Neutrophil extracellular traps induced by chemotherapy inhibit tumor growth in murine models of colorectal cancer.

Neutrophil extracellular traps (NETs), a web-like structure of cytosolic and granule proteins assembled on decondensed chromatin, kill pathogens and cause tissue damage in diseases. Whether NETs can kill cancer cells is unexplored. Here, we report that a combination of glutaminase inhibitor CB-839 and 5-FU inhibited the growth of PIK3CA-mutant colorectal cancers (CRCs) in xenograft, syngeneic, and genetically engineered mouse models in part through NETs. Disruption of NETs by either DNase I treatment or depletion of neutrophils in CRCs attenuated the efficacy of the drug combination. Moreover, NETs were present in tumor biopsies from patients treated with the drug combination in a phase II clinical trial. Increased NET levels in tumors were associated with longer progression-free survival. Mechanistically, the drug combination induced the expression of IL-8 preferentially in PIK3CA-mutant CRCs to attract neutrophils into the tumors. Further, the drug combination increased the levels of ROS in neutrophils, thereby inducing NETs. Cathepsin G (CTSG), a serine protease localized in NETs, entered CRC cells through the RAGE cell surface protein. The internalized CTSG cleaved 14-3-3 proteins, released BAX, and triggered apoptosis in CRC cells. Thus, our studies illuminate a previously unrecognized mechanism by which chemotherapy-induced NETs kill cancer cells.

Genomic Predictors Associated With Exceptional Response to Systemic Therapy in Advanced Pancreatic Cancer.

INTRODUCTION: Exceptional response to therapy is rare in patients with advanced pancreatic cancer. This study explored potential genomic differences between typical and exceptional responses that could confer more favorable biology. METHODS: We included exceptional responders and controls with advanced pancreatic cancer from Cleveland Clinic from April 2013 to August 2017. Exceptional responders were defined as patients with an overall survival of more than 18 months for metastatic disease and more than 24 months for locally advanced disease. Clinical data were obtained, and next-generation sequencing was performed. Statistical analyses comparing the 2 groups were performed using descriptive statistics, the Kaplan-Meier method, and the log-rank test. RESULTS: The study comprised 4 exceptional responders and 6 controls. Both groups were well balanced in age, sex, race, and treatment regimens. Exceptional responders had significantly fewer nonsynonymous mutations than controls (2.25 vs 5.17; P = .014). A mutation count of less than 3 was associated with significantly better progression-free survival (17.2 vs 2.3 months; P = .002) and overall survival (29.4 vs 4.6 months; P = .013). Tumor mutational burden did not differ between exceptional responders and controls (4.88 vs 5.70 mut/Mb; P = .39). CONCLUSION: A lower number of nonsynonymous mutations may correlate with exceptional outcomes in patients with pancreatic cancer. These findings should encourage future studies into genomic signatures of exceptional response.

Targeted Use of Sustainable Aviation Fuel to Maximize Climate Benefits.

Sustainable aviation fuel (SAF) can reduce aviation's CO2 and non-CO2 impacts. We quantify the change in contrail properties and climate forcing in the North Atlantic resulting from different blending ratios of SAF and demonstrate that intelligently allocating the limited SAF supply could multiply its overall climate benefit by factors of 9-15. A fleetwide adoption of 100% SAF increases contrail occurrence (+5%), but lower nonvolatile particle emissions (-52%) reduce the annual mean contrail net radiative forcing (-44%), adding to climate gains from reduced life cycle CO2 emissions. However, in the short term, SAF supply will be constrained. SAF blended at a 1% ratio and uniformly distributed to all transatlantic flights would reduce both the annual contrail energy forcing (EFcontrail) and the total energy forcing (EFtotal, contrails + change in CO2 life cycle emissions) by ∼0.6%. Instead, targeting the same quantity of SAF at a 50% blend ratio to ∼2% of flights responsible for the most highly warming contrails reduces EFcontrail and EFtotal by ∼10 and ∼6%, respectively. Acknowledging forecasting uncertainties, SAF blended at lower ratios (10%) and distributed to more flights (∼9%) still reduces EFcontrail (∼5%) and EFtotal (∼3%). Both strategies deploy SAF on flights with engine particle emissions exceeding 1012 m-1, at night-time, and in winter.

