How many sites should an orthopedic trauma prospective multicenter trial have? A marginal analysis of the Major Extremity Trauma Research Consortium completed trials.

BACKGROUND: Multicenter trials in orthopedic trauma are costly, yet crucial to advance the science behind clinical care. The number of sites is a key cost determinant. Each site has a fixed overhead cost, so more sites cost more to the study. However, more sites can reduce total costs by shortening the study duration. We propose to determine the optimal number of sites based on known costs and predictable site enrollment. METHODS: This retrospective marginal analysis utilized administrative and financial data from 12 trials completed by the Major Extremity Trauma Research Consortium. The studies varied in size, design, and clinical focus. Enrollment across the studies ranged from 1054 to 33 patients. Design ranged from an observational study with light data collection to a placebo-controlled, double-blinded, randomized controlled trial. Initial modeling identified the optimal number of sites for each study and sensitivity analyses determined the sensitivity of the model to variation in fixed overhead costs. RESULTS: No study was optimized in terms of the number of participating sites. Excess sites ranged from 2 to 39. Excess costs associated with extra sites ranged from $17K to $330K with a median excess cost of $96K. Excess costs were, on average, 7% of the total study budget. Sensitivity analyses demonstrated that studies with higher overhead costs require more sites to complete the study as quickly as possible. CONCLUSIONS: Our data support that this model may be used by clinical researchers to achieve future study goals in a more cost-effective manner. TRIAL REGISTRATION: Please see Table 1 for individual trial registration numbers and dates of registration.

Does Topical Vancomycin Powder Use in Fracture Surgery Change Bacteriology and Antibiotic Susceptibilities? An Analysis of the VANCO Trial.

OBJECTIVE: To determine whether intrawound vancomycin changes the bacteriology of surgical site infection pathogens and investigate the emergence of antibiotic-resistant pathogens. DESIGN: Secondary analysis of phase III, prospective, randomized clinical trial. SETTING: Thirty-six US trauma centers. PATIENT SELECTION CRITERIA: Patients who became infected after fixation of tibial plateau or pilon fracture. OUTCOME MEASURES AND COMPARISONS: Pathogen types and bacterial susceptibilities as determined from routine clinical culture in the operating room. RESULTS: Seventy-four patients were studied who were 67.5% male with a mean age of 48.6 years. A lower proportion of gram-positive cocci was observed in the vancomycin powder compared with the standard-of-care group (3.7% vs. 8.0%, P = 0.01). Methicillin-resistant Staphylococcus aureus infection incidence was comparable in both the vancomycin powder and the standard-of-care groups, but rates of methicillin-susceptible S. aureus infections were lower in the treatment group (1.4% vs. 4.8%, P = 0.01). The incidence of coagulase-negative Staphylococci and gram-negative rod infections were similar in both groups. There was no significant difference in susceptibilities between groups in rates of vancomycin-resistant enterococcus. CONCLUSIONS: Topical vancomycin powder decreases the likelihood of gram-positive infections consistent with the biologic activity of vancomycin. Fewer methicillin-susceptible S. aureus and coagulase-negative Staphylococci infections were observed in the group treated with vancomycin powder. An effect of vancomycin powder on methicillin-resistant S. aureus infection risk was not detected given the low incidence in both the intrawound vancomycin and the standard-of-care groups. There was no emergence of gram-negative rod infections or increased resistance patterns observed. Use of topical vancomycin powder does not seem to produce infections in these patients with greater antibiotic resistance than would have occurred without its use. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Deep Surgical Site Infection after Fracture Has a Profound Effect on Functional Outcomes.

