Failure to disclose industry funding impacts outcomes in randomized controlled trials of platelet-rich plasma
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 2022
PURPOSE Platelet-rich plasma (PRP) represents a highly profitable biological therapy. Platelet-rich plasma is widely used to treat musculoskeletal disorders despite mixed evidence of its efficacy. As evidenced by literature from other domains, industry funding may influence the results of clinical trials. The objective of the current study was to determine the association between industry funding and positive results for randomized controlled trials (RCTs) assessing the efficacy of PRP in musculoskeletal disorders. METHODS A search of four databases was conducted. Included studies were RCTs comparing PRP to any non-PRP comparator in adults (18 years old or over) with musculoskeletal disorders and had full text available in English. Studies were excluded if they were published before 2016 or were non-human trials. A multivariate binomial logistic regression model was created to explore predictors of statistically significant findings. Covariates included the presence of industry funding, sample size, and length of study follow-up. 1440 records were screened with 87 trials included in the final analysis. RESULTS Of the 87 studies, 61 (70%) reported a statistically significant primary outcome. The presence of industry funding was not predictive of a statistically significant primary outcome [OR = 0.36, 95% CI 0.096-1.36, (n.s.)]. Studies that did not state whether industry funding was present had a higher chance of reporting a statistically significant primary outcome (OR = 3.61, 95% CI 1.1-11.9, p = 0.035). Sample size and length of follow-up were not predictive of a statistically significant primary outcome. CONCLUSION The results of the current study conclude that industry funding had no impact on the reporting of positive results for RCTs investigating PRP in musculoskeletal disorders. However, not disclosing sources of funding was associated with a higher likelihood of reporting positive results. The results of trials that fail to disclose funding sources should be interpreted with caution in the PRP literature. LEVEL OF EVIDENCE I.
Effectiveness of Platelet-Rich Plasma for Patients With Carpal Tunnel Syndrome: A Systematic Review and meta-Analysis of Current Evidence in Randomized Controlled Trials
Frontiers in pharmacology. 2022;13:834213
Background: Recently, there was a series of clinical studies focusing on local injection of platelet-rich plasma (PRP) for treatment of patients with carpal tunnel syndrome (CTS). However, the safety and efficacy of PRP in these CTS patients remains controversial. Therefore, we performed a systematic review to compare PRP with other conservative treatments in treatment of CTS patients. Methods: We systematically searched from electronic databases (Cochrane, PubMed, Web of Science, and EMBASE) up to 10 December 2021. The data of clinical results were extracted and analyzed by RevMan Manager 5.4. Results: Finally, eight randomized controlled studies, involving 220 CTS patients undergoing local injection of PRP were enrolled in this systematic review. All enrolled trials were considered to be of high quality. In the short-term efficacy, the PRP group was significantly lower in symptom severity scale (SSS) compared with the control group (MD = -2.00; 95% CI, -3.15 to -0.85; p = 0.0007; I(2) = 0%). In the mid-term efficacy, the PRP group was significantly effective than the control group in the visual analogue scale (MD = -0.63; 95% CI, -1.22 to -0.04; p = 0.04; I(2) = 61%), SSS (MD = -3.56; 95% CI, -4.93 to -2.18; p < 0.00001; I(2) = 0%), functional status scale (MD = -2.29; 95% CI, -3.03 to -1.56; p < 0.00001; I(2) = 45%), sensory peak latency (MD = -0.39; 95% CI, -0.58 to -0.19; p = 0.0001; I(2) = 0%) and cross-sectional area of median nerve (MD = -0.20; 95% CI, -0.31 to -0.10; p = 0.0002; I(2) = 0%). In the mid-long-term efficacy, the PRP group was only significantly lower in SSS compared with the control group (MD = -2.71; 95% CI, -4.33 to -1.10; p = 0.001; I(2) = 38%). Conclusion: Local PRP injection is more effective than other conservative treatments in terms of mid-term efficacy in relieving pain, improving wrist function and symptoms, reducing MN swelling, and partially improving electrophysiological indicators. However, the long-term adverse side and consensus on standardization of PRP in CTS patients still need further large-scale trials.
