Assessment of wound healing activity in diabetic mice treated with a novel therapeutic combination of selenium nanoparticles and platelets rich plasma.

Diabetic wound healing is sluggish, often ending in amputations. This study tested a novel, two-punch therapy in mice-Selenium nanoparticles (Se NPs) and platelet-rich plasma (PRP)-to boost healing. First, a mouse model of diabetes was created. Then, Se NPs were crafted for their impressive antioxidant and antimicrobial powers. PRP, packed with growth factors, was extracted from the mice's blood. Wound healing was tracked for 28 days through photos, scoring tools, and tissue analysis. Se NPs alone spurred healing, and PRP added extra fuel. Furthermore, when used in combination with PRP, the healing process was accelerated due to the higher concentration of growth factors in PRP. Notably, the combination of Se NPs and PRP exhibited a synergistic effect, significantly enhancing wound healing in diabetic mice. These findings hold promise for the treatment of diabetic wounds and have the potential to reduce the need for lower limb amputations associated with diabetic foot ulcers. The innovative combination therapy using Se NPs and PRP shows great potential in expediting the healing process and addressing the challenges of impaired wound healing in individuals with diabetes. This exciting finding suggests this therapy could change diabetic wound management, potentially saving limbs and improving lives.

Trends in utilization, demographics, and costs of platelet-rich plasma injections: a ten-year nationwide investigation.

INTRODUCTION: Platelet-Rich Plasma (PRP) has become one of the most popular biologic treatments in orthopedic surgery. Despite this, its utilization over the last decade has not been investigated. METHODS: We conducted a search using Current Procedural Terminology codes to identify patients who received PRP injections between 2010 and 2019 using the PearlDiver database. The purpose was to 1) determine annual trends of PRP injections of the ankle, hip, knee, shoulder, and elbow for cartilaginous, tendinous, ligamentous, meniscal/labral, and miscellaneous pathologies; 2) compare baseline demographics of patients receiving these injections; and 3) analyze costs. RESULTS: A total of 23,716 patients who received PRP injections were identified; 54.4% were female. The incidence of PRP injections was between 1.6 and 4.3 per 100,000 orthopedic patients. The most common anatomic locations targeted for PRP therapy was the knee (36.7%), followed by the shoulder/elbow (30.5%), then the ankle (19.6%) and hip (13.6%). Subgroup analysis revealed that most common use of PRP was for knee cartilaginous pathologies, followed by shoulder/elbow tendinous pathologies. The number of injections used in the knee significantly increased between 2010 and 2019 (p< 0.001), and trended toward significantly increasing in the shoulder/elbow (p = 0.055). Average annual costs for PRP injections ranged from $711.65 for ankles and $1,711.63 for hips; costs significantly changed for 3 of the 4 anatomic locations. By 2019, average PRP injection costs for each area clustered around $1000. CONCLUSION: Between 2010 and 2019, there was an increase in usage of PRP injections in the knee (cartilaginous pathologies) and the shoulder/elbow (tendinous pathologies). PRP costs demonstrated early variability but clustered around $1000 by 2019. Further studies into drivers of prices and cost-effectiveness of PRP are needed to provide clarity into the true costs to patients and healthcare providers.

There Is Wide Variation in Platelet-rich Plasma Injection Pricing: A United States Nationwide Study of Top Orthopaedic Hospitals.

BACKGROUND: Demand for platelet-rich plasma (PRP) injections for osteoarthritis has dramatically increased in recent years despite conflicting evidence regarding its efficacy and highly variable pricing in the top orthopaedic centers in the United States, because PRP is typically not covered by insurance. A previous study investigating the mean price of PRP injections obtained information only from centers advertising online the availability of PRP injections. Thus, there is a need for further clarification of the overall availability and variability in cost of PRP injections in the orthopaedic community as well as an analysis of relevant regional demographic and hospital characteristics that could be associated with PRP pricing. QUESTIONS/PURPOSES: Our study purposes were to (1) report the availability and price variation of knee PRP injections at top-ranked United States orthopaedic centers, (2) characterize the availability of pricing information for a PRP injection over the telephone, (3) determine whether hospital characteristics (Orthopaedic Score [ U . S. News & World Report measure of hospital orthopaedic department performance], size, teaching status, and rural-urban status) were associated with PRP injection availability and pricing, and (4) characterize the price variation, if it exists, of PRP injections in three metropolitan areas and individual institutions. METHODS: In this prospective study, a scripted telephone call to publicly listed clinic telephone numbers was used to determine the availability and price estimate (amount to be paid by the patient) of a PRP injection for knee osteoarthritis from the top 25 hospitals from each United States Census region selected from the U.S. News & World Report ranking of best hospitals for orthopaedics. Univariable analyses examined factors associated with PRP injection availability and willingness to disclose pricing, differences across regions, and the association between hospital characteristics (Orthopaedic Score, size, teaching status, and rural-urban status) and pricing. The Orthopaedic Score is a score assigned to each hospital by U . S. News & World Report as a measure of hospital performance based partly on patient outcomes, with higher scores indicating better outcomes. RESULTS: Overall, 87% (87 of 100) of respondents stated they offered PRP injections. Pricing ranged from USD 350 to USD 2815 (median USD 800) per injection, with the highest prices in the Northeast. The largest price range was in the Midwest, where more than two-thirds of PRP injections given at hospitals that disclosed pricing cost USD 500 to USD 1000. Of the hospitals that offered PRP injections, 68% (59 of 87) were willing to disclose price information over the telephone. PRP injection pricing was inversely correlated with hospital Orthopaedic Score (-3% price change [95% CI -5% to -1%]; p = 0.01) and not associated with any of the other hospital characteristics that were studied, such as patient population median income and total hospital expenses. An intracity analysis revealed wide variations in PRP pricing in all metropolitan areas that were analyzed, ranging from a minimum of USD 300 within 10 miles of metropolitan area B to a maximum of USD 1269 within 20 miles of metropolitan area C. CONCLUSION: We found that although PRP injections are widely available, pricing continues to be a substantial financial burden on patients, with large price variability among institutions. We also found that if patients are willing to shop around in a metropolitan area, there is potential to save a meaningful amount of money. CLINICAL RELEVANCE: As public interest in biologics in orthopaedic surgery increases, knowledge of its pricing should be clarified to consumers. The debated efficacy of PRP injections, combined with our findings that it is an expensive out-of-pocket procedure, suggests that PRP has limited cost-effectiveness, with variable, discrete pricing. As such, the price of PRP injections should be clearly disclosed to patients so they can make informed healthcare decisions.

