Publications by authors named "Allan J Walkey"

158 Publications

Rationale and Design of the Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) Study Protocol.

Authors:
Michael A Garcia Garrett L Rampon Gheorghe Doros Shijing Jia Nikhil Jagan Kari Gillmeyer Andrew Berical James Hudspeth Michael Ieong Katherine L Modzelewski Elissa M Schechter-Perkins Craig S Ross Justin M Rucci Steven Simpson Allan J Walkey Nicholas A Bosch

Ann Am Thorac Soc 2021 Mar 1. Epub 2021 Mar 1.

Boston University, 1846, Department of Medicine, The Pulmonary Center; Division of Pulmonary, Allergy, Sleep, and Critical Care, Boston, Massachusetts, United States.

The unprecedented public health burdens of coronavirus disease 2019 (COVID-19) have intensified the urgency to identify effective, low-cost treatments that limit the need for advanced life support measures and improve clinical outcomes. However, personal protective equipment and staffing shortages, disease virulence, and infectivity have created significant barriers to traditional clinical trial practices. We present the novel design of a pragmatic, adaptive, multicenter, international, prospective randomized controlled clinical trial evaluating the safety and effectiveness of awake prone positioning in spontaneously breathing patients with COVID-19 (Awake Prone Positioning for Early Hypoxemia in COVID-19 [APPEX-19]). Key innovations of this trial include: 1) a novel smartphone-based communication process that facilitates rapid enrollment and intervention delivery while allowing social distancing and conservation of personal protective equipment; 2) a Bayesian response-adaptive randomization to allow preferential assignment to the most effective intervention and expedite trial completion compared with frequentist designs; 3) remote electronic collection of patient-reported outcomes and electronic medical record data; and 4) pragmatic prospective utilization of patient-reported data and data collected as part of routine clinical care. Clinical trial registered with www.clinicaltrials.gov (NCT04344587).
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http://dx.doi.org/10.1513/AnnalsATS.202009-1124SDDOI Listing
March 2021

Comparative Effectiveness of Heart Rate Control Medications for the Treatment of Sepsis-Associated Atrial Fibrillation.

Authors:
Nicholas A Bosch Justin M Rucci Joseph M Massaro Michael R Winter Emily K Quinn Ki H Chon David D McManus Allan J Walkey

Chest 2020 Oct 24. Epub 2020 Oct 24.

Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston University School of Public Health, Boston, MA.

Background: Atrial fibrillation (AF) with rapid ventricular response frequently complicates the management of critically ill patients with sepsis and may necessitate the initiation of medication to avoid hemodynamic compromise. However, the optimal medication to achieve rate control for AF with rapid ventricular response in sepsis is unclear.

Research Question: What is the comparative effectiveness of frequently used AF medications (β-blockers, calcium channel blockers, amiodarone, and digoxin) on heart rate (HR) reduction among critically ill patients with sepsis and AF with rapid ventricular response?

Study Design And Methods: We conducted a multicenter retrospective cohort study among patients with sepsis and AF with rapid ventricular response (HR > 110 beats/min). We compared the rate control effectiveness of β-blockers to calcium channel blockers, amiodarone, and digoxin using multivariate-adjusted, time-varying exposures in competing risk models (for death and addition of another AF medication), adjusting for fixed and time-varying confounders.

Results: Among 666 included patients, 50.6% initially received amiodarone, 10.1% received a β-blocker, 33.8% received a calcium channel blocker, and 5.6% received digoxin. The adjusted hazard ratio for HR of < 110 beats/min by 1 h was 0.50 (95% CI, 0.34-0.74) for amiodarone vs β-blocker, 0.37 (95% CI, 0.18-0.77) for digoxin vs β-blocker, and 0.75 (95% CI, 0.51-1.11) for calcium channel blocker vs β-blocker. By 6 h, the adjusted hazard ratio for HR < 110 beats/min was 0.67 (95% CI, 0.47-0.97) for amiodarone vs β-blocker, 0.60 (95% CI, 0.36-1.004) for digoxin vs β-blocker, and 1.03 (95% CI, 0.71-1.49) for calcium channel blocker vs β-blocker.

Interpretation: In a large cohort of patients with sepsis and AF with rapid ventricular response, a β-blocker treatment strategy was associated with improved HR control at 1 h, but generally similar HR control at 6 h compared with amiodarone, calcium channel blocker, or digoxin.
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http://dx.doi.org/10.1016/j.chest.2020.10.049DOI Listing
October 2020

Long-Term Implications of Abnormal Left Ventricular Strain During Sepsis.

Authors:
Sarah J Beesley Jeff Sorensen Allan J Walkey Joseph E Tonna Michael J Lanspa Ellie Hirshberg Colin K Grissom Benjamin D Horne Rebecca Burk Theodore P Abraham Robert Paine Samuel M Brown

Crit Care Med 2021 Feb 12. Epub 2021 Feb 12.

Division of Pulmonary, Department of Medicine, Intermountain Medical Center, Salt Lake City, UT. Division of Pulmonary, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT. Division of Pulmonary, Department of Medicine, Boston University, Boston, MA. Division of Cardiothoracic Surgery, University of Utah School of Medicine, Salt Lake City, UT. Division of Emergency Medicine, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT. Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT. Intermountain Medical Center Heart Institute, Intermountain Healthcare, Salt Lake City, UT. Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA. Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA.

Objectives: Septic cardiomyopathy develops frequently in patients with sepsis and likely increases short-term mortality. However, whether septic cardiomyopathy is associated with long-term outcomes after sepsis is unknown. We investigated whether septic patients with septic cardiomyopathy have worse long-term outcomes than septic patients without septic cardiomyopathy.

Design: Retrospective cohort study.

Setting: Adult ICU.

Patients: Adult ICU patients with sepsis.

Interventions: None.

Measurements And Main Results: Left ventricular global longitudinal systolic strain was our primary measure of septic cardiomyopathy. We employed a suite of multivariable survival analyses to explore linear and nonlinear associations between left ventricular global longitudinal systolic strain and major adverse cardiovascular events, which included death, stroke, and myocardial infarction. Our primary outcome was major adverse cardiovascular event through 24 months after ICU discharge. Among 290 study patients, median left ventricular global longitudinal systolic strain was -16.8% (interquartile range, -20.4% to -12.6%), and 38.3% of patients (n = 111) experienced a major adverse cardiovascular event within 24 months after discharge. On our primary, linear analysis, there was a trend (p = 0.08) toward association between left ventricular global longitudinal systolic strain and major adverse cardiovascular event (odds ratio, 1.03; CI, < 1 to 1.07). On our nonlinear analysis, the association was highly significant (p < 0.001) with both high and low left ventricular global longitudinal systolic strain associated with major adverse cardiovascular event among patients with pre-existing cardiac disease. This association was pronounced among patients who were younger (age < 65 yr) and had Charlson Comorbidity Index greater than 5.

