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Importance: Extubation Advisor (EA) is a novel software tool that generates a synoptic report for each Spontaneous Breathing Trial (SBT) conducted to inform extubation decision-making., Objectives: To assess bedside EA implementation, perceptions of utility, and identify barriers and facilitators of use., Design, Setting and Participants: We conducted a phase I mixed-methods interventional study in three mixed intensive care unit (ICUs) in two academic hospitals. We interviewed critical care physicians (MDs) and respiratory therapists (RTs) regarding user-centered design principles and usability., Analysis: We evaluated our ability to consent participants (feasibility threshold 50%), capture complete data (threshold 90%), generate and review EA reports in real-time (thresholds 75% and 80%, respectively), and MD perception of tool usefulness (6-point Likert scale). We analyzed interview transcripts using inductive coding to identify facilitators and barriers to EA implementation and perceived benefit of tool use., Results: We enrolled 31 patients who underwent 70 SBTs. Although consent rates [31/31 (100%], complete data capture [68/68 (100%)], and EA report generation [68/70 (97.1%)] exceeded feasibility thresholds, reports were reviewed by MDs for [55/70 (78.6%)] SBTs. Mean MD usefulness score was 4.0/6. Based on feedback obtained from 36 interviews (15 MDs, 21 RTs), we revised the EA report twice and identified facilitators (ability to track patient progress, enhance extubation decision-making, and provide support in resource-limited settings) and barriers (resource constraints, need for education) to tool implementation. Half of respondents (9 MDs, 9 RTs; combined 50%) perceived definite or potential benefit to EA tool use., Conclusion: This is the first study of a waveform-based variability-derived, predictive clinical decision support tool evaluated in adult ICUs. Our findings support the feasibility of integrating the EA tool into bedside workflow. Clinical trials are needed to assess the utility of the EA tool in practice and its impact on extubation decision-making and outcomes., Trial Registration: NCT04708509., Competing Interests: Declaration of Conflicting InterestsDr A Seely and Dr C Herry are named on a patent related to Extubation Advisor technology described in this paper. Dr Seely is founder and board chairman of Therapeutic Monitoring Systems, a company founded to help research, develop, and commercialize clinical decision support tools based on variability analysis, including Extubation Advisor.

Objectives: Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock., Data Sources: We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024., Study Selection: We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration., Data Extraction: Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates., Data Synthesis: We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47-0.94], low certainty) and hospital length of stay (mean difference [MD] -2.1 d [95% CI, -1.4 to -2.8], low certainty). MB may also reduce duration of vasopressors (MD -31.1 hr [95% CI, -16.5 to -45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1-14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, -0.2% to 2.0%], very low certainty). We did not find any differences in adverse events., Conclusions: Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed., Registration: Center for Open Science (https://osf.io/hpy4j)., Competing Interests: Dr. Seely holds patents related to multiorgan variability analysis and has shares in Therapeutic Monitoring Systems. Dr. Cook is supported by a Canada Research Chair in Critical Care Knowledge Translation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Increasing evidence supports specific approaches to liberate patients from invasive ventilation including the use of liberation protocols, inspiratory assistance during spontaneous breathing trials (SBTs), early extubation of patients with chronic obstructive pulmonary disease to noninvasive ventilation, and prophylactic use of noninvasive support strategies after extubation. Additional research is needed to elucidate the best criteria to identify patients who are ready to undergo an SBT and to inform optimal screening frequency, the best SBT technique and duration, extubation assessments, and extubation decision-making. Additional clarity is also needed regarding the optimal timing to measure and report extubation success., Competing Interests: Disclosure K.E.A. Burns holds a Canadian Institutes of Health Research grant to investigate weaning strategies and Physician Services Incorporated Mid Career Research Award. A.J. Seely is the founder and CEO of Therapeutic Monitoring Systems, which holds global licensing rights for intellectual property related to Extubation Advisor (a tool designed to aid extubation assessment) and tools being developed in the Ottawa Hospital Research Institute Dynamical Analysis Laboratory that require regulatory approval and commercialization for bedside application. B. Rochwerg has no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: There is limited clinical evidence to support any specific parenchymal air leak resolution criteria when using digital pleural drainage devices following lung resection. The aim of this study is to determine an optimal air leak resolution criteria, where duration of chest tube drainage is minimized while avoiding complications from premature chest tube removal., Methods: Airflow data averaged at 10-minute intervals was collected prospectively using a digital pleural drainage device (Thopaz; Medela) in 400 patients from 2015 to 2019. All permutations of air leak resolution criteria from <10 to 100 mL/minute for 4 to 12 hours were applied retrospectively to the pleural drainage data to determine air leak duration, and air leak recurrence frequency and volume. Air leak recurrence indicates potential for rather than occurrence of adverse events. Descriptive statistics were used to identify the optimal criteria based on patient safety (low frequency and volume of air leak recurrences), and efficiency (shortest initial air leak duration)., Results: The majority of the 400 patients underwent lobectomy (57% [227 out of 400]), wedge resections (29% [115 out of 400]), or segmentectomies (8% [32 out of 400]) for lung cancer (90% [360 out of 400]). An airflow threshold <50 mL/minute resulted in longer air leak duration before meeting the criteria for air leak resolution ( P  < .0001). Air leak recurrence frequency and volume were greater in patients with a monitoring period <8 consecutive hours ( P  < .0001)., Conclusions: When using a digital pleural drainage device, a postoperative air leak resolution criteria <50 mL/minute for 8 consecutive hours was associated with the best safety and efficiency profile., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Objectives: To perform a systematic review and meta-analysis to evaluate the association of various measures of glycemic variability, including time-domain and complexity-domain, with short-term mortality in patients with critical illness., Data Sources: We searched Embase Classic +, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to November 3, 2023., Study Selection: We included English language studies that assessed metrics of glycemic variation or complexity and short-term mortality in patients admitted to the ICU., Data Extraction: Two authors performed independent data abstraction and risk-of-bias assessments. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios and mean difference. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty of pooled estimates., Data Synthesis: We included 41 studies ( n = 162,259). We demonstrate that increased sd, coefficient of variance, glycemic lability index, and decreased time in range are probably associated with increased mortality in critically ill patients (moderate certainty) and that increased mean absolute glucose, mean amplitude of glycemic excursion, and detrended fluctuation analysis may be associated with increased mortality (low certainty)., Conclusions: We found a consistent association between increased measures of glycemic variability and higher short-term mortality in patient with critical illness. Further research should focus on standardized measurements of glycemic variation and complexity, along with their utility as therapeutic targets and prognostic markers., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

