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Open Access journal
ISSN (Print) 2090-1984 - ISSN (Online) 2090-1992
Published by Hindawi [333 journals]
- The Influence of Oblique Angle Forced Exercise in Surgically Destabilized
Stifle Joints Is Synergistic with Bone, but Antagonistic with Cartilage in
an Ovine Model of Osteoarthritis
Abstract: 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 we may 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.
PubDate: Mon, 27 Feb 2017 00:00:00 +000
- Combination of Interleukin-27 and MicroRNA for Enhancing Expression of
Anti-Inflammatory and Proosteogenic Genes
Abstract: 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 TGF/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.
PubDate: Tue, 07 Feb 2017 00:00:00 +000
- Infrapatellar Fat Pad: An Alternative Source of Adipose-Derived
Mesenchymal Stem Cells
Abstract: 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; value = 0.047, and 17.33 ± 10.80-, 1.56 ± 1.31-fold; 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.
PubDate: Tue, 26 Apr 2016 11:21:08 +000
- Towards Tailored Patient’s Management Approach: Integrating the Modified
2010 ACR Criteria for Fibromyalgia in Multidimensional Patient Reported
Outcome Measures Questionnaire
Abstract: 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 () with both HAQ and EQ-5D. Changes in functional disability and QoL showed significant () 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.
PubDate: Wed, 13 Apr 2016 07:26:47 +000
- Amtolmetin: A Reappraisal of NSAID with Gastroprotection
Abstract: 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.
PubDate: Tue, 22 Mar 2016 14:22:04 +000
- RNA Interference Mediated Interleukin-1β Silencing in Inflamed
Chondrocytes Decreases Target and Downstream Catabolic Responses
Abstract: 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.
PubDate: Thu, 17 Mar 2016 07:52:09 +000
- Establishing the Psychometric Properties of the ICOAP Questionnaire
through Intra-Articular Treatment of Osteoarthritic Pain: Implementation
for the Greek Version
Abstract: 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 -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.
PubDate: Sun, 13 Mar 2016 12:30:43 +000
- The Combination of the Tunnel View and Weight-Bearing Anteroposterior
Radiographs Improves the Detection of Knee Arthritis
Abstract: 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 () and medial () compartments over the AP view alone. The combined views significantly improved the identification of medial subchondral cysts (), sclerosis of the lateral tibial plateau (), and moderate-to-large osteophytes in the medial compartment (), intercondylar notch (), and tibial spine (). 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.
PubDate: Tue, 26 Jan 2016 11:03:55 +000
- Rituximab Downregulates Gene Expression Associated with Cell
Proliferation, Survival, and Proteolysis in the Peripheral Blood from
Rheumatoid Arthritis Patients: A Link between High Baseline
Autophagy-Related ULK1 Expression and Improved Pain Control
Abstract: 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 () 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 () 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.
PubDate: Sun, 24 Jan 2016 13:59:51 +000
- The Interchangeability of Plasma and Whole Blood Metal Ion Measurement in
the Monitoring of Metal on Metal Hips
Abstract: One hundred and twenty six paired samples of plasma and whole blood were measured with inductively coupled plasma mass spectrometry technique for metal ions analysis to determine a relationship between them. There was a significant difference between the mean plasma and whole blood concentrations of both cobalt (Co) and chromium (Cr) ( for both Co and Cr). The mean ratio between plasma and whole blood Cr and Co was 1.56 (range: 0.39–3.85) and 1.54 (range: 0.64–18.26), respectively, but Bland and Altman analysis illustrated that this relationship was not universal throughout the range of concentrations. There was higher variability at high concentrations for both ions. We conclude that both these concentrations should not be used interchangeably and conversion factors are unreliable due to concentration dependent variability.
