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Background: Resveratrol is a natural compound found in red wine. It has demonstrated anti-inflammatory properties in preclinical models. We compared the effect of oral resveratrol in a new patented formulation to oral placebo for individuals with painful knee osteoarthritis., Methods and Findings: ARTHROL was a double-blind, randomized, placebo-controlled, Phase 3 trial conducted in 3 tertiary care centers in France. We recruited adults who fulfilled the 1986 American College of Rheumatology criteria for knee osteoarthritis and reported a pain intensity score of at least 40 on an 11-point numeric rating scale (NRS) in 10-point increments (0, no pain, to 100, maximal pain). Participants were randomly assigned (1:1) by using a computer-generated randomization list with permuted blocks of variable size (2, 4, or 6) to receive oral resveratrol (40 mg [2 caplets] twice a day for 1 week, then 20 mg [1 caplet] twice a day; resveratrol group) or matched oral placebo (placebo group) for 6 months. The primary outcome was the mean change from baseline in knee pain on a self-administered 11-point pain NRS at 3 months. The trial was registered at ClinicalTrials.gov: (NCT02905799). Between October 20, 2017 and November 8, 2021, we assessed 649 individuals for eligibility, and from November 9, 2017, we recruited 142 (22%) participants (mean age 61.4 years [standard deviation (SD) 9.6] and 101 [71%] women); 71 (50%) were randomly assigned to the resveratrol group and 71 (50%) to the placebo group. At baseline, the mean knee pain score was 56.2/100 (SD 13.5). At 3 months, the mean reduction in knee pain was -15.7 (95% confidence interval (CI), -21.1 to -10.3) in the resveratrol group and -15.2 (95% CI, -20.5 to -9.8) in the placebo group (absolute difference -0.6 [95% CI, -8.0 to 6.9]; p = 0.88). Serious adverse events (not related to the interventions) occurred in 3 (4%) in the resveratrol group and 2 (3%) in the placebo group. Our study has limitations in that it was underpowered and the effect size, estimated to be 0.55, was optimistically estimated., Conclusions: In this study, we observed that compared with placebo, oral resveratrol did not reduce knee pain in people with painful knee osteoarthritis., Trial Registration: ClinicalTrials.gov ID: NCT02905799., Competing Interests: CN is an Academic Editor on PLOS Medicine’s editorial board. She reports receiving consulting fees from Thuasne, Merz and Ipsen; speaker fees from Actelion Pharmaceuticals France, Ipsen, Lilly, Meda pharma and Novartis; reimbursement of conference registration and accommodation by Grünenthal and Merz; and hospitality from Preciphar, Sandoz, Takeda France, and UCB Pharma SA, outside of the submitted work (<$5,000/y). CD reports receiving hospitality from Merz, outside of the submitted work. JS reports receiving personal fees from MSD, Pfizer, Abbvie, Fresenius Kabi, BMS, Roche, Chugai, Sandoz, Lilly, Novartis, Galapagos, AstraZeneca, UCB and Janssen and research grants from Pfizer, MSD, Schwa Medico, and BMS, outside of the submitted work. FB reports receiving consulting or speaker fees from AstraZeneca, Boehringer Ingelheim, Cellprothera, Galapagos, Grünenthal, GSK, Eli Lilly, MerckSerono, Nordic Bioscience, Novartis, Pfizer, Sanofi, Servier, Peptinov, Viatris, Aché Lab. Shareholder of 4Moving Biotech and 4P Pharma, outside of the submitted work. EC, IB, GB, MMLC, JZ and FR report no conflict of interest., (Copyright: © 2024 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The purpose of this study was to evaluate the safety and efficacy of transient genicular artery embolization (GAE) using an ethiodized oil-based emulsion for the treatment of knee osteoarthritis (KOA)., Materials and Methods: This prospective, single-arm, open-label, multicenter, first-in-human cohort trial was registered on ClinicalTrials.gov (NCT04733092). The main inclusion criterion was diagnosis of KOA according to a visual analogue scale (VAS) pain score ≥ 40 mm (score range: 0-100 mm), despite conservative treatment for at least three months. Treatment efficacy was assessed using changes in VAS pain score, Mean Western Ontario & McMaster Universities osteoarthritis (WOMAC) function score (normalized to 100; score ranging from 0 to100) and outcome measures in rheumatoid arthritis clinical trials (OMERACT)-Osteoarthritis Research Society (OARSI) set of responder criteria., Results: Twenty-two consecutive participants (13 women; mean age, 66 ± 9 [standard deviation (SD)]) were included and underwent GAE. Emulsion consisted in a mixture of ioversol and ethiodized oil (ratio 1:3, respectively) prepared extemporaneously. The rate of serious adverse events attributed to GAE within one month was 5% (1/22), corresponding to reversible worsening of renal function. Immediate technical success rate was 100%. Mean VAS pain score dropped from 74.4 ± 16.5 (SD) mm at baseline to 37.2 ± 26.7 (SD) mm at three months (P < 0.001). Mean WOMAC function score (normalized to 100: score ranging from 0 to 100) decreased from 57.3 ± 17.1 (SD) at baseline to 33.5 ± 25.9 (SD) at three months (P < 0.001). At three months, 16 out of 22 participants (73%) were considered responders according to the OMERACT-OARSI set of responder criteria, including high improvement in either pain or WOMAC function, or improvement in both pain and WOMAC function., Conclusion: GAE using an ethiodized oil-based emulsion is safe and improves pain and function in participants with KOA for at least three months., Competing Interests: Declaration of Competing Interest MS reports consulting fees from Guerbet France and to be a co-inventor of the patented emulsion. OP and CD are also co-inventors of the patented emulsion. The other authors have no conflicts of interest related to this work to declare., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Knee osteoarthritis (OA) is one of the most common and disabling medical conditions. In the case of moderate to severe pain, a single intervention may not be sufficient to allay symptoms and improve quality of life. Examples include first-line, background therapy with symptomatic slow-acting drugs for OA (SYSADOAs) or non-steroidal anti-inflammatory drugs (NSAIDs). Therefore, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) performed a review of a multimodal/multicomponent approach for knee OA therapy. This strategy is a particularly appropriate solution for the management of patients affected by knee OA, including those with pain and dysfunction reaching various thresholds at the different joints. The multimodal/multicomponent approach should be based, firstly, on different combinations of non-pharmacological and pharmacological interventions. Potential pharmacological combinations include SYSADOAs and NSAIDs, NSAIDs and weak opioids, and intra-articular treatments with SYSADOAs/NSAIDs. Based on the available evidence, most combined treatments provide benefit beyond single agents for the improvement of pain and other symptoms typical of knee OA, although further high-quality studies are required. In this work, we have therefore provided new, patient-centered perspectives for the management of knee OA, based on the concept that a multimodal, multicomponent, multidisciplinary approach, applied not only to non-pharmacological treatments but also to a combination of the currently available pharmacological options, will better meet the needs and expectations of patients with knee OA, who may present with various phenotypes and trajectories., (© 2022. The Author(s).)

Hand osteoarthritis is the most common joint condition and is associated with significant morbidity. It is of paramount importance that patients are thoroughly assessed and examined when complaining of hand stiffness, pain, deformity or disability and that the patient's concerns and expectations are addressed by the healthcare professional. In 2019 the American College of Rheumatology and Arthritis Foundation (ACR/AF) produced guidelines which included recommendations for the treatment of hand osteoarthritis. An ESCEO expert working group (including patients) was convened and composed this paper with the aim to assess whether these guidelines were appropriate for the treatment of hand osteoarthritis therapy in Europe and whether they met with the ESCEO patient-centered approach. Indeed, patients are the key stakeholders in healthcare and eliciting the patient's preference is vital in the context of an individual consultation but also for informing research and policy-making. The patients involved in this working group emphasised the often-neglected area of aesthetic changes in hand osteoarthritis, importance of developing pharmacological therapies which can alleviate pain and disability and the need of the freedom to choose which approach (out of pharmacological, surgical or non-pharmacological) they wished to pursue. Following robust appraisal, it was recommended that the ACR/AF guidelines were suitable for a European context (as described within the body of the manuscript) and it was emphasised that patient preferences are key to the success of individual consultations, future research and future policy-making., (© 2022. Crown.)

