Publications by authors named "Jarrod Mosier"

92 Publications

Clinical characteristics and outcomes of critically ill mechanically ventilated COVID-19 patients receiving interleukin-6 receptor antagonists and corticosteroid therapy: a preliminary report from a multinational registry.

Eur J Med Res 2021 Oct 2;26(1):117. Epub 2021 Oct 2.

Mayo Clinic, Rochester, USA.

Background: Interleukin-6 receptor antagonists (IL-6RAs) and steroids are emerging immunomodulatory therapies for severe and critical coronavirus disease (COVID-19). In this preliminary report, we aim to describe the epidemiology, clinical characteristics, and outcomes of adult critically ill COVID-19 patients, requiring invasive mechanical ventilation (iMV), and receiving IL-6RA and steroids therapy over the last 11 months.

Materials And Methods: International, multicenter, cohort study derived from Viral Infection and Respiratory Illness University Study registry and conducted through Discovery Network, Society of Critical Care Medicine. Data were collected between March 01, 2020, and January 10, 2021.

Results: Of 860 patients who met eligibility criteria, 589 received steroids, 170 IL-6RAs, and 101 combinations. Patients who received IL-6RAs were younger (median age of 57.5 years vs. 61.1 and 61.8 years in the steroids and combination groups, respectively). The median C-reactive protein level was > 75 mg/L, indicating a hyperinflammatory phenotype. The median daily steroid dose was 7.5 mg dexamethasone or equivalent (interquartile range: 6-14 mg); 80.8% and 19.2% received low-dose and high-dose steroids, respectively. Of the patients who received IL-6RAs, the majority received one dose of tocilizumab and sarilumab (dose range of 600-800 mg for tocilizumab and 200-400 mg for sarilumab). Regarding the timing of administration, we observed that steroid and IL-6RA administration on day 0 of ICU admission was only 55.6% and 39.5%, respectively. By day 28, when compared with steroid use alone, IL-6RA use was associated with an adjusted incidence rate ratio (aIRR) of 1.12 (95% confidence interval [CI] 0.88, 1.4) for ventilator-free days, while combination therapy was associated with an aIRR of 0.83 (95% CI 0.6, 1.14). IL-6RA use was associated with an adjusted odds ratio (aOR) of 0.68 (95% CI 0.44, 1.07) for the 28-day mortality rate, while combination therapy was associated with an aOR of 1.07 (95% CI 0.67, 1.70). Liver dysfunction was higher in IL-6RA group (p = 0.04), while the bacteremia rate did not differ among groups.

Conclusions: Discordance was observed between the registry utilization patterns (i.e., timing of steroids and IL-6RA administration) and new evidence from the recent randomized controlled trials and guideline recommendations. These data will help us to identify areas of improvement in prescribing patterns and enhance our understanding of IL-6RA safety with different steroid regimens. Further studies are needed to evaluate the drivers of hospital-level variation and their impact on clinical outcomes. Trial registration ClinicalTrials.gov: NCT04486521. Registered on July 2020.
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http://dx.doi.org/10.1186/s40001-021-00591-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487342PMC
October 2021

A Target for Increased Mortality Risk in Critically Ill Patients: The Concept of Perpetuity.

J Clin Med 2021 Sep 2;10(17). Epub 2021 Sep 2.

College of Medicine, Drexel University, 2900 W Queen Lane, Philadelphia, PA 19129, USA.

Background: Emergency medicine is acuity-based and focuses on time-sensitive treatments for life-threatening diseases. Prolonged time in the emergency department, however, is associated with higher mortality in critically ill patients. Thus, we explored management after an acuity-based intervention, which we call perpetuity, as a potential mechanism for increased risk. To explore this concept, we evaluated the impact of each hour above a lung-protective tidal volume on risk of mortality.

Methods: This cohort analysis includes all critically ill, non-trauma, adult patients admitted to two academic EDs between 1 November 2013 and 30 April 2017. Cox models with time-varying covariates were developed with time in perpetuity as a time-varying covariate, defined as hours above 8 mL/kg ideal body weight, adjusted for covariates. The primary outcome was the time to in-hospital death.

Results: Our analysis included 2025 patients, 321 (16%) of whom had at least 1 h of perpetuity time. A partial likelihood-ratio test comparing models with and without hours in perpetuity was statistically significant (χ(3) = 13.83, = 0.0031). There was an interaction between age and perpetuity (Relative risk (RR) 0.9995; 95% Confidence interval (CI): 0.9991-0.9998). For example, for each hour above 8 mL/kg ideal body weight, a 20-year-old with 90% oxygen saturation has a relative risk of death of 1.02, but a 40-year-old with 90% oxygen saturation has a relative risk of 1.01.