PubDate: Sun, 20 Dec 2015 14:01:04 +000
- Sucupira as a Potential Plant for Arthritis Treatment and Other Diseases
Abstract: Trees of the genus Pterodon, commonly known as “sucupira-branca” or “faveira,” are native to central Brazil. The Pterodon fruits are traditionally used in ethnomedicine as an infusion, in small doses, and at regular time intervals as an antirheumatic, anti-inflammatory, tonic, and depurative agent. The various compounds present in the Pterodon class are, generally, water-insoluble and derived from the fusion of high-molecular weight pentacarbonate units. Scientific research has shown that the major compounds isolated from Pterodon species are linear and/or tetracyclic diterpenes with vouacapane skeletons that partly underlie the pharmacological activities of the fruit-derived oil. Material from Pterodon species has several biological properties, such as analgesic, anti-inflammatory, and anticancer effects. Therefore, recent studies have sought to microencapsulate these extracts to protect them from potential chemical degradation and improve their water solubility, ensuring greater stability and quality of the end products. This review presents a succinct overview of the available scientific evidence of the biological activity and toxicity of Pterodon species in addition to other important aspects, including phytochemical and technological features.
PubDate: Tue, 03 Nov 2015 11:08:57 +000
- A Systematic Review Investigating the Presence of Inflammatory Synovitis
in Hip and Knee Joint Replacement Surgery
Abstract: Synovial tissue can display an inflammatory response in the presence of OA. There is increasing interest to better understand the role of inflammation in OA, particularly with regard to those who require joint replacement. A systematic review of inflammatory synovitis in OA of literature databases was undertaken from their inception until October 14, 2014. Independent critical appraisal of each study was undertaken using the CASP appraisal tool. From a total of sixty-six identified citations, twenty-three studies were deemed eligible for review. The studies presented moderate to strong methodological quality. Strong correlation was identified between histological and imaging synovitis severity. Correlation was weaker between clinical symptoms and imaging and/or histological synovitis severity. There was little consensus, with regard to expressed cytokines and chemokines at the different stages of OA disease progression. Few studies investigated the influence of inflammatory synovitis on the outcome of major joint replacement. Research into inflammatory synovitis in OA is an emerging field. Longitudinal studies applying proven imaging modalities, histological analysis, and longer follow-up are required in order to further define our understanding of the role of synovitis in the pathogenesis of OA and its effects on outcomes following major joint replacement.
PubDate: Sun, 18 Oct 2015 07:21:10 +000
- Relationship between Tibial Baseplate Design and Rotational Alignment
Landmarks in Primary Total Knee Arthroplasty
Abstract: This study evaluated the influence of modern tibial baseplate designs when using the anterior tibial cortex as a primary rotational landmark for the tibial baseplate in TKA. Eighty patients undergoing TKA were randomized in two groups. Group 1 included 25 females and 15 males receiving a posterior-stabilized (PS) symmetric tibial baseplate while Group 2 included 24 females and 16 males receiving a PS anatomical tibial component. Identical surgical technique, including the use of the surgical transepicondylar femoral axis (sTEA) and the anterior tibial cortex (“Curve-on-Curve”) as rotational alignment landmarks, was used. All patients underwent CT evaluation performed with the knee in full extension. Three observers independently measured the rotational alignment of the tibial component in relation to the sTEA. The rotational alignment of the symmetric baseplate showed an average external rotation of 1.3° (minimum 5°, maximum −1°): 91% of the knees showed 0 ± 3° with respect to the surgical sTEA, being internally rotated in 20%. The rotational alignment of the anatomical baseplate showed an average external rotation of 4.1° (minimum 0.4°, maximum 8.9°): only 47.5% of the knees showed 0 ± 3°, being externally rotated in 100%. The difference between the two groups was statistically significant. This study confirms the reliability of the “Curve-on-Curve” technique as an adequate rotational alignment anatomical landmark in TKA: the use of an asymmetric tibial baseplate might lead to external rotation of the tibial component when this technique is intraoperatively chosen.
