Journal»Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association
PURPOSE: We aimed to determine if the randomized controlled trials (RCTs) evaluated in the most recent meta-analysis on arthroscopic surgery for degenerative knee arthritis included documented trials of appropriate conservative treatment prior to randomization.
METHODS: We selected all RCTs of the most recent meta-analysis by Brignardello-Petersen and recorded for each RCT, if physiotherapy prior to randomization was mandatory. We compared the treatment effect of arthroscopy in studies in which physiotherapy prior to randomization was mandatory versus studies in which it was not. This review was registered in the PROSPERO database (CRD42017070091).
RESULTS: Of the 13 RCTs in the meta-analysis, there were 2 in which physiotherapy prior to randomization was mandatory. In 1 additional multicenter RCT, prior conservative treatment was mentioned as mandatory in the publication, but not in the protocol. The treatment effects attributed to arthroscopy in terms of short-term pain (P = .0037), short-term function (P = .0309), and long-term function (P = .0012) were larger in studies in which prior physiotherapy was mandatory.
CONCLUSIONS: Although the most recent meta-analysis claims that it is based "on patients who do not respond to conservative treatment," physiotherapy was mandatory prior to randomization only in 2 of the 13 studies. As several orthopaedic guidelines recommend that the first line of treatment in patients with degenerative arthritis of the knee should be conservative, for instance with physiotherapy, and the question of performing arthroscopy arises once conservative treatment fails, 11 of the 13 RCTs failed to adhere to these accepted guidelines. Therefore, patient selection in these 11 studies may not represent the typical indications for arthroscopy, where patients have tried conservative management prior to being offered surgery. When comparing studies where prior physiotherapy was mandatory to studies in which it was not mandatory, there were statistically significant effects favoring arthroscopy in terms of pain in the short term, and for function both in the short and the long term. These findings suggest that the treatment effects attributed to arthroscopy were higher when prior physiotherapy was mandatory. Given these findings, the external validity of most of these RCTs, and the resulting "strong recommendation against the use of arthroscopy in nearly all patients with degenerative knee disease," is called into question.
LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.
INTRODUCTION: Neurotrophic factors (NTFs) have been evaluated for neuroprotective effects in Parkinson's disease (PD). However, clinical trials examining the efficacy of intracerebral administration of NTFs on motor symptoms in PD have produced mixed results, and are thus inconclusive. The objective of this systematic review and meta-analysis was to determine the effects of intracerebral NTF application on motor symptoms in people with PD.
METHODS: We searched PubMed, MEDLINE, EMBASE, and Cochrane from inception through to March 31 2016 for open-label trials and randomized controlled trials (RCTs) which intracerebrally administered NTFs to PD patients, and which performed motor examination using the Unified Parkinson's Disease Rating Scale.
RESULTS: Eight studies with a total of 223 participants were included. Fixed effects analysis revealed that NTF treatment did not significantly reduce motor symptoms in PD patients compared to placebo controls (P = 0.98). Combining open-label and RCT data, both treatment with NTFs (P < 0.001) and treatment with placebo (P < 0.05) significantly improved motor function in PD patients when compared to predicted symptoms in untreated PD controls. Finally, random effects analysis revealed that NTF-treated PD patients were not significantly likely to improve following intracerebral NTF administration (P = 0.25).
CONCLUSION: In conclusion, intracerebral NTF administration does not improve motor symptoms in PD patients, when compared to placebo-treated controls. These findings may guide therapeutic decisions and inform future research on NTFs and their application in PD.
This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized placebo-controlled surgical trials.Central, MEDLINE, and EMBASE were systematically searched to identify randomized controlled trials comparing a surgical procedure to a placebo. "Surgical procedure" was defined as a medical procedure involving an incision with instruments. Placebo was defined as a blinded sham operation involving no change to the structural anatomy and without an expectable physiological response in the target body compartment.Ten randomized placebo-controlled controlled surgical trials were included, all of them published in high-ranking medical journals (mean impact factor: 20.1). Eight of 10 failed to show statistical superiority of the experimental intervention. Serious adverse events did not differ between the groups (rate ratio [RR] 1.38, 95% confidence interval [CI]: 0.92-2.06, P = 0.46). None of the trials had a high risk of bias in any domain. The ethical justification for the use of a placebo control remained unclear in 2 trials.Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity. Based on the current evidence, a pragmatic proposal for the use of placebo controls in future randomized controlled surgical trials is made.
