A linked physiologically based pharmacokinetic model for hydroxychloroquine and metabolite desethylhydroxychloroquine in SARS-CoV-2(-)/(+) populations.

Hydroxychloroquine (HCQ) is Food and Drug Administration (FDA)-approved for malaria, systemic and chronic discoid lupus erythematosus, and rheumatoid arthritis. Because HCQ has a proposed multimodal mechanism of action and a well-established safety profile, it is often investigated as a repurposed therapeutic for a range of indications. There is a large degree of uncertainty in HCQ pharmacokinetic (PK) parameters which complicates dose selection when investigating its use in new disease states. Complications with HCQ dose selection emerged as multiple clinical trials investigated HCQ as a potential therapeutic in the early stages of the COVID-19 pandemic. In addition to uncertainty in baseline HCQ PK parameters, it was not clear if disease-related consequences of SARS-CoV-2 infection/COVID-19 would be expected to impact the PK of HCQ and its primary metabolite desethylhydroxychloroquine (DHCQ). To address the question whether SARS-CoV-2 infection/COVID-19 impacted HCQ and DHCQ PK, dried blood spot samples were collected from SARS-CoV-2(-)/(+) participants administered HCQ. When a previously published physiologically based pharmacokinetic (PBPK) model was used to fit the data, the variability in exposure of HCQ and DHCQ was not adequately captured and DHCQ concentrations were overestimated. Improvements to the previous PBPK model were made by incorporating the known range of blood to plasma concentration ratios (B/P) for each compound, adjusting HCQ and DHCQ distribution settings, and optimizing DHCQ clearance. The final PBPK model adequately captured the HCQ and DHCQ concentrations observed in SARS-CoV-2(-)/(+)participants, and incorporating COVID-19-associated changes in cytochrome P450 activity did not further improve model performance for the SARS-CoV-2(+) population.

Validation of the American Association for the Surgery of Trauma Emergency General Surgery Grading System for Colorectal Resection: An EAST Multicenter Study.

BACKGROUND: The American Association for the Surgery of Trauma (AAST) has developed a grading system for emergency general surgery (EGS) conditions. We sought to validate the AAST EGS grades for patients undergoing urgent/emergent colorectal resection. METHODS: Patients enrolled in the "Eastern Association for the Surgery of Trauma Multicenter Colorectal Resection in EGS-to anastomose or not to anastomose" study undergoing urgent/emergent surgery for obstruction, ischemia, or diverticulitis were included. Baseline demographics, comorbidity severity as defined by Charlson comorbidity index (CCI), procedure type, and AAST grade were prospectively collected. Outcomes included length of stay (LOS) in-hospital mortality, and surgical complications (superficial/deep/organ-space surgical site infection, anastomotic leak, stoma complication, fascial dehiscence, and need for further intervention). Multivariable logistic regression models were used to describe outcomes and risk factors for surgical complication or mortality. RESULTS: There were 367 patients, with a mean (± SD) age of 62 ± 15 years. 39% were women. The median interquartile range (IQR) CCI was 4 (2-6). Overall, the pathologies encompassed the following AAST EGS grades: I (17, 5%), II (54, 15%), III (115, 31%), IV (95, 26%), and V (86, 23%). Management included laparoscopic (24, 7%), open (319, 87%), and laparoscopy converted to laparotomy (24, 6%). Higher AAST grade was associated with laparotomy (P = .01). The median LOS was 13 days (8-22). At least 1 surgical complication occurred in 33% of patients and the mortality rate was 14%. Development of at least 1 surgical complication, need for unplanned intervention, mortality, and increased LOS were associated with increasing AAST severity grade. On multivariable analysis, factors predictive of in-hospital mortality included AAST organ grade, CCI, and preoperative vasopressor use (odds ratio (OR) 1.9, 1.6, 3.1, respectively). The American Association for the Surgery of Trauma emergency general surgery grade was also associated with the development of at least 1 surgical complication (OR 2.5), while CCI, preoperative vasopressor use, respiratory failure, and pneumoperitoneum were not. CONCLUSION: The American Association for the Surgery of Trauma emergency general surgery grading systems display construct validity for mortality and surgical complications after urgent/emergent colorectal resection. These results support incorporation of AAST EGS grades for quality benchmarking and surgical outcomes research.