Conclusions: Among patients with sepsis and pre-existing cardiac disease who survived to ICU discharge, left ventricular global longitudinal systolic strain demonstrated a U-shaped association with cardiovascular outcomes through 24 months. The relationship was especially strong among younger patients with more comorbidities. These observations are likely of use to design of future trials.
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http://dx.doi.org/10.1097/CCM.0000000000004886DOI Listing
February 2021

Development and Validation of an Automated Algorithm to Detect Atrial Fibrillation Within Stored Intensive Care Unit Continuous Electrocardiographic Data: Observational Study.

Authors:
Allan J Walkey Syed K Bashar Md Billal Hossain Eric Ding Daniella Albuquerque Michael Winter Ki H Chon David D McManus

JMIR Cardio 2021 Feb 15;5(1):e18840. Epub 2021 Feb 15.

University of Massachusetts Medical School, Worcester, MA, United States.

Background: Atrial fibrillation (AF) is the most common arrhythmia during critical illness, representing a sepsis-defining cardiac dysfunction associated with adverse outcomes. Large burdens of premature beats and noisy signal during sepsis may pose unique challenges to automated AF detection.

Objective: The objective of this study is to develop and validate an automated algorithm to accurately identify AF within electronic health care data among critically ill patients with sepsis.

Methods: This is a retrospective cohort study of patients hospitalized with sepsis identified from Medical Information Mart for Intensive Care (MIMIC III) electronic health data with linked electrocardiographic (ECG) telemetry waveforms. Within 3 separate cohorts of 50 patients, we iteratively developed and validated an automated algorithm that identifies ECG signals, removes noise, and identifies irregular rhythm and premature beats in order to identify AF. We compared the automated algorithm to current methods of AF identification in large databases, including ICD-9 (International Classification of Diseases, 9th edition) codes and hourly nurse annotation of heart rhythm. Methods of AF identification were tested against gold-standard manual ECG review.

Results: AF detection algorithms that did not differentiate AF from premature atrial and ventricular beats performed modestly, with 76% (95% CI 61%-87%) accuracy. Performance improved (P=.02) with the addition of premature beat detection (validation set accuracy: 94% [95% CI 83%-99%]). Median time between automated and manual detection of AF onset was 30 minutes (25th-75th percentile 0-208 minutes). The accuracy of ICD-9 codes (68%; P=.002 vs automated algorithm) and nurse charting (80%; P=.02 vs algorithm) was lower than that of the automated algorithm.

Conclusions: An automated algorithm using telemetry ECG data can feasibly and accurately detect AF among critically ill patients with sepsis, and represents an improvement in AF detection within large databases.
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http://dx.doi.org/10.2196/18840DOI Listing
February 2021

Outcomes of Patients With Coronavirus Disease 2019 Receiving Organ Support Therapies: The International Viral Infection and Respiratory Illness Universal Study Registry.

Authors:
Juan Pablo Domecq Amos Lal Christopher R Sheldrick Vishakha K Kumar Karen Boman Scott Bolesta Vikas Bansal Michael O Harhay Michael A Garcia Margit Kaufman Valerie Danesh Sreekanth Cheruku Valerie M Banner-Goodspeed Harry L Anderson Patrick S Milligan Joshua L Denson Catherine A St Hill Kenneth W Dodd Greg S Martin Ognjen Gajic Allan J Walkey Rahul Kashyap

Crit Care Med 2021 03;49(3):437-448

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN.

Objectives: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry.

Design: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies.

Setting: About 168 hospitals in 16 countries within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry.

Patients: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation).

Interventions: None.

Measurements And Main Results: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support (n = 15,001). The most common organ support therapy was invasive mechanical ventilation (n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation (n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy (n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation (n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69).

Conclusions: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation.
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http://dx.doi.org/10.1097/CCM.0000000000004879DOI Listing
March 2021

Guideline-Concordant Insulin Infusion Initiation Among Critically Ill Patients With Sepsis.

Authors:
Nicholas A Bosch Kathryn L Fantasia Katherine L Modzelewski Sara M Alexanian Allan J Walkey

Endocr Pract 2021 Feb 5. Epub 2021 Feb 5.

Boston University School of Medicine, Department of Medicine, The Pulmonary Center, Boston, Massachusetts.

Objective: Our objective was to benchmark rates of guideline-concordant insulin infusion initiation, identify factors associated with guideline-concordant insulin practices, and examine the association between hospital-level guideline concordance and mortality among critically ill patients with sepsis.

Methods: We performed a multicenter retrospective cohort study of intensive care patients with sepsis who were eligible for insulin infusion initiation according to American Diabetes Association and Surviving Sepsis guidelines (persistent blood sugar ≥180 mg/dL). We then identified patients who were initiated on insulin infusions within 24 hours of eligibility. We examined patient- and hospital-level factors associated with guideline-concordant insulin infusion initiation and explored the association between the hospital-level proportion of patients who received guideline-concordant insulin infusions and hospital mortality.

Results: Among 5453 guideline-eligible patients with sepsis, 13.4% were initiated on insulin infusions. Factors most strongly associated with guideline-concordant insulin infusion initiation were mechanical ventilation and hospital of admission. The hospital-level proportion of patients who received guideline-concordant insulin infusions were not associated with mortality. Among 1501 intensive care unit patients with sepsis who were started on insulin infusions, 37.0% were initiated at a blood glucose level below 180 mg/dL, the guideline-recommended starting threshold.

Conclusion: Guideline-concordant insulin infusion initiation was uncommon among patients with sepsis admitted to U.S. intensive care units and was determined in large part by hospital of admission. The degree to which hospitals were guideline-concordant were not associated with mortality.
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http://dx.doi.org/10.1016/j.eprac.2021.01.018DOI Listing
February 2021

Informing Healthcare Decisions with Observational Research Assessing Causal Effect. An Official American Thoracic Society Research Statement.

