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.).

Reducing High-Dose Opioid Prescribing: State-Level Morphine Equivalent Daily Dose Policies, 2007-2017.

OBJECTIVE: To describe current state-level policies in the United States, January 1, 2007-June 1, 2017, limiting high morphine equivalent daily dose (MEDD) prescribing. METHODS: State-level MEDD threshold policies were reviewed using LexisNexis and Westlaw Next for legislative acts and using Google for nonlegislative state-level policies. The websites of each state's Medicaid agency, health department, prescription drug monitoring program, workers' compensation board, medical board, and pharmacy board were reviewed to identify additional policies. The final policy list was checked against existing policy compilations and academic literature and through contact with state health agency representatives. Policies were independently double-coded on the categories: state, agency/organization, policy type, effective date, threshold level, and policy exceptions. RESULTS: Currently, 22 states have at least one type of MEDD policy, most commonly guidelines (14 states), followed by prior authorizations (four states), rules/regulations (four states), legislative acts (three states), claim denials (two states), and alert systems/automatic patient reports (two states). Thresholds range widely (30-300 mg MEDD), with higher thresholds generally corresponding to more restrictive policies (e.g., claim denial) and lower thresholds corresponding to less restrictive policies (e.g., guidelines). The majority of policies exclude some groups of opioid users, most commonly patients with terminal illnesses or acute pain. CONCLUSIONS: MEDD policies have gained popularity in recent years, but considerable variation in threshold levels and policy structure point to a lack of consensus. This work provides a foundation for future evaluation of MEDD policies and may inform states considering adopting such policies.

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 local and systemic effects of immune function on fracture healing.

The immune system plays an integral role in the regulation of cellular processes responsible for fracture healing. Local and systemic influences on fracture healing correlate in many ways with fracture-related outcomes, including soft tissue healing quality and fracture union rates. Impaired soft tissue healing, restricted perfusion of a fracture site, and infection also in turn affect the immune response to fracture injury. Modern techniques used to investigate the relationship between immune system function and fracture healing include precision medicine, using vast quantities of data to interpret broad patterns of inflammatory response. Early data from the PRECISE trial have demonstrated distinct patterns of inflammatory response in polytrauma patients, which thereby directly and indirectly regulate the fracture healing response. The clearly demonstrated linkage between immune function and fracture healing suggests that modulation of immune function has significant potential as a therapeutic target that can be used to enhance fracture healing.

Venous thromboembolism prophylaxis prescribing patterns for patients with orthopedic trauma: a clinical vignette survey.

Background: A recent clinical trial suggested aspirin is a viable alternative to enoxaparin for venous thromboembolism (VTE) prophylaxis in patients after orthopedic trauma. The initial impact of these findings on VTE prophylaxis prescribing is unknown. The study aimed to evaluate stated VTE prophylaxis prescribing patterns among clinicians who treat patients after orthopedic trauma. Methods: For this clinical vignette survey, we recruited surgeons and advanced practice providers who prescribed VTE prophylaxis to patients with orthopedic trauma across 40 states. Clinicians were shown seven clinical vignettes describing hypothetical patients with orthopedic trauma based on their fracture type, treatment, VTE risk factors, additional injuries and health insurance status. We assessed the stated VTE prophylaxis medications prescribed in-hospital and at discharge, patient factors associated with changes in medication prescribing preferences and practice variation by specialty and provider training. Results: Among the 287 respondents, the median age was 43 years (IQR, 38-50), and 154 (weighted average, 63%) were men. For in-hospital VTE prophylaxis, enoxaparin was prescribed in 83% of the presented scenarios, and aspirin was prescribed in 13% (p<0.001). At discharge, aspirin was prescribed more frequently than enoxaparin (50% vs 41%, p<0.001). Healthcare providers with an aspirin discharge preference were 12% more likely to switch to enoxaparin if the patient had additional VTE risk factors, such as obesity (95% CI 4% to 19%, p=0.005). Conclusions: Despite new clinical evidence, in-hospital VTE prophylaxis prescribing practices for patients with orthopedic trauma remain consistent with those reported a decade ago. However, compared with historical data, clinicians have significantly increased their preference for aspirin for thromboprophylaxis at discharge-unless the patient has additional thromboembolic risk factors. Level of evidence: 5-expert opinion.