Importance: Multidisciplinary prehabilitation before total knee replacement (TKR) for osteoarthritis may improve outcomes in the postoperative period., Objective: To compare multidisciplinary prehabilitation with usual care before TKR for osteoarthritis in terms of functional independence and activity limitations after surgery., Design, Setting, and Participants: This prospective, open-label randomized clinical trial recruited participants 50 to 85 years of age with knee osteoarthritis according to the American College of Rheumatology criteria for whom a TKR was scheduled at 3 French tertiary care centers. Recruitment started on October 4, 2012, with follow-up completed on November 29, 2017. Statistical analyses were conducted from March 29, 2018, to March 6, 2019., Interventions: Four supervised sessions of multidisciplinary rehabilitation and education (2 sessions per week, at least 2 months before TKR, delivered to groups of 4-6 participants at each investigating center; session duration was 90 minutes and included 30 minutes of education followed by 60 minutes of exercise therapy) or usual care (information booklet and standard advice by the orthopedic surgeon) before TKR., Main Outcomes and Measures: The short-term primary end point was the proportion of participants achieving functional independence a mean (SD) of 4 (1) days after surgery defined as level 3 on the 4 functional tests. The midterm primary end point was activity limitations within 6 months after TKR assessed by the area under the receiver operating characteristic curve of the self-administered Western Ontario Questionnaire and McMaster Universities Osteoarthritis Index function subscale., Results: A total of 262 patients (mean [SD] age, 68.6 [8.0] years; 178 women [68%]) were randomized (131 to each group). A mean (SD) of 4 (1) days after surgery, 34 of 101 (34%) in the experimental group vs 26 of 95 (27%) in the control group achieved functional independence (risk ratio, 1.4; 97.5% CI, 0.9-2.1; P = .15). At 6 months, the mean (SD) area under the curve for the Western Ontario Questionnaire and McMaster Universities Osteoarthritis Index function subscale was 38.1 (16.5) mm2 in the experimental group vs 40.6 (17.8) mm2 in the control group (absolute difference, -2.8 mm2; 97.5% CI, -7.8 to 2.3; P = .31 after multiple imputation). No differences were found in secondary outcomes., Conclusions and Relevance: This randomized clinical trial found no evidence that multidisciplinary prehabilitation before TKR for osteoarthritis improves short-term functional independence or reduces midterm activity limitations after surgery., Trial Registration: ClinicalTrials.gov Identifier: NCT01671917.

Physical activity is defined as movement of the body resulting from muscle contraction and inducing energy expenditure. It can be adapted to a person's health status and have the objective of maintaining or improving health status. The link between sedentary lifestyle and the severity of symptoms in osteoarthritis is now well established, making adapted physical activity (APA) a first-line targeted treatment in osteoarthritis, in order to fight against the effects of a sedentary lifestyle, regardless of the phenotype or stage of the disease. The latest recommendations from EULAR, ACR and OARSI consider APA, in the form of structured exercise programmes for muscle strengthening, joint mobility, proprioception and aerobic exercises, as the core treatment for people with osteoarthritis. The benefits of APA in reducing pain and activity limitations in the short, mid and long terms in osteoarthritis, especially of the lower limbs, has been demonstrated in high-level clinical trials and meta-analyses, with effect sizes comparable to those observed with pharmacological treatments. In clinical practice, the prescription of APA in people with osteoarthritis should be encouraged further. Particular attention should also be paid to patients' adherence in the long term., (Copyright © 2021 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To establish recommendations for pharmacological treatment of knee osteoarthritis specific to France., Methods: On behalf of the French Society of Rheumatology (SFR), a bibliography group analyzed the literature on the efficacy and safety of each pharmacological treatment for knee osteoarthritis. This group joined a multidisciplinary working group to draw up recommendations. Strength of recommendation and quality of evidence level were assigned to each recommendation. A review committee gave its level of agreement., Results: Five general principles were established: 1) need to combine pharmacological and non-pharmacological treatments, 2) personalization of treatment, 3) symptomatic and/or functional aim of pharmacological treatments, 4) need to regularly re-assess the treatments and 5) discussion about arthroplasty if medical treatment fails. Six recommendations involved oral treatments: 1) paracetamol should not necessarily be prescribed systematically and/or continuously, 2) NSAIDs, possibly as first-line, 3) weak opioids, 4) strong opioids, 5) symptomatic slow-acting drugs of osteoarthritis, and 6) duloxetine (off-label use). Two recommendations involved topical agents (NSAIDs and capsaicin<1%). Three recommendations involved intra-articular treatments: corticosteroid or hyaluronic acid injections that can be proposed to patients. The experts did not draw a conclusion about the benefits of platelet-rich plasma injections., Conclusion: These are the first recommendations of the SFR on the pharmacological treatment of knee osteoarthritis., (Copyright © 2020 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) sought to revisit the 2014 algorithm recommendations for knee osteoarthritis (OA), in light of recent efficacy and safety evidence, in order to develop an updated stepwise algorithm that provides practical guidance for the prescribing physician that is applicable in Europe and internationally., Methods: Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process, a summary of evidence document for each intervention in OA was provided to all members of an ESCEO working group, who were required to evaluate and vote on the strength of recommendation for each intervention. Based on the evidence collected, and on the strength of recommendations afforded by consensus of the working group, the final algorithm was constructed., Results: An algorithm for management of knee OA comprising a stepwise approach and incorporating consensus on 15 treatment recommendations was prepared by the ESCEO working group. Both "strong" and "weak" recommendations were afforded to different interventions. The algorithm highlights the continued importance of non-pharmacological interventions throughout the management of OA. Benefits and limitations of different pharmacological treatments are explored in this article, with particular emphasis on safety issues highlighted by recent literature analyses., Conclusions: The updated ESCEO stepwise algorithm, developed by consensus from clinical experts in OA and informed by available evidence for the benefits and harms of various treatments, provides practical, current guidance that will enable clinicians to deliver patient-centric care in OA practice., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To develop a decision-making tool (DMT) to facilitate the prescription of knee orthoses for patients with osteoarthritis (OA) in daily practice., Methods: A steering committee gathered a multidisciplinary task force experienced in OA management/clinical research. Two members performed a literature review with qualitative analysis of the highest-quality randomized controlled trials and practice guidelines to confirm evidence concerning knee orthosis for OA. A first DMT draft was presented to the task force in a 1-day meeting in January 2016. The first version of the DMT was criticized and discussed regarding everyday practice issues. Every step was discussed and amended until consensus agreement was achieved within the task force. Then 4 successive consultation rounds occurred by electronic communication, first with primary- and secondary-care physicians, then with international experts. All corrections and suggestions by each member were shared with the rest of the task force and included to reach final consensus. The final version was validated by the steering committee., Results: The definition and indication of several types of knee orthoses (sleeve, patello-femoral, hinged or unicompartmental offloading braces) were detailed. Orthoses may be proposed in addition to first-line non-pharmacological treatment if patient acceptance is considered good. At every step, a specific clinical assessment is needed., Discussion/conclusion: Based on the latest high-level evidence, practice guidelines, and an expert panel, a DMT to facilitate daily practice prescription of knee orthoses for OA patients was designed. An evaluation of DMT implementation in a wide range of health professionals is still needed., (Copyright © 2018 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Osteoarthritis (OA) pathophysiology is driven in part by joint inflammation. Resveratrol has in vitro anti-inflammatory properties. We aim to assess the efficacy of oral resveratrol for knee pain at 3 months in people with knee OA., Methods and Analysis: We will conduct a randomised double-blind placebo-controlled trial. Overall, 164 individuals with knee OA fulfilling 1986 American College of Rheumatology criteria will be recruited in three tertiary care centres in France and randomised to receive oral resveratrol, 40 mg (two caplets) two times per day for 1 week, then 20 mg (one caplet) two times per day or a matching placebo for a total of 6 months. Randomisation will be centralised and stratified by centre. The allocation ratio of assignments will be 1:1. The primary outcome will be the mean change from baseline in knee pain on a self-administered 11-point pain Numeric Rating Scale at 3 months. Secondary outcomes will be the mean change in knee pain at 6 months, the function subscore of the Western Ontario and McMaster Universities Arthritis Index score, patient global assessment, proportion of responders according to the Osteoarthritis Research Society International-Outcome Measures in Rheumatology criteria at 3 and 6 months, and self-reported number of intra-articular injections of corticosteroids or hyaluronic acid and consumption of analgesics and non-steroidal anti-inflammatory drugs since the last contact. Other interventions will be allowed and self-reported. Adherence will be monitored by capsule counts and a booklet and adverse events recorded at 3 and 6 months. Statisticians, treating physicians and participants will be blinded to the allocated treatment., Ethics and Dissemination: The oral resveratrol in knee osteoarthritis (ARTHROL) trial has been authorised by the AgenceNationale de Sécurité du Médicament et des Produits de Santé and ethics were approved by the Comité deProtection des Personnes Île-de-France III. The findings of the study will be published in a peer-reviewed journal and disseminated at conferences. The design of ARTHROL will warrant the translation of its findings into clinical practice., Trial Registration Number: ClinicalTrials.gov identifier: NCT02905799. Pre-results. First received: 14 September 2016. Last updated: 16 September 2016. Status: not yet recruiting., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: International guidelines recommend that the management of knee osteoarthritis (OA) combine both nonpharmacological and pharmacological interventions. Intra-articular (IA) therapies are considered part of this multimodal approach and are well-established Food and Drug Administration (FDA) and European Medicines Agency (EMA)-approved treatments. Areas covered: Safety data for knee OA, including IA corticosteroids, hyaluronic acid, platelet-rich plasma and botulinum toxin are critically reviewed, and evidence- and pratice-based measures to improve safety of IA therapies are discussed. Expert opinion: The incidence of AEs attributable to IA therapies across clinical trials in knee OA is very low, and barely reaches significance when compared to the incidence of AEs in the comparator group. These events are exceptionally serious. Mild differences between products have been inconsistently reported mainly for IA HA. One can distinguish self-limited AEs such as post-injection pain and swelling that are the most frequently reported AEs, from AEs that are not self-limited but rare such as septic arthritis. The safety of IA therapies can be improved by applying simple measures designed to prevent AEs. However, even though no specific safety concerns have been raised to date about IA therapies, the quality of evidence is low, and there is a need to improve the monitoring and reporting of safety data from clinical trials and post-marketing surveillance.