Comparison of Racial, Ethnic, and Geographic Location Diversity of Participants Enrolled in Clinic-Based vs 2 Remote COVID-19 Clinical Trials.

Importance: Racial and ethnic diversity among study participants is associated with improved generalizability of clinical trial results and may address inequities in evidence that informs public health strategies. Novel strategies are needed for equitable access and recruitment of diverse clinical trial populations. Objective: To investigate demographic and geographical location data for participants in 2 remote COVID-19 clinical trials with online recruitment and compare with those of a contemporaneous clinic-based COVID-19 study. Design, Setting, and Participants: This cohort study was conducted using data from 3 completed, prospective randomized clinical trials conducted at the same time: 2 remotely conducted studies (the Early Treatment Study and Hydroxychloroquine COVID-19 Postexposure Prophylaxis [PEP] Study) and 1 clinic-based study of convalescent plasma (the Expanded Access to Convalescent Plasma for the Treatment of Patients With COVID-19 study). Data were collected from March to August 2020 with 1 to 28 days of participant follow-up. All studies had clinical sites in Seattle, Washington; the 2 remote trials also had collaborating sites in New York, New York; Syracuse, New York; Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; New Orleans, Louisiana; and Los Angeles, California. Two remote trials with inclusive social media strategies enrolled 929 participants with recent SARS-CoV-2 exposure (Hydroxychloroquine COVID-19 PEP Trial) and 231 participants with COVID-19 infection (Early Treatment Study); the clinic-based Expanded Access to Convalescent Plasma for the Treatment of Patients With COVID-19 study enrolled 250 participants with recent COVID-19 infection. Data were analyzed from April to August 2021. Interventions: Remote trials used inclusive social media strategies and clinician referral for recruitment and telehealth, courier deliveries, and self-collected nasal swabs for remotely conducted study visits. For the clinic-based study, participants were recruited via clinician referral and attended in-person visits. Main Outcomes and Measures: Google Analytics data were used to measure online participant engagement and recruitment. Participant demographics and geographical location data from remote trials were pooled and compared with those of the clinic-based study. Statistical comparison of demographic data was limited to participants with COVID infections (ie, those in the remotely conducted Early Treatment Study vs those in the clinic-based study) to improve accuracy of comparison given that the Hydroxychloroquine COVID-19 PEP Trial enrolled participants with COVID-19 exposures and thus had different enrollment criteria. Results: A total of 1410 participants were included. Among 1160 participants in remote trials and 250 participants in the clinic-based trial, the mean (range) age of participants was 39 (18-80) years vs 50 (19-79) years and 676 individuals (58.3%) vs 131 individuals (52.4%) reported female sex. The Early Treatment Study with inclusive social media strategies enrolled 231 participants in 41 US states with increased rates of racial, ethnic, and geographic diversity compared with participants in the clinic-based study. Among 228 participants in the remotely conducted Early Treatment Study with race data vs participants in the clinic-based study, 39 individuals (17.1%) vs 1 individual (0.4%) identified as Alaska Native or American Indian, 11 individuals (4.8%) vs 22 individuals (8.8%) identified as Asian, 26 individuals (11.4%) vs 4 individuals (1.6%) identified as Black, 3 individuals (1.3%) vs 1 individual identified as Native Hawaiian or Pacific Islander, 117 individuals (51.3%) vs 214 individuals (85.6%) identified as White, and 32 individuals (14.0%) vs 8 individuals (3.2%) identified as other race (P < .001). Among 230 individuals in the Early Treatment Study vs 236 individuals in the clinic-based trial with ethnicity data, 71 individuals (30.9%) vs 11 individuals (4.7%) identified as Hispanic or Latinx (P<.001). There were 29 individuals in the Early Treatment Study with nonurban residences (ie, rural, small town, or peri-urban; 12.6%) vs 6 of 248 individuals in the clinic-based trial with residence data (2.4%) (P < .001). In remote trial online recruitment, the highest engagement was with advertisements on social media platforms; among 125 147 unique users with age demographics who clicked on online recruitment advertisements, 84 188 individuals (67.3%) engaged via Facebook. Conclusions and Relevance: These findings suggest that remote clinical trials with online advertising may be considered as a strategy to improve diversity among clinical trial participants.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition Is Associated With Individual Exposure but Not Community-Level Transmission.

