Autologous blood and platelet-rich plasma injection therapy for lateral elbow pain.

Autologous whole blood or platelet-rich plasma (PRP) injections are commonly used to treat lateral elbow pain (also known as tennis elbow or lateral epicondylitis or epicondylalgia). Based on animal models and observational studies, these injections may modulate tendon injury healing, but randomised controlled trials have reported inconsistent results regarding benefit for people with lateral elbow pain. To review current evidence on the benefit and safety of autologous whole blood or platelet-rich plasma (PRP) injection for treatment of people with lateral elbow pain. We searched CENTRAL, MEDLINE, and Embase for published trials, and Clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal for ongoing trials, on 18 September 2020. We included all randomised controlled trials (RCTs) and quasi-RCTs comparing autologous whole blood or PRP injection therapy to another therapy (placebo or active treatment, including non-pharmacological therapies, and comparison between PRP and autologous blood) for lateral elbow pain. The primary comparison was PRP versus placebo. Major outcomes were pain relief (≥ 30% or ≥ 50%), mean pain, mean function, treatment success, quality of life, withdrawal due to adverse events, and adverse events; the primary time point was three months. We used standard methodological procedures expected by Cochrane. We included 32 studies with 2337 participants; 56% of participants were female, mean age varied between 36 and 53 years, and mean duration of symptoms ranged from 1 to 22 months. Seven trials had three intervention arms. Ten trials compared autologous blood or PRP injection to placebo injection (primary comparison). Fifteen trials compared autologous blood or PRP injection to glucocorticoid injection. Four studies compared autologous blood to PRP. Two trials compared autologous blood or PRP injection plus tennis elbow strap and exercise versus tennis elbow strap and exercise alone. Two trials compared PRP injection to surgery, and one trial compared PRP injection and dry needling to dry needling alone. Other comparisons include autologous blood versus extracorporeal shock wave therapy; PRP versus arthroscopic surgery; PRP versus laser; and autologous blood versus polidocanol. Most studies were at risk of selection, performance, and detection biases, mainly due to inadequate allocation concealment and lack of participant blinding. We found moderate-certainty evidence (downgraded for bias) to show that autologous blood or PRP injection probably does not provide clinically significant improvement in pain or function compared with placebo injection at three months. Further, low-certainty evidence (downgraded for bias and imprecision) suggests that PRP may not increase risk for adverse events. We are uncertain whether autologous blood or PRP injection improves treatment success (downgraded for bias, imprecision, and indirectness) or withdrawals due to adverse events (downgraded for bias and twice for imprecision). No studies measured health-related quality of life, and no studies reported pain relief (> 30% or 50%) at three months. At three months, mean pain was 3.7 points (0 to 10; 0 is best) with placebo and 0.16 points better (95% confidence interval (CI) 0.60 better to 0.29 worse; 8 studies, 523 participants) with autologous blood or PRP injection, for absolute improvement of 1.6% better (6% better to 3% worse). At three months, mean function was 27.5 points (0 to 100; 0 is best) with placebo and 1.86 points better (95% CI 4.9 better to 1.25 worse; 8 studies, 502 participants) with autologous blood or PRP injection, for absolute benefit of 1.9% (5% better to 1% worse), and treatment success was 121 out of 185 (65%) with placebo versus 125 out of 187 (67%) with autologous blood or PRP injection (risk ratio (RR) 1.00; 95% CI 0.83 to 1.19; 4 studies, 372 participants), for absolute improvement of 0% (11.1% lower to 12.4% higher). Regarding harm, we found very low-certainty evidence to suggest that we are uncertain whether withdrawal rates due to adverse events differed. Low-certainty evidence suggests that autologous blood or PRP injection may not increase adverse events compared with placebo injection. Withdrawal due to adverse events occurred in 3 out of 39 (8%) participants treated with placebo versus 1 out of 41 (2%) treated with autologous blood or PRP injection (RR 0.32, 95% CI 0.03 to 2.92; 1 study), for an absolute difference of 5.2% fewer (7.5% fewer to 14.8% more). Adverse event rates were 35 out of 208 (17%) with placebo versus 41 out of 217 (19%) with autologous blood or PRP injection (RR 1.14, 95% CI 0.76 to 1.72; 5 studies; 425 participants), for an absolute difference of 2.4% more (4% fewer to 12% more). At six and twelve months, no clinically important benefit for mean pain or function was observed with autologous blood or PRP injection compared with placebo injection. Data in this review do not support the use of autologous blood or PRP injection for treatment of lateral elbow pain. These injections probably provide little or no clinically important benefit for pain or function (moderate-certainty evidence), and it is uncertain (very low-certainty evidence) whether they improve treatment success and pain relief > 50%, or increase withdrawal due to adverse events. Although risk for harm may not be increased compared with placebo injection (low-certainty evidence), injection therapies cause pain and carry a small risk of infection. With no evidence of benefit, the costs and risks are not justified.

