Expanding the scope of quality measurement in surgery to include nonoperative care: Results from the American College of Surgeons National Surgical Quality Improvement Program emergency general surgery pilot.

BACKGROUND: Patients managed nonoperatively have been excluded from risk-adjusted benchmarking programs, including the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP). Consequently, optimal performance evaluation is not possible for specialties like emergency general surgery (EGS) where nonoperative management is common. We developed a multi-institutional EGS clinical data registry within ACS NSQIP that includes patients managed nonoperatively to evaluate variability in nonoperative care across hospitals and identify gaps in performance assessment that occur when only operative cases are considered. METHODS: Using ACS NSQIP infrastructure and methodology, surgical consultations for acute appendicitis, acute cholecystitis, and small bowel obstruction (SBO) were sampled at 13 hospitals that volunteered to participate in the EGS clinical data registry. Standard NSQIP variables and 16 EGS-specific variables were abstracted with 30-day follow-up. To determine the influence of complications in nonoperative patients, rates of adverse outcomes were identified, and hospitals were ranked by performance with and then without including nonoperative cases. RESULTS: Two thousand ninety-one patients with EGS diagnoses were included, 46.6% with appendicitis, 24.3% with cholecystitis, and 29.1% with SBO. The overall rate of nonoperative management was 27.4%, 6.6% for appendicitis, 16.5% for cholecystitis, and 69.9% for SBO. Despite comprising only 27.4% of patients in the EGS pilot, nonoperative management accounted for 67.7% of deaths, 34.3% of serious morbidities, and 41.8% of hospital readmissions. After adjusting for patient characteristics and hospital diagnosis mix, addition of nonoperative management to hospital performance assessment resulted in 12 of 13 hospitals changing performance rank, with four hospitals changing by three or more positions. CONCLUSION: This study identifies a gap in performance evaluation when nonoperative patients are excluded from surgical quality assessment and demonstrates the feasibility of incorporating nonoperative care into existing surgical quality initiatives. Broadening the scope of hospital performance assessment to include nonoperative management creates an opportunity to improve the care of all surgical patients, not just those who have an operation. LEVEL OF EVIDENCE: Care management, level IV; Epidemiologic, level III.

Measuring satisfaction: factors that drive hospital consumer assessment of healthcare providers and systems survey responses in a trauma and acute care surgery population.

Hospital quality metrics now reflect patient satisfaction and are measured by Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys. Understanding these metrics and drivers will be integral in providing quality care as this process evolves. This study identifies factors associated with patient satisfaction as determined by HCAHPS survey responses in trauma and acute care surgery patients. HCAHPS survey responses from acute care surgery and trauma patients at a single institution between 3/11 and 10/12 were analyzed. Logistic regression determined which responses to individual HCAHPS questions predicted highest hospital score (a rating of 9-10/10). Demographic and clinical variables were also analyzed as predictors of satisfaction. Subgroup analysis for trauma patients was performed. In 70.3 per cent of 182 total survey responses, a 9-10/10 score was given. The strongest predictors of highest hospital ranking were respect from doctors (odds ratio [OR] = 24.5, confidence interval [CI]: 5.44-110.4), doctors listening (OR: 9.33, CI: 3.7-23.5), nurses' listening (OR = 8.65, CI: 3.62-20.64), doctors' explanations (OR = 8.21, CI: 3.5-19.2), and attempts to control pain (OR = 7.71, CI: 3.22-18.46). Clinical factors and outcomes (complications, intensive care unit/hospital length of stay, mechanism of injury, and having an operation) were nonsignificant variables. For trauma patients, Injury Severity Score was inversely related to score (OR = 0.93, CI: 0.87-0.98). Insurance, education, and disposition were also tied to satisfaction, whereas age, gender, and ethnicity were nonsignificant. In conclusion, patient perception of interactions with the healthcare team was most strongly associated with satisfaction. Complications did not negatively influence satisfaction. Insurance status might potentially identify patients at risk of dissatisfaction. Listening to patients, treating them with respect, and explaining the care plan are integral to a positive perception of hospital stay.

