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.

The 1-Year Economic Impact of Work Productivity Loss Following Severe Lower Extremity Trauma.

BACKGROUND: Severe lower extremity trauma among working-age adults is highly consequential for returning to work; however, the economic impact attributed to injury has not been fully quantified. The purpose of this study was to examine work and productivity loss during the year following lower extremity trauma and to calculate the economic losses associated with lost employment, lost work time (absenteeism), and productivity loss while at work (presenteeism). METHODS: This is an analysis of data collected prospectively across 3 multicenter studies of lower extremity trauma outcomes in the United States. Data were used to construct a Markov model that accumulated hours lost over time due to lost employment, absenteeism, and presenteeism among patients from 18 to 64 years old who were working prior to their injury. Average U.S. wages were used to calculate economic loss overall and by sociodemographic and injury subgroups. RESULTS: Of 857 patients working prior to injury, 47.2% had returned to work at 1 year. The average number of productive hours of work lost was 1,758.8/person, representing 84.6% of expected annual productive hours. Of the hours lost, 1,542.3 (87.7%) were due to working no hours or lost employment, 71.1 (4.0%) were due to missed hours after having returned, and 145.4 (8.3%) were due to decreased productivity while working. The 1-year economic loss due to injury totaled $64,427/patient (95% confidence interval [CI], $63,183 to $65,680). Of the 1,758.8 lost hours, approximately 88% were due to not being employed (working zero hours), 4% were due to absenteeism, and 8% were due to presenteeism. Total productivity loss was higher among older adults (≥40 years), men, those with a physically demanding job, and the most severe injuries (i.e., those leading to amputation as well as Gustilo type-IIIB tibial fractures and type-III pilon/ankle fractures). CONCLUSIONS: Patients with severe lower extremity trauma carry a substantial economic burden. The costs of lost productivity should be considered when evaluating outcomes.

Assessment of Severe Extremity Wound Bioburden at the Time of Definitive Wound Closure or Coverage: Correlation With Subsequent Postclosure Deep Wound Infection (Bioburden Study).

Infection remains the most common and significant complication after high-energy fractures. The Bioburden Study is a multicenter, prospective, observational cohort study of wound bacterial bioburden and antibiotic care in severe open lower extremity fractures. The aims of this study are to (1) characterize the contemporary extremity wound "bioburden" at the time of definitive wound closure; (2) determine the concordance between polymerase chain reaction results and hospital microbiology; (3) determine, among those who develop deep infections, the concordance between the pathogens at wound closure and at deep infection; and (4) compare the probability of deep infection between those who did and did not receive an appropriate course of antibiotics based on bioburden at the time of wound closure. To address these aims, sites collected tissue samples from severe lower extremity injuries at the time of wound closure and at first surgery for treatment of a deep infection, nonunion, flap failure, amputation, or other complications (because these surgeries may be due to undetected infection). Otherwise, if no further surgical treatment occurred, participants were followed for 12 months. The study was conducted at 38 US trauma centers and has enrolled 655 participants aged 18-64 years. This is the first large multi-institutional study evaluating the wound bioburden of severe open tibia fractures and correlating this bioburden with the risk of wound complications after definitive soft tissue closure.

A Prospective Randomized Trial to Assess Fixation Strategies for Severe Open Tibia Fractures: Modern Ring External Fixators Versus Internal Fixation (FIXIT Study).

The treatment of high-energy open tibia fractures is challenging in both the military and civilian environments. Treatment with modern ring external fixation may reduce complications common in these patients. However, no study has rigorously compared outcomes of modern ring external fixation with commonly used internal fixation approaches. The FIXIT study is a prospective, multicenter randomized trial comparing 1-year outcomes after treatment of severe open tibial shaft fractures with modern external ring fixation versus internal fixation among men and women of ages 18-64. The primary outcome is rehospitalization for major limb complications. Secondary outcomes include infection, fracture healing, limb function, and patient-reported outcomes including physical function and pain. One-year treatment costs and patient satisfaction will be compared between the 2 groups, and the percentage of Gustilo IIIB fractures that can be salvaged without soft tissue flap among patients receiving external fixation will be estimated.