A Phase 1 Study of Concurrent Neoadjuvant Pembrolizumab Plus Chemoradiation Followed by Consolidation Pembrolizumab in Patients With Resectable Stage IIIA NSCLC.

Introduction: Evidence supports the addition of immunotherapy to definitive chemoradiation for unresectable stage IIIA NSCLC. Adding pembrolizumab to neoadjuvant chemoradiation in patients with resectable stage IIIA NSCLC requires study for safety and feasibility. Methods: Patients with resectable stage IIIA NSCLC received neoadjuvant cisplatin, etoposide, and pembrolizumab concurrently with thoracic radiotherapy of 45 Gy in 25 fractions. Patients without progression underwent resection followed by 6 months of consolidation pembrolizumab. Safety and feasibility were defined as less than or equal to 30% grade 3 or higher pulmonary toxicity or any grade 4 or 5 nonhematologic toxicity. A total of 10 patients were to be enrolled initially. If less than or equal to two patients had events, another 10 were to be enrolled. Results: The study closed after enrolling nine patients. The median age was 66 (range: 49-76) years. A total of 67% were female. Median follow-up was 38.3 months. Serious adverse events occurred in seven patients, including two grade 5 events: one sudden cardiac arrest in the neoadjuvant phase and one fatal pneumocystis pneumonia after resection. Eight patients were assessable for response. The overall response rate was 67%. Six underwent complete resection. Four achieved pathologic complete response, whereas one additional patient had complete nodal clearance. Median progression-free survival has not been reached. The 3-year overall survival was 64%. Conclusions: Adding pembrolizumab to neoadjuvant concurrent cisplatin, etoposide, and radiotherapy in resectable stage IIIA NSCLC resulted in an encouraging pathologic complete response rate. Higher-than-expected toxicities necessitated trial closure after meeting the rule for infeasibility. The relationship of grade 5 events to the addition of pembrolizumab is unclear.

The impact of alcohol use and withdrawal on trauma outcomes: A case control study.

INTRODUCTION: Many patients admitted to hospitals with acute trauma have positive serum blood alcohol levels. Published associations between alcohol use, injury patterns, and outcomes are inconsistent. We sought to further delineate the impact of alcohol use and alcohol withdrawal on hospital outcomes amongst acute trauma patients. METHODS: We performed a retrospective analysis of adult trauma patients hospitalized at a suburban level 1 trauma center between January 2015 and September 2019 with a blood alcohol level measurement and/or classification as alcohol withdrawal syndrome (AWS). Patients were separated into three groups: BAL ≤10 mg/dL, BAL >10 mg/dL, and alcohol withdrawal syndrome (AWS). RESULTS: Overall, 3896 patients met study criteria with 75.6% BAL ≤10, 23.2% BAL >10, and 1.2% AWS. The median age was significantly different (BAL ≤ 10: 59 years, BAL > 10: 44 years, AWS: 53.5 years). Alcohol withdrawal was experienced by patients with BAL ≤10 and BAL >10. While injury severity and mortality were similar across all 3 groups, AWS patients experienced significantly longer hospital and ICU lengths of stay, unplanned ICU admission, need for mechanical ventilation, and higher rates of complications. Patients with AWS had high rates of acute neuropsychiatric symptoms, complicating their management. CONCLUSIONS: Except for mortality, AWS patients experienced worse outcomes. The complex nature of alcohol withdrawal cases, including the possibility of developing AWS despite a negative BAL on admission, emphasizes the need for early assessment for alcohol withdrawal risk factors and input from specialists.

An Evolving Clinical Need: Discordant Oxygenation Measurements of Intubated COVID-19 Patients.