The use of platelet-rich plasma therapy in treating tennis elbow: A critical review of randomised control trials
Journal of clinical orthopaedics and trauma. 2022;32:101965
Tennis elbow (TE) is a painful and debilitating condition of the elbow. Recently, the use of orthobiologics, such as platelet-rich-plasma (PRP), has been proposed to promote tendon regeneration. Despite their popularity, there is a paucity of updated reviews on the use of PRP compared with other treatment modalities for treating TE. The aim of this review is to summarise high quality studies that compare the use of PRP therapy with other therapies for TE and to identify areas where further research is warranted. This systematic review was performed in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search of PubMed, Scopus and Cochrane Library databases was undertaken in May 2021. Articles were screened for the following criteria: randomised control trials (RCTs) involving PRP in at least one of the treatment arms for tennis elbow. The quality of the RCTs included were analysed for their risk of bias using the modified Cochrane Collaboration Risk of Bias Assessment Tool for randomised trials. A total of 20 RCTs of which 1520 TE patients were analysed. The RCTs included in this review compared PRP with various treatment modalities routinely used in clinical practice such as physiotherapy, steroid injections, Autologous Whole Blood (AWB) and surgical interventions. With regards to the quality of RCTs, collectively, selection bias was found to be low risk however, performance bias in terms of blinding of participants and personnel performed poorly. Of the 20 RCTs, only 5 studies were classified as low risk of bias. In these 5 studies, 2 RCTs compared PRP with steroids and reported contrasting results, 1 RCT compared PRP with AWB injections which reported both to be similarly efficacious, 3 RCTs included a placebo group and only 1 reported superior effects with PRP. There are 2 main types of PRP classified according to the number of pro-inflammatory leukocyte i.e. leukocyte-rich and leukocyte-poor PRP. However, only 8 studies documented the formulation of PRP used. While the heterogeneity of PRP formulations could in-part explain the reported differences in outcomes, overall there is limited robust evidence to recommend PRP therapy for TE. Further research is required to establish the optimal formulation and administration of PRP injections. Proper documentation of TE patients need to be standardised before concrete recommendations on the use of PRP therapy may be offered.
A Systematic Review on the Effect of Common Medications on Platelet Count and Function: Which Medications Should Be Stopped Before Getting a Platelet-Rich Plasma Injection?
Orthopaedic journal of sports medicine. 2022;10(4):23259671221088820
BACKGROUND Platelet-rich plasma (PRP) exerts its effect through the release of growth factors and cytokines from the platelet concentrate. Certain medications may affect platelet count or function, resulting in decreased efficacy of PRP injections. PURPOSE To systematically review the literature regarding common medications and their effects on platelets to establish guidelines for which medications should be stopped before obtaining a PRP injection. STUDY DESIGN Systematic review; Level of evidence, 2. METHODS This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search for studies assessing the effect of common medications on platelet count or platelet function was performed of the PubMed, Cochrane Library, Web of Science, and OpenGrey databases. Inclusion criteria were as follows: drug studied was aspirin, acetaminophen, a nonsteroidal anti-inflammatory drug (NSAID), a statin, or gabapentin; human participants; and article in the English language. Risk of bias was assessed using the Cochrane Risk of Bias tool and the Risk of Bias in Non-randomised Studies-of Interventions tool. RESULTS A total of 1711 studies were identified through the initial search, with 20 studies meeting all inclusion criteria. No studies involving gabapentin met all inclusion criteria. Patients treated with aspirin (268 patients) or acetaminophen (13 patients) showed a significant decrease in platelet aggregation. Statin therapy (73 patients) did not result in a significant decrease in platelet aggregation. Patients who took NSAIDs (172 patients) demonstrated significantly decreased platelet aggregation only when treated with nonselective formulations. Those treated with cyclooxygenase (COX)-2-selective NSAIDs showed no significant difference in platelet aggregation. Treatment with aspirin, acetaminophen, statins, or NSAIDs did not lead to a significant decrease in platelet count. CONCLUSION Aspirin, acetaminophen, and nonselective NSAIDs should be considered for suspension before a PRP injection because of their potential to diminish the effects of the injection. COX-2-selective NSAIDs and statins do not need to be withheld before a PRP injection.
Platelet-Rich Plasma as an Alternative to Xenogeneic Sera in Cell-Based Therapies: A Need for Standardization
International journal of molecular sciences. 2022;23(12)
There has been an explosion in scientific interest in using human-platelet-rich plasma (PRP) as a substitute of xenogeneic sera in cell-based therapies. However, there is a need to create standardization in this field. This systematic review is based on literature searches in PubMed and Web of Science databases until June 2021. Forty-one studies completed the selection criteria. The composition of PRP was completely reported in less than 30% of the studies. PRP has been used as PRP-derived supernatant or non-activated PRP. Two ranges could be identified for platelet concentration, the first between 0.14 × 10(6) and 0.80 × 10(6) platelets/µL and the second between 1.086 × 10(6) and 10 × 10(6) platelets/µL. Several studies have pooled PRP with a pool size varying from four to nine donors. The optimal dose for the PRP or PRP supernatant is 10%. PRP or PRP-derived supernatants a have positive effect on MSC colony number and size, cell proliferation, cell differentiation and genetic stability. The use of leukocyte-depleted PRP has been demonstrated to be a feasible alternative to xenogeneic sera. However, there is a need to improve the description of the PRP preparation methodology as well as its composition. Several items are identified and reported to create guidelines for future research.
