Osteoarthritis year in review 2023: Epidemiology & therapy.

OBJECTIVE: To highlight some important findings from osteoarthritis (OA) epidemiology and therapy research undertaken over the past year. METHODS: Search of MEDLINE and EMBASE databases between April 1, 2022 to March 3, 2023 using "exp *Osteoarthritis/" as the preliminary search term. The search was limited to articles published in English and including human subjects. Final inclusions were based on perceived importance and results that may inform improved identification of risk factors or OA treatments, as well as OA subgroups of potential relevance to risk factors or treatment approaches. RESULTS: 3182 studies were screened, leaving 208 eligible for inclusion. This narrative review of thirty-three selected studies was arranged into: a) OA predictors - population-based studies, b) Specific predictors of OA and OA outcome; c) Intra-articular injections, and d) OA phenotypes. There was some suggestion of sex differences in predictors of incidence or outcomes. Body mass index changes appear largely to affect knee OA outcomes. Evidence points to a lack of benefit of viscosupplementation in knee OA; findings were variable for other injectables. Studies of OA phenotypes reveal potentially relevant clinical and pathophysiological differences. CONCLUSIONS: Identifying risk factors for the incidence/progression of OA represents an ongoing and important area of OA research. Sex may play a role in this understanding and bears consideration and further study. For knee injectables other than viscosupplementation, additional high-quality trials appear warranted. Continued investigation and application of phenotyping across the OA disease, illness and care spectrum may be key to developing disease-modifying agents and their appropriate selection for individuals.

Manejo das disfunções temporomandibulares. Parte I: tratamento conservador / Management of temporomandibular joint disorders. Part I: conservative treatment

Objetivo: Apresentar as modalidades de tratamentos conservadoras e minimamente invasivas mais usadas disponíveis no arsenal terapêutico das desordens temporomandibulares (DTM). Revisão da literatura: Os objetivos do tratamento invariavelmente incluem redução da dor, diminuição das atividades parafuncionais e restauração da função. Dentre as alternativas conservadoras e minimamente invasivas, podemos citar os dispositivos interoclusais, exercícios terapêuticos, eletrofototermoterapia, agulhamento seco e infiltração de anestésicos locais em pontos gatilho, injeção de sangue autógeno para controle da luxação mandibular, terapia cognitivo comportamental, toxina botulínica, viscossuplementação, controle farmacológico da dor aguda e crônica. As DTMs afetam uma proporção significativa da população. Somente após o fracasso das opções não invasivas é que devem ser iniciados tratamentos mais invasivos e irreversíveis. No entanto, algumas condições, como a anquilose e neoplasias, por exemplo, são essencialmente tratadas cirurgicamente e tentativas de tratamentos conservadores podem trazer piora na qualidade de vida ou risco de morte. Considerações finais: Uma abordagem de equipe multidisciplinar para o manejo é essencial no cuidado fundamental de todos os pacientes com DTM, para que o tratamento possa ser especificamente adaptado às necessidades individuais do paciente.

Aim: To present the most widely used conservative and minimally invasive treatment modalities available in the therapeutic arsenal for temporomandibular disorders (TMD). Literature review: Treatment goals invariably include pain reduction, reduction of parafunctional activities and restoration of function. Among the conservative and minimally invasive alternatives, we can mention interocclusal devices, therapeutic exercises, electrophototherapy, dry needling and infiltration of local anesthetics in trigger points, autogenous blood injection to control mandibular dislocation, cognitive behavioral therapy, botulinum toxin, viscosupplementation, pharmacological control of acute and chronic pain. TMD affects a considerable proportion of the population. Only after non-invasive options have failed should more invasive and irreversible treatments be initiated. However, some conditions, such as ankylosis and neoplasms, for example, are treated surgically and attempts at conservative treatments can lead to worsening quality of life or risk of death. Conclusions: A multidisciplinary team approach to management is essential in the fundamental care of all TMD patients, so that treatment can be specifically tailored to the patient's individual needs.

Injectable Hyaluronic Acid Hydrogel Containing Platelet Derivatives for Synovial Fluid Viscosupplementation and Growth Factors Delivery.