Authors:
Andrea S Gershon Peter K Lindenauer Kevin C Wilson Louise Rose Allan J Walkey Mohsen Sadatsafavi Kevin J Anstrom David H Au Bruce G Bender M Alan Brookhart Raed A Dweik MeiLan K Han Min J Joo Valery Lavergne Anuj B Mehta Marc Miravitlles Richard A Mularski Nicolas Roche Eyal Oren Kristin A Riekert Noah C Schoenberg Therese A Stukel Curtis H Weiss Hannah Wunsch Joel J Africk Jerry A Krishnan

Am J Respir Crit Care Med 2021 01;203(1):14-23

Decisions in medicine are made on the basis of knowledge and reasoning, often in shared conversations with patients and families in consideration of clinical practice guideline recommendations, individual preferences, and individual goals. Observational studies can provide valuable knowledge to inform guidelines, decisions, and policy. The American Thoracic Society (ATS) created a multidisciplinary committee to develop a research statement to clarify the role of observational studies-alongside randomized controlled trials (RCTs)-in informing clinical decisions in pulmonary, critical care, and sleep medicine. The committee examined the strengths of observational studies assessing causal effects, how they complement RCTs, factors that impact observational study quality, perceptions of observational research, and, finally, the practicalities of incorporating observational research into ATS clinical practice guidelines. There are strengths and weakness of observational studies as well as RCTs. Observational studies can provide evidence in representative and diverse patient populations. Quality observational studies should be sought in the development of ATS clinical practice guidelines, and medical decision-making in general, when ) no RCTs are identified or RCTs are appraised as being of low- or very low-quality (); ) RCTs are of moderate quality because of indirectness, imprecision, or inconsistency, and observational studies mitigate the reason that RCT evidence was downgraded (); or ) RCTs do not provide evidence for outcomes that a guideline committee considers essential for decision-making (e.g., rare or long-term outcomes; "). Observational studies should be considered in developing clinical practice guidelines and in making clinical decisions.
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http://dx.doi.org/10.1164/rccm.202010-3943STDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781125PMC
January 2021

Management Strategies to Promote Follow-Up Care for Incidental Findings: A Scoping Review.

Authors:
Erika L Crable Timothy Feeney Joshua Harvey Valerie Grim Mari-Lynn Drainoni Allan J Walkey Katrina Steiling Frederick Thurston Drake

J Am Coll Radiol 2020 Dec 2. Epub 2020 Dec 2.

Department of Surgery, Boston Medical Center, Boston, Massachusetts; Department of Surgery, Boston University School of Medicine, Boston, Massachusetts.

Background: Incidentalomas, or unexpectedly identified masses, are frequently identified in diagnostic imaging studies. Incidentalomas may require timely follow-up care to determine if they are benign, disease-causing, or malignant lesions; however, many incidentalomas do not receive diagnostic workup. The most effective strategies to manage incidentalomas and optimal metrics for judging the efficacy of these strategies remain unclear.

Objective: To identify management strategies used to promote guideline-concordant follow-up for incidentalomas and commonly reported performance metrics associated with these strategies.

Data Sources: We searched peer-reviewed literature for incidentaloma management studies published between 2003 and 2020.

Data Extraction And Synthesis: Data extraction included anatomical location, imaging modality, clinical setting, management strategy characteristics, and metrics used to assess the management strategy. Eligible studies were analyzed qualitatively to describe strategies and metrics.

Results: In all, 15 studies met inclusion criteria. Four types of interventions designed to promote guideline-concordant follow-up care for incidentalomas were identified: (1) physical or verbal guideline reminders (n = 3); (2) electronic guideline references (n = 4); (3) enhanced radiology templates (n = 3); (4) restructured clinical and communication pathways (n = 5). Strategy efficacy was assessed by measuring rates of patients who received recommended follow-up care (n = 6) or had care recommendations documented in clinical records (n = 5). Few studies measured diagnostic outcomes associated with incidentalomas.

Conclusions: Most management strategies target changes in radiologists' behavior. Few studies address barriers to improving incidentaloma follow-up from interpretation to patient education of findings and care delivery. Hybrid effectiveness-implementation studies are needed to better address workflow barriers and rigorously evaluate care delivery outcomes.
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http://dx.doi.org/10.1016/j.jacr.2020.11.006DOI Listing
December 2020

Stability of Do-Not-Resuscitate Orders in Hospitalized Adults: A Population-Based Cohort Study.

Authors:
Anuj B Mehta Allan J Walkey Douglas Curran-Everett Daniel Matlock Ivor S Douglas

Crit Care Med 2021 Feb;49(2):240-249

Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.

Objectives: Prior work has shown substantial between-hospital variation in do-not-resuscitate orders, but stability of do-not-resuscitate preferences between hospitalizations and the institutional influence on do-not-resuscitate reversals are unclear. We determined the extent of do-not-resuscitate reversals between hospitalizations and the association of the readmission hospital with do-not-resuscitate reversal.

Design: Retrospective cohort study.

Setting: California Patient Discharge Database, 2016-2018.

Patients: Nonsurgical patients admitted to an acute care hospital with an early do-not-resuscitate order (within 24 hr of admission).

Interventions: None.

Measurements And Main Results: We identified nonsurgical adult patients who survived an initial hospitalization with an early-do-not-resuscitate order and were readmitted within 30 days. The primary outcome was the association of do-not-resuscitate reversal with readmission to the same or different hospital from the initial hospital. Secondary outcomes included association of readmission to a low versus high do-not-resuscitate-rate hospital with do-not-resuscitate reversal. Among 49,336 patients readmitted within 30 days following a first do-not-resuscitate hospitalization, 22,251 (45.1%) experienced do-not-resuscitate reversal upon readmission. Patients readmitted to a different hospital versus the same hospital were at higher risk of do-not-resuscitate reversal (59.5% vs 38.5%; p < 0.001; adjusted odds ratio = 2.4; 95% CI, 2.3-2.5). Patients readmitted to low versus high do-not-resuscitate-rate hospitals were more likely to have do-not-resuscitate reversals (do-not-resuscitate-rate quartile 1 77.0% vs quartile 4 27.2%; p < 0.001; adjusted odds ratio = 11.9; 95% CI, 10.7-13.2). When readmitted to a different versus the same hospital, patients with do-not-resuscitate reversal had higher rates of mechanical ventilation (adjusted odds ratio = 1.9; 95% CI, 1.6-2.1) and hospital death (adjusted odds ratio = 1.2; 95% CI, 1.1-1.3).

Conclusions: Do-not-resuscitate reversals at the time of readmission are more common than previously reported. Although changes in patient preferences may partially explain between-hospital differences, we observed a strong hospital effect contributing to high do-not-resuscitate-reversal rates with significant implications for patient outcomes and resource.
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http://dx.doi.org/10.1097/CCM.0000000000004726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855253PMC
February 2021

Interventions to increase appointment attendance in safety net health centers: A systematic review and meta-analysis.

Authors:
Erika L Crable Dea L Biancarelli Marisa Aurora Mari-Lynn Drainoni Allan J Walkey

J Eval Clin Pract 2020 Oct 16. Epub 2020 Oct 16.

Evans Center for Implementation and Improvement Sciences, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.

Rationale, Aims And Objectives: Missed appointments are a persistent problem across healthcare settings, and result in negative outcomes for providers and patients. We aimed to review and evaluate the effectiveness of interventions designed to reduce missed appointments in safety net settings.

Methods: We conducted a systematic review of interventions reported in three electronic databases. Data extraction and quality assessment were conducted according to PRISMA guidelines. Eligible studies were analyzed qualitatively to describe intervention types. A random effects model was used to measure the pooled relative risk of appointment adherence across interventions in the meta-analysis.

