The development of a clinical nomogram to predict medication nonadherence in patients with knee osteoarthritis.

Knee osteoarthritis (KOA) is a common bone disease in older patients. Medication adherence is of great significance in the prognosis of this disease. Therefore, this study analyzed the high-risk factors that lead to medication nonadherence in patients with KOA and constructed a nomogram risk prediction model. The basic information and clinical characteristics of inpatients diagnosed with KOA at the Department of Orthopedics, The Affiliated Hospital of Chengde Medical University, were collected from January 2020 to January 2022. The Chinese version of the eight-item Morisky scale was used to evaluate medication adherence. The Kellgren-Lawrence (KL) classification was performed in combination with the imaging data of patients. Least absolute shrinkage and selection operator regression analysis and logistic multivariate regression analysis were used to analyze high-risk factors leading to medication nonadherence, and a prediction model of the nomogram was constructed. The model was internally verified using bootstrap self-sampling. The index of concordance (C-index), area under the operating characteristic curve (AUC), decision curve, correction curve, and clinical impact curve were used to evaluate the model. A total of 236 patients with KOA were included in this study, and the non-adherence rate to medication was 55.08%. Seven influencing factors were included in the nomogram prediction: age, underlying diseases, diabetes, age-adjusted Charlson comorbidity index (aCCI), payment method, painkillers, and use of traditional Chinese medicine. The C-index and AUC was 0.935. The threshold probability of the decision curve analysis was 0.02-0.98. The nomogram model can be effectively applied to predict the risk of medication adherence in patients with KOA, which is helpful for medical workers to identify and predict the risk of individualized medication adherence in patients with KOA at an early stage of treatment, and then carry out early intervention.

Personalized Nutritional Strategies to Reduce Knee Osteoarthritis Severity and Ameliorate Sarcopenic Obesity Indices: A Practical Guide in an Orthopedic Setting.

Knee osteoarthritis (KOA) is one of the most common joint diseases, especially in individuals with obesity. Another condition within this population, and which presents frequently, is sarcopenic obesity (SO), defined as an increase in body fat and a decrease in muscle mass and strength. The current paper aims to describe recent nutritional strategies which can generally improve KOA clinical severity and, at the same time, ameliorate SO indices. Searches were carried out in the PubMed and Science Direct databases and data were summarized using a narrative approach. Certain key findings have been revealed. Firstly, the screening and identification of SO in patients with KOA is important, and to this end, simple physical performance tests and anthropometric measures are available in the literature. Secondly, adherence to a Mediterranean diet and the achievement of significant body weight loss by means of low-calorie diets (LCDs) remain the cornerstone nutritional treatment in this population. Thirdly, supplementation with certain micronutrients such as vitamin D, essential and non-essential amino acids, as well as whey protein, also appear to be beneficial. In conclusion, in the current review, we presented a detailed flowchart of three different nutritional tracks that can be adopted to improve both KOA and SO based on joint disease clinical severity.

Rehabilitation interventions in osteoarthritis.

The goals of the management of osteoarthritis (OA) are to relieve joint pain and stiffness, maintain or increase joint mobility and stability, improve activities and participation, and enhance quality of life. The first step in the management is to make a comprehensive holistic assessment to understand the impact of the disease on the individual. Then, an individualized management plan can be set via a shared-decision making process between the patient and the clinician taking into account all components of functioning affected by the disease. Rehabilitation interventions serve as the basis of OA management whereas pharmacological modalities are usually administered for additional symptom control. This study aimed to overview the rehabilitation interventions used for people with OA with an update of the recent evidence. First, core management approaches that include patient education, physical activity and exercises, and weight loss were addressed; then adjunctive treatments including biomechanical interventions (e.g. orthoses, assistive devices) and physical modalities were overviewed.

Laser therapy versus pulsed electromagnetic field therapy as treatment modalities for early knee osteoarthritis: a randomized controlled trial.