Osteoarthritisis a highly prevalent musculoskeletal disorder characterized by degradation of cartilage and synovial fluid (SF). Platelet derivatives as platelet-rich plasma (PRP) and platelet lysate have great potential in the treatment of osteoarthritis because they contain biologically active substances including growth factors (GFs). Rapid release of GFs and their short biological half-life are factors that can limit the therapeutic impact of PRP therapy. Herein, the first work that describes hydrogels based on polyaldehyde derivative of hyaluronic acid (HA-OX) as carriers of platelet derivatives for in situ applications is presented, which can be a possible solution to the problem. HA-OX hydrogels containing 50% (w/w) of PRP or platelet lysate can be injected using a syringe due to low viscosity(<10 Pa s) and injection force (<20 N), and reach elastic modulus up to 2000 Pa. Insulin-like GF-1 and Platelet-derived GF-AB release from HA-OX hydrogels (mesh size 297-406 nm) by Fickian and non-Fickian diffusion respectively. The released PRP GFs maintain their ability to induce cell proliferation (87%-92%). Based on the obtained results, the unique concept of a new material that can restore viscoelastic properties of SF and at the same time gradually deliver GFs from platelet derivatives is designed.

EUROVISCO Good Practice Recommendations for a First Viscosupplementation in Patients with Knee Osteoarthritis.

RATIONALE: Viscosupplementation (VS) with hyaluronic acid is widely used in the management of knee osteoarthritis. There is no clear recommendation on the decision-making to achieve VS. DESIGN: Based on extensive research of the literature and expert opinion, the members of the EUROVISCO (European Viscosupplementation Consensus Group) task force were asked to give their degree of agreement with 60 issues, using a Delphi method. RESULTS: The expert panel achieved unanimous agreement in favor of the following statements: It is recommended to assess pain on a visual or 10-point numeric scale before considering VS. VS can be considered for patients with pain scores between 3 and 8. A standard x-ray must be obtained before the decision of VS. If the x-ray is normal, osteoarthritis must be confirmed by MRI or computed tomography (CT) arthrogram before considering VS. The aims of VS are relieving pain, improving function, and reducing non-steroidal anti-inflammatory drug (NSAID) consumption. The use of VS must not be considered for treating an osteoarthritis flare. VS can be envisaged as a first-line pharmacological treatment in patients having a contra-indication to NSAIDs or analgesics. VS can be considered in patients with contra-indications to arthroplasty. In the case of severe comorbidities (diabetes, hypertension, gastrointestinal disorders, renal failure), VS can avoid the use of potentially dangerous treatments. VS can be considered in patients receiving antiplatelet agents, vitamin K antagonists, and direct factor Xa or thrombin inhibitors. Five other statements obtained a high level of consensus. CONCLUSION: These recommendations, illustrated in a decision algorithm, have been established to help practitioners in the decision-making of knee VS.

A composite device for viscosupplementation treatment resistant to degradation by reactive oxygen species and hyaluronidase.

Osteoarthritis (OA) is one of the most common musculoskeletal disorders in the world. OA is often associated with the loss of viscoelastic and tribological properties of synovial fluid (SF) due to degradation of hyaluronic acid (HA) by reactive oxygen species (ROS) and hyaluronidases. Viscosupplementation is one of the ways how to effectively restore SF functions. However, current viscosupplementation products provide only temporal therapeutic effect because of short biological half-life. In this article we describe a novel device for viscosupplementation (NV) based on the cross-linked tyramine derivative of HA, chondroitin sulfate (CS), and high molecular weight HA by online determination of viscoelastic properties loss during degradation by ROS and hyaluronidase. Rheological and tribological properties of developed viscosupplement were compared with HA solutions with different molecular weights in the range 500-2000 kDa, which are currently commonly used as medical devices for viscosupplementation treatment. Moreover, based on clinical practice and scientific literature all samples were also diluted by model OA SF in the ratio 1:1 (vol/vol) to better predict final properties after injection to the joint. The observed results confirmed that NV exhibits appropriate rheological properties (viscosity, elastic, and viscous moduli) comparable with healthy SF and maintain them during degradation for a significantly longer time than HA solutions with molecular weight in the range 500-2000 kDa and cross-linked material without CS.

Bone marrow aspirate concentrate injections provide similar results versus viscosupplementation up to 24 months of follow-up in patients with symptomatic knee osteoarthritis. A randomized controlled trial.