Assessment of short-term effect of platelet-rich plasma treatment of tendinosis using texture analysis of ultrasound images.

BACKGROUND: Computer-aided diagnosis (i.e., texture analyses) tools are becoming increasingly beneficial methods to monitor subtle tissue changes. The aim of this pilot study was to investigate short-term effect of platelet rich plasma (PRP) treatment in supraspinatus and common extensor of the forearm tendinosis by using texture analysis of ultrasound (US) images as well as by clinical questionnaires. PATIENTS AND METHODS: Thirteen patients (7 male and 6 female, age 36-60 years, mean age 51.2 ± 5.2) were followed after US guided PRP treatment for tendinosis of two tendons (9 patients with lateral epicondylitis and 4 with supraspinatus tendinosis). Clinical and US assessment was performed prior to as well as 3 months after PRP treatment with validated clinical questionnaires. Tissue response in tendons was assessed by using gray level run length matrix method (GLRLM) of US images. RESULTS: All patients improved of tendinosis symptoms after PRP treatment according to clinical questionnaires. Almost all GLRLM features were statistically improved 3 months after PRP treatment. GLRLM-long run high gray level emphasis (LRLGLE) revealed the best moderate positive and statistically significant correlation after PRP (r = 0.4373, p = 0.0255), followed by GLRLM-low gray level run emphasis (LGLRE) (r = 0.3877, p = 0.05). CONCLUSIONS: Texture analysis of tendinosis US images was a useful quantitative method for the assessment of tendon remodeling after minimally invasive PRP treatment. GLRLM features have the potential to become useful imaging biomarkers to monitor spatial and time limited tissue response after PRP, however larger studies with similar protocols are needed.

Assessment of a Synergistic Effect of Platelet-Rich Plasma and Stem Cell-Seeded Hydrogel for Healing of Rat Chronic Rotator Cuff Injuries.

Outcomes after repair of chronic rotator cuff injuries remain suboptimal. Type-1 collagen-rich tendon hydrogel was previously reported to improve healing in a rat chronic rotator cuff injury model. Stem cell seeding of the tendon hydrogel improved bone quality in the same model. This study aimed to examine whether there was a synergistic and dose-dependent effect of platelet-rich plasma (PRP) on tendon-bone interface healing by combining PRP with stem cell-seeded tendon hydrogel. Human cadaveric tendons were processed into a hydrogel. PRP was prepared at two different platelet concentrations: an initial concentration (initial PRP group) and a higher concentration (concentrated PRP group). Tendon hydrogel was mixed with adipose-derived stem cells and one of the platelet concentrations. Methylcellulose, as opposed to saline, was used as a negative control due to comparable viscosity. The supraspinatus tendon was detached bilaterally in 33 Sprague-Dawley rats (66 shoulders). Eight weeks later, each detached tendon was repaired, and a hydrogel mixture or control was injected at the repair site. Eight weeks after repair, shoulder samples were harvested and assigned for biomechanical testing (n = 42 shoulders) or a combination of bone morphological and histological assessment (n = 24 shoulders). Biomechanical testing showed significantly higher failure load and stiffness in the concentrated PRP group than in control. Yield load in the initial and concentrated PRP groups were significantly higher than that in the control. There were no statistically significant differences between the initial and concentrated PRP groups. The addition of the highly concentrated PRP to stem cells-seeded tendon hydrogel improved healing biomechanically after chronic rotator cuff injury in rats compared to control. However, synergistic and dose-dependent effects were not seen.

Multifactorial assessment of leukocyte reduced platelet rich plasma injection in dogs undergoing tibial plateau leveling osteotomy: A retrospective study.