BACKGROUND: Transmission rates after exposure to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive individual within households and healthcare settings varies significantly between studies. Variability in the extent of exposure and community SARS-CoV-2 incidence may contribute to differences in observed rates. METHODS: We examined risk factors for SARS-CoV-2 infection in a randomized controlled trial of hydroxychloroquine as postexposure prophylaxis. Study procedures included standardized questionnaires at enrollment and daily self-collection of midturbinate swabs for SARS-CoV-2 polymerase chain reaction testing. County-level incidence was modeled using federally sourced data. Relative risks and 95% confidence intervals were calculated using modified Poisson regression. RESULTS: Eighty-six of 567 (15.2%) household/social contacts and 12 of 122 (9.8%) healthcare worker contacts acquired SARS-CoV-2 infection. Exposure to 2 suspected index cases (vs 1) significantly increased risk for both household/social contacts (relative risk [RR], 1.86) and healthcare workers (RR, 8.18). Increased contact time also increased risk for healthcare workers (3-12 hours: RR, 7.82, >12 hours: RR, 11.81, vs ≤2 hours), but not for household/social contacts. County incidence did not impact risk. CONCLUSIONS: In our study, increased exposure to SARS-CoV-2 within household or healthcare settings led to higher risk of infection, but elevated community incidence did not. This reinforces the importance of interventions to decrease transmission in close contact settings.

Detection and Kinetics of Subgenomic Severe Acute Respiratory Syndrome Coronavirus 2 RNA Viral Load in Longitudinal Diagnostic RNA-Positive Samples.

While detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by diagnostic reverse-transcription polymerase chain reaction (RT-PCR) is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNAs) that are the product of viral replication may more accurately identify replication. We characterized the diagnostic RNA and sgRNA detection by RT-PCR from nasal swab samples collected daily by participants in postexposure prophylaxis or treatment studies for SARS-CoV-2. Among 1932 RT-PCR-positive swab samples with sgRNA tests, 40% (767) had detectable sgRNA. Above a diagnostic RNA viral load (VL) threshold of 5.1 log10 copies/mL, 96% of samples had detectable sgRNA with VLs that followed a linear trend. The trajectories of diagnostic RNA and sgRNA VLs differed, with 80% peaking on the same day but duration of sgRNA detection being shorter (8 vs 14 days). With a large sample of daily swab samples we provide comparative sgRNA kinetics and a diagnostic RNA threshold that correlates with replicating virus independent of symptoms or duration of illness.

Traumatized attendings - When the doctor has the disease.

BACKGROUND: This study aims to compare PTSD prevalence between seven medical specialties and to identify potential risk factors for PTSD. METHODS: A cross-sectional national survey of attending physicians (n = 2216) was conducted and screened for PTSD using the Primary Care PTSD Screen. Stepwise multivariable regression analysis with backward elimination identified potential risk factors. RESULTS: Overall prevalence of PTSD was 14% and ranged from 7% to 18% for psychiatrists and OBGYNs, respectively (p = 0.004). Six potential risk factors for PTSD included: emotional exhaustion, job dissatisfaction, lack of autonomy, working >60 h per week, poor camaraderie, and female gender (p < 0.05). CONCLUSIONS: The prevalence of PTSD in attending physicians is more than double that of the general population. Higher risk specialties include OBGYN and general surgery. Specialty-specific interventions targeted at reducing physician burnout and improving the physician work-environment are needed to improve physician wellness and reduce PTSD.