PURPOSE: The purpose of this double-blind randomized controlled trial (RCT) was to compare clinical improvement and radiographic findings up to 2 years of follow-up of a single intra-articular injection of bone marrow aspirate concentrate (BMAC) versus hyaluronic acid (HA) for the treatment of knee osteoarthritis (OA). The hypothesis was that BMAC injection could lead to better clinical and radiographic results compared to viscosupplementation. METHODS: Patients with bilateral knee OA were randomized to one intra-articular injection of tibial-derived BMAC in one knee and one HA injection in the contralateral knee. Sixty patients were enrolled, and 56 were studied up to the final follow-up (35 men, 21 women, mean age 57.8 ± 8.9 years), for a total of 112 knees. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the IKDC subjective score, VAS for pain, and the KOOS score. Minimal clinically important difference (MCID), patient treatment judgement, and adverse events were documented, as well as bilateral X-Rays (Rosenberg view) before and after treatment. RESULTS: No severe adverse events nor differences were reported in terms of mild adverse events (7.1% vs 5.4%, p = ns) and treatment failures (10.7% vs 12.5%, p = ns) in BMAC and HA groups, respectively. The IKDC subjective score improved from baseline to all follow-ups for BMAC (p < 0.0005), while it improved up to 12 months (p < 0.0005) and then decreased at 24 months (p = 0.030) for HA. Compared to HA, BMAC showed a higher improvement for VAS pain at 12 (2.2 ± 2.6 vs 1.7 ± 2.5, p = 0.041) and 24 months (2.2 ± 2.6 vs 1.4 ± 2.8, p = 0.002). The analysis based on OA severity confirmed this difference only in Kellgren-Lawrence 1-2 knees, while comparable results were observed in moderate/severe OA. Radiographic evaluation did not show knee OA deterioration for both treatment groups, without intergroup differences. CONCLUSION: BMAC did not demonstrate a clinically significant superiority at short-term compared to viscosupplementation, reporting overall comparable results in terms of clinical scores, failures, adverse events, radiographic evaluation, MCID achievement, and patient treatment judgment. However, while HA results decreased over time, BMAC presented more durable results in mild OA knees. LEVEL OF EVIDENCE: Level I.

Severe Acute Localized Reactions Following Intra-Articular Hyaluronic Acid Injections in Knee Osteoarthritis.

OBJECTIVE: Concerns have been raised about severe acute localized reactions (SALR) following intra-articular (IA) hyaluronic acid (HA) injections for knee osteoarthritis (OA). We compared surrogate SALR measures between hylan G-F 20 and non-hylan G-F 20 HA patients and evaluated corresponding SALR risk factors for hylan G-F 20 patients. DESIGN: Knee OA patients were identified from the Optum Clinformatics dataset (January 2006 to June 2016), stratified into hylan G-F 20 and non-hylan G-F 20 HA users. Occurrences of surrogate SALR measures including inflammation/infection, intra-articular corticosteroid (CS) injections, arthrocentesis/aspiration, and office visits were evaluated within 3 days of HA use. Risk factors were evaluated using logistic regression. RESULTS: The cohort involved 748,428 HA patients (23.2% in the hylan G-F 20 group). Inflammation/infection rate was 0.001% for hylan G-F 20 and 0.002% for non-hylan G-F 20 HA groups. Risk of CS injection (any diagnosis) was greater for hylan G-F 20 patients by 28% (P < 0.001). Combined rates of CS injection and arthrocentesis/aspiration (any diagnosis) were comparable for both groups (hylan G-F 20, 2.2%; non-hylan G-F 20 HA, 2.6%). The risk of any visit or studied responses was lower for the hylan G-F 20 cohort by 12% (P < 0.001). Clinical characteristics, such as CS injections within 1 week before HA and fluoroscopic imaging, were associated with the outcomes. CONCLUSIONS: The diagnosis of inflammations or infections within 3 days of the HA injection was extremely rare. The overall risk of surrogate SALR measures was similar for hylan G-F 20 and non-hylan G-F 20 HA patients.

Factors Associated with Knee Arthroplasty in a Knee Osteoarthritis Patient Cohort Treated with Intra-articular Injections of Hylan G-F 20.

