A retrospective claims data analysis of health care utilization and cost among patients receiving multi-injection intraarticular hyaluronic acid.

BACKGROUND: With the rising costs for knee arthroplasty, therapies that allow patients to avoid or delay surgery following knee osteoarthritis (KOA) may help in reducing overall health care costs. Multiple intraarticular hyaluronic acid (HA) products are available on the market, varying by formulation, molecular weight, and number of injections, but clinical and economic benefits may differ by product. OBJECTIVES: To evaluate the all-cause and KOA-related health care resource utilization (HCRU) and costs among newly diagnosed patients with KOA treated with multi-injection HA. METHODS: A retrospective cohort study using a large commercial claims database (Merative MarketScan database) to identify patients with KOA treated with high molecular weight (HMW) (n = 11,200), medium molecular weight (MMW) (n = 10,225), or low molecular weight (LMW) HAs (n = 8,473) between 2016 and 2019. KOA-related and all-cause HCRU and costs were compared within 12 months after the index HA treatment date. The association between outcomes and HA treatments was evaluated using a doubly robust method to adjust for confounding factors. HCRU and costs among the propensity score-weighted HA groups were compared using generalized linear models. RESULTS: HMW HA patients were found to have lower adjusted KOA-related medical costs by $265.37 (P < 0.001) and pharmacy costs by $19.90 (P < 0.001) compared with LMW HA patients, as well as lower all-cause total medical costs by $130.42 (P = 0.013) and pharmacy costs by $63.33 (P < 0.001). HMW HA patients also had a lower adjusted KOA-related medical cost by $205.74 (P < 0.001) and pharmacy cost by $14.39 (P < 0.001) compared with MMW HA patients, as well as lower all-cause medical by $1,195.66 (P < 0.001) and pharmacy by $196.99 (P < 0.001). Three-injection treatment patients (HMW HA, 84%; MMW HA, 82%) had high completion rate, compared with the 5-injection treatment cohort (LMW HA, 48%). CONCLUSIONS: HMW HA patients had statistically significantly lower adjusted all-cause and KOA-related medical and pharmacy costs at 1 year follow-up compared with MMW HA and LMW HA patients. It is unclear if this is related to differences in molecular weight or specific mechanism of actions.

Ultrasound-guided infiltration with hyaluronic acid compared with corticosteroid for the treatment of Morton's neuroma.

Aims: A local injection may be used as an early option in the treatment of Morton's neuroma, and can be performed using various medications. The aim of this study was to compare the effects of injections of hyaluronic acid compared with corticosteroid in the treatment of this condition. Methods: A total of 91 patients were assessed for this trial, of whom 45 were subsequently included and randomized into two groups. One patient was lost to follow-up, leaving 22 patients (24 feet) in each group. The patients in the hyaluronic acid group were treated with three ultrasound-guided injections (one per week) of hyaluronic acid (Osteonil Plus). Those in the corticosteroid group were treated with three ultrasound-guided injections (also one per week) of triamcinolone (Triancil). The patients were evaluated before treatment and at one, three, six, and 12 months after treatment. The primary outcome measure was the visual analogue scale for pain (VAS). Secondary outcome measures included the American Orthopaedic Foot and Ankle Society (AOFAS) score, and complications. Results: Both groups showed significant improvement in VAS and AOFAS scores (p < 0.05) after 12 months. The corticosteroid group had a significantly greater reduction in VAS and increase in AOFAS scores compared with the hyaluronic acid group, at one, three, and six months, but with no significant difference at 12 months. There were no complications in the hyaluronic acid group. There were minor local complications in six patients (six feet) (25.0%) in the corticosteroid group, all with discolouration of the skin at the site of the injection. These minor complications might have been due to the three weekly injections of a relatively high dose of corticosteroid. No patient subsequently underwent excision of the neuroma. Conclusion: An ultrasound-guided corticosteroid injection showed statistically significantly better functional and pain outcomes than an ultrasound-guided injection of hyaluronic acid for the treatment of a Morton's neuroma at many timepoints. Thus, a corticosteroid injection should be regarded as a primary option in the treatment of these patients, and the only indication for an injection of hyaluronic acid might be in patients in whom corticosteroid is contraindicated.

Evaluation of orthobiological ozonized platelet-rich plasma therapy post-arthroscopic suturing and lone partial meniscectomy in the treatment of meniscal tears within degenerative knee osteoarthritis.

