Plasma metagenomic sequencing to detect and quantify bacterial DNA in ICU patients suspected of sepsis: A proof-of-principle study.

BACKGROUND: Timely recognition of sepsis and identification of pathogens can improve outcomes in critical care patients but microbial cultures have low accuracy and long turnaround times. In this proof-of-principle study, we describe metagenomic sequencing and analysis of nonhuman DNA in plasma. We hypothesized that quantitative analysis of bacterial DNA (bDNA) levels in plasma can enable detection and monitoring of pathogens. METHODS: We enrolled 30 patients suspected of sepsis in the surgical trauma intensive care unit and collected plasma samples at the time of diagnostic workup for sepsis (baseline), and 7 days and 14 days later. We performed metagenomic sequencing of plasma DNA and used computational classification of sequencing reads to detect and quantify total and pathogen-specific bDNA fraction. To improve assay sensitivity, we developed an enrichment method for bDNA based on size selection for shorter fragment lengths. Differences in bDNA fractions between samples were evaluated using t test and linear mixed-effects model, following log transformation. RESULTS: We analyzed 72 plasma samples from 30 patients. Twenty-seven samples (37.5%) were collected at the time of infection. Median total bDNA fraction was 1.6 times higher in these samples compared with samples with no infection (0.011% and 0.0068%, respectively, p < 0.001). In 17 patients who had active infection at enrollment and at least one follow-up sample collected, total bDNA fractions were higher at baseline compared with the next sample (p < 0.001). Following enrichment, bDNA fractions increased in paired samples by a mean of 16.9-fold. Of 17 samples collected at the time when bacterial pathogens were identified, we detected pathogen-specific DNA in 13 plasma samples (76.5%). CONCLUSION: Bacterial DNA levels in plasma are elevated in critically ill patients with active infection. Pathogen-specific DNA is detectable in plasma, particularly after enrichment using selection for shorter fragments. Serial changes in bDNA levels may be informative of treatment response. LEVEL OF EVIDENCE: Epidemiologic/Prognostic, Level V.

Survival outcomes after prolonged intensive care unit length of stay among trauma patients: The evidence for never giving up.

BACKGROUND: Prolonged intensive care unit length of stay (ICU-LOS) is associated with high mortality for medical and surgical patients. Existing literature suggests that this may not be true for trauma patients. The objective of this study was to determine mortality associated with varying ICU-LOS among trauma patients and to assess for independent predictors of mortality. METHODS: Adult ICU patients (16-64 years) in the National Trauma Data Bank (2007-2012) were categorized by ICU-LOS: 1, 2-9, 10-40, and >40 days (determined based on inflection points). Multivariable logistic regression was used to determine associations with mortality for each. Models accounted for clustering of patients within hospitals and potential confounding associated with: age, gender, race/ethnicity, insurance status, Injury Severity Score, blunt/penetrating injury, Glasgow Coma Scale, in-hospital complications, ventilator dependency, and emergency department disposition. RESULTS: Among the 596,598 patients included, 6.5% (n = 38,812) died. Mortality varied with ICU-LOS: 9.9%, 4.9%, 6.6%, and 9.8%. Age >35 years was a significant predictor of mortality in each. Injury Severity Score and the Glasgow Coma Scale independently predicted mortality in patients with LOS ≤40 days as did penetrating injuries, cardiac arrest, and renal failure. Identification with non-Hispanic black race/ethnicity was also consistently significant. Once patients survived 9 days, mortality steadily decreased, remaining relatively stable until 40 days. Thereafter, trauma patients continued to demonstrate high survival with >87% remaining alive in the ICU >90 days. CONCLUSION: The results reveal that in contrast to expectations of high mortality associated with prolonged ICU-LOS, critically injured adult trauma patients who do not die within the first few days demonstrate an enhanced ability to survive, with an overall survival of >92% and maintained at >85% among extreme ICU-LOS (>40 days). The data advocate the utility of aggressive critical-care support for trauma patients, irrespective of duration of ICU stay.

Beyond incidence: Costs of complications in trauma and what it means for those who pay.

