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Efficacy of a Combination of Conservative Therapies vs an Education Comparator on Clinical Outcomes in Thumb Base Osteoarthritis: A Randomized Clinical Trial.
Deveza, LA, Robbins, SR, Duong, V, Bennell, KL, Vicenzino, B, Hodges, PW, Wajon, A, Jongs, R, Riordan, EA, Fu, K, et al
JAMA internal medicine. 2021;(4):429-438
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Abstract
IMPORTANCE A combination of conservative treatments is commonly used in clinical practice for thumb base osteoarthritis despite limited evidence for this approach. OBJECTIVE To determine the efficacy of a 6-week combination of conservative treatments compared with an education comparator. DESIGN, SETTING, AND PARTICIPANTS Randomized, parallel trial with 1:1 allocation ratio among people aged 40 years and older with symptomatic and radiographic thumb base osteoarthritis in a community setting in Australia. INTERVENTIONS The intervention group (n = 102) received education on self-management and ergonomic principles, a base-of-thumb splint, hand exercises, and diclofenac sodium, 1%, gel. The comparator group (n = 102) received education on self-management and ergonomic principles alone. Intervention use was at participants' discretion from 6 to 12 weeks. MAIN OUTCOMES AND MEASURES Hand function (Functional Index for Hand Osteoarthritis; 0-30) and pain (visual analog scale; 0-100 mm) were measured at week 6 (primary time point) and week 12. An α of .027 was used at week 6 to account for co-primary outcomes. RESULTS Of the 204 participants randomized, 195 (96%) and 194 (95%) completed follow-ups at 6 and 12 weeks, respectively; the mean (SD) age of the population was 65.6 (8.1) years, and 155 (76.0%) were female. At week 6, hand function improved significantly more in the intervention group than the comparator (between-group difference, -1.7 units; 97.3% CI, -2.9 to -0.5; P = .002). This trend was sustained at 12 weeks (-2.4 units; 95% CI, -3.5 to -1.3; P < .001). Pain scores improved similarly at week 6 (between-group difference, -4.2 mm; 97.3% CI, -11.3 to 3.0; P = .19). At week 12, pain reduction was significantly greater in the intervention group (-8.6 mm; 95% CI, -15.2 to -2.0; P = .01). There were 34 nonserious adverse events, all in the intervention group-mostly skin reactions and exercise-related pain exacerbations. CONCLUSIONS AND RELEVANCE In this randomized clinical trial of people with thumb base osteoarthritis, combined treatments provided small to medium and potentially clinically beneficial effects on hand function but not pain. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000353493.
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Comparative Analyses of Pharmaceuticals or Food Supplements Containing Chondroitin Sulfate: Are Their Bioactivities Equivalent?
Stellavato, A, Restaino, OF, Vassallo, V, Finamore, R, Ruosi, C, Cassese, E, De Rosa, M, Schiraldi, C
Advances in therapy. 2019;(11):3221-3237
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INTRODUCTION Oral supplementation of chondroitin sulfate (CS) and glucosamine (GlcN), symptomatic slow-acting molecules, is recommended by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and Musculoskeletal Diseases (ESCEO) and other European Union (EU) guidelines for the restoration of the articular cartilage surface in patients affected by osteoarthritis (OA). They are commercialized as pharmaceutical grade products and as food supplements in combination with plant extracts hyaluronic acid, methylsulfonylmethane, and other components. Food supplements do not need to undergo the strict regulatory controls of pharmaceutical grade products; thus, composition and contaminants that could be present may not be evidenced before commercialization and these uncertainties may give rise to concerns about the bioactivity of these formulations. METHODS In this paper 10 different food supplements (FS) from diverse European countries were analyzed in comparison with two pharmaceutical grade products (Ph) using updated analytical approaches and biochemical cell-based assays. The purity, the titer, and the origin of CS in Ph and FS samples were initially assessed in order to successively compare the biological function. Both food supplements and pharmaceutical formulations were tested in vitro, using the same final CS concentration, on primary chondrocytes and synoviocytes in terms of (i) cell viability, (ii) activation of the NF-κB-mediated inflammation pathway, (iii) cartilage oligomeric matrix protein (COMP-2), IL-6, and IL-8 production. RESULTS All the FS presented a certain insoluble fraction; the CS and the GlcN contents were lower than the declared ones in 9/10 and 8/10 samples, respectively. All FS contained keratan sulfate (KS) at up to 50% of the total glycosaminoglycan amount declared on the label. Primary cells treated with the samples diluted to present the same CS concentration in the medium showed cytotoxicity in 7/10 FS while Ph preserved viability and reduced NF-κB, COMP-2, and secreted inflammatory cytokines. CONCLUSION Among all samples tested, the pharmaceutical grade products demonstrated effective modulation of biomarkers counteracting the inflammation status and improving viability and the physiological condition of OA human primary chondrocyte and synoviocyte cells. In contrast to that, most FS were cytotoxic at the tested concentrations, and only 3/10 of them showed similarities to Ph sample behavior in vitro. FUNDING This work was partially supported by PON01_1226 NUTRAFAST, MIUR Ministero dell'Università e della Ricerca Scientifica. Bioteknet financed two short-term grants for graduate technicians. The journal's Rapid Service and Open Access fees were funded by IBSA CH.
