Assessment of the Feasibility of Objective Parameters as Primary End Points for Patients Affected by Knee Osteoarthritis: Protocol for a Pilot, Open Noncontrolled Trial (:SMILE:).

BACKGROUND: Osteoarthritis (OA) is a disabling condition that affects more than one-third of people older than 65 years. Currently, 80% of these patients report movement limitations, 20% are unable to perform major activities of daily living, and approximately 11% require personal care. In 2014, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommended, as the first step in the pharmacological treatment of knee osteoarthritis, a background therapy with chronic symptomatic slow-acting osteoarthritic drugs such as glucosamine sulfate, chondroitin sulfate, and hyaluronic acid. The latter has been extensively evaluated in clinical trials as intra-articular and oral administration. Recent reviews have shown that studies on oral hyaluronic acid generally measure symptoms using only subjective parameters, such as visual analog scales or quality of life questionnaires. As a result, objective measures are lacking, and data validity is generally impaired. OBJECTIVE: The main goal of this pilot study with oral hyaluronic acid is to evaluate the feasibility of using objective tools as outcomes to evaluate improvements in knee mobility. We propose ultrasound and range of motion measurements with a goniometer that could objectively correlate changes in joint mobility with pain reduction, as assessed by the visual analog scale. The secondary objective is to collect data to estimate the time and budget for the main double-blind study randomized trial. These data may be quantitative (such as enrollment rate per month, number of screening failures, and new potential outcomes) and qualitative (such as site logistical issues, patient reluctance to enroll, and interpersonal difficulties for investigators). METHODS: This open-label pilot and feasibility study is conducted in an orthopedic clinic (Timisoara, Romania). The study includes male and female participants, aged 50-70 years, who have been diagnosed with symptomatic knee OA and have experienced mild joint discomfort for at least 6 months. Eight patients must be enrolled and treated with Syalox 300 Plus (River Pharma) for 8 weeks. It is a dietary supplement containing high-molecular-weight hyaluronic acid, which has already been marketed in several European countries. Assessments are made at the baseline and final visits. RESULTS: Recruitment and treatment of the 8 patients began on February 15, 2018, and was completed on May 25, 2018. Data analysis was planned to be completed by the end of 2018. The study was funded in February 2019. We expect the results to be published in a peer-reviewed clinical journal in the last quarter of 2024. CONCLUSIONS: The data from this pilot study will be used to assess the feasibility of a future randomized clinical trial in OA. In particular, the planned outcomes (eg, ultrasound and range of motion), safety, and quantitative and qualitative data must be evaluated to estimate in advance the time and budget required for the future main study. Finally, the pilot study should provide preliminary information on the efficacy of the investigational product. TRIAL REGISTRATION: ClinicalTrials.gov NCT03421054; https://clinicaltrials.gov/study/NCT03421054. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/13642.

Cost-effectiveness of strength exercise or aerobic exercise compared with usual care for patients with knee osteoarthritis: secondary results from a multiarm randomised controlled trial in Norway.

OBJECTIVES: To evaluate the 1-year cost-effectiveness of strength exercise or aerobic exercise compared with usual care for patients with symptomatic knee osteoarthritis (OA), from a societal and healthcare perspective. DESIGN: Cost-effectiveness analysis embedded in a three-arm randomised controlled trial. PARTICIPANTS AND SETTING: A total of 161 people with symptomatic knee OA seeking Norwegian primary or secondary care were included in the analyses. INTERVENTIONS: Participants were randomised to either 12 weeks of strength exercise (n=54), 12 weeks of aerobic exercise (n=53) or usual care (n=54). OUTCOME MEASURES: Quality-adjusted life-years (QALYs) estimated by the EuroQol-5 Dimensions-5 Levels, and costs related to healthcare utilisation and productivity loss estimated in euros (€), aggregated for 1 year of follow-up. Cost-effectiveness was expressed with mean incremental cost-effectiveness ratios (ICERs). Bootstrapping was used to estimate ICER uncertainty. RESULTS: From a 1-year societal perspective, the mean cost per patient was €7954, €8101 and €17 398 in the strength exercise, aerobic exercise and usual care group, respectively. From a 1-year healthcare perspective, the mean cost per patient was €848, €2003 and €1654 in the strength exercise, aerobic exercise and usual care group, respectively. Mean differences in costs significantly favoured strength exercise and aerobic exercise from a 1-year societal perspective and strength exercise from a 1-year healthcare perspective. There were no significant differences in mean QALYs between groups. From a 1-year societal perspective, at a willingness-to-pay threshold of €27 500, the probability of strength exercise or aerobic exercise being cost-effective was ≥98%. From a 1-year healthcare perspective, the probability of strength exercise or aerobic exercise being cost-effective was ≥97% and ≥76%, respectively. CONCLUSION: From a 1-year societal and healthcare perspective, a 12-week strength exercise or aerobic exercise programme is cost-effective compared with usual care in patients with symptomatic knee OA. TRIAL REGISTRATION NUMBER: NCT01682980.