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.

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.

Minimal Clinically Important Difference (MCID) for the Short Musculoskeletal Function Assessment (SMFA) in Severe Lower Extremity Trauma: Pooled Data from 7 Multicenter, Prospective Clinical Trials.

BACKGROUND: The Short Musculoskeletal Function Assessment (SMFA) is a well validated, widely used patient-reported outcome (PRO) measure for orthopaedic patients. Despite its widespread use and acceptance, this measure does not have an agreed upon minimal clinically important difference (MCID). The purpose of the present study was to create distributional MCIDs with use of a large cohort of research participants with severe lower extremity fractures. METHODS: Three distributional approaches were used to calculate MCIDs for the Dysfunction and Bother Indices of the SMFA as well as all its domains: (1) half of the standard deviation (one-half SD), (2) twice the standard error of measurement (2SEM), and (3) minimal detectable change (MDC). In addition to evaluating by patient characteristics and the timing of assessment, we reviewed these calculations across several injury groups likely to affect functional outcomes. RESULTS: A total of 4,298 SMFA assessments were collected from 3,185 patients who had undergone surgical treatment of traumatic injuries of the lower extremity at 60 Level-I trauma centers across 7 multicenter, prospective clinical studies. Depending on the statistical approach used, the MCID associated with the overall sample ranged from 7.7 to 10.7 for the SMFA Dysfunction Index and from 11.0 to 16.8 for the SMFA Bother Index. For the Dysfunction Index, the variability across the scores was small (<5%) within the sex and age subgroups but was modest (12% to 18%) across subgroups related to assessment timing. CONCLUSIONS: A defensible MCID can be found between 7 and 11 points for the Dysfunction Index and between 11 and 17 points for the Bother Index. The precise choice of MCID may depend on the preferred statistical approach and the population under study. While differences exist between MCID values based on the calculation method, values were consistent across the categories of the various subgroups presented. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Effect of Aspirin Versus Low-Molecular-Weight Heparin Thromboprophylaxis on Medication Satisfaction and Out-of-Pocket Costs: A Secondary Analysis of a Randomized Clinical Trial.

BACKGROUND: Current guidelines recommend low-molecular-weight heparin for thromboprophylaxis after orthopaedic trauma. However, recent evidence suggests that aspirin is similar in efficacy and safety. To understand patients' experiences with these medications, we compared patients' satisfaction and out-of-pocket costs after thromboprophylaxis with aspirin versus low-molecular-weight heparin. METHODS: This study was a secondary analysis of the PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT) trial, conducted at 21 trauma centers in the U.S. and Canada. We included adult patients with an operatively treated extremity fracture or a pelvic or acetabular fracture. Patients were randomly assigned to receive 30 mg of low-molecular-weight heparin (enoxaparin) twice daily or 81 mg of aspirin twice daily for thromboprophylaxis. The duration of the thromboprophylaxis, including post-discharge prescription, was based on hospital protocols. The study outcomes included patient satisfaction with and out-of-pocket costs for their thromboprophylactic medication measured on ordinal scales. RESULTS: The trial enrolled 12,211 patients (mean age and standard deviation [SD], 45 ± 18 years; 62% male), 9725 of whom completed the question regarding their satisfaction with the medication and 6723 of whom reported their out-of-pocket costs. The odds of greater satisfaction were 2.6 times higher for patients assigned to aspirin than those assigned to low-molecular-weight heparin (odds ratio [OR]: 2.59; 95% confidence interval [CI]: 2.39 to 2.80; p < 0.001). Overall, the odds of incurring any out-of-pocket costs for thromboprophylaxis medication were 51% higher for patients assigned to aspirin compared with low-molecular-weight heparin (OR: 1.51; 95% CI: 1.37 to 1.66; p < 0.001). However, patients assigned to aspirin had substantially lower odds of out-of-pocket costs of at least $25 (OR: 0.15; 95% CI: 0.12 to 0.18; p < 0.001). CONCLUSIONS: Use of aspirin substantially improved patients' satisfaction with their medication after orthopaedic trauma. While aspirin use increased the odds of incurring any out-of-pocket costs, it protected against costs of ≥$25, potentially improving health equity for thromboprophylaxis. LEVEL OF EVIDENCE: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Outcomes of Patients With Large Versus Small Bone Defects in Open Tibia Fractures Treated With an Intramedullary Nail: A Descriptive Analysis of a Multicenter Retrospective Study.