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Comfrey root: from tradition to modern clinical trials.
Staiger, C
Wiener medizinische Wochenschrift (1946). 2013;(3-4):58-64
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Comfrey (Symphytum officinale L.) has been used over many centuries as a medicinal plant. In particular, the use of the root has a longstanding tradition. Today, several randomised controlled trials have demonstrated the efficacy and safety. Comfrey root extract has been used for the topical treatment of painful muscle and joint complaints. It is clinically proven to relieve pain, inflammation and swelling of muscles and joints in the case of degenerative arthritis, acute myalgia in the back, sprains, contusions and strains after sports injuries and accidents, also in children aged 3 years and older. This paper provides information on clinical trials, non-interventional studies and further literature published on comfrey root till date.
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Intra-articular injection of hyaluronic acid is not superior to saline solution injection for ankle arthritis: a randomized, double-blind, placebo-controlled study.
DeGroot, H, Uzunishvili, S, Weir, R, Al-omari, A, Gomes, B
The Journal of bone and joint surgery. American volume. 2012;(1):2-8
Abstract
BACKGROUND Intra-articular injections of hyaluronic acid are potentially useful to treat ankle osteoarthritis, yet their effectiveness has not been proven. Both single and multiple-dose treatments for ankle arthritis with use of various hyaluronic acid products have been recommended, but few high-quality studies have been published. The aim of this study was to compare the effectiveness of a single intra-articular injection of hyaluronic acid with a single intra-articular injection of normal saline solution (placebo) for osteoarthritis of the ankle. METHODS Sixty-four patients with ankle osteoarthritis who met all study criteria were randomly assigned to a single intra-articular injection of 2.5 mL of low-molecular-weight, non-cross-linked hyaluronic acid or a single intra-articular injection of 2.5 mL of normal saline solution. The primary outcome measure was the change from baseline in the American Orthopaedic Foot & Ankle Society (AOFAS) clinical rating score at the six-week and twelve-week follow-up examination. Secondary outcome measures included the Ankle Osteoarthritis Scale score and patient-reported pain with use of a visual analog pain scale. RESULTS Of the sixty-four patients randomized and treated, eight patients withdrew, leaving fifty-six patients who completed the entire study. There was one mild adverse event (1.6%) among the sixty-four patients. At six weeks and twelve weeks, the mean AOFAS scores in the hyaluronic acid group had improved from baseline by 4.9 and 4.9 points, respectively, whereas the mean AOFAS scores in the placebo group initially worsened by 0.4 point at six weeks and then improved by 5.4 points at twelve weeks. While the change at twelve weeks from baseline was substantial for both groups, the between-group differences were not significant. CONCLUSIONS We found that a single intra-articular injection of low-molecular-weight, non-cross-linked hyaluronic acid is not demonstrably superior to a single intra-articular injection of saline solution for the treatment of osteoarthritis of the ankle.
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Two-needle vs. single-needle technique for TMJ arthrocentesis plus hyaluronic acid injections: a comparative trial over a six-month follow up.
Guarda-Nardini, L, Ferronato, G, Manfredini, D
International journal of oral and maxillofacial surgery. 2012;(4):506-13
Abstract
The aim of the study was to compare the effectiveness of five weekly two-needle arthrocentesis plus hyaluronic injections vs. the same protocol performed with a single-needle technique in patients with inflammatory-degenerative disorders of the temporomandibular joint (TMJ). 80 patients with TMJ osteoarthritis were randomly assigned to the two-needle or single-needle protocol and followed up for 6 months after treatment. Several outcome parameters, such as maximum pain at rest and maximum pain on chewing, subjective chewing efficiency, limitation in jaw function, jaw range of motion in mm, were recorded at baseline and multiple follow up assessments. Both treatment groups recorded significant improvement with respect to baseline levels in almost all outcome variables. The rate of improvement was not significantly different between the treatment protocols in any of the outcome variables (p-values between 0.143 and 0.970). No between-group differences emerged for the perceived subjective efficacy (p=0.321) and the treatment tolerability (p=0.783). The present investigation did not support the existence of significant differences in the treatment effectiveness for inflammatory-degenerative TMJ disorders of a cycle of five weekly injections of arthrocentesis plus hyaluronic acid injections performed according to the classical two-needle or the single-needle technique.
