Matthew B. Singer

Influence of resident involvement on trauma care outcomes

HYPOTHESIS Discrepancies exist in complications and outcomes at teaching trauma centers (TTCs) vs nonteaching TCs (NTCs). DESIGN Retrospective review of the National Trauma Data Bank research data sets (January 1, 2007, through December 31, 2008). SETTING Level II TCs. PATIENTS Patients at TTCs were compared with patients at NTCs using demographic, clinical, and outcome data. Regression modeling was used to adjust for confounding factors to determine the effect of house staff presence on failure to rescue, defined as mortality after an in-house complication. MAIN OUTCOME MEASURES The primary outcome measures were major complications, in-hospital mortality, and failure to rescue. RESULTS In total, 162 687 patients were available for analysis, 36 713 of whom (22.6%) were admitted to NTCs. Compared with patients admitted to TTCs, patients admitted to NTCs were older (52.8 vs 50.7 years), had more severe head injuries (8.3% vs 7.8%), and were more likely to undergo immediate operation (15.0% vs 13.2%) or ICU admission (28.1% vs 22.8%) (P < .01 for all). The mean Injury Severity Scores were similar between the groups (10.1 for patients admitted to NTCs vs 10.4 for patients admitted to TTCs, P < .01). Compared with patients admitted to TTCs, patients admitted to NTCs experienced fewer complications (adjusted odds ratio [aOR], 0.63; P < .01), had a lower adjusted mortality rate (aOR, 0.87; P = .01), and were less likely to experience failure to rescue (aOR, 0.81; P = .01). CONCLUSIONS Admission to level II TTCs is associated with an increased risk for major complications and a higher rate of failure to rescue compared with admission to level II NTCs. Further investigation of the differences in care provided by level II TTCs vs NTCs may identify areas for improvement in residency training and processes of care.

Vitamin D in a Northern Canadian First Nation Population: Dietary Intake, Serum Concentrations and Functional Gene Polymorphisms

The wide spectrum of vitamin D activity has focused attention on its potential role in the elevated burden of disease in a northern Canadian First Nations (Dené) cohort. Vitamin D insufficiency, and gene polymorphisms in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) have been implicated in susceptibility to infectious and chronic diseases. The objectives of this study were to determine the contribution of vitamin D from food, and measure the serum concentrations of 25-hydroxyvitamin D3 (25-OHD3) and VDBP in Dené participants. Single nucleotide polymorphisms (SNPs) associated with the dysregulation of the innate immune response were typed and counted. Potential correlations between the SNPs and serum concentrations of 25-OHD3 and VDBP were evaluated. Venous blood was collected in summer and winter over a one-year period and analyzed for 25-OHD3 and VDBP concentrations (N = 46). A questionnaire was administered to determine the amount of dietary vitamin D consumed. Sixty-one percent and 30% of the participants had 25-OHD3 serum concentrations <75 nmol/L in the winter and summer respectively. Mean vitamin D binding protein concentrations were within the normal range in the winter but below normal in the summer. VDBP and VDR gene polymorphisms affect the bioavailability and regulation of 25-OHD3. The Dené had a high frequency of the VDBP D432E-G allele (71%) and the Gc1 genotype (90%), associated with high concentrations of VDBP and a high binding affinity to 25-OHD3. The Dené had a high frequency of VDR Fok1-f allele (82%), which has been associated with a down-regulated Th1 immune response. VDBP and VDR polymorphisms, and low winter 25-OHD3 serum concentrations may be risk factors for infectious diseases and chronic conditions related to the dysregulation of the vitamin D pathway.