PubDate: Mon, 28 Sep 2015 10:00:21 +000
- Role of Health Literacy in Self-Reported Musculoskeletal Disorders
Abstract: Self-report of musculoskeletal conditions is often used to estimate population prevalence and to determine disease burden and influence policy. However, self-report of certain musculoskeletal conditions is frequently inaccurate, suggesting inadequate communication to the patient of their diagnosis. The aim of this study is to determine the association between functional health literacy (FHL) and self-reported musculoskeletal conditions in a representative population survey. FHL was measured using Newest Vital Sign in 2824 randomly selected adults. Participants also self-reported medically diagnosed arthritis, gout, and osteoporosis. Multiple logistic regression was adjusted for age and sex. The prevalence of self-reported arthritis, gout, and osteoporosis was 25.2%, 4.9%, and 5.6%, respectively. The prevalence of those at risk for inadequate FHL was 24.0% and high likelihood of inadequate FHL was 21.0%. However, over 50% of respondents with arthritis or gout had at risk/inadequate FHL, increasing to 70% of those self-reporting osteoporosis. After adjustment for age and sex, respondents in the arthritis subgroup of “don’t know” and self-reported osteoporosis were significantly more likely to have inadequate FHL than the general population. This study indicates a substantial burden of low health literacy amongst people with musculoskeletal disease. This has implications for provider-patient communication, individual healthcare, population estimates of musculoskeletal disease, and impact of public health messages.
PubDate: Tue, 18 Aug 2015 12:31:19 +000
- Screening Optimization of Latent Tuberculosis Infection in Rheumatoid
Abstract: Objective. Rheumatoid arthritis (RA) patients are at increased risk of latent tuberculosis infection (LTBI) but there are no clear guidelines for LTBI screening with Tuberculin Skin Test (TST) or Quantiferon TB Gold testing (QFT-G). Methods. A retrospective study was conducted in a high risk, largely foreign-born, inner city, RA population. After screening 280 RA patients, 134 patients who had both TST and QFT-G testing performed during their initial evaluation were included. Results. Out of 132 RA patients included in our analysis, 50 (37.8%) patients were diagnosed with LTBI with either positive TST 42 (31.8%) or QFT-G 23 (17.4%). 15 (11.4%) were positive and 82 (62.1%) were negative for both tests. The agreement between TST and QFT-G was 73.5% (Kappa 0.305, CI = 95% 0.147–0.463, ). Conclusions. There was low-moderate agreement between TST and QFT-G. In the absence of clearly defined gold standard and limitations associated with both tests, we propose early screening with both tests for patients who need prompt treatment with BRMs. Patients who are not immediate candidates for BRM treatment may be safely and cost effectively screened with a two-step process: initial screening with TST and if negative, IGRA testing. Patients positive for either test should be promptly treated.
PubDate: Wed, 29 Jul 2015 11:01:07 +000
- Pain Sensitisation in Women with Active Rheumatoid Arthritis: A
Comparative Cross-Sectional Study
Abstract: Objectives. In some rheumatoid arthritis (RA) patients, joint pain persists without signs of inflammation. This indicates that central pain sensitisation may play a role in the generation of chronic pain in a subgroup of RA. Our aim was to assess the degree of peripheral and central pain sensitisation in women with active RA compared to healthy controls (HC). Methods. 38 women with active RA () and 38 female HC were included in, and completed, the study. Exclusion criteria were polyneuropathy, pregnancy, and no Danish language. Cuff Pressure Algometry measurements were carried out on the dominant lower leg. Pain threshold, pain tolerance, and pain sensitivity during tonic painful stimulation were recorded. Results. Women with active RA had significantly lower pain threshold () and pain tolerance () than HC. The mean temporal summation- (TS-) index in RA patients was 0.98 (SEM: 0.09) and 0.71 (SEM: 0.04) in HC (). Conclusion. Patients with active RA showed decreased pressure-pain threshold compared to HC. In addition, temporal summation of pressure-pain was increased, indicating central pain sensitization, at least in some patients. Defining this subgroup of patients may be of importance when considering treatment strategies.
PubDate: Tue, 21 Jul 2015 07:58:11 +000
- Depression and the Overall Burden of Painful Joints: An Examination among
Individuals Undergoing Hip and Knee Replacement for Osteoarthritis
Abstract: 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, )) 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.