Background: Viscosupplementation is a symptomatic treatment of the knee osteoarthritis based on the intra-articular injection of hyaluronic acid (IAHA). Although many studies have investigated its effect on symptoms, few clinical studies have focused on its effects on biologicals markers of cartilage metabolism. In this study, we assessed the effect of an intra-articular injection of a reticulated hyaluronic acid compound on the level of a specific biomarker of type II collagen degradation., Methods: Eighty one patients with symptomatic knee osteoarthritis were included in this randomized placebo controlled trial testing a reticulated hyaluronic acid (HA) with mannitol (KARTILAGE® CROSS, 16 mg/ml, one single injection of 2.2 mL; IAHA) versus saline solution. Primary outcome was the percentage of patients with a reduction of at least 10 nmol/l of serum Coll2-1 between baseline and day 90 (D90, 3 months after injection). Secondary outcomes concerned clinical evaluation and tolerance to the study product., Results: A significant effect of IAHA was revealed by the sensitivity analysis of the decrease in cartilage marker. In the intention-to-treat population, the percentage of patients showing a decrease in the levels of serum Coll2-1 between inclusion and D90 showed was higher in HA (56.8%) than in placebo group (28.6%; P = 0.01). The same significant difference was observed between groups in the per protocol population (57.1% vs 29.0%; P = 0.02) corresponding to all patients having received the intra-articular injection (IA), being evaluated for the primary outcome on D-10 and D90, and with no major defined deviation. No significant differences between groups were observed on the changes in function (Lequesne index) or pain and on the number of adverse events., Conclusions: This is the first randomized double-blind placebo controlled trial showing that IA injection of reticulated HA with mannitol in knee osteoarthritis patients can reduce the serum levels of Coll2-1, a marker specific of type II collagen degradation. This finding suggests that IAHA may have a beneficial effect on cartilage degradation and that Coll2-1 could be used for the assessment of a single intra-articular treatment in clinical trials., Trial Registration: NCT02951585 ; clinicaltrial.gov. Retrospectively registered on October 28, 2016.

Background: The McMaster-Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR) measurement of function may be more comprehensive and add useful information about disability than traditional fixed-item questionnaires, especially about issues that really matter to the patient, for developing personalized medicine., Objectives: We aimed to assess priorities in disability and restriction in participation in patients with disabling knee osteoarthritis (OA) by the MACTAR and evaluate its validity and responsiveness., Methods: We evaluated 127 in- and outpatients with knee OA in two tertiary care teaching hospitals between August 2010 and July 2012 by using the MACTAR, the Western Ontario and McMaster Universities Osteoarthritis Index, Lequesne scale, Fear Avoidance Beliefs Questionnaire, a life satisfaction score and pain, global assessment of disease activity and functional impairment scores on a numerical rating scale. Validity was assessed by Pearson correlation and responsiveness by the standardized response mean (SRM) and effect size (ES)., Results: Patients ranked 35 different activities by the MACTAR; the 3 domains of the International Classification of Functioning, Disability and Health most often identified were mobility (cited 233 times, 52.3%); community, social and civic life (cited 122 times, 27.4%); and domestic life (cited 64 times, 14.4%). The MACTAR score was best correlated with functional impairment (r=0.5). Convergent and divergent validity was as expected. In all, 108 patients completed a 6-month follow-up evaluation: 27 patients shifted their priorities at 6 months, for a decrease in SRM and ES. The SRM (0.64) and ES (0.92) for the MACTAR without shifts in priorities were the highest among the outcome measures tested; for patients considering their condition improved, the values were 0.85 and 1.17, respectively., Conclusions: For assessing priorities in disability and restriction in participation among patients with knee OA, the MACTAR has acceptable validity and responsiveness., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