Avoiding Cribari gridlock 2: The standardized triage assessment tool outperforms the Cribari matrix method in 38 adult and pediatric trauma centers.

OBJECTIVES: The Cribari Matrix Method (CMM) is the current standard to identify over/undertriage but requires manual trauma triage reviews to address its inadequacies. The Standardized Triage Assessment Tool (STAT) partially emulates triage review by combining CMM with the Need For Trauma Intervention, an indicator of major trauma. This study aimed to validate STAT in a multicenter sample. METHODS: Thirty-eight adult and pediatric US trauma centers submitted data for 97,282 encounters. Mixed models estimated the effects of overtriage and undertriage versus appropriate triage on the odds of complication, odds of discharge to a continuing care facility, and differences in length of stay for both CMM and STAT. Significance was assessed at p <0.005. RESULTS: Overtriage (53.49% vs. 30.79%) and undertriage (17.19% vs. 3.55%) rates were notably lower with STAT than with CMM. CMM and STAT had significant associations with all outcomes, with overtriages demonstrating lower injury burdens and undertriages showing higher injury burdens than appropriately triaged patients. STAT indicated significantly stronger associations with outcomes than CMM, except in odds of discharge to continuing care facility among patients who received a full trauma team activation where STAT and CMM were similar. CONCLUSIONS: This multicenter study strongly indicates STAT safely and accurately flags fewer cases for triage reviews, thereby reducing the subjectivity introduced by manual triage determinations. This may enable better refinement of activation criteria and reduced workload.

Colorectal resection in emergency general surgery: An EAST multicenter trial.

OBJECTIVE: Evidence comparing stoma creation (STM) versus anastomosis after urgent or emergent colorectal resection is limited. This study examined outcomes after colorectal resection in emergency general surgery patients. METHODS: This was an Eastern Association for the Surgery of Trauma-sponsored prospective observational multicenter study of patients undergoing urgent/emergent colorectal resection. Twenty-one centers enrolled patients for 11 months. Preoperative, intraoperative, and postoperative variables were recorded. χ, Mann-Whitney U test, and multivariable logistic regression models were used to describe outcomes and risk factors for surgical complication/mortality. RESULTS: A total of 439 patients were enrolled (ANST, 184; STM, 255). The median (interquartile range) age was 62 (53-71) years, and the median Charlson Comorbidity Index (CCI) was 4 (1-6). The most common indication for surgery was diverticulitis (28%). Stoma group was older (64 vs. 58 years, p < 0.001), had a higher CCI, and were more likely to be immunosuppressed. Preoperatively, STM patients were more likely to be intubated (57 vs. 15, p < 0.001), on vasopressors (61 vs. 13, p < 0.001), have pneumoperitoneum (131 vs. 41, p < 0.001) or fecal contamination (114 vs. 33, p < 0.001), and had a higher incidence of elevated lactate (149 vs. 67, p < 0.001). Overall mortality was 13%, which was higher in STM patients (18% vs. 8%, p = 0.02). Surgical complications were more common in STM patients (35% vs. 25%, p = 0.02). On multivariable analysis, management with an open abdomen, intraoperative blood transfusion, and larger hospital size were associated with development of a surgical complication, while CCI, preoperative vasopressor use, steroid use, open abdomen, and intraoperative blood transfusion were independently associated with mortality. CONCLUSION: This study highlights a tendency to perform fecal diversion in patients who are acutely ill at presentation. There is a higher morbidity and mortality rate in STM patients. Independent predictors of mortality include CCI, preoperative vasopressor use, steroid use, open abdomen, and intraoperative blood transfusion. Following adjustment by clinical factors, method of colon management was not associated with surgical complications or mortality. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Predictors of retained hemothorax in trauma: Results of an Eastern Association for the Surgery of Trauma multi-institutional trial.