OBJECTIVES: To compare outcomes in patients with open tibia shaft fractures based on defect size. DESIGN: Retrospective review. SETTING: Eighteen trauma centers. POPULATION: The study included 132 patients with diaphyseal tibia bone defects >1 cm and ≥50% cortical loss treated with intramedullary nail. OUTCOMES: The primary outcome was number of secondary surgeries to promote healing (bone graft, revision fixation, or bone transport). Additional outcomes included occurrence of secondary surgeries (bone graft, infection, amputation, and flap failure) and proportion healed at one year. Results are compared by "radiographic apparent bone gap" of <2.5 or ≥2.5 cm. RESULTS: The estimated conditional probability of bone grafting within one year given graft-free at 90 days was 44% and 47% in the <2.5 cm and ≥2.5 cm groups, respectively. An estimated infection risk of 14% was observed in both groups [adjusted hazard ratio (HR) 0.98, 95% confidence interval (CI): 0.33-2.92], estimated amputation risk was 9% (<2.5 cm) and 4% (≥2.5 cm) (unadjusted HR 0.66, 95% CI: 0.13-3.29), and estimated flap failure risk (among those with flaps) was 10% and 13%, respectively (unadjusted HR 1.71, 95% CI: 0.24-12.25). There was no appreciable difference in the proportion healed at one year between defect sizes [adjusted HR: 1.07 (95% CI, 0.63-1.82)]. CONCLUSIONS: Larger size bone defects were not associated with higher number of secondary procedures to promote healing or a lower overall one-year healing rate. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Defining Incidence of Acute Compartment Syndrome in the Research Setting: A Proposed Method From the PACS Study.

OBJECTIVE: To compare the retrospective decision of an expert panel who assessed likelihood of acute compartment syndrome (ACS) in a patient with a high-risk tibia fracture with decision to perform fasciotomy. DESIGN: Prospective observational study. SETTING: Seven Level 1 trauma centers. PATIENTS/PARTICIPANTS: One hundred eighty-two adults with severe tibia fractures. MAIN OUTCOME MEASUREMENTS: Diagnostic performance (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver-operator curve) of an expert panel's assessment of likelihood ACS compared with fasciotomy as the reference diagnostic standard. SECONDARY OUTCOMES: The interrater reliability of the expert panel as measured by the Krippendorff alpha. Expert panel consensus was determined using the percent of panelists in the majority group of low (expert panel likelihood of ≤0.3), uncertain (0.3-0.7), or high (>0.7) likelihood of ACS. RESULTS: Comparing fasciotomy (the diagnostic standard) and the expert panel's assessment as the diagnostic classification (test), the expert panel's determination of uncertain or high likelihood of ACS (threshold >0.3) had a sensitivity of 0.90 (0.70, 0.99), specificity of 0.95 (0.90, 0.98), PPV of 0.70 (0.50, 0.86), and NPV of 0.99 (0.95, 1.00). When a threshold of >0.7 was set as a positive diagnosis, the expert panel assessment had a sensitivity of 0.67 (0.43, 0.85), specificity of 0.98 (0.95, 1.00), PPV of 0.82 (0.57, 0.96), and NPV of 0.96 (0.91, 0.98). CONCLUSION: In our study, the retrospective assessment of an expert panel of the likelihood of ACS has good specificity and excellent NPV for fasciotomy, but only low-to-moderate sensitivity and PPV. The discordance between the expert panel-assessed likelihood of ACS and the decision to perform fasciotomy suggests that concern regarding potential diagnostic bias in studies of ACS is warranted. LEVEL OF EVIDENCE: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

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.