BACKGROUND: Knee joint osteoarthritis (OA)-related meniscal tears are still sometimes treated in centers by arthroscopic partial meniscectomy (APM), which is then followed by a solitary physical therapy regimen. OBJECTIVE: The present study was conducted to compare the efficacy of intra-articular injection of ozonized platelet-rich plasma (PRP) and hyaluronic acid following arthroscopic suturing, and APM to treat meniscal tear degenerative type. METHODS: In a randomized trial of prospective comparative research, 104 patients, all of whom had meniscal tears due to OA of the knee, were randomly divided into two groups. The participants in Group A (55 patients) were given intra-articular ozonized PRP and hyaluronate therapeutics, following arthroscopic suturing of meniscal tear treatment (ASMT) of degenerative knee joint OA. Group B (49 patients) was prepared for APM alone. Both groups were followed by physical therapy and a follow up visit throughout 12, 24, and 36 months. The WOMAC and Lequesne scores were evaluated. RESULTS: At every follow up visit for 6, 12, and 24, months, there was a significant decline in the mean of WOMAC and Lequesne scores in Groups A and B relative to baseline. Additionally, Group A significantly (P<0.0001) outperformed Group B at 12, 24, and 36 months for both Lequesne's and WOMAC scores. There were infection, stiffness, and widespread OA knee degeneration detected in Group B while no serious adverse effects were observed in Group A. CONCLUSION: The study's findings demonstrated that physical and intra-articular orthobiological ozonized PRP and hyaluronate therapies were more effective than APM in treating degenerative knee joint OA.

Platelet-Rich Plasma, Bone Marrow Aspirate Concentrate, and Hyaluronic Acid Injections Outperform Corticosteroids in Pain and Function Scores at a Minimum of 6 Months as Intra-Articular Injections for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis.

PURPOSE: To compare the efficacy of common intra-articular injections used in the treatment of knee osteoarthritis, including corticosteroid (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and bone marrow aspirate concentrate (BMAC), with a minimum follow-up of 6-months. METHODS: A literature search was conducted using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in August 2022 in the following databases: PubMed/MEDLINE, Scopus, Cochrane Database of Controlled Trials, and the Cochrane Database of Systematic Reviews. Level I to II randomized clinical trials with a minimum follow-up of 6 months that investigated the treatments of interest were included. Patient-reported outcome scores for pain and function at baseline and at latest follow-up were extracted, and the change in scores was converted to uniform 0 to 100 scales. Arm-based Bayesian network meta-analysis using a random-effects model was created to compare the treatment arms in pain and function. RESULTS: Forty-eight studies comprising a total of 9,338 knees were included. The most studied intra-articular injection was HA (40.9%), followed by placebo (26.2%), PRP (21.5%), CS (8.8%), and then BMAC (2.5%). HA and PRP both led to a significant improvement in pain compared with placebo. HA, PRP, and BMAC all led to a significant improvement in function scores when compared with placebo. Surface under the cumulative ranking curves (SUCRAs) of the interventions revealed that PRP, BMAC, and HA were the treatments with the highest likelihood of improvement in both pain and function, with overall SUCRA scores of 91.54, 76.46, and 53.12, respectively. The overall SUCRA scores for CS and placebo were 15.18 and 13.70, respectively. CONCLUSIONS: At a minimum 6-month follow-up, PRP demonstrated significantly improved pain and function for patients with knee osteoarthritis compared with placebo. Additionally, PRP exhibited the highest SUCRA values for these outcomes when compared with BMAC, HA, and CS. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I to II studies.

Effects and safety of hyaluronic acid gel on intrauterine adhesion and fertility after intrauterine surgery: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