BACKGROUND: The natural history of traumatic hemothorax (HTX) remains unclear. We aimed to describe outcomes of HTX following tube thoracostomy drainage and to delineate factors that predict progression to a retained hemothorax (RH). We hypothesized that initial large-volume HTX predicts the development of an RH. METHODS: We conducted a prospective, observational, multi-institutional study of adult trauma patients diagnosed with an HTX identified on computed tomography (CT) scan with volumes calculated at time of diagnosis. All patients were managed with tube thoracostomy drainage within 24 hours of presentation. Retained hemothorax was defined as blood-density fluid identified on follow-up CT scan or need for additional intervention after initial tube thoracostomy placement for HTX. RESULTS: A total of 369 patients who presented with an HTX initially managed with tube thoracostomy drainage were enrolled from 17 trauma centers. Retained hemothorax was identified in 106 patients (28.7%). Patients with RH had a larger median (interquartile range) HTX volume on initial CT compared with no RH (191 [48-431] mL vs. 88 [35-245] mL, p = 0.013) and were more likely to be older with a higher burden of thoracic injury. After controlling for significant differences between groups, RH was independently associated with a larger HTX on presentation, with a 15% increase in risk of RH for each additional 100 mL of HTX on initial CT imaging (odds ratio, 1.15; 95% confidence interval, 1.08-1.21; p < 0.001). Patients with an RH also had higher rates of pneumonia and longer hospital length of stay than those with successful initial management. Retained hemothorax was also associated with worse functional outcomes at discharge and first outpatient follow-up. CONCLUSION: Larger initial HTX volumes are independently associated with RH, and unsuccessful initial management with tube thoracostomy is associated with worse patient outcomes. Future studies should use this experience to assess a range of options for reducing the risk of unsuccessful initial management. LEVEL OF EVIDENCE: Therapeutic/care management study, level III.

Evaluation of a water-soluble contrast protocol for small bowel obstruction: A southwestern surgical congress multicenter trial.

Differentiation between SBO that will resolve with supportive measures and those requiring surgery remains challenging. WSC administration may be diagnostic and therapeutic. The purpose of this study was to evaluate use of a SBO protocol using WSC challenge. A protocol was implemented at five tertiary care centers. Demographics, prior surgical history, time to operation, complications, and LOS were analyzed. 283 patients were admitted with SBO; 13% underwent immediate laparotomy; these patients had a median LOS of 7.5 days. The remaining 245 were candidates for WSC challenge. Of those, 80% received contrast. 139 (71%) had contrast passage to the colon. LOS in these patients was 4 days. Sixty-five patients (29%) failed contrast passage within 24 h and underwent surgery. LOS was 9 days. 8% of patients in whom contrast passage was observed at 24 h nevertheless subsequently underwent surgery. 4% of patients who failed WSC challenge did not proceed to surgery. Our multicenter trial revealed that implementation of a WSC protocol may facilitate early recognition of partial from complete obstruction.

Traumatized Residents - It's Not Surgery. It's Medicine.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been shown to be more common in surgical residents than the general population. This may be due to the rigors of a surgical residency. This study aims to compare the prevalence of screening positive for PTSD (PTSD+) among 7 medical specialties. Further, we intend to identify independent risk factors for the development of PTSD. METHODS: A cross-sectional national survey of residents (n = 1904) was conducted from September 2016 to May 2017. Residents were screened for PTSD. Traumatic stressors were identified in those who reported symptoms of PTSD. Potential risk factors for PTSD were assessed using multivariate regression analysis with stepwise backward elimination against 30 demographic, occupational, psychological, work-life balance, and work-environment variables. RESULTS: Residents from anesthesiology (n = 180), emergency medicine (n = 222), internal medicine (n = 473), general surgery (n = 464), obstetrics and gynecology (n = 226), psychiatry (n = 208), and surgical subspecialties (n = 131) were surveyed. No statistical difference was found in the prevalence of PTSD between specialties. Prevalence ranged from 14% to 23%. Eight independent risk factors for the development of PTSD+ were identified: higher postgraduate year, female gender, public embarrassment, emotional exhaustion, feeling unhealthy, job dissatisfaction, hostile hospital culture, and unsafe patient load. CONCLUSIONS: The prevalence of PTSD in surgery residents was not statistically different when compared to those in other medical specialties. However, the overall prevalence of PTSD (20%) remains more than 3 times that of the general population. Overall, 8 risk factors for PTSD were identified. These risk factors varied by specialty. This may highlight the unique challenges of training in each discipline. Specialty specific interventions to improve resident wellness should be emphasized in the development of our young physicians.