Conclusions: Perpetuity, illustrated through the lens of mechanical ventilation, may represent a target for improving outcomes in critically ill patients, starting in the emergency department. Research is needed to evaluate the types of patients and interventions in which perpetuity plays a role.
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http://dx.doi.org/10.3390/jcm10173971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432225PMC
September 2021

In Response.

Anesth Analg 2021 07;133(1):e12

Department of Emergency Medicine, University of Arizona College of Medicine, Tucson, Arizona, Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep, University of Arizona College of Medicine, Tucson, Arizona.

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http://dx.doi.org/10.1213/ANE.0000000000005573DOI Listing
July 2021

Variation in Early Management Practices in Moderate-to-Severe ARDS in the United States: The Severe ARDS: Generating Evidence Study.

Chest 2021 Oct 4;160(4):1304-1315. Epub 2021 Jun 4.

Department of Emergency Medicine, Temple University Hospital, Philadelphia, PA.

Background: Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown.

Research Question: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States?

Study Design And Methods: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pao to Fio ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm HO, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed.

Results: A total of 2,466 patients were enrolled. Median baseline Pao to Fio ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm HO) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR.

Interpretation: Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes.

Trial Registry: ClinicalTrials.gov; No.: NCT03021824; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.05.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176896PMC
October 2021

SARS-CoV-2 Rapid Antigen Testing of Symptomatic and Asymptomatic Individuals on the University of Arizona Campus.

Biomedicines 2021 May 12;9(5). Epub 2021 May 12.

Office of the Senior Vice-President for Health Sciences, University of Arizona, Tucson, AZ 85724, USA.

SARS-CoV-2, the cause of COVID19, has caused a pandemic that has infected more than 80 M and killed more than 1.6 M persons worldwide. In the US as of December 2020, it has infected more than 32 M people while causing more than 570,000 deaths. As the pandemic persists, there has been a public demand to reopen schools and university campuses. To consider these demands, it is necessary to rapidly identify those individuals infected with the virus and isolate them so that disease transmission can be stopped. In the present study, we examined the sensitivity of the Quidel Rapid Antigen test for use in screening both symptomatic and asymptomatic individuals at the University of Arizona from June to August 2020. A total of 885 symptomatic and 1551 asymptomatic subjects were assessed by antigen testing and real-time PCR testing. The sensitivity of the test for both symptomatic and asymptomatic persons was between 82 and 90%, with some caveats.
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http://dx.doi.org/10.3390/biomedicines9050539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150898PMC
May 2021

Phenotyping COVID-19 Patients by Ventilation Therapy: Data Quality Challenges and Cohort Characterization.

Stud Health Technol Inform 2021 May;281:198-202

The University of Arizona, Tucson, AZ, USA.

The COVID-19 pandemic introduced unique challenges for treating acute respiratory failure patients and highlighted the need for reliable phenotyping of patients using retrospective electronic health record data. In this study, we applied a rule-based phenotyping algorithm to classify COVID-19 patients requiring ventilatory support. We analyzed patient outcomes of the different phenotypes based on type and sequence of ventilation therapy. Invasive mechanical ventilation, noninvasive positive pressure ventilation, and high flow nasal insufflation were three therapies used to phenotype patients leading to a total of seven subgroups; patients treated with a single therapy (3), patients treated with either form of noninvasive ventilation and subsequently requiring intubation (2), and patients initially intubated and then weaned onto a noninvasive therapy (2). In addition to summary statistics for each phenotype, we highlight data quality challenges and importance of mapping to standard terminologies. This work illustrates potential impact of accurate phenotyping on patient-level and system-level outcomes including appropriate resource allocation under resource constrained circumstances.
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http://dx.doi.org/10.3233/SHTI210148DOI Listing
May 2021

Airway Management in the Critically Ill Patient.

Curr Anesthesiol Rep 2021 Apr 19:1-12. Epub 2021 Apr 19.

Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Medicine, University of Arizona College of Medicine, Tucson, AZ USA.

Purpose Of Review: This paper will evaluate the recent literature and best practices in airway management in critically ill patients.

Recent Findings: Cardiac arrest remains a common complication of intubation in these high-risk patients. Patients with desaturation or peri-intubation hypotension are at high risk of cardiac arrest, and each of these complications have been reported in up to half of all intubations in critically ill patient populations.

Summary: There have been significant advances in preoxygenation and devices available for performing laryngoscopy and rescue oxygenation. However, the risk of cardiovascular collapse remains concerningly high with few studies to guide therapeutic maneuvers to reduce this risk.
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http://dx.doi.org/10.1007/s40140-021-00448-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053895PMC
April 2021

First Pass Success Without Adverse Events Is Reduced Equally with Anatomically Difficult Airways and Physiologically Difficult Airways.