OBJECTIVE: This study aimed to determine the efficacy and safety of hyaluronic acid gel for the prevention of intrauterine adhesions and improved fertility after intrauterine surgery. DATA SOURCES: PubMed, EMBASE, Cochrane Library, Web of science, and ClinicalTrials.gov were searched up to November 1, 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that reported intrauterine adhesion and fertility outcomes among women who used hyaluronic acid after intrauterine surgery. METHODS: The risk of bias was assessed using criteria of the Cochrane Handbook, and the quality of the evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A trial sequential analysis was conducted to assess the outcomes, and Stata 14 was used for sensitivity analyses and publication bias analyses. RESULTS: Data from 16 randomized controlled trials involving 2359 patients were extracted and analyzed. The analysis revealed that hyaluronic acid reduced the incidence of intrauterine adhesion (risk ratio, 0.53; 95% confidence interval, 0.42-0.67; I2=48%) and improve pregnancy rates (risk ratio, 1.24; 95% confidence interval, 1.02-1.50; I2=0%). A subgroup analysis was conducted to evaluate factors that influence the effect of hyaluronic acid on the incidence of intrauterine adhesion. It was found that a small volume of hyaluronic acid reduced the incidence of intrauterine adhesions. Hyaluronic acid exhibited a protective effect among patients who underwent various intrauterine surgeries and who had different gynecologic medical histories. The protective effect was statistically significant after a follow-up of 6 to 12 weeks. The results of the trial sequential analysis indicated that the effect of hyaluronic acid on the incidence of mild intrauterine adhesions, pregnancy rates, live birth rates, and miscarriage rates after intrauterine surgery may be inconclusive and thus further evaluation is required in the form of additional clinical trials. However, the remaining effects were found to be verifiable and did not require more clinical trials for confirmation. CONCLUSION: Hyaluronic acid can safely and effectively reduce the incidence of intrauterine adhesions and may improve fertility outcomes.

Effects of adipose tissue-derived stromal vascular fraction on osteochondral defects treated by hyaluronic acid-based scaffold: An experimental study.

OBJECTIVES: This study aims to evaluate the effect of adipose-derived stromal vascular fraction (SVF) on osteochondral defects treated by hyaluronic acid (HA)-based scaffold in a rabbit model. MATERIALS AND METHODS: Eighteen white New Zealand rabbits were randomly grouped into the experimental group (n=9) and control group (n=9). In all groups, osteochondral defects were induced on the weight-bearing surfaces of the right femoral medial condyles, and a HA-based scaffold was applied to the defect area with microfractures (MFs). In this study, 1 mL of adipose-derived SVF was injected into the knee joints of the rabbits in the experimental group. For histological and macroscopic evaluation, four rabbits were randomly selected from each group at Week 4, and the remaining rabbits were sacrificed at the end of Week 8. Macroscopic assessments of all samples were performed based on the Brittberg scoring system, and microscopic evaluations were performed based on the O'Driscoll scores. RESULTS: Samples were taken at Weeks 4 and 8. At Week 4, the O'Driscoll scores were significantly higher in the control group than the experimental group (p=0.038), while there was no significant difference in the Brittberg scores between the two groups (p=0.108). At Week 8, the O'Driscoll score and Brittberg scores were statistically higher in the experimental group than in the control group (p=0.008 and p=0.007, respectively). According to the microscopic evaluation, at the end of Week 8, the cartilage thickness was greater in the experimental group, and nearly all of the defect area was filled with hyaline cartilage. CONCLUSION: Application of adipose-derived SVF with MF-HA-based scaffold was better than MF-HA-based scaffold treatment in improving osteochondral regeneration. Therefore, it can be used in combination with microfracture and scaffold to accelerate cartilage regeneration, particularly in the treatment of secondary osteoarthritis.

Evolution of the Hyaluronic Acid in Viscosupplementation - from Linear Particles to Hybrid Complexes.

The discovery of unique properties of the hyaluronic acid and learning about the role of this aid in pathophysiology of extracellular matrices resulted in using this substance in pharmacological support in cases of tissue dysfunction due to numerous disease units. Therefore, the products containing this substance are now widely used in medicine including dermatology and aesthetic medicine, ophthalmology, facial-mandibular surgery and orthopedics, being among the most effective products used in the treatment of numerous cases of function impairment and deformation of tissues and organs. There are applied in both post-traumatic and post-inflammatory conditions as well as in symptoms due to chronic conditions. Their therapeutic effects result from joint surface moisturizing, reduction of the coefficient of friction (COF) and good bio-tolerance and biocompatibility confirmed by a low percentage of side effects and biocompatibility. The introduction of hyaluronic acid hybrid complexes with high and low molecular mass (H/L-HA) has increased the clinical usefulness of hyaluronic acid products thanks to their increased viscoelasticity, increased anti-inflammatory and chondroprotective properties and thermodynamic stabilization of the product guaranteeing its half-life. Thanks to the above mentioned pro-perties it becomes more effective in the non-surgical treatment of osteoarthritis.