Hylan G-F 20 viscosupplementation can be used to treat knee osteoarthritis pain. This study evaluated time to knee arthroplasty (KA), KA risk factors, and health care resource utilization in patients aged ≥18 years with claims in the Optum Clinformatics Data Mart database (2006-2016) for knee osteoarthritis treated with at least one course of hylan G-F 20. Kaplan-Meier analysis estimated KA risk from osteoarthritis diagnosis and first hylan G-F 20 treatment. KA risk factors were determined using multivariate Cox regression. Among 62,033 patients treated with hylan G-F 20 and/or hylan G-F 20 single intra-articular injection, 60 to 64% did not undergo KA 8 years following first injection. KA risk factors from time of osteoarthritis diagnosis and first hylan G-F 20 treatment were similar: increased age, fewer comorbidities, fewer hylan G-F 20 treatments, female sex, and no ultrasound/fluoroscopy for injection guidance. Patients who underwent KA versus those who did not had more office visits and claims for opioids, nonsteroidal anti-inflammatory drugs, and physical therapy. Patients less likely to undergo KA were younger (<40 years), had more comorbidities, received more courses of hylan G-F 20, were males, or received ultrasound/fluoroscopic injection guidance. Patients who did not receive KA versus those who did used fewer health care resources.

Viscossuplementation for the treatment of osteoarthritis of the knee: A protocol for an umbrella review of systematic reviews with meta-analyses of randomized controlled trials.

BACKGROUND: Knee osteoarthritis (KOA) is a common chronic disease with worldwide prevalence of 10% to 79%, with costs ranging from $560 to $635 billion for year in United States of America. The main guidelines recommend interventions with undesirable adverse events (AE) or highly dependent on the patient's persistence. Thus, intra-articular (IA) therapies appear to be attractive in patients with KOA, as well as a valid therapy by maximizing effects locally in the joint and limiting systemic AE. Presently, the main available IA therapies are corticosteroids and hyaluronic acid.As several meta-analyses about the efficacy of intra-articular hyaluronic acid (IAHA) for treatment of KOA with discordant results were published, we decided to conduct an umbrella review to summarize this efficacy METHODS:: We will search MEDLINE/PubMed, EMBASE, Cochrane Library, and Virtual Health Library (BVS) from inception to February 2020 for systematic reviews with meta-analyses of randomized clinical trials that investigate IAHA for therapy of KOA. Grey literature will be searched in Opengray platform, Research Gate, and Google Scholar. The reference lists of eligible studies will be screened. The search will be performed without language restriction.We will include any type of IAHA as experimental intervention and different types of oral or intra-articular placebo or medications as controls. The primary outcome will be measures of efficacy as the Western Ontario and McMaster Universities Osteoarthritis Index.A synthesis of the evidence will be conducted and data will be presented in tables.Two reviewers will independently appraise the quality of included meta-analyses using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool and will classify the included systematic reviews into high, moderate, low, or critically low levels of confidence. RESULTS: The results of this study will be published in a peer-reviewed journal. ETHICS AND DISSEMINATION: No ethical approval is required since this study data is based on published literature. PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42019120269 (https://www.crd.york.ac.uk/PROSPERO/#joinuppage).

A hydrogel system based on a lactose-modified chitosan for viscosupplementation in osteoarthritis.

Osteoarthritis (OA) is a chronic disease affecting joint functionality and often managed with hyaluronic acid (HA) administration. In this study, a hydrogel based on a lactose-modified chitosan (CTL) reticulated with boric acid has been developed as a viscosupplement for OA treatment. The rheological characterization allowed to identify a composition whose properties were in line with those of commercial products (in the order of tens of Pascal). The selected CTL-hydrogel showed biocompatibility and antioxidant activity in vitro, and it did not influence cytokines release by macrophages. Degradation studies carried out over 24 h pointed out its higher resistance to chemical degradation with respect to HA samples. Overall, this study underlines the advantages of the CTL-hydrogel to address the treatment of OA and shed light on an innovative application of CTL polymer, which is one of the main component of the proposed hydrogel system and not used in mixture with other molecules.

The Cost-Effectiveness of Platelet-Rich Plasma Compared With Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis.

