Objective To evaluate effectiveness, in terms of patient-reported outcome measures, of platelet-rich plasma (PRP) injections for knee osteoarthritis compared to placebo and other intraarticular treatments. Design PubMed, Cochrane Library, Scopus, Embase, Web of Science, as well as the gray literature were searched on January 17, 2020. Randomized controlled trials (RCTs) comparing PRP injections with placebo or other injectable treatments, in any language, on humans, were included. Risk of bias was assessed following the Cochrane guidelines; quality of evidence was graded using the GRADE guidelines. Results Thirty-four RCTs, including 1403 knees in PRP groups and 1426 in control groups, were selected. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score favored PRP, with a statistically and clinically significant difference versus placebo at 12-month follow-up ( P = 0.02) and versus HA (hyaluronic acid) at 6-month ( P < 0.001) and 12-month ( P < 0.001) follow-ups. A clinically significant difference favoring PRP versus steroids was documented for VAS (Visual Analogue Scale) pain ( P < 0.001), KOOS (Knee Injury and Osteoarthritis Outcome Score) pain ( P < 0.001), function in daily activities ( P = 0.001), and quality of life ( P < 0.001) at 6-month follow-up. However, superiority of PRP did not reach the minimal clinically important difference for all outcomes, and quality of evidence was low. Conclusions The effect of platelet concentrates goes beyond its mere placebo effect, and PRP injections provide better results than other injectable options. This benefit increases over time, being not significant at earlier follow-ups but becoming clinically significant after 6 to 12 months. However, although substantial, the improvement remains partial and supported by low level of evidence. This finding urges further research to confirm benefits and identify the best formulation and indications for PRP injections in knee OA.

Objectives To quantify the placebo effect of intraarticular injections for knee osteoarthritis in terms of pain, function, and objective outcomes. Factors influencing placebo effect were investigated. Design Meta-analysis of randomized controlled trials; Level of evidence, 2. PubMed, Web of Science, Cochrane Library, and grey literature databases were searched on January 8, 2020, using the string: (knee) AND (osteoarthritis OR OA) AND (injections OR intra-articular) AND (saline OR placebo). The following inclusion criteria were used: double-blind, randomized controlled trials on knee osteoarthritis, including a placebo arm on saline injections. The primary outcome was pain variation. Risk of bias was assessed using the RoB 2.0 tool, and quality of evidence was graded following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) guidelines. Results Out of 2,363 records, 50 articles on 4,076 patients were included. The meta-analysis showed significant improvements up to the 6-month follow-up: Visual Analogue Scale (VAS)-pain −13.4 mean difference (MD) (95% confidence interval [CI]: −21.7/−5.1; P < 0.001), Western Ontario and McMaster Osteoarthritis Index (WOMAC)-pain −3.3 MD (95% CI: −3.9/−2.7; P < 0.001). Other significant improvements were WOMAC-stiffness −1.1 MD (95% CI: −1.6/−0.6; P < 0.001), WOMAC-function −10.1 MD (95% CI: −12.2/−8.0; P < 0.001), and Evaluator Global Assessment −21.4 MD (95% CI: −29.2/−13.6; P < 0.001). The responder rate was 52% (95% CI: 40% to 63%). Improvements were greater than the “minimal clinically important difference” for all outcomes (except 6-month VAS-pain). The level of evidence was moderate for almost all outcomes. Conclusions The placebo effect of knee injections is significant, with functional improvements lasting even longer than those reported for pain perception. The high, long-lasting, and heterogeneous effects on the scales commonly used in clinical trials further highlight that the impact of placebo should not be overlooked in the research on and management of knee osteoarthritis.