This study assessed the effects of concurrent intra-articular injection and Tibial Plateau Leveling Osteotomy (TPLO) plate surface treatment with leukoreduced platelet rich plasma (lPRP) on outcomes of dogs undergoing TPLO. A retrospective study of medical records for cases presenting from January 2018 to December 2020 was performed. Client-owned dogs with naturally occurring cranial cruciate ligament rupture that underwent TPLO surgery were divided into two groups. The lPRP group included cases that underwent intra-articular injection and plate surface treatment at the time of their TPLO. The control group (C) underwent TPLO without PRP treatment. Data analyzed included: presence of surgical site infection, implant removal rate, degree of change in OA progression score, lameness score progression and radiographic bone healing. The short- and long-term complication rate, hospitalization and antibiotic therapy were also compared between the groups. Descriptive statistics, comparison analyses (Chi square test, t-test, Fisher's exact test) and multi-level logistic regression models were used for statistical analysis. A total of 110 cases met the study inclusion criteria: 54 = lPRP, 56 = C. There were no significant differences between groups with regard to gender, age, presence of meniscal tear, weight, or body condition score. Significant findings included: improved radiographic healing of the osteotomy in the lPRP group, improved global OA scores in the lPRP group, and improved lameness score at recheck examination in the lPRP group. There was no significant difference between the lPRP and C group with regard to surgical site infection and implant removal rate. Concurrent intra-articular injection and plate surface treatment with leukocyte reduced PRP at the time of TPLO, is beneficial in slowing the progression of OA, hastening the radiographic evidence of osteotomy healing, and improved lameness score on recheck examination. Leukocyte reduced PRP was not a significant factor in reducing SSI or implant removal rate.

Production of Modified Autologous Conditioned Serum and Ex Vivo Assessment of Its Healing Potential in Murine Corneal Epithelium.

Human blood-derived topical therapies have been a boon to clinicians in recent decades. Autologous serum (AS) and platelet-rich plasma (PRP) are enriched in epitheliotropic growth factors that are essential in corneal wound healing. Unlike AS, PRP is based on a differential centrifugation system, yielding more platelet-derived growth factors. Autologous conditioned serum (ACS) not only preserves the preparation of AS and PRP, but also focuses on immune-modulating properties, which are important in inflammatory diseases. The lack of standardized protocols and high preparation costs are limitations for the clinical application of ACS. This video experiment demonstrates a standard operating procedure for preparing modified autologous conditioned serum (mACS) eye drops. First, glycerol was added into heparin syringes as the blood cell stabilizer during hypoxic incubation. To activate the blood cells, a 4 h incubation at 37 °C was initiated. Then, the blood samples were centrifuged at 3,500 × g for 10 min at room temperature. After filtration of the supernatant through a 0.22 µm filter, the mACS eye drops were fully prepared. A tentative try-out of the therapeutic effect of mACS showed that it may have competitive advantages over conventional AS in the corneal wound healing in ex vivo mouse eyes. The AS used in this study was prepared according to published studies and the clinical practice in our hospital. Therefore, the efficacy of mACS on ocular surface diseases could be evaluated in future research through in vivo animal studies and clinical trials.

Platelet-Rich Plasma and Marrow Venting May Serve as Cost-Effective Augmentation Techniques for Isolated Meniscal Repair: A Decision-Analytical Markov Model-Based Analysis.

PURPOSE: To evaluate the cost-effectiveness of 3 isolated meniscal repair (IMR) treatment strategies: platelet-rich plasma (PRP)-augmented IMR, IMR with a marrow venting procedure (MVP), and IMR without biological augmentation. METHODS: A Markov model was developed to evaluate the baseline case: a young adult patient meeting the indications for IMR. Health utility values, failure rates, and transition probabilities were derived from the published literature. Costs were determined based on the typical patient undergoing IMR at an outpatient surgery center. Outcome measures included costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). RESULTS: Total costs of IMR with an MVP were $8,250; PRP-augmented IMR, $12,031; and IMR without PRP or an MVP, $13,326. PRP-augmented IMR resulted in an additional 2.16 QALYs, whereas IMR with an MVP produced slightly fewer QALYs, at 2.13. Non-augmented repair produced a modeled gain of 2.02 QALYs. The ICER comparing PRP-augmented IMR versus MVP-augmented IMR was $161,742/QALY, which fell well above the $50,000 willingness-to-pay threshold. CONCLUSIONS: IMR with biological augmentation (MVP or PRP) resulted in a higher number of QALYs and lower costs than non-augmented IMR, suggesting that biological augmentation is cost-effective. Total costs of IMR with an MVP were significantly lower than those of PRP-augmented IMR, whereas the number of additional QALYs produced by PRP-augmented IMR was only slightly higher than that produced by IMR with an MVP. As a result, neither treatment dominated over the other. However, because the ICER of PRP-augmented IMR fell well above the $50,000 willingness-to-pay threshold, IMR with an MVP was determined to be the overall cost-effective treatment strategy in the setting of young adult patients with isolated meniscal tears. LEVEL OF EVIDENCE: Level III, economic and decision analysis.

Use of intraoperative platelet-rich plasma during rotator cuff repair is correlated with increased patient-level charges across multiple categories.