PURPOSE: To examine the cost-effectiveness of a series (total of 3 injections) of intra-articular platelet-rich plasma (PRP) injections in comparison to that of hyaluronic acid (HA) viscosupplementation for the treatment of symptomatic knee osteoarthritis. METHODS: Outcome data regarding the use of PRP or HA injections for the treatment of symptomatic knee osteoarthritis were determined from the highest-quality data (Level I) available in the literature until 2015. Health utility values were then derived from these high-quality data. Costs were determined by examining typical charges for patients undergoing a series of either PRP or HA injections for the treatment of this condition at a large private orthopaedic practice. These health utility values and costs were used to create an expected-value decision analysis model. RESULTS: The results of the model revealed that the cost per quality-adjusted life-year (QALY) of a series of PRP injections was $8,635.23/QALY and that of a series of HA injections was $5,331.75/QALY. A series of PRP injections was associated with a higher initial cost than a series of HA injections (difference, $1,433.67); however, PRP was also more effective (higher utility value) than HA by 0.11 QALYs (0.69 vs 0.58, P = .0062) at 1 year. The incremental cost-effectiveness ratio of the use of PRP injections as opposed to HA was $12,628.15/QALY. CONCLUSIONS: Although a series of either PRP ($8,635.23/QALY) or HA ($5,331.75/QALY) injections for the treatment of symptomatic knee osteoarthritis would be considered cost-effective (cost per QALY < $50,000), PRP injections were not more cost-effective than HA injections. However, PRP was significantly more effective at 1 year, and being associated with an incremental cost-effectiveness ratio of $12,628.15/QALY when compared with HA, a series of PRP injections should be considered a reasonable and acceptable alternative to HA injections for the treatment of symptomatic knee osteoarthritis. LEVEL OF EVIDENCE: Level II, economic and decision analysis of Level I studies.

Platelet-rich plasma for the treatment of knee osteoarthritis: an expert opinion and proposal for a novel classification and coding system.

INTRODUCTION: Platelet-rich plasma (PRP) is able to modulate the joint environment by reducing the inflammatory distress and promoting tissue anabolism. Therefore, it has gained increasing popularity among clinicians in the treatment of osteoarthritis (OA), and it is currently proposed beside consolidated options such as viscosupplementation. AREAS COVERED: A systematic review of all available meta-analyses evaluating intra-articular PRP injections in patients affected by knee OA was performed, to understand how this biologic treatment approach compares to the traditional injective therapies available in clinical practice. Moreover, a novel coding system and 'minimum reporting requirements' are proposed to improve future research in this field and promote a better understanding of the mechanisms of action and indications. EXPERT OPINION: The main limitation in the current literature is the extreme variability of PRP products used, with often paucity or even lack of data on the biologic features of PRP, which should not be considered as a simple substance, but rather a 'procedure' requiring accurate reporting of the characteristics of the product but also all preparation and application modalities. This approach will aid in matching the optimal PRP product to specific patient factors, leading to improved outcomes and the elucidation of the cost-effectiveness of this treatment.

Rethinking Viscosupplementation: Ultrasound- Versus Landmark-Guided Injection for Knee Osteoarthritis.

OBJECTIVES: Viscosupplementation, intra-articular injection of hyaluronic acid (HA), for knee osteoarthritis has fallen somewhat out of favor, with studies failing to show consistent benefits in pain reduction. Hyaluronic acid must enter the joint space to be beneficial; however, landmark-guided injection can be substantially inaccurate, especially in obese patients. We aimed to determine whether ultrasound (US) guidance to ensure needle placement for HA knee injection resulted in improved outcomes as reflected by surgery-free survival compared to landmark-guided HA knee injection. METHODS: All community-dwelling patients in 6 contiguous surrounding counties receiving HA knee injection either by landmark guidance (n = 647) or by US guidance (n = 500) were analyzed for the degree of arthritis, body mass index, follow-up injection, and subsequent need for knee arthroplasty. A subgroup analysis of obese patients was also performed. RESULTS: The US- and landmark-guided HA injection cohorts were similar with respect to sex, body mass index, and the degree of arthritis. Of 1147 patients receiving knee HA injection, 462 subsequently underwent knee arthroplasty. Significantly fewer patients in the US-guided HA injection cohort went to surgery (33.2%) compared to the landmark-guided cohort (45.8%; P < .001). The subgroup analysis for obese patients showed even larger differences (34.8% versus 51.8%; P < .001). CONCLUSIONS: Knee osteoarthritis treatment by viscosupplementation can be optimized by US guidance, ensuring intra-articular needle placement. Using an objective surgical outcome, our study shows that rethinking viscosupplementation to ensure intra-articular delivery improves effectiveness. Patients receiving US-guided knee HA injection were significantly less likely to undergo subsequent knee arthroplasty than patients receiving landmark-guided HA injection.