Background: There is no agreement on the best treatment for displaced midshaft clavicle fractures (MCFs), which are currently addressed by nonoperative or surgical approaches. Purpose: To compare fracture healing and functional outcome after surgical versus nonsurgical treatment of MCFs, to help specialists in deciding between these different strategies by providing a synthesis of the best literature evidence. Study Design: Meta-analysis. Methods: A systematic research of the literature was performed in different online databases: PubMed, Web of Science, Cochrane library, and grey literature. PRISMA (Preferred Reporting Items for Systematic Meta-Analyses) guidelines were used. The risk of bias was evaluated with the Cochrane Collaboration’s “risk of bias” tool, and the quality of evidence was graded according to Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Randomized controlled trials investigating differences between surgery and nonoperative treatment for displaced MCFs were included. The primary outcome was the nonunion rate. Other outcomes analyzed were time to union and to return to activities, Constant score, and Disabilities of the Arm, Shoulder and Hand (DASH) index. Patients’ satisfaction, secondary operations, and complications were also recorded. Results: Out of 832 records found, 14 randomized controlled trials with 1546 patients were included. A significantly lower risk ratio was found for nonunion (10%; 95% CI, 6%-18%, P < .001) favoring surgery. Time to union was 5.1 weeks shorter with surgery ( P = .007). The complication rate (including the number of reinterventions) was higher in the surgical group (31.3% vs 20.5%, P < .001). Shoulder function at short-term follow-up was significantly better in the surgical group (DASH index mean difference = 4.0 points), while no statistical difference was found in the Constant score and in the DASH index at midterm follow-up ( P = .41 and .80, respectively). At long-term follow-up, both shoulder functional scores were significantly better in the surgery group: the overall Constant score mean difference was 5.3 points (95% CI, 2.3-8.4 points; P < .001), and the DASH index mean difference was 4.3 points (95% CI, 0.2-8.4 points; P = .04). Conclusion: Surgical treatment of MCFs significantly reduces the nonunion rate and shortens the time to union as compared with the nonoperative approach and, despite a slightly higher incidence of complications, leads to better shoulder functional scores at short- and long-term follow-up. Further studies should address the clinical significance of the documented improvement.

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Background: Injury-to-surgery time has been identified as a key point in anterior cruciate ligament (ACL) reconstruction, with early versus delayed treatment remaining a debated and controversial topic in the management of ACL tears. Purpose/Hypothesis: The aim was to quantitatively synthesize the best literature evidence by including only randomized controlled trials (RCTs) comparing early versus delayed ACL reconstruction, with a clear and univocal definition of cutoffs of early or delayed surgery. The hypothesis was that early treatment would lead to similar final clinical results compared with the delayed approach while providing a faster recovery without an increase in complications after ACL reconstruction. Study Design: Meta-analysis. Methods: A systematic literature search was performed on February 12, 2019, using PubMed, Web of Science, Cochrane Library, and gray literature databases. According to previous literature, 2 analyses with different cutoffs for injury-to-surgery time (3 weeks and 10 weeks) were performed to distinguish early and delayed reconstruction. The influence of timing was analyzed through meta-analyses in terms of patient-reported outcome measures (PROMs), risk of complications, range of motion (ROM) limitation, risk of retears, and residual laxity. Risk of bias and quality of evidence were assessed following the Cochrane guidelines. Results: Eight studies (5 in 3-week cutoff analysis and 3 in 10-week cutoff analysis) were included. No differences were found in terms of PROMs, risk of complications, ROM limitation, risk of retears, and residual laxity either in the 3-week cutoff analysis or in the 10-week cutoff analysis ( P > .05). The level of evidence was moderate to low for the outcomes of the 3-week cutoff analysis and low to very low for the outcomes of the 10-week cutoff analysis. Conclusion: This meta-analysis did not confirm the previously advocated benefits of delaying ACL surgery to avoid the acute posttraumatic phase. In fact, RCTs demonstrated that timing of surgery after ACL tears has no influence on the final functional outcome, risk of retears, or residual instability. While no data were available about the recovery time, literature results showed that early ACL reconstruction could be performed without increasing the risk of complications. Study Registration: CRD42019119319 (PROSPERO).