Background: Fracture-related infection is one of the most challenging complications in orthopaedic trauma surgery. However, the effect of infection on functional and pain-related outcomes has not been well established. The aims of this study were to evaluate functional recovery for patients with fracture and a deep surgical site infection compared with patients with fracture without infection and to evaluate whether pain severity, social support, and preinjury mental health have a moderating effect on the magnitude and direction of the relationship between deep surgical site infection and functional recovery. Methods: This is a secondary retrospective cohort study using prospectively collected data from the VANCO trial (Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection) and the OXYGEN (Supplemental Perioperative Oxygen to Reduce Surgical Site Infection After High Energy Fracture Surgery) trial. In this study, 2,116 patients with tibial plateau, pilon, or calcaneal fractures at high risk for infection were included. Patients were divided into cohorts of patients who experienced a deep surgical site infection and those who did not. The primary outcome measure was the functional outcome using the Veterans RAND 12-Item Health Survey (VR-12). Results: After controlling for covariates, deep surgical site infection was independently associated with functional outcome, with a 3.3-point reduction in the VR-12 Physical Component Score, and pain severity was independently associated with functional outcome, with a 2.5-point reduction in the VR-12 Physical Component Score. Furthermore, the Brief Pain Inventory pain severity demonstrated an important moderating effect on the relationship between infection and functional outcome. In patients with lower pain scores, infection had a large negative impact on functional outcome, whereas, in patients with higher pain scores, infection had no significant impact on functional outcome. Furthermore, the functional outcome in the entire cohort remains at only 61% of baseline. Conclusions: This study documents the negative impact of postoperative infection on functional recovery after injury, as well as the novel finding of pain severity as an important moderating factor. This study emphasizes not only the importance of developing effective interventions designed to reduce postoperative infection, but also the role that factors that moderate pain severity plays in limiting recovery of physical function. Level of evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Risk-stratified thromboprophylaxis effects of aspirin versus low-molecular-weight heparin in orthopedic trauma patients: A secondary analysis of the PREVENT CLOT trial.

BACKGROUND: The PREVENT CLOT trial concluded that thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin (LMWH) in preventing death after orthopedic trauma. However, it was unclear if these results applied to patients at highest risk of thrombosis. Therefore, we assessed if the effect of aspirin versus LMWH differed based on patients' baseline risk of venous thromboembolism (VTE). METHODS: The PREVENT CLOT trial enrolled 12,211 adult patients with fractures. This secondary analysis stratified the study population into VTE risk quartiles: low (<1%) to high (>10%) using the Caprini score. We assessed stratum-specific treatment effects using the win ratio method, in which each patient assigned to aspirin was paired with each assigned to LMWH. In each pair, we compared outcomes hierarchically, starting with death, then pulmonary embolism, deep vein thrombosis, and bleeding. The secondary outcome added patients' medication satisfaction as a fifth composite component. RESULTS: In the high-risk quartile (n = 3052), 80% had femur fracture, pelvic, or acetabular fractures. Thoracic (47%) and head (37%) injuries were also common. In the low risk quartile (n = 3053), most patients had a tibia fracture (67%), 5% had a thoracic injury, and less than 1% had head or spinal injuries. Among high risk patients, thromboembolic events did not differ statistically between aspirin and LMWH (win ratio, 0.94; 95% confidence interval [CI], 0.82-1.08, p = 0.42). This result was consistent in the low (win ratio, 1.15; 95% CI, 0.90-1.47, p = 0.27), low-medium (win ratio, 1.05; 95% CI, 0.85-1.29, p = 0.68), and medium-high risk quartiles (win ratio, 0.94; 95% CI, 0.80-1.11, p = 0.48). When medication satisfaction was considered, favorable outcomes were 68% more likely with aspirin (win ratio, 1.68; 95% CI, 1.60-1.77; p < 0.001). CONCLUSION: Thromboembolic outcomes were similar with aspirin or LMWH, even among patients at highest risk of VTE. Aspirin was favored if medication satisfaction was also considered. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

The VANCO Trial Findings Are Generalizable to a North American Trauma Registry.