Patient-Specific Precision Injury Signatures to Optimize Orthopaedic Interventions in Multiply Injured Patients (PRECISE STUDY).

SUMMARY: Optimal timing and procedure selection that define staged treatment strategies can affect outcomes dramatically and remain an area of major debate in the treatment of multiply injured orthopaedic trauma patients. Decisions regarding timing and choice of orthopaedic procedure(s) are currently based on the physiologic condition of the patient, resource availability, and the expected magnitude of the intervention. Surgical decision-making algorithms rarely rely on precision-type data that account for demographics, magnitude of injury, and the physiologic/immunologic response to injury on a patient-specific basis. This study is a multicenter prospective investigation that will work toward developing a precision medicine approach to managing multiply injured patients by incorporating patient-specific indices that quantify (1) mechanical tissue damage volume; (2) cumulative hypoperfusion; (3) immunologic response; and (4) demographics. These indices will formulate a precision injury signature, unique to each patient, which will be explored for correspondence to outcomes and response to surgical interventions. The impact of the timing and magnitude of initial and staged surgical interventions on patient-specific physiologic and immunologic responses will be evaluated and described. The primary goal of the study will be the development of data-driven models that will inform clinical decision-making tools that can be used to predict outcomes and guide intervention decisions.

Cognitive-Behavioral-Based Physical Therapy for Improving Recovery After Traumatic Orthopaedic Lower Extremity Injury (CBPT-Trauma).

SUMMARY: Physical and psychological impairment resulting from traumatic injuries is often significant and affects employment and functional independence. Extremity trauma has been shown to negatively affect long-term self-reported physical function, the ability to work, and participation in recreational activities and contributes to increased rates of anxiety and/or depression. High pain levels early in the recovery process and psychosocial factors play a prominent role in recovery after traumatic lower extremity injury. Cognitive-behavioral therapy pain programs have been shown to mitigate these effects. However, patient access issues related to financial and transportation constraints and the competing demands of treatment focused on the physical sequelae of traumatic injury limit patient participation in this treatment modality. This article describes a telephone-delivered cognitive-behavioral-based physical therapy (CBPT-Trauma) program and design of a multicenter trial to determine its effectiveness after lower extremity trauma. Three hundred twenty-five patients from 7 Level 1 trauma centers were randomized to CBPT-Trauma or an education program after hospital discharge. The primary hypothesis is that compared with patients who receive an education program, patients who receive the CBPT-Trauma program will have improved physical function, pain, and physical and mental health at 12 months after hospital discharge.

Can financial payments incentivize short-term smoking cessation in orthopaedic trauma patients? Evidence from a discrete choice experiment.

BACKGROUND: Smoking increases the risk of complications and related costs after an orthopaedic fracture. Research in other populations suggests that a one-time payment may incentivize smoking cessation. However, little is known on fracture patients' willingness to accept financial incentives to stop smoking; and the level of incentive required to motivate smoking cessation in this population. This study aimed to estimate the financial threshold required to motivate fracture patients to stop smoking after injury. METHODS: This cross-sectional study utilized a discrete choice experiment (DCE) to elicit patient preferences towards financial incentives and reduced complications associated with smoking cessation. We presented participants with 12 hypothetical options with several attributes with varying levels. The respondents' data was used to determine the utility of each attribute level and the relative importance associated with each attribute. RESULTS: Of the 130 enrolled patients, 79% reported an interest in quitting smoking. We estimated the financial incentive to be of greater relative importance (ri) (45%) than any of the included clinical benefits of smoking cessations (deep infection (ri: 24%), bone healing complications (ri: 19%), and superficial infections (ri: 12%)). A one-time payment of $800 provided the greatest utility to the respondents (0.64, 95% CI: 0.36 to 0.93), surpassing the utility associated with a single $1000 financial incentive (0.36, 95% CI: 0.18 to 0.55). CONCLUSIONS: Financial incentives may be an effective tool to promote smoking cessation in the orthopaedic trauma population. The findings of this study define optimal payment thresholds for smoking cessation programs.