BACKGROUND: This randomized controlled trial aimed to compare the effects of pulsed electromagnetic field therapy (PEMFT) and low-level laser therapy (LLLT) on pain and physical function of participants with knee osteoarthritis (KOA). METHODS: According to the Kellgren-Lawrence classification, participants with grade 2-3 KOA were randomized to receive PEMFT or LLLT for six sessions lasting 15 min/session over a 3-week period. Pain at rest and when walking, standing from a sitting position, and climbing the stairs was assessed using the visual analog scale. Functional level was measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), timed up-and-go test (TUG), and 10-m walk (10 MW) test. Measurements were obtained before and after the interventions. Significance was determined at p ≤ 0.05. RESULTS: Forty participants were included in the study. Pain and physical function improved significantly (p < 0.0001) in both groups. PEMFT was significantly more effective in reducing pain at rest, when standing from a sitting position, and when climbing the stairs, and in improving both WOMAC scores and TUG results (p ≤ 0.0003). The improvements in pain during the activities and the WOMAC scores reached the minimal clinically important difference. No adverse events occurred. CONCLUSION: Six sessions of PEMFT and LLLT had immediate positive effects on pain and physical function in individuals with low-grade KOA, with PEMFT resulting in significantly better results. TRIAL REGISTRATION: ISRCTN registry trial ID: ISRCTN17001174.

The influence of vitamin D supplementation on the expression of mediators of inflammation in knee osteoarthritis.

This trial aimed to determine the possible therapeutic and immunomodulatory effects of vitamin D3 in patients with knee OA. In this open-label clinical trial, symptoms were assessed over 3 months in patients with primary knee OA receiving oral vitamin D3 4000 IU/day. Clinical response was evaluated at baseline and 3 months using WOMAC subscores and VAS. Serum levels of cytokines IL-1ß, TNF-α, IL-13, IL-17, IL-33, IL-4, and IL-10 were determined by ELISA method. Eighty patients with knee OA were included. All 80 completed the study; the median 25(OH)D3 level was 23.1 ng/ml at baseline and increased by 12.3 ng/ml after treatment. Vitamin D3 after 3 months of supplementation induced a significant reduction in VAS pain and WOMAC subscores. Using OMERACT-OARSI criteria, 86.7% of patients treated with vitamin D3 responded to treatment. At the end of 3 months, systemic values of IL-1ß (p < 0.01), IL-23 (p < 0.01), and IL-33 (p < 0.01) were significantly increased, values of TNF-α (p < 0.01), IL-13 (p < 0.01), and IL-17 (p < 0.01) were significantly decreased, while value of IL-4 was not significantly changed. No adverse events were detected. Treatment with vitamin D is associated with improvement in pain, as well as stiffness and physical function. Vitamin D supplementation increased systemic values of IL-33. Our results indicate that vitamin D3 supplementation may be used as a novel therapeutic in knee OA. Future studies are needed to investigate a potential role of IL-33 in the pathogenesis of knee OA.

Efficacy and safety of Sri Lankan traditional medicine regimen for knee osteoarthritis: study protocol for an open-label, active comparator, randomized controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) is the most common form of arthritis, causing disability and impaired quality of life especially in the elderly. Sri Lankan traditional medicine (STM) is widely used to treat OA, but no clinical trial evaluated on STM regimens for KOA to discuss their safety and efficacy in the treatment. The aim of this study is to compare the efficacy and safety of STM regimen for KOA in comparison to recommended conventional pain management therapy over a period of 8 weeks on relieving the condition. STUDY DESIGN: This is a clinical trial following a protocol-driven open-labeled randomized controlled study enrolling patients with KOA that will be conducted as a single-center trial in the National Ayurveda Teaching Hospital, Sri Lanka. Rasnadvigunabhagasaya herbal decoction (RDBD) and an herbal pill Yoaraja Guggulu were selected as the rescue medication for treating joint disorders. The two Ayurvedic dosage forms will be tested against the non-steroidal anti-inflammatory drugs tab paracetamol and tab ibuprofen as the rescue medication for their safety and efficacy. As test products for external application, oil with an herbal fomentation-Kumburuetaperumkayam Pottani (KAP)-and paste-Sandivadam Lepaya (SVL)-were selected. External applications will be tested against the diclofenac sodium gel and hot water fomentation. KOA patients will be allocated randomly into two arms, and the medications will be given orally for 60 days and externally for 30 days. The primary endpoint is the change in the score on the WOMAC after 08 weeks. WOMAC and KOOS will be recorded and compared between the two arms prior to visiting 1, at the end of 15 days and end of 30 days, and end of the 45 days and end of the second month and 3 months of follow-up. KOOS and WOMAC subscales, a pain disability index, a visual analog scale for pain and sleep quality, and a quality-of-life index are used as secondary outcome measurements. DISCUSSION: This clinical trial will be able to provide evidence-based scientific data on Sri Lankan traditional medicine regimens in the management of KOA. This trial is expected to develop capacity to scientifically evaluate various STM that are claimed to have efficacy in treatment of various disease conditions. TRIAL REGISTRATION: ISRCTN58050062 .