OBJECTIVES: To estimate the generalizability of treatment effects observed in the VANCO trial to a broader population of patients with tibial plateau or pilon fractures. METHODS: Design and Setting: Clinical trial data from 36 United States trauma centers and Trauma Quality Programs registry data from more than 875 Level I-III trauma centers in the United States and Canada.Patient Selection Criteria: Patients enrolled in the VANCO trial treated with intrawound vancomycin powder from January 2015 to June 2017 and 31,924 VANCO-eligible TQP patients admitted in 2019 with tibial plateau and pilon fractures.Outcome Measure and Comparisons: Deep surgical site infection and gram-positive deep surgical site infection estimated in the TQP sample weighed by the inverse probability of trial participation. RESULTS: The 980 patients in the VANCO trial were highly representative of 31,924 TQP VANCO-eligible patients (Tipton generalizability index 0.96). It was estimated that intrawound vancomycin powder reduced the odds of deep surgical infection by odds ratio (OR) = 0.46 (95% confidence interval [CI] 0.25-0.86) and gram-positive deep surgical infection by OR = 0.39 (95% CI, 0.18-0.84) within the TQP sample of VANCO-eligible patients. For reference, the trial average treatment effects for deep surgical infection and gram-positive deep surgical infection were OR = 0.60 (95% CI, 0.37-0.98) and OR = 0.44 (95% CI, 0.23-0.80), respectively. CONCLUSIONS: This generalizability analysis found that the inferences of the VANCO trial generalize and might even underestimate the effects of intrawound vancomycin powder when observed in a wider population of patients with tibial plateau and pilon fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture.

BACKGROUND: Clinical guidelines recommend low-molecular-weight heparin for thromboprophylaxis in patients with fractures, but trials of its effectiveness as compared with aspirin are lacking. METHODS: In this pragmatic, multicenter, randomized, noninferiority trial, we enrolled patients 18 years of age or older who had a fracture of an extremity (anywhere from hip to midfoot or shoulder to wrist) that had been treated operatively or who had any pelvic or acetabular fracture. Patients were randomly assigned to receive low-molecular-weight heparin (enoxaparin) at a dose of 30 mg twice daily or aspirin at a dose of 81 mg twice daily while they were in the hospital. After hospital discharge, the patients continued to receive thromboprophylaxis according to the clinical protocols of each hospital. The primary outcome was death from any cause at 90 days. Secondary outcomes were nonfatal pulmonary embolism, deep-vein thrombosis, and bleeding complications. RESULTS: A total of 12,211 patients were randomly assigned to receive aspirin (6101 patients) or low-molecular-weight heparin (6110 patients). Patients had a mean (±SD) age of 44.6±17.8 years, 0.7% had a history of venous thromboembolism, and 2.5% had a history of cancer. Patients received a mean of 8.8±10.6 in-hospital thromboprophylaxis doses and were prescribed a median 21-day supply of thromboprophylaxis at discharge. Death occurred in 47 patients (0.78%) in the aspirin group and in 45 patients (0.73%) in the low-molecular-weight-heparin group (difference, 0.05 percentage points; 96.2% confidence interval, -0.27 to 0.38; P<0.001 for a noninferiority margin of 0.75 percentage points). Deep-vein thrombosis occurred in 2.51% of patients in the aspirin group and 1.71% in the low-molecular-weight-heparin group (difference, 0.80 percentage points; 95% CI, 0.28 to 1.31). The incidence of pulmonary embolism (1.49% in each group), bleeding complications, and other serious adverse events were similar in the two groups. CONCLUSIONS: In patients with extremity fractures that had been treated operatively or with any pelvic or acetabular fracture, thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin in preventing death and was associated with low incidences of deep-vein thrombosis and pulmonary embolism and low 90-day mortality. (Funded by the Patient-Centered Outcomes Research Institute; PREVENT CLOT ClinicalTrials.gov number, NCT02984384.).

Application of Bayesian Methods to Help Interpret the VANCO Trial Results.

