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/.

Impact of oxandrolone treatment on acute outcomes after severe burn injury.

Pharmacologic modulation of hypermetabolism clearly benefits children with major burns, however, its role in adult burns remains to be defined. Oxandrolone appears to be a promising anabolic agent although few outcome data are as yet available. We examined whether early oxandrolone treatment in severely burned adults was associated with improved outcomes during acute hospitalization. We evaluated for potential associations between oxandrolone treatment and outcomes in a large cohort of severely burned adults in the context of a multicenter observational study. Patients were dichotomized with respect to oxandrolone treatment, defined as administration within 7 days after admission, with duration of at least 7 days. Acute hospitalization outcomes were compared with univariate and multivariate analyses. One hundred seventeen patients were included in this analysis. Mean patient age was 42.6 years (range, 18-86); 77% were male, with an average TBSA of 44.1%. Baseline and injury characteristics were similar among treatment and nontreatment cohorts. Oxandrolone treatment (N = 59) did not impact length of stay but was associated with a lower mortality rate (P = .01) by univariate analysis. Oxandrolone treatment was independently associated with higher survival by adjusted analyses (P = .02). Examination of early oxandrolone treatment in this cohort of severely burned adults suggests that this therapy is safe and may be associated with improved survival. Further studies are necessary to define the exact mechanisms by which oxandrolone is beneficial during inpatient treatment.

Adverse clinical outcomes associated with elevated blood alcohol levels at the time of burn injury.

Elevated blood alcohol content (BAC) on admission is associated with poorer outcomes, larger burns and more inhalation injury. This study's purpose was to examine the effects of alcohol through a matched case-controlled study, measuring early and extended markers of clinical outcomes. The hypothesis was that patients with an elevated admission BAC would require more resuscitation and have a longer hospital stay. Admissions 16 to 75 years of age with 15 to 75% TBSA and admission BACs were identified. Patients with BAC >30 mg/dl (BAC+, cases) were matched with patients with undetectable BAC (BAC-, controls), according to age, sex, TBSA, inhalation injury and mechanism. Screening identified 258 patients, 146 with admission BACs. Twenty-seven had a BAC > or = 30 mg/dl. There were 24 matched pairs. At 24 hours, BAC+ group had larger acute physiology and chronic health evaluation II scores (23.33 vs 18.75, P < .05), fluid requirements (5.25 vs 3.82 L (cc/kg/TBSA), P < .05), and base deficit (11.15 vs 7.15, P < .05). The duration of mechanical ventilation (14.85 vs 4.23 days, P < .05), intensive care unit length of stay (22.85 vs 9.38, P < .05), hospital length of stay (28.95 vs 15.68, P < .05), and mean hospital charges ($239,507 vs $144,598, P < .05) were increased in the BAC+ patients. Despite matched baseline injury characteristics, elevated BAC was associated with poorer short term and extended clinical outcomes, illustrating the impact of alcohol intoxication on physiologic derangement after burn injury.

Ecthyma gangrenosum following toxic epidermal necrolysis syndrome in a 3-year-old boy-a survivable series of events.

Toxic epidermal necrolysis syndrome (TENS) is a severe but rare skin reaction leading to epidermal desquamation of greater than 30% of the TBSA. It is most commonly precipitated by the administration of medication. Frequent complications of this syndrome include local wound infections, respiratory, mucocutaneous, and ocular complications. Ecthyma gangrenosum (EG) is a rare disease characterized by a milliary seeding of the cutaneous tissue with Gram-negative bacteria; it is most commonly seen in immunocompromised individuals. Here we report a 3-year-old boy who developed EG subsequent to TENS. Although he had a complicated and prolonged hospital course, he survived these series of events. To our knowledge, this is the first reported case of TENS/EG in the pediatric population, and the first report of survivability following these illnesses.

Microbial contamination in burn patients undergoing urgent intubation as part of their early airway management.