EUROVISCO Recommendations for Optimizing the Clinical Results of Viscosupplementation in Osteoarthritis.

OBJECTIVES: The 3 aims of the work were to identify population subgroups that can benefit the most from viscosupplementation (VS), to provide recommendations on injection techniques, and to discuss VS appropriateness in clinical situations that are commonplace in daily practice. METHODS: The task force members voted on their degree of agreement on 27 statements, 36 recommendations, and 22 clinical scenarios using a 9-point scale. The strength of agreement/appropriateness/recommendation (SOA/SOR) was classified as strong if the median agreement score was ≥8. The level of consensus (LOC) was also obtained. RESULTS: Among the assumed predictors for VS failure, obesity, radiographic severity, large synovial fluid effusion, severe patellofemoral involvement, major malalignment, and gross joint instability received a large majority of agreements. The lateral mid-patellar approach was recommended for knee injection. Imaging guidance was unanimously recommended for hip and ankle. Agreement was achieved to strictly respect the dosing regimen proven by controlled trials. There was agreement for treating with VS patients with mild to moderate knee and hip OA, with normal weight or moderate overweight, insufficiently improved by first-line therapies, or who do not wish get oral treatment or who have contraindications to pain killers. The group considered the patient's wishes as a key element in therapeutic decision making. CONCLUSION: Based on literature data and clinical experience, the EUROVISCO group proposed a set of recommendations for optimizing the results of VS, aimed to help practitioners, especially in some cases in which the patients' specificities make the therapeutic decision difficult.

EUROVISCO Guidelines for the Design and Conduct of Clinical Trials Assessing the Disease-Modifying Effect of Knee Viscosupplementation.

OBJECTIVES: Hyaluronic acid viscosupplementation is a commonly used intra-articular treatment for osteoarthritis (OA). Some recent preclinical and clinical trials have demonstrated a potential for its disease-modifying effects. The goal of this expert opinion, consensus-driven exercise is to provide guidelines for the design and conduct of clinical trials assessing the disease-modifying effect of viscosupplementation in the knee. METHODS: The EUROVISCO group constitutes 10 members who had expertise in clinical research methodology in the field of OA and viscosupplementation. They initially drafted issues through an iterative process and had to vote on their degree of agreement on these recommendations. The scores were pooled to generate a median agreement score for each recommendation. RESULTS: The document includes 31 recommendations regarding study population, imaging, clinical and biological assessment of disease-modifying effects of viscosupplementation. Agreements were reached on some recommendations. In particular, the experts reached unanimous agreement on double-blind study design, imaging primary outcomes, time interval between 2 radiographs, x-ray procedure standardization, and the combined use of imaging and biological markers. The group did not recommend the use of ultrasonography, computed tomography (CT) scan and CT arthrography as a tool for OA diagnosis or to assess progression over time. CONCLUSION: In summary, the working group identified 31 recommendations that represent the current best practices regarding clinical trials that target the assessment of viscosupplementation disease-modifying effects in patients with knee OA. These recommendations integrate new imaging technologies and soluble biomarkers.

Viscosupplementation improves pain, function and muscle strength, but not proprioception, in patients with knee osteoarthritis: a prospective randomized trial.