The integration of large language models (LLMs) and artificial intelligence (AI) into scientific writing, especially in medical literature, presents both unprecedented opportunities and inherent challenges. This manuscript evaluates the transformative potential of LLMs for the synthesis of information, linguistic enhancements, and global knowledge dissemination. At the same time, it raises concerns about unintentional plagiarism, the risk of misinformation, data biases, and an over-reliance on AI. To address these, we propose governing principles for AI adoption that ensure integrity, transparency, validity, and accountability. Additionally, guidelines for reporting AI involvement in manuscript development are delineated, and a classification system to specify the level of AI assistance is introduced. This approach uniquely addresses the challenges of AI in scientific writing, emphasizing transparency in authorship, qualification of AI involvement, and ethical considerations. Concerns regarding access equity, potential biases in AI-generated content, authorship dynamics, and accountability are also explored, emphasizing the human author's continued responsibility. Recommendations are made for fostering collaboration between AI developers, researchers, and journal editors and for emphasizing the importance of AI's responsible use in academic writing. Regular evaluations of AI's impact on the quality and biases of medical manuscripts are also advocated. As we navigate the expanding realm of AI in scientific discourse, it is crucial to maintain the human element of creativity, ethics, and oversight, ensuring that the integrity of scientific literature remains uncompromised., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hryciw, Seely and Kyeremanteng.)

Background: This study provides an update to a landmark 2004 report describing demographics, training, and trends in adherence to thoracic surgery practice standards in Canada., Methods: An updated questionnaire was administered to all members of the Canadian Association of Thoracic Surgeons via email (n=142, compared to n=68 in 2004). Our report incorporates internal data from Ontario Health and the Canadian Partnership Against Cancer., Results: Forty-eight surgeons completed the survey (male, 70.8%; mean±standard deviation age, 50.3±9.3 years). This represents a 33.8% response rate, compared to 64.7% in 2004. Most surgeons (69%) served a patient population of over 1 million per center; 32%-34% reported an on-call ratio of 1:4-1:5 days, and the average weekly hours worked was 56.4±11.9. Greater access to dedicated geographic units per center (73% in 2021 vs. 53% in 2004) has improved thoracic-associated services and house staff, notably endoscopy units (100% vs. 91%), with 73% of respondents having access to both endobronchial and endoscopic ultrasound. Access to thoracic radiology has also improved, particularly regarding positron emission tomography scanners per center (76.9% vs. 13%). Annual case volumes for lung (255 vs. 128), esophageal (41 vs. 19), and mediastinal resections (30 vs. 13), along with hiatal hernia repair (45 vs. 20), have increased substantially despite reports of operating room availability and radiology as rate-limiting steps., Conclusion: This survey characterizes compliance with current practice standards, addressing the needs of thoracic surgeons across Canada. Over 85% of respondents were aware of the 2004 compliance paper, and 35% had applied for resources and equipment in response.

Background: This update summarizes key changes made to the protocol for the Frequency of Screening and Spontaneous Breathing Trial (SBT) Technique Trial-North American Weaning Collaborative (FAST-NAWC) trial since the publication of the original protocol. This multicenter, factorial design randomized controlled trial with concealed allocation, will compare the effect of both screening frequency (once vs. at least twice daily) to identify candidates to undergo a SBT and SBT technique [pressure support + positive end-expiratory pressure vs. T-piece] on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American intensive care units., Methods/design: Protocols for the pilot, factorial design trial and the full trial were previously published in J Clin Trials ( https://doi.org/10.4172/2167-0870.1000284 ) and Trials (https://doi: 10.1186/s13063-019-3641-8). As planned, participants enrolled in the FAST pilot trial will be included in the report of the full FAST-NAWC trial. In response to the onset of the coronavirus disease of 2019 (COVID-19) pandemic when approximately two thirds of enrollment was complete, we revised the protocol and consent form to include critically ill invasively ventilated patients with COVID-19. We also refined the statistical analysis plan (SAP) to reflect inclusion and reporting of participants with and without COVID-19. This update summarizes the changes made and their rationale and provides a refined SAP for the FAST-NAWC trial. These changes have been finalized before completion of trial follow-up and the commencement of data analysis., Trial Registration: Clinical Trials.gov NCT02399267., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Complex living systems, such as the human organism, are characterized by their self-organized and dissipative behaviors, where irreversible processes continuously produce entropy internally and export it to the environment; however, a means by which to measure human entropy production and entropy flow over time is not well-studied. In this article, we leverage prior experimental data to introduce an experimental approach for the continuous measurement of external entropy flow (released to the environment) and internal entropy production (within the body), using direct and indirect calorimetry, respectively, for humans exercising under heat stress. Direct calorimetry, performed with a whole-body modified Snellen calorimeter, was used to measure the external heat dissipation from the change in temperature and relative humidity between the air outflow and inflow, from which was derived the rates of entropy flow of the body. Indirect calorimetry, which measures oxygen consumption and carbon dioxide production from inspired and expired gases, was used to monitor internal entropy production. A two-compartment entropy flow model was used to calculate the rates of internal entropy production and external entropy flow for 11 middle-aged men during a schedule of alternating exercise and resting bouts at a fixed metabolic heat production rate. We measured a resting internal entropy production rate of (0.18 ± 0.01) W/(K·m 2 ) during heat stress only, which is in agreement with published measurements. This research introduces an approach for the real-time monitoring of entropy production and entropy flow in humans, and aims for an improved understanding of human health and illness based on non-equilibrium thermodynamics.