West J Emerg Med 2021 Feb 1;22(2):360-368. Epub 2021 Feb 1.

University of Arizona College of Medicine, Department of Emergency Medicine, Tucson, Arizona.

Introduction: The goal of emergency airway management is first pass success without adverse events (FPS-AE). Anatomically difficult airways are well appreciated to be an obstacle to this goal. However, little is known about the effect of the physiologically difficult airway with regard to FPS-AE. This study evaluates the effects of both anatomically and physiologically difficult airways on FPS-AE in patients undergoing rapid sequence intubation (RSI) in the emergency department (ED).

Methods: We analyzed prospectively recorded intubations in a continuous quality improvement database between July 1, 2014-June 30, 2018. Emergency medicine (EM) or emergency medicine/pediatric (EM-PEDS) residents recorded patient, operator, and procedural characteristics on all consecutive adult RSIs performed using a direct or video laryngoscope. The presence of specific anatomically and physiologically difficult airway characteristics were also documented by the operator. Patients were analyzed in four cohorts: 1) no anatomically or physiologically difficult airway characteristics; 2) one or more anatomically difficult airway characteristics; 3) one or more physiologically difficult airway characteristics; and 4) both anatomically and physiologically difficult airway characteristics. The primary outcome was FPS-AE. We performed a multivariable logistic regression analysis to determine the association between anatomically difficult airways or physiologically difficult airways and FPS-AE.

Results: A total of 1513 intubations met inclusion criteria and were analyzed. FPS-AE for patients without any difficult airway characteristics was 92.4%, but reduced to 82.1% (difference = -10.3%, 95% confidence interval (CI), -14.8% to -5.6%) with the presence of one or more anatomically difficult airway characteristics, and 81.7% (difference = -10.7%, 95% CI, -17.3% to -4.0%) with the presence of one or more physiologically difficult airway characteristics. FPS-AE was further reduced to 70.9% (difference = -21.4%, 95% CI, -27.0% to -16.0%) with the presence of both anatomically and physiologically difficult airway characteristics. The adjusted odds ratio (aOR) of FPS-AE was 0.37 [95% CI, 0.21 - 0.66] in patients with anatomically difficult airway characteristics and 0.36 [95% CI, 0.19 - 0.67] for patients with physiologically difficult airway characteristics, compared to patients with no difficult airway characteristics. Patients who had both anatomically and physiologically difficult airway characteristics had a further decreased aOR of FPS-AE of 0.19 [95% CI, 0.11 - 0.33].

Conclusion: FPS-AE is reduced to a similar degree in patients with anatomically and physiologically difficult airways. Operators should assess and plan for potential physiologic difficulty as is routinely done for anatomically difficulty airways. Optimization strategies to improve FPS-AE for patients with physiologically difficult airways should be studied in randomized controlled trials.
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http://dx.doi.org/10.5811/westjem.2020.10.48887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972367PMC
February 2021

Identifying Barriers to and Opportunities for Telehealth Implementation Amidst the COVID-19 Pandemic by Using a Human Factors Approach: A Leap Into the Future of Health Care Delivery?

JMIR Hum Factors 2021 Apr 9;8(2):e24860. Epub 2021 Apr 9.

Department of Systems and Industrial Engineering, College of Engineering, The University of Arizona, Tucson, AZ, United States.

The extensive uptake of telehealth has considerably transformed health care delivery since the beginning of the COVID-19 pandemic and has imposed tremendous challenges to its large-scale implementation and adaptation. Given the shift in paradigm from telehealth as an alternative mechanism of care delivery to telehealth as an integral part of the health system, it is imperative to take a systematic approach to identifying barriers to, opportunities for, and the overall impact of telehealth implementation amidst the current pandemic. In this work, we apply a human factors framework, the Systems Engineering Initiative for Patient Safety model, to guide our holistic analysis and discussion of telehealth implementation, encompassing the health care work system, care processes, and outcomes.
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http://dx.doi.org/10.2196/24860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041052PMC
April 2021

Healthcare disparities among anticoagulation therapies for severe COVID-19 patients in the multi-site VIRUS registry.

J Med Virol 2021 Jul 30;93(7):4303-4318. Epub 2021 Mar 30.

nference, Inc., Cambridge, Massachusetts, USA.