Results: Thirty-four studies met inclusion criteria for the qualitative synthesis, and 21 studies reported sufficient outcome data for inclusion in the meta-analysis. Qualitative analysis classified nine types of interventions used to increase attendance; however, application of each intervention type varied widely between studies. Across all study types (N = 12 000), RR was 1.08, (95% CI 1.03, 1.13) for any intervention used to increase appointment attendance. No single intervention was clearly effective: facilitated appointment scheduling [RR = 3.31 (95% CI: 0.30, 37.13)], financial incentives [RR = 1.88 (0.73, 4.82)] case management/patient navigator [RR = 1.09, (0.96, 1.24)], text messages [RR = 1.02 (0.96, 1.08)], transportation, [RR = 1.05 (0.98, 1.13)], telephone reminder calls [RR 1.12, (0.87, 1.45)], in-person referrals, [RR = 1.01 (0.90, 1.13)], patient contracts [RR = 0.87 (0.52, 1.46)] or combined strategies, [RR = 1.16 (1.03, 1.32)]. No strategy was clearly superior to others, p interaction = .50.

Conclusions: Strategies to improve appointment adherence in safety net hospitals varied widely and were only modestly effective. Further research harmonizing intervention delivery within each strategy and comparing strategies with the most potential for success is needed.
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http://dx.doi.org/10.1111/jep.13496DOI Listing
October 2020

Preliminary Results on Density Poincare Plot Based Atrial Fibrillation Detection from Premature Atrial/Ventricular Contractions

Authors:
Syed Khairul Bashar Dong Han Fearass Zieneddin Eric Ding Allan J Walkey David D McManus Ki H Chon

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:2594-2597

Detection of Atrial fibrillation (AF) from premature atrial contraction (PAC) and premature ventricular contraction (PVC) is challenging as frequent occurrences of these ectopic beats can mimic the typical irregular patterns of AF. In this paper, we present a preliminary study of using density Poincare plot based machine learning method to detect AF from PAC/PVCs using electrocardiogram (ECG) recordings. First, we propose creation of this new density Poincare plot which is derived from the difference of the heart rate. Next, from this density Poincare plot, template correlation and discrete wavelet transform are used to extract suitable image-based features, which is followed by infinite latent feature selection algorithm to rank the features. Finally, classification of AF vs PAC/PVC is performed using K-Nearest Neighbor, discriminant analysis and support vector machine (SVM) classifiers. Our method is developed and validated using a subset of Medical Information Mart for Intensive Care (MIMIC) III database containing 8 AF and 8 PAC/PVC subjects. Both 10-fold and leave-one-subject-out cross validations are performed to show the robustness of our proposed method. During the 10-fold cross-validation, SVM achieved the best performance with 99.49% sensitivity, 94.51% specificity and 97.29% accuracy with the extracted features while for the leave-one-subject-out, the highest overall accuracy is 90.91%. Moreover, when compared with two state-of-the-art methods, the proposed algorithm achieves superior AF vs. PAC/PVC discrimination performance.Clinical Relevance-This preliminary study shows that with the help of density Poincare plot, AF can be separated from PAC/PVC with better accuracy.
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http://dx.doi.org/10.1109/EMBC44109.2020.9175216DOI Listing
July 2020

Racial Disparities in Guideline-Concordant Insulin Infusions during Critical Illness.

Authors:
Nicholas A Bosch Kathryn L Fantasia Katherine L Modzelewski Sara M Alexanian Allan J Walkey

Ann Am Thorac Soc 2021 02;18(2):368-371

Boston University School of Medicine Boston, Massachusetts.

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http://dx.doi.org/10.1513/AnnalsATS.202007-893RLDOI Listing
February 2021

Lung-Protective Ventilation and Associated Outcomes and Costs Among Patients Receiving Invasive Mechanical Ventilation in the ED.

Authors:
Shannon M Fernando Eddy Fan Bram Rochwerg Karen E A Burns Laurent J Brochard Deborah J Cook Allan J Walkey Niall D Ferguson Catherine L Hough Daniel Brodie Andrew J E Seely Venkatesh Thiruganasambandamoorthy Jeffrey J Perry Alexandre Tran Peter Tanuseputro Kwadwo Kyeremanteng

Chest 2021 Feb 20;159(2):606-618. Epub 2020 Sep 20.

Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Division of Palliative Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada; Institut du Savoir Montfort, Ottawa, ON, Canada.

Background: Invasive mechanical ventilation is often initiated in the ED, and mechanically ventilated patients may be kept in the ED for hours before ICU transfer. Although lung-protective ventilation is beneficial, particularly in ARDS, it remains uncertain how often lung-protective tidal volumes are used in the ED, and whether lung-protective ventilation in this setting impacts patient outcomes.

Research Question: What is the association between the use of lung-protective ventilation in the ED and outcomes among invasively ventilated patients?

Study Design And Methods: A retrospective analysis (2011-2017) of a prospective registry from eight EDs enrolling consecutive adult patients (≥ 18 years) who received invasive mechanical ventilation in the ED was performed. Lung-protective ventilation was defined by use of tidal volumes ≤ 8 mL/kg predicted body weight. The primary outcome was hospital mortality. Secondary outcomes included development of ARDS, hospital length of stay, and total hospital costs.

Results: The study included 4,174 patients, of whom 2,437 (58.4%) received lung-protective ventilation in the ED. Use of lung-protective ventilation was associated with decreased odds of hospital death (adjusted OR [aOR], 0.91; 95% CI, 0.84-0.96) and development of ARDS (aOR, 0.87; 95% CI, 0.81-0.92). Patients who received lung-protective ventilation in the ED had shorter median duration of mechanical ventilation (4 vs 5 days; P < 0.01), shorter median hospital length of stay (11 vs 14 days; P < .001), and reduced total hospital costs (Can$44,348 vs Can$52,484 [US$34,153 vs US$40,418]; P = .03) compared with patients who received higher tidal volumes.

Interpretation: Use of lung-protective ventilation in the ED was associated with important patient- and system-centered outcomes, including lower hospital mortality, decreased incidence of ARDS, lower hospital length of stay, and decreased total costs. Protocol development promoting the regular use of lung-protective ventilation in the ED may be of value.
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http://dx.doi.org/10.1016/j.chest.2020.09.100DOI Listing
February 2021

Guiding Principles for the Conduct of Observational Critical Care Research for Coronavirus Disease 2019 Pandemics and Beyond: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study Registry.

Authors:
Allan J Walkey R Christopher Sheldrick Rahul Kashyap Vishakha K Kumar Karen Boman Scott Bolesta Fernando G Zampieri Vikas Bansal Michael O Harhay Ognjen Gajic

Crit Care Med 2020 11;48(11):e1038-e1044

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN.