Cost-Effectiveness of Community-Based Diet and Exercise for Patients with Knee Osteoarthritis and Obesity or Overweight.

OBJECTIVE: Obesity exacerbates pain and functional limitation in persons with knee osteoarthritis (OA). In the Weight Loss and Exercise for Communities with Arthritis in North Carolina (WE-CAN) study, a community-based diet and exercise (D + E) intervention led to an additional 6 kg weight loss and 20% greater pain relief in persons with knee OA and body mass index (BMI) >27 kg/m2 relative to a group-based health education (HE) intervention. We sought to determine the incremental cost-effectiveness of the usual care (UC), UC + HE, and UC + (D + E) programs, comparing each strategy with the "next-best" strategy ranked by increasing lifetime cost. METHODS: We used the Osteoarthritis Policy Model to project long-term clinical and economic benefits of the WE-CAN interventions. We considered three strategies: UC, UC + HE, and UC + (D + E). We derived cohort characteristics, weight, and pain reduction from the WE-CAN trial. Our outcomes included quality-adjusted life years (QALYs), cost, and incremental cost-effectiveness ratios (ICERs). RESULTS: In a cohort with mean age 65 years, BMI 37 kg/m2, and Western Ontario and McMaster Universities Osteoarthritis Index pain score 38 (scale 0-100, 100 = worst), UC leads to 9.36 QALYs/person, compared with 9.44 QALYs for UC + HE and 9.49 QALYS for UC + (D + E). The corresponding lifetime costs are $147,102, $148,139, and $151,478. From the societal perspective, UC + HE leads to an ICER of $12,700/QALY; adding D + E to UC leads to an ICER of $61,700/QALY. CONCLUSION: The community-based D + E program for persons with knee OA and BMI >27kg/m2 could be cost-effective for willingness-to-pay thresholds greater than $62,000/QALY. These findings suggest that incorporation of community-based D + E programs into OA care may be beneficial for public health.

Effectiveness of a telehealth-delivered clinician-supported exercise and weight loss program for hip osteoarthritis - protocol for the Better Hip randomised controlled trial.

BACKGROUND: Hip osteoarthritis (OA) is a leading cause of chronic pain and disability worldwide. Self-management is vital with education, exercise and weight loss core recommended treatments. However, evidence-practice gaps exist, and service models that increase patient accessibility to clinicians who can support lifestyle management are needed. The primary aim of this study is to determine the effectiveness of a telehealth-delivered clinician-supported exercise and weight loss program (Better Hip) on the primary outcomes of hip pain on walking and physical function at 6 months, compared with an information-only control for people with hip OA. METHODS: A two-arm, parallel-design, superiority pragmatic randomised controlled trial. 212 members from a health insurance fund aged 45 years and over, with painful hip OA will be recruited. Participants will be randomly allocated to receive: i) Better Hip; or ii) web-based information only (control). Participants randomised to the Better Hip program will have six videoconferencing physiotherapist consultations for education about OA, prescription of individualised home-based strengthening and physical activity programs, behaviour change support, and facilitation of other self-management strategies. Those with a body mass index > 27 kg/m2, aged < 80 years and no specific health conditions, will also be offered six videoconferencing dietitian consultations to undertake a weight loss program. Participants in the control group will be provided with similar educational information about managing hip OA via a custom website. All participants will be reassessed at 6 and 12 months. Primary outcomes are hip pain on walking and physical function. Secondary outcomes include measures of pain; hip function; weight; health-related quality of life; physical activity levels; global change in hip problem; willingness to undergo hip replacement surgery; rates of hip replacement; and use of oral pain medications. A health economic evaluation at 12 months will be conducted and reported separately. DISCUSSION: Findings will determine whether a telehealth-delivered clinician-supported lifestyle management program including education, exercise/physical activity and, for those with overweight or obesity, weight loss, is more effective than information only in people with hip OA. Results will inform the implementation of such programs to increase access to core recommended treatments. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ACTRN12622000461796).

Longer-term quality of care, effectiveness, and cost-effectiveness of implementing a model of care for osteoarthritis: A cluster-randomized controlled trial.

