Nathan Evaniew

Arthroscopic surgery for degenerative tears of the meniscus: a systematic review and meta-analysis

Background: Arthroscopic surgery for degenerative meniscal tears is a commonly performed procedure, yet the role of conservative treatment for these patients is unclear. This systematic review and meta-analysis evaluates the efficacy of arthroscopic meniscal débridement in patients with knee pain in the setting of mild or no concurrent osteoarthritis of the knee in comparison with nonoperative or sham treatments. Methods: We searched MEDLINE, Embase and the Cochrane databases for randomized controlled trials (RCTs) published from 1946 to Jan. 20, 2014. Two reviewers independently screened all titles and abstracts for eligibility. We assessed risk of bias for all included studies and pooled outcomes using a random-effects model. Outcomes (i.e., function and pain relief) were dichotomized to short-term (< 6 mo) and long-term (< 2 yr) data. Results: Seven RCTs (n = 805 patients) were included in this review. The pooled treatment effect of arthroscopic surgery did not show a significant or minimally important difference (MID) between treatment arms for long-term functional outcomes (standardized mean difference [SMD] 0.07, 95% confidence interval [CI] −0.10 to 0.23). Short-term functional outcomes between groups were significant but did not exceed the threshold for MID (SMD 0.25, 95% CI 0.02 to 0.48). Arthroscopic surgery did not result in a significant improvement in pain scores in the short term (mean difference [MD] 0.20, 95% CI −0.67 to 0.26) or in the long term (MD −0.06, 95% CI −0.28 to 0.15). Statistical heterogeneity was low to moderate for the outcomes. Interpretation: There is moderate evidence to suggest that there is no benefit to arthroscopic meniscal débridement for degenerative meniscal tears in comparison with nonoperative or sham treatments in middle-aged patients with mild or no concomitant osteoarthritis. A trial of nonoperative management should be the first-line treatment for such patients.

A Translational Study of the Neoplastic Cells of Giant Cell Tumor of Bone Following Neoadjuvant Denosumab

BACKGROUND Giant cell tumor of bone is a primary bone tumor that is treated surgically and is associated with high morbidity in many cases. This tumor consists of giant cells expressing RANK (receptor activator of nuclear factor-κB) and mesenchymal spindle-like stromal cells expressing RANKL (RANK ligand); the interaction of these cells leads to bone resorption. Denosumab is a monoclonal antibody that binds RANKL and directly inhibits osteoclastogenesis. Clinical studies have suggested clinical and histological improvement when denosumab was administered to patients with a giant cell tumor. However, no studies have yet examined the viability and functional characteristics of tumor cells following denosumab treatment. METHODS Specimens were obtained from six patients with a histologically confirmed giant cell tumor. Two of the patients had been treated with denosumab for six months. Primary cultures of stromal cells from fresh tumor tissue were established. Cell proliferation was measured over a two-day time course. The expression of RANKL and osteoprotegerin was analyzed with use of real-time PCR (polymerase chain reaction). RESULTS Histological specimens from both patients who had completed denosumab treatment showed the absence of giant cells but persistence of stromal cells. Cell proliferation studies indicated that proliferation of stromal cells cultured from clinical specimens following denosumab treatment was approximately 50% slower than that of specimens from untreated patients. The expression of RANKL in the specimens from the treated patients was almost completely eliminated. CONCLUSIONS Once the giant cell tumor tissue was no longer exposed to denosumab, the stromal cells continued to proliferate in vitro, albeit to a lesser degree. However, they also showed almost complete loss of RANKL expression. CLINICAL RELEVANCE It is clear that treatment with denosumab only partially addresses the therapeutic need of patients with a giant cell tumor by wiping out the osteoclasts but leaving the neoplastic stromal cells proliferative.

Methylprednisolone for the Treatment of Patients with Acute Spinal Cord Injuries: A Systematic Review and Meta-Analysis