Supplemental Perioperative Oxygen to Reduce Surgical Site Infection After High-Energy Fracture Surgery (OXYGEN Study).

Supplemental perioperative oxygen (SPO) therapy has been proposed as one approach for reducing the risk of surgical site infection (SSI). Current data are mixed regarding efficacy in decreasing SSI rates and hospital inpatient stays in general and few data exist for orthopaedic trauma patients. This study is a phase III, double-blind, prospective randomized clinical trial with a primary goal of assessing the efficacy of 2 different concentrations of perioperative oxygen in the prevention of SSIs in adults with tibial plateau, pilon (tibial plafond), or calcaneus fractures at higher risk of infection and definitively treated with plate and screw fixation. Patients are block randomized (within center) in a 1:1 ratio to either treatment group (FiO2 80%) or control group (FiO2 30%) and stratified by each study injury location. Secondary objectives of the study are to compare species and antibacterial sensitivities of the bacteria in patients who develop SSIs, to validate a previously developed risk prediction model for the development of SSI after fracture surgery, and to measure and compare resource utilization and cost associated with SSI in the 2 study groups. SPO is a low cost and readily available resource that could be easily disseminated to trauma centers across the country and the world if proved to be effective.

Increased Cost of Negative Pressure Dressings Is Not Justified for Split-Thickness Skin Grafting of Low-Risk Wounds.

OBJECTIVES: (1) To determine whether negative pressure dressings (NPDs) are superior to conventional compressive dressings (CDs) for split-thickness skin grafts (STSGs) placed on healthy, low-risk wounds, (2) To determine the cost difference of NPDs versus that of CDs. DESIGN: Retrospective. SETTING: Level I Trauma Center. PATIENTS/PARTICIPANTS: One hundred ninety-five traumatic wounds treated with STSG. MAIN OUTCOME MEASUREMENTS: Patients were assigned outcomes based on postoperative documentation: completely healed, incompletely healed (small areas of graft necrosis), failed, or lost to follow-up. The costs associated with each dressing type were documented. RESULTS: Thirty five of 195 STSGs were lost to follow-up, leaving n = 120 STSG-NPD, n = 40 STSG-CD. Of the remaining 120 STSGs treated with NPD, 91 completely healed, 23 incompletely healed, and 6 failed. Of the 40 STSGs treated with a CD, 37 completely healed, 1 incompletely healed, and 2 failed. Patients treated with CDs had a higher likelihood of healing relative to those treated with the NPD (P = 0.018). Analyzing the outcomes as failed versus "not failed" revealed no significant difference between the groups (P = 1.00). There were more smokers in the CD group (P = 0.022). In this series, the mean cost associated with NPD compared with that of CD was $2370 more per patient. CONCLUSIONS: There is a high rate of successful healing of STSGs for traumatic extremity wounds regardless of the dressing used. The increased cost of NPDs is not justified in wounds that are at a low risk of developing STSG failure. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Measurement of functional outcomes in the Major Extremity Trauma Research Consortium (METRC).

Measurement of functional outcome is a central tool in the assessment of the human and economic consequences of trauma. As such, functional outcome is the ideal basis against which to judge the efficacy of surgical approaches, drugs, and devices in the context of evidence-based medicine. A well-designed outcome measurement plan improves the validity of clinical research, facilitates the optimal use of limited research resources, and maximizes opportunities for future secondary data analyses. However, a key challenge in the development of a study measurement plan is the identification of appropriate, practical, well-validated measures. The Major Extremity Trauma Research Consortium (METRC) is a large 5-year research effort to develop and conduct multicenter clinical studies relevant to the treatment and outcomes of orthopaedic trauma. METRC is funded to conduct nine clinical studies. One of the main goals is to benefit from the consortium approach by standardizing data collection across these studies. METRC investigators have developed a standard set of measurement instruments designed to examine outcomes across a defined set of key domains: complications, depression, posttraumatic stress disorder, pain, activity and participation, health-related quality of life, patient satisfaction, and healthcare utilization. In addition, METRC investigators have developed a standard set of sociodemographic and clinical covariates to be collected across all studies.