Here we analyze hospitalized andintensive care unit coronavirus disease 2019 (COVID-19) patient outcomes from the international VIRUS registry (https://clinicaltrials.gov/ct2/show/NCT04323787). We find that COVID-19 patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (390 of 1012 = 39%) compared to patients administered enoxaparin but not unfractionated heparin (270 of 1939 = 14%), presenting a risk ratio of 2.79 (95% confidence interval [CI]: [2.42, 3.16]; p = 4.45e-52). This difference persists even after balancing on a number of covariates including demographics, comorbidities, admission diagnoses, and method of oxygenation, with an increased mortality rate on discharge from the hospital of 37% (268 of 733) for unfractionated heparin versus 22% (154 of 711) for enoxaparin, presenting a risk ratio of 1.69 (95% CI: [1.42, 2.00]; p = 1.5e-8). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to patients administered enoxaparin, including acute kidney injury, acute cardiac injury, septic shock, and anemia. Furthermore, a higher percentage of Black/African American COVID patients (414 of 1294 [32%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (671 of 2644 [25%]), risk ratio 1.26 (95% CI: [1.14, 1.40]; p = 7.5e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (311 of 1047 [30%] for Black/African American vs. 263 of 1047 [25%] for White/Caucasian, p = .02, risk ratio 1.18; 95% CI: [1.03, 1.36]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research into the observed racial disparity in anticoagulant use and outcomes for severe COVID-19 patients.
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http://dx.doi.org/10.1002/jmv.26918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013987PMC
July 2021

Mode of Arrival to the Emergency Department and Outcomes in Nontraumatic Critically Ill Adults.

Crit Care Explor 2021 Mar 25;3(3):e0350. Epub 2021 Feb 25.

Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Arizona, Tucson, AZ.

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http://dx.doi.org/10.1097/CCE.0000000000000350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909384PMC
March 2021

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

JAMA 2020 12;324(21):2165-2176

Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed.

Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19.

Design, Setting, And Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients.

Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237).

Main Outcomes And Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality.

Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]).

Conclusions And Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults.

Trial Registration: ClinicalTrials.gov: NCT04332991.
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http://dx.doi.org/10.1001/jama.2020.22240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653542PMC
December 2020

Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity.

Immunity 2020 11 14;53(5):925-933.e4. Epub 2020 Oct 14.

Division of Geriatrics, General Medicine and Palliative Care, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.

We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months after onset, whereas α-N titers diminished. Testing 5,882 members of the local community revealed only 1 sample with seroreactivity to both RBD and S2 that lacked neutralizing antibodies. This fidelity could not be achieved with either RBD or S2 alone. Thus, inclusion of multiple independent assays improved the accuracy of antibody tests in low-seroprevalence communities and revealed differences in antibody kinetics depending on the antigen. We conclude that neutralizing antibodies are stably produced for at least 5-7 months after SARS-CoV-2 infection.
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http://dx.doi.org/10.1016/j.immuni.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554472PMC
November 2020

Evaluation and Management of the Physiologically Difficult Airway: Consensus Recommendations From Society for Airway Management.

Anesth Analg 2021 02;132(2):395-405

Department of Emergency Medicine, University of Arizona College of Medicine, Tucson, Arizona.

Multiple international airway societies have created guidelines for the management of the difficult airway. In critically ill patients, there are physiologic derangements beyond inadequate airway protection or hypoxemia. These risk factors contribute to the "physiologically difficult airway" and are associated with complications including cardiac arrest and death. Importantly, they are largely absent from international guidelines. Thus, we created management recommendations for the physiologically difficult airway to provide practical guidance for intubation in the critically ill. Through multiple rounds of in-person and telephone conferences, a multidisciplinary working group of 12 airway specialists (Society for Airway Management's Special Projects Committee) over a time period of 3 years (2016-2019) reviewed airway physiology topics in a modified Delphi fashion. Consensus agreement with the following recommendations among working group members was generally high with 80% of statements showing agreement within a 10% range on a sliding scale from 0% to 100%. We limited the scope of this analysis to reflect the resources and systems of care available to out-of-operating room adult airway providers. These recommendations reflect the practical application of physiologic principles to airway management available during the analysis time period.
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http://dx.doi.org/10.1213/ANE.0000000000005233DOI Listing
February 2021

Aerosol Risk with Noninvasive Respiratory Support in Patients with COVID-19.

J Am Coll Emerg Physicians Open 2020 May 21. Epub 2020 May 21.

Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine University of Arizona College of Medicine Tucson AZ.

Objectives: This study evaluates aerosol production with high flow nasal cannula () and noninvasive positive pressure ventilation () compared to six liters per minute by low-flow nasal cannula.

Methods: Two healthy volunteers were randomized to control (six liters per minute by low-flow nasal cannula), NIPPV, or HFNC using block randomization. NIPPV conditions were studied using continuous positive airway pressures of 5, 10, and 15 cm HO with an FiO of 1.0 delivered via full-face mask. HFNC conditions included flow rates of 30 and 40 liters per minute with an FiO of 1.0 with and without coughing. HFNC and low-flow nasal cannula conditions were repeated with and without participants wearing a surgical mask. Six aerosol sizes (0.3, 1.0, 2.5, 5, and 10 μm) and total aerosol mass were measured at two feet and six feet from the participant's nasopharynx.