Inhalation injuries occur in approximately one third of all major burns and account for a significant number of deaths in burn patients each year. Previous studies have examined ventilator-associated pneumonia in patients with inhalation injury, but no study to date has evaluated the incidence of bacterial contamination of the airways on admission in patients with inhalation injuries. Because pulmonary complications have been found to cause or directly contribute to mortality in as high as 77% of patients, with combined inhalation injury and thermal injury, early detection of community-acquired pneumonia may significantly alter treatment outcomes. The authors conducted a retrospective review of all burn patients with early intubation and inhalation injury admitted between January 1, 2004 and December 31, 2006 who underwent bronchoscopy with bronchoalveolar lavage (BAL) within 24 hours of admission. Seventy-four consecutive patients fulfilled the inclusion criteria. Age, sex, percentage of total body surface area (%TBSA), presence of alcohol, site of intubation, grade of injury, and BAL results were examined. Analysis revealed a patient population that was 67.6% male, with a 42.0 +/- 17.1-year-old mean age, 27.0 +/- 24.7 %TBSA average burn, 1.6 +/- 1.2 inhalation grade, 17.8 +/- 24.4 ventilator days requirement, 27.3 +/- 31.4 days of length of stay, and 21.6% mortality. BAL results were grouped into four categories: 1) No growth, 2) Normal flora, 3) <100,000 colony-forming units (cfu), and 4) >100,000 cfu. By this criteria, 13 patients (17.6%) had no growth, 22 (29.7%) had normal flora, 27 (36.5%) had <100,000 cfu, and 12 (16.2%) had >100,000 cfu on the initial BAL. Therefore, 53% grew pathogenic organisms and 16% had >100,000 cfu on BAL with initial bronchoscopy. The predominant organisms were gram-positive cocci, with Streptococcus viridans found in 15 patients (20%), Staphylococcus aureus in eight (11%), and Streptococcus pneumonia in four (6%). Analysis of the patients with the highest bacterial loads revealed that they were 75% female and had a trend toward an increased ventilator requirement and longer length of stay. Patients with combined thermal and inhalation injury requiring urgent intubation have a high incidence of bacterial bronchial contamination. Inhalation injury creates a damaged tracheobronchial mucosa and early intubation provides a portal for bacterial contamination. Further studies with a larger patient population and randomization to treatment and nontreatment of the BAL culture results may show statistically significant differences in ventilator days, length of stay, and mortality.

A silver-coated antimicrobial barrier dressing used postoperatively on meshed autografts: a dressing comparison study.

In an effort to optimize the management of freshly grafted burn wounds, a silver-coated, low-adherence dressing, Acticoat (Smith & Nephew Inc., Largo, FL), was compared with 5% sulfamylon-soaked Exu-Dry burn wound dressings. Twenty subjects admitted to the Loyola University Medical Center were randomized to either Acticoat dressings or 5% sulfamylon-soaked burn wound dressings. Dressings were applied immediately after grafting in the operating room. Acticoat dressings were left in place for 3 days and then changed every 3 days thereafter. Sulfamylon-soaked dressings were changed at 48 hours and then every day. Subjects continued to have dressing changes on a twice-daily basis to wounds that were not grafted managed. Subjects were assessed for graft take, time to wound healing, and the number of dressings required until healing. Hospital charges and labor costs were retrospectively tabulated, yielding an expense estimate for each group. There were no significant differences between the two groups with respect to age, %TBSA, %TBSA of the grafted test sites, graft take, time to graft healing, or infectious complications. The median number of dressing changes to the test site was significantly less in the Acticoat group (P < .05). The average expense per dressing change was not significantly different between the two groups; however, the average total expense per patient was significantly lower for the Acticoat group because of the reduced number of dressing changes. Acticoat and 5% sulfamylon-soaked burn wound dressings were equivalent with respect to wound healing and infectious complications. The use of Acticoat was found to be a safe alternative to the use of 5% sulfamylon as a postsurgical dressing in this group of subjects. Because of the reduced number of dressing changes, the use of Acticoat was a less expensive alternative to 5% sulfamylon dressing changes in this study.

Standard operating procedures for the clinical management of patients enrolled in a prospective study of Inflammation and the Host Response to Thermal Injury.

As part of the National Institutes of General Medical Sciences (NIGMS)-funded Inflammation and the Host Response to Injury study, participating investigators created a database, a clinical data collection protocol, and web-based case report form. To obtain high-quality clinical endpoints for correlation with genomic data, a uniform approach to patient management between centers was required. Standard operating procedures (SOPs) were generated to minimize variability and promote a uniform standard of patient care. The SOPs are necessary to enable validation of the clinical endpoints to be used for comparison with genomic and proteomic information derived from samples of blood and tissue obtained from thermally injured patients. Participating investigators identified areas of potential practice variation and developed a set of SOPs based on available data and sound clinical principles. In the absence of sufficient clinical data to identify a single management strategy, SOPs were designed to apply the best approach to management without interfering with local standards of care. The data- collection instrument, or case report form, was constructed concurrently with the SOPs. Wherever possible, the case report form was modified to collect data that might resolve controversial management issues. Modifications in management strategies that were necessary for children are delineated as needed. Data queries and site visits were conducted to audit compliance. SOPs for 10 areas of clinical care were developed. The institution of the SOPs required minor changes in clinical practice patterns and personnel training but did not require participating centers to procure new technology or alter the utilization of clinical resources significantly. The SOPs represent current management strategies applied to the study population to reduce variation in patient management. The SOPs are easily adaptable to other burn-related clinical protocols as well as to the routine daily management burn patients.