In this critical narrative review, we examine the role of physical activity (PA), recreational and elite sports in the development of knee/hip osteoarthritis (OA), taking into account the role of injury in this relationship. The process of article selection was unsystematic. Articles were selected on the basis of the authors' expertise, self-knowledge, and reflective practice. In the general adult population, self-reported diagnosis of knee/hip OA was not associated with low, moderate or high levels of PA. For studies using radiographic knee/hip OA as a primary outcome, the incidence of asymptomatic radiographic OA was higher for subjects with the highest quartile of usual PA than the least active subjects. The risk of incident radiographic knee/hip OA features was increased for subjects with a history of regular sports participation (for osteophyte formation but not joint space narrowing). This risk depended on the type of sport (team and power sports but not endurance and running), and certain conditions (high level of practice) were closely related to the risk of injury. The prevalence of radiographic OA was significantly higher, especially the presence of osteophytes, in former elite athletes than controls. The risk of OA was higher with participation in mixed sports, especially soccer or power sports, than endurance sport. However, the prevalence of clinical OA between former elite athletes and controls was similar, with less hip/knee disability in former athletes. Moderate daily recreational or sport activities, whatever the type of sport, are not a consistent risk factor for clinical or radiographic knee/hip OA. Risk of injury in different sports may be the key factor to understanding the risk of OA related to sport., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Pharmacological treatments are widely recommended in international guidelines for management of osteoarthritis (OA). However, the use of intra-articular (IA) therapies of diverse active drugs remains controversial. We critically reviewed studies of the efficacy and safety of IA injections of corticosteroids (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and botulinum toxin A (BTA) and evidence-based international recommendations for their use in treating knee OA. The process of article selection was unsystematic. Articles were selected on the basis of authors' expertise, self-knowledge, and reflective practice. Only studies assessing knee OA were included. IA CS and HA injections were conditionally to fully recommended for treating knee OA. No recommendations have been formulated for IA PRP or BTA. The evidence remains inconsistent and controversial for the use of IA therapies for knee OA. The characteristics of and selection criteria for the OA population that would likely benefit from these therapies need to be identified. Accurately phenotyping and selecting patients is mandatory in future randomized controlled trials. Therefore, efficacy and safety meta-analyses should be performed, as should qualitative and sensitivity analyses of published trial results., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends intra-articular (IA) hyaluronic acid (HA) for management of knee osteoarthritis (OA) as second-line treatment in patients who remain symptomatic despite use of non-steroidal anti-inflammatory drugs (NSAIDs). This recommendation is based upon accumulating evidence that IA HA provides a significant benefit in knee OA. There is good evidence that IA HA injections reduce pain and increase function in knee OA, and the benefits are long-lasting as compared with IA corticosteroids. Evidence from real-life studies of repeat courses of IA HA demonstrates an improvement in pain or function lasting up to 40 months (12 months after the last injection cycle), a reduction in use of concomitant analgesia by up to 50%, and suggests that there may be a delay in the need for total knee replacement (TKR) of around 2 years. The clinical benefit of IA HA on knee OA may be 2-fold: (i) mechanical viscosupplementation of the joint (allowing lubrication and shock absorption) and (ii) the re-establishment of joint homeostasis through induction of endogenous HA production, which continues long after the exogenous injection has left the joint. The magnitude of the clinical effect may be different for different HA products, but this has not been proven so far and requires further investigation. IA HA injections are generally considered to be safe, although a slightly higher number of cases of local reactions and post-injection non-septic arthritis has been reported with high molecular weight cross-linked HAs. The use of IA HA in knee OA patients with mild-moderate disease, and for more severe patients wishing to delay TKR surgery, is recommended by the ESCEO task force. Further investigation into the OA patient types most likely to benefit from IA HA is warranted. Viscosupplementation with IA HA is a safe and effective component of the multi-modal management of knee OA., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) published a treatment algorithm for the management of knee osteoarthritis (OA) in 2014, which provides practical guidance for the prioritization of interventions. Further analysis of real-world data for OA provides additional evidence in support of pharmacological interventions, in terms of management of OA pain and function, avoidance of adverse events, disease-modifying effects and long-term outcomes, e.g., delay of total joint replacement surgery, and pharmacoeconomic factors such as reduction in healthcare resource utilization. This article provides an updated assessment of the literature for selected interventions in OA, focusing on real-life data, with the aim of providing easy-to-follow advice on how to establish a treatment flow in patients with knee OA in primary care clinical practice, in support of the clinicians' individualized assessment of the patient. In step 1, background maintenance therapy with symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) is recommended, for which high-quality evidence is provided only for the prescription formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. Paracetamol may be added for rescue analgesia only, due to limited efficacy and increasing safety signals. Topical non-steroidal anti-inflammatory drugs (NSAIDs) may provide additional symptomatic treatment with the same degree of efficacy as oral NSAIDs without the systemic safety concerns. Oral NSAIDs maintain a central role in step 2 advanced management of persistent symptoms. However, oral NSAIDs are highly heterogeneous in terms of gastrointestinal and cardiovascular safety profile, and patient stratification with careful treatment selection is advocated to maximize the risk:benefit ratio. Intra-articular hyaluronic acid as a next step provides sustained clinical benefit with effects lasting up to 6 months after a short-course of weekly injections. As a last step before surgery, the slow titration of sustained-release tramadol, a weak opioid, affords sustained analgesia with improved tolerability., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate the prevalence of inadequate pain relief (IPR) among patients with symptomatic knee OA prescribed analgesic therapy and to characterize patients with IPR., Methods: Patients ≥50 years old with physician-diagnosed knee OA who had taken topical or oral pain medication for at least 14 days were recruited for this prospective non-interventional study in six European countries. Pain and function were assessed using the Brief Pain Inventory (BPI) and the WOMAC; quality of life (QoL) was assessed using the 12-item short form. IPR was defined as an average pain score of >4 out of 10 on BPI question 5., Results: Of 1187 patients enrolled, 68% were female and the mean age was 68 years (s.d. 9); 639 (54%) met the definition of IPR. Patient responses for the BPI average pain question were well correlated with responses on the WOMAC pain subscale (Spearman r = 0.64, P < 0.001). In multivariate logistic regression, patients with IPR had greater odds of being female [adjusted odds ratio (adjOR) 1.90 (95% CI 1.46, 2.48)] and having OA in both knees [adjOR 1.48 (95% CI 1.15, 1.90)], higher BMI, longer OA duration, depression or diabetes. Patients with IPR (vs non-IPR) were more likely to have worse QoL, greater function loss and greater pain interference., Conclusion: IPR is common among patients with knee OA requiring analgesics and is associated with large functional loss and impaired QoL. Patients at particular risk of IPR, as characterized in this study, may require greater attention towards their analgesic treatment options., Trial Registration: https://clinicaltrials.gov/ (NCT01294696)., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, and allied healthcare professionals worldwide., Method: Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1-10 risk and benefit scores., Results: Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation)., Conclusion: These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

To measure the evolution of the serum levels of specific Osteoarthritis (OA) biomarker, Coll2-1 and Coll2-1 NO₂ in knee osteoarthritic patients after viscosupplementation (VS). Fifty-one patients with unilateral symptomatic knee were recruited for this prospective open label study. They received three intra-articular injections of 2 ml of hyaluronic acid (Hylan GF-20) and were followed for 3 months. Walking pain was evaluated and serum samples were taken at each visit. Coll2-1 and Coll2-1 NO₂ were measured in the serum using specific immunoassays. Variations over time of each parameter and predictive factor of response were studied. Forty-five patients were analyzed. The serum concentrations of Coll2-1 and Coll2-1 NO₂ were significantly higher in KL III/IV patients compared to KL I/II patients at baseline and decreased systematically over time after VS. Its effect was ever more pronounced in patients with KL III/IV. The serum concentration of Coll2-1 was significantly lower at baseline in responders than in non-responders. This study suggests a rapid slowdown of type II collagen degradation and joint inflammation after VS with Hylan G-20 and gives additional information for the validation of accurate biomarkers for OA. The serum level of Coll2-1 appeared to be a predictive factor for response to treatment., (Copyright © 2013 Orthopaedic Research Society.)