Trends in Surgeon Wellness (Take a Sad Song and Make It Better): A Comparison of Surgical Residents, Fellows, and Attendings.

We aim to investigate the prevalence of posttraumatic stress disorder (PTSD), physician burnout (PBO), and work-life balance (WLB) among surgical residents, fellows, and attendings to illustrate the trends in surgeon wellness. A cross-sectional national survey of surgical residents, fellows, and attendings was conducted screening for PTSD, PBO, and WLB. The prevalence of screening positive for PTSD was more than two times that of the general population at all levels of experience, and more than half have an unhealthy WLB. The prevalence of PTSD, PBO, and unhealthy WLB declined with increasing level of experience (P < 0.001). One deviation in this trend was a lower prevalence of PBO among surgical fellows compared with residents and attendings (P < 0.001). Surgeon wellness improved with increasing level of experience. The incorporation of wellness programs into surgical residencies is essential to the professional development of young surgeons to cultivate healthy lasting habits for a well-balanced career and life.

Rethinking the definition of major trauma: The need for trauma intervention outperforms Injury Severity Score and Revised Trauma Score in 38 adult and pediatric trauma centers.

BACKGROUND: Patients' trauma burdens are a combination of anatomic damage, physiologic derangement, and the resultant depletion of reserve. Typically, Injury Severity Score (ISS) >15 defines major anatomic injury and Revised Trauma Score (RTS) <7.84 defines major physiologic derangement, but there is no standard definition for reserve. The Need For Trauma Intervention (NFTI) identifies severely depleted reserves (NFTI+) with emergent interventions and/or early mortality. We hypothesized NFTI would have stronger associations with outcomes and better model fit than ISS and RTS. METHODS: Thirty-eight adult and pediatric U.S. trauma centers submitted data for 88,488 encounters. Mixed models tested ISS greater than 15, RTS less than 7.84, and NFTI's associations with complications, survivors' discharge to continuing care, and survivors' length of stay (LOS). RESULTS: The NFTI had stronger associations with complications and LOS than ISS and RTS (odds ratios [99.5% confidence interval]: NFTI = 9.44 [8.46-10.53]; ISS = 5.94 [5.36-6.60], RTS = 4.79 [4.29-5.34]; LOS incidence rate ratios (99.5% confidence interval): NFTI = 3.15 [3.08-3.22], ISS = 2.87 [2.80-2.94], RTS = 2.37 [2.30-2.45]). NFTI was more strongly associated with continuing care discharge but not significantly more than ISS (relative risk [99.5% confidence interval]: NFTI = 2.59 [2.52-2.66], ISS = 2.51 [2.44-2.59], RTS = 2.37 [2.28-2.46]). Cross-validation revealed that in all cases NFTI's model provided a much better fit than ISS greater than 15 or RTS less than 7.84. CONCLUSION: In this multicenter study, NFTI had better model fit and stronger associations with the outcomes than ISS and RTS. By determining depletion of reserve via resource consumption, NFTI+ may be a better definition of major trauma than the standard definitions of ISS greater than 15 and RTS less than 7.84. Using NFTI may improve retrospective triage monitoring and statistical risk adjustments. LEVEL OF EVIDENCE: Prognostic, level IV.

Infection after penetrating brain injury-An Eastern Association for the Surgery of Trauma multicenter study oral presentation at the 32nd annual meeting of the Eastern Association for the Surgery of Trauma, January 15-19, 2019, in Austin, Texas.