Effects of Modified Duhuo Jisheng Decoction Combined with Arthroscopic Surgery on Bone Metabolism, Oxidative Stress, and Serum TLR4 and TGF-ß1 in Patients with Knee Osteoarthritis.

Objective: To analyze the effects of modified Duhuo Jisheng Decoction combined with arthroscopic surgery on bone metabolism, oxidative stress, and serum TLR4 and TGF-ß1 in patients with knee osteoarthritis (KOA). Methods: Prospectively select 82 patients with KOA from January 2020 to January 2022 in our hospital and divide them into the control group and observation group according to the random number table method, with 41 patients in each group. The control group was treated with arthroscopic surgery alone and routine anti-infection after operation. The observation group was treated with Duhuo Jisheng Decoction on the basis of the treatment of the control group. The patients in the two groups were treated continuously for 4 weeks. The improvement of patients' symptoms was evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Before treatment and 4 weeks after treatment, the scores of traditional Chinese medicine (TCM) symptoms, bone metabolism indicators (cartilage oligomeric matrix protein (COMP), collagen type II carboxy terminal peptide (ctx-II), and matrix metalloproteinase-3 (MMP-3)), oxidative stress indicators (superoxide dismutase (SOD), glutathione peroxidase (GSHPx), malondialdehyde (MDA), nitric oxide (NO)), serum Toll-like receptor 4 (TLR4), and transforming growth factor ß (TGF-ß) level were compared between the two groups. Results: After treatment, the WOMAC score of the two groups decreased (42.45 ± 10.83) in the observation group and (67.81 ± 14.63) in the control group. The WOMAC score of the observation group was lower than that of the control group (P < 0.05). After treatment, the levels of COMP, CTX-II, and MMP-3 in the two groups decreased, and the levels of COMP, CTX-II, and MMP-3 in the observation group were lower than those in the control group (P < 0.05). After treatment, the levels of SOD and GSHPx increased, while the levels of MDA and NO decreased in the two groups. The levels of SOD and GSHPx in the observation group were higher than those in the control group, while the levels of MDA and NO were lower than those in the control group (P < 0.05). After treatment, the TLR4 level in the observation group was lower than that of the control group, and the level of TGF-ß in the observation group was higher than that of the control group (P < 0.05). Conclusion: Compared with arthroscopic surgery alone, combined with modified Duhuo Jisheng Decoction can better alleviate the clinical symptoms of patients with KOA, improve their bone metabolism, oxidative stress indicators, and serum TLR4 and TGF-ß 1 level, and reduce the inflammatory injury of knee joint.

Rubus idaeus extract improves symptoms in knee osteoarthritis patients: results from a phase II double-blind randomized controlled trial.