Objectives: To identify factors associated with failure of noninvasive ventilation (NIV) in the post-extubation period., Data Sources: We searched Embase Classic +, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to February 28, 2022., Study Selection: We included English language studies that provided predictors of post-extubation NIV failure necessitating reintubation., Data Extraction: Two authors conducted data abstraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios (ORs) mean difference (MD), respectively. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty., Data Synthesis: We included 25 studies ( n = 2,327). Illness-related factors associated with increased odds of post-extubation NIV failure were higher critical illness severity (OR, 3.56; 95% CI, 1.96-6.45; high certainty) and a diagnosis of pneumonia (OR, 6.16; 95% CI, 2.59-14.66; moderate certainty). Clinical and biochemical factors associated with moderate certainty of increased risk of NIV failure post-extubation include higher respiratory rate (MD, 1.54; 95% CI, 0.61-2.47), higher heart rate (MD, 4.46; 95% CI, 1.67-7.25), lower Pa o2 :F io2 (MD, -30.78; 95% CI, -50.02 to -11.54) 1-hour after NIV initiation, and higher rapid shallow breathing index (MD, 15.21; 95% CI, 12.04-18.38) prior to NIV start. Elevated body mass index was the only patient-related factor that may be associated with a protective effect (OR, 0.21; 95% CI, 0.09-0.52; moderate certainty) on post-extubation NIV failure., Conclusions: We identified several prognostic factors before and 1 hour after NIV initiation associated with increased risk of NIV failure in the post-extubation period. Well-designed prospective studies are required to confirm the prognostic importance of these factors to help further guide clinical decision-making., Competing Interests: Dr. Seely is Founder and Chief Operating Officer for Therapeutic Monitoring Systems, a company dedicated to research, development, and commercialization of variability-derived clinical decision support tools, including a tool designed to improve extubation decision-making. However, there is no direct relationship with this study, its methodology or results. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Positive deviance (PD) seminars, which have shown excellent results in improving the quality of surgical practices, use individual performance feedback to identify team members who outperform their peers; the strategies from those with exemplary performance are used to improve team members' practices. Our study aimed to use the PD approach with arthroplasty surgeons and nurses to identify multidisciplinary strategies and recommendations to improve operating room (OR) efficiency., Methods: We recruited 5 surgeons who performed high-volume primary arthroplasty and had participated in 4-joint rooms since 2012, and 29 nurses who had participated in 4-joint rooms and in at least 16 cases in our data set. Three 1-hour PD sessions were held in February and March 2021: 1 with surgeons, 1 with nurses, and 1 with both surgeons and nurses to select recommendations for implementation. The sessions were led by a member of the nonorthopedic surgical faculty who was familiar with the subjects discussed and with PD seminars. To determine the success of the recommendations, we compared OR efficiency before and after implementation. We defined success as performance of 4 joint procedures within 8 hours., Results: Eleven recommendations were recorded from the session with nurses and 7 from the session with surgeons, of which 11 were selected for implementation. During the month after implementation, there were great improvements across all time intervals of surgical procedures, with the greatest improvements seen in mean anesthesia preparation time in the room (4.51 min [26.3%]), mean procedure duration (9.75 min [14.0%]) and mean anesthesia finish time (5.78 min [44.0%]) (all p < 0.001). The total time saved per day was 49.84 minutes; this led to a success rate of 69.0%, a relative increase of 73.8% from our 2012-2020 success rate of 39.7% ( p < 0.001)., Conclusion: The recommendations and increased motivation owing to the individualized feedback reduced time spent per case, allowing more days to finish on time. Positive deviance seminars offer an inexpensive, efficient and collegial means for process improvement in the OR., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: Postoperative adverse events (AEs) following pulmonary resection enormously impact patient well-being, length of stay (LOS) and healthcare costs. Standardised AE data collection can be used to identify positive outliers demonstrating positive deviance (PD) who may be helpful to inform the best practice. Here, we describe our initial experience of a novel quality improvement process using PD to reduce LOS and AEs., Methods: AE rates and LOS were collected from four centres (2014-2020) using a common dictionary. Surgeons repeatedly participated in 60 to 90 min seminars consisting of the following process: identify outcome and procedure targeted, review relevant best evidence literature, view all data anonymised by surgeon or centre (if multicentre), choose and reveal identity of best performance PD outliers, who discuss their management principles while all receive self-evaluation reports, followed by collegial discussion to generate consensus recommendations, voted by all. We assessed overall impact on AEs and LOS using aggregate data in a before/after analysis., Results: A total of 131 surgeons (average 12/seminar) participated in 11 PD seminars (8 local and 3 multicentre), yielding 85 consensus recommendation (average 8/seminar). Median LOS following lobectomy decreased from 4.0 to 3.0 days (p=0.04) following local PD seminars and from 4.0 to 3.5 days (p=0.11) following multicentre seminars. Trends for reductions in multiple AE rates were also observed., Conclusion: While limited by the longitudinal design, these findings provide preliminary support for this data-driven, collegial and actionable quality improvement process to help standardise and improve patient care, and merits further more rigorous investigation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: As postoperative adverse events (AEs) drive worsened patient experience, longer length of stay, and increased costs of care, surgeons have long sought to engage in innovative approaches aimed at reducing AEs to improve the quality and safety of surgical care. While data-driven AE performance measurement and feedback (PMF) as a form of continuing professional development (CPD) has been presented as a possible approach to continuous quality improvement (CQI), little is known about the barriers and facilitators that influence surgeons' engagement and uptake of these CPD programs. The purpose of this knowledge translation informed CPD study was to examine surgeons' perspectives of the challenges and facilitators to participating in surgical CQI with the broader objective of enhancing future improvements of such CPD interventions., Methods: Using Everett Rogers diffusion of innovations framework as a sampling frame, the participants were recruited across five surgical divisions. An exploratory case study approach, including in-depth semistructured interviews, was employed. Interview transcripts were analyzed and directly coded using the Theoretical Domains Framework., Results: Directed coding yielded a total of 527 coded barriers and facilitators to behavior change pertaining to the implementation and adoption of PMF with the majority of barriers and facilitators coded in four key theoretical domains environmental context and resources, social influences, knowledge, and beliefs about consequences. A key barrier was the lack of support from the hospital necessitating surgeons' self-funding their own PMF programs. Facilitators included having a champion to drive CQI and using seminars to facilitate discussions around CQI principles and practices., Discussion: This study identified multiple barriers and facilitators to surgeons' engagement and uptake of a data-driven PMF system in surgery. A key finding of the study was the identification of the influential role of positive deviance seminars as a quality improvement and patient safety mechanism that encourages surgeon engagement in PMF systems., Competing Interests: Disclosures: The authors declare no conflict of interest., (Copyright © 2022 The Alliance for Continuing Education in the Health Professions, the Association for Hospital Medical Education, and the Society for Academic Continuing Medical Education.)