OBJECTIVE: To determine whether a Bayesian analysis changes the results of the VANCO trial. DESIGN: A secondary analysis of a randomized clinical trial using Bayesian methods. SETTING: Thirty-six US trauma centers. PATIENTS: Patients ages 18-80 years with a tibial plateau or pilon fracture deemed high risk of infection and definitively treated with plate and screw fixation. INTERVENTION: Patients were randomly allocated to receive 1000 mg of intrawound vancomycin powder at their definitive fixation or to a control group that received no topical antibiotics. MAIN OUTCOME MEASUREMENTS: A deep surgical site infection requiring operative treatment within 6 months of definitive fixation. Secondary outcomes included gram-positive and gram-negative-only deep surgical site infections. RESULTS: Of the 980 patients randomized, 874 (89%) had at least 140 days of follow-up and were included in this Bayesian analysis. The estimated probability that intrawound vancomycin powder reduces the risk of a deep surgical site infection is >98% [relative risk (RR), 0.66; 95% credible interval (CrI), 0.46-0.98]. There is a >99% chance intrawound vancomycin powder reduces gram-positive infections and an 80% chance the magnitude of this risk reduction exceeds 35% (RR, 0.52; 95% CrI, 0.33-0.84) exists. It is unlikely (44%) that intrawound vancomycin powder prevents gram-negative surgical site infections (RR, 1.06; 95% CrI, 0.48-2.45). CONCLUSIONS: There is a high probability (>98%) that intrawound vancomycin powder reduces deep surgical site infections in patients with tibial plateau or pilon fractures at high risk of infection and even more likely it reduces deep infections with gram-positive pathogens (>99%). LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Time to Completion of Pediatric PROMIS Computerized Adaptive Testing Measures and the SRS-22r in an Adolescent Idiopathic Scoliosis Population.

BACKGROUND: Patient-reported outcome measures are useful tools to quantify patients' pre-treatment and post-treatment symptoms. Historically used "legacy measures", such as the Scoliosis Research Society-22 revised questionnaire (SRS-22r), are often disease-specific and can be time-intensive. Recently developed Patient-Reported Outcomes Measurement Information System (PROMIS) computerized adaptive testing (CAT) measures may reduce administrative burdens and permit more efficient outcome collection within clinic workflows. In an era of medicine where payments are becoming tied to outcomes, we sought to assess the time to completion (TTC) of 8 pediatric PROMIS CAT measures and the SRS-22r in adolescents with idiopathic scoliosis. MATERIALS AND METHODS: Patients presenting to a large, urban tertiary referral hospital were prospectively enrolled into the study. Subjects were first-time survey respondents in various phases and types of treatment for adolescent idiopathic scoliosis. In total, 200 patients ranging from 10 to 17 years old completed 8 Pediatric PROMIS CATs and the SRS-22r. PROMIS CATs administered include Physical Activity, Mobility, Anxiety, Depressive symptoms, Peer Relationships, Physical Stress Experiences, Pain Behavior and Pain Interference. TTC was calculated using start and stop timestamps in the REDCap software. RESULTS: The mean (±SD) TTC for each PROMIS CAT was 1.1 (±0.9) minutes with physical activity, mobility, anxiety, depressive symptoms, peer relationships, physical stress experiences, pain behavior, and pain interference taking 1.2, 1.4, 1.0, 0.9, 1.2, 1.0, 1.0, and 1.2 minutes on average to complete, respectively. Mean TTC for the SRS-22r was 5.2 (±3.0) minutes. CONCLUSIONS: In this pediatric orthopaedic cohort, completion of 8 PROMIS CATs demonstrated minimal test-taker burden and time required for completion. These findings support rapid and easily integrable PROMIS CATs in clinical practice to aid in increased delivery of efficient, patient-centered care. LEVEL OF EVIDENCE: III, cross-sectional study.

Long-Term Consequences of Major Extremity Trauma: A Pilot Study.