BACKGROUND: As the efficacy of platelet-rich plasma (PRP) as an adjunct in rotator cuff repair (RCR) is debated, the decision to use PRP may be more heavily affected by its cost. We sought to quantify whether augmenting arthroscopic RCR with PRP injections at the time of surgery is correlated with increased patient-level charges. METHODS: All outpatient records reported in Texas from 2010 to 2018 were obtained from the publicly available Texas Healthcare Information Collection database through the Texas Department of State Health Services. All records including a Current Procedural Terminology code for arthroscopic RCR were included. Of the 139,587 records identified within this group, 1662 also contained a Current Procedural Terminology code for intraoperative PRP injection. Patient-level charge data were compared between those who received and those who did not receive concomitant PRP injection during the same outpatient surgical encounter. Subgroup analyses were performed across surgical facilities and insurance types. Mann-Whitney U tests were used to compare charges between PRP and non-PRP cases. Linear regression was used to predict the change in billed charges according to standard charge categories. P values less than .05 were considered statistically significant. RESULTS: The total charges for arthroscopic RCR over the 8-year period were $4.66 billion, coming to $33,371 ± $22,118 per case. Cases that included PRP injection were found to have significantly greater overall charges than cases that did not ($54,452 ± $33,637 vs. $33,117 ± $21,818; P < .001). Linear regression indicated that concomitant PRP injections predicted an increase in combined total charges by $22,027 (95% confidence interval, $20,425-$23,628; P < .001). CONCLUSIONS: PRP utilization at the time of rotator cuff surgery is correlated with increased patient-level charges overall, which occur across all charge subcategories and persist across surgical facility, surgeon volume, and insurance type. Detailed cost analysis is recommended to explore this charge correlation, and future cost-benefit analyses of PRP use in RCR should explore costs beyond that solely associated with PRP preparation, as these may have previously been overlooked.

Cost-utility analysis and net monetary benefit of Platelet Rich Plasma (PRP), intra-articular injections in compared to Plasma Rich in Growth Factors (PRGF), Hyaluronic Acid (HA) and ozone in knee osteoarthritis in Iran.

PURPOSE: To evaluate the cost-effectiveness of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factors (PRGF), Hyaluronic Acid (HA) and ozone as effective treatment approaches in knee osteoarthritis management from Iran Health care perspective. METHODS: A decision tree model was conducted to assess the cost-effectiveness of four common intra-articular treatment approaches in patients with mild and moderate knee osteoarthritis. The data on clinical effectiveness was obtained from a randomized controlled trial (RCT) conducted in Iran and used to estimate utility values. The direct medical costs were estimated according to tariffs for public medical centers and hospitals, approved by the Iran Ministry of Health and Medical Education in 2021. The incremental cost-effectiveness ratio (ICER) and the net monetary benefit (NMB) were used to evaluate the cost-utility analysis. Deterministic and probabilistic sensitivity analyses are performed to investigate the robustness of the results and account for the different sources of uncertainty. RESULTS: In this study, HA intra-articular injection-related costs ($581.67/patient) were defined as the highest cost, followed by PRGF ($328.10/patient), PRP (318.58/patient), and Ozone (103.20/patient). According to the utility value, PRP and PRGF (0.68) have the same and the most utility among Intra-articular injections in knee osteoarthritis management. However, the PRP injection method was identified as the most cost-effective intervention due to its high NMB and ICER estimates. Based on the Monte Carlo Simulation, PR intervention, compared to other ones, was introduced as the dominant strategy regarding knee OA management, with a WTP of $10,000 for 100% of cases. CONCLUSION: The study result demonstrated that intra-articular injection of PRP, compare to other injections, is a cost-effective treatment option for patients with mild and moderate knee osteoarthritis. In addition, intra-articular injection of PRP was identified as the best injection, with the highest level of net monetary benefit, for knee OA management.

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.

Platelet-rich plasma: a comparative and economical therapy for wound healing and tissue regeneration.

Rise in the incidences of chronic degenerative diseases with aging makes wound care a socio-economic burden and unceasingly necessitates a novel, economical, and efficient wound healing treatment. Platelets have a crucial role in hemostasis and thrombosis by modulating distinct mechanistic phases of wound healing, such as promoting and stabilizing the clot. Platelet-rich plasma (PRP) contains a high concentration of platelets than naïve plasma and has an autologous origin with no immunogenic adverse reactions. As a consequence, PRP has gained significant attention as a therapeutic to augment the healing process. Since the past few decades, a robust volume of research and clinical trials have been performed to exploit extensive role of PRP in wound healing/tissue regeneration. Despite these rigorous studies and their application in diversified medical fields, efficacy of PRP-based therapies is continuously questioned owing to the paucity of large samplesizes, controlled clinical trials, and standard protocols. This review systematically delineates the process of wound healing and involvement of platelets in tissue repair mechanisms. Additionally, emphasis is laid on PRP, its preparation methods, handling, classification,application in wound healing, and PRP as regenerative therapeutics combined with biomaterials and mesenchymal stem cells (MSCs).

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.

Utilisation du plasma autologue riche en plaquettes pour le traitement de l'arthrose du genou / Use of platelet-rich plasma for the treatment of knee osteoarthritis