Rationale: The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive care units (ICUs) prioritized patient care and COVID-specific research. The international randomized controlled trial CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) was forced to halt recruitment at all sites in March 2020, creating immediate challenges. We applied the CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance) statement as a framework to report the impact of the pandemic on CYCLE and describe our mitigation approaches., Methods: On March 23, 2020, the CYCLE Methods Centre distributed a standardized email to determine the number of patients still in-hospital and those requiring imminent 90-day endpoint assessments. We assessed protocol fidelity by documenting attempts to provide the in-hospital randomized intervention (cycling or routine physiotherapy) and collect the primary outcome (physical function 3-days post-ICU discharge) and 90-day outcomes. We advised sites to prioritize data for the study's primary outcome. We sought feedback on pandemic barriers related to trial procedures., Results: Our main Methods Centre mitigation strategies included identifying patients at risk for protocol deviations, communicating early and frequently with sites, developing standardized internal tools focused on high-risk points in the protocol for monitoring patient progress, data entry, and validation, and providing guidance to conduct some research activities remotely. For study sites, our strategies included determining how institutional pandemic research policies applied to CYCLE, communicating with the Methods Centre about capacity to continue any part of the research, and developing contingency plans to ensure the protocol was delivered as intended. From 15 active sites (12 Canada, 2 US, 1 Australia), 5 patients were still receiving the study intervention in ICUs, 6 required primary outcomes, and 17 required 90-day assessments. With these mitigation strategies, we attempted 100% of ICU interventions, 83% of primary outcomes, and 100% of 90-day assessments per our protocol., Conclusions: We retained all enrolled patients with minimal missing data using several time-sensitive strategies. Although CONSERVE recommends reporting only major modifications incurred by extenuating circumstances, we suggest that it also provides a helpful framework for reporting mitigation strategies with the goal of improving research transparency and trial management., Trial Registration: NCT03471247. Registered on March 20, 2018., (© 2022. The Author(s).)

Background: Women and people of color are often underrepresented in medicine. This study examined the inclusivity and diversity of the recent history of the Canadian Association of Thoracic Surgeons (CATS) in both its executive committees and invited participation at its annual meeting., Methods: CATS internal records and previous programs of CATS annual meetings were reviewed from 1997 to 2020. Leadership positions, invited speakers, and award recipients were categorized by sex and race., Results: Of 199 CATS members in 2020, 93 (47%) were White men, 64 (32%) were men of color, 24 (12%) were White women, and 18 (9%) were women of color. The majority of CATS presidents (86%), committee chairs (57%), named lecturers (88%), other invited speakers (67%), and major award winners (90%) were White men. Women and people of color were underrepresented. The Resident Research Award was the most diverse: of 23 awards, 10 (44%) have been to men of color, 6 (26%) to White men, 4 (15%) to women of color, and 2 (8%) to White women., Conclusions: There is a need for more representation and inclusion of both women and people of color at multiple levels in CATS. This includes opportunities for improvement in the make-up of its executive committees, the speakers at its annual conference, and the recipients of its awards. CATS has established an Equity, Diversity and Inclusion Task Force to address this critical issue., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: To estimate the minimum percent change in failed extubation to make a tool designed to reduce extubation failure (Extubation Advisor [EA]) economically viable., Methods: We conducted an early return on investment (ROI) analysis using data from intubated intensive care unit (ICU) patients at a large Canadian tertiary care hospital. We obtained input parameters from the hospital database and published literature. We ran generalized linear models to estimate the attributable length of stay, total hospital cost, and time to subsequent extubation attempt following failure. We developed a Markov model to estimate the expected ROI and performed probabilistic sensitivity analyses to assess the robustness of findings. Costs were presented in 2020 Canadian dollars (C$)., Results: The model estimated a 1 percent reduction in failed extubation could save the hospital C$289 per intubated patient (95 percent CI: 197, 459). A large center seeing 2,500 intubated ICU patients per year could save C$723,124/year/percent reduction in failed extubation. At the current annual price of C$164,221, the EA tool must reduce extubation failure by at least 0.24 percent (95 percent CI: .14, .41) to make the tool cost-effective at our site., Conclusions: Clinical decision-support tools like the EA may play an important role in reducing healthcare costs by reducing the rate of extubation failure, a costly event in the ICU.

