an effective tool to provide additional information on affected compartments in the painful knee, not provided by the AP image alone.
Posttraumatic activation of the catabolic cascade plays a major role in degradation of cartilage. Interleukin-1β (IL-1β), a primary instigator in the catabolic axis, is upregulated in chondrocytes following injury. IL-1β activates key degradative enzymes, including MMPs and aggrecanases, and other proinflammatory mediators such as PGE2 which contribute to ECM breakdown. Posttranscriptional silencing of IL-1β by RNA interference (RNAi) may drive a reduction in IL-1β. We hypothesized that transduction of chondrocytes using rAAV2 expressing a short hairpin RNAi motif targeting IL-1β (shIL-1β) would significantly decrease IL-1β expression and, in turn, decrease expression of other catabolic enzymes. Chondrocyte cultures were transduced with rAAV2-tdT-shIL-1β in serum-free media. The fluorescent protein, tdTomato, was used to determine transduction efficiency via flow cytometry and fluorescent microscopy. Cells were stimulated with lipopolysaccharide (LPS) 48 hours following transduction. After 24-hour stimulation, supernatants were collected for cytokine analysis, and cells lysed for gene expression analysis. IL-1β knockdown led to significantly decreased expression of IL-1β, TNF-α, and ADAMTS5. PGE2 synthesis was also significantly downregulated. Overall, effective silencing of IL-1β using rAAV2 vector expressing a short hairpin IL-1β knockdown sequence was shown. Additionally, significant downstream effects were evident, including decreased expression of TNF-α and ADAMTS5. Targeted silencing of catabolic cytokines may provide a promising treatment avenue for osteoarthritic (OA) joints.
Objectives . To study adherence to methotrexate (MTX) and factors of importance thereof in patients with rheumatoid arthritis (RA). Methods . Patients with a hospital diagnosis of RA (ICD10 codes M05.X or M06.X) after January 1, 1997, and aged ≥18 years at the date of first diagnosis/contact, with at least one prescription of MTX (L04AX03), were included. Results . A total of 18,703 (47.6%) patients had ever used MTX among 39,286 with a diagnosis of RA; among the MTX users, 16,503 (88.2%) had filed more than one MTX prescription. The median time from diagnosis to first MTX prescription was 0.66 (IQR 0.26–1.80) years. In those who filed more than one MTX prescription, the mean adherence time for ≥7.5 mg MTX per week was 1,925 (IQR 467–3,056) days for patients treated in private practice versus 1,892 (IQR 452–3,316) days for patients treated in hospital. The main determinants of nonadherence were female gender, younger age, and time from diagnosis to initiation of MTX. Conclusions . Treatment at hospital or in private practice did not influence the adherence to MTX. Nonmodifiable factors of importance were gender and age, while adherence to MTX therapy decreased with time lapse between diagnosis and prescription.
The majority of patients with hip or knee osteoarthritis (OA) report one or more symptomatic joints apart from the one targeted for surgical care. Therefore, the purpose of the present study was to investigate the association between the burden of multiple symptomatic joints and self-reported depression in patients awaiting joint replacement for OA. Four hundred and seventy-five patients at a single centre were evaluated. Patients self-reported joints that were painful and/or symptomatic most days of the previous month on a homunculus, with nearly one-third of the sample reporting 6 or more painful joints. The prevalence of depression was 12.2% (58/475). When adjusted for age, sex, education level, hip or knee OA, body mass index, chronic condition count, and joint-specific WOMAC scores, each additional symptomatic joint was associated with a 19% increased odds (odds ratio: 1.19 (95% CI: 1.08, 1.31, P < 0.01)) of self-reported depression. Individuals reporting 6 or more painful joints had 2.5-fold or greater odds of depression when compared to those patients whose symptoms were limited to the surgical joint. A focus on the surgical joint alone is likely to miss a potentially important determinant of postsurgical patient-reported outcomes in patients undergoing hip or knee replacement.