OBJECTIVE: To assess the quality of care, effectiveness, and cost-effectiveness over 12 months after implementing a structured model of care for hip and knee osteoarthritis (OA) in primary healthcare as compared to usual care. DESIGN: In this pragmatic cluster-randomized, controlled trial with a stepped-wedge cohort design, we recruited 40 general practitioners (GPs), 37 physiotherapists (PTs), and 393 patients with symptomatic hip or knee OA from six municipalities (clusters) in Norway. The model included the delivery of a 3-hour patient education and 8-12 weeks individually tailored exercise programs, and interactive workshops for GPs and PTs. At 12 months, the patient-reported quality of care was assessed by the OsteoArthritis Quality Indicator questionnaire (16 items, pass rate 0-100%, 100%=best). Costs were obtained from patient-reported and national register data. Cost-effectiveness at the healthcare perspective was evaluated using incremental net monetary benefit (INMB). RESULTS: Of 393 patients, 109 were recruited during the control periods (control group) and 284 were recruited during interventions periods (intervention group). At 12 months the intervention group reported statistically significant higher quality of care compared to the control group (59% vs. 40%; mean difference: 17.6 (95% confidence interval [CI] 11.1, 24.0)). Cost-effectiveness analyses showed that the model of care resulted in quality-adjusted life-years gained and cost-savings compared to usual care with mean INMB €2020 (95% CI 611, 3492) over 12 months. CONCLUSIONS: This study showed that implementing the model of care for OA in primary healthcare, improved quality of care and showed cost-effectiveness over 12 months compared to usual care. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02333656.

Racial variation in healthcare resource utilization and expenditures in knee/hip osteoarthritis patients: a retrospective analysis of a Medicaid population.

BACKGROUND: Osteoarthritis (OA) is a leading cause of chronic pain and disability. Prior studies have documented racial disparities in the clinical management of OA. The objective of this study was to assess the racial variations in the economic burden of osteoarthritis within the Medicaid population. METHODS: We conducted a retrospective observational study using the MarketScan Multi-State Medicaid database (2012-2019). Newly diagnosed, adult, knee and/or hip OA patients were identified and followed for 24 months. Demographic and clinical characteristics were collected at baseline; outcomes, including OA treatments and healthcare resource use (HCRU) and expenditures, were assessed during the 24-month follow-up. We compared baseline patient characteristics, use of OA treatments, and HCRU and costs in OA patients by race (White vs. Black; White vs. Other) and evaluated racial differences in healthcare costs while controlling for underlying differences. The multivariable models controlled for age, sex, population density, health plan type, presence of non-knee/hip OA, cardiovascular disease, low back pain, musculoskeletal pain, presence of moderate to severe OA, and any pre-diagnosis costs. RESULTS: The cohort was 56.7% White, 39.9% Black and 3.4% of Other race (American Indian/Alaska Native, Hispanic, Asian, Native Hawaiian/Other Pacific Islander, two or more races and other). Most patients (93.8%) had pharmacologic treatment for OA. Inpatient admission during the 24-month follow-up period was lowest among Black patients (25.8%, p < .001 White vs. Black). In multivariable-adjusted models, mean all-cause expenditures were significantly higher in Black patients ($25,974) compared to White patients ($22,913, p < .001). There were no significant differences between White patients and patients of Other race ($22,352). CONCLUSIONS: The higher expenditures among Black patients were despite a lower rate of inpatient admission in Black patients and comparable length and number of hospitalizations in Black and White patients, suggesting that other unmeasured factors may be driving the increased costs among Black OA patients.

Higher healthcare costs were observed in Black Medicaid patients with knee/hip osteoarthritis despite lower rates of inpatient admission. We observed these differences in this Medicaid population, where socioeconomic status is more homogeneous.Black patients had significantly higher healthcare costs compared to White patients and the difference persisted even after accounting for underlying differences in Black and White patients.Higher healthcare costs among Black patients were found in both the baseline and follow-up periods overall for all types of healthcare (hospitalizations, ER, office visit, other services).Higher hospitalization costs in Black patients were observed despite lower rates of hospitalizations in Black patients. These increased costs cannot be attributed to either longer or more frequent hospitalizations; no significant difference in either the length of stay or the number of hospitalizations was observed when comparing Black patients to White patients.

A Model for Evaluating Total Costs of Care and Cost Savings of Specialty Condition-Based Care for Hip and Knee Osteoarthritis in an Integrated Practice Unit.