PubDate: Wed, 11 Mar 2015 09:17:35 +000
- Whole-Foods, Plant-Based Diet Alleviates the Symptoms of Osteoarthritis
Abstract: Objective. To evaluate the effectiveness of a whole-foods, plant-based diet (WFPB) to reduce symptoms of osteoarthritis. Methods. Six-week, prospective randomized open-label study of patients aged 19–70 with osteoarthritis. Participants were randomized to a WFPB (intervention) or continuing current diet (control). Outcomes were assessed by mixed models analysis of participant self-assessed weekly SF-36v2 domain t scores, weekly Patient Global Impression of Change (PGIC) scales, and mean weekly Visual Analog Scale (VAS) pain assessment. Mixed models analysis also evaluated pre-post change from baseline level for standard clinical measures: weight, BMI, body temperature, pulse, and blood pressure. Results. Forty participants were randomized. Thirty-seven of them, 18 control and 19 intervention, completed the study. The intervention group reported a significantly greater improvement than the control group in SF-36v2 energy/vitality, physical functioning, role physical, and the physical component summary scale. The differences between the intervention and control PGIC scales were statistically significant over time. Intervention group improvement in VAS weekly mean was also significantly greater than that of the control group from week 2 onward. Conclusion. Study results suggest that a whole-foods, plant-based diet significantly improves self-assessed measures of functional status among osteoarthritis patients.
PubDate: Sat, 28 Feb 2015 14:11:57 +000
- Adherence to Methotrexate in Rheumatoid Arthritis: A Danish Nationwide
Abstract: 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.
PubDate: Wed, 25 Feb 2015 14:13:14 +000
- Early Metacarpal Bone Mineral Density Loss Using Digital X-Ray
Radiogrammetry and 3-Tesla Wrist MRI in Established Rheumatoid Arthritis:
A Longitudinal One-Year Observational Study
Abstract: Objectives. Early change in rheumatoid arthritis (RA) is characterised by periarticular osteopenia. We investigated the relationship of early metacarpal digital X-ray radiogrammetry bone mineral density (DXR-BMD) change rate (RC-BMD, mg/cm2/month) to longitudinal changes in hand and feet radiographic and wrist MRI scores over 1 year. Materials and Methods. 10 RA patients completed the study and had wrist 3T-MRI and hand and feet X-rays at various time points over 1 year. MRI was scored by RAMRIS, X-ray was done by van der Heijde modified Sharp scoring, and RC-BMD was analysed using dxr-online. Results. There was good correlation amongst the two scorers for MRI measures and ICC for erosions: 0.984, BME: 0.943, and synovitis: 0.657. Strong relationships were observed between RC-BMD at 12-week and 1-year change in wrist marrow oedema (BME) (, ) but not with erosion, synovitis, or radiographic scores. Conclusion. Early RC-BMD correlates with 1-year wrist BME change, which is a known predictor of future erosion and joint damage. However, in our pilot study, early RC-BMD did not show relationships to MRI erosion or radiographic changes over 1 year. This may reflect a slower kinetic in the appearance of MRI/radiographic erosions, generating the hypothesis that RC-BMD may be a more sensitive and early structural prognostic marker in RA follow-up.
PubDate: Tue, 17 Feb 2015 09:53:46 +000
- Antibodies to Infliximab and Adalimumab in Patients with Rheumatoid
Arthritis in Clinical Remission: A Cross-Sectional Study
Abstract: Objective. To investigate if antibodies towards biological TNF-α inhibitors (anti-TNFi Abs) are present in patients with rheumatoid arthritis (RA) in clinical remission and to relate any anti-TNFi Abs to circulating level of TNF-α inhibitor (TNFi). Methods. Patients with RA, treated with infliximab or adalimumab, and in clinical remission (DAS28(CRP) < 2.6) were included from 6 out-patient clinics. In blood samples, presence of anti-TNFi Abs was determined by radioimmunoassay, and concentration of bioactive TNFi was measured by a cell-based reporter gene assay. Results. Anti-TNFi Abs were present in 8/44 patients (18%) treated with infliximab and 1/49 patients (2%) treated with adalimumab (). In the former group, anti-TNFi Abs corresponded with low levels of TNFi (). Anti-TNFi Ab-positive patients had shorter disease duration at initiation of TNFi therapy () but were similar for the rest of the compared parameters. Conclusions. In RA patients in clinical remission, anti-TNFi Abs occur frequently in patients treated with infliximab, while they occur rarely in patients treated with adalimumab. Presence of anti-infliximab Abs is accompanied by low or undetectable levels of infliximab. These data suggest that continued infliximab treatment may be redundant in a proportion of RA patients treated with infliximab and in clinical remission.