A randomized study protocol comparing the platelet-rich plasma with hyaluronic acid in the treatment of symptomatic knee osteoarthritis.

BACKGROUND: In recent years, intra articular injection of platelet rich plasma has attracted increasing attention. The major aim of our current randomized controlled double-blind study was to compare long-term outcomes of intra-articular injection of hyaluronic acid or platelet rich plasma in the treatment of the patients with knee osteoarthritis. METHODS: This is a kind of double-blind, randomized, prospective, and comparative clinical investigation with the allocation ratio of 1:1 and was approved by our institutional review Committee. Between 2020 and 2021, altogether 2 hundred patients will be selected to participate in our present study. We will report the randomized experiments in accordance with the guidelines of Consolidated Standards of Reporting Trials and then offer the Consolidated Standards of Reporting Trials flow chart. The inclusion criteria were: patients aged from 40 to 70 years old, patients with chief complaint history of at least 1 month and knee joint pain for nearly 6 months, need the analgesic drug treatment, and radiology confirmed knee osteoarthritis. The eligible patients would be randomly divided into 2 groups through applying the random numbers generated by computer before surgery. Outcomes after treatment were assessed using the Western Ontario and McMaster University and the scoring systems of visual analogue scale which were recorded through questionnaires accomplished via the patients prior to the first injection and then at three and six months, 1 and 2 years follow-up. Any adverse events occurred within 1 year after surgery were recorded during follow-up. RESULTS: This should suggest whether biological methods can offer more lasting outcomes than the viscosification. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry6265).

Effects of a Thermosensitive Antiadhesive Agent on Single-Row Arthroscopic Rotator Cuff Repair.

BACKGROUND: Postoperative stiffness after rotator cuff repair is a common complication that can lead to poor outcomes and patient discomfort. The application of an antiadhesive agent at the time of repair recently became an option for clinicians, but little information is available on its effects. PURPOSE: To evaluate and compare retear rates, the incidence of postoperative stiffness, and the clinical outcomes of patients who underwent cuff repair with or without the application of an antiadhesive agent. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Among 296 patients who underwent arthroscopic rotator cuff repair surgery, we compared the outcomes of those injected with a thermosensitive gel antiadhesive agent into the subacromial space (112 cases) versus noninjected controls (184 cases). Retear rates in the 2 groups were determined by magnetic resonance imaging at 1 year after surgery. Shoulder joint range of motion and functional scores were evaluated serially. RESULTS: The rate of retear was significantly lower in the injection group (20/112 cases; 17.9%) than the control group (53/184 cases; 28.8%) (P = .034). Postoperative stiffness was not significantly different between the 2 groups (P = .710). Among the data regarding range of motion, only forward flexion at 6 months after surgery showed superior results in the injection group. Functional scores showed conflicting results: The control group had better visual analog scale scores for pain (injection vs control: 2.17 vs 1.68 at 6 months; 1.82 vs 1.28 at 12 months), American Shoulder and Elbow Surgeons scores (79.89 vs 89.64 at 12 months), and simple shoulder test scores (8.70 vs 10.06 at 12 months), whereas the injection group had better Constant-Murley scores (injection vs control: 59.49 vs 55.60 at 3 months; 77.35 vs 71.98 at 6 months; 87.28 vs 81.56 at 12 months). CONCLUSION: The tendon healing rate was significantly higher in the group receiving an antiadhesive agent than in the control group. No intergroup difference was seen in the occurrence of postoperative stiffness. However, the pain-related functional score showed inferior results in the injection group at 12 months. The biological action of antiadhesive agents in rotator cuff repair should be further evaluated.

Knee OA cost comparison for hyaluronic acid and knee arthroplasty.