SUMMARY: Limited data are available on the longer-term physical and psychosocial consequences after major extremity trauma apart from literature on the consequences after major limb amputation. The existing literature suggests that although variations in outcome exist, a significant proportion of service members and civilians sustaining major limb trauma will have less than optimal outcomes or health and rehabilitation needs over their life course. The proposed pilot study will address this gap in current research by locating and consenting METRC participants with the period of 5-7 years postinjury, identifying potential participation barriers and appropriate use of incentives, and conducting the follow-up examination at several data collection sites. The resulting data will inform the primary objective of refining and developing specific hypotheses to determine the design, scope, and feasibility of the main long-term consequences of major extremity trauma. Three METRC enrollment centers will contact past participants to achieve the goal of completing an interview, select patient-reported outcomes, perform a medical record review, and conduct an in-person clinic visit that will consist of a physical examination, blood draw, and x-ray of the study injury area. If successful, it will be possible to design studies to further examine these effects and develop future therapeutic interventions.

Streamlining Trauma Research Evaluation With Advanced Measurement (STREAM) Study: Implementation of the PROMIS Toolbox Within an Orthopaedic Trauma Clinical Trials Consortium.

LEVEL OF EVIDENCE: Prognostic Level II.

Risk factors for treatment failure of fracture-related infections.

OBJECTIVE: Infection after fracture fixation is a potentially devastating outcome, and surgical management is frequently unsuccessful at clearing these infections. The purpose of this study is to determine if factors can be identified that are associated with treatment failure after operative management of a deep surgical site infection. METHODS: We retrospectively reviewed the billing system at a Level I trauma center between March 2006 and December 2015. We identified 451 patients treated for deep surgical site infection after fracture fixation at our center. A multivariate regression analysis was then performed to evaluate for factors associated with treatment failure. RESULTS: Mean follow-up was 2.3 years. One hundred fifty-six patients (35%) failed initial surgical management. Risk factors associated with treatment failure included initial culture results positive for polymicrobial organisms (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.4), removal of implants (OR, 1.9; 95% CI, 1.2-2.9), or Gustilo-Anderson IIIB/IIIC injury (OR, 2.0; 95% CI, 1.1-3.7). Increased body mass index and fulfilling the criteria to have a methicillin-resistant Staphylococcus aureus (MRSA) nasal swab screening showed a trend toward increased risk of failure. CONCLUSION: Treatment failure after deep surgical site infection was relatively common. Three distinct factors (polymicrobial infection, removal of implants, and IIIB/C fracture) were associated with failure to eradicate the infection in the first series of surgeries and antibiotics. These data might help guide clinicians as they counsel patients on the risk of treatment failure and might focus efforts to improve treatment toward patients at higher risk of treatment failure.

PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT): a randomised pragmatic trial protocol comparing aspirin versus low-molecular-weight heparin for blood clot prevention in orthopaedic trauma patients.

INTRODUCTION: Patients who sustain orthopaedic trauma are at an increased risk of venous thromboembolism (VTE), including fatal pulmonary embolism (PE). Current guidelines recommend low-molecular-weight heparin (LMWH) for VTE prophylaxis in orthopaedic trauma patients. However, emerging literature in total joint arthroplasty patients suggests the potential clinical benefits of VTE prophylaxis with aspirin. The primary aim of this trial is to compare aspirin with LMWH as a thromboprophylaxis in fracture patients. METHODS AND ANALYSIS: PREVENT CLOT is a multicentre, randomised, pragmatic trial that aims to enrol 12 200 adult patients admitted to 1 of 21 participating centres with an operative extremity fracture, or any pelvis or acetabular fracture. The primary outcome is all-cause mortality. We will evaluate non-inferiority by testing whether the intention-to-treat difference in the probability of dying within 90 days of randomisation between aspirin and LMWH is less than our non-inferiority margin of 0.75%. Secondary efficacy outcomes include cause-specific mortality, non-fatal PE and deep vein thrombosis. Safety outcomes include bleeding complications, wound complications and deep surgical site infections. ETHICS AND DISSEMINATION: The PREVENT CLOT trial has been approved by the ethics board at the coordinating centre (Johns Hopkins Bloomberg School of Public Health) and all participating sites. Recruitment began in April 2017 and will continue through 2021. As both study medications are currently in clinical use for VTE prophylaxis for orthopaedic trauma patients, the findings of this trial can be easily adopted into clinical practice. The results of this large, patient-centred pragmatic trial will help guide treatment choices to prevent VTE in fracture patients. TRIAL REGISTRATION NUMBER: NCT02984384.

Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial.

Importance: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist. Objective: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections. Design, Setting, and Participants: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers. Interventions: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder. Main Outcomes and Measures: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence. Results: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections. Conclusions and Relevance: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin. Trial Registration: ClinicalTrials.gov Identifier: NCT02227446.

NURD 2.0: Prediction of tibial nonunion after intramedullary nail fixation at any time within 3 months after injury.

Introduction Nonunion after fixation of long bones negatively impacts outcomes and requires additional surgery. The ability to predict likelihood of nonunion after tibial shaft fracture would be helpful to clinicians and patients. The goal of this work was to combine three previous models of tibial shaft nonunion at different time points into one overall model that incorporates time as a continuous variable. Methods We conducted a retrospective review at a Level I academic trauma center. The study cohort consisted of patients with tibial shaft fractures treated with nail insertion from 2007 through 2014, excluding patients who did not have contact between bone ends, those who had planned bone grafting for acute bone defects, and those who lacked adequate follow-up. Three previous models were combined: 382 patients at time 0, 323 at 6 weeks, and 240 at 12 weeks. The primary outcome variable was surgery for nonunion. Bivariate and multivariate regression analyses determined which of 42 clinical and radiographic variables were significantly associated with nonunion. Predictive power was evaluated using area under the curve (AUC). Results The original nonunion risk determination (NURD) score was significantly improved through addition of 6- and 12-week radiographic union scores for tibial fractures, infection and complications, smoking status, and need for flaps. Overall, over the course of 12 weeks, the NURD-based model produced an AUC of 0.87 at initial time of fixation that improved to >0.9 at 6 and 12 weeks. Data were used to bin patients into five clinically important risk strata (p < 0.001). Patients in the lowest risk strata had 0% probability of nonunion (0 of 97 patients); in the second lowest risk strata, 4% (three of 73 patients); and in the highest risk strata, 48% (38 of 80 patients). Conclusions We created a NURD 2.0 score that predicts nonunion at various time points during the first 3 months after fracture. The new model is a notable improvement over previous models. A computerized version allows surgeons and patients to use the score when making treatment decisions regarding need for nonunion surgery.

Systemic Absorption and Nephrotoxicity Associated With Topical Vancomycin Powder for Fracture Surgery.

OBJECTIVES: To determine whether using topical vancomycin powder in fracture surgery may result in low levels of vancomycin in the serum and not result in nephrotoxicity. DESIGN: Prospective observational at a single site as a substudy of the VANCO trial. SETTING: Single, large urban level I trauma center. PATIENTS/PARTICIPANTS: Fifty-eight patients with tibial plateau and pilon fractures randomized to the treatment arm at the principal investigator's site. INTERVENTION: Topical vancomycin powder (1000 mg) applied directly in the wound over all metal implants at the time of wound closure. MAIN OUTCOME MEASUREMENTS: Serum vancomycin levels at 1 hour and 6-8 hours after surgery. Secondary outcomes included serum creatinine before surgery, a day after surgery, and at 2 weeks postoperatively and complete blood count at 2 weeks postoperatively. RESULTS: Except in 2 patients who also received intravenous vancomycin, none of the study patients had detectable (>5 µg/mL) serum vancomycin levels at 1 hour and 6-8 hours after surgery. One patient with a history of elevation of serum creatinine had a minor increase of serum creatinine but had undetectable vancomycin levels. None of the other patients had a clinically significant increase in creatinine levels. CONCLUSIONS: Despite its relatively widespread usage, little data exist regarding the systemic levels and nephrotoxicity associated with the topical use of vancomycin powder in orthopaedic fracture surgery. These prospective data indicate that there seems to be little clinical concern regarding toxicity associated with systemic absorption of vancomycin powder in this specific clinical application. LEVEL OF EVIDENCE: Therapeutic Level IV. See instructions for authors for a complete description of levels of evidence.