Results: There was no significant difference in aerosol production between either HFNC or NIPPV and control. There was also no significant difference with the use of procedural mask over the HFNC. There was significant variation between the two participants, but in neither case was there a difference compared to control. There was an aerosol-time trend, but there does not appear to be a difference between either flow rate, pressure, or control. Furthermore, there was no accumulation of total aerosol particles over the total duration of the experiment in both HFNC and NIPPV conditions.

Conclusions: HFNC and NIPPV did not increase aerosol production compared to six liters per minute by low-flow nasal cannula in this experiment involving healthy volunteers.This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/emp2.12152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280651PMC
May 2020

Comparison of a Novel Rapid Lateral Flow Assay to Enzyme Immunoassay Results for Early Diagnosis of Coccidioidomycosis.

Clin Infect Dis 2021 11;73(9):e2746-e2753

The Valley Fever Center for Excellence, University of Arizona College of Medicine-Tucson, Tucson, Arizona, USA.

Background: Coccidioidomycosis (CM) is a common cause of community-acquired pneumonia where CM is endemic. Manifestations include self-limited pulmonary infection, chronic fibrocavitary pulmonary disease, and disseminated coccidioidomycosis. Most infections are identified by serological assays including enzyme-linked immunoassay (EIA), complement fixation, and immunodiffusion. These are time-consuming and take days to result, impeding early diagnosis. A new lateral flow assay (LFA; Sōna; IMMY, Norman, OK) improves time-to-result to 1 hour.

Methods: We prospectively enrolled 392 patients with suspected CM, compared the LFA with standard EIA and included procalcitonin evaluation.

Results: Compared with standard EIA, LFA demonstrates 31% sensitivity (95% confidence interval [CI], 20-44%) and 92% specificity (95% CI, 88-95%). Acute pulmonary disease (74%) was the most common clinical syndrome. Hospitalized patients constituted 75% of subjects, and compared with outpatients, they more frequently had ≥3 previous healthcare facility visits (P = .05), received antibacterials (P < .01), and had >3 antibacterial courses (P < .01). Procalcitonin (PCT) was <0.25 ng/mL in 52 (83%) EIA-positive patients, suggesting infection was not bacterial.

Conclusions: When CM is a possible diagnosis, LFA identified nearly one-third of EIA-positive infections. Combined with PCT <0.25 ng/mL, LFA could reduce unnecessary antibacterial use by 77%.
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http://dx.doi.org/10.1093/cid/ciaa1205DOI Listing
November 2021

Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure.

medRxiv 2020 Aug 15. Epub 2020 Aug 15.

Division of Geriatrics, General Medicine and Palliative Care, Department of Medicine, University of Arizona College of Medicine-Tucson, Tucson, USA.

We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.
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http://dx.doi.org/10.1101/2020.08.14.20174490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430613PMC
August 2020

Time to Loss of Preoxygenation in Emergency Department Patients.

J Emerg Med 2020 Nov 5;59(5):637-642. Epub 2020 Aug 5.

Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, Minnesota.

Background: In patients requiring emergency rapid sequence intubation (RSI), 100% oxygen is often delivered for preoxygenation to replace alveolar nitrogen with oxygen. Sometimes, however, preoxygenation devices are prematurely removed from the patient prior to the onset of apnea, which can lead to rapid loss of preoxygenation.

Objective: We sought to determine the elapsed time, on average, between removing the oxygen source and the loss of preoxygenation among non-critically ill patients in the emergency department (ED).

Methods: We conducted a prospective, crossover study of non-critically ill patients in the ED. Each patient received two identical preoxygenation trials for 4 min using a non-rebreather mask with oxygen flow at flush rate and a nasal cannula with oxygen flow at 10 L/min. After each preoxygenation trial, patients underwent two trials in random order while continuing spontaneous breathing: 1) removal of both oxygen sources and 2) removal of non-rebreather mask with nasal cannula left in place. We defined loss of preoxygenation as an end-tidal oxygen (exhaled oxygen percentage; EtO) value < 70%. We measured EtO breath by breath until loss of preoxygenation occurred.

Results: We enrolled 42 patients, median age was 43 years (interquartile range [IQR] 30 to 54 years) and 72% were male. Median time to loss of preoxygenation was 20 s (IQR 17-25 s, 4.5 breaths) when all oxygen devices were removed, and 39 s (IQR 21-56 s, 8 breaths) when the nasal cannula was left in place.

Conclusions: In this population of non-critically ill ED patients, most had loss of preoxygenation after 5 breaths if all oxygen devices were removed, and after 8 breaths if a nasal cannula was left in place. These data suggest that during ED RSI, preoxygenation devices should be left in place until the patient is completely apneic.
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http://dx.doi.org/10.1016/j.jemermed.2020.06.064DOI Listing
November 2020

The Importance of the Intubation Process for the Safety of Emergency Airway Management.