Elevated postinjury thrombospondin 1-CD47 triggering aids differentiation of patients' defective inflammatory CD1a+dendritic cells.

A subset of Pts develops dysfunctional MO to inflammatory DC differentiation and immunosuppression. MDDC, a newly described DC subset, is pivotal in initiating antibacterial responses. Endogenous proteins are known to alter MO to MDDC differentiation. In particular, trauma-elevated TSP-1, a protein that is known to affect MO functions, could trigger MDDC differentiation defects. We hypothesized that TSP-1-deranged differentiation of inflammatory CD1a(+)MDDC would negatively alter activation of immune functions, thereby increasing the risk of postinjury infections. Post-trauma increased TSP-1 levels in patients' plasma and MO correlated with two distinct MDDC differentiation dysfunctions: the previously described decreased CD1a(+)DC yields but also, development of an immunoincompetent CD1a(+)MDDC. The Pts' development of Dysf DC correlated to increased infectious complications. TSP-1 triggered its inhibitory receptor, CD47, activating an inhibitory phosphatase, SHP-1. Increased pSHP-1, decreased antigen processing, and depressed T cell stimulation characterized Pt Dysf DC. TSP-1 mimics added during Cnt MDDC differentiation depressed CD1a(+)DC yields but more importantly, also induced defective CD1a(+)MDDC, reproducing Pts' MDDC differentiation dysfunctions. CD47 triggering during Cnt MDDC differentiation increased SHP-1 activation, inhibiting IL-4-induced STAT-6 activation (critical for CD1a(+)MDDC differentiation). SHP-1 inhibition during MDDC differentiation in the presence of TSP-1 mimics restored pSTAT-6 levels and CD1a(+)MDDC immunogenicity. Thus, postinjury-elevated TSP-1 can decrease CD1a(+)DC yields but more critically, also induces SHP-1 hyperactivity, deviating MDDC differentiation to defective CD1a(+) inflammatory MDDCs by inhibiting STAT-6.

Risk factors associated with venous thromboembolism in isolated blunt chest trauma.

Isolated chest trauma is not historically considered to be a major risk factor for venous thromboembolism (VTE). After blunt chest trauma, VTE may be underappreciated because pain, immobility, and inadequate prophylaxis as a result of hemorrhage risk may all increase the risk of VTE. This investigation determines the predictors and rate of VTE after isolated blunt chest trauma. A review of patients admitted to a Level I trauma center with chest trauma between 2007 and 2009 was performed. Demographics, injuries, VTE occurrence, prophylaxis, comorbidities, Injury Severity Score, intensive care unit/hospital length of stay, chest tube, and mechanical ventilation use were recorded. VTE rate was compared between those with isolated chest injury and those with chest injury plus extrathoracic injury. Predictors of VTE were determined with regression analysis. Three hundred seventy patients had isolated chest trauma. The incidence of VTE was 5.4 per cent (n = 20). The VTE rate in those with chest injury plus extrathoracic injury was not significantly different, 4.8 per cent (n = 56 of 1140, P = 0.58). Independent risk factors for VTE after isolated chest trauma were aortic injury (P < 0.01, odds ratio [OR], 47.7), mechanical ventilation (P < 0.01; OR, 6.8), more than seven rib fractures (P < 0.01; OR, 6.1), hemothorax (P < 0.05; OR, 3.9), hypercoagulable state (P < 0.05; OR, 6.3), and age older than 65 years (P < 0.05; OR, 1.03). Patients with the risk factors mentioned are at risk for VTE despite only having thoracic injury and might benefit from more aggressive surveillance and prophylaxis.

Trauma-associated human neutrophil alterations revealed by comparative proteomics profiling.