MANDAT: L'Institut national d'excellence en santé et en service sociaux (INESSS) a reçu le mandat du ministère de la Santé et des Services sociaux (MSSS) de produire un avis sur la pertinence d'une couverture publique des injections de plasma autologue riche en plaquettes (PRPa) pour le traitement de l'arthrose du genou. Le MSSS a également soulevé la nécessité de se questionner sur l'éventualité d'un encadrement de cette pratique. DÉMARCHE DE L'ÉVALUATION: L'évaluation a été réalisée selon l'approche basée sur l'appréciation globale de la valeur que l'Institut préconise dans son Énoncé de principes et fondements éthiques2 et qui stipule qu'une intervention apporte de la valeur dans la mesure où son usage ou sa mise en place contribue à la triple finalité du système de santé et de services sociaux (dimensions clinique, populationnelle et économique) dans le contexte québécois (dimensions organisationnelle et socioculturelle). Une revue des données issues de la littérature a été réalisée afin d'évaluer le PRPa pour le traitement de l'arthrose du genou. Une collecte de données contextuelles et expérientielles auprès des parties prenantes a été également effectuée par l'entremise de plusieurs consultations ad hoc, de comités consultatifs et d'un groupe de discussion d'experts. De plus, un questionnaire destiné aux patients souffrant d'arthrose du genou a été mis en ligne sur le site Web de l'INESSS et diffusé via les médias sociaux. DIMENSION POPULATIONNELLE La prévalence de l'arthrose du genou s'établit à environ 7,9 % dans la population québécoise âgée de 20 ans et plus. La nature évolutive de cette maladie a des répercussions grandissantes sur la qualité de vie des patients, leur fonctionnalité et leur autonomie. Il n'existe actuellement pas de traitement curatif pour l'arthrose. La prise en charge consiste en l'utilisation concomitante de divers modes d'intervention, incluant des traitements conservateurs (physiothérapie, analgésiques, anti-inflammatoires, etc.) ainsi que des injections intra-articulaires lorsque le soulagement n'est pas atteint et éventuellement une chirurgie. Ces traitements visent à soulager les symptômes et à maintenir une certaine fonctionnalité. Toutefois, ceux-ci ne permettent de combler que partiellement les besoins de santé et une minorité de traitements et services sont accessibles ou couverts par le système public de santé. Des préoccupations au regard de l'équité d'accès se posent dans la mesure où des patients n'ayant pas de moyens financiers ou d'assurances privées ont accès à moins d'options. Certains patients peuvent donc se retrouver dans une impasse thérapeutique pendant plusieurs années, ce qui peut grandement affecter leur qualité de vie. Au Québec, le traitement de PRPa est considéré comme une option supplémentaire s'ajoutant aux traitements par injections de corticostéroïdes ou d'acides hyaluroniques lorsque les traitements conservateurs, pharmacologiques ou non, sont un échec. Contrairement aux injections de corticostéroïdes qui sont assurées par le système public, celles de PRPa ne sont présentement disponibles que dans les cliniques privées et à des tarifs variables (environ de 700 $ à 1 100$ selon les prix affichés sur certains sites Web de cliniques). Chez les patients ne répondant ni aux traitements conservateurs ni aux injections, le traitement chirurgical tel que l'arthroplastie du genou est souvent le dernier recours. Cette procédure fait l'objet d'une liste d'attente dont le délai est variable (de 11 à 90 semaines) d'une région à l'autre au Québec. DIMENSION CLINIQUE Le PRPa est un traitement de médecine régénératrice autologue. Les méthodes de préparation et d'isolement du PRPa ne font l'objet d'aucune standardisation et sont très variables à travers les études cliniques. Le volume de plasma isolé est enrichi d'une concentration en plaquettes supérieure au niveau de base. La littérature sur le PRPa est abondante en études cliniques et en méta-analyses. Cependant, un bon nombre parmi celles-ci présentent des faiblesses méthodologiques importantes. Résultats d'efficacité: Parmi les 9 études cliniques prospectives considérées, le PRPa a été comparé aux corticostéroïdes, à l'acide hyaluronique SynviscMD, qui a déjà été évalué par l'INESSS, ou à une solution saline. La capacité du PRPa à procurer un bénéfice clinique se manifesterait dans la mesure où les moyennes des scores de douleur indiquent soit un maintien, soit une amélioration chez les patients. Il est cependant difficile de définir l'ampleur de ce bénéfice clinique par rapport à celui procuré par les comparateurs. Les niveaux de preuve pour les paramètres d'efficacité (impact sur la douleur et la fonctionnalité) sont très faibles. Résultats d'innocuité: Un total de 37 études cliniques prospectives et de 10 méta-analyses ont été analysées pour l'évaluation de ce paramètre. Les données issues de ces études démontreraient que la proportion d'événements indésirables est semblable à la suite d'une injection de PRPa, de corticostéroïdes, d'acides hyaluroniques ou d'une solution saline. Ces événements indésirables (douleur au site d'injection, enflure, etc.) sont généralement de faible gravité et se résolvent d'eux-mêmes dans les jours suivant l'injection. Selon ces données, les injections de PRPa pour l'arthrose du genou ne semblent pas soulever de risque majeur d'innocuité. Le niveau de preuve pour les résultats d'innocuité est modéré. Résultats de qualité de vie: Les résultats de qualité de vie demeurent hétérogènes à travers les 5 études cliniques prospectives considérées. Une amélioration de la qualité de vie des patients après les injections de PRPa serait démontrée dans 3 études, mais uniquement avec l'outil de mesure Knee injury and Osteoarthritis Outcome Score (KOOS), un questionnaire spécifique pour évaluer la qualité de vie à la suite d'une intervention au genou. Les autres outils de mesure de la qualité de vie plus généraux, SF-36 et AQoL-8D, utilisés dans 3 études, n'ont pas décelé d'amélioration chez les patients après les injections de PRPa. Une seule étude démontrerait une supériorité du PRPa par rapport aux corticostéroïdes, en matière de qualité de vie, à 6 mois de suivi. Le niveau de preuve pour les résultats d'impact sur la qualité de vie est faible. DIMENSION ORGANISATIONNELLE: Actuellement, aucun encadrement ne balise la pratique lors de la préparation et de l'injection du PRPa. La consultation d'experts a mis en lumière le fait que, dans l'éventualité du remboursement public de ce traitement, des défis d'implantation importants seront soulevés tels que le choix des établissements dans lesquels le PRPa pourrait être offert de même que l'élaboration de modalités d'encadrement de la pratique. DIMENSION SOCIOCULTURELLE: La population québécoise est vieillissante et les besoins associés à l'arthrose du genou sont en croissance, ce qui soulève certaines préoccupations en matière d'utilisation des services de santé. L'intérêt général pour le PRPa est aussi en croissance. Un nombre important de cliniques privées en font la promotion en idéalisant souvent les vertus de ce traitement. Des patients dont le besoin de santé n'est pas comblé par les traitements conservateurs veulent savoir si cette approche leur serait bénéfique, si elle pourrait améliorer leur qualité de vie, ralentir la dégradation du cartilage ainsi que retarder ou éviter une chirurgie. Le positionnement des agences internationales ou des guides de pratique sur la pertinence d'utiliser le PRPa pour l'arthrose du genou demeure toutefois équivoque. Les différents organismes soulèvent des limites relatives aux données probantes en matière de qualité, notamment en raison de la variabilité des résultats obtenus et du manque de standardisation dans le mode de préparation du PRPa. DIMENSION ÉCONOMIQUE: L'analyse d'efficience a consisté en une analyse de minimisation des coûts selon la perspective du système public de soins de santé et de services sociaux du Québec et s'est appuyée sur l'équivalence d'efficacité et d'innocuité des injections de PRPa comparativement aux corticostéroïdes. Cette analyse démontre que le PRPa n'est pas efficient. Une analyse d'impact budgétaire a été réalisée et celle-ci prend en considération les coûts liés à l'introduction du PRPa dans la prise en charge de l'arthrose du genou ainsi qu'une croissance du marché advenant une couverture publique. En considérant les hypothèses formulées, le remboursement du PRPa engendrerait des coûts supplémentaires de 467 000 $, 1 M$ et 1,7 M$ pour chacune des 3 premières années, pour un total de 3,2 M$ pour 4 100 cas d'arthrose du genou qui recevraient le PRPa, ce qui correspond à des parts de marché de 5 %, 10 % et 15 %.