Acad Emerg Med 2020 12 23;27(12):1362-1365. Epub 2020 Jun 23.

Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.

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http://dx.doi.org/10.1111/acem.14041DOI Listing
December 2020

Pragmatic recommendations for intubating critically ill patients with suspected COVID-19.

J Am Coll Emerg Physicians Open 2020 Apr 13. Epub 2020 Apr 13.

Department of Emergency Medicine Carolinas Medical Center Charlotte North Carolina USA.

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http://dx.doi.org/10.1002/emp2.12063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228350PMC
April 2020

The difficult airway refocused.

Br J Anaesth 2020 07 8;125(1):e18-e21. Epub 2020 May 8.

Department of Emergency Medicine, University of Arizona College of Medicine, Tucson, AZ, USA; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep, University of Arizona College of Medicine, Tucson, AZ, USA.

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http://dx.doi.org/10.1016/j.bja.2020.04.008DOI Listing
July 2020

Rule-Based Cohort Definitions for Acute Respiratory Failure: Electronic Phenotyping Algorithm.

JMIR Med Inform 2020 Apr 15;8(4):e18402. Epub 2020 Apr 15.

College of Engineering, The University of Arizona, Tucson, AZ, United States.

Background: Acute respiratory failure is generally treated with invasive mechanical ventilation or noninvasive respiratory support strategies. The efficacies of the various strategies are not fully understood. There is a need for accurate therapy-based phenotyping for secondary analyses of electronic health record data to answer research questions regarding respiratory management and outcomes with each strategy.

Objective: The objective of this study was to address knowledge gaps related to ventilation therapy strategies across diverse patient populations by developing an algorithm for accurate identification of patients with acute respiratory failure. To accomplish this objective, our goal was to develop rule-based computable phenotypes for patients with acute respiratory failure using remotely monitored intensive care unit (tele-ICU) data. This approach permits analyses by ventilation strategy across broad patient populations of interest with the ability to sub-phenotype as research questions require.

Methods: Tele-ICU data from ≥200 hospitals were used to create a rule-based algorithm for phenotyping patients with acute respiratory failure, defined as an adult patient requiring invasive mechanical ventilation or a noninvasive strategy. The dataset spans a wide range of hospitals and ICU types across all US regions. Structured clinical data, including ventilation therapy start and stop times, medication records, and nurse and respiratory therapy charts, were used to define clinical phenotypes. All adult patients of any diagnoses with record of ventilation therapy were included. Patients were categorized by ventilation type, and analysis of event sequences using record timestamps defined each phenotype. Manual validation was performed on 5% of patients in each phenotype.

Results: We developed 7 phenotypes: (0) invasive mechanical ventilation, (1) noninvasive positive-pressure ventilation, (2) high-flow nasal insufflation, (3) noninvasive positive-pressure ventilation subsequently requiring intubation, (4) high-flow nasal insufflation subsequently requiring intubation, (5) invasive mechanical ventilation with extubation to noninvasive positive-pressure ventilation, and (6) invasive mechanical ventilation with extubation to high-flow nasal insufflation. A total of 27,734 patients met our phenotype criteria and were categorized into these ventilation subgroups. Manual validation of a random selection of 5% of records from each phenotype resulted in a total accuracy of 88% and a precision and recall of 0.8789 and 0.8785, respectively, across all phenotypes. Individual phenotype validation showed that the algorithm categorizes patients particularly well but has challenges with patients that require ≥2 management strategies.

Conclusions: Our proposed computable phenotyping algorithm for patients with acute respiratory failure effectively identifies patients for therapy-focused research regardless of admission diagnosis or comorbidities and allows for management strategy comparisons across populations of interest.
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http://dx.doi.org/10.2196/18402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191347PMC
April 2020

Impact of Point-of-Care Ultrasound in the Emergency Department on Care Processes and Outcomes in Critically Ill Nontraumatic Patients.

Crit Care Explor 2019 Jun 26;1(6):e0019. Epub 2019 Jun 26.

Department of Emergency Medicine, University of Arizona, Tucson, AZ.

Outcomes data on point-of-care ultrasound (POCUS) in critically ill patients are lacking. This study examines the association between POCUS in the emergency department and outcomes in critically ill patients.

Design: Retrospective cohort study of critically ill emergency department patients in two academic emergency departments. All emergency department patients admitted to the intensive care unit or that die in the emergency department were entered prospectively into a registry.

Setting: Two academic emergency departments.

Patients: All adult (> 18 years old) non-trauma patients with hemodynamic instability [shock index (heart rate/systolic blood pressure) > 0.6] between November 1, 2013-October 31, 2016, were included.