Objectives: The prominence of "enhanced recovery after surgery" (ERAS) protocols being adopted in thoracic surgery requires a re-evaluation of mechanical venous thromboembolism (VTE) prophylaxis guidelines. The goal of this study was to assess the role of sequential compression devices (SCD) in the prevention of VTEs such as deep vein thrombosis and pulmonary embolism (PE) in thoracic surgical patients., Methods: We identified 200 patients who underwent elective oncological thoracic surgery between December 2018 and December 2020 in 2 cohorts-1 with SCDs and 1 without (i.e. non-SCD). All patients followed a standardized enhanced recovery after surgery (ERAS) protocol. The quality of care provided by SCDs was evaluated by the incidence and severity of postoperative and follow-up VTEs. Cohorts were compared by the Caprini score (CS) and the Charlson Comorbidity Index (CCI) with a two one-sided t-test analysis. Secondary outcomes include perioperative characteristics and follow-up data., Results: Only 2 patients within the SCD group developed a PE with average CS and CCI metrics, both after hospital discharge and treated with anticoagulants, raising concern over the prophylactic nature of SCDs. The CS (6.9 ± 1.3 and 6.9 ± 1.5; P = 0.96) and the CCI (3.8 ± 2.0 and 4.1 ± 2.6; P = 0.33) for non-SCD and SCD, respectively, did not differ. The two one-sided t-test analysis for CS (P < 0.001) and CCI (P < 0.001) demonstrated equivalence., Conclusions: Although larger studies are required to confirm these results, routine SCD use may not be required when implementing ERAS protocols because clinically significant VTE rates were minimal., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objective: Triple normal lymph nodes, appearing benign on computed tomography, positron emission tomography, and endobronchial ultrasound, have less than a 6% probability of malignancy. We hypothesized that targeted sampling (TS), which omits biopsy of triple normal lymph nodes during endobronchial ultrasound, is not an inferior staging strategy to systematic sampling (SS) of all lymph nodes., Methods: A prospective randomized feasibility trial was conducted to decide on the progression to a pan-Canadian trial comparing TS with SS. Patients with cN0-N1 non-small cell lung cancer undergoing endobronchial ultrasound were randomized to TS or SS. Lymph nodes in the TS arm crossed over to receive SS. Progression criteria included recruitment rate (70% minimum), procedure length (no significant increase for TS), and incidence of missed nodal metastasis (<6%). Mann-Whitney U test and McNemar's test on paired proportions were used for statistical comparisons., Results: The progression criterion of 70% recruitment rate was achieved early, triggering a planned early stoppage of the trial. Nineteen patients were allocated to each arm. The median procedure length for TS was significantly shorter than SS (3.07 vs 19.07 minutes; P < .001). After crossover analysis, 5.45% (95% confidence interval, 1.87-14.85) of lymph nodes in the TS arm were upstaged from N0 to N2, but this incidence of missed nodal metastasis was below the 6% threshold. During surgical resection, the nodal upstaging incidence from N0 to N2 was 0% for 15 lymph nodes in each arm., Conclusions: Progression criteria to a pan-Canadian, noninferiority crossover trial comparing TS with SS have been met, and such a trial is warranted., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction., Methods: In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28., Results: A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event., Conclusions: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.)., (Copyright © 2022 Massachusetts Medical Society.)

Objectives: Data regarding enhanced recovery after thoracic surgery (ERATS) are sparse and inconsistent. This study aims to evaluate the effects of implementing an enhanced ERATS programme on postoperative outcomes, patient experience and quality of life (QOL)., Methods: We conducted a prospective, longitudinal study evaluating 9 months before (pre-ERATS) and 9 months after (post-ERATS) a 3-month implementation of an ERATS programme in a single academic tertiary care centre. All patients undergoing major thoracic surgeries were included. The primary outcomes included length of stay (LOS), adverse events (AEs), 6-min walk test scores at 4 weeks, 30-day emergency room visits (without admission) and 30-day readmissions. The process-of-care outcomes included time to 'out-of-bed', independent ambulation, successful fluid intake, last chest tube removal and removal of urinary catheter. Perioperative anaesthesia-related outcomes were examined as well as patient experience and QOL scores., Results: The pre-ERATS group (n = 352 patients) and post-ERATS group (n = 352) demonstrated no differences in demographics. Post-ERATS patients had improved LOS (4.7 vs 6.2 days, P < 0.02), 6-min walk test scores (402 vs 371 m, P < 0.05) and 30-day emergency room visits (13.7% vs 21.6%, P = 0.03) with no differences in AEs and 30-day readmissions. Patients experienced shorter mean time to 'out-of-bed', independent ambulation, successful fluid intake, last chest tube removal and urinary catheter removal. There were no differences in postoperative analgesia administration, patient satisfaction and QOL scores., Conclusions: ERATS implementation was associated with improved LOS, expedited feeding, ambulation and chest tube removal, without increasing AEs or readmissions, while maintaining a high level of patient satisfaction and QOL., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Early oral intake (EOI: initiated within 1 day) and early nasogastric tube removal (ENR: removed ≤2 days) post-esophagectomy is controversial and subject to significant variation., Aim: Our aim is to provide the most up-to-date evidence from published randomized controlled trials (RCTs) addressing both topics., Methods: We searched MEDLINE and Embase (1946-06/2019) for RCTs that investigated the effect of EOI and/or ENR post-esophagectomy with gastric conduit for reconstruction. Our main outcomes of interest were anastomotic leak, aspiration pneumonia, mortality, and length of hospital stay (LOS). Pooled mean differences (MD) and risk ratios (RR) estimates were obtained using a DerSimonian random effects model., Results: Two reviewers screened 613 abstracts and identified 6 RCTs eligible for inclusion; 2 regarding EOI and 4 for ENR. For EOI (2 studies, n = 389), was not associated with differences in risk of: anastomotic leak (RR: 1.01; 95% CI: 0.407, 2.500; I 2 : 0%), aspiration pneumonia (RR: 1.018; 95% CI: 0.407, 2.500), mortality (RR: 1.00; 95% CI: 0.020, 50.0). The LOS was significantly shorter in the EOI group: LOS (MD: -2.509; 95% CI: -3.489, -1.529; I 2 : 90.44%). For ENR (4 studies, n = 295), ENR (removed at POD0-2 vs. 5-8 days) was not associated with differences in risk of: anastomotic leak (RR: 1.11; 95% CI 0.336, 3.697; I 2 : 25.75%) and pneumonia group (RR: 1.11; 95% CI: 0.336, 3.697; I 2 : 25.75%), mortality (RR: 0.87; 95% CI: 0.328, 2.308; I 2 : 0%)or LOS (MD: 1.618; 95% CI: -1.447, 4.683; I 2 : 73.03%)., Conclusions: Our analysis showed that EOI as well as ENR post-esophagectomy do not significantly increase the risk of anastomotic leak, pneumonia, and mortality. The LOS was significantly shorter in the EOI group, and there was no significant difference in the ENR group. A paucity of RCTs has evaluated this question, highlighting the need for further high-quality evidence to address these vital aspects to post-esophagectomy care., Systematic Review Registration: CRD42019138600., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