MANDATE: The Institut national d'excellence en santé et en service sociaux (INESSS) was asked by the Ministère de la Santé et des Services sociaux (MSSS) to assess the relevance of including autologous platelet-rich plasma (aPRP) injections as a treatment covered by the public insurance plan for patients with knee osteoarthritis. The MSSS also raised the need to consider the possibility of a framework for this practice. EVALUATION PROCESS The evaluation was conducted according to the INESSS framework based on the overall value assessment according to its Énoncé de principes et fondements éthiques3 , which stipulates that an intervention provides value to the extent that its implementation contributes to the triple purpose of the health and social services system (clinical, population and economic dimensions) in the Quebec context (organizational and sociocultural dimensions). A review of data from the scientific literature was performed in order to document the efficacy, safety and efficiency of aPRP for the treatment of knee osteoarthritis. Contextual and experiential data were gathered from the stakeholders through several ad hoc consultations, advisory committees, and an expert focus group. In addition, patients with knee osteoarthritis were consulted using a questionnaire posted on INESSS's website and disseminated via social media. POPULATIONAL Dimension The prevalence of knee osteoarthritis is approximately 7.9% in the Québec population aged 20 years and older. The progressive nature of this disease has an increasing impact on patients' quality of life, functionality and autonomy. There is currently no curative treatment for knee osteoarthritis. The management consists of the concomitant use of various types of intervention, including conservative treatments (physiotherapy, analgesics, anti-inflammatory drugs, etc.), intra-articular injections when relief is not achieved, and possibly surgery. These treatments are intended to relieve symptoms and maintain a certain level of functionality. However, they only partially meet the health needs, and only a minority of the treatments and services are accessible or covered by the public healthcare system. There are certain equity of access issues whereby patients without financial means or private insurance have access to fewer treatment options and services. Some patients may find themselves at a therapeutic impasse for several years, which can greatly affect their quality of life. In Québec, aPRP therapy is considered an additional option to treatment with corticosteroids or hyaluronic acid injections when conservative treatments, pharmacological or otherwise, have failed. Unlike corticosteroids injections, which are covered by the public system, aPRP injections are currently available only at private clinics and at varying fees (approximately $700 to $1,100, according to prices posted on certain clinic websites). For patients who do not respond to conservative treatments or injections, surgical treatment, such as knee replacement, is often the last resort. There is a waiting list for this procedure, with waiting times in Québec varying from region to region (from 11 to 90 weeks). CLINICAL: dimension aPRP is an autologous regenerative medicine treatment. The techniques for preparing and isolating aPRP are not standardized and differ significantly across clinical studies. The volume of isolated plasma is enriched with a platelet concentration above the baseline. The aPRP literature is rich in clinical studies and meta-analyses, but many of them have significant methodological weaknesses. EFFICACY RESULTS: In the 9 prospective clinical studies considered, aPRP was compared with corticosteroids, Synvisc® hyaluronic acid, which had previously been evaluated by INESSS, or saline solution. The ability of aPRP to confer a clinical benefit appears to have been demonstrated in that the mean pain scores indicate either maintenance or improvement in patients. However, it is difficult to define the extent of this clinical benefit relative to that conferred by the comparators. The levels of evidence for the efficacy endpoints (impact on pain and functionality) are very low. SAFETY RESULTS: A total of 37 prospective clinical studies and 10 meta-analyses were analyzed for the purpose of evaluating this parameter. The data from these studies appear to show that the proportion of adverse events is similar following the injection of aPRP, corticosteroids, hyaluronic acids or saline solution. These adverse events (pain at the injection site, swelling, etc.) are generally mild and resolve on their own within days following the injection. Based on these data, aPRP injections for knee osteoarthritis do not seem to pose any major safety risks. The level of evidence for the safety results is moderate. QUALITY-OF-LIFE RESULTS: The quality-of-life results are heterogeneous across the 5 prospective clinical studies that were considered. An improvement in patients' post-aPRP injection quality of life appears to have been demonstrated in 3 studies, but only with the Knee Injury and Osteoarthritis. Outcome Score (KOOS) measurement instrument, a specific questionnaire for assessing quality of life following a knee intervention. The other, more general quality-of-life measures, SF-36 and AQoL-8D, used in 3 studies, did not reveal an improvement in patients after aPRP injections. Only one study appears to have shown aPRP to be superior to corticosteroids in terms of quality of life at 6-month follow-up. The level of evidence for quality-of-life impact outcomes is low. ORGANIZATIONAL DIMENSION: Currently, there is no framework for guiding the preparation and injection of aPRP. The expert consultations brought out the fact that, should this treatment be covered by the public plan, significant implementation challenges will arise, such as choosing the facilities where aPRP might be offered and developing mechanisms to guide the practice. SOCIOCULTURAL DIMENSION: The Québec population is aging, and the needs associated with knee osteoarthritis are growing, which raises certain concerns about the use of healthcare services. General interest in aPRP is also growing. A large number of private clinics are promoting it, often extolling this treatment's virtues. Patients whose health needs are not met by conservative treatments want to know if they could obtain some benefit from this approach, if it could improve their quality of life, slow cartilage degradation and delay or obviate the need for surgery. However, the position of international agencies and practise guidelines on the advisability of using aPRP for knee osteoarthritis is equivocal. The various bodies point out limitations regarding the quality of the evidence, particularly because of the variability of the results obtained and the lack of standardization in the way aPRP is prepared. ECONOMIC DIMENSION: The economic evaluation consisted of a cost-minimization analysis from the perspective of MSSS and was based on the efficacy and safety equivalence assumption of aPRP injections relative to corticosteroids. This analysis shows that aPRP is not cost-effective. A budget impact analysis, which considered the costs associated with introducing aPRP into the management of knee osteoarthritis, and market growth in the eventuality of public reimbursement was performed. Based on the assumptions made, public reimbursement of aPRP would result in additional costs of $467,000, $1 million, and $1.7 million for each of the first 3 years, for a total of $3.2 million for 4100 knee osteoarthritis cases receiving aPRP, which works out to market shares of 5%, 10% and 15%.