Objective: Hypoxia/reoxygenation (H/R) is an important feature in the osteoarthritis (OA) physiopathology. Nitric oxide (NO) is a significant proinflammatory mediator in the inflamed synovium. The purpose of this study was to investigate the effects of H/R on inducible NO synthase (iNOS) activity and expression in OA synoviocytes. In addition we studied the relationship between nitrosative stress and NADPH oxidase (NOX) in such conditions., Methods: Human cultured synoviocytes from OA patients were treated for 24 h with interleukin 1-β (IL-1β), tumour necrosis factor α (TNF-α) or neither; for the last 6 h, they were submitted to either normoxia or three periods of 1-h of hypoxia followed by 1-h of reoxygenation. ·NO metabolism (iNOS expression, nitrite and peroxynitrite measurements) was investigated. Furthermore, superoxide anion O2(·-) production, NOX subunit expression and nitrosylation were also assessed., Results: iNOS expression and nitrite (but not peroxynitrite) production were ~0.20 to ~0.12 nmol min(-1) mg proteins(-1) (P < 0.05), while NOXs' subunit expression and p47-phox phosphorylation were increased. NOXs and p47-phox were dramatically nitrosylated under H/R conditions (P < 0.05 vs normoxia). Using NOS inhibitors under H/R conditions, p47-phox nitrosylation was prevented and O2(·-) production was restored at normoxic levels (0.21 nmol min(-1) mg of proteins(-1))., Conclusions: Our results provide evidence for an up-regulation of iNOS activity in OA synoviocytes under H/R conditions, associated to a down-regulation of NOX activity through nitrosylation. These findings highlight the importance of radical production to OA pathogenesis, and appraise the metabolic modifications of synovial cells under hypoxia., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Introduction: Intra-articular injections of hyaluronic acid (HA) could have potential interest in therapy of acute knee trauma injuries, but few results are available in humans., Objective: We reviewed the literature for animal studies of intra-articular HA injections after knee trauma injury to determine the interest of human clinical research into and/or use of such injections for knee trauma., Methods: Systematic literature search on MEDLINE for studies involving animal models of osteoarthritis created by acute knee trauma injury, with HA injections beginning during the 2 weeks after injury., Results: The search revealed 14 studies with a high methodological quality: 7 related to meniscus injury, 3 ACL injury, 1 combined ACL-meniscus injury and 3 cartilage injury. The animal models were rabbits in 10 studies. Four studies demonstrated positive effects and 3 moderate effects of intra-articular HA injection for meniscus injury; 1 positive effects and 2 no effect for ACL injury; 1 positive effects for combined ACL-meniscus injury; and 2 moderate effects and 1 no effect for cartilage injury., Conclusions: With a high strength of recommendation, intra-articular HA injections in animal models with meniscus injury improved the healing process and/or had a protective role in articular cartilage, a slightly protective role in ACL injury animal models and low or no effect on healing in articular cartilage injury animal models., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: To develop a questionnaire assessing the expectations of patients regarding management of osteoarthritis (OA of the knee., Methods: A detailed document reporting on a qualitative analysis of interviews of patients with knee OA was sent to experts and a Delphi procedure was adopted for item generation. Eighty physicians (64 general practitioners, 16 rheumatologists) recruited 566 patients with knee OA to test the provisional questionnaire. Items were reduced according to their metric properties and exploratory factor analysis. The reliability of the questionnaire was tested by the Cronbach α coefficient. Construct validity was tested by divergent validity and confirmatory factor analysis. Test-retest reliability was assessed by the intraclass correlation coefficient (ICC) and the Bland-Altman technique., Results: Sixty items were extracted from analysis of the interview data. The experts needed three Delphi rounds to obtain consensus on a 33-item provisional questionnaire. The item reduction process resulted in an 18-item questionnaire. Exploratory factor analysis extracted three main factors: factor 1 represented expectations for education, factor 2 expectations for information on technical and human support, and factor 3 expectations for physician empathy. The Cronbach α coefficient was 0.91 (95% CI 0.89 to 0.92). Expected divergent validity was observed. Confirmation factor analyses confirmed higher intra-factor than inter-factor correlations. Test-retest reliability was good with an ICC of 0.79, and Bland-Altman analysis did not reveal a systematic trend., Conclusions: A new 18-item questionnaire assessing patient expectations of management of knee OA by their physicians is proposed. The questionnaire has good content and construct validity.

Objective: We aimed to develop a questionnaire assessing fears and beliefs of patients with knee OA., Design: We sent a detailed document reporting on a qualitative analysis of interviews of patients with knee OA to experts, and a Delphi procedure was adopted for item generation. Then, 80 physicians recruited 566 patients with knee OA to test the provisional questionnaire. Items were reduced according to their metric properties and exploratory factor analysis. Reliability was tested by the Cronbach α coefficient. Construct validity was tested by divergent validity and confirmatory factor analysis. Test-retest reliability was assessed by the intra-class correlation coefficient (ICC) and the Bland and Altman technique., Results: 137 items were extracted from analysis of the interview data. Three Delphi rounds were needed to obtain consensus on a 25-item provisional questionnaire. The item-reduction process resulted in an 11-item questionnaire. Selected items represented fears and beliefs about daily living activities (3 items), fears and beliefs about physicians (4 items), fears and beliefs about the disease (2 items), and fears and beliefs about sports and leisure activities (2 items). The Cronbach α coefficient of global score was 0.85. We observed expected divergent validity. Confirmation factor analyses confirmed higher intra-factor than inter-factor correlations. Test-retest reliability was good, with an ICC of 0.81, and Bland and Altman analysis did not reveal a systematic trend., Conclusions: We propose an 11-item questionnaire assessing patients' fears and beliefs concerning knee OA with good content and construct validity.

Objectives: To compare the effects of an intermediate molecular weight (MW) intra-articular hyaluronic acid (HA) with a low MW product on knee osteoarthritis (OA) symptoms., Methods: Patients with symptomatic knee OA were enrolled inarandomised, controlled, double-blind, parallel-group, non-inferiority trial with the possibility to shift to superiority. Patients were randomised to GO-ON(MW 800-1500 kD, 25 mg/2.5 ml) or Hyalgan(MW 500-730 kD, 20 mg/2 ml) injected at 3-weekly intervals. The primary outcome was 6-month change in the WOMAC pain subscale (0-100 mm). Sample size was calculated on a non-inferiority margin of 9 mm, lower than the minimum perceptible clinical improvement. Secondary endpoints included OARSI-OMERACT responder rates, Results: The intention-to-treat (ITT) and per-protocol (PP) populations consisted of 217 and 209 patients and 171 and 172 patients in the GO-ON and Hyalgan groups, respectively. ITT WOMAC pain of 47.5±1.0(SE) and 48.8±1.0 mm decreased by 22.9±1.4 mm with GO-ON and 18.4±1.5 mm with Hyalgan after 6 months. The primary analysis was conducted in the PP population followed by the ITT population.Mean (95% CI) differences in WOMAC pain change were 5.2 (0.9 to 9.6)mm and 4.5 (0.5 to 8.5)mm, respectively,favouring GO-ON, satisfying the claim for non-inferiority (lower limit>-9 mm) and for statistical superiority (95% CI all>0, p=0.021). Ahigher proportion of OARSI/OMERACT responders was observed with GO-ONthan with Hyalgan (73.3% vs58.4%, p=0.001). Both preparations were well tolerated., Conclusions: Treatment with 3-weekly injections of intermediate MW HA may be superior to low MW HA on knee OA symptoms over 6 months, with similar safety.

The aim of the study was to investigate the effect of hyaluronic acid (HA) intra articular injections (IA) on osteoarthritis (OA) biomarkers in patients with knee OA. Prospective open label study. Fifty-one patients with unilateral symptomatic K-OA received IA injections of 2mL of HA on days (D) 1, 7, 14 and were followed 3 months. At D-15 patients were examined and X-rays performed, to exclude patients with bilateral K-OA, or those with more than three symptomatic OA joints. From 15 days (D-15) before the first injection to D90 concomitant therapies were unchanged. Walking pain (WP) on VAS was obtained at each visit. Urine (U) and serum (S) samples were obtained at D-15, D1, D30, and D90. S-C2C, S-Cartilage oligomeric matrix protein, S-HA, S-CS 846 epitope, S-type II collagen propeptide, and U-type II collagen C telopeptide (U-CTX II/creatinin) were assayed. Predictive factors of response were analyzed using logistic regression. Correlations between variables were obtained using Spearman test. Forty-five patients were analyzed. Between D-15 and D1 there was no difference for any biomarkers At D1, WP (SD) was correlated with U-CTX II/creat (p = 0.006). Between D1 and D90: U-CTX II/creat decreased significantly. After adjustment for confounding variables there was a significant correlation between clinical response and U-CTX II/creat variation. U-CTX II and S-HA at baseline were independently predictive of clinical response. This study showed that 90 days after HA IA injections, U-CTX II levels significantly decrease compared to baseline, suggesting a slowdown of type II collagen degradation., (Copyright © 2011 Orthopaedic Research Society.)