INTRODUCTION: Trauma patients have greater rates of complications than general surgery patients; however, existing surgical pay-for-performance (P4P) guidelines have yet to be adapted for trauma care. To better understand whether current P4P measures are applicable to trauma, this study used nationally representative data to determine the mortality and attributable costs associated with the presence or absence of both Centers for Medicare and Medicaid Services-recognized complications (urinary tract infections, surgical site infections [SSIs], and pneumonia) and other major trauma-related complications. METHODS: Trauma admissions were extracted from the 2008 National Inpatient Sample using primary ICD-9-CM diagnosis codes (range, 800-905, 910-939, 950-958). Patients aged 18-65 years with a duration of hospital stay of >3 days and isolated complications were included. To account for differences in patient factors, coarsened-exact matching was used to create comparable cohorts of adult patients with and without complications. Multivariable regression was then performed within matched groups to determine differences in cost and mortality, controlling for hospital characteristics and wage index. RESULTS: Of 493,372 trauma patients, 78,156 met inclusion criteria, of whom 24.4% had an isolated complication. Consistent with surgical P4P guidelines, SSI, urinary tract infections, and pneumonia had the greatest incidence (8.0%, 5.2%, and 4.4%, respectively); however, mortality in matched patients with complications was greatest for sepsis (odds ratio [OR], 9.76; 95% CI, 3.84-24.80), myocardial infarction (MI; OR, 4.21; 95% CI, 1.70-10.44) and stroke (OR, 3.02; 95% CI, 1.40-6.52). Excess costs associated with a complication were similarly greatest for sepsis (relative cost, 1.84; 95% CI, 1.57-2.17), followed by acute respiratory distress syndrome (ARDS; relative cost, 1.84; 95% CI, 1.7-1.99) and MI (relative cost, 1.73; 95% CI, 1.51-1.99). CONCLUSION: Consideration of attributable costs and mortality suggest that additional complications have a substantial impact among trauma patients, beyond the conditions used in general surgery P4P guidelines. These aspects of trauma should be prioritized to capture the influence of complications in trauma that the incidence of frequent but less costly conditions overlooks.

Increased mortality associated with EMS transport of gunshot wound victims when compared to private vehicle transport.

BACKGROUND: Recent studies suggest that mode of transport affects survival in penetrating trauma patients. We hypothesised that there is wide variation in transport mode for patients with gunshot wounds (GSW) and there may be a mortality difference for GSW patients transported by emergency medical services (EMS) vs. private vehicle (PV). STUDY DESIGN: We studied adult (≥16 years) GSW patients in the National Trauma Data Bank (2007-2010). Level 1 and 2 trauma centres (TC) receiving ≥50 GSW patients per year were included. Proportions of patients arriving by each transport mode for each TC were examined. In-hospital mortality was compared between the two groups, PV and EMS, using multivariable regression analyses. Models were adjusted for patient demographics, injury severity, and were adjusted for clustering by facility. RESULTS: 74,187 GSW patients were treated at 182 TCs. The majority (76%) were transported by EMS while 12.6% were transported by PV. By individual TC, the proportion of patients transported by each category varied widely: EMS (median 78%, interquartile range (IQR) 66-85%), PV (median 11%, IQR 7-17%), or others (median 7%, IQR 2-18%). Unadjusted mortality was significantly different between PV and EMS (2.1% vs. 9.7%, p<0.001). Multivariable analysis demonstrated that EMS transported patients had a greater than twofold odds of dying when compared to PV (OR=2.0, 95% CI 1.73-2.35). CONCLUSIONS: Wide variation exists in transport mode for GSW patients across the United States. Mortality may be higher for GSW patients transported by EMS when compared to private vehicle transport. Further studies should be performed to examine this question.

Disparities in mortality after blunt injury: does insurance type matter?

BACKGROUND: Insurance-related outcomes disparities are well-known, but associations between distinct insurance types and trauma outcomes remain unclear. Prior studies have generally merged various insurance types into broad groups. The purpose of this study is to determine the association of specific insurance types with mortality after blunt injury. MATERIALS AND METHODS: Cases of blunt injury among adults aged 18-64 y with an injury severity score >9 were identified using the 2007-2009 National Trauma Data Bank. Crude mortality was calculated for 10 insurance types. Multivariable logistic regression was employed to determine difference in odds of death between insurance types, controlling for injury severity score, Glasgow Coma Scale motor, mechanism of injury, sex, race, and hypotension. Clustering was used to account for possible inter-facility variations. RESULTS: A total of 312,312 cases met inclusion criteria. Crude mortality ranged from 3.2 to 6.0% by insurance type. Private Insurance, Blue Cross Blue Shield, Workers Compensation, and Medicaid yielded the lowest relative odds of death, while Not Billed and Self Pay yielded the highest. Compared with Private Insurance, odds of death were higher for No Fault (OR 1.25, P = 0.022), Not Billed (OR 1.77, P < 0.001), and Self Pay (OR 1.77, P < 0.001). Odds of death were higher for Medicare (OR 1.52, P < 0.001) and Other Government (OR 1.35, P = 0.049), while odds of death were lower for Medicaid (OR 0.89, P = 0.015). CONCLUSIONS: Significant differences in mortality after blunt injury were seen between insurance types, even among those commonly grouped in other studies. Policymakers may use this information to implement programs to monitor and reduce insurance-related disparities.