Medicare's bundling of trauma care codes violates relative value principles.

BACKGROUND: Physician payment by Medicare is based on a Resource-Based Relative Value Scale (RBRVS). The Correct Coding Initiative (CCI) was introduced to counter unbundling by pairing component procedures with more comprehensive procedures. We hypothesized that Medicare's rebundling process ignored relative value concepts. METHODS: CCI tables were downloaded from Medicare's website. Each comprehensive code's Relative Value Units (RVUs) were compared with component RVUs. Trauma, Burn, and Critical Care (TBC) surgeon charges were analyzed to determine whether component services had higher RVUs than the comprehensive charge. RESULTS: 2,990 component CPT codes had total RVUs exceeding the RVUs of their paired comprehensive codes. If the undervalued comprehensive codes had been valued at their highest component's value, the minimum additional revenue would have been $211,600.59 per surgeon per year. CONCLUSION: A relative value scale depends upon equity in value units. Disregarding RVUs when bundling services and procedures results in severe physician underpayment.

A survey of airway and ventilator management strategies in North American pediatric burn units.

A survey was used to gather information regarding airway management patterns in thermally injured children. North American pediatric burn centers listed by the American Burn Association were sent a survey designed to examine patterns of pediatric airway management in children with acute respiratory failure. The sample population means for the number of patients ventilated more than 48 hours and the number of patients ventilated more than 48 hours with inhalation injury were used to separate centers into large and small pediatric burn centers. Small pediatric burn centers had less than 50 patients who were intubated during a 5-year period. A five-point nominal scale was used to facilitate statistical analysis. Twenty-five pediatric burn centers included in the analysis estimated that 11,494 children were admitted during the 5-year period. There was no statistically dominant ventilator mode being used in the setting of acute respiratory failure identified by this survey. Large pediatric burn centers reported more frequent use of cuffed endotracheal tubes and more frequent change from an uncuffed to a cuffed endotracheal tube in patients who were difficult to ventilate because of an excess leak. Large pediatric burn centers reported a higher prevalence of tracheomalacia then small pediatric burn centers. Steroids were used by most centers before extubation in patients with persistent airway edema. No centers reported complications from steroid use. There is lack of clear consensus regarding the application of various ventilator modes in the setting of acute respiratory failure irrespective of center volume. There were divergent of practice patterns between large and small pediatric burn centers regarding the use of cuffed endotracheal tubes and the timing of tracheostomy. There was agreement between large and small pediatric burn centers in tracheostomy use in children older the age of 7 and the use of steroids as an adjunct to extubation in patients with lingering airway edema. Pediatric burn patients may benefit from clinical trials that clarify the advantages and disadvantages of various ventilator modes, the use of cuffed tubes, and the timing of tracheostomy.

Inferior vena cava endograft to control surgically inaccessible hemorrhage.

Open surgical repair of retrohepatic inferior vena cava (IVC) injuries can be technically difficult, usually requiring extensive hepatic mobilization and associated with significant morbidity. We report a case of uncontrolled hemorrhage from the retrohepatic inferior vena cava (IVC), which occurred during attempted resection of a large retroperitoneal leiomyosarcoma, and was successfully managed using an endoluminal stent-graft. This case demonstrates that endoluminal grafts can be successfully applied to control life-threatening hemorrhage arising from lesions in the retrohepatic IVC that are otherwise extremely difficult or inaccessible to direct surgical repair.

Reducing trauma payment denials with computerized collaborative billing.

BACKGROUND: Trauma care demands constant physician availability, resulting in rotational coverage systems. Third-party payors consider separate trauma surgeon bills as originating from the same individual. Trauma surgeons may be unaware of their colleagues' billing history on jointly managed patients. Not all postoperative procedures and evaluation and management services are denied by global surgical package rules. We investigated whether a networked billing program designed to crosscheck for global package coding concerns would reduce payment denials. METHODS: A networked relational database was created for trauma surgeons to enter billable encounters, displaying global periods and operative diagnoses while prompting for postoperative modifiers. Denials were compared for equivalent time periods before and after program initiation. RESULTS: Payment denials fell from 361 to 16 for "bundled" evaluation and management services and from 55 to 13 for bundled postoperative procedures. Time spent on billing decreased and legibility improved. Overall savings totaled $183,404. CONCLUSION: Collaborative billing can improve payments for professional trauma care.