BACKGROUND: Osteoarthritis (OA) is the most frequent cause of disability in elderly people. In daily practice, the main objective of the physician is to reduce patient symptoms using treatments without adverse effects. However, the most prescribed treatment to manage OA symptoms remains nonsteroidal anti-inflammatory drugs which are associated with severe adverse effects. Therefore, we need a safe alternative to managing OA. One candidate is Rubus idaeus leaf extracts known to inhibit inflammatory responses. OBJECTIVE: This study aimed to evaluate the effects of a 12-weeks intervention with an ethanolic extract from Rubus idaeus leaf on symptoms of knee osteoarthritis. METHOD: The study was a randomized, double-blind, placebo-controlled, monocentric trial of 198 participants with femorotibial osteoarthritis. Participants were randomized equally to receive one daily during 3 months either 1 capsule of Rubus idaeus leaf extract 400 mg, 1 capsule of Rubus idaeus leaf extract 200 mg, or 1 capsule of placebo. The participants were assessed at baseline and after one and three months of treatment. The primary endpoint was an absolute change of the Western Ontario McMaster osteoarthritis index (WOMAC) pain subscale. The secondary endpoints were WOMAC global score, stiffness and function sub-scales, knee pain VAS score at walking, the Short Form (SF)-36, the Short Physical Performance Battery (SPPB), the 20-m walk test, and the International Physical Activity Questionnaire (IPAQ) and Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) responders rate. Statistical analyses were conducted on the intent-to-treat (ITT) population. RESULTS: In the Intention-to-treat population, WOMAC pain was not significantly modified by Rubus idaeus leaf extract compared to placebo. In contrast, Rubus idaeus leaf extract 400 mg after 12 weeks of treatment significantly reduced pain measured by the VAS. The mean pain decrease induced by Rubus ideaus leaf extract was over -7 mm which is clinically relevant and reached a clinically statistical difference compared to placebo with the highest dose. Rubus Ideaus was not significantly more efficient than the placebo on WOMAC global score, stiffness, and physical function subscores, IPAQ, SF-36, walking distance in treadmill test, SPPB, and evaluation of associated treatments needed to manage OA. CONCLUSION: Rubus idaeus leaf extract was well tolerated and effective to relieve pain in a patient with knee osteoarthritis. TRIAL REGISTRATION: NCT03703024  (11/10/2018).

Effects of pulsed electromagnetic field therapy on outcomes associated with osteoarthritis : A systematic review of systematic reviews.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative disease of multiple joints with a rising prevalence. Pulsed electromagnetic field (PEMF) therapy may provide a cost-effective, noninvasive, and safe therapeutic modality with growing popularity and use in physical medicine and rehabilitation. The purpose of this study was to synthesize the current knowledge on the use of PEMF in OA. METHODS: A systematic review of systematic reviews was performed. The PubMed, Embase, PEDro and Web of Science databases were searched based on a predetermined protocol. RESULTS: Overall, 69 studies were identified. After removing the duplicates and then screening title, abstract and full text, 10 studies were included in the final analysis. All studies focused on knee OA, and four studies also reported on cervical, two on hand, and one on ankle OA. In terms of the level of evidence and bias, most studies were of low or medium quality. Most concurrence was observed for pain reduction, with other endpoints such as stiffness or physical function showing a greater variability in outcomes. CONCLUSION: The PEMF therapy appears to be effective in the short term to relieve pain and improve function in patients with OA. The existing studies used very heterogeneous treatment schemes, mostly with low sample sizes and suboptimal study designs, from which no sufficient proof of efficacy can be derived. A catalogue of measures to improve the quality of future studies has been drawn up.

Quantitative Sensory Testing Protocols to Evaluate Central and Peripheral Sensitization in Knee OA: A Scoping Review.

OBJECTIVE: This scoping review analyzed various quantitative sensory testing methodologies used in the assessment of sensitization and how sensitization is defined in people with knee osteoarthritis. DESIGN: A scoping review. SETTING: All clinical and research settings. SUBJECTS: Non-surgical adults with knee osteoarthritis. METHODS: This scoping review was guided by existing scoping review methodologies. Relevant studies were extracted from the following electronic databases: Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Allied and Complementary Medicine Database, and the Cumulative Index to Nursing Allied Health Literature. Abstract and full article screening and data extraction were performed in pairs. Information on quantitative sensory testing techniques and parameters was extracted and summarized in tables. General and technique specific definitions of sensitization were extracted from included texts. RESULTS: Our search yielded 4,199 articles, of which 50 were included in our review. The most common quantitative sensory test was pressure pain threshold. In total 28 unique testing sites were found speaking to the high degree of variability between studies. Sensitization was poorly defined with only 8 studies fully operationalizing it, 22 partially, and the remainder did not provide sufficient information to meet our criteria. CONCLUSIONS: This scoping review has provided an overview of the most common methods of quantitative sensory testing being implemented in the assessment of nervous system sensitization to nociceptive signaling in people with knee osteoarthritis. This study provides a foundation for future development of quantitative sensory testing methodology for research and clinical practice in the osteoarthritis population.

Increased Ratio of CD14++CD80+ Cells/CD14++CD163+ Cells in the Infrapatellar Fat Pad of End-Stage Arthropathy Patients.