BACKGROUND: Fatality rates following penetrating traumatic brain injury (pTBI) are extremely high and survivors are often left with significant disability. Infection following pTBI is associated with worse morbidity. The modern rates of central nervous system infections (INF) in civilian survivors are unknown. This study sought to determine the rate of and risk factors for INF following pTBI and to determine the impact of antibiotic prophylaxis. METHODS: Seventeen institutions submitted adult patients with pTBI and survival of more than 72 hours from 2006 to 2016. Patients were stratified by the presence or absence of infection and the use or omission of prophylactic antibiotics. Study was powered at 85% to detect a difference in infection rate of 5%. Primary endpoint was the impact of prophylactic antibiotics on INF. Mantel-Haenszel χ and Wilcoxon's rank-sum tests were used to compare categorical and nonparametric variables. Significance greater than p = 0.2 was included in a logistic regression adjusted for center. RESULTS: Seven hundred sixty-three patients with pTBI were identified over 11 years. 7% (n = 51) of patients developed an INF. Sixty-six percent of INF patients received prophylactic antibiotics. Sixty-two percent of all patients received one dose or greater of prophylactic antibiotics and 50% of patients received extended antibiotics. Degree of dural penetration did not appear to impact the incidence of INF (p = 0.8) nor did trajectory through the oropharynx (p = 0.18). Controlling for other variables, there was no statistically significant difference in INF with the use of prophylactic antibiotics (p = 0.5). Infection was higher in patients with intracerebral pressure monitors (4% vs. 12%; p = <0.001) and in patients with surgical intervention (10% vs. 3%; p < 0.001). CONCLUSION: There is no reduction in INF with prophylactic antibiotics in pTBI. Surgical intervention and invasive intracerebral pressure monitoring appear to be risk factors for INF regardless of prophylactic use. LEVEL OF EVIDENCE: Therapeutic, level IV.

The Crossroads of Posttraumatic Stress Disorder and Physician Burnout: A National Review of United States Trauma and Nontrauma Surgeons.

Posttraumatic stress disorder (PTSD) among trauma surgeons is three times that of the general population, and physician burnout (PBO) among surgeons is rising. Given that PTSD and PBO are both stress-based syndromes, we aim to identify the prevalence and risk factors for PTSD among trauma and nontrauma surgeons, and determine if a relationship exists. A cross-sectional survey of surgeons was conducted between September 2016 and May 2017. Respondents were screened for PTSD and PBO. Traumatic stressors were identified, and 20 potential risk factors were assessed. The respondents (n = 1026) were grouped into trauma (n = 350) and nontrauma (n = 676). Between the cohorts, there was no significant difference in prevalence of screening positive for PTSD (17% vs 15%) or PBO (30% vs 25%). A relationship was found between PTSD and PBO (P < 0.001). The most common traumatic stressor was overwhelming work responsibilities. Potential risk factors for PTSD differed, but overlapping risk factors included hospital culture, hospital support, and salary (P < 0.05). Our findings of an association between PTSD and PBO is concerning. Interventions to reduce rates of PTSD should target changing the existing culture of surgery, improving hospital support, and ensuring equitable pay.

The why and how our trauma patients die: A prospective Multicenter Western Trauma Association study.