BACKGROUND: Limiting treatment to those recommended by the American Academy of Orthopaedic Surgeon Clinical Practice Guidelines has been suggested to decrease costs by 45% in the year prior to total knee arthroplasty, but this only focuses on expenditures leading up to, but not including, the surgery and not the entire episode of care. We evaluated the treatment costs following knee osteoarthritis (OA) diagnosis and determined whether these are different for patients who use intra-articular hyaluronic acid (HA) and/or knee arthroplasty. METHODS: Claims data from a large commercial database containing de-identified data of more than 100 million patients with continuous coverage from 2012 to 2016 was used to evaluate the cumulative cost of care for over 2 million de-identified members with knee OA over a 4.5-year period between 2011 and 2015. Median cumulative costs were then stratified for patients with or without HA and/or knee arthroplasty. RESULTS: Knee OA treatment costs for 1,567,024 patients over the 4.5-year period was $6.60 billion (mean $4210/patient) as calculated by the authors. HA and knee arthroplasty accounted for 3.0 and 61.5% of the overall costs, respectively. For patients who underwent knee arthroplasty, a spike in median costs occurred sooner for patients without HA use (around the 5- to 6-month time point) compared to patients treated with HA (around the 16- to 17-month time point). CONCLUSIONS: Non-arthroplasty therapies, as calculated by the authors, accounted for about one third of the costs in treating knee OA in our cohort. Although some have theorized that limiting the use of HA may reduce the costs of OA treatment, HA only comprised a small fraction (3%) of the overall costs. Among patients who underwent knee arthroplasty, those treated with HA experienced elevated costs from the surgery later than those without HA, which reflects their longer time to undergoing knee arthroplasty. The ability to delay or avoid knee arthroplasty altogether can have a substantial impact on the cost to the healthcare system.

Minimally Invasive Therapies for Osteoarthritic Hip Pain: a Comprehensive Review.

PURPOSE OF REVIEW: Osteoarthritis (OA) is a highly prevalent cause of chronic hip pain, affecting 27% of adults aged over 45 years and 42% of adults aged over 75 years. Though OA has traditionally been described as a disorder of "wear-and-tear," recent studies have expanded on this understanding to include a possible inflammatory etiology as well, damage to articular cartilage produces debris in the joint that is phagocytosed by synovial cells which leads to inflammation. RECENT FINDINGS: Patients with OA of the hip frequently have decreased quality of life due to pain and limited mobility though additional comorbidities of diabetes, cardiovascular disease, poor sleep quality, and obesity have been correlated. Initial treatment with conservative medical management can provide effective symptomatic relief. Physical therapy and exercise are important components of a multimodal approach to osteoarthritic hip pain. Patients with persistent pain may benefit from minimally invasive therapeutic approaches prior to consideration of undergoing total hip arthroplasty. The objective of this review is to provide an update of current minimally invasive therapies for the treatment of pain stemming from hip osteoarthritis; these include intra-articular injection of medication, regenerative therapies, and radiofrequency ablation.

Efficacy Comparison of Hyaluronic Acid and Corticosteroid Injection in Treatment of Trigger Digits: A Randomized Controlled Trial.

Background: Although the current nonsurgical treatment for trigger digits is corticosteroid (CS) injection, it often comes with adverse effects that may cause some limitations. Currently, Hyaluronic acid (HA) has been successfully used in tendinopathy and may be used in stenosing tenosynovitis. The aim of this study is to compare the efficacy of ultrasound-guided injection between the HA and CS in trigger digits treatment. Methods: Double-blind randomized controlled trial was conducted. Fifty patients with 66 trigger digits were randomly assigned into an intervention group (1 ml of low-molecular weight HA) and a control group (1 ml of 10mg/ml triamcinolone acetate). The ultrasound-guided injection and local anesthesia (0.5 ml of 1% lidocaine without adrenaline) were used. The Quinnell grading, Visual Analog Scale (VAS) score of pain, Disabilities of the Arm, Shoulder and Hand (DASH) score and complications were collected at 1-, 3-and 6-month follow-up. Results: The mean age of HA group (33 digits) and CS group (33 digits) were 58.3 years and 54.7 years respectively. Nine patients were loss of follow-up (7 in HA group and 2 in CS group). The Quinnell grades have shown an improvement in both group. The CS group had a significant better improvement at 1-month (p-value < 0.001) and there was no significant difference at 3-and 6-month follow-up between the two groups. The median of VAS and DASH score were significantly improved by time in both groups (p-value < 0.01). The CS group showed a better significant improvement in early period of follow-up (p-value < 0.05). However, there was no significant difference between the two groups in the last follow-up. Conclusions: HA and CS injection has a comparable therapeutic effect in treatment of trigger digits. However, CS injection has higher efficacy of pain and inflammation reduction in the early phase of the disease.