PubDate: Wed, 11 Feb 2015 09:49:33 +000
- The Safety and Efficacy of an Enzyme Combination in Managing Knee
Osteoarthritis Pain in Adults: A Randomized, Double-Blind,
Abstract: This randomized, double-blind, placebo-controlled, and comparator-controlled trial evaluated the safety and efficacy of an enzyme combination, as Wobenzym, in adults with moderate-to-severe osteoarthritis (OA) of the knee. Adults () received Wobenzym, diclofenac (a nonsteroidal anti-inflammatory drug, NSAID), or placebo for 12 weeks. Improvement in pain scores (Lequesne Functional Index) did not differ between subjects treated with Wobenzym or diclofenac, and both treatment groups improved compared to placebo (). Reduction in total WOMAC scores (secondary outcome measure) did not differ between Wobenzym and diclofenac, although only diclofenac emerged as different from placebo (). The median number of rescue medication (paracetamol) tablets consumed was less in the Wobenzym group compared to placebo (), while there was no difference between diclofenac and placebo. Adverse events were similar in frequency in Wobenzym and placebo groups (7.2% and 9.1% of subjects, resp.) and higher in diclofenac group (15.6%). Wobenzym is comparable to the NSAID diclofenac in relieving pain and increasing function in adults with moderate-to-severe painful knee OA and reduces reliance on analgesic medication. Wobenzym is associated with fewer adverse events and, therefore, may be appropriate for long-term use.
PubDate: Sat, 31 Jan 2015 11:18:25 +000
- Validity and Agreement between the 28-Joint Disease Activity Score Based
on C-Reactive Protein and Erythrocyte Sedimentation Rate in Patients with
Abstract: Objective. To validate the agreement between the 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) and the 28-joint disease activity score based on C-reactive protein (DAS28-CRP) in a group of Danish patients with rheumatoid arthritis (RA). Methods. Data from 109 Danish RA patients initiating biologic treatment were analysed at baseline and following one year of treatment. Participants were retrospectively enrolled from a previous cohort study and were considered eligible for this project if CRP and ESR were measured at baseline and at the follow-up visit. To assess the extent of agreement between the two DAS28 definitions, the “European League Against Rheumatism” (EULAR) response criteria based on each definition were calculated with cross-classification. Weighted Kappa (κ) coefficients were calculated, and Bland-Altman plots were used to illustrate degree of agreement between DAS28 definitions. Results. The 75 eligible patients were classified as EULAR good, moderate, and nonresponders with good agreement (61/75; 81%) between DAS28-CRP and DAS28-ESR ( (95% CI: 0.63 to 0.88)). Conclusions. According to our findings, DAS28-CRP and DAS28-ESR are interchangeable when assessing RA patients and the two versions of DAS28 are comparable between studies.
PubDate: Tue, 06 Jan 2015 10:15:42 +000
- Epicardial Fat Thickness as Cardiovascular Risk Factor and Therapeutic
Target in Patients with Rheumatoid Arthritis Treated with Biological and
Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with high cardiovascular morbidity and mortality. Epicardial adipose tissue (EAT) thickness may act as a therapeutic target during treatments with drugs modulating the adipose tissue. We evaluate EAT thickness in RA patients treated with biological and nonbiological disease-modifying antirheumatic drugs (DMARDs). A cross-sectional study was conducted with a cohort of 34 female RA patients and 16 controls matched for age and body mass index (BMI). Plasma glucose, basal insulin, plasma lipids, and high-sensitivity C-reactive protein (hs-CRP) were assessed. EAT thickness and left ventricular mass (LVM) were measured by echocardiography. No significant differences in waist circumference (WC), blood pressure, fasting blood glucose, basal insulin, and lipid parameters were found between the groups. The control group showed lower concentrations () of hs-CRP and LVM () than those of the two RA groups. Patients treated with TNF-α inhibitors showed significantly lower EAT thickness than those treated with nonbiological DMARDs (8.56 ± 1.90 mm versus 9.71 ± 1.45 mm; ). Women with no RA revealed reduced EAT thickness (5.39 ± 1.52 mm) as compared to all RA patients (). Results suggest that RA patients have greater EAT thickness than controls regardless of BMI and WC.