OBJECTIVES: The viability of specialty condition-based care via integrated practice units (IPUs) requires a comprehensive understanding of total costs of care. Our primary objective was to introduce a model to evaluate costs and potential costs savings using time-driven activity-based costing comparing IPU-based nonoperative management with traditional nonoperative management and IPU-based operative management with traditional operative management for hip and knee osteoarthritis (OA). Secondarily, we assess drivers of incremental cost differences between IPU-based care and traditional care. Finally, we model potential cost savings through diverting patients from traditional operative management to IPU-based nonoperative management. METHODS: We developed a model to evaluate costs using time-driven activity-based costing for hip and knee OA care pathways within a musculoskeletal IPU compared with traditional care. We identified differences in costs and drivers of cost differences and developed a model to demonstrate potential cost savings through diverting patients from operative intervention. RESULTS: Weighted average costs of IPU-based nonoperative management were lower than traditional nonoperative management and lower in IPU-based operative management than traditional operative management. Key drivers of incremental cost savings included care led by surgeons in partnership with associate providers, modified physical therapy programs with self-management, and judicious use of intra-articular injections. Substantial savings were modeled by diverting patients toward IPU-based nonoperative management. CONCLUSIONS: Costing models involving musculoskeletal IPUs demonstrate favorable costs and cost savings compared with traditional management of hip or knee OA. More effective team-based care and utilization of evidence-based nonoperative strategies can drive the financial viability of these innovative care models.

Reducing the burden of knee osteoarthritis through community pharmacy: Protocol for a randomised controlled trial of the Knee Care for Arthritis through Pharmacy Service.

INTRODUCTION: Knee osteoarthritis (OA) negatively impacts the health outcomes and equity, social and employment participation, and socio-economic wellbeing of those affected. Little community-based support is offered to people with knee OA in Aotearoa New Zealand. Identifying Maori and non-Maori with knee OA in community pharmacy and providing co-ordinated, evidence- and community-based care may be a scalable, sustainable, equitable, effective and cost-effective approach to improve health and wellbeing. AIM: Assess whether the Knee Care for Arthritis through Pharmacy Service (KneeCAPS) intervention improves knee-related physical function and pain (co-primary outcomes). Secondary aims assess impacts on health-related quality of life, employment participation, medication use, secondary health care utilisation, and relative effectiveness for Maori. METHODS AND ANALYSIS: A pragmatic randomised controlled trial will compare the KneeCAPS intervention to the Pharmaceutical Society of New Zealand Arthritis Fact Sheet and usual care (active control) at 12 months for Maori and non-Maori who have knee OA. Participants will be recruited in community pharmacies. Knee-related physical function will be measured using the function subscale of the Short Form of the Western Ontario and McMaster Universities Osteoarthritis Index. Knee-related pain will be measured using an 11-point numeric pain rating scale. Primary outcome analyses will be conducted on an intention-to-treat basis using linear mixed models. Parallel within-trial health economic analysis and process evaluation will also be conducted. ETHICS AND TRIAL DISSEMINATION: Ethical approval was obtained from the Central Health and Ethics Committee (2022-EXP-11725). The trial is registered with ANZCTR (ACTRN12622000469718). Findings will be submitted for publication and shared with participants.

A systematic review, umbrella review, and quality assessment on clinical translation of stem cell therapy for knee osteoarthritis: Are we there yet?

BACKGROUND: The success of stem cell therapy for knee osteoarthritis (KOA) in preclinical animal models has accelerated the pace of clinical translation. However, it remains uncertain whether the current scientific evidence supports the clinical application of stem cells in treating KOA. A comprehensive evaluation of the safety and efficacy of stem cell therapies and scientific evidence quality is necessary. METHODS: Using "stem cells" and "knee osteoarthritis" as the search terms, several databases, including PubMed, Web of Science, Cochrane, Embase, and Clinicaltrials.gov, were searched on August 25, 2022, and updated on February 27, 2023. Clinical studies that reported adverse reactions (ARs) of stem cell therapy in KOA patients were included without limiting the type of studies. Quantitative systematic reviews of stem cell therapy for KOA that conducted meta-analysis were included. Two researchers conducted literature screening and data extraction independently, and the evidence quality was evaluated according to the Institute of Health Economics and AMSTAR 2 criteria. RESULTS: Fifty clinical studies and 13 systematic reviews/meta-analyses (SRs/MAs) were included. Nineteen ARs were reported in 50 studies, including five knee-related ARs, seven common ARs, and seven other ARs. Some studies reported over 10% prevalence of knee pain (24.5%; 95% CI [14.7%, 35.7%]), knee effusion (12.5%; 95% CI [4.8%, 22.5%]), and knee swelling (11.9%; 95% CI [3.5%, 23.5%]). Additionally, two studies have reported cases of prostate cancer and breast tumors, respectively. However, these two studies suggest that stem cell therapy does not bring significant ARs to patients. SRs/MAs results revealed that stem cell therapy relieved pain in patients over time but did not improve knee function. However, current clinical studies have limited evidence regarding study objectives, test designs, and patient populations. Similarly, SRs/MAs have inadequate evidence regarding study design, risk of bias assessment, outcome description, comprehensive discussion, and potential conflicts of interest. CONCLUSIONS: The inefficacy of stem cells, the risk of potential complications, and the limited quality of evidence from current studies precluded any recommendation for using stem cell products in patients with KOA. Clinical translation of stem cell therapies remains baseless and should be cautiously approached until more robust evidence is available. PROSPERO registration number: CRD42022355875.