Umbilical cord-derived mesenchymal stem cells for treating osteoarthritis of the knee: a single-arm, open-label study.

BACKGROUND: Despite being a common cause of quality-of-life impairment, there are no efficacious therapies that could prevent the progression of knee osteoarthritis (KOA). We conducted an open-label trial of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and hyaluronic acid (HA) for treating KOA. METHODS: This open-label study was conducted from July 2015 to December 2018 at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Patients diagnosed with KOA were injected three times, comprising of 10 × 106 units of hUC-MSCs in 2-ml secretome implantation and 2-ml hyaluronic acid (HA) injection in the first week, followed with 2-ml HA injection twice in the second and third week. RESULTS: Twenty-nine subjects (57 knees) were recruited. Seventeen (58.6%) subjects were male, and the mean age was 58.3 ± 9.6 years. Thirty-three (57.9%) knees were classified into Kellgren-Lawrence grade I-II KOA (mild OA). hUC-MSCs significantly decreased pain measured by visual analogue scale in severe KOA from initial to 6th month follow-up [5 ± 2.97 to 3.38 ± 2.44 (p = 0.035)]. The International Knee Documentation Committee score significantly increased at 6th month follow-up (53.26 ± 16.66 to 65.49 ± 13.01, p < 0.001, in subjects with grade I-II and 48.84 ± 18.41 to 61.83 ± 18.83, p = 0.008, in subjects with severe KOA). The Western Ontario and McMaster Universities Osteoarthritis decreased significantly in both groups from initial to 6th month follow-up (from 22.55 ± 15.94 to 13.23 ± 10.29, p = 0.003, and from 27.57 ± 15.99 to 17.92 ± 19.1, p = 0.003, in those with mild and severe KOA, respectively). CONCLUSIONS: hUC-MSCs could be a potentially new regenerative treatment for KOA. The maximum effect of hUC-MSCs was achieved after 6 months of injection. LEVEL OF EVIDENCE: Therapeutic level II.

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.

How to Treat Osteoarthritis in Obese Patients?

The close association between osteoarthritis (OA) and obesity is well established. Mechanisms linking obesity and OA involve multifactorial phenomena such as systemic factors (i.e. adipokines and pro-inflammatory cytokines), hormonal disturbances (hyperinsulinemia) and muscule changes (i.e. sarcopenia and lower muscular tone). The concomitant increasing prevalence of the two diseases have major health, social and economic consequences. However, to date no specific recommendation for the medical management of obese patients with OA have been published. Current recommendations only specify that obese patients must lose weight and practice regular physical activity in addition to the usual care. Weight loss improves not only OA symptoms but also metabolic abnormalities and cardiovascular risk factors commonly altered in subjects with obesity. OA symptoms' improvement has been shown to become clinically relevant from a weight loss > 5% of the body weight. In case of morbid obesity, bariatric surgery may be the only alternative for pain relief. After bariatric surgery, an appropriate calcium and vitamin D intake is recommended, since it has been shown that bariatric surgery was associated with a reduction in the bone mineral density and increased risk of fractures. An exercise program is essential for preserving healthy muscles during weight loss. Non-steroidal anti-inflammatory drugs and corticosteroids must be avoided, especially in obese patients with metabolic syndrome. In such patients symptomatic slow acting drugs for OA (i.e. glucosamine, chondroitin) and some anti-oxidant drugs (i.e. curcumin, ginger extracts, copper) may be helpful thanks to their excellent benefit/risk ratio and their mode of action which may have a positive impact on both OA and obesity-related metabolic disorders. Recent research focuses on the development of molecules aimed for promoting the production of heme oxygenase (HO-1). HO-1 decreases the production of oxygen free radicals and protects tissues from oxidative stress in the insulin resistance syndrome. Intra-articular (IA) injections of hyaluronic acid and corticosteroid have few adverse events. However, physicians must inform patients that IA treatments have a lower success rate in obese patients than in those with normal body mass index. Spa therapy contributes to relief pain, favour weight-loss and reduces metabolic abnormalities with a favourable risk/benefit balance.

[Budget impact analysis of viscosupplementation for non-surgical treatment of knee osteoarthritis]. / Análise do impacto orçamentário da viscossuplementação no tratamento não cirúrgico da osteoartrite de joelho.