Vancomycin Powder Use in Fractures at High Risk of Surgical Site Infection.

OBJECTIVES: To determine if the use of intrawound vancomycin powder reduces surgical-site infection after open reduction and internal fixation of bicondylar tibial plateau, tibial pilon, and calcaneus fractures. DESIGN: Retrospective analysis. SETTING: Level I trauma center. PATIENTS: All fractures operatively treated from January 2011 to February 2015 were reviewed; 583 high-risk fractures were included, of which 35 received topical vancomycin powder. A previously published prospectively collected cohort of 235 similar high-risk fractures treated at our center from 2007 through 2010 served as a second comparison group. INTERVENTION: Topical vancomycin powder at wound closure. MAIN OUTCOME MEASUREMENTS: Deep surgical-site infection. Analyses used both univariate comparison of all patients and 1:2 matching analysis using both nearest neighbor and propensity-based matching. RESULTS: Compared with a control group of fractures treated during the same time period without vancomycin powder, the infection rate with vancomycin powder was significantly lower [0% (0/35) vs. 10.6% (58/548), P = 0.04]. Compared with our previously published historical infection rate of 13% for these injuries, vancomycin powder was also associated with significantly decreased deep surgical-site infection (0% vs. 13%, P = 0.02). These results agreed with the matched analyses, which also showed lower infection in the vancomycin powder group (0% vs. 11%-16%, P ≤ 0.05). CONCLUSIONS: Vancomycin powder may play a role in lowering surgical-site infection rates after fracture fixation. A larger randomized controlled trial is needed to validate our findings. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Pain, Depression, and Posttraumatic Stress Disorder Following Major Extremity Trauma Among United States Military Serving in Iraq and Afghanistan: Results From the Military Extremity Trauma and Amputation/Limb Salvage Study.

OBJECTIVES: Assess the burden and co-occurrence of pain, depression, and posttraumatic stress disorder (PTSD) among service members who sustained a major limb injury, and examine whether these conditions are associated with functional outcomes. DESIGN: A retrospective cohort study. SETTING: Four U.S. military treatment facilities: Walter Reed Army Medical Center, National Naval Medical Center, Brooke Army Medical Center, and Naval Medical Center San Diego. PATIENTS/PARTICIPANTS: Four hundred twenty-nine United States service members who sustained a major limb injury while serving in Afghanistan or Iraq met eligibility criteria upon review of their medical records. INTERVENTION: Not applicable. MAIN OUTCOME MEASUREMENTS: Outcomes assessed were: function using the short musculoskeletal functional assessment; PTSD using the PTSD Checklist and diagnostic and statistical manual criteria; pain using the chronic pain grade scale. RESULTS: Military extremity trauma and amputation/limb salvage patients without pain, depression, or PTSD, were, on average, about one minimally clinically important difference (MCID) from age- and gender-adjusted population norms. In contrast, patients with low levels of pain and no depression or PTSD were, on average, one to 2 MCIDs from population norms. Military extremity trauma and amputation/limb salvage patients with either greater levels of pain, and who experience PTSD, depression, or both, were 4 to 6 MCIDs from population norms. Regression analyses adjusting for injury type (upper or lower limb, salvage or amputation, and unilateral or bilateral), age, time to interview, military rank, presence of a major upper limb injury, social support, presence of mild traumatic brain injury/concussion, and combat experiences showed that higher levels of pain, depression, and PTSD were associated with lower one-year functional outcomes. CONCLUSIONS: Major limb trauma sustained in the military results in significant long-term pain and PTSD. Overall, the results are consistent with the hypothesis that pain, depression, and PTSD are associated with disability in this population. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Barriers and Facilitators to the Implementation of Injury Prevention Programs: A Qualitative Exploration and Model Development.