Delayed timing of physical therapy initiation increases the risk of future opioid use in individuals with knee osteoarthritis: a real-world cohort study.

OBJECTIVE: We assessed whether late versus early initiation of physical therapy (PT) was related to greater risk of future opioid use in people with knee osteoarthritis (OA) who receive PT. METHODS: We used Commercial and Medicare Advantage claims data from 1999 to 2018 from American adults with incident knee OA referred for PT within 1 year of diagnosis. We categorised people as opioid naïve or opioid experienced based on prior prescriptions. We examined the association of timing of PT initiation with any and chronic opioid use over 1 year. RESULTS: Of the 67 245 individuals with incident knee OA, 35 899 were opioid naïve and 31 346 were opioid experienced. In the opioid naïve group, compared with PT within 1 month, PT 1 to <3, 3 to <6, 6 to <9, 9-12 months from diagnosis was associated with adjusted risk ratio (aRR (95% CIs)) for any opioid use of 1.18 (1.10 to 1.28), 1.49 (1.37 to 1.61), 1.73 (1.58 to 1.89) and 1.93 (1.76 to 2.12), respectively; aRRs (95% CIs) for chronic opioid use were 1.25 (1.01 to 1.54), 1.83 (1.48 to 2.26), 2.29 (1.82 to 2.89) and 2.50 (1.96 to 3.19). Results were similar among opioid experienced; aRRs (95% CIs) for any opioid use were 1.19 (1.14 to 1.24), 1.32 (1.26 to 1.37), 1.39 (1.32 to 1.45) and 1.54 (1.46 to 1.61); aRRs (95% CIs) for chronic opioid use were 1.25 (1.17 to1.34), 1.43 (1.33 to 1.54), 1.53 (1.41 to 1.66) and 1.65 (1.51 to 1.80). CONCLUSION: Compared with PT initiation within 1 month, delayed PT initiation was associated with higher risk of opioid use in people with incident knee OA. The longer the delay in PT initiation, the greater was the risk.

Multimodal data analysis of knee osteoarthritis assessment: factors selection for conservative care decision making.

When assessing a patient with knee osteoarthritis (OA), a number of factors are considered to guide treatment plan, namely, demographic, radiographic, clinical, musculoskeletal, and biomechanical factors. The aim of this study is to identify which of these factors are the most related to each other to potentially better prioritize the modifiable factors to be addressed as they may influence treatment outcomes. We investigated a multimodal canonical correlation analysis to evaluate associations between these factors. The analysis was performed on 415 OA patients who were not candidates for knee arthroplasty, to identify factors that are associated to the patients' clinical conditions.

Medicare coverage patterns favor non-invasive and minimally-invasive treatments of knee osteoarthritis compared to temporomandibular joint osteoarthritis.

OBJECTIVE: To compare Medicare coverage patterns for treatments of knee osteoarthritis (OA) to those of temporomandibular joint (TMJ) OA. METHODS: The International Classification of Diseases (ICD)-10 codes were used to identify knee OA, TMJ OA, and related diagnoses. The AAPC Coder was utilized to search for Medicare insurance coverage by state/district for the indicated CPT codes. The coverage for treatments of TMJ OA and knee OA was analyzed by Fisher's exact test. RESULTS: There was a statistically significant difference in the coverage of physical therapy, massage therapy, and arthrocentesis for TMJ OA and knee OA. The current study showed that arthrocentesis was covered 100% in all states/districts for knee OA and 0% for TMJ OA. CONCLUSION: Medicare covers TMJ OA treatments to a lesser degree than knee treatments. Documentation of this discrepancy serves as an important first step in advocating for improvements in coverage, and subsequently, in access to care.

Platelet-rich plasma outcomes do not correlate with patient satisfaction or perceived cost-effectiveness.