To develop a predictive model using vital sign (heart rate and arterial blood pressure) variability to predict time to death after withdrawal of life-supporting measures., Design: Retrospective analysis of observational data prospectively collected as part of the Death Prediction and Physiology after Removal of Therapy study between May 1, 2014, and May 1, 2018., Setting: Adult ICU., Patients: Adult patients in the ICU with a planned withdrawal of life-supporting measures and an expectation of imminent death., Interventions: None., Measurements and Main Results: Vital sign waveforms and clinical data were prospectively collected from 429 patients enrolled from 20 ICUs across Canada, the Czech Republic, and the Netherlands. Vital sign variability metrics were calculated during the hour prior to withdrawal. Patients were randomly assigned to the derivation cohort (288 patients) or the validation cohort (141 patients), of which 103 and 54, respectively, were eligible for organ donation after circulatory death. Random survival forest models were developed to predict the probability of death within 30, 60, and 120 minutes following withdrawal using variability metrics, features from existing clinical models, and/or the physician's prediction of rapid death. A model employing variability metrics alone performed similarly to a model employing clinical features, whereas the combination of variability, clinical features, and physician's prediction achieved the highest area under the receiver operating characteristics curve of all models at 0.78 (0.7-0.86), 0.79 (0.71-0.87), and 0.8 (0.72-0.88) for 30-, 60- and 120-minute predictions, respectively., Conclusions: Machine learning models of vital sign variability data before withdrawal of life-sustaining measures, combined with clinical features and the physician's prediction, are useful to predict time to death. The impact of providing this information for decision support for organ donation merits further investigation., Competing Interests: Dr. Seely is a patent holder, director, and shareholder of Therapeutic Monitoring Systems and focused on commercialization of variability-derived clinical decision support tools developed at the Ottawa Hospital Research Institute's Dynamical Analysis Laboratory. Dr. Scales, Dr. Herry, Dr. van Beinum, Ms. Hornby, Dr. Dhanani, and Dr. Seely are named on a patent related to estimating the time to death employing variability monitoring and physiological waveform analysis. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: A time course analysis was undertaken to evaluate how perioperative process-of-care and outcome measures evolved after implementation of an enhanced recovery after thoracic surgery (ERATS) program., Methods: Outcome and process-of-care measures were compared between patients undergoing major elective thoracic surgery during a 9-month pre-ERATS implementation period to those at 1-3, 4-6, and 7-9 months post-ERATS implementation. Outcome measures included length of stay, the 30-day readmission rate, 30-day emergency department visits, and minor and major adverse events. Process measures included first time to activity, out-of-bed, ambulation, fluid diet, diet as tolerated, as well as removal of the first and last chest tube, epidural, patient-controlled analgesia, and Foley and intravenous catheters., Results: In total, 704 patients (352 pre-ERATS, 352 post-ERATS) were included. Mobilization-related process measures, including time to first activity (16.5 vs. 6.8 hours, p<0.001), out-of-bed (17.6 vs. 8.9 hours, p<0.001), and ambulation (32.4 vs. 25.4 hours, p=0.04) saw statistically significant improvements by 1-3 months post-ERATS implementation compared to pre-ERATS. Time to Foley removal improved by 4-6 months post-ERATS (19.5 vs. 18.2 hours, p=0.003). Outcome measures, including the 30-day readmission rate and emergency department visits, steadily decreased post-ERATS. By 7-9 months post-ERATS, both minor (18.2% vs. 7.9%, p=0.009) and major (13.6% vs. 4.4%, p=0.007) adverse events demonstrated statistically significant improvements. Length of stay trended towards improvement from 6.2 days pre-ERATS to 4.8 days by 7-9 months post-ERATS (p=0.06)., Conclusion: The adoption of ERATS led to improvements in multiple process-of-care measures, which may collectively and gradually achieve optimization of clinical outcomes.

Early warning of infection is critical to reduce the risk of deterioration and mortality, especially in neutropenic patients following hematopoietic stem cell transplantation (HCT). Given that heart rate variability (HRV) is a sensitive and early marker for infection, and that serum inflammatory biomarkers can have high specificity for infection, we hypothesized their combination may be useful for accurate early warning of infection. In this study, we developed and evaluated a composite predictive model using continuous HRV with daily serum biomarker measurements to provide risk stratification of future deterioration in HCT recipients. A total of 116 ambulatory outpatients about to undergo HCT consented to collection of prospective demographic, clinical (daily vital signs), HRV (continuous electrocardiography [ECG] monitoring, laboratory [daily serum samples frozen at -80 °C]), and infection outcome variables (defined as the time of escalation of antibiotics), all from 24 hours pre-HCT to the onset of infection or 14 days post-HCT. Indications for antibiotic escalation were adjudicated as "true infection" or not by 2 blinded HCT clinicians. A composite time series of 8 HRV metrics was created for each patient, and the probability of deterioration within the next 72 hours was estimated using logistic regression modeling of composite HRV and serum biomarkers using a rule-based naïve Bayes model if the HRV-based probability exceeded a median threshold. Thirty-five patients (30%) withdrew within <24 hours owing to intolerability of ECG monitoring, leaving 81 patients, of whom 48 (59%) had antibiotic escalation adjudicated as true infection. The combined HRV and biomarker (TNF-α, IL-6, and IL-7) predictive model began increasing at ~48 hours on average before the diagnosis of infection, could distinguish between high risk of impending infection (>90% incidence of subsequent infection within 72 hours), average risk (~50%), and low risk (<10%), with an area under the receiver operating characteristic curve of 0.87. However, given that prophylactic predictive ECG monitoring and daily serum collection proved challenging for many patients, further refinement in measurement is necessary for further study., (Copyright © 2022. Published by Elsevier Inc.)