PURPOSE: Polymorphonuclear neutrophils (PMNs) play an important role in mediating the innate immune response after severe traumatic injury; however, the cellular proteome response to traumatic condition is still largely unknown. EXPERIMENTAL DESIGN: We applied 2D-LC-MS/MS-based shotgun proteomics to perform comparative proteome profiling of human PMNs from severe trauma patients and healthy controls. RESULTS: A total of 197 out of ~2500 proteins (being identified with at least two peptides) were observed with significant abundance changes following the injury. The proteomics data were further compared with transcriptomics data for the same genes obtained from an independent patient cohort. The comparison showed that the protein abundance changes for the majority of proteins were consistent with the mRNA abundance changes in terms of directions of changes. Moreover, increased protein secretion was suggested as one of the mechanisms contributing to the observed discrepancy between protein and mRNA abundance changes. Functional analyses of the altered proteins showed that many of these proteins were involved in immune response, protein biosynthesis, protein transport, NRF2-mediated oxidative stress response, the ubiquitin-proteasome system, and apoptosis pathways. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest increased neutrophil activation and inhibited neutrophil apoptosis in response to trauma. The study not only reveals an overall picture of functional neutrophil response to trauma at the proteome level, but also provides a rich proteomics data resource of trauma-associated changes in the neutrophil that will be valuable for further studies of the functions of individual proteins in PMNs.

Genomic responses in mouse models poorly mimic human inflammatory diseases.

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

Impact of a graduated driver's license law on crashes involving young drivers in New York State.

BACKGROUND: Motor vehicle crashes constitute the greatest risk of injury for young adults. Graduated driver licensing (GDL) laws have been used to reduce the number of injuries and deaths in the young driver population. The New York State GDL law increased supervision of young driver and limited both time-of-day driven and number of passengers. This review examines the impact of a GDL enacted in New York in September 2003. METHODS: A retrospective review of New York State administrative databases from 2001 to 2009 was performed. During this period, a state-wide GDL requirement was implemented. Database review included all reported crashes to the New York State Department of Motor Vehicles by cause and driver age as well as motor fuel tax receipts by the New York State Comptroller's Office. Motor fuel tax receipts and consumption information were used as a proxy for overall miles driven. RESULTS: Before 2003, drivers younger than 18 years were involved in 90 fatal crashes and 10,406 personal-injury (PI) crashes, constituting 4.49% and 3.38% of all fatal and PI crashes in New York State, respectively. By 2009, the number of fatal and PI crashes involving drivers who are younger than 18 years decreased to 44 (2.87%) and 5,246 (2.24%), respectively. Of note, the number of crashes experienced by the age group 18 years to 20 years during this period also declined, from 192 (9.59% of all fatal crashes) and 25,407 (8.24% of all PI crashes) to 135 (8.81%) and 18,114 (7.73%), respectively. Overall numbers of crashes reported remained relatively stable, between 549,000 in 2001 and 520,000 in 2009. Motor fuel use during this period also declined, but to a lesser degree ($552 million to $516 million or 6.6%). CONCLUSION: The use of a GDL law in New York State has shown a large decrease in the number of fatalities and PI crashes involving young drivers. The delay in full driver privileges from the GDL did not result in an increase in fatal or PI crashes in the next older age group.

Trauma patients' elevated tumor necrosis related apoptosis inducing ligand (TRAIL) contributes to increased T cell apoptosis.

Immunosuppression resulting from excessive post-trauma apoptosis of hyperactivated T cells is controversial. TRAIL mediated T cell apoptosis decreases highly activated T cells' responses. Caspase-10, a particular TRAIL target, was increased in trauma patients' T cells with concomitantly elevated plasma TRAIL levels. These patients' T cells developed anergy, implicating increased TRAIL-mediated T cell apoptosis in post-trauma T cell anergy. Control T cells cultured with patients' sera containing high TRAIL levels increased their caspase-10 activity and apoptosis. Stimulated primary T cells are TRAIL apoptosis resistant. Increased plasma thrombospondin-1 and T cell expression of CD47, a thrombospondin-1 receptor, preceded patients' T cell anergy. CD47 triggering of T cells increased their sensitivity to TRAIL-induced apoptosis. Augmentation of T cell TRAIL-induced apoptosis was secondary to CD47 triggered activation of the Src homology-containing phosphatase-1 (SHP-1) and was partially blocked by a SHP-1 inhibitor. We suggest that combined post-trauma CD47 triggering, SHP-1 mediated NFκB suppression, and elevated TRAIL levels increase patients' CD47 expressing T cell apoptosis, thus contributing to subsequent T cell anergy.