BACKGROUND: Historically, hemorrhage has been attributed as the leading cause (40%) of early death. However, a rigorous, real-time classification of the cause of death (COD) has not been performed. This study sought to prospectively adjudicate and classify COD to determine the epidemiology of trauma mortality. METHODS: Eighteen trauma centers prospectively enrolled all adult trauma patients at the time of death during December 2015 to August 2017. Immediately following death, attending providers adjudicated the primary and contributing secondary COD using standardized definitions. Data were confirmed by autopsies, if performed. RESULTS: One thousand five hundred thirty-six patients were enrolled with a median age of 55 years (interquartile range, 32-75 years), 74.5% were male. Penetrating mechanism (n = 412) patients were younger (32 vs. 64, p < 0.0001) and more likely to be male (86.7% vs. 69.9%, p < 0.0001). Falls were the most common mechanism of injury (26.6%), with gunshot wounds second (24.3%). The most common overall primary COD was traumatic brain injury (TBI) (45%), followed by exsanguination (23%). Traumatic brain injury was nonsurvivable in 82.2% of cases. Blunt patients were more likely to have TBI (47.8% vs. 37.4%, p < 0.0001) and penetrating patients exsanguination (51.7% vs. 12.5%, p < 0.0001) as the primary COD. Exsanguination was the predominant prehospital (44.7%) and early COD (39.1%) with TBI as the most common later. Penetrating mechanism patients died earlier with 80.1% on day 0 (vs. 38.5%, p < 0.0001). Most deaths were deemed disease-related (69.3%), rather than by limitation of further aggressive care (30.7%). Hemorrhage was a contributing cause to 38.8% of deaths that occurred due to withdrawal of care. CONCLUSION: Exsanguination remains the predominant early primary COD with TBI accounting for most deaths at later time points. Timing and primary COD vary significantly by mechanism. Contemporaneous adjudication of COD is essential to elucidate the true understanding of patient outcome, center performance, and future research. LEVEL OF EVIDENCE: Epidemiologic, level II.

The southwestern surgical congress multi-center trial on suspected common duct stones.

BACKGROUND: Choledocholithiasis is present in up to 15% of cholecystectomy patients. Treatment can be surgical, endoscopic, or via interventional radiology. We hypothesized significant heterogeneity between hospitals exists in the approach to suspected common duct stones. METHODS: A retrospective review of patients that had a preoperative MRCP, endoscopic ultrasound, endoscopic retrograde cholangiopancreatogram (ERCP), or intra-operative cholangiogram was performed. Comparisons were by Wilcoxon-Mann-Whitney tests with significance of p < 0.05 for paired variables and p < 0.017 for multiple comparisons. RESULTS: Twelve participating institutions identified 1263 patients (409 men and 854 women) with a median age of 49 years (IQR: 31-94). Liver function tests (LFT's) were elevated in 939 patients (75%), median bilirubin level 1.75 mg/dl (IQ: 0.8-3.7 mg/dl) and median common duct size 7 mm (IQR 5-10 mm). The most common initial procedure was cholecystectomy with IOC at seven institutions, endoscopy at four and MRCP at one. CONCLUSION: Significant variation exists within the surgical community regarding suspected common duct stones. These results underscore the need for a protocol for common duct stones to minimize multiple, redundant interventions.

When Minutes Fly by: What Is the True "Golden Hour" for Air Care?

Air transport was developed to hasten patient transport based on the "golden hour" belief that delayed care leads to poorer outcome. The primary aim of our study was to identify the critical inflection point of increased nonsurvivors on total prehospital time. This was a multicenter review of adult trauma patients transported by air between November 2014 and August 2015. Primary outcome of interest was all-cause inhospital mortality. Total helicopter emergency medical services times of nonsurvivors were plotted to visualize the distribution of prehospital time. Of 636 patients included, 71 per cent were male and 86 per cent suffered blunt trauma. Among nonsurvivors, mortality doubled once total helicopter emergency medical services time exceeded 30 minutes (P < 0.001). Nonsurvivors presented with significantly lower median [interquartile range (IQR)] Glasgow Coma Score compared with survivors [3 (3-13) vs 15 (12-15), respectively; P < 0.001] as well as a significantly higher median (IQR) Injury Severity Score [26 (19-41) vs 12 (5-22); P < 0.001], increased incidence of penetrating mechanism of injury [21 vs 8%; P = 0.002], and higher median (IQR) shock index [0.84 (0.63-1.06) vs 0.71 (0.6-0.87); P = 0.023]. We identified an inflection point of doubling in mortality after 30 minutes. This suggests a possible threshold effect between time and mortality in severely injured patients. Revised field criteria for determining which injured patients would most benefit from helicopter transport are needed.