Knee osteoarthritis affects 3.8% of the world population and manifests as pain, edema, stiffness, and reduced joint function, impacting the patient's quality of life. Treatment consists of the pharmacological, non-pharmacological, and surgical modalities. Viscosupplementation (intraarticular hyaluronate) has been proposed to relieve symptoms and potentially postpone surgery. This study estimated the budget impact of the association of this drug and non-surgical treatment (standard treatment) from the perspective of the Brazilian Unified National Health System. Based on the assumption that 5% of patients proceed to treatment and on the direct costs of the pharmacological and non-pharmacological modalities, the authors calculated the reference and alternative scenarios that compared the different treatment options in a three-year timeline. The principal analysis estimated an incremental budget impact of approximately BRL 126 million (U$ 32 million) for one vial of hyaluronate a year and BRL 252 million (USD 64 million) for two vials a year. Diacerein, an oral chondroprotector, assessed as an alternative, showed a budget impact of BRL 334 million (USD 86 million) in relation to standard treatment, representing a 24% cost increase compared to two vials a year of hyaluronate, making it less economically advantageous. Viscosupplementation can provide better quality of life for patients, reduce costs for the health system, and optimize the flow of care in health services. The estimates presented in this study can assist administrators in the best use of resources and thus in decision-making on the technology's incorporation.

A osteoartrite de joelho afeta cerca de 3,8% da população mundial e se manifesta por dor, edema, rigidez e redução da função articular, impactando na qualidade de vida do paciente. O tratamento consiste na modalidade farmacológica, não farmacológica e cirúrgica. A viscossuplementação (ácido hialurônico intra-articular) se propõe a oferecer alívio dos sintomas e a possibilidade de adiamento da cirurgia. Este estudo estimou o impacto orçamentário entre a associação desse medicamento e o tratamento não cirúrgico (tratamento padrão), sob a perspectiva do Sistema Único de Saúde. Com base no pressuposto de que 5% dos portadores da doença seguem para tratamento e nos custos diretos das modalidades: farmacológica e não farmacológica foram calculados os cenários de referência e alternativos que compararam as diferentes opções de tratamento para um horizonte temporal de três anos. A análise principal estimou um impacto orçamentário incremental de aproximadamente R$ 126 milhões (1 ampola anual) e R$ 252 milhões (2 ampolas anuais). Já a diacereína, um condroprotetor oral, avaliada como uma opção alternativa, mostrou um impacto de R$ 334 milhões no orçamento em relação ao tratamento padrão, o que proporciona um aumento de 24% no custo em relação ao uso de 2 ampolas anuais de ácido hialurônico, tornando-a economicamente menos vantajosa. A viscossuplementação pode proporcionar maior qualidade de vida ao paciente, redução de custos para o sistema e otimização do fluxo de atendimento nas unidades de saúde. As estimativas apresentadas neste estudo podem auxiliar o gestor quanto à melhor utilização dos recursos financeiros e consequente tomada de decisão quanto à incorporação da tecnologia.

La osteoartritis de rodilla afecta a cerca de un 3,8% de la población mundial y se manifiesta por dolor, edema, rigidez y reducción de la función articular, impactando en la calidad de vida del paciente. El tratamiento consiste en la modalidad farmacológica, no farmacológica y quirúrgica. La viscosuplementación (ácido hialurónico intraarticular) se propone ofrecer un alivio de los síntomas y la posibilidad de un aplazamiento de la cirugía. Este estudio estimó el impacto presupuestario entre la asociación de este medicamento y el tratamiento no quirúrgico (tratamiento estándar), desde la perspectiva del Sistema Único de Salud. Basándonos en el supuesto de que un 5% de los portadores de la enfermedad siguen el tratamiento y en los costos directos de las modalidades tanto farmacológica, como no farmacológica, se calcularon los escenarios de referencia y alternativos que compararon las diferentes opciones de tratamiento para un horizonte temporal de tres años. El análisis principal estimó un impacto presupuestario incremental de aproximadamente BRL 126 millones (1 ampolla anual) y BRL 252 millones (2 ampollas anuales). En el caso de la diacereína, un condroprotector oral, evaluado como una opción alternativa, mostró un impacto de BRL 334 millones en el presupuesto, respecto al tratamiento estándar, lo que proporciona un aumento de un 24% en el costo, en relación con el uso de 2 ampollas anuales de ácido hialurónico, haciéndola económicamente menos ventajosa. La viscosuplementación puede proporcionar mayor calidad de vida al paciente, reducción de costes para el sistema y la optimización del flujo de atención en las unidades de salud. Las estimaciones presentadas en este estudio pueden ayudar al gestor en lo referente a una mejor utilización de los recursos financieros y, consecuentemente, en la toma de decisiones respecto a la incorporación de tecnología.