Essentials of disaster management: the role of the orthopaedic surgeon.

Disaster preparedness and management education is essential for allowing orthopaedic surgeons to play a valuable, constructive role in responding to disasters. The National Incident Management System, as part of the National Response Framework, provides coordination between all levels of government and uses the Incident Command System as its unified command structure. An "all-hazards" approach to disasters, whether natural, man-made, intentional, or unintentional, is fundamental to disaster planning. To respond to any disaster, command and control must be established, and emergency management must be integrated with public health and medical care. In the face of increasing acts of terrorism, an understanding of blast injury pathophysiology allows for improved diagnostic and treatment strategies. A practical understanding of potential biologic, chemical, and nuclear agents and their attendant clinical symptoms is also prerequisite. Credentialing and coordination between designated organizations and the federal government are essential to allow civilian orthopaedic surgeons to access systems capable of disaster response.

Perceived need and unmet need for vocational, mental health, and other support services after severe lower-extremity trauma.

OBJECTIVES: To examine the perceived need and unmet need for support services, the reasons for not obtaining services, and the factors contributing to unmet need for vocational and mental health services in patients with traumatic lower-extremity injury. DESIGN: Multicenter, prospective observational study. SETTING: Eight level I trauma centers. PARTICIPANTS: Patients (N=545) undergoing lower-extremity reconstruction or amputation from March 1994 to June 1997. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Perceived need and unmet need for support services at 3, 6, and 12 months after hospitalization. RESULTS: Eighty-five percent of patients reported a need for at least 1 support service, and 32% reported an unmet need over the 12 months. The highest perceived need was for home nursing and legal, and for unmet need was vocational and mental health services. The main reason for patients not trying to obtain mental health assistance was thinking they would get better on their own, and for other support services was not knowing where to go. Patients treated by reconstruction compared with amputation, and being nonwhite were statistically associated with unmet needs for vocational and mental health services. CONCLUSIONS: The results suggest a significant amount of unmet need for vocational and mental health services during the first year after hospitalization in the severe lower-extremity trauma population with perceived need. Areas for future research are to objectively measure need and unmet need, and further investigate the disparities in unmet need by race and treatment type in this patient population. Recommendations for trauma centers include education and screening for mental health conditions and the need for support services during hospitalization and clinic visits, and increasing communication between surgeons and providers specializing in vocational, psychological, and socioeconomic issues.

Orthopedic surgeons and physical therapists differ in assessment of need for physical therapy after traumatic lower-extremity injury.

BACKGROUND: Lower-extremity injuries constitute the leading cause of trauma hospitalizations among people under the age of 65 years. Rehabilitation has the potential to favorably influence the outcomes associated with traumatic lower-extremity injuries. OBJECTIVES: The objectives of this study were to explore variability in surgeon and physical therapist assessments of the need for physical therapy in patients with traumatic lower-extremity injuries and to determine the factors associated with assessments of need. DESIGN: This study was a retrospective cohort investigation. METHODS: Participants were 395 patients treated by reconstruction in the Lower-Extremity Assessment Project. They were evaluated at 8 level I trauma centers at 3, 6, and 12 months after hospitalization by an orthopedic surgeon and a physical therapist to determine the need for physical therapy. Analyses included multilevel logistic regression. RESULTS: Chi-square analyses showed that surgeon and therapist assessments of need differed statistically across trauma centers. Surgeons were more likely to assess a need for therapy at 3 months when participants had low work self-efficacy, impaired knee flexion range of motion (ROM), and weight-bearing limitations and at 6 and 12 months when participants had impaired knee flexion ROM and weight-bearing and balance limitations. Therapists were more likely to assess a need for therapy at 3 months when participants had moderate to severe pain and at 6 and 12 months when participants had low work self-efficacy, pain, impaired knee flexion ROM, and balance limitations. CONCLUSIONS: The results revealed variability in assessments of the need for physical therapy at the provider and trauma center levels. Differences in provider assessments highlight the need for communication and further investigation into the outcomes and timing of physical therapy for the treatment of traumatic lower-extremity injuries.