Objectives: This study sought to identify the ratio of M1/M2 cells in the infrapatellar fat pads (IFP) and subcutaneous fat tissues (SC) of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. The clinical features of OA and RA patients treated with or without biological disease-modifying anti-rheumatic drugs (bDMARDs) were also assessed. Methods: IFP and SC were collected from patients with OA and RA who are undergoing total knee arthroplasty (TKA). CD14-positive cells were then isolated from these samples. Flow cytometry was used to determine the number of CD14++CD80+ cells and CD14++CD163+ cells. The expression levels of lipid transcription factors, such as sterol regulatory element-binding protein 1 (SREBP1) and liver X receptor alpha (LXRA), and inflammatory cytokines were also evaluated. Results: Twenty OA patients and 22 RA patients were enrolled in this study. Ten of the RA patients (45.4%) received bDAMRDs before TKA. On average, a fivefold increase in the number of CD14-positive cells and lower expression levels of SREBP1C and LXRA were observed in OA IFP relative to OA SC; however, these results were not obtained from the RA samples. The median ratio of CD14++CD80+ cells/CD14++CD163+ cells of OA IFP was 0.87 (0.76-1.09, interquartile range), which is higher to that of OA SC with a lower ratio (p = 0.05835). Conclusions: The quantity and quality of CD14-positive cells differed between IFP and SC in arthropathy patients. To our knowledge, this is the first study to characterize the ratio of M1/M2 cells in the IFP and SC of end-stage OA and RA patients. The increased ratio of CD14++CD80+ cells/CD14++CD163+ cells in the IFP from patients with OA and RA treated with bDMARDs indicated that inflammation was localized in the IFP. As adipose tissue-derived innate immune cells were revealed as one of the targets for regulating inflammation, further analysis of these cells in the IFP may reveal new therapeutic strategies for inflammatory joint diseases.

Effectiveness and safety of acupotomy for knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Acupotomy may be effective for KOA, but the evidence is limited. This trial aims to determine the effectiveness and safety of acupotomy for KOA. METHODS/DESIGN: This is a parallel-group, assessor-blinded randomized controlled trial. Two hundred patients with KOA will be recruited and randomly assigned to two groups (group A or group D) in a 1:1 ratio. Patients in group A will receive acupotomy and topical diclofenac diethylamine for 4 weeks, while patients in group D will receive topical diclofenac diethylamine alone for 4 weeks. The primary outcome will be the response rate-the proportion of patients who achieve the minimal clinically important improvement in pain and function at week 4 compared with baseline. Secondary outcomes will include pain, function, quality of life, the use of rescue medicine (loxoprofen sodium), and adverse events at weeks 4, 8, and 24 after randomization. Besides, joint fluid and serum will be collected to assess the level of inflammatory cytokines, like TNF-α, IL-1ß, and MMP-3. DISCUSSION: This study will contribute to a better understanding of the effectiveness and safety of acupotomy in combination with topical nonsteroidal anti-inflammatory drugs. If the hypothesis is confirmed, acupotomy may be recommended as adjunctive therapy for patients with KOA. Results of the study will be of great importance for the guidelines of clinical therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100043005 Registered on 4 February 2021.

Synopsis of the 2020 US Department of Veterans Affairs/US Department of Defense Clinical Practice Guideline: The Non-Surgical Management of Hip and Knee Osteoarthritis.

In July 2020, the US Department of Veterans Affairs (VA) and US Department of Defense (DoD) approved a new joint clinical practice guideline for the non-surgical management of hip and knee osteoarthritis. This synopsis highlights some of the recommendations. In February 2019, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched (ie, Cochrane Database of Systematic Reviews, EMBASE, MEDLINE PreMEDLINE, PubMed, and the Agency for Healthcare Research and Quality website) and evaluated the literature, created a simple 1-page algorithm, and advanced 19 recommendations using the Grading of Recommendations Assessment, Development, and Evaluation system. This synopsis summarizes key recommendations in all 6 topics covered in the guideline. These topics are diagnosis, self-management, physical therapy, pharmacotherapy, orthobiologics, and complementary and integrative health.

Efficacy of GCWB106 (Chrysanthemum zawadskii var. latilobum extract) in osteoarthritis of the knee: A 12-week randomized, double-blind, placebo-controlled study.