Objectives: Use of observational data to inform the response and care of patients during a pandemic faces unique challenges.

Design: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID 2019 Registry Core data and research methodology team convened over virtual meetings throughout March to June 2020 to determine best practice goals for development of a pandemic disease registry to support rapid data collection and analysis.

Setting: International, multi-center registry of hospitalized patients.

Patients: None.

Interventions: None.

Measurements And Main Results: Large-scale observational data collection requires: 1) quality assurance and harmonization across many sites; 2) a transparent process for selecting from among many potential research questions; 3) the use of best practices in design of descriptive, predictive, and inferential studies; (4) innovative approaches to characterize random error in the setting of constantly updated data; (5) rapid peer-review and reporting; and (6) transitions from a focus on discovery to implementation. Herein, we describe the guiding principles to best practices and suggestions for innovations to study design and reporting within the coronavirus disease 2019 Viral Infection and Respiratory Illness Universal Study pandemic registry.

Conclusions: Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry sought to develop and implement prespecified best practices combined with grassroots efforts from clinical sites worldwide in order to develop clinically useful knowledge in response to a pandemic.
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http://dx.doi.org/10.1097/CCM.0000000000004572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540620PMC
November 2020

Use of Vasoactive Medications after Cardiac Surgery in the United States.

Authors:
Emily A Vail Meng-Shiou Shieh Penelope S Pekow Hayley B Gershengorn Allan J Walkey Peter K Lindenauer Hannah Wunsch

Ann Am Thorac Soc 2021 01;18(1):103-111

Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; and.

Patients undergoing cardiac surgery often require vasopressor or inotropic ("vasoactive") medications, but patterns of postoperative use are not well described. This study aimed to describe vasoactive medication administration throughout hospitalization for cardiac surgery, to identify patient- and hospital-level factors associated with postoperative use, and to quantify variation in treatment patterns among hospitals. Retrospective study using the Premier Healthcare Database. The cohort included adult patients who underwent coronary artery bypass grafting or open valve repair or replacement (or in combination) from January 1, 2016, to June 30, 2018. Primary outcome was receipt of vasoactive medication(s) on the first postoperative day (POD1). We identified patient- and hospital-level factors associated with receipt of vasoactive medications using multilevel mixed-effects logistic regression modeling. We calculated adjusted median odds ratios to determine the extent to which receipt of vasoactive medications on POD1 was determined by each hospital, then calculated quotients of Akaike Information Criteria to compare the relative contributions of patient and hospital characteristics and individual hospitals with observed variation. Among 104,963 adults in 294 hospitals, 95,992 (92.2%) received vasoactive medication(s) during hospitalization; 30,851 (29.7%) received treatment on POD1, most commonly norepinephrine ( = 11,427, 37.0%). A median of 29.0% (range, 0.0-94.4%) of patients in each hospital received vasoactive drug(s) on POD1. After adjustment, hospital of admission was associated with twofold increased odds of receipt of any vasoactive medication on POD1 (adjusted median odds ratio, 2.07; 95% confidence interval, 1.93-2.21). Admitting hospital contributed more to observed variation in POD1 vasoactive medication use than patient or hospital characteristics (quotients of Akaike Information Criteria 0.58, 0.44, and <0.001, respectively). Nearly all cardiac surgical patients receive vasoactive medications during hospitalization; however, only one-third receive treatment on POD1, with significant variability by institution. Further research is needed to understand the causes of variability across hospitals and whether these differences are associated with outcomes.
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http://dx.doi.org/10.1513/AnnalsATS.202005-465OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780981PMC
January 2021

Barriers and facilitators to implementing priority inpatient initiatives in the safety net setting.

Authors:
Erika L Crable Dea Biancarelli Allan J Walkey Mari-Lynn Drainoni

Implement Sci Commun 2020 11;1:35. Epub 2020 Mar 11.

Evans Center for Implementation and Improvement Sciences, Boston University School of Medicine, 801 Massachusetts Avenue, Crosstown 2030, Boston, 02118 MA USA.

Background: Safety net hospitals, which serve vulnerable and underserved populations and often operate on smaller budgets than non-safety net hospitals, may experience unique implementation challenges. We sought to describe common barriers and facilitators that affect the implementation of improvement initiatives in a safety net hospital, and identify potentially transferable lessons to enhance implementation efforts in similar settings.

Methods: We interviewed leaders within five inpatient departments and asked them to identify the priority inpatient improvement initiative from the last year. We then conducted individual, semi-structured interviews with 25 stakeholders across the five settings. Interviewees included individuals serving in implementation oversight, champion, and frontline implementer roles. The Consolidated Framework for Implementation Research informed the discussion guide and a priori codes for directed content analysis.

Results: Despite pursuing diverse initiatives in different clinical departments, safety net hospital improvement stakeholders described common barriers and facilitators related to inner and outer setting dynamics, characteristics of individuals involved, and implementation processes. Implementation barriers included (1) limited staffing resources, (2) organizational recognition without financial investment, and (3) the use of implementation strategies that did not adequately address patients' biopsychosocial complexities. Facilitators included (1) implementation approaches that combined passive and active communication styles, (2) knowledge of patient needs and competitive pressure to perform well against non-SNHs, (3) stakeholders' personal commitment to reduce health inequities, and (4) the use of multidisciplinary task forces to drive implementation activities.

Conclusion: Inner and outer setting dynamics, individual's characteristics, and process factors served as implementation barriers and facilitators within the safety net. Future work should seek to leverage findings from this study toward efforts to enact positive change within safety net hospitals.
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http://dx.doi.org/10.1186/s43058-020-00024-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427845PMC
March 2020

Comparing the Effects of Tidal Volume, Driving Pressure, and Mechanical Power on Mortality in Trials of Lung-Protective Mechanical Ventilation.

Authors:
Jose Dianti John Matelski Manuel Tisminetzky Allan J Walkey Laveena Munshi Lorenzo Del Sorbo Eddy Fan Eduardo Lv Costa Carol L Hodgson Laurent Brochard Ewan C Goligher

Respir Care 2021 Feb 25;66(2):221-227. Epub 2020 Aug 25.

Interdepartmenal Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.

Background: The unifying goal of lung-protective ventilation strategies in ARDS is to minimize the strain and stress applied by mechanical ventilation to the lung to reduce ventilator-induced lung injury (VILI). The relative contributions of the magnitude and frequency of mechanical stress and the end-expiratory pressure to the development of VILI is unknown. Consequently, it is uncertain whether the risk of VILI is best quantified in terms of tidal volume (V), driving pressure (ΔP), or mechanical power.