Knee dislocations with vascular injury: outcomes in the Lower Extremity Assessment Project (LEAP) Study.

OBJECTIVES: The purpose of this study is to report the clinical and functional results of a cohort of patients with knee dislocations associated with vascular injury. METHODS: Patients with knee dislocation and associated vascular injury were prospectively assessed for outcome of severe lower extremity trauma during 2 years. The Sickness Impact Profile was used to assess the functional recovery of the patient. Surgeon and therapist assessments documented clinical metrics and treatment, including salvage or amputation, neurologic recovery, knee stability, and knee motion. RESULTS: Eighteen patients sustained a knee dislocation and an associated popliteal artery injury. Seven patients were found to have an additional vascular injury. All patients underwent repair of the vascular injury. At the time of final follow-up, 14 knees were successfully salvaged and four required amputation (1 below knee amputation, 2 through knee amputation, and 1 above knee amputation). Eighteen patients had at least a popliteal injury and underwent repair of the vascular injury. The patients with a limb-threatening knee dislocation that was successfully reconstructed had Sickness Impact Profile scores of 20.12 at 3 months, 13.18 at 6 months, 12.08 at 1 year, and 7.0 at 2 years after injury. CONCLUSIONS: Patients who sustain a limb-threatening knee dislocation have a moderate to high level of disability 2 years after injury. Nearly one in five patients who present to a Level I trauma center with a dysvascular limb associated with a knee dislocation will require amputation. Prolonged warm ischemia time was associated with a high rate of amputation. Patients who sustain vascular injuries associated with a knee dislocation need immediate transport to a trauma hospital, rapid assessment and diagnosis at presentation, and revascularization. Patients with these injuries can be effectively treated without angiography before surgery.

Health-care costs associated with amputation or reconstruction of a limb-threatening injury.

BACKGROUND: Recent reports have suggested that functional outcomes are similar following either amputation or reconstruction of a severely injured lower extremity. The goal of this study was to compare two-year direct health-care costs and projected lifetime health-care costs associated with these two treatment pathways. METHODS: Two-year health-care costs were estimated for 545 patients with a unilateral limb-threatening lower-extremity injury treated at one of eight level-I trauma centers. Included in the calculation were costs related to (1) the initial hospitalization, (2) all rehospitalizations for acute care related to the limb injury, (3) inpatient rehabilitation, (4) outpatient doctor visits, (5) outpatient physical and occupational therapy, and (6) purchase and maintenance of prosthetic devices. All dollar figures were inflated to constant 2002 dollars with use of the medical service Consumer Price Index. To estimate projected lifetime costs, the number of expected life years was multiplied by an estimate of future annual health-care costs and added to an estimate of future costs associated with the purchase and maintenance of prosthetic devices. RESULTS: When costs associated with rehospitalizations and post-acute care were added to the cost of the initial hospitalization, the two-year costs for reconstruction and amputation were similar. When prosthesis-related costs were added, there was a substantial difference between the two groups ($81,316 for patients treated with reconstruction and $91,106 for patients treated with amputation). The projected lifetime health-care cost for the patients who had undergone amputation was three times higher than that for those treated with reconstruction ($509,275 and $163,282, respectively). CONCLUSIONS: These estimates add support to previous conclusions that efforts to improve the rate of successful reconstructions have merit. Not only is reconstruction a reasonable goal at an experienced level-I trauma center, it results in lower lifetime costs.