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Comparison of 2 hyaluronic acid drugs for the treatment of temporomandibular joint osteoarthritis.
Guarda-Nardini, L, Cadorin, C, Frizziero, A, Ferronato, G, Manfredini, D
Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 2012;(11):2522-30
Abstract
PURPOSE To compare the effectiveness of 2 treatment protocols providing 5 weekly temporomandibular joint (TMJ) arthrocenteses immediately followed by injections of 2 different molecular weight hyaluronic acid (HA) drugs to manage symptoms in patients with inflammatory-degenerative TMJ disease. MATERIALS AND METHODS Patients with a Research Diagnostic Criteria for Temporomandibular Disorders diagnosis of osteoarthritis were randomly assigned to 1 of 2 study groups receiving either low- or medium-molecular weight HA after arthrocentesis. The level of maximum pain at chewing was the primary outcome variable, and maximum pain at rest, subjective chewing efficiency, functional limitation, treatment tolerability, perceived treatment effectiveness, and jaw range-of-motion function in millimeters were the secondary outcomes. All variables were assessed and compared between groups at baseline, at the end of treatment, and 3 months later. RESULTS Forty subjects entered the study. At the end of the follow-up period, all the outcome variables improved in both groups of patients. A between-group comparison of changes over time showed that differences were not significant for any of the outcome variables, that is, pain at chewing (F = 0.056, P = .815), pain at rest (F = 0.383, P = .541), chewing efficiency (F = 0.050, P = .825), functional limitation (F = 0.268, P = .609), and mouth opening (F = 0.003, P = .954). In addition, no between-group differences were shown for perceived treatment effectiveness and treatment tolerability. CONCLUSIONS Similar positive effectiveness was shown for 2 treatment protocols for TMJ osteoarthritis (ie, 5-session single-needle arthrocentesis plus low- or medium-molecular weight HA).
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A comparative subjective assessment study of PENNSAID® and Voltaren Gel®, two topical formulations of diclofenac sodium.
Galer, BS
Pain practice : the official journal of World Institute of Pain. 2011;(3):252-60
Abstract
Osteoarthritis (OA) is a chronic degenerative joint disease that is debilitating for many individuals. While oral nonsteroidal anti-inflammatory drugs (NSAIDs) remain a common and effective treatment approach to managing OA, concerns over cardiovascular and gastrointestinal adverse events can potentially limit their use. Various formulations of topical NSAIDs have been shown to provide effective localized treatment with minimal adverse events. A patient perception study was conducted to evaluate patient preference between topical diclofenac sodium gel and that of diclofenac sodium topical solution with the penetration enhancer dimethyl sulfoxide (DMSO). Twenty-four healthy volunteers were randomized and asked to administer one dose of the topical products. Surveys were provided and assessed immediately after application, 5 minutes after application, and after the application had dried to gauge subjects' overall experience with the topical preparation. Overall, each drug's application was well tolerated and no adverse events were reported. Results of the patient preference survey demonstrated that topical diclofenac solution with DMSO had a number of characteristics that were rated significantly better than for diclofenac sodium gel. Mean subjective responses to topical diclofenac solution with DMSO were also more favorable for most items in the questionnaire, and more subjects preferred or highly preferred topical diclofenac solution with DMSO over diclofenac sodium gel.
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Effects of intra-articular administration of sodium hyaluronate on plasminogen activator system in temporomandibular joints with osteoarthritis.
Tang, YL, Zhu, GQ, Hu, L, Zheng, M, Zhang, JY, Shi, ZD, Liang, XH
Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 2010;(4):541-7
Abstract
OBJECTIVE The aim of this study was to investigate the effect of intra-articular sodium hyaluronate (SH) injections on the main components of plasminogen activator (PA) system in the synovial fluid of temporomandibular joint (TMJ) osteoarthritis (OA). STUDY DESIGN Forty patients diagnosed with TMJ OA and 20 healthy control subjects were included in this study. Synovial fluid was collected in the OA group and the healthy group at baseline. The OA patients were randomly divided into 2 groups (20 patients for each group): One group received 5 injections of SH, and the other received 5 injections of physiologic saline solution in the upper joint space at weekly intervals. Synovial fluid was collected before and after treatment. Urokinase-type PA (uPA), soluble uPA receptor (suPAR) and PA inhibitor 1 (PAI-1) levels in synovial fluid were quantified by enzyme-linked immunosorbent assay. RESULTS The OA patients had significantly higher uPA activity and levels of uPA (median 80.01 ng/L), suPAR (median 7.54 ng/L), and PAI-1 (median 54.9 ng/mL) than the healthy control subjects (median 20.47 ng/L uPA, 2.34 ng/L suPAR, and 19.9 ng/mL PAI-1; (P < .05). The uPA activity and levels of uPA, suPAR, and PAI-1 were significantly decreased after SH injections in TMJs of OA patients (P < .05), and there was no difference after saline injection. Visual analog pain score reduction correlated with changes in uPA and uPAR levels as well as uPA activity. CONCLUSION The effects of SH on PA system provide new insight into a possible underlying mechanism by which SH alleviates pain of patients with TMJ OA.