Background: To minimise the rate of recurrent prolapse after traditional native tissue repair (anterior colporrhaphy), clinicians have utilised a variety of surgical techniques. Objectives: To determine the safety and effectiveness of surgery for anterior compartment prolapse. Search methods: We searched the Cochrane Incontinence Group Specialised Register, including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In Process (23 August 2016), handsearched journals and conference proceedings (15 February 2016) and searched trial registers (1 August 2016). Selection criteria: Randomised controlled trials (RCTs) that examined surgical operations for anterior compartment prolapse. Data collection and analysis: Two review authors independently selected trials, assessed risk of bias and extracted data. Primary outcomes were awareness of prolapse, repeat surgery and recurrent prolapse on examination. Main results: We included 33 trials (3332 women). The quality of evidence ranged from very low to moderate. Limitations were risk of bias and imprecision. We have summarised results for the main comparisons. Native tissue versus biological graft Awareness of prolapse: Evidence suggested few or no differences between groups (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.52 to 1.82; five RCTs; 552 women; I2 = 39%; low-quality evidence), indicating that if 12% of women were aware of prolapse after biological graft, 7% to 23% would be aware after native tissue repair. Repeat surgery for prolapse: Results showed no probable differences between groups (RR 1.02, 95% CI 0.53 to 1.97; seven RCTs; 650 women; I2 = 0%; moderate-quality evidence), indicating that if 4% of women required repeat surgery after biological graft, 2% to 9% would do so after native tissue repair. Recurrent anterior compartment prolapse: Native tissue repair probably increased the risk of recurrence (RR 1.32, 95% CI 1.06 to 1.65; eight RCTs; 701 women; I2 = 26%; moderate-quality evidence), indicating that if 26% of women had recurrent prolapse after biological graft, 27% to 42% would have recurrence after native tissue repair. Stress urinary incontinence (SUI): Results showed no probable differences between groups (RR 1.44, 95% CI 0.79 to 2.64; two RCTs; 218 women; I2 = 0%; moderate-quality evidence). Dyspareunia: Evidence suggested few or no differences between groups (RR 0.87, 95% CI 0.39 to 1.93; two RCTs; 151 women; I2 = 0%; low-quality evidence). Native tissue versus polypropylene mesh Awareness of prolapse: This was probably more likely after native tissue repair (RR 1.77, 95% CI 1.37 to 2.28; nine RCTs; 1133 women; I2 = 0%; moderate-quality evidence), suggesting that if 13% of women were aware of prolapse after mesh repair, 18% to 30% would be aware of prolapse after native tissue repair. Repeat surgery for prolapse: This was probably more likely after native tissue repair (RR 2.03, 95% CI 1.15 to 3.58; 12 RCTs; 1629 women; I2 = 39%; moderate-quality evidence), suggesting that if 2% of women needed repeat surgery after mesh repair, 2% to 7% would do so after native tissue repair. Recurrent anterior compartment prolapse: This was probably more likely after native tissue repair (RR 3.01, 95% CI 2.52 to 3.60; 16 RCTs; 1976 women; I2 = 39%; moderate-quality evidence), suggesting that if recurrent prolapse occurred in 13% of women after mesh repair, 32% to 45% would have recurrence after native tissue repair. Repeat surgery for prolapse, stress urinary incontinence or mesh exposure (composite outcome): This was probably less likely after native tissue repair (RR 0.59, 95% CI 0.41 to 0.83; 12 RCTs; 1527 women; I2 = 45%; moderate-quality evidence), suggesting that if 10% of women require repeat surgery after polypropylene mesh repair, 4% to 8% would do so after native tissue repair. De novo SUI: Evidence suggested few or no differences between groups (RR 0.67, 95% CI 0.44 to 1.01; six RCTs; 957 women; I2 = 26%; low-quality evidence). No evidence suggested a difference in rates of repeat surgery for SUI. Dyspareunia (de novo): Evidence suggested few or no differences between groups (RR 0.54, 95% CI 0.27 to 1.06; eight RCTs; n = 583; I2 = 0%; low-quality evidence). Native tissue versus absorbable mesh Awareness of prolapse: It is unclear whether results showed any differences between groups (RR 0.95, 95% CI 0.70 to 1.31; one RCT; n = 54; very low-quality evidence), Repeat surgery for prolapse: It is unclear whether results showed any differences between groups (RR 2.13, 95% CI 0.42 to 10.82; one RCT; n = 66; very low-quality evidence). Recurrent anterior compartment prolapse: This is probably more likely after native tissue repair (RR 1.50, 95% CI 1.09 to 2.06; three RCTs; n = 268; I2 = 0%; moderate-quality evidence), suggesting that if 27% have recurrent prolapse after mesh repair, 29% to 55% would have recurrent prolapse after native tissue repair. SUI: It is unclear whether results showed any differences between groups (RR 0.72, 95% CI 0.50 to 1.05; one RCT; n = 49; very low-quality evidence). Dyspareunia: No data were reported. Authors' conclusions: Biological graft repair or absorbable mesh provides minimal advantage compared with native tissue repair. Native tissue repair was associated with increased awareness of prolapse and increased risk of repeat surgery for prolapse and recurrence of anterior compartment prolapse compared with polypropylene mesh repair. However, native tissue repair was associated with reduced risk of de novo SUI, reduced bladder injury, and reduced rates of repeat surgery for prolapse, stress urinary incontinence and mesh exposure (composite outcome). Current evidence does not support the use of mesh repair compared with native tissue repair for anterior compartment prolapse owing to increased morbidity. Many transvaginal polypropylene meshes have been voluntarily removed from the market, and newer light-weight transvaginal meshes that are available have not been assessed by RCTs. Clinicans and women should be cautious when utilising these products, as their safety and efficacy have not been established.
