Christopher A. Smith

Cancer Care Ontario and American Society of Clinical Oncology Adjuvant Chemotherapy and Adjuvant Radiation Therapy for Stages I-IIIA Resectable Non–Small-Cell Lung Cancer Guideline

PURPOSEnTo determine the role of adjuvant chemotherapy and radiation therapy in patients with completely resected stage IA-IIIA non-small-cell lung cancer (NSCLC).nnnMETHODSnThe Cancer Care Ontario Program in Evidence-Based Care and the American Society of Clinical Oncology convened a Joint Expert Panel in August 2006 to review the evidence and draft recommendations for these therapies.nnnRESULTSnAvailable data support the use of adjuvant cisplatin-based chemotherapy in completely resected NSCLC; however, the strength of the data and consequent recommendations vary by disease stage. Adjuvant radiation therapy appears detrimental to survival in stages IB and II, with a possible modest benefit in stage IIIA.nnnCONCLUSIONnAdjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages IIA, IIB, and IIIA disease. Although there has been a statistically significant overall survival benefit seen in several randomized clinical trials (RCTs) enrolling a range of people with completely resected NSCLC, results of subset analyses for patient populations with stage IB disease were not significant, and adjuvant chemotherapy in stage IB disease is not currently recommended for routine use. To date, very few patients with stage IA NSCLC have been enrolled onto RCTs of adjuvant therapy; adjuvant chemotherapy is not recommended in these cases. Evidence from RCTs demonstrates a survival detriment for adjuvant radiotherapy with limited evidence for a reduction in local recurrence. Adjuvant radiation therapy appears detrimental to survival in stage IB and II, and may possibly confer a modest benefit in stage IIIA.

The Management of Thymoma: A Systematic Review and Practice Guideline

Introduction: Thymoma is a rare tumor for which there is little randomized evidence to guide treatment. Because of the lack of high-quality evidence, a formal consensus-based approach was used to develop recommendations on treatment. Methods: A systematic refview of the literature was performed. Recommendations were formed from available evidence and developed through a two-round modified Delphi consensus approach. Results: The treatment recommendations are summarized as follows: Stage I—complete resection of the entire thymus without neoadjuvant or adjuvant therapy. Stage II—complete resection of the entire thymus with consideration of adjuvant radiation for high-risk tumors. Stage IIIA—surgery either initially or after neoadjuvant therapy, or surgery followed by adjuvant therapy. Stage IIIB—treatment may include a combination of chemotherapy, radiation, and/or surgery, or if technically possible, surgery in combination with chemoradiotherapy (concurrent cisplatin based). For bulky tumors, consideration should be given to sequential chemotherapy followed by radiation. Stage IVA—as per stage III, with surgery only if metastases can be resected. Stage IVB—treatment on an individual case basis (no generic recommendations). Recurrent disease—consider surgery, radiation, and/or chemoradiation. Chemoradiation should be considered in all medically inoperable and technically inoperable patients. Conclusion: Consensus was achieved on these recommendations, which serve to provide practical guidance to the physician treating this rare disease.

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

BACKGROUND CONTEXTnRandomized 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.nnnPURPOSEnThe aim was to determine the robustness of statistically significant results from RCTs of spine surgery interventions.nnnSTUDY DESIGN/SETTINGnThis was a systematic survey.nnnPATIENT SAMPLEnThe sample included RCTs of spine surgery interventions.nnnOUTCOME MEASURESnThe 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.nnnMETHODSnWe 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.nnnRESULTSnWe 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).nnnCONCLUSIONSnStatistically 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.

How much science is there in injury prevention and control

Objectives: To determine what proportion of research papers at an injury prevention conference reported an evaluation. Methods: A random sample of 250 abstracts from the 6th World Conference on Injury Prevention and Control were classified by methodological type. Those that described any evaluation were further subdivided by whether the evaluation was of process or if it used an intermediate or “true” outcome. Results: Of 250 abstracts, 20 (8%; 95% confidence interval 5.0% to 12.1%) showed evaluations with intermediate or true outcomes. Research designs were weak. Among the 20 reports, none was a randomized trial and only two conducted a before and after study with control group. The remaining 17 used before-after or “after only” designs. Conclusion: The conference papers included few evaluations. To ensure that resources are best used, those in the injury prevention field must increase their use of rigorous evaluation.

The Scholarly Influence of Orthopaedic Research According to Conventional and Alternative Metrics: A Systematic Review

Background: Researchers are experiencing an innovative shift toward online distribution of their work, and metrics related to online scholarly influence are gaining importance. Our objectives were to determine which types of online activity are most prevalent in orthopaedics, to identify associated factors, and to explore a complementary approach to measuring overall scholarly influence using online activity and conventional citations. Methods: We performed a systematic review of randomized controlled trials of surgical or nonsurgical interventions in participants with, or at specific risk for, injuries and diseases of the musculoskeletal system. We collected data on online activity in social media, mainstream media, blogs, forums, and other sources from a commercial provider of alternative metric data for medical journals. We tested associations with use of negative binomial regression. Results: We identified 1,697 trials, published between 2011 and 2014, that had a total of 12,995 conventional citations and 15,068 online mentions. The median number of online mentions of each trial was 2 (interquartile range, 0 to 5). Twitter (82%) and Facebook (13%) mentions were the most prevalent types of online activity. Counts of online mentions correlated with conventional citations (r = 0.11, p < 0.01) but accumulated more rapidly. Higher total counts of online mentions were consistently associated with longer time since publication, higher journal impact factor, higher author h-index values, and less risk of bias (p < 0.01 for each). We found the best model fit for a complementary approach by weighting citations and online mentions equally. Conclusions: Online activity in orthopaedics is dominated by activity on Twitter and Facebook and is associated with increasing time since publication, journal impact factor, and author h-index values, and less risk of bias. Institutions, publishers, funding agencies, and clinicians may consider a complementary approach to measuring scholarly influence that weights online mentions and conventional citations equally.