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.

Perfusion Pressure Lacks Diagnostic Specificity for the Diagnosis of Acute Compartment Syndrome.

OBJECTIVE: To evaluate the diagnostic performance of perfusion pressure (PP) thresholds for fasciotomy. DESIGN: Prospective observational study. SETTING: Seven Level-1 trauma centers. PATIENTS/PARTICIPANTS: One hundred fifty adults with severe leg injuries and ≥2 hours of continuous PP data who had been enrolled in a multicenter observational trial designed to develop a clinical prediction rule for acute compartment syndrome (ACS). MAIN OUTCOME MEASUREMENTS: For each patient, a given PP criterion was positive if it was below the specified threshold for at least 2 consecutive hours. The diagnostic performance of PP thresholds between 10 and 30 mm Hg was determined using 2 reference standards for comparison: (1) the likelihood of ACS as determined by an expert panel who reviewed each patient's data portfolio or (2) whether the patient underwent fasciotomy. RESULTS: Using the likelihood of ACS as the diagnostic standard (ACS considered present if median likelihood ≥70%, absent if <30%), a PP threshold of 30 mm Hg had diagnostic sensitivity 0.83, specificity 0.53, positive predictive value 0.07, and negative predictive value 0.99. Results were insensitive to more strict likelihood categorizations and were similar for other PP thresholds between 10- and 25-mm Hg. Using fasciotomy as the reference standard, the same PP threshold had diagnostic sensitivity 0.50, specificity 0.50, positive predictive value 0.04, negative predictive value 0.96. CONCLUSION: No value of PP from 10 to 30 mm Hg had acceptable diagnostic performance, regardless of which reference diagnostic standard was used. These data question current practice of diagnosing ACS based on PP and suggest the need for further research. LEVEL OF EVIDENCE: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

A national evaluation of the effect of trauma-center care on mortality.

BACKGROUND: Hospitals have difficulty justifying the expense of maintaining trauma centers without strong evidence of their effectiveness. To address this gap, we examined differences in mortality between level 1 trauma centers and hospitals without a trauma center (non-trauma centers). METHODS: Mortality outcomes were compared among patients treated in 18 hospitals with a level 1 trauma center and 51 hospitals non-trauma centers located in 14 states. Patients 18 to 84 years old with a moderate-to-severe injury were eligible. Complete data were obtained for 1104 patients who died in the hospital and 4087 patients who were discharged alive. We used propensity-score weighting to adjust for observable differences between patients treated at trauma centers and those treated at non-trauma centers. RESULTS: After adjustment for differences in the case mix, the in-hospital mortality rate was significantly lower at trauma centers than at non-trauma centers (7.6 percent vs. 9.5 percent; relative risk, 0.80; 95 percent confidence interval, 0.66 to 0.98), as was the one-year mortality rate (10.4 percent vs. 13.8 percent; relative risk, 0.75; 95 percent confidence interval, 0.60 to 0.95). The effects of treatment at a trauma center varied according to the severity of injury, with evidence to suggest that differences in mortality rates were primarily confined to patients with more severe injuries. CONCLUSIONS: Our findings show that the risk of death is significantly lower when care is provided in a trauma center than in a non-trauma center and argue for continued efforts at regionalization.

Inter-Rater Reliability of the Modified Radiographic Union Score for Diaphyseal Tibial Fractures With Bone Defects.