Interventions: Cohorts were assigned as follows: no POCUS (cohort 1), POCUS prior to a key intervention (cohort 2), and POCUS after a key intervention (cohort 3). A key intervention was either a fluid bolus or vasoactive drug initiation.

Measurements And Main Results: Multivariable logistic regression was used to evaluate the association between POCUS use and the primary outcome of in-hospital mortality. We conducted several sensitivity analyses including propensity score matching and inverse-probability-weighted regression-adjustment along with multiple imputation to account for non-random assignment of POCUS as well as bias due to missing data. Of the 7,734 eligible patients, 2,293 patients were excluded. The remaining 5,441 patients were included in the analysis: 4165 in Cohort 1, 614 in Cohort 2, and 662 in Cohort 3. Mortality was 22%, 29%, and 26%, respectively ( < 0.001). POCUS prior to an intervention was associated with an adjusted odds ratio for death of 1.41 (95% CI, 1.12-1.76) compared to no POCUS. The sensitivity analyses showed an absolute increased mortality of +0.05 (95% CI, 0.02-0.09) for cohort 2 compared to 1.

Conclusions: POCUS use prior to interventions appears to be associated with care delays and increased in-hospital mortality compared to critically ill patients with no POCUS. Further explorations of the impact of POCUS in the emergency department appear warranted.
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http://dx.doi.org/10.1097/CCE.0000000000000019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063915PMC
June 2019

High-Flow Oxygen Therapy Concepts: Time to Standardize Nomenclature and Avoid Confusion.

J Intensive Care Med 2020 May 27;35(5):519-523. Epub 2020 Feb 27.

Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Arizona College of Medicine, Tucson, AZ, USA.

High-flow nasal oxygen systems are rapidly being adopted as an initial noninvasive treatment for acute respiratory failure. However, the term "high-flow nasal cannula" is nonspecific and leads to imprecise communication between physicians, respiratory therapists, and nurses with the potential for patient harm. In this viewpoint and a brief review of the technology, we argue for a change in nomenclature in order to reduce the chance for future clinical, administrative, and research misunderstanding surrounding high-flow nasal oxygen systems.
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http://dx.doi.org/10.1177/0885066620908243DOI Listing
May 2020

Tracheal Intubation in the Critically Ill. Where We Came from and Where We Should Go.

Am J Respir Crit Care Med 2020 04;201(7):775-788

Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada.

Tracheal intubation is commonly performed in critically ill patients. Unfortunately, this procedure also carries a high risk of complications; half of critically ill patients with difficult airways experience life-threatening complications. The high complication rates stem from difficulty with laryngoscopy and tube placement, consequences of physiologic derangement, and human factors, including failure to recognize and reluctance to manage the failed airway. The last 10 years have seen a rapid expansion in devices available that help overcome anatomic difficulties with laryngoscopy and provide rescue oxygenation in the setting of failed attempts. Recent research in critically ill patients has highlighted other important considerations for critically ill patients and evaluated interventions to reduce the risks with repeated attempts, desaturation, and cardiovascular collapse during emergency airway management. There are three actions that should be implemented to reduce the risk of danger: ) preintubation assessment for potential difficulty (e.g., MACOCHA score); ) preparation and optimization of the patient and team for difficulty-including using a checklist, acquiring necessary equipment, maximizing preoxygenation, and hemodynamic optimization; and ) recognition and management of failure to restore oxygenation and reduce the risk of cardiopulmonary arrest. This review describes the history of emergency airway management and explores the challenges with modern emergency airway management in critically ill patients. We offer clinically relevant recommendations on the basis of current evidence, guidelines, and expert opinion.
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http://dx.doi.org/10.1164/rccm.201908-1636CIDOI Listing
April 2020

Physiologically difficult airway in critically ill patients: winning the race between haemoglobin desaturation and tracheal intubation.

Authors:
Jarrod M Mosier

Br J Anaesth 2020 07 24;125(1):e1-e4. Epub 2019 Dec 24.

Department of Emergency Medicine, University of Arizona College of Medicine, Tucson, AZ, USA; Division of Pulmonary, Allergy, Critical Care and Sleep, Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA. Electronic address:

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http://dx.doi.org/10.1016/j.bja.2019.12.001DOI Listing
July 2020

Ketamine as Monotherapy in Difficult Airways Is Not Ready for Prime Time.

West J Emerg Med 2019 10 17;20(6):970-971. Epub 2019 Oct 17.

University of Arizona, Department of Emergency Medicine, Section of Pulmonary, Critical Care, Allergy, and Sleep, Department of Medicine, Tucson, Arizona.