Since the first appearance of the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) earlier this year, clinicians and researchers alike have been faced with dynamic, daily challenges of recognizing, understanding, and treating the coronavirus disease 2019 (COVID-19) due to SARS-CoV-2. Those who are moderately to severely ill with COVID-19 are likely to develop acute hypoxemic respiratory failure and require administration of supplemental oxygen. Assessing the need to initiate or titrate oxygen therapy is largely dependent on evaluating the patient's existing blood oxygenation status, either by direct arterial blood sampling or by transcutaneous arterial oxygen saturation monitoring, also referred to as pulse oximetry. While the sampling of arterial blood for measurement of dissolved gases provides a direct measurement, it is technically challenging to obtain, is painful to the patient, and can be time and resource intensive. Pulse oximetry allows for non-invasive, real-time, continuous monitoring of the percent of hemoglobin molecules that are saturated with oxygen, and usually closely predicts the arterial oxygen content. As such, it was particularly concerning when patients with severe COVID-19 requiring endotracheal intubation and mechanical ventilation within one of our intensive care units were observed to have significant discordance between their predicted arterial oxygen content via pulse oximetry and their actual measured oxygen content. We offer these preliminary observations along with our speculative causes as a timely, urgent clinical need. In the setting of a COVID-19 intensive care unit, entering a patient room to obtain a fresh arterial blood gas sample not only takes exponentially longer to do given the time required for donning and doffing of personal protective equipment (PPE), it involves the consumption of already sparce PPE, and it increases the risk of viral exposure to the nurse, physician, or respiratory therapist entering the room to obtain the sample. As such, technology similar to pulse oximetry which can be applied to a patients finger, and then continuously monitored from outside the room is essential in preventing a particularly dangerous situation of unrealized hypoxia in this critically-ill patient population. Additionally, it would appear that conventional two-wavelength pulse oximetry may not accurately predict the arterial oxygen content of blood in these patients. This discordance of oxygenation measurements poses a critical concern in the evaluation and management of the acute hypoxemic respiratory failure seen in patients with COVID-19.

Clinical impact of rapid influenza PCR in the adult emergency department on patient management, ED length of stay, and nosocomial infection rate.

BACKGROUND: Seasonal influenza causes significant morbidity and mortality and incurs large economic costs. Influenza like illness is a common presenting concern to Emergency Departments (ED), and optimizing the diagnosis of influenza in the ED has the potential to positively affect patient management and outcomes. Therapeutic guidelines have been established to identify which patients most likely will benefit from anti-viral therapy. OBJECTIVES: We assessed the impact of rapid influenza PCR testing of ED patients on laboratory result generation and patient management across two influenza seasons. METHODS: A pre-post study was performed following a multifaceted clinical redesign including the implementation of rapid influenza PCR at three diverse EDs comparing the 2016-2017 and 2017-2018 influenza seasons. Testing parameters including turn-around-time and diagnostic efficiency were measured along with rates of bed transfers, hospital-acquired (HA) influenza, and ED length of stay (LOS). RESULTS: More testing of discharged patients was performed in the post-intervention period, but influenza rates were the same. Identification of influenza-positive patients was significantly faster, and there was faster and more appropriate prescription of anti-influenza medication. There were no differences in bed transfer rates or HA influenza, but ED LOS was reduced by 74 minutes following clinical redesign. CONCLUSIONS: Multifaceted clinical redesign to optimize ED workflow incorporating rapid influenza PCR testing can be successfully deployed across different ED environments. Adoption of rapid influenza PCR can streamline testing and improve antiviral stewardship and ED workflow including reducing LOS. Further study is needed to determine if other outcomes including bed transfers and rates of HA influenza can be affected by improved testing practices.

Integrated Fragility Hip Fracture Program: A Model for High Quality Care.

BACKGROUND: Hip fractures are a significant cause of morbidity and mortality among elderly patients. Coordinated multidisciplinary care is required to optimize medical outcomes. OBJECTIVE: To determine the effect of the implementation of standardized, evidence-based protocols on clinical outcomes and mortality in patients with fragility hip fractures. INTERVENTIONS: A multidisciplinary group was convened to define best practices in fragility hip fracture care and implement a fragility hip fracture clinical protocol at Yale-New Haven Hospital. Clinical outcomes in 2015, prior to program initiation, were compared with 2018, after the program was well established. MAIN OUTCOMES AND MEASURES: Measured outcomes included 30-day mortality, blood transfusion utilization, adverse effects of drugs, venous thromboembolic complications, sepsis, myocardial infarction, mechanical surgical fixation complications during the index admission, length of stay, 30-day readmission, unexpected return to the operating room (OR) and time to the OR. RESULTS: The implementation of the Integrated Fragility Hip Fracture Program was associated with significant reductions in 30-day mortality from 8.0% in 2015 to 2.8% in 2018 (P = .001). Significant reductions were also seen in use of blood transfusions (46.6% to 28.1%; P < .001), adverse effects of drugs (4.0% to 0%; P < .001), length of stay (5.12 to 4.47 days; P = .004), unexpected return to the OR (5.1% to 0%; P < .001), and time to the OR <24 hours (41.8% to 55.0%, P = .001). CONCLUSIONS: An Integrated Fragility Hip Fracture Program using multidisciplinary care, physician and nursing engagement, evidence-based protocols, data tracking with feedback, and accountability can reduce mortality and improve clinical outcomes in patients with hip fractures.