Benchmarking outcomes in the critically injured trauma patient and the effect of implementing standard operating procedures.

OBJECTIVE: To determine and compare outcomes with accepted benchmarks in trauma care at 7 academic level I trauma centers in which patients were treated on the basis of a series of standard operating procedures (SOPs). BACKGROUND: Injury remains the leading cause of death for those younger than 45 years. This study describes the baseline patient characteristics and well-defined outcomes of persons hospitalized in the United States for severe blunt trauma. METHODS: We followed 1637 trauma patients from 2003 to 2009 up to 28 hospital days using SOPs developed at the onset of the study. An extensive database on patient and injury characteristics, clinical treatment, and outcomes was created. These data were compared with existing trauma benchmarks. RESULTS: The study patients were critically injured and were in shock. SOP compliance improved 10% to 40% during the study period. Multiple organ failure and mortality rates were 34.8% and 16.7%, respectively. Time to recovery, defined as the time until the patient was free of organ failure for at least 2 consecutive days, was developed as a new outcome measure. There was a reduction in mortality rate in the cohort during the study that cannot be explained by changes in the patient population. CONCLUSIONS: This study provides the current benchmark and the overall positive effect of implementing SOPs for severely injured patients. Over the course of the study, there were improvements in morbidity and mortality rates and increasing compliance with SOPs. Mortality was surprisingly low, given the degree of injury, and improved over the duration of the study, which correlated with improved SOP compliance.

A genomic storm in critically injured humans.

Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected "genomic storm." In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.

An association of ABO non-identical platelet and cryoprecipitate transfusions with altered red cell transfusion needs in surgical patients.

BACKGROUND: Transfusion of ABO non-identical plasma, platelets and cryoprecipitate is routine practice even though adverse effects can occur. METHODS AND MATERIALS: Our hospital changed transfusion practice in 2005 and adopted a policy of providing ABO-identical blood components to all patients when feasible. We retrospectively compared the transfusion requirements, length of stay and in-hospital mortality in relation to ABO blood group in surgical patients who received platelet transfusions before and after this change to determine whether it resulted in any benefit. RESULTS: Prior to the change in practice, both group B and AB patients received more ABO non-identical platelet transfusion (P=0·0004), required significantly greater numbers of red cell transfusions (P=0·04) and had 50% longer hospital stays (P=0·039) than group O and A patients. Following the policy change, there was a trend for fewer red cell transfusions (P=0·17) and length of stay in group B and AB patients than group O or A patients. Overall, the mortality rate per red cell transfusion decreased from 15·2 per 1000 to 11·0 per 1000 (P=0·013). CONCLUSIONS: These results, in the context of previous findings, suggest that providing ABO-identical platelets and cryoprecipitate might be associated with reduction in transfusion requirements and improve outcomes in surgical patients.

Helicopters improve survival in seriously injured patients requiring interfacility transfer for definitive care.

BACKGROUND: Helicopter transport (HT) is frequently used for interfacility transfer of injured patients to a trauma center. The benefits of HT over ground transport (GT) in this setting are unclear. By using a national sample, the objective of this study was to assess whether HT impacted outcomes following interfacility transfer of trauma patients. METHODS: Patients transferred by HT or GT in 2007 were identified using the National Trauma Databank (version 8). Injury severity, resource utilization, and survival to discharge were compared. Stepwise logistic regression was used to determine whether transport modality was a predictor of survival after adjusting for covariates. Regression analysis was repeated in subgroups with Injury Severity Score (ISS)≤15 and ISS>15. RESULTS: There were 74,779 patients transported by helicopter (20%) or ground (80%). Mean ISS was higher in patients transported by helicopter (17±11 vs. 12±9; p<0.01) as was the proportion with ISS>15 (49% vs. 28%; odds ratio [OR], 2.53; 95% confidence interval [CI], 2.43-2.63). Patients transported by helicopter had higher rates of intensive care unit admission (54% vs. 29%; OR, 2.86; 95% CI, 2.75-2.96), had shorter transport time (61±55 minutes vs. 98±71 minutes; p<0.01), and had shorter overall prehospital time (135±86 minutes vs. 202±132 minutes; p<0.01). HT was not a predictor of survival overall or in patients with ISS≤15. In patients with ISS>15, HT was a predictor of survival (OR, 1.09; 95% CI, 1.02-1.17; p=0.01). CONCLUSIONS: Patients transported by helicopter were more severely injured and required more hospital resources than patients transported by ground. HT offered shorter transport and overall prehospital times. For patients with ISS>15, HT was a predictor of survival. These findings should be considered when developing interfacility transfer policies for patients with severe injuries.