In vivo assessment of bone repair by an injectable nanocomposite scaffold for local co-delivery of autologous platelet-rich plasma and calcitonin in a rat model.

BACKGROUND: Gellan gum is obtained from the bacterium Sphingomonas elodea and is a polysaccharide with carboxylic acid functional groups. The goal of this project was to investigate the osteoinductive effect of local administration of calcitonin through an injectable scaffold of gellan gum containing salmon calcitonin loaded in silsesquioxane nanoparticles, hydroxyapatite, and platelets rich plasma. METHODS: The femur of rats was defected by creating a 2 × 5 mm2 hole using an electric drill. The defect was filled with an injectable hydrogel scaffold composed of gellan gum enriched with salmon calcitonin loaded in silsesquioxane nanoparticles, hydroxyapatite, platelets rich plasma, and then the radiologic images were taken. Bone densitometry and the histologic studies were carried out by Hematoxylin & Eosin test. Biochemical analysis was done to measure the serum alkaline phosphatase (ALP), calcium, and calcitonin concentration. RESULTS: Healing of the bone defects and bone densitometry in the treated group by calcitonin-loaded scaffold was significantly higher (p < 0.05) and bone formation occupied 75% of the defect was greater than in other groups. Serum ALP and calcium levels in the scaffold-loaded calcitonin group were more than in the other groups (p < 0.05). The osteogenic marker genes also increased significantly (p < 0.05) with free calcitonin and the scaffold. CONCLUSIONS: Gellan gum-based scaffold loaded with calcitonin may be considered a promising local treatment to progress bone formation in repairing skeletal injuries.

Functional and structural assessment of the possible protective effect of platelet-rich plasma against ischemia/reperfusion-induced ovarian injury in adult rats.

This study aimed to evaluate the possible protective effect of platelet-rich plasma (PRP) on ischemia reperfusion (I/R)-induced ovarian injury in a rat model. Forty adult female albino rats were randomly assigned to four groups: control, ischemia, I/R, and I/R + intraperitoneal PRP. Induction of ischemia was done by bilateral ovarian torsion for 3 h, while reperfusion was done by subsequent detorsion for another 3 h. PRP was injected 30 min before detorsion. Histological assessment and measurement of ovarian anti-Mullerian hormone (AMH) were done to assess the degree of tissue damage and the remaining ovarian reserve. Ovarian malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured to evaluate the oxidant-antioxidant balance. Tumor necrosis factor-α (TNF-α) was measured to assess degree of inflammation. Immunohistochemical assessment of ovarian vascular endothelial growth factor-A (VEGF-A) was also done. PRP treated I/R group revealed a significant decrease in MDA (P = 0.007), TNF-α (P = 0.001), and a significant increase in TAC (P = 0.001) and VEGF-A (P = 0.003) in comparison to the untreated I/R group. Furthermore, limited vascular congestion and inflammatory infiltration were observed after PRP treatment. However, no significant difference was detected in AMH after PRP treatment. Our results denoted that PRP may help in preservation of ovarian function and structure during surgical conservative detorsion of the torsioned ovary. These protective effects could be attributed to its ability to reduce oxidative stress, inflammation and also to its high content of growth factors especially VEGF.