BACKGROUND: GreenCross Wellbeing Corporation (GCWB) 106 is a food item based on Chrysanthemum zawadskii var. latilobum extract. It has an inhibitory effect on joint inflammation. OBJECTIVE: This study investigated the efficacy and safety of GCWB106 for osteoarthritis (OA) of the knee joint. METHODS: Overall, 121 participants with mild OA were recruited and randomly divided into two groups. One group received GCWB106 for 12 weeks and the other group received placebo for 12 weeks. Outcomes were evaluated using the Korean-Western Ontario and McMaster Universities Index (K-WOMAC), visual analog scale, Korean Short Form Health Survey 36 score, and laboratory test results. RESULTS: After 12 weeks of study treatment, the GCWB106 group exhibited a significant improvement compared with the placebo group in overall K-WOMAC score (P = .042) and K-WOMAC physical function score (P = .015). The GCWB106 group showed significant improvement in the visual analog scale pain score (P < .001) compared with the placebo group after 6 weeks and 12 weeks; no adverse drug reactions or serious adverse events were reported in either group. CONCLUSION: GCWB106 can safely reduce pain and improve knee function with therapeutic effects in OA of the knee joint. LEVEL OF EVIDENCE: Randomized, double-blind, placebo-controlled clinical study, Level I.

Association of Serum Vitamin D with Serum Cytokine Profile in Patients with Knee Osteoarthritis.

OBJECTIVE: The role of vitamin D in the pathogenesis of osteoarthritis (OA) is not well understood. In this study, we aimed to investigate the association of serum vitamin D with the serum cytokine profile in patients with primary knee OA. DESIGN: In a cross-sectional study, 116 patients with radiologic diagnosis of grade I to III knee OA were included. The study population included 79 (75.9%) females and 25 (24.1%) males with a mean age of 55.1 ± 9.6 years. The serum concentration of IL-6, IL-8, TNF-α, IL-4, IL-10, IL-13, and vitamin D were assessed using an enzyme-linked immunosorbent assay. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used for the assessment of patient's reported disability associated with knee OA. RESULTS: Serum vitamin D status was deficient, insufficient, and sufficient in 18 (15.5%), 63 (54.3%), 35 (30.2%) patients, respectively. Higher levels of serum IL-6 were observed in patients with vitamin D deficiency (P = 0.022). The mean serum vitamin D level was not associated with OA grade (P = 0.88) and WOMAC scores of the patients (P = 0.67). Serum IL-6 level was significantly associated with both OA grade and WOMAC scores of the patients (P < 0.001 and P = 0.001, respectively). The vitamin D status was not significantly associated with the serum levels of other evaluated cytokines. CONCLUSION: Vitamin D deficiency in knee OA seems to be associated with a higher release of IL-6. Therefore, vitamin D supplementation could reduce the disease burden by controlling the IL-6 release.

Efficacy and safety of Biqi capsule in the treatment of knee osteoarthritis: A protocol of a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic and degenerative bone and joint disease, with KOA, cartilage degeneration, destruction and subchondral bone remodeling as the main pathological features. Its clinical symptoms are knee pain, swelling, limited activity, and long course of disease can cause joint deformities. At present, the early treatment of Western medicine is mainly the use of nonsteroidal drugs for anti-inflammation and removing pain, but because the efficacy of these drugs is unstable, the disease is easy to repeat after treatment, and the clinical effect is not good. Although Biqi capsule has advantages in the treatment of KOA, there is a lack of standard clinical studies to verify it, so the purpose of this randomized controlled study is to evaluate the efficacy and safety of Biqi capsule in the treatment of KOA. METHODS: This is a prospective randomized controlled trial to study the efficacy and safety of Biqi capsule in the treatment of KOA. The patients were randomly divided into a treatment group and a control group according to 1:1. Among them, treatment group: Biqi capsule combined with diclofenac sodium sustained release tablets; Control group: Diclofenac sodium sustained-release tablets alone. Both groups were treated with standard treatment for 2 weeks and were followed up for 30 days to pay attention to the efficacy and safety indexes. Observation indicators included: the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Hospital for Special Surgery Knee Score (HSS), liver and kidney function, adverse reactions, and so on. SPSS 25.0 software is used for data analysis. DISCUSSION: This study will evaluate the efficacy and safety of Biqi capsule in the treatment of KOA, and the results of this experiment will provide a clinical basis for Biqi capsule in the treatment of KOA. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/6HB9D.