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http://dx.doi.org/10.5811/westjem.2019.8.43881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6860380PMC
October 2019

The ED-SED Study: A Multicenter, Prospective Cohort Study of Practice Patterns and Clinical Outcomes Associated With Emergency Department SEDation for Mechanically Ventilated Patients.

Crit Care Med 2019 11;47(11):1539-1548

Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO.

Objectives: To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes.

Design: Multicenter, prospective cohort study.

Setting: The emergency department and ICUs of 15 medical centers.

Patients: Mechanically ventilated adult emergency department patients.

Interventions: None.

Measurements And Main Results: All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p < 0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI, -0.40 to 4.13). Similar results according to emergency department sedation depth existed for ICU-free days (mean difference, 1.6; 95% CI, -0.54 to 3.83) and hospital-free days (mean difference, 2.3; 95% CI, 0.26-4.32). Mortality was 21.1% in the deep sedation group and 17.0% in the light sedation group (between-group difference, 4.1%; odds ratio, 1.30; 0.74-2.28). The occurrence rate of acute brain dysfunction (delirium and coma) was 68.4% in the deep sedation group and 55.6% in the light sedation group (between-group difference, 12.8%; odds ratio, 1.73; 1.10-2.73).

Conclusions: Early deep sedation in the emergency department is common, carries over into the ICU, and may be associated with worse outcomes. Sedation practice in the emergency department and its association with clinical outcomes is in need of further investigation.
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http://dx.doi.org/10.1097/CCM.0000000000003928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323907PMC
November 2019

Improvement in the Safety of Rapid Sequence Intubation in the Emergency Department with the Use of an Airway Continuous Quality Improvement Program.

West J Emerg Med 2019 Jul 3;20(4):610-618. Epub 2019 Jun 3.

University of Arizona College of Medicine, Department of Emergency Medicine, Tucson, Arizona.

Introduction: Airway management in the critically ill is associated with a high prevalence of failed first attempts and adverse events which negatively impacts patient care. The purpose of this investigation is to describe an airway continuous quality improvement (CQI) program and its effect on the safety of rapid sequence intubation (RSI) in the emergency department (ED) over a 10-year period.

Methods: An airway CQI program with an ongoing airway registry was initiated in our ED on July 1, 2007 (Academic Year 1) and continued through June 30, 2017 (Academic Year 10). Data were prospectively collected on all patients intubated in the ED during this period using a structured airway data collection form. Key data points included method of intubation, drugs and devices used for intubation, operator specialty and level of training, number of intubation attempts, and adverse events. Adult patients who underwent RSI in the ED with an initial intubation attempt by emergency medicine (EM) resident were included in the analysis. The primary outcome was first pass success which was defined as successful tracheal intubation with a single laryngoscope insertion. The secondary outcome was the prevalence of adverse events associated with intubation. Educational and clinical interventions were introduced throughout the study period with the goal of optimizing these outcomes. Data were analyzed by academic year and are reported descriptively with 95% confidence intervals (CI) of the difference of means.

Results: EM residents performed RSI on 342 adult patients during Academic Year 1 and on 445 adult patients during Academic Year 10. Over the 10-year study period, first pass success increased from 73.1% to 92.4% (difference = 19.3%, 95% CI 14.0% to 24.6%). The percentage of patients who experienced an adverse event associated with intubation decreased from 22.5% to 14.4% (difference = -7.9%, 95% CI -13.4% to -2.4%). The percentage of patients with first pass success without an adverse event increased from 64.0% to 80.9% (difference = 16.9%, 95% CI 10.6% to 23.1%).

Conclusion: The use of an airway CQI program with an ongoing airway registry resulted in a substantial improvement in the overall safety of RSI in the ED as evidenced by an increase in first pass success and a decrease in adverse events.
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http://dx.doi.org/10.5811/westjem.2019.4.42343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625676PMC
July 2019

Mechanical Ventilation Strategies for the Patient with Severe Obstructive Lung Disease.

Emerg Med Clin North Am 2019 Aug;37(3):445-458

Department of Emergency Medicine, University of Arizona College of Medicine, 1501 North Campbell Avenue, PO Box 245057, Tucson, AZ 85724-5057, USA; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep, University of Arizona College of Medicine, Tucson, AZ, USA.

Patients with respiratory failure due to obstructive lung disease present a challenge to the emergency physician. These patients have physiologic abnormalities that prevent adequate gas exchange and lung mechanics which render them at increased risk of cardiopulmonary decompensation when managed with invasive mechanical ventilation. This article addresses key principles when managing these challenging patients: patient-ventilator synchrony, air trapping and auto-positive end-expiratory pressure, and airway pressures. This article provides a practical workflow for the emergency physician responsible for managing these patients.
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http://dx.doi.org/10.1016/j.emc.2019.04.003DOI Listing
August 2019
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