OBJECTIVES: This study aimed to evaluate the clinical outcomes of intra-articular infiltration with hyaluronic acid and dexamethasone alone and in combination in the treatment of knee osteoarthritis (OA). METHOD: This prospective randomized trial evaluated 44 patients undergoing treatment for OA. Patients were selected through clinical and radiological analysis using the American College of Rheumatology criteria. We included patients aged between 50 and 70 years who presented with K-L stage ≤2 knee OA and normal limb alignment. Patients with a previous history of knee injury (ligamentous, meniscal or traumatic), infection, patellofemoral OA or chondroprotective drug use in the previous year were excluded. Participants were randomized into 3 groups and underwent treatment with viscosupplementation (VS, n=16), viscosupplementation plus dexamethasone (VD, n=16) or dexamethasone (DX, n=12). All patients were evaluated before and 6 weeks, 3 months and 6 months after infiltration. Analysis included a physical examination, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire (total score and domain subscores) and an evaluation of knee extensor and flexor strength and proprioception using an isokinetic dynamometer. RESULTS: VS significantly improved the WOMAC total score and subscores for pain, stiffness and function for up to 6 months after infiltration. It also improved knee extensor and flexor strength during the same period. Proprioception was not affected by any of the treatments. CONCLUSIONS: VS alone improved pain, stiffness and function according to the WOMAC total score and subscores and improved knee extensor and flexor strength, but not proprioception, for up to six months after infiltration. These findings suggest that VS has a positive effect on quadriceps arthrogenic inhibition.

A placebo-controlled study comparing the efficacy of intra-articular injections of hyaluronic acid and a novel hyaluronic acid-platelet-rich plasma conjugate in a canine model of osteoarthritis.

BACKGROUND: The objective of this study was to assess the efficacy of intra-articular injections of hyaluronic acid (HA) and a novel, on-site conjugate of HA with autologous fibrinogen in platelet-rich plasma (HA-PRP) in a canine model of osteoarthritis (OA) METHODS: Twelve beagle dogs underwent a unilateral resection of the cranial cruciate ligament (CrCL) of the stifle joint. Clinical and radiographic signs of OA were confirmed in all dogs 8 weeks following CrCL resection and prior to treatment. The dogs were randomized into three groups: saline (n = 4), HA (n = 4), and HA-PRP (n = 4). Each dog received intra-articular injections of the respective substance into the affected joint at pre-determined time points. The dogs were assessed for adverse effects for 3 days after each injection and for lameness, pain, range of motion, kinetics, and radiographic OA severity prior to treatment and 3 months after injection. OA severity as determined by radiographic examination was not significantly different among the groups at any time point. The dogs were then humanely euthanatized and the stifle joint assessed by gross and histological examinations. RESULTS: Dogs treated with four weekly injections of HA or two biweekly injections of HA-PRP were significantly (p < 0.05) better than dogs treated with four weekly injections of saline at 2-, 4-, and 12-week time points based on a comfortable range of motion (CROM) and clinical lameness score. Gait analysis measuring symmetry and weight distribution on pressure sensor walkway showed significantly (p < 0.05) improved limb function for dogs treated with HA and HA-PRP compared with dogs treated with saline yet with better clinical outcome for the HA-PRP-treated group at 12 and 20 weeks follow-up. Gross and histological analysis of synovium and articular cartilage demonstrated significant (p < 0.05) improvement by both treatments groups compared to controls. There was however significantly (p < 0.05) less damage to the cartilage in the HA-PRP group compared to the HA-treated group. CONCLUSIONS: These data suggest that while injection of HA and HA-PRP may be sufficient for short-term amelioration of the symptoms associated with OA, treatment with HA-PRP conjugates may be superior, providing significantly better long-term cartilage preservation.

Impact of obesity, structural severity and their combination on the efficacy of viscosupplementation in patients with knee osteoarthritis.