Preliminary cost variance modeling to compare autologous intraovarian platelet-rich plasma vs. standard hormone replacement therapy for menopause management.

BACKGROUND: Menopause symptoms and hormone replacement therapy (HRT) are among the most common reasons patients seek gynecological advice. Although at least half of all women in developed countries will use HRT during their lifetime, the treatment is not without risk and guidance on HRT is mixed. Greater awareness of HRT risks from extended use has piqued interest in safer options. Menopause reversal with autologous ovarian platelet-rich plasma (OPRP) has brought this restorative approach forward for consideration, but appropriateness and cost-effectiveness require examination. METHODS: HRT and OPRP data from USA were projected to compare cumulative 1yr patient costs using stochastic Monte Carlo modeling. RESULTS: Mean ± SD cost-to-patient for HRT including initial consult plus pharmacy refills was estimated at about $576 ± 246/yr. While OPRP included no pharmacy component, an estimated 4 visits over 1yr for OPRP maintenance entailed ultrasound, phlebotomy/sample processing, surgery equipment, and incubation/laboratory expense, yielding mean ± SD cost for OPRP at $8,710 ± 4,911/yr ( P < 0.0001 vs. HRT, by T-test). Upper-bound estimates for annual HRT and OPRP costs were $1,341 and $22,232, respectively. CONCLUSIONS: While HRT and OPRP may have similar efficacy and safety for menopause therapy, they diverge sharply in cost-effectiveness. Most patients would likely find OPRP too complex, invasive, and expensive to be competitive vs. HRT. Although OPRP is an interesting and cautiously useful technique for selected menopause patients reluctant to use HRT, repurposing this infertility treatment for wider use appears inefficient compared to standard HRT options that are currently marketed.

Assessment of the intracavernosal injection platelet-rich plasma in addition to daily oral tadalafil intake in diabetic patients with erectile dysfunction non-responding to on-demand oral PDE5 inhibitors.

This study aimed to evaluate the effectiveness of ICI of platelet-rich plasma (PRP) in addition to daily oral tadalafil intake in diabetic erectile dysfunction (ED) patients non-responding to PDE5 inhibitors. Overall, 48 patients complaining of ED non-responding to on-demand PDE5 inhibitors were allocated into 2 equal groups, diabetics and non-diabetics that were given a daily dose of 5 mg tadalafil plus vardenafil 20 mg on demand during the study besides being subjected to 3 doses of ICI of PRP, 4 weeks apart. Responses to on-demand PDE5 inhibitors, International index of erectile function-5 (IIEF-5) score, erection hardness scores (EHS) and pharmaco-dynamic duplex studies were assessed. After PRP injections, 33% and 50% of cases were satisfied with on-demand PDE5 inhibitors, respectively, whereas 41% and 66% of them showed improved EHS response. Compared with baseline scores, the mean IIEF-5 scores were significantly improved after PRP therapy in the diabetic ED group (12.1 vs. 8.04, p = 0.003) as well as in the non-diabetic ED group (14.8 vs. 10.2, p = 0.001) linked to pharmaco-penile duplex readings. Both good and fair diabetic control exhibited significant responses to ICI therapy of PRP compared with bad controlled cases. The significant improvement included; the IIEF-5 score increase (86.7%, 126% vs. 16.1%), improved EHS as well as penile duplex readings. Baseline HbA1C demonstrated a significant negative correlation with IIEF-5 score before (p = 0.019) and after PRP therapy (p = 0.002) respectively. It could be concluded that ICI of PRP could be an effective therapy for treating ED patients non-responding to on-demand oral PDE5 treatment.

Why might ovarian rejuvenation fail? Decision analysis of variables impacting reproductive response after autologous platelet-rich plasma.

Experience with platelet-rich plasma (PRP) has accumulated from use in dental restoration, postinfarct myocardial repair, tendon surgery, pain management, and aesthetic enhancements. Reproductive medicine joined this arena in 2016, beginning with reports of menopause reversal and fertility recovery after autologous PRP for senescent ovaries. Although recent publications have highlighted benefits of "ovarian rejuvenation," the absence of randomized placebo-controlled clinical trial data has limited its acceptance. Because selection bias tends to underreport negative outcomes, reliable estimates cannot be calculated for how often intraovarian PRP is unsuccessful. However, ample information is available to permit an operational root-cause analysis when failures are considered. This assessment uses a PRP treatment care path with a decision theory model to critique pre-intake screening, baseline audit, sample processing, ovarian tissue placement method, equipment selection, and follow-up monitoring. These branched choice points enable interventions likely to determine outcome. Specimen handling for intraovarian PRP merits particular scrutiny, since enormous variation in platelet protocols already exists across unrelated clinical areas. As a new addition to fertility practice, intraovarian PRP requires validation of safety and efficacy to gain wider support. Borrowing PRP knowledge from other domains can facilitate this goal, ideally with appreciation of aspects unique to intraovarian use.