Karjalainen TV ，Silagy M ，O'Bryan E ，Johnston RV ，Cyril S ，Buchbinder R ... -  《Cochrane Database of Systematic Reviews》

Subacromial decompression surgery for rotator cuff disease.

Karjalainen TV ，Jain NB ，Page CM ，Lähdeoja TA ，Johnston RV ，Salamh P ，Kavaja L ，Ardern CL ，Agarwal A ，Vandvik PO ，Buchbinder R ... -  《Cochrane Database of Systematic Reviews》

Arthroscopic surgery for degenerative knee disease (osteoarthritis including degenerative meniscal tears).

Arthroscopic knee surgery remains a common treatment for symptomatic knee osteoarthritis, including for degenerative meniscal tears, despite guidelines strongly recommending against its use. This Cochrane Review is an update of a non-Cochrane systematic review published in 2017. To assess the benefits and harms of arthroscopic surgery, including debridement, partial menisectomy or both, compared with placebo surgery or non-surgical treatment in people with degenerative knee disease (osteoarthritis, degenerative meniscal tears, or both). We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two trials registers up to 16 April 2021, unrestricted by language. We included randomised controlled trials (RCTs), or trials using quasi-randomised methods of participant allocation, comparing arthroscopic surgery with placebo surgery or non-surgical interventions (e.g. exercise, injections, non-arthroscopic lavage/irrigation, drug therapy, and supplements and complementary therapies) in people with symptomatic degenerative knee disease (osteoarthritis or degenerative meniscal tears or both). Major outcomes were pain, function, participant-reported treatment success, knee-specific quality of life, serious adverse events, total adverse events and knee surgery (replacement or osteotomy). Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias and the certainty of evidence using GRADE. The primary comparison was arthroscopic surgery compared to placebo surgery for outcomes that measured benefits of surgery, but we combined data from all control groups to assess harms and knee surgery (replacement or osteotomy). Sixteen trials (2105 participants) met our inclusion criteria. The average age of participants ranged from 46 to 65 years, and 56% of participants were women. Four trials (380 participants) compared arthroscopic surgery to placebo surgery. For the remaining trials, arthroscopic surgery was compared to exercise (eight trials, 1371 participants), a single intra-articular glucocorticoid injection (one trial, 120 participants), non-arthroscopic lavage (one trial, 34 participants), non-steroidal anti-inflammatory drugs (one trial, 80 participants) and weekly hyaluronic acid injections for five weeks (one trial, 120 participants). The majority of trials without a placebo control were susceptible to bias: in particular, selection (56%), performance (75%), detection (75%), attrition (44%) and selective reporting (75%) biases. The placebo-controlled trials were less susceptible to bias and none were at risk of performance or detection bias. Here we limit reporting to the main comparison, arthroscopic surgery versus placebo surgery. High-certainty evidence indicates arthroscopic surgery leads to little or no difference in pain or function at three months after surgery, moderate-certainty evidence indicates there is probably little or no improvement in knee-specific quality of life three months after surgery, and low-certainty evidence indicates arthroscopic surgery may lead to little