BACKGROUND: As platelet-rich plasma injection for knee osteoarthritis (OA) has increased in popularity, it has become more important to assess its effectiveness and satisfaction with its use in the context of its high cost. The purpose of this study was to determine satisfaction, commercial appeal, and effectiveness of platelet-rich plasma (PRP) for the treatment of knee OA. METHODS: A retrospective review of patients who underwent PRP injection in the knee from 2016 to 2019 was performed. Various patient-reported outcomes were collected, including: satisfaction with the PRP injection (out of 100), whether the patient would want to undergo PRP injection again, whether they would recommend the injection and whether they felt that the injection was worth the cost was collected. VAS pain scores were collected and measured out of 100. Demographics and radiographical information were obtained via chart review. Statistical analyses were conducted including descriptive statistics and binary logistic and linear regressions. RESULTS: Overall, 114 patients were included. The mean pre-injectionpain score was 70.4, and the mean pain level decreased after injection to 36.8. Patients rated their satisfaction on average as neutral along the aforementioned continuous scale (49.2), , 50.9% stated that they would get the PRP injection again, 60.5% would recommend to a friend, and 50.9% felt the injection was worth the cost. Younger age and improved post-injection pain correlated with increasing likelihood of desiring further PRP injection. CONCLUSIONS: Patients on average rated satisfaction slightly below average, indicating net neutrality in terms of satisfaction with their injection. Furthermore, only half of the patients indicated that it was worth the cost and that they would receive it again. Younger age and post-injection pain relief increased desire for further injection, but pain-relief did not correlate with patients saying that the injection was worth the cost.

The Epidemiology of Platelet-Rich Plasma Injections From 2010 to 2020 in a Large US Commercial Insurance Claims Database: A Recent Update.

INTRODUCTION: The popularity of platelet-rich plasma (PRP) injections for the treatment of orthopaedic conditions has grown markedly. We sought to better define the trends in the usage of orthopaedic PRP injections across an insured US population over the past decade. METHODS: The PearlDiver M91Ortho commercial administrative claims database was queried for all patients receiving PRP injections for orthopaedic conditions from 2010 through the first quarter of 2020 (Q1.2020). Trends in PRP use, reimbursement charges, demographics, joints injected, and administering physicians were assessed over time and reported as year-over-year (YOY) changes. RESULTS: Over the study period, 14,096 unique patients had 17,759 orthopaedic PRP injections. The number of PRP injections administered had a YOY increase of 7.1% (144 injections/year, 95% confidence interval [CI] = 89 to 199, Ptrend = 0.0009). A YOY increase of 895% was observed in total nonsurgical charges ($683,974/yr, 95% CI 441,504 to 926,444, Ptrend = 0.0009). The median age of PRP recipients increased (YOY change = +0.6 years, 95% CI 0.4 to 0.8, Ptrend = 0.0005). Injections to the elbow (YOY change = -0.8%, 95% CI -0.10% to [-0.06%], Ptrend = 0.005) and foot/ankle (YOY change = -1.0%, 95% CI -1.4% to [-0.06%], Ptrend = 0.002) decreased, whereas hip (YOY change = +0.4%, 95% CI 0.2% to 0.6%, Ptrend = 0.019), knee (YOY change = +0.9%, 95% CI 0.3% to 1.2%, Ptrend = 0.016), and spine (YOY change = +0.2%, 95% CI 0.0% to 0.4%, Ptrend = 0.033) injections increased. PRP injections given by sports medicine orthopaedic surgeons (YOY change = +0.8%, 95% CI 0.6% to 1.2%, Ptrend <0.0001) increased over time, whereas those by general orthopaedic surgeons decreased (YOY change = -0.9, 95% CI -1.2 to [-0.6%], Ptrend = 0.001). CONCLUSION: PRP injections quadrupled in prevalence from 2010 to Q1.2020, with a projected increase in annual usage in this data set of 66% by 2030. As greater evidence-based indications for PRP use are identified, more specialists and insurance providers may consider expanding their involvement in this growing field. LEVEL OF EVIDENCE: III, retrospective cohort study.

Does gabapentin provide benefit for patients with knee OA? A benefit-harm and cost-effectiveness analysis.

OBJECTIVE: Gabapentin can treat neuropathic pain syndromes and has increasingly been prescribed to treat nociplastic pain. Some patients with knee osteoarthritis (OA) suffer from both nociceptive and nociplastic pain. We examined the cost-effectiveness of adding gabapentin to knee OA care. METHOD: We used the Osteoarthritis Policy Model, a validated Monte Carlo simulation of knee OA, to examine the value of gabapentin in treating knee OA by comparing three strategies: 1) usual care, gabapentin sparing (UC-GS); 2) targeted gabapentin (TG), which provides gabapentin plus usual care for those who screen positive for nociplastic pain on the modified PainDETECT questionnaire (mPD-Q) and usual care only for those who screen negative; and 3) universal gabapentin plus usual care (UG). Outcomes included cumulative quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. We derived model inputs from published literature and national databases and varied key input parameters in sensitivity analyses. RESULTS: UC-GS dominated both gabapentin-containing strategies, as it led to lower costs and more QALYs. TG resulted in a cost increase of $689 and a cumulative QALY reduction of 0.012 QALYs. UG resulted in a further $1,868 cost increase and 0.036 QALY decrease. The results were robust to plausible changes in input parameters. The lowest TG strategy ICER of $53,000/QALY was reported when mPD-Q specificity was increased to 100% and AE rate was reduced to 0%. CONCLUSION: Incorporating gabapentin into care for patients with knee OA does not appear to offer good value.