Abstract Previous meta-analyses of methylprednisolone (MPS) for patients with acute traumatic spinal cord injuries (TSCIs) have not addressed confidence in the quality of evidence used for pooled effect estimates, and new primary studies have been recently published. We aimed to determine whether MPS improves motor recovery and is associated with increased risks for adverse events. We searched MEDLINE, EMBASE, and The Cochrane Library, and two reviewers independently screened articles, extracted data, and evaluated risk of bias. We pooled outcomes from randomized, controlled trials (RCTs) and controlled observational studies separately and used the Grades of Recommendation, Assessment, Development, and Evaluation approach to evaluate confidence. We included four RCTs and 17 observational studies. MPS was not associated with an increase in long-term motor score recovery (two RCTs: 335 participants; mean difference [MD], −1.11; 95% confidence interval [CI], −4.75 to 2.53; p = 0.55, low confidence; two observational studies: 528 participants; MD, 1.37; 95% CI, −3.08 to 5.83; p = 0.55, very low confidence) or improvement by at least one motor grade (three observational studies: 383 participants; risk ratio [RR], 0.84; 95% CI, 0.53–1.33; p = 0.46, very low confidence). Evidence from two RCTs demonstrated superior short-term motor score improvement if MPS was administered within 8 h of injury (two RCTs: 250 participants; MD, 4.46; 95% CI, 0.97–7.94; p = 0.01, low confidence), but risk of bias and imprecision limit confidence in these findings. Observational studies demonstrated a significantly increased risk for gastrointestinal bleeding (nine studies: 2857 participants; RR, 2.18; 95% CI, 1.13–4.19; p = 0.02, very low confidence), but RCTs did not. Pooled evidence does not demonstrate a significant long-term benefit for MPS in patients with acute TSCIs and suggests it may be associated with increased gastrointestinal bleeding. These findings support current guidelines against routine use, but strong recommendations are not warranted because confidence in the effect estimates is limited.

Prophylactic antibiotic regimens in tumour surgery (PARITY): protocol for a multicentre randomised controlled study

Introduction Limb salvage with endoprosthetic reconstruction is the standard of care for the management of lower-extremity bone tumours in skeletally mature patients. The risk of deep postoperative infection in these procedures is high and the outcomes can be devastating. The most effective prophylactic antibiotic regimen remains unknown, and current clinical practice is highly varied. This trial will evaluate the effect of varying postoperative prophylactic antibiotic regimens on the incidence of deep infection following surgical excision and endoprosthetic reconstruction of lower-extremity bone tumours. Methods and analysis This is a multicentre, blinded, randomised controlled trial, using a parallel two-arm design. 920 patients 15 years of age or older from 12 tertiary care centres across Canada and the USA who are undergoing surgical excision and endoprosthetic reconstruction of a primary bone tumour will receive either short (24 h) or long (5 days) duration postoperative antibiotics. Exclusion criteria include prior surgery or infection within the planned operative field, known colonisation with methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus at enrolment, or allergy to the study antibiotics. The primary outcome will be rates of deep postoperative infections in each arm. Secondary outcomes will include type and frequency of antibiotic-related adverse events, patient functional outcomes and quality-of-life scores, reoperation and mortality. Randomisation will be blocked, with block sizes known only to the methods centre responsible for randomisation, and stratified by location of tumour and study centre. Patients, care givers and a Central Adjudication Committee will be blinded to treatment allocation. The analysis to compare groups will be performed using Cox regression and log-rank tests to compare survival functions at α=0.05. Ethics and dissemination This study has ethics approval from the McMaster University/Hamilton Health Sciences Research Ethics Board (REB# 12-009). Successful completion will significantly impact on clinical practice and enhance patients’ lives. More broadly, this trial will develop a network of collaboration from which further high-quality trials in Orthopaedic Oncology will follow.

Use of a calcium sulfate-calcium phosphate synthetic bone graft composite in the surgical management of primary bone tumors.

Benign primary bone tumors are commonly treated with intralesional curettage with or without the use of surgical adjuvants. The reconstructive approach to the resulting contained bone defects is controversial, and clinical practice is varied. Synthetic bone substitutes may provide early mechanical support while minimizing the risks of disease transmission, nonunion, infection, and donor-site morbidity. Limited data exists regarding the use of calcium sulfate-calcium phosphate composite bone substitute for this purpose. The authors retrospectively reviewed the clinical outcomes of 24 patients with benign primary bone tumors who underwent intralesional curettage followed by reconstruction with a calcium sulfate-calcium phosphate composite bone substitute. Mean follow-up was 23 months. The most common diagnosis was giant cell tumor of bone. Six patients had upper-extremity tumors and 18 had lower-extremity tumors. Mean preoperative radiographic tumor volume was 41.0 cm(3). Mean volume of PRO-DENSE (Wright Medical Technology, Arlington, Tennessee) used in each patient was 15.6 cm(3). Mean time to full weight bearing for all patients was 7.3 weeks. Two patients sustained local tumor recurrences. No postoperative fractures occurred, and no complications occurred related to the use of the calcium sulfate-calcium phosphate composite. One case of deep infection occurred secondary to wound breakdown. The use of a calcium sulfate-calcium phosphate composite was associated with rapid biological integration and an early return to activities of daily living, with no composite-related complications. This technique is a viable option in the reconstruction of cavitary bone defects following intralesional curettage of primary benign bone tumors.