OBJECTIVE: To determine benefits and harms of arthroscopic knee surgery involving partial meniscectomy, debridement, or both for middle aged or older patients with knee pain and degenerative knee disease.
DESIGN: Systematic review and meta-analysis.
MAIN OUTCOME MEASURES: Pain and physical function.
DATA SOURCES: Systematic searches for benefits and harms were carried out in Medline, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to August 2014. Only studies published in 2000 or later were included for harms.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials assessing benefit of arthroscopic surgery involving partial meniscectomy, debridement, or both for patients with or without radiographic signs of osteoarthritis were included. For harms, cohort studies, register based studies, and case series were also allowed.
RESULTS: The search identified nine trials assessing the benefits of knee arthroscopic surgery in middle aged and older patients with knee pain and degenerative knee disease. The main analysis, combining the primary endpoints of the individual trials from three to 24 months postoperatively, showed a small difference in favour of interventions including arthroscopic surgery compared with control treatments for pain (effect size 0.14, 95% confidence interval 0.03 to 0.26). This difference corresponds to a benefit of 2.4 (95% confidence interval 0.4 to 4.3) mm on a 0-100 mm visual analogue scale. When analysed over time of follow-up, interventions including arthroscopy showed a small benefit of 3-5 mm for pain at three and six months but not later up to 24 months. No significant benefit on physical function was found (effect size 0.09, -0.05 to 0.24). Nine studies reporting on harms were identified. Harms included symptomatic deep venous thrombosis (4.13 (95% confidence interval 1.78 to 9.60) events per 1000 procedures), pulmonary embolism, infection, and death.
CONCLUSIONS: The small inconsequential benefit seen from interventions that include arthroscopy for the degenerative knee is limited in time and absent at one to two years after surgery. Knee arthroscopy is associated with harms. Taken together, these findings do not support the practise of arthroscopic surgery for middle aged or older patients with knee pain with or without signs of osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009145.
OBJECTIVE: To determine benefits and harms of arthroscopic knee surgery involving partial meniscectomy, debridement, or both for middle aged or older patients with knee pain and degenerative knee disease.
DESIGN: Systematic review and meta-analysis.
MAIN OUTCOME MEASURES: Pain and physical function.
DATA SOURCES: Systematic searches for benefits and harms were carried out in Medline, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to August 2014. Only studies published in 2000 or later were included for harms.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials assessing benefit of arthroscopic surgery involving partial meniscectomy, debridement, or both for patients with or without radiographic signs of osteoarthritis were included. For harms, cohort studies, register based studies, and case series were also allowed.
RESULTS: The search identified nine trials assessing the benefits of knee arthroscopic surgery in middle aged and older patients with knee pain and degenerative knee disease. The main analysis, combining the primary endpoints of the individual trials from three to 24 months postoperatively, showed a small difference in favour of interventions including arthroscopic surgery compared with control treatments for pain (effect size 0.14, 95% confidence interval 0.03 to 0.26). This difference corresponds to a benefit of 2.4 (95% confidence interval 0.4 to 4.3) mm on a 0-100 mm visual analogue scale. When analysed over time of follow-up, interventions including arthroscopy showed a small benefit of 3-5 mm for pain at three and six months but not later up to 24 months. No significant benefit on physical function was found (effect size 0.09, -0.05 to 0.24). Nine studies reporting on harms were identified. Harms included symptomatic deep venous thrombosis (4.13 (95% confidence interval 1.78 to 9.60) events per 1000 procedures), pulmonary embolism, infection, and death.
CONCLUSIONS: The small inconsequential benefit seen from interventions that include arthroscopy for the degenerative knee is limited in time and absent at one to two years after surgery. Knee arthroscopy is associated with harms. Taken together, these findings do not support the practise of arthroscopic surgery for middle aged or older patients with knee pain with or without signs of osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009145.