Background: Following cancer treatment, adults commonly report worsened patient-reported outcomes (PROs) such as anxiety, stress, depression, persistent and upsetting cognitive complaints, unrelenting fatigue, and reduced quality of life. Poorer PROs are associated with disrupted autonomic nervous system functioning as measured by heart rate variability (HRV), both of which have been associated with greater morbidity and mortality. Interventions to improve HRV and PROs among adults following cancer treatment are needed. Yoga therapy holds promise as an intervention to improve HRV and PROs. Therefore, we conducted a single-subject exploratory experimental study to investigate the effects of yoga therapy on HRV and specific PROs (ie, cancer-related fatigue, anxiety, cognitive function, depression, stress, quality of life) in adults treated for cancer. To reduce publication bias, improve reproducibility, and serve as a reference for forthcoming reporting of study results, we present the study protocol for this study herein., Methods: Participants were adults who completed cancer treatment that were recruited from the Ottawa Integrative Cancer Centre. Consenting and eligible participants received one 1:1 yoga therapy session (ie, 1 participant, 1 Yoga Therapist) and 6 weekly group-based yoga therapy sessions (ie, 2-3 participants, 1 Yoga Therapist). Participants completed assessments 7 times: 3 times prior to the program (ie, -6 weeks, -3 weeks, immediately prior to the 1:1 yoga therapy session), immediately following the 1:1 yoga therapy session, prior to the first group-based yoga therapy session, after the last group-based yoga therapy session, and at a 6-week follow-up. Hierarchical linear modeling will be used to test the average effects of the yoga therapy program across participants., Discussion: This study will explore several novel hypotheses, including whether yoga therapy can improve HRV and/or specific PROs among adults treated for cancer acutely (ie, during a 1:1 yoga therapy session) and/or through repeated exposure (ie, after completing 6 weeks of group-based yoga therapy). Although the findings will require confirmation or refutation in future trials, they may provide initial evidence that YT may benefit adults treated for cancer., Trial Registration: ISRCTN registry, ISRCTN64763228. Registered on December 12, 2021. This trial was registered retrospectively. URL of trial registry record: https://www.isrctn.com/ISRCTN64763228.

There is great potential for standardized postoperative adverse events data collection to document, inform, audit, and feedback, all to optimize patient care. Adverse events, defined as any deviation from expected recovery from surgery, have harmful implications for patients, their families, and clinicians. Postoperative adverse events occur frequently in thoracic surgery, predominately due to the high-stakes (ie, high potential for cure) and high-risk (ie, vital physiology and anatomy and preexisting disease) nature of the surgery. As discussed, engaging surgeons in audit and feedback practices informed by standardized data collection would generate consensus recommendations to reduce adverse events and improve patient outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: New-onset post-operative atrial fibrillation (POAF) is a frequent adverse event following major thoracic surgery and is associated with increased risk of perioperative morbidity, length of stay and stroke. It is managed initially with rate and rhythm control therapy; however, optimal duration and the need for anticoagulation are poorly understood. This study aims to assess practice variation regarding POAF management and duration., Methods: This retrospective, single-center cohort study included patients who underwent major thoracic surgery and developed POAF between 2008 and 2017, managed with rate and rhythm control therapy alone. Demographic, clinical, and surgical variables/outcomes, POAF management, and incidence of POAF recurrence in the 30-day post-operative period were collected. Chi-square and T-tests determined significance., Results: Of 2054 patients undergoing thoracic surgery, 155 (75%) patients developed POAF. Different rate and rhythm control agents were used, most commonly metoprolol. 107 (69%) continued rate and rhythm control therapy upon hospital discharge for a mean of 56 days. Among the 48 patients with discontinuation of rate and rhythm control therapy on discharge, none demonstrated recurrence of POAF; in contrast to 3 of 107 patients who continued on therapy. Among patients with CHA 2 DS 2 -VASc score ≥ 2, 15% were prescribed anticoagulation on discharge., Conclusions: Use of rate and rhythm control therapy and anticoagulation for POAF is significantly varied in practice. Many patients are not continued on rate and rhythm control after hospital discharge, which does not appear to impact risk of POAF recurrence. Further research to inform guidelines for POAF management, including therapy duration and indications for anticoagulation is warranted., (© 2021. The Japanese Association for Thoracic Surgery.)

Rationale: Understanding the magnitude of moral distress and its associations may point to solutions. Objectives: To understand the magnitude of moral distress and other measures of wellness in Canadian critical care physicians, to determine any associations among these measures, and to identify potentially modifiable factors. Methods: This was an online survey of Canadian critical care physicians whose e-mail addresses were registered with either the Canadian Critical Care Society or the Canadian Critical Care Trials Group. We used validated measures of moral distress, burnout, compassion fatigue, compassion satisfaction, and resilience. We also measured selected individual, practice, and workload characteristics. Results: Of the 499 physicians surveyed, 239 (48%) responded and there were 225 usable surveys. Respondents reported moderate scores of moral distress (107 ± 59; mean ± standard deviation, maximum 432), one-third of respondents had considered leaving or had previously left a position because of moral distress, about one-third met criteria for burnout syndrome, and a similar proportion reported medium-high scores of compassion fatigue. In contrast, about one-half of respondents reported a high score of compassion satisfaction, and overall, respondents reported a moderate score of resilience. Each of the "negative" wellness measures (moral distress, burnout, and compassion fatigue) were associated directly with each of the other "negative" wellness measures, and inversely with each of the "positive" wellness measures (compassion satisfaction and resilience), but moral distress was not associated with resilience. Moral distress was lower in respondents who were married or partnered compared with those who were not, and the prevalence of burnout was lower in respondents who had been in practice for longer. There were no differences in any of the wellness measures between adult and pediatric critical care physicians. Conclusions: Canadian critical care physicians report moderate scores of moral distress, burnout, and compassionate fatigue, and moderate-high scores of compassion satisfaction and resilience. We found no modifiable factors associated with any wellness measures. Further quantitative and qualitative studies are needed to identify interventions to reduce moral distress, burnout, and compassion fatigue.