Gender impacts mortality after traumatic brain injury in teenagers

BACKGROUND Gender may influence outcomes following traumatic brain injury (TBI) although the mechanism is unknown. Animal TBI studies suggest that gender differences in endogenous hormone production may be the source. Limited retrospective clinical studies on gender present varied conclusions. Pediatric patients represent a unique population as pubescent children experience up-regulation of endogenous hormones that varies dramatically by gender. Younger children do not have these hormonal differences. The aim of this study was to compare pubescent and prepubescent females with males after isolated TBI to identify independent predictors of mortality. METHODS We performed a retrospective review of the National Trauma Data Bank Research Data Sets from 2007 and 2008 looking at all blunt trauma patients 18 years or younger who required hospital admission after isolated, moderate-to-severe TBI, defined as head Abbreviated Injury Scale (AIS) score 3 or greater. We excluded all individuals with AIS score of 3 or greater for any other region to limit the confounding effect of comorbidities. Based on the median age of menarche, we defined two age groups as follows: prepubescent (0–12 years) and pubescent (>12 years). Analysis was performed to compare trauma profiles and outcomes between groups. Our primary outcome measure was in-hospital mortality. RESULTS A total of 20,280 patients met inclusion criteria; 10,135 were prepubescent, and 10,145 were pubescent. Overall mortality was 6.9%, and lower mortality was noted among prepubescent patients compared with pubescent (5.2% vs. 8.6%, p < 0.0001). Although female gender did not predict reduced mortality in the prepubescent cohort (adjusted odds ratio, 1.05; 95% confidence interval, 0.85–1.30; p = 0.63), female gender was associated with reduced mortality in the pubescent (adjusted odds ratio, 0.78; 95% confidence interval, 0.65–0.93; p = 0.007). CONCLUSION In contrast to prepubescent female gender, pubescent female gender predicts reduced mortality following isolated, moderate-to-severe TBI. Endogenous hormonal differences may be a contributing factor and require further investigation. LEVEL OF EVIDENCE Prognostic study, level III.

Insurance-and race-related disparities decrease in elderly trauma patients

BACKGROUND Little focus is on health care disparities in the elderly, a population largely covered by public insurance. We characterized insurance type and race in elderly trauma patients to determine if lack of insurance or minority status predict increased mortality. METHODS The National Trauma Data Bank (version 7.0) was queried for all adult blunt trauma patients. We divided patients into two cohorts (15–64 or ≥65 years) based on age for universal Medicare eligibility. Our primary outcome measure was in-hospital mortality. Multiple logistic regression was used to control for confounding variables. RESULTS A total of 541,471 patients met inclusion criteria. Among younger patients, the most common insurance type was private (41.0%), with 26.9% uninsured. In contrast, the most common insurance type among older patients was Medicare (64.6%), with 6.0% uninsured. Within the younger cohort, private insurance (adjusted odds ratio [AOR], 0.6; p < 0.01) and other insurance (AOR, 0.8; p < 0.01) predicted reduced mortality, while Medicare predicted similar mortality (AOR, 1.1; p = 0.18) compared with no insurance. Black race (AOR, 1.4; p < 0.01) and Hispanic ethnicity (AOR, 1.4; p < 0.01) predicted higher mortality compared with white race. Within the older cohort, no insurance predicted similar mortality as Medicare (AOR, 1.0; p = 0.43), private insurance (AOR, 1.0; p = 0.51), and other insurance (AOR, 1.0; p = 0.71). Hispanic ethnicity predicted increased mortality (AOR, 1.4; p < 0.01), while Asian race was protective (AOR, 0.7; p = 0.01) compared with white race. CONCLUSION Elderly trauma patients present primarily with Medicare, while younger trauma patients are mostly privately insured; elderly patients are four times more likely to be insured. Disparities caused by lack of insurance and minority race are reduced in elderly trauma patients. LEVEL OF EVIDENCE Epidemiologic/prognostic study, level III.

Impact of prehospital hypothermia on transfusion requirements and outcomes.

BACKGROUND Prehospital hypothermia (PH) is known to increase mortality following traumatic injury. PH relationship with transfusion requirements has not been documented. The purpose of this investigation was to analyze the impact of PH on blood product requirements and subsequent outcomes. METHODS The Los Angeles County Trauma System Database was queried for all patients admitted between 2005 and 2009. Demographics, physiologic parameters, and transfusion requirements were obtained and dichotomized by admission temperatures with a core temperature of less than 36.5°C considered hypothermic. Multivariate analysis was performed to determine factors contributing to transfusion requirements and to derive adjusted odds ratios (AORs) for mortality and rates of adult respiratory distress syndrome and pneumonia. RESULTS A total of 21,023 patients were analyzed in our study with 44.6% presenting with PH. Hypothermic patients required 26% more fluid resuscitation (p < 0.001) in the emergency department and 17% more total blood products (p < 0.001) than those who were admitted with a normal temperature. There was a trend toward an increase in emergency department transfusion (8%, p = 0.06). PH was independently associated with the need for a transfusion (AOR, 1.1; p = 0.047), increased mortality (AOR, 2.0; p < 0.01), as well as incidence of adult respiratory distress syndrome (AOR, 1.8; p < 0.05) and pneumonia (AOR, 2.6; p < 0.01). CONCLUSION PH is associated with increased transfusion and fluid requirements and subsequently worse outcomes. Interventions that correct hypothermia may decrease transfusion requirements and improve outcomes. Prospective studies investigating correction of hypothermia in trauma patients are warranted. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level III.