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.

Comparison of treatment efficacy between hyaluronic acid and arthrocentesis plus hyaluronic acid in internal derangements of temporomandibular joint.

The aim of the study was to compare the effectiveness of hyaluronic acid (HA) injection and arthrocentesis plus HA injection for treating disc displacement with reduction (DDwR) and disc displacement without reduction (DDwoR). In this randomized clinical trial, patients were divided into 2 main groups: group I (DDwR) and group II (DDwoR). Sub-groups were made depending on allocated treatment: group Ia (arthrocentesis plus HA), group Ib (single HA), group Ic (control), group IIa (arthrocentesis plus HA), group IIb (single HA), and group IIc (control). The primary outcome variable was maximum pain on chewing, while maximum pain at rest, maximum non-assisted and assisted mouth opening, chewing efficiency, temporomandibular joint (TMJ) sounds, quality of life, treatment tolerability, and treatment effectiveness were secondary outcomes. The influences of individual study variables (gender, involved side, and duration of symptoms) on clinical outcomes were also examined. The study consisted of 116 TMJs of 90 patients (n = 45 in both main groups, TMJs = 58) aged 15-82 years. At the 6-month follow-up, improvement in all parameters, except for TMJ sounds, was recorded in all treatment groups, with no improvements in control groups. Notably, arthrocentesis plus HA showed superior improvement in chewing efficiency (p = 0.041) and quality of life (p = 0.047) of group I and quality of life (p = 0.004) in group II, compared to single HA. Furthermore, the duration of symptoms correlated with clinical outcomes. Both procedures successfully improved the symptoms of DDwR and DDwoR patients, but arthrocentesis plus HA injection seemed superior.

Specifically Sized Hyaluronan (35 kDa) Prevents Ethanol-Induced Disruption of Epithelial Tight Junctions Through a layilin-Dependent Mechanism in Caco-2 Cells.

BACKGROUND: Specific-sized species of the carbohydrate hyaluronan elicit a variety of cellular responses mediating tissue integrity and repair, as well as regulating inflammatory responses. Orally provided hyaluronan with an average molecular weight of 35 kDa (HA35) protects mice from short-term ethanol (EtOH)-induced liver injury. This protection was associated with maintenance of the colocalization of zonula occludens-1 (ZO-1) and occludin at tight junctions in the proximal colon. However, it is not known whether HA35 also protects other regions of the intestine or whether protection is due to a direct and/or indirect interaction of HA35 with the intestinal epithelium. METHODS: Female C57BL/6J mice were fed an EtOH containing diet or pair-fed control diet (4 days) and treated with or without HA35 via daily gavage during the last 3 days of EtOH feeding. Intestinal morphology and tight junction integrity were assessed. Differentiated Caco-2 cells were transfected or not with scrambled siRNA or siRNA targeting layilin, a hyaluronan receptor. Caco-2 cells were treated with or without HA35 prior to challenge with EtOH. Localization of tight junction proteins, fluorescein isothiocyanate (FITC)-dextran permeability, and transepithelial electrical resistance (TEER) were evaluated. RESULTS: While short-term EtOH did not result in any apparent changes in the gross morphology of the intestine, colocalization of ZO-1 and occludin at tight junctions was decreased in the proximal and distal colon. HA35 prevented these effects of EtOH. In differentiated Caco-2 cells, EtOH decreased the localization of ZO-1 and occludin at tight junctions and increased permeability of FITC-dextran. At higher concentrations, EtOH also decreased TEER. Pretreatment with HA35 prevented these changes. When the hyaluronan receptor layilin was knocked down in Caco-2 cells, HA35 no longer protected cells from EtOH-induced loss of tight junctions. CONCLUSIONS: Taken together, these data indicate that HA35 interacts with layilin on intestinal epithelial cells and maintains intestinal tight junction integrity during short-term EtOH exposure.