Cost-Effectiveness Assessment of Different Glucosamines in Patients with Knee Osteoarthritis: A Simulation Model Adapted to Germany.

BACKGROUND: The use of symptomatic slow-acting drugs for osteoarthritis (OA) (e.g., glucosamine, chondroitin) is largely debated in the scientific literature. Indeed, multiple formulations of these agents are available, both as pharmaceutical-grade products and as nutritional supplements , but while all preparations may claim to deliver a therapeutic effect, not all are supported by clinical evidence. Moreover, few data are available regarding the cost-effectiveness of all these formulations. Usually, access to individual patient data is required to perform economic evaluations of treatments, but it can be challenging to obtain. We previously developed a model to simulate individual health utility scores from aggregated data obtained from published OA trials. OBJECTIVE: In the present study, using our new simulation model, we investigated the costeffectiveness of different glucosamines used in Germany. METHODS: We used our validated model to simulate the utility scores of 10 published trials that used different glucosamine preparations. Using the simulated utility scores, the quality-adjusted life years (QALYs) were calculated using the area-under-the-curve method. We used the 2018 public costs of glucosamine products available in Germany to calculate the Incremental Cost/Effectiveness Ratio (ICER). We performed analyses for pharmaceutical-grade Crystalline Glucosamine Sulfate (pCGS) and other formulations of glucosamine (OFG). A cost-effectiveness cut-off of 30,000 €/QALY was considered. RESULTS: Of 10 studies in which utility was simulated, four used pCGS, and six used OFG. The ICER analyses showed that pCGS was cost-effective compared to a placebo, with an ICER of 4489 €/QALY at month 3, 4112 €/QALY at month 6, and 9983 €/QALY at year 3. The use of OFG was not cost-effective at any of the time points considered. CONCLUSION: Using our previously published model to simulate the individual health utility scores of patients, we showed that, in the German context, the use of pCGS could be considered costeffective, while the use of OFG could not. These results highlight the importance of the formulation of glucosamine.

Effect of a prebiotic supplement on knee joint function, gut microbiota, and inflammation in adults with co-morbid obesity and knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Osteoarthritis (OA) is a chronic and painful condition where the articular cartilage surfaces progressively degenerate, resulting in loss of function and progressive disability. Obesity is a primary risk factor for the development and progression of knee OA, defined as the "metabolic OA" phenotype. Metabolic OA is associated with increased fat deposits that release inflammatory cytokines/adipokines, thereby resulting in systemic inflammation which can contribute to cartilage degeneration. There is currently no cure for OA. Prebiotics are a type of dietary fiber that can positively influence gut microbiota thereby reducing systemic inflammation and offering protection of joint integrity in rodents. However, no human clinical trials have tested the effects of prebiotics in adults with obesity suffering from knee OA. Therefore, the purpose of this double-blind, placebo-controlled, randomized trial is to determine if prebiotic supplementation can, through positive changes in the gut microbiota, improve knee function and physical performance in adults with obesity and knee OA. METHODS: Adults (n = 60) with co-morbid obesity (BMI > 30 kg/m2) and knee OA (Kellgren-Lawrence grade II-III) will be recruited from the Alberta Hip and Knee Clinic and the Rocky Mountain Health Clinic and surrounding community of Calgary, Canada, and randomized (stratified by sex, BMI, and age) to prebiotic (oligofructose-enriched inulin; 16 g/day) or a calorie-matched placebo (maltodextrin) for 6 months. Anthropometrics, performance-based tests, knee pain, serum inflammatory markers and metabolomics, quality of life, and gut microbiota will be assessed at baseline, 3 months, 6 months (end of prebiotic supplementation), and 3 months following the end of the prebiotic supplementation. CLINICAL SIGNIFICANCE: There is growing pressure on health care systems for aggressive OA treatment such as total joint replacement. Less aggressive, yet effective, conservative treatment options have the potential to address the growing prevalence of co-morbid obesity and knee OA by delaying the need for joint replacement or ideally preventing its need altogether. The results of this clinical trial will provide the first evidence regarding the efficacy of prebiotic supplementation on knee joint function and pain in adults with obesity and knee OA. If successful, the results may provide a simple, safe, and easy to adhere to intervention to reduce knee joint pain and improve the quality of life of adults with co-morbid knee OA and obesity. TRIAL REGISTRATION: Clinical Trials.gov NCT04172688 . Registered on 21 November 2019.