Long-term effect of trauma splenectomy on blood glucose

BACKGROUND Increasing evidence suggests that the spleen harbors stem cells that act as precursors to insulin-producing pancreas cells. Additionally, small studies with short-term follow-up associate splenectomy with increased rates of diabetes mellitus. The purpose of this study was to analyze the long-term effect of trauma splenectomy on blood glucose. MATERIALS AND METHODS Patients were included if a blood glucose level was measured more than 5 y after trauma splenectomy or laparotomy with bowel repair. Mean blood glucose level was then compared between the two groups. RESULTS During the 10-y study period 61 patients underwent trauma splenectomy and 50 survived until discharge. In comparison, 229 patients underwent trauma laparotomy and bowel repair and 207 survived until discharge. Nine splenectomy patients compared with 12 control patients had, blood glucose measured at least 5 y after initial trauma. Mean follow-up period was not significantly different between groups (splenectomy 82.8 ± 17.6 mo versus control 96.0 ± 44.3 mo, P = 0.41). In the splenectomy cohort mean glucose level was significantly higher compared with the control (114 ± 34 mg/dL versus 90 ± 13 mg/dL, P = 0.04), as was the number of patients with recorded blood glucose level greater than 130 mg/dL (4 patient versus 0 patients P = 0.02). One new diagnosis of diabetes mellitus was noted only in the trauma splenectomy cohort. CONCLUSIONS This small study suggests that trauma splenectomy may be associated with hyperglycemia at long-term follow-up.

Elevated admission systolic blood pressure after blunt trauma predicts delayed pneumonia and mortality.

BACKGROUND Although avoiding hypotension is a primary focus after trauma, elevated systolic blood pressure (SBP) is frequently disregarded. The purpose of this study was to determine the association between elevated admission SBP and delayed outcomes after trauma. METHODS The Los Angeles County Trauma System Database was queried for all patients between 2003 and 2008 with blunt injuries who survived for at least 2 days after admission. Demographics and outcomes (pneumonia and mortality) were compared at various admission SBP subgroups (≥160 mm Hg, ≥170 mm Hg, ≥180 mm Hg, ≥190 mm Hg, ≥200 mm Hg, ≥210 mm Hg, and ≥220 mm Hg). Patients with moderate-to-severe traumatic brain injury (TBI), defined as head Abbreviated Injury Score ≥3, were then identified and compared with those without using multivariable logistic regression. RESULTS Data accessed from 14,382 blunt trauma admissions identified 2,601 patients with moderate-to-severe TBI (TBI group) and 11,781 without moderate-to-severe TBI (non-TBI group) who were hospitalized ≥2 days. Overall mortality was 2.9%, 7.1% for TBI patients, and 1.9% for non-TBI patients. Overall pneumonia was 4.6%, 9.5% for TBI patients, and 3.6% for non-TBI patients. Regression modeling determined SBP ≥160 mm Hg was a significant predictor of mortality in TBI patients (adjusted odds ratio [AOR], 1.59; confidence interval [CI], 1.10-2.29; p = 0.03) and non-TBI patients (AOR, 1.47; CI, 1.14-1.90; p = 0.003). Similarly, SBP ≥160 mm Hg was a significant predictor for increased pneumonia in TBI patients (AOR, 1.79; CI, 1.30-2.46; p = 0.0004), compared with non-TBI patients (AOR, 1.28; CI, 0.97-1.69; p = 0.08). CONCLUSIONS In blunt trauma patients with or without TBI, elevated admission SBP was associated with worse delayed outcomes. Prospective research is necessary to determine whether algorithms that manage elevated blood pressure after trauma, especially after TBI, affect mortality or pneumonia.