or no difference in participant-reported success at up to five years, compared with placebo surgery. Mean post-operative pain in the placebo group was 40.1 points on a 0 to 100 scale (where lower score indicates less pain) compared to 35.5 points in the arthroscopic surgery group, a difference of 4.6 points better (95% confidence interval (CI) 0.02 better to 9 better; I2 = 0%; 4 trials, 309 participants). Mean post-operative function in the placebo group was 75.9 points on a 0 to 100 rating scale (where higher score indicates better function) compared to 76 points in the arthroscopic surgery group, a difference of 0.1 points better (95% CI 3.2 worse to 3.4 better; I2 = 0%; 3 trials, 302 participants). Mean post-operative knee-specific health-related quality of life in the placebo group was 69.7 points on a 0 to 100 rating scale (where higher score indicates better quality of life) compared with 75.3 points in the arthroscopic surgery group, a difference of 5.6 points better (95% CI 0.36 better to 10.68 better; I2 = 0%; 2 trials, 188 participants). We downgraded this evidence to moderate certainty as the 95% confidence interval does not rule in or rule out a clinically important change. After surgery, 74 out of 100 people reported treatment success with placebo and 82 out of 100 people reported treatment success with arthroscopic surgery at up to five years (risk ratio (RR) 1.11, 95% CI 0.66 to 1.86; I2 = 53%; 3 trials, 189 participants). We downgraded this evidence to low certainty due to serious indirectness (diversity in definition and timing of outcome measurement) and serious imprecision (small number of events). We are less certain if the risk of serious or total adverse events increased with arthroscopic surgery compared to placebo or non-surgical interventions. Serious adverse events were reported in 6 out of 100 people in the control groups and 8 out of 100 people in the arthroscopy groups from eight trials (RR 1.35, 95% CI 0.64 to 2.83; I2 = 47%; 8 trials, 1206 participants). Fifteen out of 100 people reported adverse events with control interventions, and 17 out of 100 people with surgery at up to five years (RR 1.15, 95% CI 0.78 to 1.70; I2 = 48%; 9 trials, 1326 participants). The certainty of the evidence was low, downgraded twice due to serious imprecision (small number of events) and possible reporting bias (incomplete reporting of outcome across studies). Serious adverse events included death, pulmonary embolism, acute myocardial infarction, deep vein thrombosis and deep infection. Subsequent knee surgery (replacement or high tibial osteotomy) was reported in 2 out of 100 people in the control groups and 4 out of 100 people in the arthroscopy surgery groups at up to five years in four trials (RR 2.63, 95% CI 0.94 to 7.34; I2 = 11%; 4 trials, 864 participants). The certainty of the evidence was low, downgraded twice due to the small number of events. Arthroscopic surgery provides little or no clinically important benefit in pain or function, probably does not provide clinically important benefits in knee-specific quality of life, and may not improve treatment success compared with a placebo procedure. It may lead to little or no difference, or a slight increase, in serious and total adverse events compared to control, but the evidence is of low certainty. Whether or not arthroscopic surgery results in slightly more subsequent knee surgery (replacement or osteotomy) compared to control remains unresolved.