Complex limb salvage or early amputation for severe lower-limb injury: a meta-analysis of observational studies.

PURPOSE: Leg threatening injuries present patients and clinicians with a difficult decision: whether to pursue primary amputation or limb salvage? The purpose of our study was to review the literature in an effort to inform this management decision. METHODS: We systematically searched and selected observational studies that reported on individuals presenting with leg threatening injuries comparing outcomes of limb salvage versus primary amputation. We searched MEDLINE, CINAHL, and EMBASE. We reported on the following outcomes, and pooled data across trials when possible: length of hospital stay, total rehabilitation time, cost, clinical outcomes, failure rate for limb salvage, function & quality of life, pain, return to work, factors associated with poor outcome, and patient preference. RESULTS: Nine observational studies contributed data to our systematic review. The current evidence suggests that while length of hospital stay is similar for limb salvage and primary amputation, length of rehabilitation and total costs are higher for limb salvage patients. Salvage patients requires greater additional surgery and are significantly more likely to undergo re-hospitalization. Long-term functional outcomes (up to 7 years post injury) are equivalent between limb salvage and primary amputation; both forms of management are associated with high rates of self-reported disability (40%; to 50%;), and functional status continues to worsen over time. Report of pain following limb salvage or primary amputation is similar. Return to work is essentially the same between limb salvage and primary amputation groups, with approximately half of such patients returning to competitive employment at 2 years post injury. Both clinical and psychosocial factors are associated with poorer functional outcomes. At the time of injury patients prefer limb salvage, but the majority of failed salvage patients would opt for early amputation if they could decide again. CONCLUSION AND SIGNIFICANCE: Functional outcome among patients who present with leg-threatening injuries are not significantly different, at least up to 7 years, whether they are managed with limb salvage or primary amputation. Research to optimize triage decisions to avoid failed limb salvage as well as on interventions targeting important psychosocial prognostic variables should be considered a priority.

Factors influencing outcome following limb-threatening lower limb trauma: lessons learned from the Lower Extremity Assessment Project (LEAP).

The Lower Extremity Assessment Project (LEAP) is a multicenter study of severe lower extremity trauma in the US civilian population. At 2- and 7-year follow-ups, the LEAP study found no difference in functional outcome between patients who underwent either limb salvage surgery or amputation. However, outcomes on average were poor for both groups. This study and others provide evidence of wide-ranging variations in outcome following major limb trauma, with a substantial proportion of patients experiencing long-term disability. In addition, outcomes often are more affected by the patient's economic, social, and personal resources than by the initial treatment of the injury--specifically, amputation or reconstruction and level of amputation. A conceptual framework for examining outcomes after injury may be used to identify opportunities for interventions that would improve outcomes. Because of essential differences between the civilian and military populations, the findings of the LEAP study may correlate only roughly with combat casualty outcomes.

Factors influencing the decision to amputate or reconstruct after high-energy lower extremity trauma.

BACKGROUND: Factors thought to influence the decision for limb salvage include injury severity, physiologic reserve of the patient, and characteristics of the patient and their support system. METHODS: Eligible patients were between the ages of 16 and 69 with Gustilo type IIIB and IIIC tibial fractures, dysvascular limbs resulting from trauma, type IIIB ankle fractures, or severe open midfoot or hindfoot injuries. Data collected at enrollment relevant to the decision-making process included injury characteristics and its treatment, and the nature and severity of other injuries. Logistic regression and stepwise modeling were used to determine the effect of each covariate on the variable salvage/ amputation. RESULTS: Of 527 patients included in the analysis, 408 left the hospital with a salvaged limb. Of the 119 amputations performed, 55 were immediate and 64 were delayed. The multivariate analysis confirmed the bivariate analysis: all injury characteristics remained significant predictors of limb status with the exception of bone loss; and soft tissue injury and absence of plantar sensation were the most important factors in accounting for model validity. CONCLUSION: Soft tissue injury severity has the greatest impact on decision making regarding limb salvage versus amputation.