Purpose: To identify the views of patients and care providers regarding the management of knee osteoarthritis (OA) and to reveal potential obstacles to improving health care strategies., Methods: We performed a qualitative study based on semi-structured interviews of a stratified sample of 81 patients (59 women) and 29 practitioners (8 women, 11 general practitioners [GPs], 6 rheumatologists, 4 orthopedic surgeons, and 8 [4 GPs] delivering alternative medicine)., Results: Two main domains of patient views were identified: one about the patient-physician relationship and the other about treatments. Patients feel that their complaints are not taken seriously. They also feel that practitioners act as technicians, paying more attention to the knee than to the individual, and they consider that not enough time is spent on information and counseling. They have negative perceptions of drugs and a feeling of medical uncertainty about OA, which leads to less compliance with treatment and a switch to alternative medicine. Patients believe that knee OA is an inevitable illness associated with age, that not much can be done to modify its evolution, that treatments are of little help, and that practitioners have not much to propose. They express unrealistic fears about the impact of knee OA on daily and social life. Practitioners' views differ from those of patients. Physicians emphasize the difficulty in elaborating treatment strategies and the need for a tool to help in treatment choice., Conclusions: This qualitative study suggests several ways to improve the patient-practitioner relationship and the efficacy of treatment strategies, by increasing their acceptability and compliance. Providing adapted and formalized information to patients, adopting more global assessment and therapeutic approaches, and dealing more accurately with patients' paradoxal representation of drug therapy are main factors of improvement that should be addressed.

Objective: To assess therapeutic education program impact for lower limb osteoarthritis (OA) at both the medical and surgical stage. Factors limiting efficiency and implementation of these programs such as patients' beliefs will be highlighted., Method: A non systematic literature review on Medline and Cochrane Library databases from 1966 to 2009 using following key words "knee/hip osteoarthritis", "self-care/therapeutic education", "total hip/knee replacement/arthroplasty", "patients' beliefs" is conducted. Clinical trials and randomized clinical trials, as well as literature reviews and practice guidelines, published in English and French will be analysed., Results: Therapeutic education is part of the non-pharmacological management of chronic illnesses such as OA. The aim of education at an early stage of OA is to change patients' lifestyle, especially the regular practice of physical activity and weight reduction. Fears and avoidance assessment is necessary before patients' education process. When a surgical option is considered, the aim of education is to hasten patient recovery, improve autonomy after surgery, facilitate the return home and reduce the rate of transfer to a rehabilitation unit., Conclusion: The efficacy of therapeutic education could be optimised for the management of OA with use of standardized rules and methods to deliver information and education. One way to improve therapeutic education in the management of OA could be to propose dedicated continuing medical education programs supported by specific economic sources for health care professionals., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Purpose of Review: Recommendations for nonpharmacological treatment for knee osteoarthritis are based mainly on modifying the symptomatic loading joint compartment. Braces are one of the modalities used to modify joint loading. Knee osteoarthritis braces consist of rest orthoses, knee sleeves, and unloading-knee braces. This review examines the most recent publications regarding the various bracing modalities proposed for different knee osteoarthritis compartments., Recent Findings: The effectiveness of rest orthoses for lower-limb osteoarthritis has not been studied in clinical trials. Knee sleeves are elastic nonadhesive orthoses associated with various devices aimed at patellar or femoro-tibial stabilization. They may decrease knee pain. Unloading-knee braces are functional devices composed of external stems, hinges, and straps. Several recent biomechanical studies have established the effectiveness of modifying loading with unloading-knee braces. Such braces may decrease knee pain, and improve knee function., Summary: Braces are recommended for treating knee osteoarthritis. The different bracing modalities that are available must be adapted to the symptomatic knee osteoarthritis compartment. This nonpharmacological approach must be added to the other nonpharmacological, and pharmacological modalities to decrease pain and improve function and thereby increase the quality of life of osteoarthritis patients. The structural effect of bracing has not yet been evaluated. High-quality clinical trials of the addition of various treatment modalities for knee osteoarthritis are still necessary.

For the most part, non-pharmacological approaches are recommended for osteoarthritis treatment. This recommendation is based mainly on biomechanical observations leading to a modulation of the symptomatic loading joint. Approaches include orthoses, insoles, exercise, diet and patient education. The approach used for each osteoarthritis site must be adapted for the individual patient. Here, we use an evidence-based approach, including the European League Against Rheumatism (EULAR) and Osteoarthritis Research Society International (OARSI) recommendations, to summarise the non-pharmacological treatments available for knee, hip and hand osteoarthritis and to help the physician in daily clinical practice., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Objective: To develop clinical practice guidelines concerning the use of bracing--rest orthosis, knee sleeves and unloading knee braces--for knee osteoarthritis., Methods: The French Physical Medicine and Rehabilitation Society (SOFMER) methodology, associating a systematic literature review, collection of everyday clinical practice, and external review by multidisciplinary expert panel, was used., Results: Few high-level studies of bracing for knee osteoarthritis were found. No evidence exists for the effectiveness of rest orthosis. Evidence for knee sleeves suggests that they decrease pain in knee osteoarthritis, and their use is associated with subjective improvement. These actions do not appear to depend on a local thermal effect. The effectiveness of knee sleeves for disability is not demonstrated for knee osteoarthritis. Short- and mid-term follow-up indicates that valgus knee bracing decreases pain and disability in medial knee osteoarthritis, appears to be more effective than knee sleeves, and improves quality of life, knee proprioception, quadriceps strength, and gait symmetry, and decreases compressive loads in the medial femoro-tibial compartment. However, results of response to valgus knee bracing remain inconsistent; discomfort and side effects can result. Thrombophlebitis of the lower limbs has been reported with the braces. Braces, whatever kind, are infrequently prescribed in clinical practice for osteoarthritis of the lower limbs., Conclusion: Modest evidence exists for the effectiveness of bracing--rest orthosis, knee sleeves and unloading knee braces--for knee osteoarthritis, with only low level recommendations for its use. Braces are prescribed infrequently in French clinical practice for osteoarthritis of the knee. Randomized clinical trials concerning bracing in knee osteoarthritis are still necessary.

Aims of the Study: To examine the clinical and demographic correlates of pain intensity in patients with hip and knee osteoarthritis (OA)., Patients and Methods: In a national cross-sectional survey, 1811 general practitioners recruited and assessed 5324 patients with hip and knee OA. The patients rated the intensity of pain at rest, on movement over the last 24 hours, and during the last 8 days on 11-point numeric rating scales. The patients also completed the Western Ontario and McMaster Universities Osteoarthritis Index. Clinical and demographic correlates of pain intensity and function were investigated by univariate, stepwise multiple logistic regression and odds ratio analyses., Results: Data for 4598 patients were analyzed (86.4% of surveyed patients). The mean pain intensity was 4.1+/-2.2 at rest, 5.9+/-1.8 on movement during the last 24 hours, and 5.1+/-1.7 during the last 8 days. Pain on movement during the last 24 hours and during the last 8 days showed a strong positive correlation (r=0.78; P<0.0001), which suggests that the most of the latter pain was related to movement. Patients with knee or hip OA did not differ in pain intensity, but patients with both joints affected rated pain intensity significantly higher than did those with only 1 affected joint [4.6+/-2.1, 6.3+/-1.8, and 5.5+/-1.6, for the 3 pain assessments, respectively (P>0.01)]. Patients with high pain ratings were more likely to be women, be older than 75 years, and have a body mass index of greater than 40 kg/m. In addition, patients who were retired, unemployed, farmers, or widowed, or had a long duration of OA gave high pain ratings. Patients with regular physical activities reported less intense pain., Conclusions: Pain intensity ratings for patients with lower limb OA differed significantly with respect to sex, age, body mass index, physical activity, professional activity, marital status, and conditions of assessment.