O'Connor D ，Johnston RV ，Brignardello-Petersen R ，Poolman RW ，Cyril S ，Vandvik PO ，Buchbinder R ... -  《Cochrane Database of Systematic Reviews》

Manual therapy and exercise for lateral elbow pain.

Manual therapy and prescribed exercises are often provided together or separately in contemporary clinical practice to treat people with lateral elbow pain. To assess the benefits and harms of manual therapy, prescribed exercises or both for adults with lateral elbow pain. We searched the databases CENTRAL, MEDLINE and Embase, and trial registries until 31 January 2024, unrestricted by language or date of publication. We included randomised or quasi-randomised trials. Participants were adults with lateral elbow pain. Interventions were manual therapy, prescribed exercises or both. Primary comparators were placebo or minimal or no intervention. We also included comparisons of manual therapy and prescribed exercises with either intervention alone, with or without glucocorticoid injection. Exclusions were trials testing a single application of an intervention or comparison of different types of manual therapy or prescribed exercises. Two review authors independently selected studies for inclusion, extracted trial characteristics and numerical data, and assessed study risk of bias and certainty of evidence using GRADE. The main comparisons were manual therapy, prescribed exercises or both compared with placebo treatment, and with minimal or no intervention. Major outcomes were pain, disability, heath-related quality of life, participant-reported treatment success, participant withdrawals, adverse events and serious adverse events. The primary endpoint was end of intervention for pain, disability, health-related quality of life and participant-reported treatment success and final time point for adverse events and withdrawals. Twenty-three trials (1612 participants) met our inclusion criteria (mean age ranged from 38 to 52 years, 47% female, 70% dominant arm affected). One trial (23 participants) compared manual therapy to placebo manual therapy, 12 trials (1124 participants) compared manual therapy, prescribed exercises or both to minimal or no intervention, six trials (228 participants) compared manual therapy and exercise to exercise alone, one trial (60 participants) compared the addition of manual therapy to prescribed exercises and glucocorticoid injection, and four trials (177 participants) assessed the addition of manual therapy, prescribed exercises or both to glucocorticoid injection. Twenty-one trials without placebo control were susceptible to performance and detection bias as participants were not blinded to the intervention. Other biases included selection (nine trials, 39%, including two quasi-randomised), attrition (eight trials, 35%) and selective reporting (15 trials, 65%) biases. We report the results of the main comparisons. Manual therapy versus placebo manual therapy Low-certainty evidence, based upon a single trial (23 participants) and downgraded due to indirectness and imprecision, indicates manual therapy may reduce pain and elbow disability at the end of two to three weeks of treatment. Mean pain at the end of treatment was 4.1 points with placebo (0 to 10 scale) and 2.0 points with manual therapy, MD -2.1 points (95% CI -4.2 to -0.1). Mean disability was 40 points with placebo (0 to 100 scale) and 15 points with manual therapy, MD -25 points (95% CI -43 to -7). There was no follow-up beyond the end of treatment to show if these effects were sustained, and no other major outcomes were reported. Manual therapy, prescribed exercises or both versus minimal intervention Low-certainty evidence indicates manual therapy, prescribed exercises or both may slightly reduce pain and disability at the end of treatment, but the effects were not sustained, and there may be little to no improvement in health-related quality of life or number of participants reporting treatment success. We downgraded the evidence due to increased risk of performance bias and detection bias across all the trials, and indirectness due to the multimodal nature of the interventions included in the trials. At four weeks to three months, mean pain was 5.10 points with minimal treatment and manual therapy, prescribed exercises or both reduced pain by a MD of -0.53 points (95% CI -0.92 to -0.14, I2 = 43%; 12 trials, 1023 participants). At four weeks to three months, mean disability was 63.8 points with minimal or no treatment and manual therapy, prescribed exercises or both reduced disability by a MD of -5.00 points (95% CI -9.22 to -0.77, I2 = 63%; 10 trials, 732 participants). At four weeks to three months, mean quality of life was 73.04 points with minimal treatment on a 0 to 100 scale and prescribed exercises reduced quality of life by a MD of -5.58 points (95% CI -10.29 to -0.99; 2 trials, 113 participants). Treatment success was reported by 42% of participants with minimal or no treatment and 57.1% of participants with manual therapy, prescribed exercises or both, RR 1.36 (95% CI 0.96 to 1.93, I2 = 73%; 6 trials, 770 participants). We are uncertain if manual therapy, prescribed exercises or both results in more withdrawals or adverse events. There were 83/566 participant withdrawals (147 per 1000) from the minimal or no intervention group, and 77/581 (126 per 1000) from the manual therapy, prescribed exercises or both groups, RR 0.86 (95% CI 0.66 to 1.12, I2 = 0%; 12 trials). Adverse events were mild and transient and included pain, bruising and gastrointestinal events, and no serious adverse events were reported. Adverse events were reported by 19/224 (85 per 1000) in the minimal treatment group and 70/233 (313 per 1000) in the manual therapy, prescribed exercises or both groups, RR 3.69 (95% CI 0.98 to 13.97, I2 = 72%; 6 trials). Low-certainty evidence from a single trial in people with lateral elbow pain indicates that, compared with placebo, manual therapy may provide a clinically worthwhile benefit in terms of pain and disability at the end of treatment, although the 95% confidence interval also includes both an important improvement and no improvement, and the longer-term outcomes are unknown. Low-certainty evidence from 12 trials indicates that manual therapy and exercise may slightly reduce pain and disability at the end of treatment, but this may not be clinically worthwhile and these benefits are not sustained. While pain after treatment was an adverse event from manual therapy, the number of events was too small to be certain.

Wallis JA ，Bourne AM ，Jessup RL ，Johnston RV ，Frydman A ，Cyril S ，Buchbinder R ... -  《Cochrane Database of Systematic Reviews》

Surgery for rotator cuff tears.