Methods: The correlation between differences in V, ΔP, and mechanical power and the magnitude of mortality benefit in trials of lung-protective ventilation strategies in adult subjects with ARDS was assessed by meta-regression. Modified mechanical power was computed including PEEP (Power), excluding PEEP (Power), and using ΔP (Power). The primary analysis incorporated all included trials. A secondary subgroup analysis was restricted to trials of lower versus higher PEEP strategies.

Results: We included 9 trials involving 4,731 subjects in the analysis. Odds ratios for moderation derived from meta-regression showed that variations in V, ΔP, and Power were associated with increased mortality with odds ratios of 1.24 (95% CI 1.03-1.49), 1.31 (95% CI 1.03-1.66), and 1.37 (95% CI 1.05-1.78), respectively. In trials comparing higher versus lower PEEP strategies, Power was increased in the higher PEEP arm (24 ± 1.7 vs 20 ± 1.5 J/min, respectively), whereas the other parameters were not affected on average by a higher PEEP ventilation strategy.

Conclusions: In trials of lung-protective ventilation strategies, V, ΔP, Power, Power, and Power exhibited similar moderation of treatment effect on mortality. In this study, modified mechanical power did not add important information on the risk of death from VILI in comparison to V or ΔP.
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http://dx.doi.org/10.4187/respcare.07876DOI Listing
February 2021

Atrial Fibrillation Detection During Sepsis: Study on MIMIC III ICU Data.

Authors:
Syed Khairul Bashar Md Billal Hossain Eric Ding Allan J Walkey David D McManus Ki H Chon

IEEE J Biomed Health Inform 2020 Nov 6;24(11):3124-3135. Epub 2020 Nov 6.

Sepsis is defined by life-threatening organ dysfunction during infection and is one of the leading causes of critical illness. During sepsis, there is high risk that new-onset of atrial fibrillation (AF) can occur, which is associated with significant morbidity and mortality. As a result, computer aided automated and reliable detection of new-onset AF during sepsis is crucial, especially for the critically ill patients in the intensive care unit (ICU). In this paper, a novel automated and robust two-step algorithm to detect AF from ICU patients using electrocardiogram (ECG) signals is presented. First, several statistical parameters including root mean square of successive differences, Shannon entropy, and sample entropy were calculated from the heart rate for the screening of possible AF segments. Next, Poincaré plot-based features along with P-wave characteristics were used to reduce false positive detection of AF, caused by the premature atrial and ventricular beats. A subset of the Medical Information Mart for Intensive Care (MIMIC) III database containing 198 subjects was used in this study. During the training and validation phases, both the simple thresholding as well as machine learning classifiers achieved very high segment-wise AF classification performance. Finally, we tested the performance of our proposed algorithm using two independent test data sets and compared the performance with two state-of-the-art methods. The algorithm achieved an overall 100% sensitivity, 98% specificity, 98.99% accuracy, 98% positive predictive value, and 100% negative predictive value on the subject-wise AF detection, thus showing the efficacy of our proposed algorithm in critically ill sepsis patients. The annotations of the data have been made publicly available for other investigators.
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http://dx.doi.org/10.1109/JBHI.2020.2995139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670858PMC
November 2020

Novel Density Poincaré Plot Based Machine Learning Method to Detect Atrial Fibrillation From Premature Atrial/Ventricular Contractions.

Authors:
Syed Khairul Bashar Dong Han Fearass Zieneddin Eric Ding Timothy P Fitzgibbons Allan J Walkey David D McManus Bahram Javidi Ki H Chon

IEEE Trans Biomed Eng 2021 Feb 20;68(2):448-460. Epub 2021 Jan 20.

Objective: Detection of Atrial fibrillation (AF) from premature atrial contraction (PAC) and premature ventricular contraction (PVC) is difficult as frequent occurrences of these ectopic beats can mimic the typical irregular patterns of AF. In this paper, we present a novel density Poincaré plot-based machine learning method to detect AF from PAC/PVCs using electrocardiogram (ECG) recordings.

Methods: First, we propose the generation of this new density Poincaré plot which is derived from the difference of the heart rate (DHR) and provides the overlapping phase-space trajectory information of the DHR. Next, from this density Poincaré plot, several image processing domain-based approaches including statistical central moments, template correlation, Zernike moment, discrete wavelet transform and Hough transform features are used to extract suitable features. Subsequently, the infinite latent feature selection algorithm is implemented to rank the features. Finally, classification of AF vs. PAC/PVC is performed using K-Nearest Neighbor, Support vector machine (SVM) and Random Forest (RF) classifiers. Our method is developed and validated using a subset of Medical Information Mart for Intensive Care (MIMIC) III database containing 10 AF and 10 PAC/PVC subjects. Results- During the segment-wise 10-fold cross-validation, SVM achieved the best performance with 98.99% sensitivity, 95.18% specificity and 97.45% accuracy with the extracted features. In subject-wise scenario, RF achieved the highest accuracy of 91.93%. Moreover, we further validated the proposed method using two other databases: wearable armband ECG data and the Physionet AFPDB. 100% PAC detection accuracy was obtained for both databases without any further training.

Conclusion: Our proposed density Poincaré plot-based method showed superior performance when compared with four existing algorithms; thus showing the efficacy of the extracted image domain-based features.

Significance: From intensive care unit's ECG to wearable armband ECGs, the proposed method is shown to discriminate PAC/PVCs from AF with high accuracy.
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http://dx.doi.org/10.1109/TBME.2020.3004310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863548PMC
February 2021

Use of Hydrocortisone, Ascorbic Acid, and Thiamine in Adults with Septic Shock.

Authors:
Emily A Vail Hannah Wunsch Ruxandra Pinto Nicholas A Bosch Allan J Walkey Peter K Lindenauer Hayley B Gershengorn

Am J Respir Crit Care Med 2020 12;202(11):1531-1539

Division of Pulmonary, Critical Care, and Sleep Medicine, University of Miami Miller School of Medicine, Miami, Florida; and.

In December 2016, a single-center study describing significant improvements in mortality among a small group of patients with severe sepsis and septic shock treated with hydrocortisone, high-dose ascorbic acid, and thiamine (HAT therapy) was published online. This study aims to describe the administration of HAT therapy among U.S. adults with septic shock before and after study publication and to compare outcomes between patients who received and did not receive HAT therapy. We performed a retrospective cohort study of 379 acute care hospitals in the Premier Healthcare Database including patients discharged from October 1, 2015, to September 30, 2018. Exposure was quarter year of hospital discharge; postpublication was defined as January 2017 onward (July 2017 for effectiveness analyses). The primary outcome was receipt of HAT at least once during hospitalization. We conducted unadjusted segmented regression analyses to examine temporal trends in HAT administration. In patients with early septic shock, we compared the association of early HAT therapy (within 2 d of hospitalization) with hospital mortality using multivariable modeling and propensity score matching. Among 338,597 patients, 3,574 (1.1%) received HAT therapy, 98.7% in the postpublication period. HAT administration increased from 0.03% of patients (95% confidence interval [CI], 0.02-0.04) before publication to 2.65% (95% CI, 2.46-2.83) in the last quarter, with a significant step up in use after December 2016 ( < 0.001). Receipt of early HAT was associated with higher hospital mortality (28.2% vs. 19.7%;  < 0.001; adjusted odds ratio, 1.17 [95% CI, 1.02-1.33]; primary propensity-matched model adjusted odds ratio, 1.19 [95% CI, 1.02-1.40]). Publication of a single-center retrospective study was associated with significantly increased administration of HAT. Among patients with early septic shock, receipt of HAT was not associated with mortality benefit.
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http://dx.doi.org/10.1164/rccm.202005-1829OCDOI Listing
December 2020

Temporal trends in pharmacologic prophylaxis for venous thromboembolism after hip and knee replacement in older adults.