Mechanism of injury and special consideration criteria still matter: an evaluation of the National Trauma Triage Protocol.

BACKGROUND: The Centers for Disease Control recently updated the National Trauma Triage Protocol. This field triage algorithm guides emergency medical service providers through four decision steps (physiologic [PHY], anatomic [ANA], mechanism, and special considerations) to identify patients who would benefit from trauma center care. The study objective was to analyze whether trauma center need (TCN) was accurately predicted solely by the PHY and ANA criteria using national data. METHODS: Trauma patients aged 18 years and older were identified in the NTDB (2002-2006). PHY data and ANA injuries (International Classification of Diseases, ninth revision codes) were collected. TCN was defined as Injury Severity Score (ISS)>15, intensive care unit admission, or need for urgent surgery. Test characteristics were calculated according to steps in the triage algorithm. Logistic regression was performed to determine independent association of criteria with outcomes. Receiver operating characteristic curves were constructed for each model. RESULTS: A total of 1,086,764 subjects were identified. Sensitivity of PHY criteria was highest for ISS>15 (42%) and of ANA criteria for urgent surgery (37%). By using PHY and ANA steps, sensitivity was highest (56%) and undertriage lowest (45%) for ISS>15. Undertriage for TCN based on actual treating trauma center level was 11%. CONCLUSION: Current PHY and ANA criteria are highly specific for TCN but result in a high degree of undertriage when applied independently. This implies that additional factors such as mechanism of injury and the special considerations included in the Centers for Disease Control decision algorithm contribute significantly to the effectiveness of this field triage tool.

Helicopters and the civilian trauma system: national utilization patterns demonstrate improved outcomes after traumatic injury.

BACKGROUND: The role of helicopter transport (HT) in civilian trauma care remains controversial. The objective of this study was to compare patient outcomes after transport from the scene of injury by HT and ground transport using a national patient sample. METHODS: Patients transported from the scene of injury by HT or ground transport in 2007 were identified using the National Trauma Databank version 8. Injury severity, utilization of hospital resources, and outcomes were compared. Stepwise logistic regression was used to determine whether transport modality was a predictor of survival or discharge to home after adjusting for covariates. RESULTS: There were 258,387 patients transported by helicopter (16%) or ground (84%). Mean Injury Severity Score was higher in HT patients (15.9 ± 12.3 vs. 10.2 ± 9.5, p < 0.01), as was the percentage of patients with Injury Severity Score >15 (42.6% vs. 20.8%; odds ratio [OR], 2.83; 95% confidence interval [CI], 2.76-2.89). HT patients had higher rates of intensive care unit admission (43.5% vs. 22.9%; OR, 2.58; 95% CI, 2.53-2.64) and mechanical ventilation (20.8% vs. 7.4%; OR, 3.30; 95% CI, 3.21-3.40). HT was a predictor of survival (OR, 1.22; 95% CI, 1.17-1.27) and discharge to home (OR, 1.05; 95% CI, 1.02-1.07) after adjustment for covariates. CONCLUSIONS: Trauma patients transported by helicopter were more severely injured, had longer transport times, and required more hospital resources than those transported by ground. Despite this, HT patients were more likely to survive and were more likely to be discharged home after treatment when compared with those transported by ground. Despite concerns regarding helicopter utilization in the civilian setting, this study shows that HT has merit and impacts outcome.