This review is one in a series of Cochrane Reviews of interventions for shoulder disorders. To synthesise the available evidence regarding the benefits and harms of rotator cuff repair with or without subacromial decompression in the treatment of rotator cuff tears of the shoulder. We searched the CENTRAL, MEDLINE, Embase, Clinicaltrials.gov and WHO ICRTP registry unrestricted by date or language until 8 January 2019. Randomised controlled trials (RCTs) including adults with full-thickness rotator cuff tears and assessing the effect of rotator cuff repair compared to placebo, no treatment, or any other treatment were included. As there were no trials comparing surgery with placebo, the primary comparison was rotator cuff repair with or without subacromial decompression versus non-operative treatment (exercises with or without glucocorticoid injection). Other comparisons were rotator cuff repair and acromioplasty versus rotator cuff repair alone, and rotator cuff repair and subacromial decompression versus subacromial decompression alone. Major outcomes were mean pain, shoulder function, quality of life, participant-rated global assessment of treatment success, adverse events and serious adverse events. The primary endpoint for this review was one year. We used standard methodologic procedures expected by Cochrane. We included nine trials with 1007 participants. Three trials compared rotator cuff repair with subacromial decompression followed by exercises with exercise alone. These trials included 339 participants with full-thickness rotator cuff tears diagnosed with magnetic resonance imaging (MRI) or ultrasound examination. One of the three trials also provided up to three glucocorticoid injections in the exercise group. All surgery groups received tendon repair with subacromial decompression and the postoperative exercises were similar to the exercises provided for the non-operative groups. Five trials (526 participants) compared repair with acromioplasty versus repair alone; and one trial (142 participants) compared repair with subacromial decompression versus subacromial decompression alone. The mean age of trial participants ranged between 56 and 68 years, and females comprised 29% to 56% of the participants. Symptom duration varied from a mean of 10 months up to 28 months. Two trials excluded tears with traumatic onset of symptoms. One trial defined a minimum duration of symptoms of six months and required a trial of conservative therapy before inclusion. The trials included mainly repairable full-thickness supraspinatus tears, six trials specifically excluded tears involving the subscapularis tendon. All trials were at risk of bias for several criteria, most notably due to lack of participant and personnel blinding, but also for other reasons such as unclearly reported methods of random sequence generation or allocation concealment (six trials), incomplete outcome data (three trials), selective reporting (six trials), and other biases (six trials). Our main comparison was subacromial decompression versus non-operative treatment and results are reported for the 12 month follow up. At one year, moderate-certainty evidence (downgraded for bias) from 3 trials with 258 participants indicates that surgery probably provides little or no improvement in pain; mean pain (range 0 to 10, higher scores indicate more pain) was 1.6 points with non-operative treatment and 0.87 points better (0.43 better to 1.30 better) with surgery.. Mean function (zero to 100, higher score indicating better outcome) was 72 points with non-operative treatment and 6 points better (2.43 better to 9.54 better) with surgery (3 trials; 269 participants), low-certainty evidence (downgraded for bias and imprecision). Participant-rated global success rate was 873/1000 after non-operative treatment and 943/1000 after surgery corresponding to (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.96 to 1.22; low-certainty evidence (downgraded for bias and imprecision). Health-related quality of life was 57.5 points (SF-36 mental component score, 0 to 100, higher score indicating better quality of life) with non-operative treatment and 1.3 points worse (4.5 worse to 1.9 better) with surgery (1 trial; 103 participants), low-certainty evidence (downgraded for bias and imprecision). We were unable to estimate the risk of adverse events and serious adverse events as only one event was reported across the trials (very low-certainty evidence; downgraded once due to bias and twice due to very serious imprecision). At the moment, we are uncertain whether rotator cuff repair surgery provides clinically meaningful benefits to people with symptomatic tears; it may provide little or no clinically important benefits with respect to pain, function, overall quality of life or participant-rated global assessment of treatment success when compared with non-operative treatment. Surgery may not improve shoulder pain or function compared with exercises, with or without glucocorticoid injections. The trials included have methodology concerns and none included a placebo control. They included participants with mostly small degenerative tears involving the supraspinatus tendon and the conclusions of this review may not be applicable to traumatic tears, large tears involving the subscapularis tendon or young people. Furthermore, the trials did not assess if surgery could prevent arthritic changes in long-term follow-up. Further well-designed trials in this area that include a placebo-surgery control group and long follow-up are needed to further increase certainty about the effects of surgery for rotator cuff tears.

Karjalainen TV ，Jain NB ，Heikkinen J ，Johnston RV ，Page CM ，Buchbinder R ... -  《Cochrane Database of Systematic Reviews》