TabSINT: open-source mobile software for distributed studies of hearing.

Objective: The recent emphasis on outcomes-based medical research has motivated a need for technology that allows researchers and clinicians to reach a larger and more diverse subject population for recruitment and testing.Design: This article reports on open-source mobile software (TabSINT) that enables researchers to administer customised hearing tests and questionnaires on tablets located across multiple sites. Researchers create and modify test protocols using text-based templates and deploy it to the tablets via a cloud-based repository or USB-computer connection. Results are exported locally to the tablet SD card and can also be automatically posted to a cloud-based database.Results: Between 2014 and 2019, TabSINT collected 25,000+ test results using more than 200+ unique test protocols for researchers located worldwide.Conclusions:TabSINT is a powerful software system with the potential to greatly enhance research across multiple disciplines by enabling access to subject cohorts in remote and disparate locations. Released open-source, this software is available to researchers across the world to use and adapt to their specific needs. Researchers with engineering resources can contribute to the repository to extend the capability and robustness of this software.

Electronic Health Record-Assisted Reflex Urine Culture Testing Improves Emergency Department Diagnostic Efficiency.

The authors evaluated the effectiveness of an electronic health record (EHR)-based reflex urine culture testing algorithm on urine test utilization and diagnostic yield in the emergency department (ED). The study implemented a reflex urine culture order with EHR decision support. The primary outcome was the number of urine culture orders per 100 ED visits. The secondary outcome was the diagnostic yield of urine cultures. After the intervention, the mean number of urine cultures ordered was 5.95 fewer per 100 ED visits (9.3 vs 15.2), and there was a decrease in normal, or negative, cultures by 2.42 per 100 ED visits. There also was a statistically significant decrease in urine culture utilization and an increase in the positive proportion of cultures. Simple EHR clinical decision-support tools along with reflex urine culture testing can significantly reduce the number of urine cultures performed while improving diagnostic yield in the ED.

Impact of Urgent Care Openings on Emergency Department Visits to Two Academic Medical Centers Within an Integrated Health Care System.

STUDY OBJECTIVE: The effect of urgent cares on local emergency department (ED) patient volumes is presently unknown. In this paper, we aimed to assess the change in low-acuity ED utilization at 2 academic medical centers in relation to patient proximity to an affiliated urgent care. METHODS: We created a geospatial database of ED visits occurring between April 2016 and March 2018 to 2 academic medical centers in an integrated health care system, geocoded by patient home address. We used logistic regression to characterize the relationship between the likelihood of patients visiting the ED for a low-acuity condition, based on ED discharge diagnosis, and urgent care center proximity, defined as living within 1 mile of an open urgent care center, for each of the academic medical centers in the system, adjusting for spatial, temporal, and patient factors. RESULTS: We identified a statistically significant reduction in the likelihood of ED visits for low-acuity conditions by patients living within 1 mile of an urgent care center at 1 of the 2 academic medical centers, with an adjusted odds ratio of 0.87 (95% confidence interval 0.78 to 0.98). There was, however, no statistically significant reduction at the other affiliated academic medical center. Further analysis showed a statistically significant temporal relationship between time since urgent care center opening and likelihood of a low-acuity ED visit, with approximately a 1% decrease in the odds of a low-acuity visit for every month that the proximal urgent care center was open (odds ratio 0.99; 95% confidence interval 0.985 to 0.997). CONCLUSION: Although further research is needed to assess the factors driving urgent care centers' variable influence on low-acuity ED use, these findings suggest that in similar settings urgent care center development may be an effective strategy for health systems hoping to decrease ED utilization for low-acuity conditions at academic medical centers.