Objective: To develop clinical practice guidelines for the use of foot orthotics (FO) in the treatment of knee and hip osteoarthritis., Method: The SOFMER (French Physical Medicine and Rehabilitation Society) methodology, associating a systematic review of the literature, input from every day clinical practice and external review by a multidisciplinary expert committee, was used. The selected analysis criteria were pain, disability, medications used and X-ray evolution of osteoarthritis. The recommendations are classified according to the level of proof in Grade A, B or C according to the French National Agency for Health Accreditation and Evaluation (NAHAE)., Results: In medial knee osteoarthritis, foot pronation orthotics--when there are no contraindications--can be proposed for their symptomatic impact, especially in the decrease of NSAIDs consumption (Grade B). To this day, there is no evidence of a structural or functional impact on osteoarthritis (Grade B). Outside of this specific clinical framework, there is no validated indication for prescribing foot orthotics in the treatment of knee or hip OA (Grade C)., Conclusion: It is necessary to have further randomized controlled trials to better define the indication of Foot orthotics (severity of knee OA, genu varum), test the efficacy of other orthoses such as cushioning FO. The long-term side effects, mainly on the external femorotibial compartment could also be assessed. A medical and economical assessment of FO prescriptions is also quite necessary.

Objective: To study pain coping strategies in patients with hip and knee osteoarthritis (OA), and to assess the psychometric qualities of the French version of the Pain Coping Inventory (PCI)., Methods: We conducted a national, cross-sectional survey in a primary care setting in France. A total of 1,811 general practitioners included 5,324 patients with hip and knee OA who completed several questionnaires, including the PCI, which assesses ability to cope with pain., Results: The records of 4,719 (86.4%) patients were analyzed (knee 2,781; hip 1,553; hip and knee 385). Supporting the structure of the original questionnaire, we found that the 33 PCI questionnaire items could be grouped into 3 domains defining active coping strategies and 3 defining passive coping strategies. Acceptable convergent validity was found for the PCI (Cronbach's alpha coefficient for each domain >0.68). Coping strategy scores were significantly higher in patients with both knee and hip involvement (mean +/- SD 2.3 +/- 0.4) than for patients with OA at 1 site (mean +/- SD 2.1 +/- 0.4), and in women compared with men (P < 0.001). The use of passive pain coping strategies increased with OA duration, and was greater in older and overweight patients, in patients with no current physical activity or major impairment, in retired and nonworking patients, and in patients who were not married, and to a lesser extent in patients with higher pain intensity. Compared with previous data, patients with OA demonstrated lower active and higher passive strategies than patients with rheumatoid arthritis and other chronic painful conditions., Conclusion: The PCI has good structural validity and is highly suitable for analyzing active and passive pain coping strategies in OA. In OA, active and passive coping strategies differ significantly as a function of age, body mass index, OA involvement, professional and marital status, sport activities, and OA duration, with pain intensity having a weaker effect.

Objective: To develop recommendations regarding adherence to physical therapy programs by patients with hip or knee osteoarthritis., Methods: We used the method recommended by the French Society for Physical and Rehabilitation Therapy (SOFMER), which combines a systematic literature review, a practice survey, and validation by a multidisciplinary panel of experts., Results: When setting up exercise programs for patients with lower limb osteoarthritis, measures should be taken to increase effectiveness by optimizing adherence. Patient selection is among these measures, as exercise programs are more likely to succeed in patients with a history of being physically active, a positive view of the suggested program, and/or favorable social and material conditions. Regardless of the type of exercise, the program should be tailored to exercise capacity and pain level (professional consensus). Patient adherence can be improved by explaining the expected results to the patient, asking the patient to keep a self-evaluation diary, conducting long-term evaluations (by phone or mail), and providing follow-up visits., Conclusion: Studies of adherence according to the type of exercise are needed. The relevance of widely used incentives in patients with hip or knee osteoarthritis should be evaluated in new therapeutic trials.

Objective: To assess disability and health-related quality of life (HRQoL) of patients with knee or hip OA in primary care and to determine factors associated with GPs' opinion that their patients will need prosthetic replacement within 1 year after the consultation., Design: A cross-sectional national survey., Setting: Primary care in France., Participants: 1471 GPs and 4183 patients with hip or knee OA., Measures: Pain on an 11-point numeric scale (0-10), disability on the Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) (1-100) and Lequesne index (0-24), and quality of life on the Medical Outcomes Study 36-item Short Form (MOS SF-36; 0-100)., Results: We analyzed records of 4121 patients (2540 knee, 1581 hip OA). Patients with knee or hip OA exhibited high and similar levels of pain (5.2+/-2.1 and 5.3+/-2.3) and disability (Lequesne score: 12.0+/-4.2 and 11.8+/-4.3; WOMAC score: 45.7+/-19.3 and 45.2+/-17.3) The decrease in HRQoL was similar for patients with either location of the disease. GPs more often considered that their patients with hip OA would need prosthetic replacement within 1 year (28.1%) than those with knee OA (15.8%). Most factors associated with GPs' opinion were identified for both locations of disease and were related to disability and pain levels., Conclusions: In the primary care setting, patients with knee or hip OA have similar, high disability levels and substantially low HRQoL. Patients' disability seems to play a central role in GPs' opinion of the need for their patients with either type of OA to undergo prosthetic replacement within 1 year.

Objective: To assess the interleukin 1 receptor antagonist (IL-1Ra)/IL-1beta ratio in synovial fluid (SF) of patients with knee osteoarthritis (OA) or rheumatoid arthritis (RA) to determine a possible relation between cytokine level and disease activity., Methods: IL-1beta and IL-1Ra concentrations were measured by ELISA in knee SF from patients with OA (n = 42) or RA (n = 11). For OA patients, pain and disability were assessed by a visual analog scale (VAS) and the Lequesne index. RA disease activity was assessed using the Disease Activity Score 28 Joint Count (DAS28)., Results: Patients with OA showed lower median levels of IL-1beta and IL-1Ra in SF than patients with RA (p < 0.001) but a higher IL-1Ra/IL-1beta ratio: 1793 (584-6221) versus 773.5 (187.64-1570.5) (p = 0.05). For patients with OA, the IL-1Ra/IL-1beta ratio was not associated with pain or disability. For patients with RA, the IL-1Ra/IL-1beta ratio and IL-1Ra and IL-1beta levels were related to SF white blood cell count., Conclusion: High endogenous IL-1Ra/IL-1beta ratio occurs in SF from knee OA and does not correlate with pain or Lequesne index. Our results suggest that intraarticular injection of IL-1Ra might be self-limited in patients with knee OA and a naturally high SF ratio.

Objectives: To develop clinical practice guidelines about the use of taping in the management of lower limb osteoarthritis., Method: We used the methodology advocated by the SOFMER (French Society for Physical and Rehabilitation Medicine), which combines a literature review, collection of data on current practice patterns, and validation of the recommendations by a multidisciplinary panel of experts. Our evaluation focused on the effectiveness of taping in relieving symptoms of lower limb osteoarthritis., Results: Ankle taping for osteoarthritis is not recommended, given the absence of published data and very low level of use in France. Few studies are available on knee taping for osteoarthritis., Conclusions: Published studies exhibit a number of methodological weaknesses. There is no strong evidence that taping is effective in knee osteoarthritis, and this treatment modality is rarely used in France. Therefore, there is no strong basis at present for recommending taping as part of the management of knee osteoarthritis. Well-designed studies of patellar taping to modify the relationships between the patellar and the trochlea are desirable to determine whether this treatment modality benefits patients with knee osteoarthritis, most notably those with involvement of the femoropatellar compartment.

Objective: To develop clinical practice guidelines concerning individual and group exercise therapy for knee and/or hip osteoarthritis (OA)., Method: We used the SOFMER (French Physical Medicine and Rehabilitation Society) methodology, combining systematic literature review, collection of everyday clinical practice, and external review by a multidisciplinary expert panel, to develop the guidelines., Results: Physical exercises are proposed for knee and hip OA. The benefit of individual exercises is low to moderate for pain, strength and ability to walk. The effectiveness is not maintained over time if the individual exercise program is not continued. The benefit of group exercise is also low to moderate for pain, strength, balance and ability to walk. There is no evidence of the superiority of one modality over the other (individual or group)., Conclusion: More randomised controlled trials with good methodology are needed to compare the effectiveness of individual versus group exercise therapy for knee and hip OA.