Authors:
Darae Ko Alok Kapoor Adam J Rose Amresh D Hanchate Donald Miller Michael R Winter Joseph N Palmisano Lori E Henault Lisa Fredman Allan J Walkey Yorghos Tripodis Anita Karcz Elaine M Hylek

Vasc Med 2020 10 9;25(5):450-459. Epub 2020 Jun 9.

Section of General Internal Medicine, Boston University Medical Center, Boston University School of Medicine, Boston, MA, USA.

Trends in prescription for venous thromboembolism (VTE) prophylaxis following total hip (THR) and knee replacement (TKR) since the approval of direct oral anticoagulants (DOACs) and the 2012 guideline endorsement of aspirin are unknown, as are the risks of adverse events. We examined practice patterns in the prescription of prophylaxis agents and the risk of adverse events during the in-hospital period (the 'in-hospital sample') and 90 days following discharge (the 'discharge sample') among adults aged ⩾ 65 undergoing THR and TKR in community hospitals in the Institute for Health Metrics database over a 30-month period during 2011 to 2013. Eligible medications included fondaparinux, DOACs, low molecular weight heparin (LMWH), other heparin products, warfarin, and aspirin. Outcomes were validated by physician review of source documents: VTE, major hemorrhage, cardiovascular events, and death. The in-hospital and the discharge samples included 10,503 and 5722 adults from 65 hospitals nationwide, respectively (mean age 73, 74 years; 61%, 63% women). Pharmacologic prophylaxis was near universal during the in-hospital period (93%) and at discharge (99%). DOAC use increased substantially and was the prophylaxis of choice for nearly a quarter (in-hospital) and a third (discharge) of the patients. Aspirin was the sole discharge prophylactic agent for 17% and 19% of patients undergoing THR and TKR, respectively. Warfarin remained the prophylaxis agent of choice for patients aged 80 years and older. The overall risk of adverse events was low, at less than 1% for both the in-hospital and discharge outcomes. The low number of adverse events precluded statistical comparison of prophylaxis regimens.
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http://dx.doi.org/10.1177/1358863X20927096DOI Listing
October 2020

The Viral Infection and Respiratory Illness Universal Study (VIRUS): An International Registry of Coronavirus 2019-Related Critical Illness.

Authors:
Allan J Walkey Vishakha K Kumar Michael O Harhay Scott Bolesta Vikas Bansal Ognjen Gajic Rahul Kashyap

Crit Care Explor 2020 Apr 29;2(4):e0113. Epub 2020 Apr 29.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN.

The coronavirus disease 2019 pandemic has disproportionally strained intensive care services worldwide. Large areas of uncertainly regarding epidemiology, physiology, practice patterns, and resource demands for patients with coronavirus disease 2019 require rapid collection and dissemination of data. We describe the conception and implementation of an intensive care database rapidly developed and designed to meet data analytic needs in response to the coronavirus disease 2019 pandemic-the multicenter, international Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study.

Design: Prospective cohort study and disease registry.

Setting: Multinational cohort of ICUs.

Patients: Critically ill patients with a diagnosis of coronavirus disease 2019.

Interventions: None.

Measurements And Main Results: Within 2 weeks of conception of the Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study, study leadership was convened, registry case report forms were designed, electronic data entry set up, and more than 250 centers had submitted the protocol for institutional review board approval, with more than 100 cases entered.

Conclusions: The Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study provides an example of a rapidly deployed, international, pandemic registry that seeks to provide near real-time analytics and information regarding intensive care treatments and outcomes for patients with coronavirus disease 2019.
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http://dx.doi.org/10.1097/CCE.0000000000000113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188422PMC
April 2020

Assessing the Course of Organ Dysfunction Using Joint Longitudinal and Time-to-Event Modeling in the Vasopressin and Septic Shock Trial.

Authors:
Michael O Harhay Alessandro Gasparini Allan J Walkey Gary E Weissman Michael J Crowther Sarah J Ratcliffe James A Russell

Crit Care Explor 2020 Apr 29;2(4):e0104. Epub 2020 Apr 29.

Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada.

Non-mortality septic shock outcomes (e.g., Sequential Organ Failure Assessment score) are important clinical endpoints in pivotal sepsis trials. However, comparisons of observed longitudinal non-mortality outcomes between study groups can be biased if death is unequal between study groups or is associated with an intervention (i.e., informative censoring). We compared the effects of vasopressin versus norepinephrine on the Sequential Organ Failure Assessment score in the Vasopressin and Septic Shock Trial to illustrate the use of joint modeling to help minimize potential bias from informative censoring.

Design: Secondary analysis of the Vasopressin and Septic Shock Trial data.

Setting: Twenty-seven ICUs in Canada, Australia, and United States.

Subjects: Seven hundred sixty-three participants with septic shock who received blinded vasopressin ( = 389) or norepinephrine infusions ( = 374).

Measurements And Main Results: Sequential Organ Failure Assessment scores were calculated daily until discharge, death, or day 28 after randomization. Mortality was numerically higher in the norepinephrine arm (28 d mortality of 39% vs 35%; = 0.25), and there was a positive association between higher Sequential Organ Failure Assessment scores and patient mortality, characteristics that suggest a potential for bias from informative censoring of Sequential Organ Failure Assessment scores by death. The best-fitting joint longitudinal (i.e., linear mixed-effects model) and survival (i.e., Cox proportional hazards model for the time-to-death) model showed that norepinephrine was associated with a more rapid improvement in the total Sequential Organ Failure Assessment score through day 4, and then the daily Sequential Organ Failure Assessment scores converged and overlapped for the remainder of the study period.

Conclusions: Short-term reversal of organ dysfunction occurred more rapidly with norepinephrine compared with vasopressin, although differences between study arms did not persist after day 4. Joint models are an accessible methodology that could be used in critical care trials to assess the effects of interventions on the longitudinal progression of key outcomes (e.g., organ dysfunction, biomarkers, or quality of life) that may be informatively truncated by death or other censoring events.
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http://dx.doi.org/10.1097/CCE.0000000000000104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188432PMC
April 2020

Tracking respiratory mechanics around natural breathing rates via variable ventilation.