OrthoEvidence™: A Clinical Resource for Evidence-Based Orthopedics.

The prevalence of musculoskeletal issues in clinical practice, and the limited focus placed upon musculoskeletal conditions by current electronic summary resources, highlights the need for a resource that provides access to simple and concise summaries of top-quality orthopedic literature for orthopedic surgeons and allied healthcare professionals. OrthoEvidence™ is an online clinical resource that addresses the paucity of adequate evidence-based summary tools in the field of orthopedic surgery. OrthoEvidence™ uses a rigorous, transparent, and unique process to review, evaluate, and summarize high quality research studies and their implications for orthopedic clinical practice. Randomized controlled trials and meta-analyses are identified and reviewed by an expert medical writing team, who prepare Advanced Clinical Evidence (ACETM) reports: one or two detailed pages including critical appraisals and synopses of key research. These timely and targeted reports provide a clear understanding about the quality of evidence associated with each summarized study, and can be organized by users to identify trending information. OrthoEvidence™ allows members to use their time efficiently and to stay current by having access to a breadth of timely, high-quality research output. OrthoEvidence™ is easily accessible through the internet and is available at the point-of-care, which allows treating orthopedic surgeons and allied health professionals to easily practice the principles of evidence-based medicine within their clinical practices..

Combined intra-articular injection of corticosteroid and hyaluronic acid reduces pain compared to hyaluronic acid alone in the treatment of knee osteoarthritis

PurposeIntra-articular injections of corticosteroid (CS) and hyaluronic acid (HA) have individually demonstrated efficacy for knee osteoarthritis (OA); however, both treatments are limited by the trajectory of symptom relief. The combination of CS and HA in the management of knee OA may provide improved symptomatic relief for patients who are candidates for intra-articular therapies.MethodsElectronic databases Medline, EMBASE and Cochrane Library were used to identify relevant publications. Randomized controlled trials (RCT) that evaluated intra-articular injections of combined CS and HA in comparison to HA alone were included. Outcomes eligible for meta-analysis were WOMAC pain, WOMAC total, OMERACT-OARSI responder rate, and treatment-related adverse events. Standardized mean differences (SMD) were calculated for continuous outcomes using an inverse variance method and a random-effects model. Odds ratios (OR) were calculated for dichotomous outcomes using the Mantel–Haenszel method and a random-effects model. Heterogeneity was assessed using the I2 statistic.ResultsEight trials (nu2009=u2009751 patients) were included. Reduction in WOMAC pain scores at 2–4xa0weeks favoured the combined CS and HA group compared to HA alone [SMD 0.60, 95% CI (0.23, 0.97); pu2009=u20090.002, I2u2009=u200975%]. Longer term improvements at 24–26 and 52xa0weeks WOMAC pain scores also favoured the combined CS and HA group {[SMD 0.25, 95% CI (0.09, 0.41); pu2009=u20090.002, I2u2009=u20090%] and [SMD 0.39, 95% CI (0.01, 0.77); pu2009=u20090.05, I2u2009=u20090%]} compared to HA alone, respectively. There were no significant differences in WOMAC total scores, OMERACT-OARSI responder rate, or treatment-related adverse events.ConclusionCombined intra-articular injections of CS and HA led to reductions in pain at 2–4, 24–26 and 52xa0weeks compared to HA injections alone.Level of evidenceLevel II—meta-analysis.

Intra-articular Injections in the Treatment of Symptoms from Ankle Arthritis: A Systematic Review:

Background: Intra-articular (IA) injections are commonly used to treat knee arthritis pain; however, whether their efficacy generalizes to ankle arthritis remains debatable. We aimed to evaluate the evidence for IA therapies in the management of this patient population. Methods: We performed a literature search for observational and randomized controlled trials (RCTs). Treatments included corticosteroids (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and mesenchymal stem cells (MSC). We extracted study details, patient demographics, treatment characteristics, efficacy outcomes, and safety. When feasible, data from RCTs were meta-analyzed using a random-effects model and 95% confidence intervals (CIs) were calculated. A P value <.05 was considered statistically significant. Results: We identified 27 studies (1085 patients). Ankle OA, rheumatoid arthritis (RA), and hemophilic arthropathy populations were examined. The majority of studies were observational (20 studies); the only RCTs were those evaluating HA. Case series demonstrated favorable results in terms of symptomatic relief with CS, HA, PRP, and MSC injections; however, the effects of CS may only be short term and the evidence on MSCs was limited to 1 study with 6 ankle OA patients. Pooled results (3 RCTs, 109 patients) suggested significantly improved Ankle Osteoarthritis Scale scores with HA over saline at 6 months, with a mean difference of 12.47 points (95% CI 1.18-23.77, P = .03). Conclusion: Evidence from small trials favors HA and PRP injections for the treatment of pain associated with ankle osteoarthritis. However, the relative efficacy of all injectable therapies is far from definitive and warrants further high-quality comparative trials. Level of Evidence: Level III, systematic review.