Development of an Emergency Department Trigger Tool Using a Systematic Search and Modified Delphi Process.

OBJECTIVE: This study aimed to develop an emergency department (ED) trigger tool to improve the identification of adverse events in the ED and that can be used to direct patient safety and quality improvement. This work describes the first step toward the development of an ED all-cause harm measurement tool by experts in the field. METHODS: We identified a multidisciplinary group of emergency medicine safety experts from whom we solicited candidate triggers. We then conducted a modified Delphi process consisting of 4 stages as follows: (1) a systematic literature search and review, including an independent oversampling of review for inclusion, (2) solicitation of empiric triggers from participants, (3) a Web-based survey ranking triggers on specific performance constructs, and (4) a final in-person meeting to arrive at consensus triggers for testing. Results of each step were shared with participants between each stage. RESULTS: Among an initial 804 unique articles found using our search criteria, we identified 94 that were suitable for further review. Interrater reliability was high (κ = 0.80). Review of these articles yielded 56 candidate triggers. These were supplemented by 58 participant-submitted triggers yielding a total of 114 candidate triggers that were shared with team members electronically along with their definitions. Team members then voted on each measure via a Web-based survey, ranking triggers on their face validity, utility for quality improvement, and fidelity (sensitivity/specificity). Participants were also provided the ability to flag any trigger about which they had questions or they felt merited further discussion at the in-person meeting. Triggers were ranked by combining the first 2 categories (face validity and utility), and information on fidelity was reviewed for decision making at the in-person meeting. Seven redundant triggers were eliminated. At an in-person meeting including representatives from all facilities, we presented the 50 top-ranked triggers as well as those that were flagged on the survey by 2 or more participants. We reviewed each trigger individually, identifying 41 triggers about which there was a clear agreement for inclusion. Of the seven additional triggers that required subsequent voting via e-mail, 5 were adopted, arriving at a total of 46 consensus-derived triggers. CONCLUSIONS: Our modified Delphi process resulted in the identification of 46 final triggers for the detection of adverse events among ED patients. These triggers should be pilot field tested to quantify their individual and collective performance in detecting all-cause harm to ED patients.

Impact of Type and Number of Complications on Mortality in Admitted Elderly Blunt Trauma Patients.

BACKGROUND: Advanced age and comorbidities are recognized risk factors for adverse outcomes in elderly trauma patients. However, the contribution of the number and type of complications to in-hospital mortality in elderly blunt trauma admissions has not been extensively studied. METHODS: A retrospective review of the trauma registry at a level 1 trauma center for blunt trauma patients age ≥65 y hospitalized for at least 2 d between 2010 and 2015. RESULTS: There were 2467 admissions, with a median age of 81 y and median injury severity score of 9. The most common mechanism of injury was a low-level fall. Approximately 19.6% of admissions had a complication: 11.1% major complications, 8.6% other complications. The in-hospital mortality rate was significantly different (P < 0.001) among the three groups at 16.1% of major complications group, 7.1% of other, and 2.1% of no complications (P < 0.001). On multivariate logistic regression, each major complication increased the odds for in-hospital mortality by 1.59-fold. CONCLUSIONS: Complications are not infrequent in elderly blunt trauma admissions, despite a generally lower energy mechanism of injury. Each major complication is associated with increased odds of mortality. Multifaceted interventions for prevention and mitigation of complications are indicated.

An Open-Label Phase II Trial of Bevacizumab plus Docetaxel and Gemcitabine in Advanced, Previously Untreated Nonsquamous Non-Small Cell Lung Cancer.