PubDate: Wed, 10 Dec 2014 12:25:43 +000
- Progression of Gene Expression Changes following a Mechanical Injury to
Articular Cartilage as a Model of Early Stage Osteoarthritis
Abstract: An impact injury model of early stage osteoarthritis (OA) progression was developed using a mechanical insult to an articular cartilage surface to evaluate differential gene expression changes over time and treatment. Porcine patellae with intact cartilage surfaces were randomized to one of three treatments: nonimpacted control, axial impaction (2000 N), or a shear impaction (500 N axial, with tangential displacement to induce shear forces). After impact, the patellae were returned to culture for 0, 3, 7, or 14 days. At the appropriate time point, RNA was extracted from full-thickness cartilage slices at the impact site. Quantitative real-time PCR was used to evaluate differential gene expression for 18 OA related genes from four categories: cartilage matrix, degradative enzymes and inhibitors, inflammatory response and signaling, and cell apoptosis. The shear impacted specimens were compared to the axial impacted specimens and showed that shear specimens more highly expressed type I collagen (Col1a1) at the early time points. In addition, there was generally elevated expression of degradative enzymes, inflammatory response genes, and apoptosis markers at the early time points. These changes suggest that the more physiologically relevant shear loading may initially be more damaging to the cartilage and induces more repair efforts after loading.
PubDate: Sun, 16 Nov 2014 09:25:59 +000
- Evaluation of Antiarthritic Potential of Methanolic Extract of Gentiana
Abstract: Rheumatoid arthritis is a systemic disorder which involves the activation of immune system against the self-tissues. The main targets of this disease are the joints. Being systemic the development of this disease involves different mechanisms and thus the exact cause of this disease remains unknown. Although different drugs have been developed, none has been found to be the cure for this disease. In the current study the rat carrageenin paw was used as a model for acute inflammation and mycobacterium induced adjuvant arthritic model was used for exploring the antiarthritic potential of methanolic extract of Gentiana kurroo. In this study the different extracts tested showed less inhibition of acute inflammation than methanolic extract. The methanolic extract was further used in different doses and the anti-inflammatory efficacy was found to be dose dependent. The results obtained were significant with the control and the standard groups. In the arthritic model the methanolic extract showed decrease in the paw volume of arthritic animals and also in the arthritic symptoms. Again the results obtained were found to be significantly dose dependent. From the results obtained it can be concluded that this extract may serve as a source of drug against the rheumatoid arthritis.
PubDate: Thu, 06 Nov 2014 11:45:38 +000
- Short Term Recovery of Function following Total Knee Arthroplasty: A
Randomised Study of the Medial Parapatellar and Midvastus Approaches
Abstract: This pilot double blind randomised controlled study aimed to investigate whether the midvastus (MV) approach without patellar eversion in total knee arthroplasty (TKA) resulted in improved recovery of function compared to the medial parapatellar (MP) approach. Patients were randomly allocated to either the MV approach or the MP approach. Achievements of inpatient mobility milestones were recorded. Knee kinematics, muscle strength, Timed Up and Go, WOMAC, and daily step count were assessed before and up to six months after surgery. Cohen’s effect size was calculated to inform the sample size in future trials. Twenty-eight participants (16 males, 12 females) participated. Patient mobility milestones such as straight leg raise were achieved on average 1.3 days (95% CI −3.4 to 0.7, ) earlier in the MV group. Knee extensor strength at 6 weeks after surgery was higher (95% CI −0.38 to 0.61, ) in the MV group. No trends for differences between the groups were observed in knee kinematics, TUG, WOMAC, or step count. Our results suggest a short term advantage in the first 6 weeks after surgery of the MV approach over the MP approach, but a larger study is required to confirm these findings. This trial is registered with NCT056445.