The effects on pain, physical function, and quality of life of quadriceps strengthening exercises combined with Baduanjin qigong in older adults with knee osteoarthritis: a quasi-experimental study.

BACKGROUND: Exercise is recommended as a principal treatment for individuals with knee osteoarthritis (KOA). However, the best choice for an optimal exercise program able to promote long-term compliance in KOA patients is not clear. This study aims to compare the effect of combined exercise (CE: quadriceps strengthening exercises (QSE) and Baduanjin qigong training (BDJ)) versus QSE alone and BDJ alone on older adults with KOA. METHODS: A three-arm, quasi-experimental trial with repeated measurements was used. As a cluster randomized trial, participants from three community centers were assigned respectively to QSE group, BDJ group and CE group. We assessed pain intensity, physical function, self-efficacy, and health-related quality-of-life (HRQoL) using standardized instruments at baseline, 3 months and 6 months follow-up. RESULTS: One hundred and twenty-eight participants with KOA aged over 60 completed the study. Over the 6 months, there were significant group interaction effects on pain intensity (F = 28.888, P < 0.001), physical function (F = 26.646, P < 0.001), and self-efficacy (F = 22.359, P < 0.001), and, based on a short form-12 item health survey questionnaire (SF-12), physical component summary (F = 7.470, P < 0.001), and mental component summary (F = 10.207, P < 0.001). Overall, the CE group exhibited significantly greater improvement in all outcomes when compared to the QSE group and the BDJ group. CONCLUSIONS: CE treatment is more effective than QSE and BDJ in pain relief, increasing physical function, improving self-efficacy, and raising quality-of-life in community-dwelling KOA older adults. Moreover, it promotes long-term compliance in KOA community patients. TRIAL REGISTRATION: Chinese Clinical Trails Registry number ChiCTR2000033387 (retrospectively registered). Registered 30 May 2020.

The effect of oral low molecular weight liquid hyaluronic acid combination with glucosamine and chondroitin on knee osteoarthritis patients with mild knee pain: An 8-week randomized double-blind placebo-controlled trial.

BACKGROUND: The popularity of dietary supplements for knee osteoarthritis (OA) management is on the rise; however, their effects are still debated. METHODS: This study aimed to investigate the effect of an oral low molecular weight liquid hyaluronic acid supplement in the treatment of knee OA patients with mild knee pain (visual analogue scale [VAS] ≤ 3) in Taiwan population. This was a randomized, double-blind, placebo-controlled study. Forty-seven subjects were enrolled and randomly allocated to either the A+HA or the placebo groups. The subjects were required to drink a bottle contained 20 mL of A+HA or placebo daily throughout an 8-week study period. The efficacy was assessed by using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the 36-item Short Form Survey (SF-36). RESULTS: At Week 8, significant reductions from baseline in the WOMAC pain (-2.6 ±â€Š1.68, P < .0001), stiffness (-1.2 ±â€Š1.50, P = .007), physical function (-5.8 ±â€Š4.39, P < .0001), and total (-9.4 ±â€Š5.82, P < .0001) scores were observed in the A+HA group but not in the placebo group. Significant differences in the mean change of WOMAC scores from baseline at Week 8 between groups were detected (P < .01). At Week 8, the A+HA group also showed significant improvements in SF-36 physical functioning (2.7 ±â€Š3.10, P = .001) and bodily pain (0.7 ±â€Š1.50, P < .05) domains. Although the A+HA group had a higher increase in the SF-36 total score than the placebo group but the difference was not statistically significant (2.1 ±â€Š12.75 vs 0.3 ±â€Š19.66, P = .12). CONCLUSIONS: Oral administration of low molecular weight liquid HA appeared to be effective for knee OA patients with mild knee pain (VAS ≤ 3) in the relief of knee OA symptoms, particularly in pain and physical function.Clinical Trial Registration: NCT04352322.