Assessment of Mobile Health Applications for Management of Knee and/or Hip Osteoarthritis Using the Mobile Application Rating Scale.

BACKGROUND: Mobile health applications (apps) can help individuals with knee and/or hip osteoarthritis (OA) learn about, monitor, and manage their condition. These apps have not been formally evaluated. OBJECTIVE: The aim of this study was to evaluate the publicly available mobile health apps for individuals with knee and/or hip OA using a systematic review. METHODS: We searched the Apple App Store, Android Google Play, and Amazon Appstore using the terms "arthritis," "osteoarthritis," "hip OA," "knee OA," "hip," "knee," "rehabilitation," "rehab," and "physical therapy" in December of 2021. Applications that met the inclusion/exclusion criteria were reviewed using the Mobile Application Rating Scale (MARS; 29 items across 6 sections, each rated at 1-5). RESULTS: Among 1104 identified apps, 94 met the inclusion/exclusion criteria for MARS appraisal. Fourteen apps met the predetermined score thresholds for final summary. Of the 14 apps appraised, the total overall mean app score on the MARS ranged from 3.12 to 4.20 (mean, 3.51 ± 0.37). Although app features varied, common features were symptom tracking, exercise recommendations, education, goal setting, and improving well-being. Many apps allowed for sharing with health care providers and included some measures to protect privacy. Jointfully Osteoarthritis was the top-rated app in both the Apple App Store and Android Google Play. CONCLUSIONS: The majority of the apps we identified for knee and/or hip OA did not meet predetermined score thresholds for final summary. Many failed to provide comprehensive education and deliver management plans and lacked scientific testing. Future research should focus on apps that fit the needs of health care providers and patients including quality information, structured exercise programs tailored to individual needs, secure communication methods, and health information protection.

Cost-Effectiveness of Telehealth-Delivered Exercise and Dietary Weight Loss Programs for Knee Osteoarthritis Within a Twelve-Month Randomized Trial.

OBJECTIVE: To evaluate the cost-effectiveness of telehealth-delivered exercise and diet-plus-exercise programs within 12 months. METHODS: An economic evaluation within a 12-month, 3-arm, parallel randomized trial of two 6-month telehealth-delivered exercise programs, with and without a dietary component. A total of 415 people with knee osteoarthritis ages 45-80 years and body mass index of 28-40 kg/m2 were assigned to 1 of 2 telehealth-delivered exercise programs, 1 without (n = 172) and 1 with (n = 175) a dietary component (ketogenic very low calorie diet), or to an education control (n = 67), for 6 months, with 6 months follow-up. The primary economic outcomes were quality-adjusted life years (QALYs) and health system costs. Measured costs were the direct intervention (consultations, equipment/resources, and meal replacements) and health care use in 2020 Australian dollars ($AU1.5 = $US1). Secondary analysis included weight loss and work productivity gains. RESULTS: The clinical trial demonstrated greater improvements in pain and function compared to information only for individuals with knee osteoarthritis and overweight/obesity. We can be 88% confident that diet plus exercise is cost effective ($45,500 per QALY), 53% confident that exercise is cost-effective ($67,600 per QALY) compared to the control, and 86% confident that augmenting exercise with the diet program is cost effective ($21,100 per QALY). CONCLUSION: Telehealth-delivered programs targeting exercise with dietary intervention for people with knee osteoarthritis who have overweight/obesity are likely to be cost-effective, particularly if potential long-term gains from weight loss and work productivity are realized.

Cost Effectiveness of Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Patients with Knee Osteoarthritis.