LESSONS LEARNED: The combination of bevacizumab with docetaxel-gemcitabine resulted in unacceptable toxicity, particularly a high rate of pulmonary toxicity (30%).Despite promising efficacy, excessive toxicity of this regimen does not support its use in patients with advanced nonsquamous non-small cell lung cancer. BACKGROUND: Prior to immunotherapy, standard treatment for advanced non-small cell lung cancer (NSCLC) was platinum doublet chemotherapy. In a previous phase II study, docetaxel-gemcitabine demonstrated comparable efficacy and tolerability to platinum doublets. In this phase II trial, we evaluated the efficacy and tolerability of adding bevacizumab to docetaxel- gemcitabine in patients with advanced nonsquamous NSCLC. METHODS: Patients with untreated advanced nonsquamous NSCLC were treated with up to six cycles of docetaxel-gemcitabine-bevacizumab, followed by bevacizumab until progression. The primary endpoint for this study was 1-year progression-free survival (PFS); secondary endpoints were safety, overall response rate (ORR) and overall survival (OS). The planned sample size was 46 patients. RESULTS: A total of 13 patients were enrolled and received a median of six cycles of chemotherapy and four cycles of bevacizumab. The treatment was poorly tolerated, with five patients requiring dose reduction and four discontinuing treatment for toxicity. Grade 3-5 nonhematologic toxicity was seen in 10 patients, and 4 (30%) were hospitalized with pulmonary toxicity possibly related to study drugs. At this point, enrollment was halted for safety concerns. The 12-month PFS was 8%. In 11 evaluable patients, ORR was 72%, median PFS 6 months, and median OS was 11 months. CONCLUSION: Docetaxel, gemcitabine, and bevacizumab at this dose and schedule resulted in excessive toxicity. Despite promising efficacy, in light of efficacious and safe alternative therapies, this regimen should not be used to treat advanced NSCLC.

SELECT: A Phase II Trial of Adjuvant Erlotinib in Patients With Resected Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer.

PURPOSE: Given the pivotal role of epidermal growth factor receptor (EGFR) inhibitors in advanced EGFR-mutant non-small-cell lung cancer (NSCLC), we tested adjuvant erlotinib in patients with EGFR-mutant early-stage NSCLC. MATERIALS AND METHODS: In this open-label phase II trial, patients with resected stage IA to IIIA (7th edition of the American Joint Committee on Cancer staging system) EGFR-mutant NSCLC were treated with erlotinib 150 mg per day for 2 years after standard adjuvant chemotherapy with or without radiotherapy. The study was designed for 100 patients and powered to demonstrate a primary end point of 2-year disease-free survival (DFS) greater than 85%, improving on historic data of 76%. RESULTS: Patients (N = 100) were enrolled at seven sites from January 2008 to May 2012; 13% had stage IA disease, 32% had stage IB disease, 11% had stage IIA disease, 16% had stage IIB disease, and 28% had stage IIIA disease. Toxicities were typical of erlotinib; there were no grade 4 or 5 adverse events. Forty percent of patients required erlotinib dose reduction to 100 mg per day and 16% to 50 mg per day. The intended 2-year course was achieved in 69% of patients. The median follow-up was 5.2 years, and 2-year DFS was 88% (96% stage I, 78% stage II, 91% stage III). Median DFS and overall survival have not been reached; 5-year DFS was 56% (95% CI, 45% to 66%), 5-year overall survival was 86% (95% CI, 77% to 92%). Disease recurred in 40 patients, with only four recurrences during erlotinib treatment. The median time to recurrence was 25 months after stopping erlotinib. Of patients with recurrence who underwent rebiopsy (n = 24; 60%), only one had T790M mutation detected. The majority of patients with recurrence were retreated with erlotinib (n = 26; 65%) for a median duration of 13 months. CONCLUSION: Patients with EGFR-mutant NSCLC treated with adjuvant erlotinib had an improved 2-year DFS compared with historic genotype-matched controls. Recurrences were rare for patients receiving adjuvant erlotinib, and patients rechallenged with erlotinib after recurrence experienced durable benefit.

Malnutrition and the Orthopaedic Trauma Patient: A Systematic Review of the Literature.

OBJECTIVES: To evaluate the available literature for associations between nutrition and outcomes after operative treatment of long bone and long bone periarticular fractures. DATA SOURCES: Systematic review of English-language articles in the MEDLINE, Embase, PubMed, and Cochrane computerized literature databases (through December 2015) using PRISMA guidelines. STUDY SELECTION: Randomized controlled trials, quasi-randomized controlled trials, case-control studies, and cohort studies (retrospective and prospective) involving long bone and long bone periarticular fractures that included the effect of nutritional status on fracture union, time to union, and any related soft-tissue complication were eligible for review. DATA EXTRACTION: Two authors independently extracted data from the selected studies using a standardized data collection form with predefined data fields for demographics, interventions, study methods, complications, and management outcomes. DATA SYNTHESIS: Although one of the original aims of the study was to conduct a meta-analysis, the available literature did not offer sufficient data for meta-analysis. CONCLUSIONS: Although our systematic review demonstrates a possible role for oral nutritional supplementation and vitamin supplementation in the orthopaedic trauma patient, there remains a need for well-designed trials to clarify this role. There is likely benefit to multidisciplinary approaches to nutritional optimization in the orthopaedic trauma patient, and this should be explored further in forthcoming work. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Applying advanced analytics to guide emergency department operational decisions: A proof-of-concept study examining the effects of boarding.