Objectives: To develop clinical practice guidelines concerning supervised or unsupervised kinesiotherapy for treating lower-limb osteoarthritis (OA)., Method: The SOFMER (French Physical Medicine and Rehabilitation Society) methodology, associating systematic literature review, collection of everyday clinical practice, and external review by a multidisciplinary expert panel, was used to develop guidelines. RESULTS-CONCLUSION: Physical exercise is a part of the treatment of lower-limb OA. An educational pre-program is recommended to inform the patient about the ease and effectiveness of the physical exercise. Use of the SOFMER methodology led to recommending a program of initial physical exercise supervised by a physiotherapist, then an unsupervised program at home with compliance. The type, intensity, and frequency of the exercises must be adapted to each patient. Complementary randomized controlled studies are necessary to characterize the best exercises and their intensity and frequency. The OA location and gravity, functional need, and characteristics of patients will be useful in future studies.

Objective: To assess the relevance of using the aggregate physical component score (PCS) and mental component score (MCS) of the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) for patients with knee and hip osteoarthritis (OA)., Methods: We conducted a cross-sectional national survey in a primary care setting in France. A total of 1474 general practitioners enrolled 4183 patients with hip or knee OA. Construct validity of PCS and MCS was assessed by convergent and divergent validity and factor analysis., Results: Records of 4133 patients (98.8%) were analyzed (2540 knee, 1593 hip OA). PCS mean scores were 32.0+/-8.4 and 31.8+/-8.4 and MCS scores 47.1+/-11.0 and 46.8+/-11.1, for knee and hip OA, respectively. Acceptable convergent and divergent validity was observed, and correlation between PCS and MCS mean scores was low (r=0.14). However, factor analysis performed on the eight subscale scores failed to support the use of PCS and MCS aggregate scores. It extracted two factors which were similar for both OA types and differed from the a priori stratification. Scores for two subscales usually attributed to MCS - emotional role and social functioning - were shared between factors, and scores for another subscale - general health perception - usually belonging to the PCS was in the mental component factor., Conclusions: Our results suggest that aggregate scores from the PCS and MCS of the SF-36 as they are currently defined may not be optimal for used in hip and knee OA patients to assess health-related quality of life.

Objective: The development of a rigorous methodology based on published results of clinical trials, evaluation of daily practice in France and multidisciplinary expert opinion to elaborate recommendations for rehabilitation interventions., Methods and Results: The following describes the methodology of SOFMER (Société Française de Médecine Physique et de Réadaptation [French Society of Physical Medicine and Rehabilitation]) for developing recommendations for rehabilitation interventions. The test case was developing recommendations for rehabilitation in hip or knee osteoarthritis (OA) and hip or knee arthroplasty. Physicians in rehabilitation, orthopedic surgery and rheumatology identified, synthesized, and analyzed data from the literature by use of the usual French system of grading trials (the French Agency for Accreditation and Evaluation in Healthcare [ANAES] scale). The data were published results of comparative controlled studies such as randomized controlled trials, controlled clinical trials, cohort studies, case control studies, reviews of clinical trials, and case series, as well as uncontrolled cohort studies. The resulting recommendations were presented to the three annual French national congresses of rehabilitation, rheumatology, and orthopedic surgery for comment and for adapting to French professional practice. Finally, a panel of multidisciplinary experts (physicians in physical medicine and rehabilitation, rheumatologists, orthopedic surgeons, general practitioners, physical therapists, social workers, podologists, occupational therapists, nurses, and patients) validated the recommendations., Conclusion: The SOFMER methodology could be an interesting tool for use in developing recommendations elaborated by all the concerned medical and surgical specialists in the wide domain of rehabilitation.

Objective: To assess the test-retest reliability and the construct validity of a modified version of the French-Canadian version of the WOMAC index., Methods: Open prospective study conducted in departments of Rheumatology, Rehabilitation and Orthopedic surgery of a tertiary care teaching hospital. Eighty-eight patients with symptomatic knee osteoarthritis (OA) fulfilling the revised criteria of the American College of Rheumatology were included. The French-Canadian version of the WOMAC index was completed twice at a 3-h interval. Impairment outcome measures, patients' perceived discomfort in walking and handicap were recorded. An item-by-item analysis was performed. Test-retest reliability was assessed using the intra-class correlation coefficient (ICC) and the Bland and Altman method. Construct validity was investigated using the Spearman rank correlation coefficient and a factor analysis was performed., Results: Eight questions assessing function (section C) and the two questions assessing stiffness (section B) had insufficient psychometric properties and were excluded. Although test-retest reliability of the questionnaire was fair to good (0.82, 0.85, for the WOMAC section A, and modified section C, respectively), construct validity could not be demonstrated. Factor analysis of the modified form of the WOMAC extracted four factors, which differed from the a priori stratification. However, factor analysis of the modified section C extracted two factors explaining 68.4% of the variance, which could be clinically characterized., Conclusion: Despite its good test-retest reliability, the modified WOMAC index is not valid for assessing pain and disability induced by knee OA in a French population. Section A and modified section C could be used separately to assess, respectively, pain and function.

Objectives: To assess the test-retest reliability and the construct validity of a modified version of the Lequesne index., Methods: Patients with symptomatic knee osteoarthritis (OA) fulfilling the revised criteria of the American College of Rheumatology completed the Lequesne index twice at a 3-h interval. Impairment outcome measures and patients' perceived discomfort in walking and handicap were recorded. An item-by-item analysis was performed. Items having insufficient psychometric properties were excluded. Test-retest reliability was assessed using the intra-class correlation coefficient (ICC) and the Bland and Altman method. Construct validity was investigated using Spearman rank correlation coefficient and a factor analysis was performed., Results: Eighty-eight patients were included. One question assessing pain (question IE) had a weak reliability (Kappa (kappa) = 0.39) and was excluded. The test-retest reliability of the modified questionnaire was excellent (ICC = 0.95). Expected convergent and divergent correlations were achieved except for visual analog scale pain (VAS P) and VAS handicap (VAS H) (0.46 and 0.40, respectively), and the "a priori" double stratification was confirmed by factor analysis, explaining 48.7% of the variance., Conclusion: The modified form of the Lequesne index has sufficient psychometric properties to be used to assess pain and function in knee OA in a French population.

Objective: To assess and compare the test-retest reliability and the construct validity of the Lequesne and the French-Canadian version of the WOMAC indexes., Design: Patients with symptomatic knee osteoarthritis (OA) fulfilling the revised criteria of the American College of Rheumatology completed both the Lequesne and the French-Canadian version of the WOMAC indexes twice at a 3-h interval. Impairment outcome measures, patients' perceived discomfort in walking and handicap were recorded. For both questionnaires, an analysis was performed item by item. Repeatability was assessed using the intraclass correlation coefficient (ICC) and the Bland and Altman method. Construct validity was investigated using the Spearman rank correlation coefficient and a factor analysis was performed., Results: 88 patients were included. Eight questions of the WOMAC section C and one question of the Lequesne index had insufficient psychometric properties. Although repeatability of questionnaires was fair to excellent (0.82, 0.68, 0.74, 0.95 for the WOMAC sections A, B, C and Lequesne index respectively), construct validity could not be demonstrated. Factor analysis of the WOMAC extracted five factors which differed from the a priori triple stratification. Factor analysis of the WOMAC section C extracted two factors explaining 71% of the variance which could not be clinically characterized. For the Lequesne index, expected convergent correlations were not always achieved. Three factors were extracted by factor analysis explaining 58% of the variance., Conclusion: Despite their good test-retest reliability, the two composite indexes evaluated are not valid to assess the concept of functional disability induced by knee OA in a French population.