OBJECTIVES: The aim of this study was to assess the cost effectiveness of allogeneic umbilical cord blood-derived mesenchymal stem cells with sodium hyaluronate (hUCB-MSC) compared with microfracture in patients with knee cartilage defects caused by osteoarthritis (OA) in South Korea. METHODS: A partitioned survival model approach was taken consisting of five mutually exclusive health states: excellent, good, fair, poor, and death over a 20-year time horizon. Utility values were obtained from a randomized clinical trial. Cost data were extracted from a database provided by the Health Insurance Review & Assessment Service, and the utilization of healthcare services was estimated from an expert panel of orthopedic surgeons using a structured questionnaire. The incremental cost-effectiveness ratio (ICER) in terms of quality-adjusted life-years (QALY) was calculated. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: In the base case, the incremental costs of US$14,410 for hUCB-MSC therapy along with its associated QALY gain of 0.857 resulted in an ICER of US$16,812 (₩18,790,773) per QALY (95% confidence interval [CI] US$13,408-US$20,828) when compared with microfracture treatment from a healthcare payer perspective. From a societal perspective, the ICER was US$268 (₩299,255) per QALY (95% CI -US$2915 to US$3784). When using a willingness-to-pay threshold of US$22,367/QALY, the probability of hUCB being cost effectiveness compared with microfracture was 99% from the healthcare payer perspective and 100% from the societal perspective. CONCLUSIONS: The study demonstrated that hUCB-MSC therapy was cost effective compared with microfracture when treating patients with knee OA. These findings should inform health policy decision makers about considerations for cost-effective therapy for treating knee OA to ultimately enhance population health.

Assessment of clinical, biochemical, and radiological outcomes following intra-articular injection of Wharton jelly-derived mesenchymal stromal cells in patients with knee osteoarthritis: A prospective clinical study.

The aim of the present study was to perform clinical, biochemical, and radiological evaluation of the efficacy of mesenchymal stem cells derived from Wharton jelly (WJ) present within the human umbilical cord in the treatment of knee osteoarthritis. Between 2018 and 2019, 10 patients with knee osteoarthritis for whom the conservative treatment was not beneficial were included in the study. Patients were clinically, radiologically, and biochemically evaluated before treatment initiation. Thereafter, the patients were intra-articularly injected using a solution containing 1 × 108 WJ-derived MSCs. Evaluations were performed on day 21 (V1) and 42 (V2) and month 3 (V3), 6 (V4), and 12 (V5) after the procedure. At 1-year post-injection, visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Lequesne scores of patients were lower than those observed during the initial evaluation, whereas the mean 36-Item Short Form Health Survey score was higher. Cartilage thicknesses were found to be increased in all regions except in the medial femur, medial posterior femur, lateral posterior femur, and lateral posterior tibia regions in magnetic resonance imaging. A significant increase was observed in tumor necrosis factor-alpha, interleukin-1ß, adiponectin, resistin, and interleukin-6 levels compared with pre-injection values. The leptin levels at 6-month and 1-year controls were lower than the pre-injection levels, and the decrease observed at 6 months was significant. In patients with knee osteoarthritis, intra-articular WJ-derived MSC injection causes significant pain reduction, satisfactory functional improvement, and increased patient satisfaction following a 1-year follow-up. These clinical improvements were supported by magnetic resonance images, along with changes in adiponectin and leptin levels in synovial fluid. Level of evidence: IV.

Implementation of clinical guidelines for osteoarthritis together (IMPACT): protocol for a participatory health research approach to implementing high value care.

BACKGROUND: The evidence-based interventions of exercise and education have been strongly recommended as part of prominent clinical guidelines for hip and knee osteoarthritis (OA) for more than ten years. Despite the wealth of strong evidence that exists, implementation in practice is sub-optimal. This paper describes the key methodologies used in the co-design, tailoring, and evaluation of the IMPACT project implementation strategies, to confront this problem across multiple levels (micro, meso, macro) in public and private healthcare settings in Ireland. METHODS: Using a type III hybrid implementation-effectiveness design, a participatory, dynamic and iterative process will be used to tailor and evaluate multi-level implementation strategies using the following stages: 1) Co-design the implementation strategies with key stakeholders using best evidence, a theory-driven implementation framework (Consolidated Framework for Implementation Research), local context and expert consensus; 2) Pilot and evaluate the implementation strategies by training physiotherapists to deliver the evidence-based Good Life with osteoArthritis Denmark (GLA:D®) education and exercise programme using the implementation strategies, and conduct a mixed-methods process evaluation; 3) Adapt the implementation strategies based on implementation process evaluation indicators from stage two. The adapted strategies will be used for scale-up and sustainability in subsequent GLA:D® Ireland training programmes that will be rolled out nationally. Evaluation of effectiveness on patient and cost outcomes will continue up to 12 months post-programme delivery, using an online patient registry and pre-post design. DISCUSSION: This implementation science project aims to use participatory health research to address a gap in management of OA across public and private healthcare settings. This research has the potential to change practice and promote a policy of exercise and physical activity referral for chronic musculoskeletal disease that utilises community engagement effectively and enacts change 'together', with involvement of researchers, decision-makers, clinicians and patients.