The fragility of statistically significant findings from randomized trials in spine surgery: a systematic survey

BACKGROUND CONTEXT Randomized controlled trials (RCTs) are the most trustworthy source for evaluating treatment effects, but RCTs of spine surgery interventions often produce discordant results. The Fragility Index is a novel metric to inform about the robustness of statistically significant results. PURPOSE The aim was to determine the robustness of statistically significant results from RCTs of spine surgery interventions. STUDY DESIGN/SETTING This was a systematic survey. PATIENT SAMPLE The sample included RCTs of spine surgery interventions. OUTCOME MEASURES The Fragility Index is the minimum number of patients in a trial whose status would have to change from a nonevent to an event to change a statistically significant result to a nonsignificant result. Events refer to the occurrence of any dichotomous outcome, such as successful fusion, incident fracture, adjacent segment degeneration, or achievement of a certain functional score. A small Fragility Index indicates that the statistical significance of a result hinges on only a few events, and a large Fragility Index increases ones confidence in the observed treatment effects. METHODS We systematically reviewed a database for evidence-based orthopedics and identified all the RCTs that reported at least one positive outcome (ie, p<.05). Two reviewers independently assessed eligibility and extracted data. We used the Fisher exact test to compute Fragility Index values and multivariable linear regression to evaluate potential associated factors. RESULTS We identified 40 eligible RCTs with a median sample size of 132 patients (interquartile range [IQR] 79-208) and a median total number of outcome events for the chosen outcome of 31 (IQR 13-63). The median Fragility Index was two (IQR 1-3), which means that adding two events to one of the trials treatment arms eliminated its statistical significance. The Fragility Index was less than or equal to three events in 75% of the trials, and was less than or equal to the number of patients lost to follow-up in 65% of the trials. Fragility Index values correlated positively with total sample size (r=0.35; p<.05). When adjusted for losses to follow-up and risk of bias, increasing Fragility Index values were associated only with increasingly significant reported p values (p<.01). CONCLUSIONS Statistically significant results in spine surgery RCTs are frequently fragile. The addition of only a small number of outcome events can completely eliminate significance. Surgeons, researchers, and other evidence users should exercise caution when interpreting the findings from RCTs with low Fragility Index values and applying these results to patient care.

Operative vs non-operative management of displaced proximal humeral fractures in the elderly: A systematic review and meta-analysis of randomized controlled trials

AIM To perform a systematic review and meta-analysis comparing operative vs non-operative treatment of displaced proximal humerus fractures in elderly patients. METHODS A systematic literature search was performed using EMBASE and MEDLINE through the OVID interface, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), Proquest, Web of Science, SAE digital library, and Transportation Research Boards TRID database. Searches of conference proceedings were also conducted. All available randomized controlled trials comparing operative vs non-operative management of displaced three- and four-part proximal humerus fractures in elderly patients were included. The primary outcomes measures included physical function, pain, health related quality of life, mortality, and the re-operation rate. RESULTS Six randomized controlled trials (n = 287) were included. There was no statistically significant difference in function (MD = 1.72, 95%CI: -2.90-6.34, P = 0.47), as measured by the Constant score, between the operative and the non-operative treatment groups. There was no statistically significance difference in secondary outcomes of health related quality of life (standardized MD = 0.27, 95%CI: -0.05-0.59, P = 0.09), and mortality (relative risk 1.29, 95%CI: 0.50- 3.35, P = 0.60). Operative treatment had a statistically significant higher re-operation rate (relative risk 4.09, 95%CI: 1.50-11.15, P = 0.006), and statistically significant decreased pain (MD = 1.26, 95%CI: 0.02- 2.49, P = 0.05). CONCLUSION There is moderate quality evidence to suggest that there is no difference in functional outcomes between the two treatments. Further high quality randomized controlled trials are required to determine if certain subgroup populations benefit from surgical management.

Knee arthroscopy versus conservative management in patients with degenerative knee disease: a systematic review