BACKGROUND: Obesity and radiological severity have been identified to be independent predictors of a low rate of response to viscosupplementation (VS), in patients with knee osteoarthritis (OA). Is that enough to formally refute VS in such patients in whom surgery is sometimes contraindicated? OBJECTIVES: To compare pain and function scores before and 6 months after knee VS, according to the weight status (obese versus non obese), the radiological severity (mild/moderate versus severe) and both combined. METHODS: Post-hoc analysis of a prospective, double blind, randomized, multicentre trial, comparing 2 viscosupplements, in patients with symptomatic knee OA. Patients were classified according to body mass index (BMI < or ≥ 30 kg.- 2), OARSI radiological grade (1-2 versus 3) and OMERACT-OARSI response criteria (Yes/No). WOMAC between-group comparisons (obese versus non-obese, OARSI 1-2 versus 3, and both combined) in all patients and in OMERACT-OARSI Responders, were achieved using Mannn-Whitney U test. RESULTS: One-hundred and sixty-six patients were analyzed: 28.3% were obese, 44% were OARSI grade 3, 42,2% were neither obese nor OARSI 3, whereas 14.5% were obese and OARSI 3. At baseline WOMAC pain score did not differ according to the patients sub-groups (p > 0.05). Six months after VS, WOMAC pain decreased significantly in all patient sub-groups (all p < 0.01). At month 6, WOMAC pain sub-score was significantly lower in non-obese than in obese patients (4.9 ± 4.1 versus 7.1 ± 4.9; p = 0.008) and in patients OARSI 1-2 versus 3 (4.8 ± 4.3 versus 6.4 ± 4.5; p = 0.009). However, in responder patients there was no difference in pain score and pain decrease related to the weight status and the radiological score. CONCLUSION: These results do not confirm our previous conclusions that recommended not performing VS in obese patients with severe knee OA. Although the chances of being a responder were much reduced in these patients, the benefit of patients who respond to treatment was similar to that of subjects with normal weight and mild/moderate OA. Different pain phenotypes, more than overweight and advanced disease, might be the main reason for the success or failure of VS.

Comparison of the Neodymium-doped Yttrium Aluminum Garnet Capsulotomy Rate with Viscoimplantation and the Hydroimplantation Intraocular Lens Technique.

PURPOSE: To investigate the rate of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy in the hydroimplantation intraocular lens (IOL) technique. METHODS: This retrospective study was comprised of 6,192 eyes in 3,790 patients who underwent surgery from January 2013 to September 2017 and then were followed up for at least 1 year. The eyes of these patients were divided into two groups: either viscoimplantation or hydroimplantation. The follow-up examinations were carried out on the 1st day, 4th day, 1st month, and 3 months to 1 year postoperatively. The Nd:YAG capsulotomy rates were evaluated by the different IOL implantation techniques and IOL materials. RESULTS: The mean follow-up duration of the patients was in the viscoimplantation group 14.85 ± 2.43 and 15.05 ± 1.93 months in the hydroimplantation group. The Nd:YAG capsulotomy rate was significantly lower in the hydroimplantation group compared with the viscoimplantation group for the entire hydrophilic IOL model (p < 0.001). In addition, the Nd:YAG rate was lower in the hydroimplantation group that used a hydrophilic IOL than it was in the viscoimplantation group, which used a hydrophobic IOL. CONCLUSIONS: The hydroimplantation technique reduced the Nd:YAG capsulotomy rate.

Predictors of placebo response to local (intra-articular) therapy in osteoarthritis: an individual patient data meta-analysis protocol.

INTRODUCTION: Osteoarthritis (OA) is a highly prevalent and disabling condition with limited safe and effective treatment options. Intra-articular therapies are increasingly being used, however whether the effect of these agents is due to active treatment or placebo remains unclear. As the placebo response can be attributed to multiple factors, assessment of the placebo response using individual patient data (IPD) meta-analysis will give insight into the different modifiers of response to placebo. The aim of this IPD meta-analysis is to investigate the predictors of placebo response in intra-articular injection trials in OA. IPD meta-analysis is considered to be superior to conventional meta-analysis, as it combines multiple trial data, facilitates the standardisation of analyses across different studies and allows measuring derivation of the desired information. METHOD AND ANALYSIS: A systematic literature search will be conducted for randomised clinical trials comparing corticosteroid and viscosupplementation/hyaluronic acid intra-articular injections with placebo for knee and hip OA. Pubmed (Medline), EMBASE, Web of Science, Cochrane Central and SCOPUS will be searched from inception to September 2018. Corresponding authors of the original trials will be contacted to obtain IPD. Risk of bias will be assessed using the Cochrane Collaboration's tool. The primary outcome will be change in pain from baseline. Secondary outcomes will be change in function and patient's global assessment. Potential predictors of placebo response assessed will include patient's characteristics, pain mechanism characteristics, radiographic severity, pain severity, intervention characteristics and trial design characteristics. A multilevel logistic regression analyses will be applied. Results will be reported using the Preferred Reporting Items for Systematic review and Meta-Analysis -IPD guidelines. ETHICS AND DISSEMINATION: This study does not include identifiable data and ethical approval was obtained by the original investigators. Results of the IPD meta-analysis will be disseminated for publication in peer-reviewed journals and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42018095188.