Knee arthroscopy has historically been a common treatment for knee osteoarthritis. A Cochrane review of the literature up to 2006 has resulted in guidance that arthroscopy is not effective in knee osteoarthritis. It cited that deficiencies in the evidence base prevented widespread acceptance of the recommendations. The aim of this review is to update the evidence base for the efficacy of arthroscopy in knee osteoarthritis. The authors searched CINHAL, EMBASE, MEDLINE, and CENTRAL for randomised controlled trials that compared arthroscopic surgery in knee osteoarthritis with a control group (e.g. lavage, best medical care). The primary outcome measure was patient reported functional outcome. The study methodology was registered on Prospero, a systematic review register: Registration number CRD42012002891. Five randomised controlled trials included 516 patients, almost double the 271 episodes contained in previous reviews. Two high quality studies, according to the Jadad classification, published since the Cochrane review, addressed many of the methodological flaws criticised in previous reviews. However, certain subgroup analyses (e.g. patients with meniscal tears and mechanical symptoms) are still underpowered.
OBJECTIVES: To analyse the impact of placebo effects on outcome in trials of selected minimally invasive procedures and to assess reported adverse events in both trial arms.
DESIGN: A systematic review and meta-analysis.
DATA SOURCES AND STUDY SELECTION: We searched MEDLINE and Cochrane library to identify systematic reviews of musculoskeletal, neurological and cardiac conditions published between January 2009 and January 2014 comparing selected minimally invasive with placebo (sham) procedures. We searched MEDLINE for additional randomised controlled trials published between January 2000 and January 2014.
DATA SYNTHESIS: Effect sizes (ES) in the active and placebo arms in the trials' primary and pooled secondary end points were calculated. Linear regression was used to analyse the association between end points in the active and sham groups. Reported adverse events in both trial arms were registered.
RESULTS: We included 21 trials involving 2519 adult participants. For primary end points, there was a large clinical effect (ES≥0.8) after active treatment in 12 trials and after sham procedures in 11 trials. For secondary end points, 7 and 5 trials showed a large clinical effect. Three trials showed a moderate difference in ES between active treatment and sham on primary end points (ES ≥0.5) but no trials reported a large difference. No trials showed large or moderate differences in ES on pooled secondary end points. Regression analysis of end points in active treatment and sham arms estimated an R(2) of 0.78 for primary and 0.84 for secondary end points. Adverse events after sham were in most cases minor and of short duration.
CONCLUSIONS: The generally small differences in ES between active treatment and sham suggest that non-specific mechanisms, including placebo, are major predictors of the observed effects. Adverse events related to sham procedures were mainly minor and short-lived. Ethical arguments frequently raised against sham-controlled trials were generally not substantiated.
INTRODUCTION: The mean age of onset of Parkinson's disease is about 65 years, with a median time of 9 years between diagnosis and death.
METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of fetal cell or stem cell-derived therapy in people with Parkinson's disease? We searched: Medline, Embase, The Cochrane Library and other important databases up to September 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS: We found two studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: fetal cell therapy versus deep brain stimulation; fetal cell therapy versus sham surgery; stem cell-derived therapy versus deep brain stimulation; stem cell-derived therapy versus sham surgery.
Double-blind, sham-controlled neurosurgical trials for neurodegenerative disorders are debated as an ethical dilemma, particularly regarding subjects randomized to the sham surgery group with general anesthesia.
OBJECTIVE:
The objective of this study was to examine the safety of sham surgeries in Parkinson's disease (PD) clinical trials through complications related to the procedure.
METHODS:
A systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Rates and odds ratios (OR) were compared using random effects analysis.
RESULTS:
Seven studies, all randomized, double-blind, sham surgery-controlled trials, with 309 patients with PD, were qualitatively and quantitatively analyzed: 141 patients in sham groups and 168 patients in the experimental arms of gene or cell therapy trials. Sham subjects had lower rates of gastrointestinal, positioning, incision-site, respiratory (hypoxic or hypercapnic respiratory failure), cardiovascular, thromboembolism, postoperative cognitive decline, skull fracture, and intracranial or spinal complications when compared with active treatment subjects. Sham subjects, however, had a higher rate of perioperative respiratory infections, such as pneumonia or sinusitis. Further, sham subjects were less likely to experience postoperative cognitive decline (OR, 0.23; 95% confidence interval [CI]: 0.11-0.47), intracranial or spinal complications (OR, 0.10; 95% CI.: 0.01-0.75), total major morbidity (OR, 0.30; 95% CI.: 0.19-0.47), or overall complications (OR, 0.59; 95% CI.: 0.47-0.75) when compared with patients receiving experimental therapy.