Objective To determine the effects and complications of arthroscopic surgery compared with conservative management strategies in patients with degenerative knee disease. Design Systematic review. Main outcome measures Pain, function, adverse events. Data sources MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar and Open Grey up to August 2016. Eligibility criteria For effects, randomised clinical trials (RCTs) comparing arthroscopic surgery with a conservative management strategy (including sham surgery) in patients with degenerative knee disease. For complications, RCTs and observational studies. Review methods Two reviewers independently extracted data and assessed risk of bias for patient-important outcomes. A parallel guideline committee (BMJ Rapid Recommendations) provided input on the design and interpretation of the systematic review, including selection of patient-important outcomes. We used the GRADE approach to rate the certainty (quality) of the evidence. Results We included 13 RCTs and 12 observational studies. With respect to pain, the review identified high-certainty evidence that knee arthroscopy results in a very small reduction in pain up to 3 months (mean difference =5.4 on a 100-point scale, 95% CI 2.0 to 8.8) and very small or no pain reduction up to 2 years (mean difference =3.1, 95% CI −0.2 to 6.4) when compared with conservative management. With respect to function, the review identified moderate-certainty evidence that knee arthroscopy results in a very small improvement in the short term (mean difference =4.9 on a 100-point scale, 95% CI 1.5 to 8.4) and very small or no improved function up to 2 years (mean difference =3.2, 95% CI −0.5 to 6.8). Alternative presentations of magnitude of effect, and associated sensitivity analyses, were consistent with the findings of the primary analysis. Low-quality evidence suggested a very low probability of serious complications after knee arthroscopy. Conclusions Over the long term, patients who undergo knee arthroscopy versus those who receive conservative management strategies do not have important benefits in pain or function. Trial registration number PROSPERO CRD42016046242.

The Fragility of Statistically Significant Findings from Randomized Trials in Sports Surgery: A Systematic Survey

Background: High-quality, evidence-based orthopaedic care relies on the generation and translation of robust research evidence. The Fragility Index is a novel method for evaluating the robustness of statistically significant findings from randomized controlled trials (RCTs). It is defined as the minimum number of patients in 1 arm of a trial that would have to change status from a nonevent to an event to alter the results of the trial from statistically significant to nonsignificant. Purpose: To calculate the Fragility Index of statistically significant results from clinical trials in sports medicine and arthroscopic surgery to characterize the robustness of the RCTs in these fields. Methods: A search was conducted in Medline, EMBASE, and PubMed for RCTs related to sports medicine and arthroscopic surgery from January 1, 2005, to October 30, 2015. Two reviewers independently assessed titles and abstracts for study eligibility, performed data extraction, and assessed risk of bias. The Fragility Index was calculated using the Fisher exact test for all statistically significant dichotomous outcomes from parallel-group RCTs. Bivariate correlation was performed to evaluate associations between the Fragility Index and trial characteristics. Results: A total of 48 RCTs were included. The median sample size was 64 (interquartile range [IQR], 48.5-89.5), and the median total number of outcome events was 19 (IQR, 10-27). The median Fragility Index was 2 (IQR, 1-2.8), meaning that changing 2 patients from a nonevent to an event in the treatment arm changed the result to a statistically nonsignificant result, or P ≥ .05. Conclusion: Most statistically significant RCTs in sports medicine and arthroscopic surgery are not robust because their statistical significance can be reversed by changing the outcome status on only a few patients in 1 treatment group. Future work is required to determine whether routine reporting of the Fragility Index enhances clinicians’ ability to detect trial results that should be viewed cautiously.

What are the levels of evidence on which we base decisions for surgical management of lower extremity bone tumors

BackgroundBenign and malignant lower extremity primary bone tumors are among the least common conditions treated by orthopaedic surgeons. The literature supporting their surgical management has historically been in the form of observational studies rather than prospective controlled studies. Observational studies are prone to confounding bias, sampling bias, and recall bias.Questions/purposes(1) What are the overall levels of evidence of articles published on the surgical management of lower extremity bone tumors? (2) What is the overall quality of reporting of studies in this field based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist? (3) What are the most common pitfalls in reporting that authors might improve on?MethodsAll studies describing the surgical management of lower extremity primary bone tumors from 2002 to 2012 were systematically reviewed. Two authors independently appraised levels of evidence. Quality of reporting was assessed with the STROBE checklist. Pitfalls in reporting were quantified by determining the 10 most underreported elements of research study design in the group of studies analyzed, again using the STROBE checklist as the reference standard. Of 1387 studies identified, 607 met eligibility criteria.ResultsThere were no Level I studies, two Level II studies, 47 Level III studies, 308 Level IV studies, and 250 Level V studies. The mean percentage of STROBE points reported satisfactorily in each article as graded by the two reviewers was 53% (95% confidence interval, 42%–63%). The most common pitfalls in reporting were failures to justify sample size (2.2% reported), examine sensitivity (2.2%), account for missing data (9.8%), and discuss sources of bias (14%). Followup (66%), precision of outcomes (64%), eligibility criteria (55%), and methodological limitations (53%) were variably reported.ConclusionsObservational studies are the dominant evidence for the surgical management of primary lower extremity bone tumors. Numerous deficiencies in reporting limit their clinical use. Authors may use these results to inform future work and improve reporting in observational studies, and treating surgeons should be aware of these limitations when choosing among the various options with their patients.