The Efficacy of Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis Symptoms and Structural Changes: A Systematic Review and Meta-Analysis
The Journal of arthroplasty. 2022
BACKGROUND Platelet-rich plasma (PRP) usage in orthopaedics continues to rise despite guidelines suggesting non-superiority to comparative cohorts. Therefore, we performed a systematic review and meta-analysis on PRP efficacy using two clinical assessments: (1) Visual Analog Scale (VAS) and (2) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We assessed consistency and clinical relevancy by determining study heterogeneity (e.g., sample sizes, ages, BMIs, arthritic severities, etc.). Comparative cohorts were: (A) hyaluronic acid (HA); (B) corticosteroid (CS); (C) normal saline (NS); and (D) exercise therapy. We performed sub-analyses of structural changes assessed on ultrasound, radiograph, or magnetic resonance imaging (MRI). METHODS We utilized PubMed, Cochrane Library, and Embase databases up to December 1, 2021, according to Preferred Reporting Items for Systematic-Reviews and Meta-Analyses guidelines. Twenty-four studies met criteria, with comparisons to: HA (n=11); CS (n=6); NS (n=5); and exercise therapy (n=3). Seven studies assessed structural changes. Evaluations utilized a methodological scoring system. I(2) statistics and forest plots pooled analyses and delineated study results. RESULTS PRP led to VAS and WOMAC improvements in most studies when compared to HA, CS, and NS (p≤0.05). Comparison to exercise therapy resulted in inconclusive findings (p≥0.05). However, substantial heterogeneity (I(2) ≥76%) was reported due to study variability. No differences were found when assessing structural changes or cartilage thickness by MRI (standardized mean difference -0.01 [-0.19, 0.18], p=0.91). CONCLUSIONS PRP may be associated with pain and functional improvements but was not clinically relevant (inconsistent study- and patient-metrics). Additionally, PRP did not confer superiority when assessing knee-related structural changes.
A systematic review on efficacy of different types of Platelet-Rich Plasma in the management of lateral epicondylitis
Journal of shoulder and elbow surgery. 2022
BACKGROUND Platelet-rich plasma (PRP) is reported as an effective treatment for lateral epicondylitis (LE). Theoretically, different types of PRP have different therapeutic effects. However, there is controversy on the effects of different types of PRP in the treatment of LE. PURPOSE To systematically compare the pain relief, functional improvement and successful rates on treatment of two different types of PRP, by reviewing and summarizing the data available in the current literature on LE after PRP injection. METHODS The PubMed, Medline, Embase, Cochrane Library and Web of science were reviewed. A computerized literature search was performed for related studies published from inception to August 2021 by terms of lateral epicondylitis, tennis elbow, tendinopathy, lateral elbow pain, PRP. PRP involved in present study were divided into leukocyte-poor PRP and leukocyte-rich PRP groups according to different preparation methods. Outcomes of interest included characteristics of the subjects, types and preparations of PRP, clinical outcomes, successful rate and safety of treatment of short-term and long-term follow-up. RESULTS A total of 33 studies included 2420 LE patients. There were 19 studies with LP-PRP, 13 studies with LR-PRP and 1 study involved both LP-PRP and LR-PRP. Patients had significant improved clinical outcomes post-treatment compared to pre-treatment in both groups of PRP. The mean of VAS was ranged from 6.1 to 8.0 before the treatment, 1.5 to 4.0 at short-term and 0.6 to 3.3 at the long-term follow-up in LR-PRP group. The mean of VAS was ranged from 4.2 to 8.4 before the treatment, 1.6 to 5.9 at short-term and 0.7 to 2.7 in the long-term follow-up in LP-PRP group. The DASH score of LR-PRP and LP-PRP were ranged from 47.0 to 54.3 and 30.0 to 67.7 separately before the treatment and 20.0 to 22.0 and 5.5 to 19.0 separately at long-term follow-up. LR-PRP and LP-PRP groups reflected successful rate ranged from 70%-100% and 36%-100% respectively. The complication rate lower in LP-PRP group (3.9%) than LR-PRP group (6.4%), with the major complication was temporary pain after PRP treatment (P = 0.029). CONCLUSION PRP treatment demonstrated a significant improvement with pain relief and functional improvement on lateral epicondylitis regardless types of PRP. There was no significant difference between LR-PRP and LP-PRP in pain relief and functional improvement. The major complication was temporary pain after PRP injection and the complication rate in LP-PRP was lower than LR-PRP.