BACKGROUND: In 2006, the American College of Surgeons Committee on Trauma mandated implementation of injury prevention programs as a requirement for Level I and II trauma center designation. Little is known about the factors that facilitate or create barriers to establishing evidence-based injury prevention program implementation. The purpose of this research is to generate hypotheses regarding processes used to implement injury prevention programs at trauma centers, identify the factors that facilitate and serve as a barrier to implementation, and develop a model reflecting these factors and relationships. METHODS: This is a qualitative study of injury prevention programs at trauma centers. Study participants were chosen from 24 sites representing trauma centers of different patient volumes, geographic regions, and settings in the United States. Subjects participated in phone interviews based on guides developed from pilot interviews with prevention coordinators. Transcribed interviews from eight subjects were analyzed using a system of member checking to code; analysis informed the identification of factors that influence the establishment of evidence-based injury prevention programs. RESULTS: Five themes emerged from the data analysis: external factors, internal organizational factors, program capacity, program selection, and program success. Analysis revealed that successful program implementation was related to supportive leaders and collaborative, interdepartmental relationships. Additional themes indicated that while organizations were motivated primarily by verification requirements (external factor), strong institutional leadership (internal factor) was lacking. Employee readiness (program capacity) was hindered by limited training opportunities, and programs were often chosen (selection) based on implementation ease rather than evidence base or local data. CONCLUSIONS: Data analysis reveals five emerging themes of program implementation; using these data, we suggest an initial model of barriers and facilitators for implementing evidence-based injury prevention programs that could serve as the springboard for additional research involving a larger representative sample.

The Military Extremity Trauma Amputation/Limb Salvage (METALS) Study: Outcomes of Amputation Compared with Limb Salvage Following Major Upper-Extremity Trauma.

BACKGROUND: Severe upper-extremity injuries account for almost one-half of all extremity trauma in recent conflicts in the Global War on Terror. Few long-term outcomes studies address severe combat-related upper-extremity injuries. This study's objective was to describe long-term functional outcomes of amputation compared with those of limb salvage in Global War on Terror veterans who sustained severe upper-extremity injuries. Limb salvage was hypothesized to result in better arm and hand function scores, overall functional status, and quality of life, with similar pain interference. METHODS: This retrospective cohort study utilized data from the Military Extremity Trauma Amputation/Limb Salvage (METALS) study for a subset of 155 individuals who sustained major upper-extremity injuries treated with amputation or limb salvage. Participants were interviewed by telephone 40 months after injury, assessing social support, personal habits, and patient-reported outcome instruments for function, activity, depression, pain, and posttraumatic stress. Outcomes were evaluated for participants with severe upper-extremity injuries and were compared with participants with concomitant severe, lower-extremity injury. The analysis of outcomes comparing limb salvage with amputation was restricted to the 137 participants with a unilateral upper-extremity injury because of the small number of patients with bilateral upper-extremity injuries (n = 18). RESULTS: Overall, participants with upper-extremity injuries reported moderate to high levels of physical and psychosocial disability. Short Musculoskeletal Function Assessment (SMFA) scores were high across domains; 19.4% screened positive for posttraumatic stress disorder (PTSD), and 12.3% were positive for depression. Nonetheless, 63.6% of participants were working, were on active duty, or were attending school, and 38.7% of participants were involved in vigorous recreational activities. No significant differences in outcomes were observed between patients who underwent limb salvage and those who underwent amputation. CONCLUSIONS: Severe, combat-related upper-extremity injuries result in diminished self-reported function and psychosocial health. Our results suggest that long-term outcomes are equivalent for those treated with amputation or limb salvage. Addressing or preventing PTSD, depression, chronic pain, and associated health habits may result in less disability burden in this population. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.