PubDate: Wed, 01 Oct 2014 00:00:00 +000
- Psychometric Properties of the 8-Item English Arthritis Self-Efficacy
Scale in a Diverse Sample
Abstract: Arthritis self-efficacy is important for successful disease management. This study examined psychometric properties of the 8-item English version of the Arthritis Self-Efficacy Scale (ASES-8) and differences in ASES-8 scores across sample subgroups. In 401 participants with self-reported doctor-diagnosed arthritis, exploratory factor analysis and tests of internal consistency were conducted. Concurrent validity was examined by associating ASES-8 scores with disease-specific, psychosocial, functional, and behavioral measures expected to be related to arthritis self-efficacy. All analyses were conducted for the full sample and within subgroups (gender, race, age, education, and weight status). Exploratory factor analysis for the entire sample and in all 12 subgroups demonstrated a one factor solution (factor loadings: 0.61 to 0.89). Internal consistency was high for measures of Cronbach’s alpha (0.87 to 0.94), omega (0.87 to 0.93), and greatest lower bound (0.90 to 0.95). ASES-8 scores were significantly correlated with all measures assessed , demonstrating concurrent validity. Those with a high school education or greater had higher ASES-8 scores than those with less than a high school education ; no other subgroup differences were found. The ASES-8 is a valid and reliable tool to measure arthritis self-efficacy efficiently and thereby reduce participant burden in research studies.
PubDate: Thu, 21 Aug 2014 11:13:13 +000
- Individual and Community Socioeconomic Status: Impact on Mental Health in
Individuals with Arthritis
Abstract: To examine the impact of individual and community socioeconomic status (SES) measures on mental health outcomes in individuals with arthritis, participants with self-reported arthritis completed a telephone survey assessing health status, health attitudes and beliefs, and sociodemographic variables. Regression analyses adjusting for race, gender, BMI, comorbidities, and age were performed to determine the impact of individual and community level SES on mental health outcomes (i.e., Medical Outcomes Study SF-12v2 mental health component, the Centers for Disease Control and Prevention Health-Related Quality of Life Healthy Days Measure, Center for Epidemiological Studies Depression [CES-D] scale). When entered singly, lower education and income, nonmanagerial occupation, non-homeownership, and medium and high community poverty were all significantly associated with poorer mental health outcomes. Income, however, was more strongly associated with the outcomes in comparison to the other SES variables. In a model including all SES measures simultaneously, income was significantly associated with each outcome variable. Lower levels of individual and community SES showed most consistent statistical significance in association with CES-D scores. Results suggest that both individual and community level SES are associated with mental health status in people with arthritis. It is imperative to consider how interventions focused on multilevel SES factors may influence existing disparities.
PubDate: Mon, 04 Aug 2014 00:00:00 +000
- Zingiber officinale: A Potential Plant against Rheumatoid Arthritis
Abstract: Rheumatoid arthritis (RA) is an autoimmune disease particularly affecting elderly people which leads to massive bone destruction with consequent inflammation, pain, and debility. Allopathic medicine can provide only symptomatic relief. However, Zingiber officinale is a plant belonging to the Zingiberaceae family, which has traditionally been used for treatment of RA in alternative medicines of many countries. Many of the phytochemical constituents of the rhizomes of this plant have therapeutic benefits including amelioration of RA. This review attempts to list those phytochemical constituents with their reported mechanisms of action. It is concluded that these phytochemicals can form the basis of discovery of new drugs, which not only can provide symptomatic relief but also may provide total relief from RA by stopping RA-induced bone destruction. As the development of RA is a complex process, further research should be continued towards elucidating the molecular details leading to RA and drugs that can stop or reverse these processes by phytoconstituents of ginger.
PubDate: Tue, 27 May 2014 06:18:17 +000