Ground level falls are associated with significant mortality in elderly patients.

BACKGROUND: Falls from height are considered to be high risk for multisystem injury. Ground-level falls (GLF) are often deemed a low-energy mechanism of injury (MOI) and not a recommended triage criterion for trauma team activation. We hypothesize that in elderly patients, a GLF may represent a high-risk group for injury and concurrent comorbidities that warrant trauma service evaluation and should be triaged appropriately. METHODS: This is a retrospective study based on the National Trauma Data Bank. All patients with MOI consistent with GLF were identified. Demographics, type and severity of injuries, and outcomes were analyzed. RESULTS: We identified 57,302 patients with GLF. The group had 34% men, with mean age of 68 years ± 17 years and injury severity score of 8 ± 5. Overall mortality was 3.2%. There were 32,320 elderly patients (older than 70 years). The mortality in the elderly was significantly higher than the nonelderly (4.4% vs. 1.6%, p < 0.0001). The elderly were more likely to sustain long-bone fracture (54.5% vs. 35.9%, p < 0.0001), pelvic fracture (7.6% vs. 2.4%, p < 0.0001), and intracranial injury (10.6% vs. 8.7%, p<0.0001). Multivariate analysis showed that Glasgow Coma Scale (GCS) score <15 (odds ratio, 4.98) and older than 70 years (odds ratio, 2.75) were significant predictors of mortality inpatients after GLF. CONCLUSIONS: Patients older than 70 years and with GCS score <15 represent a group with significant inhospital mortality.

Clinical microfluidics for neutrophil genomics and proteomics.

Neutrophils have key roles in modulating the immune response. We present a robust methodology for rapidly isolating neutrophils directly from whole blood with 'on-chip' processing for mRNA and protein isolation for genomics and proteomics. We validate this device with an ex vivo stimulation experiment and by comparison with standard bulk isolation methodologies. Last, we implement this tool as part of a near-patient blood processing system within a multi-center clinical study of the immune response to severe trauma and burn injury. The preliminary results from a small cohort of subjects in our study and healthy controls show a unique time-dependent gene expression pattern clearly demonstrating the ability of this tool to discriminate temporal transcriptional events of neutrophils within a clinical setting.

Trauma center designation correlates with functional independence after severe but not moderate traumatic brain injury.

BACKGROUND: The mortality of traumatic brain injury (TBI) continues to decline, emphasizing functional outcomes. Trauma center designation has been linked to survival after TBI, but the impact on functional outcomes is unclear. The objective was to determine whether trauma center designation influenced functional outcomes after moderate and severe TBI. METHODS: Trauma subjects presenting to an American College of Surgeons (ACS) Level I or II trauma center with a Glasgow Coma Score (GCS)

Analysis of factorial time-course microarrays with application to a clinical study of burn injury.

Time-course microarray experiments are capable of capturing dynamic gene expression profiles. It is important to study how these dynamic profiles depend on the multiple factors that characterize the experimental condition under which the time course is observed. Analytic methods are needed to simultaneously handle the time course and factorial structure in the data. We developed a method to evaluate factor effects by pooling information across the time course while accounting for multiple testing and nonnormality of the microarray data. The method effectively extracts gene-specific response features and models their dependency on the experimental factors. Both longitudinal and cross-sectional time-course data can be handled by our approach. The method was used to analyze the impact of age on the temporal gene response to burn injury in a large-scale clinical study. Our analysis reveals that 21% of the genes responsive to burn are age-specific, among which expressions of mitochondria and immunoglobulin genes are differentially perturbed in pediatric and adult patients by burn injury. These new findings in the body's response to burn injury between children and adults support further investigations of therapeutic options targeting specific age groups. The methodology proposed here has been implemented in R package "TANOVA" and submitted to the Comprehensive R Archive Network at http://www.r-project.org/. It is also available for download at http://gluegrant1.stanford.edu/TANOVA/.