Clinical Trials: A Practical Approach

Results: One thousand two hundred and twenty-six participants (93%) completed one year of follow-up. Of these, 622 patients were randomized to reamed nailing and 604 patients were randomized to unreamed nailing. Among all patients, fifty-seven(4.6%)requiredimplantexchangeorbone-graftingbecauseofnonunion.Amongallpatients,105inthereamed nailing group and 114 in the unreamed nailing group experienced a primary outcome event (relative risk, 0.90; 95% confidenceinterval,0.71to1.15).Inpatientswithclosedfractures,forty-five(11%)of416inthereamednailinggroupand sixty-eight (17%) of 410 in the unreamed nailing group experienced a primary event (relative risk, 0.67; 95% confidence interval, 0.47 to 0.96; p = 0.03). This difference was largely due to differences in dynamization. In patients with open fractures,sixtyof206inthereamednailinggroupandforty-sixof194intheunreamednailinggroupexperiencedaprimary event (relative risk, 1.27; 95% confidence interval, 0.91 to 1.78; p = 0.16). Conclusions: The present study demonstrates a possible benefit for reamed intramedullary nailing in patients with closed fractures. We found no difference between approaches in patients with open fractures. Delaying reoperation for nonunion for at least six months may substantially decrease the need for reoperation. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

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Randomized trial of reamed and unreamed intramedullary nailing of tibial shaft fractures.

Clinicians, when trying to apply trial results to patient care, need to individualize patient care and, potentially, manage patients based on results of subgroup analyses. Apparently compelling subgroup effects often prove spurious, and guidance is needed to differentiate credible from less credible subgroup claims. We therefore provide 5 criteria to use when assessing the validity of subgroup analyses: (1) Can chance explain the apparent subgroup effect; (2) Is the effect consistent across studies; (3) Was the subgroup hypothesis one of a small number of hypotheses developed a priori with direction specified; (4) Is there strong preexisting biological support; and (5) Is the evidence supporting the effect based on within- or between-study comparisons. The first 4 criteria are applicable to individual studies or systematic reviews, the last only to systematic reviews of multiple studies. These criteria will help clinicians deciding whether to use subgroup analyses to guide their patient care.

How to Use a Subgroup Analysis: Users’ Guide to the Medical Literature

Objective To determine whether total hip arthroplasty is associated with lower reoperation rates, mortality, and complications, and better function and quality of life than hemiarthroplasty for displaced fractures of the femoral neck in older patients. Design Systematic review and meta-analysis of randomised trials, quasirandomised trials, and cohort studies. Data sources Medline, Embase, Cochrane register of controlled trials, publishers’ databases, and manual search of bibliographies. Study selection Randomised controlled trials, quasirandomised trials, and cohort studies (retrospective and prospective) comparing hemiarthroplasty with total hip arthroplasty for treating displaced femoral neck fractures in patients aged more than 60 years. Data extraction Relative risks, risk differences, and mean differences from each trial, aggregated using random effects models. Analyses were stratified for experimental and non-experimental designs, and two way sensitivity analyses and tests for interaction were done to assess the influence of various criteria of methodological quality on pooled estimates. Data synthesis 3821 references were identified. Of the 202 full papers inspected, 15 were included (four randomised controlled trials, three quasirandomised trials, and eight retrospective cohort studies, totalling 1890 patients). Meta-analysis of 14 studies showed a lower risk of reoperation after total hip arthroplasty compared with hemiarthroplasty (relative risk 0.57, 95% confidence interval 0.34 to 0.96, risk difference 4.4%, 95% confidence interval 0.2% to 8.5%), although this effect was mainly driven by investigations without concealed treatment allocation. Total hip arthroplasty consistently showed better ratings in the Harris hip score (three studies, 246 patients, weighted mean difference 5.4, 95% confidence interval 2.7 to 8.2) after follow-up periods of 12 to 48 months. The standardised mean difference of different scores from five studies was 0.42 (95% confidence interval 0.24 to 0.61), indicating a medium functional advantage of total hip arthroplasty over hemiarthroplasty. Total hip arthroplasty was associated with a slightly higher risk of dislocation (relative risk 1.48, 95% confidence interval 0.89 to 2.46) and general complications (1.14, 0.87 to 1.48). Conclusion Single stage total hip arthroplasty may lead to lower reoperation rates and better functional outcomes compared with hemiarthroplasty in older patients with displaced femoral neck fractures. However, heterogeneity across the available trials and distinct subgroup effects preclude definitive statements and require further research in this area.

https://www.bmj.com/content/bmj/340/bmj.c2332.full.pdf

Primary total hip arthroplasty versus hemiarthroplasty for displaced intracapsular hip fractures in older patients: systematic review