Platelet-Rich Plasma Therapy Ensures Pain Reduction in the Management of Lateral Epicondylitis - A PRISMA-compliant Network Meta-Analysis of Randomised Controlled Trials
Expert opinion on biological therapy. 2022
OBJECTIVES We aim to analyze the effectiveness of platelet-rich plasma (PRP) therapy in comparison to all the available treatments in the management of lateral epicondylitis. MATERIALS AND METHODS We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library till June 2021 for randomized controlled trials (RCTs), analyzing the efficacy and safety of PRP in the management of lateral epicondylitis. Visual Analog Score (VAS) for pain, Disabilities of the Arm, Shoulder and Hand (DASH) Score, Patient Reported Tennis-Elbow Evaluation (PRETEE) Score were the outcomes analyzed. Analysis was performed in R-platform using MetaInsight. Available treatment methods in the network were ranking based on the p-score approach. The quality of results from network analysis was appraised with Cochrane's CINeMA approach. RESULTS 25 RCTs with 2040 patients were included in the network analysis. Compared to saline control, only leucocyte-rich PRP resulted in significant pain relief (WMD -14.8 95% CI [-23.18,-6.39]; low confidence) on network analysis of VAS outcome compared to other treatment methods such as steroid, local anesthetic, laser, and surgery. Concerning functional outcome parameters such as DASH score or PRETEE score, none of the above-mentioned treatment methods were superior to saline control. On subgroup analysis of the outcomes at various time points, LR-PRP resulted in clinically significant improvement at all time points analyzed. Upon ranking the probabilities of being best of all the interventions analyzed in the network, leucocyte-rich PRP seems more promising with a p score of 0.415. CONCLUSION PRP therapy offers significant pain relief compared to saline control when employed in the management lateral epicondylitis. However, we did not note similar improvement in functional outcomes measures. With the available low-quality evidence, PRP is ranked to be the most promising therapy that needs further exploration. Further high-quality RCTs are needed to explore its usefulness in lateral epicondylitis.
Intra-Articular Leukocyte-Rich Platelet-Rich Plasma versus Intra-Articular Hyaluronic Acid in the Treatment of Knee Osteoarthritis: A Meta-Analysis of 14 Randomized Controlled Trials
Pharmaceuticals (Basel, Switzerland). 2022;15(8)
(1) Background: To evaluate the clinical effects of leukocyte-rich platelet-rich plasma (LR-PRP) and hyaluronic acid (HA) injections in treating patients suffering from knee osteoarthritis (OA); (2) Methods: Randomized controlled trials (RCTs) were searched from PubMed, Web of Science, and Cochrane Library. Keywords were: platelet-rich plasma, LR-PRP, leukocyte-rich, hyaluronic acid, and knee osteoarthritis. The included RCTs were published between the 1st of November 2011 and the 3rd of February 2021. Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, visual analog scale (VAS) scores, International Knee Documentation Committee (IKDC) scores, and adverse events were used as outcomes for evaluation; (3) Results: A total of 14 RCTs were enrolled. At 6 months, revealed that the LR-PRP group was better than the HA group in WOMAC total, pain, and physical function scores. At 12 months, the LR-PRP group was better than the HA group in WOMAC stiffness and physical function scores. There was no significant difference in adverse events; (4) Conclusion: LR-PRP injection showed no significant pain relief effect as compared with HA injection. However, LR-PRP demonstrated better overall outcomes as compared to HA in knee OA patients at the follow-up periods of 3, 6, and 12 months. LR-PRP injection may be recommended as a feasible option in treating patients with knee OA.
Platelet-rich plasma in the treatment of scars, to suggest or not to suggest? A systematic review and meta-analysis
Journal of tissue engineering and regenerative medicine. 2022
Despite the rising trend for applying platelet-rich plasma (PRP) in the management of various types of scars, there is no convincing evidence supporting its use. This motivated us to review the randomized clinical trials that examine the effectiveness and safety of PRP, alone or in combination with other methods, for the management of atrophic or hypertrophic/keloidal scars. The Web of Science, Scopus, Google Scholar, and Cochrane Library databases were systematically searched until September 1(st) , 2020. Thirteen clinical trials were enrolled in the meta-analysis, and 10 more were reviewed for their results. The random effect meta-analysis method was used to assess the effect size of each outcome for each treatment type, and I(2) was used to calculate the statistical heterogeneity between the studies. Patients treated with PRP experienced an overall response rate of 23%, comparable to the results seen with laser or micro-needling (22% and 23%, respectively) When used alone, moderate improvement was the most frequently observed degree of response with PRP (36%) whereas, when added to laser or micro-needling, most patients experienced marked (33%, 43%, respectively) or excellent (32% and 23%, respectively) results. Concerning the hypertrophic/keloid scars, the only study meeting the required criteria reported a better improvement and fewer adverse effects when PRP was added to the intralesional corticosteroids. Platelet-rich plasma appears to be a safe and effective treatment for various types of atrophic scars. In addition, when added to ablative lasers or micro-needling, it seems to considerably add to the efficacy of treatment and reduce the side effects.