Authors:
Samer Bou Jawde Allan J Walkey Arnab Majumdar George T O'Connor Bradford J Smith Jason H T Bates Kenneth R Lutchen Béla Suki

Sci Rep 2020 04 21;10(1):6722. Epub 2020 Apr 21.

Department of Biomedical Engineering, Boston University, Boston, MA, USA.

Measuring respiratory resistance and elastance as a function of time, tidal volume, respiratory rate, and positive end-expiratory pressure can guide mechanical ventilation. However, current measurement techniques are limited since they are assessed intermittently at non-physiological frequencies or involve specialized equipment. To this end, we introduce ZVV, a practical approach to continuously track resistance and elastance during Variable Ventilation (VV), in which frequency and tidal volume vary from breath-to-breath. ZVV segments airway pressure and flow recordings into individual breaths, calculates resistance and elastance for each breath, bins them according to frequency or tidal volume and plots the results against bin means. ZVV's feasibility was assessed clinically in five human patients with acute lung injury, experimentally in five mice ventilated before and after lavage injury, and computationally using a viscoelastic respiratory model. ZVV provided continuous measurements in both settings, while the computational study revealed <2% estimation errors. Our findings support ZVV as a feasible technique to assess respiratory mechanics under physiological conditions. Additionally, in humans, ZVV detected a decrease in resistance and elastance with time by 12.8% and 6.2%, respectively, suggesting that VV can improve lung recruitment in some patients and can therefore potentially serve both as a dual diagnostic and therapeutic tool.
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http://dx.doi.org/10.1038/s41598-020-63663-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174375PMC
April 2020

Update in Critical Care 2019.

Authors:
Yaseen M Arabi Rama Mallampalli Joshua A Englert Nicholas A Bosch Allan J Walkey Hasan M Al-Dorzi

Am J Respir Crit Care Med 2020 05;201(9):1050-1057

Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.1164/rccm.202002-0285UPDOI Listing
May 2020

How Closely Do Clinical Trial Participants Resemble "Real-World" Patients with Groups 2 and 3 Pulmonary Hypertension? A Structured Review.

Authors:
Kari R Gillmeyer Seppo T Rinne Allan J Walkey Shirley X Qian Renda Soylemez Wiener

Ann Am Thorac Soc 2020 06;17(6):779-783

Edith Nourse Rogers Veterans HospitalBedford, Massachusettsand.

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http://dx.doi.org/10.1513/AnnalsATS.202001-003RLDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258417PMC
June 2020

Vasopressor Dosing in Septic Shock Clinical Trials: A Systematic Review and Ecologic Study.

Authors:
Bijan Teja Nicholas A Bosch Allan J Walkey Ruxandra Pinto Hannah Wunsch

Ann Am Thorac Soc 2020 06;17(6):773-776

University of TorontoToronto, Ontario, Canada.

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http://dx.doi.org/10.1513/AnnalsATS.201908-599RLDOI Listing
June 2020

Initial Precipitants and Recurrence of Atrial Fibrillation.

Authors:
Elizabeth Y Wang Olivia L Hulme Shaan Khurshid Lu-Chen Weng Seung Hoan Choi Allan J Walkey Jeffrey M Ashburner David D McManus Daniel E Singer Steven J Atlas Emelia J Benjamin Patrick T Ellinor Ludovic Trinquart Steven A Lubitz

Circ Arrhythm Electrophysiol 2020 03 12;13(3):e007716. Epub 2020 Feb 12.

Division of Cardiology (S.K., S.A.L.), Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston.

Background: Atrial fibrillation (AF) may occur after an acute precipitant and subsequently resolve. Management guidelines for AF in these settings are unclear as the risk of recurrent AF and related morbidity is poorly understood. We examined the relations between acute precipitants of AF and long-term recurrence of AF in a clinical setting.

Methods: From a multi-institutional longitudinal electronic medical record database, we identified patients with newly diagnosed AF between 2000 and 2014. We developed algorithms to identify acute AF precipitants (surgery, sepsis, pneumonia, pneumothorax, respiratory failure, myocardial infarction, thyrotoxicosis, alcohol, pericarditis, pulmonary embolism, and myocarditis). We assessed risks of AF recurrence in individuals with and without a precipitant and the relations between AF recurrence and heart failure, stroke, and mortality.

Results: Among 10 723 patients with newly diagnosed AF (67.9±9.9 years, 41% women), 19% had an acute AF precipitant, the most common of which were cardiac surgery (22%), pneumonia (20%), and noncardiothoracic surgery (15%). The cumulative incidence of AF recurrence at 5 years was 41% among individuals with a precipitant compared with 52% in those without a precipitant (adjusted hazard ratio [HR], 0.75 [95% CI, 0.69-0.81]; <0.001). The lowest risk of recurrence among those with precipitants occurred with postoperative AF (5-year incidence 32% in cardiac surgery and 39% in noncardiothoracic surgery). Regardless of the presence of an initial precipitant, recurrent AF was associated with increased adjusted risks of heart failure (hazard ratio, 2.74 [95% CI, 2.39-3.15]; <0.001), stroke (hazard ratio, 1.57 [95% CI, 1.30-1.90]; <0.001), and mortality (hazard ratio, 2.96 [95% CI, 2.70-3.24]; <0.001).

Conclusions: AF after an acute precipitant frequently recurs, although the risk of recurrence is lower than among individuals without an acute precipitant. Recurrence is associated with substantial long-term morbidity and mortality. Future studies should address surveillance and management after newly diagnosed AF in the setting of an acute precipitant.
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http://dx.doi.org/10.1161/CIRCEP.119.007716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141776PMC
March 2020

The authors reply.

Authors:
Anica C Law Jennifer P Stevens Allan J Walkey

Crit Care Med 2020 03;48(3):e249-e250

Center for Healthcare Delivery Science, Beth Israel Deaconess Medical Center, Boston, MA, and Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA Evans Center for Implementation and Improvement Sciences and The Pulmonary Center, Department of Medicine, Boston University School of Medicine and Department of Health Law, Policy and Management, Boston University School of Public Health, Boston, MA.

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http://dx.doi.org/10.1097/CCM.0000000000004168DOI Listing
March 2020

"Microclimates" of Care for Hospitalized Patients with Pulmonary Disease: An Idea That Will Bear Fruit?

Authors:
Patrick G Lyons Allan J Walkey

Ann Am Thorac Soc 2020 02;17(2):175-177

The Pulmonary Center, and.

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http://dx.doi.org/10.1513/AnnalsATS.201910-809EDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993803PMC
February 2020