OBJECTIVE: To investigate whether surgery by open reduction and internal fixation provides benefit compared with non-operative treatment for displaced, intra-articular calcaneal fractures DESIGN: Pragmatic, multicentre, two arm, parallel group, assessor blinded randomised controlled trial (UK Heel Fracture Trial) SETTING: 22 tertiary referral hospitals, United Kingdom PARTICIPANTS: 151 patients with acute displaced intra-articular calcaneal fractures randomly allocated to operative (n=73) or non-operative (n=78) treatment MAIN OUTCOME MEASURES: The primary outcome measure was patient reported Kerr-Atkins score for pain and function (scale 0-100, 100 being the best possible score) at two years after injury Secondary outcomes were complications; hindfoot pain and function (American Orthopaedic Foot and Ankle Society score); general health (SF-36); quality of life (EQ-5D); clinical examination; walking speed; and gait symmetry Analysis was by intention to treat RESULTS: 95% follow-up was achieved for the primary outcome (69 in operative group and 74 in non-operative group), and a complete set of secondary outcomes were available for 75% of participants There was no significant difference in the primary outcome (mean Kerr-Atkins score 698 in operative group v 657 in non-operative group; adjusted 95% confidence interval of difference -71 to 70) or in any of the secondary outcomes between treatment groups Complications and reoperations were more common in those who received operative care (estimated odds ratio 75, 95% confidence interval 20 to 418) CONCLUSIONS: Operative treatment compared with non-operative care showed no symptomatic or functional advantage after two years in patients with typical displaced intra-articular fractures of the calcaneus, and the risk of complications was higher after surgery Based on these findings, operative treatment by open reduction and internal fixation is not recommended for these fracturesTrial registration Current Controlled Trials ISRCTN37188541

https://www.bmj.com/content/bmj/349/bmj.g4483.full.pdf

Operative versus non-operative treatment for closed, displaced, intra-articular fractures of the calcaneus: randomised controlled trial

BACKGROUND The management of open fractures requires wound irrigation and debridement to remove contaminants, but the effectiveness of various pressures and solutions for irrigation remains controversial. We investigated the effects of castile soap versus normal saline irrigation delivered by means of high, low, or very low irrigation pressure. METHODS In this study with a 2-by-3 factorial design, conducted at 41 clinical centers, we randomly assigned patients who had an open fracture of an extremity to undergo irrigation with one of three irrigation pressures (high pressure [>20 psi], low pressure [5 to 10 psi], or very low pressure [1 to 2 psi]) and one of two irrigation solutions (castile soap or normal saline). The primary end point was reoperation within 12 months after the index surgery for promotion of wound or bone healing or treatment of a wound infection. RESULTS A total of 2551 patients underwent randomization, of whom 2447 were deemed eligible and included in the final analyses. Reoperation occurred in 109 of 826 patients (13.2%) in the high-pressure group, 103 of 809 (12.7%) in the low-pressure group, and 111 of 812 (13.7%) in the very-low-pressure group. Hazard ratios for the three pairwise comparisons were as follows: for low versus high pressure, 0.92 (95% confidence interval [CI], 0.70 to 1.20; P = 0.53), for high versus very low pressure, 1.02 (95% CI, 0.78 to 1.33; P = 0.89), and for low versus very low pressure, 0.93 (95% CI, 0.71 to 1.23; P = 0.62). Reoperation occurred in 182 of 1229 patients (14.8%) in the soap group and in 141 of 1218 (11.6%) in the saline group (hazard ratio, 1.32, 95% CI, 1.06 to 1.66; P = 0.01). CONCLUSIONS The rates of reoperation were similar regardless of irrigation pressure, a finding that indicates that very low pressure is an acceptable, low-cost alternative for the irrigation of open fractures. The reoperation rate was higher in the soap group than in the saline group. (Funded by the Canadian Institutes of Health Research and others; FLOW ClinicalTrials.gov number, NCT00788398.)

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A Trial of Wound Irrigation in the Initial Management of Open Fracture Wounds.

Background Calcaneal fractures comprise 1 to 2 percent of all fractures. Approximately 75% of calcaneal fractures are intra-articular. The management of intra-articular calcaneal fractures remains controversial. Nonoperative treatment options include elevation, ice, early mobilization, and cyclic compression of the plantar arch. Operative treatment options include closed reduction and percutaneous pin fixation, open reduction and internal fixation, and arthrodesis. The effect of operative versus nonoperative treatment has been the focus of several comparative studies. Objective This study was designed to determine the effect of operative treatment compared with nonoperative treatment on the rate of union, complications, and functional outcome after intra-articular calcaneal fracture in adults.

Displaced intra-articular calcaneal fractures.