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Comparison of therapeutic effects of sodium hyaluronate and corticosteroid injections on trapeziometacarpal joint osteoarthritis.
Bahadir, C, Onal, B, Dayan, VY, Gürer, N
Clinical rheumatology. 2009;(5):529-33
Abstract
This was a randomized, open-label, evaluator-blinded clinical study including 40 women with stage II or III trapeziometacarpal joint osteoarthritis. The steroid group (n = 20) received one injection of 20 mg triamcinolone acetonide once and the hyaluronate group (n = 20) received three injections of 5 mg sodium hyaluronate at 1-week intervals. The pain level was assessed using a visual analog scale and grip and pinch strengths were measured using a hand grip dynomemeter and pinch gauge. The Duruöz Hand Index was used to evaluate hand function. Pain level decreased significantly over 12 months for the steroid group and over 6 months for the sodium hyaluronate group. Pinch strength did not improve in either group, but grip strength improved significantly in both groups. Hand function improved in both groups but it was only significant in the steroid group. Our findings showed that both intra-articular injection of steroid and sodium hyalurunate are effective in trapeziometacarpal joint osteoarthritis. However the steroid injection was found to be superior to sodium hyaluronate injection in reducing pain and improving hand function.
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Gastrointestinal side effects of etoricoxib in patients with osteoarthritis: results of the Etoricoxib versus Diclofenac Sodium Gastrointestinal Tolerability and Effectiveness (EDGE) trial.
Baraf, HS, Fuentealba, C, Greenwald, M, Brzezicki, J, O'Brien, K, Soffer, B, Polis, A, Bird, S, Kaur, A, Curtis, SP, et al
The Journal of rheumatology. 2007;(2):408-20
Abstract
OBJECTIVE . To compare the gastrointestinal (GI) tolerability, safety, and efficacy of etoricoxib and diclofenac in patients with osteoarthritis (OA). METHODS In total, 7111 patients (mean age 64 yrs) diagnosed with OA were enrolled in a randomized, double-blind trial. Patients received etoricoxib 90 mg qd (n = 3593) or diclofenac sodium 50 mg tid (n = 3518). Gastroprotective agents and low-dose aspirin were prescribed per treatment guidelines. The primary endpoint was the cumulative rate of discontinuations due to clinical and laboratory GI adverse experiences (AE). General safety was assessed, including adjudication of thrombotic cardiovascular (CV) safety data. Efficacy was evaluated using the least-square (LS) mean change from baseline patient global assessment of disease status (PGADS; 0-4 point scale). RESULTS Mean (SD, maximum) duration of treatment was 9.3 (4.4, 16.5) and 8.9 (4.5, 16.6) months in the etoricoxib and diclofenac groups, respectively. The cumulative discontinuation rate due to GI AE was significantly lower with etoricoxib than diclofenac [9.4 vs 19.2 events per 100 patient-years (PY), respectively; hazard ratio (HR) 0.50 (95% CI 0.43, 0.58; p < 0.001). Rates of thrombotic CV events were similar with etoricoxib and diclofenac [1.25 vs 1.15 events per 100 PY, respectively; HR 1.07 (95% CI 0.65, 1.74)]. The incidence of patients who discontinued due to hypertension-related AE was significantly higher with etoricoxib compared to diclofenac (2.3% vs 0.7%; p < 0.001), although few AE were severe (3 etoricoxib, 1 diclofenac). Etoricoxib and diclofenac treatment resulted in similar improvements in PGADS from baseline of -0.78 (95% CI -0.80, -0.75) and -0.75 (95% CI -0.77, -0.72), respectively. CONCLUSION Treatment with etoricoxib 90 mg was associated with significantly better GI tolerability compared to diclofenac in this population of patients with OA. Etoricoxib 90 mg, a dose 50% higher than indicated for OA, resulted in more discontinuations due to hypertension-related AE.