OBJECTIVES: To evaluate inter-rater reliability of the modified Radiographic Union Score for Tibial (mRUST) fractures among patients with open, diaphyseal tibia fractures with a bone defect treated with intramedullary nails (IMNs), plates, or definitive external fixation (ex-fix). DESIGN: Retrospective cohort study. SETTING: Fifteen-level one civilian trauma centers; 2 military treatment facilities. PATIENTS/PARTICIPANTS: Patients ≥18 years old with open, diaphyseal tibia fractures with a bone defect ≥1 cm surgically treated between 2007 and 2012. INTERVENTION: Three of 6 orthopedic traumatologists reviewed and applied mRUST scoring criteria to radiographs from the last clinical visit within 13 months of injury. MAIN OUTCOME MEASUREMENTS: Inter-rater reliability was assessed using Krippendorff's alpha (KA) statistic; intraclass correlation coefficient (ICC) is presented for comparison with previous publications. RESULTS: Two hundred thirteen patients met inclusion criteria including 115 IMNs, 24 plates, 29 ex-fixes, and 45 cases that no longer had instrumentation at evaluation. All reviewers agreed on the pattern of scoreable cortices for 90.4% of IMNs, 88.9% of those without instrumentation, 44.8% of rings, and 20.8% of plates. Thirty-one (15%) cases, primarily plates and ex-fixes, did not contribute to KA and ICC estimates because <2 raters scored all cortices. The overall KA for the 85% that could be analyzed was 0.64 (ICC 0.71). For IMNs, plates, ex-fixes, and no instrumentation, KA (ICC) was 0.65 (0.75), 0.88 (0.90), 0.47 (0.62), and 0.48 (0.57), respectively. CONCLUSIONS: In tibia fractures with bone defects, the mRUST seems similarly reliable to previous work in patients treated with IMN but is less reliable in those with plates or ex-fixes, or after removal of instrumentation.

Continuous Near-Infrared Spectroscopy Demonstrates Limitations in Monitoring the Development of Acute Compartment Syndrome in Patients with Leg Injuries.

BACKGROUND: We recorded measurements of muscle perfusion using near-infrared spectroscopy (NIRS) and intramuscular pressure (IMP) in a study designed to develop a decision rule for predicting acute compartment syndrome (ACS). The purpose of this study was to report our experience measuring NIRS data in the context of this broader investigation and to explore factors related to variations in data capture. METHODS: One hundred and eighty-five patients with lower-leg injuries had data consisting of continuous NIRS measurement of the O2 saturation in the anterior compartment of the injured limb and the contralateral (control) limb, and continuous IMP recording in the anterior and deep posterior compartments of the injured leg as part of their participation in an institutional review board-approved multicenter trial. All monitoring was done for a prescribed period of time. For both types of data, the percentage of valid data capture was defined as the ratio of the minutes of observed data points within a physiological range to the total minutes of expected data points. Clinically useful NIRS data required simultaneous data from the injured and control limbs to calculate the ratio. Statistical tests were used to compare the 2 methods as well as factors associated with the percent of valid NIRS data capture. RESULTS: For the original cohort, clinically useful NIRS data were available a median of 9.1% of the expected time, while IMP data were captured a median of 87.6% of the expected time (p < 0.001). Excluding 46 patients who had erroneous NIRS data recorded, the median percentage was 31.6% for NIRS compared with 87.4% for IMP data (p < 0.00001). Fractures with an associated hematoma were less likely to have valid data points (odds ratio [OR], 0.53; p = 0.04). Gustilo types-I and II open fractures were more likely than Tscherne grades C0 and C1 closed fractures to have valid data points (OR, 1.97; p = 0.03). CONCLUSIONS: In this study, NIRS data were not collected reliably. In contrast, IMP measurements were collected during >85% of the expected monitoring period. These data raise questions about the utility of current NIRS data capture technology for monitoring oxygenation in patients at risk of ACS.