Background Surgeons agree on the benefits of operative treatment of tibial fractures - the most common of long bone fractures - with an intramedullary rod or nail. Rates of re-operation remain high - between 23% and 60% in prior trials - and the two alternative nailing approaches, reamed or non-reamed, each have a compelling biological rationale and strong proponents, resulting in ongoing controversy regarding which is better. Methods/design The objective of this trial was to assess the impact of reamed versus non-reamed intramedullary nailing on rates of re-operation in patients with open and closed fractures of the tibial shaft. The study to prospectively evaluate reamed intramedullary nails in tibial fractures (S.P.R.I.N.T) was a multi-center, randomized trial including 29 clinical sites in Canada, the United States and the Netherlands which enrolled 1200 skeletally mature patients with open (Gustilo Types I-IIIB) or closed (Tscherne Types 0-3) fractures of the tibial shaft amenable to surgical treatment with an intramedullary nail. Patients received a statically locked intramedullary nail with either reamed or non-reamed insertion. The first strategy involved fixation of the fracture with an intramedullary nail following reaming to enlarge the intramedullary canal (Reamed Group). The second treatment strategy involved fixation of the fracture with an intramedullary nail without prior reaming of the intramedullary canal (Non-Reamed Group). Patients, outcome assessors, and data analysts were blinded to treatment allocation. Peri-operative care was standardized, and re-operations before 6 months were proscribed. Patients were followed at discharge, 2 weeks post-discharge, and at 6 weeks, 3, 6, 9, and 12 months post surgery. A committee, blinded to allocation, adjudicated all outcomes. Discussion The primary outcome was re-operation to promote healing, treat infection, or preserve the limb (fasciotomy for compartment syndrome after nailing). The primary outcome was a composite comprising the following re-operations: bone grafts, implant exchanges, and dynamizations, in patients with fracture gaps less than 1 cm post intramedullary nail insertion. Infections and fasciotomies were considered events irrespective of the fracture gap. We planned a priori to conduct a subgroup analysis of outcomes in patients with open and closed fractures. S.P.R.I.N.T is the largest collaborative trial evaluating alternative orthopaedic surgical interventions in patients with tibial shaft fractures. The methodological rigor will set new benchmarks for future trials in the field and its results will have important impact on patient care. The S.P.R.I.N.T trial was registered [ID NCT00038129] and received research ethics approval (REB#99-077).

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Study to prospectively evaluate reamed intramedually nails in patients with tibial fractures (S.P.R.I.N.T.): study rationale and design.

OBJECTIVE: To identify current opinions among orthopedic traumatologists relating to technical aspects of internal fixation and arthroplasty for patients with femoral neck fractures. METHODS: We developed and administered a survey to orthopedic surgeons who were members of the Orthopedic Trauma Association and European clinics affiliated with AO International (Davos, Switzerland). Surgeons reported preferences in specific aspects of the surgical technique for internal fixation as well as arthroplasty. Each surgeon received either a mailed package (7-page survey, a personalized cover letter, and a stamped return envelope) or an email with a link to the same survey on the Internet with an identification code. At 6 weeks, 12 weeks, and 18 weeks after the initial mailing, we remailed the questionnaire to all nonresponders. RESULTS: Of the 442 surgeons who were sent the questionnaire, 298 (68%) responded. The typical respondent was a North American aged more than 40 years, in academic practice, supervised residents, had fellowship training in trauma, and worked in a low-volume center. Among surgeons who treated displaced femoral neck fractures with arthroplasty, significant disparities existed in terms of the type of anesthesia (51% preferring general anesthesia), surgical approach (47% used posterior approach), and placement of unipolar implants (50%). Surgeons tended to agree on the use of cement fixation (69%), repairing the capsule (80%), and not using a drain postoperatively (68%). Surgeons who preferentially treated hip fractures with internal fixation tended to have a lack of consensus in terms of what constituted acceptable surgical delays (43% allowing greater than 48 hours) and which screw configuration to use, with more than half using a triangle with base inferior construct. Surgeons tended to agree on the use of closed fracture reduction techniques (69%), three cannulated screws (73%), and did not routinely perform a capsulotomy (80%) or aspirate the fracture hematoma (90%). Within both treatment groups (internal fixation and arthroplasty), surgeons tended to agree on the use of perioperative antibiotics (>92%), thromboprophylaxis (98%), and postoperative weight bearing status (>87%). CONCLUSIONS: A general lack of consensus exists among orthopedic trauma surgeons in the management of displaced femoral neck fractures. With an ever-growing emphasis upon the practice of evidence-based medicine, we have demonstrated several disparities in the technical aspects of fixation and perioperative care likely caused by a general lack of available evidence. We recommend the need for future research and large collaborative efforts.

Technical considerations in the operative management of femoral neck fractures in elderly patients: a multinational survey.

In five years, approximately 800 ankle fractures were seen at the authors' institution, forty-four (5 percent) of which were of the supination-adduction pattern. Nineteen of these injuries had displaced vertical medial malleolus fractures, of which eight (42 percent) showed marginal impaction of the tibial plafond. All eight patients underwent open reduction and internal fixation with elevation of the impacted articular component and had good to excellent functional outcome with no arthritis on radiograph at the time of the most recent follow-up. The index of suspicion of marginal impaction of the tibial plafond should be high when treating supination-adduction pattern ankle fractures with displaced medial malleolus.

Tornetta P rd

Papers

A Trial of Wound Irrigation in the Initial Management of Open Fracture Wounds.

Displaced intra-articular calcaneal fractures.

Study to prospectively evaluate reamed intramedually nails in patients with tibial fractures (S.P.R.I.N.T.): study rationale and design.

Technical considerations in the operative management of femoral neck fractures in elderly patients: a multinational survey.

Marginal plafond impaction in association with supination-adduction ankle fractures: a report of eight cases.