BACKGROUND: Emergency Department (ED) leaders are increasingly confronted with large amounts of data with the potential to inform and guide operational decisions. Routine use of advanced analytic methods may provide additional insights. OBJECTIVES: To examine the practical application of available advanced analytic methods to guide operational decision making around patient boarding. METHODS: Retrospective analysis of the effect of boarding on ED operational metrics from a single site between 1/2015 and 1/2017. Times series were visualized through decompositional techniques accounting for seasonal trends, to determine the effect of boarding on ED performance metrics and to determine the impact of boarding "shocks" to the system on operational metrics over several days. RESULTS: There were 226,461 visits with the mean (IQR) number of visits per day was 273 (258-291). Decomposition of the boarding count time series illustrated an upward trend in the last 2-3 quarters as well as clear seasonal components. All performance metrics were significantly impacted (p<0.05) by boarding count, except for overall Press Ganey scores (p<0.65). For every additional increase in boarder count, overall length-of-stay (LOS) increased by 1.55min (0.68, 1.50). Smaller effects were seen for waiting room LOS and treat and release LOS. The impulse responses indicate that the boarding shocks are characterized by changes in the performance metrics within the first day that fade out after 4-5days. CONCLUSION: In this study regarding the use of advanced analytics in daily ED operations, time series analysis provided multiple useful insights into boarding and its impact on performance metrics.

Reducing Unnecessary Blood Chemistry Testing in the Emergency Department: Implementation of Choosing Wisely.

Point of care (POC) laboratory testing is used to improve emergency department (ED) throughput but often overuses resources by duplicating formal laboratory testing. This study sought to evaluate the effect of a multimodal intervention on duplicate chemistry testing. This pre-post analysis included all visits to 2 urban EDs between June 2014 and June 2016. The multimodal intervention including provider education, signage, electronic health record redesign, and audit and feedback focused on reducing duplicate chemistry testing. The primary outcome was the number of duplicate chemistry tests per 100 visits. Autoregressive integrated moving-average models were used to account for secular changes. A total of 299 701 ED visits were included. The daily number of duplicate chemistry and POC chemistry tests significantly decreased following the intervention (3.3 fewer duplicates and 10.2 fewer POC per 100 ED visits, P < .0001). This implementation of a multimodal quality improvement intervention yielded substantial reductions in the overuse of blood chemistry testing in the ED.

Risk assessment of the blunt trauma victim: The role of the quick Sequential Organ Failure Assessment Score (qSOFA).

BACKGROUND: A number or risk assessment tools are used in trauma victims. Because of its simplicity, we examined the ability of the recently described quick Sequential Organ Failure Assessment Score (qSOFA) to predict outcomes in blunt trauma patients presenting to the Emergency Department. METHODS: We queried the trauma registry at a Level 1 Trauma Center for all adult blunt trauma admissions between 1/1/10 and 9/30/15. qSOFA scores were the sum of binary scores for 3 variables (RR ≥ 22, SBP≤100 mmHg, and GCS≤13). RESULTS: There were 7064 admissions (5664 admissions had qSOFA = 0, 1164 had qSOFA = 1, 223 had qSOFA = 2, and 13 had qSOFA = 3). Higher qSOFA scores were associated with greater injury severity, increased ICU admission, and higher complication rates. qSOFA scores were associated with in-hospital mortality (1.7% with qSOFA = 0; 8.7% with qSOFA = 1; 22.4% with qSOFA = 2; 23.1% with qSOFA = 3; p < 0.001). On multivariate analysis, qSOFA score was an independent predictor of mortality. CONCLUSIONS: qSOFA scores are directly associated with adverse outcomes in blunt trauma victims.