Reactive Oxygen Species-Activated Nanoprodrug of Ibuprofen for Targeting Traumatic Brain Injury in Mice

Traumatic brain injury (TBI) is an enormous public health problem, with 1.7 million new cases of TBI recorded annually by the Centers for Disease Control. However, TBI has proven to be an extremely challenging condition to treat. Here, we apply a nanoprodrug strategy in a mouse model of TBI. The novel nanoprodrug contains a derivative of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen in an emulsion with the antioxidant α-tocopherol. The ibuprofen derivative, Ibu2TEG, contains a tetra ethylene glycol (TEG) spacer consisting of biodegradable ester bonds. The biodegradable ester bonds ensure that the prodrug molecules break down hydrolytically or enzymatically. The drug is labeled with the fluorescent reporter Cy5.5 using nonbiodegradable bonds to 1-octadecanethiol, allowing us to reliably track its accumulation in the brain after TBI. We delivered a moderate injury using a highly reproducible mouse model of closed-skull controlled cortical impact to the parietal region of the cortex, followed by an injection of the nanoprodrug at a dose of 0.2 mg per mouse. The blood brain barrier is known to exhibit increased permeability at the site of injury. We tested for accumulation of the fluorescent drug particles at the site of injury using confocal and bioluminescence imaging of whole brains and brain slices 36 hours after administration. We demonstrated that the drug does accumulate preferentially in the region of injured tissue, likely due to an enhanced permeability and retention (EPR) phenomenon. The use of a nanoprodrug approach to deliver therapeutics in TBI represents a promising potential therapeutic modality.

Trauma center level impacts survival for cirrhotic trauma patients

BACKGROUND Cirrhosis is known to be a significant risk factor for morbidity and mortality following trauma such that its presence is a requirement for trauma center transfer. The impact of trauma center level on post-injury survival in cirrhotic patients has not been well studied. METHODS The National Trauma Databank (version 7) was used to identify patients admitted with cirrhosis as a preexisting comorbidity. Patients who were dead on arrival, died in the emergency department, or had missing trauma center information were excluded. Our primary outcome measure was overall mortality stratified by admission trauma center level. Logistic regression analysis was used to derive adjusted mortality results. RESULTS A total of 3,395 patients met inclusion criteria (0.16% of all National Trauma Databank patients). Patients admitted to a Level I center were more likely to be younger and minorities, experience penetrating injuries, and require immediate operative intervention despite similar Injury Severity Scores (ISS). Overall mortality was lower at Level I centers compared with other centers (10.3% vs. 14.0%, p = 0.001). After logistic regression, Level I centers were associated with significantly lower mortality compared with non–Level I centers (adjusted odds ratio, 0.70; 95% confidence interval, 0.53–0.89; p = 0.004). CONCLUSION The mortality for cirrhotic patients admitted to a Level I trauma center was significantly less compared with those admitted to non–Level I centers. The etiology of this improved outcome needs to be identified and transmitted to non–Level I centers. LEVEL OF EVIDENCE Epidemiologic study, level III.

Dietary intake of vitamin D in a northern Canadian Dene´ First Nation community

Background Increased awareness of the wide spectrum of activity of vitamin D has focused interest on its role in the health of Canadas Aboriginal peoples, who bear a high burden of both infectious and chronic disease. Cutaneous vitamin D synthesis is limited at northern latitudes, and the transition from nutrient-dense traditional to nutrient-poor market foods has left many Canadian Aboriginal populations food insecure and nutritionally vulnerable. Objective The study was undertaken to determine the level of dietary vitamin D in a northern Canadian Aboriginal (Dené) community and to determine the primary food sources of vitamin D. Design Cross-sectional study. Methods Dietary vitamin D intakes of 46 adult Dené men and women were assessed using a food frequency questionnaire and compared across age, gender, season and body mass index. The adequacy of dietary vitamin D intake was assessed using the 2007 Adequate Intake (AI) and the 2011 Recommended Dietary Allowance (RDA) values for Dietary Reference Intake (DRI). Results Mean daily vitamin D intake was 271.4 IU in winter and 298.3 IU in summer. Forty percent and 47.8% of participants met the vitamin D 1997 AI values in winter and summer, respectively; this dropped to 11.1 and 13.0% in winter and summer using 2011 RDA values. Supplements, milk, and local fish were positively associated with adequate vitamin D intake. Milk and local fish were the major dietary sources of vitamin D. Conclusions Dietary intake of vitamin D in the study population was low. Only 2 food sources, fluid milk and fish, provided the majority of dietary vitamin D. Addressing low vitamin D intake in this population requires action aimed at food insecurity present in northern Aboriginal populations.