Background: Postoperative atrial fibrillation (POAF) is a frequent adverse event after thoracic surgery with associated morbidity, mortality, and healthcare costs. It has been shown to be preventable with prophylactic amiodarone, which is only recommended in high-risk individuals due to the potential associated side effects. Risk factors for POAF have been identified and incorporated into a prediction model to identify high-risk patients. Further evaluation in the form of a multicenter clinical trial is required to assess the effectiveness of prophylaxis specifically in this high-risk population. The feasibility of such a trial first needs to be assessed., Methods: The PREP-AF trial is a double-blind randomized controlled feasibility trial. Individuals undergoing major thoracic surgery who are identified to be high-risk by the POAF prediction model will be randomized 1:1 to receive a short course of amiodarone vs. placebo in the immediate postoperative period. The primary outcome is feasibility, which will be measured by the number of eligible patients identified, consented, and randomized; intervention adherence; and measurement of future outcomes of a full trial., Discussion: This study will determine the feasibility of a randomized controlled trial to assess the effectiveness of prophylactic amiodarone, in high-risk patients undergoing major thoracic surgery. This will inform the development of a multi-center trial to establish if prophylactic amiodarone is safe and effective at reducing the incidence of POAF. Preventing this adverse event will not only improve outcomes for patients but also reduce the associated health resource utilization and costs., Trial Registration: ClinicalTrials.gov NCT04392921 . Registered on 19 May 2020.

Background: Staging guidelines for lung cancer recommend endobronchial ultrasound (EBUS) and systematic biopsy of at least three mediastinal lymph node (LN) stations for accurate staging. A four-point ultrasonographic score (Canada Lymph Node Score [CLNS]) was developed to determine the probability of malignancy in each LN. A LN with a CLNS of < 2 is considered low probability for malignancy. We hypothesized that, in patients with cN0 non-small cell lung cancer, LNs with CLNS of < 2 may not require routine biopsy because they represent true node-negative disease., Research Question: Do LNs considered triple normal on CT scanning, PET scanning, and CLNS evaluation require routine biopsy?, Study Design and Methods: LNs were evaluated for ultrasonographic features at the time of EBUS and the CLNS was applied. Triple-normal LNs were defined as cN0 on CT scanning (short axis, < 1 cm), PET scanning (no hypermetabolic activity), and EBUS (CLNS, < 2). Specificity and negative predictive value (NPV) were calculated against the gold standard pathologic diagnosis from surgically excised specimens., Results: In total, 143 LNs from 57 cN0 patients were assessed. Triple-normal LNs showed a specificity and NPV of 60% (95% CI, 51.2%-68.3%) and 93.1% (95% CI, 85.6%-97.4%), respectively. After pathologic assessment, only 5.6% (n = 8/143) of triple-normal nodes were proven to be malignant., Interpretation: At the time of staging for lung cancer, combining CT scanning, PET scanning, and CLNS criteria can identify triple-normal LNs that have a high NPV for malignancy. This raises the question of whether triple-normal LNs require routine sampling during EBUS and transbronchial needle aspiration. A prospective trial is required to confirm these findings., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Achalasia is a primary esophageal motility disorder in which there is incomplete relaxation of the lower esophageal sphincter and absence of peristalsis in the lower two thirds of the esophagus. A favored treatment is laparoscopic modified Heller myotomy with Dor fundoplication (LHMDor) with more than 90% immediate beneficial effect. The short-term outcomes of LHMDor are well documented, but stability and durability of postoperative symptom control over time is less understood., Methods: Between 2004 and 2016, 54 patients with achalasia underwent LHMDor (single center). Using validated questionnaires, patients rated their symptoms in five domains: pain, gastroesophageal reflux disease (GERD), dysphagia, regurgitation, and quality of life. Symptom ratings were done preoperatively, 4 weeks postoperatively, 6 months postoperatively, and yearly after the operation., Results: As expected, patients reported marked improvement in dysphagia, odynophagia, regurgitation, GERD, and quality of life after the operation (P < .001). From then on, the symptom control remained durable with respect to absence of pain, regurgitation, and odynophagia; however, we observed a recurrence of GERD symptoms beginning 3 to 5 years postoperatively (P = .001 and P = .04, respectively), with associated increased antireflux medication use. After initial LHMDor, 5 patients required endoscopic dilatation an average of 1.5 years postoperatively, and no patient required reoperation. Patients reported preserved improved quality of life to 11 years after the operation (P = .001)., Conclusions: These results demonstrate the durability of LHMDor in the definitive management of achalasia, offering consistent symptomatic relief and significant improvement in quality of life over the decade after surgery, despite some increase in GERD symptoms and antireflux medication use., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: We sought to evaluate if incorporating an early warning system (EWS), the Visensia Safety Index (VSI) and the National Early Warning Systems 2 (NEWS2), may lead to earlier identification of rapid response team (RRT) patients., Methods: This was a retrospective study (2015-2018) of patients experiencing RRT activation within a tertiary care network. We evaluated the proportion of patients with an EWS alert prior to RRT activation and their associated outcomes (primary: hospital mortality)., Results: There were 6,346 RRT activations over the study period. Of these, 2042 (50.8%) patients would have had a VSI alert prior to RRT activation, with a median advanced time of 3.6 (IQR 0.5-12.8) hours, compared to 2351 (58.4%) patients and 9.8 (IQR 2.0-18.7) hours for NEWS2. Patients with a potential alert prior to RRT activation had an increased odds of mortality for both VSI (OR 1.2, 95%CI 1.1-1.3) and NEWS2 (OR 2.7, 95% CI 2.4-3.1). Prognostic accuracy for hospital mortality was similar between groups., Conclusion: Utilization of an EWS by an RRT has potential to provide earlier recognition of deterioration and mortality risk among hospitalized inpatients.

Objective: Thoracic surgery carries significant risk of postoperative adverse events (AEs). Multiple international recording systems are used to define and collect AEs following thoracic surgery procedures. We hypothesized that a simple-yet-ubiquitous approach to AE documentation could be developed to allow universal data entry into separate international databases., Methods: AE definitions of the Canadian Association of Thoracic Surgeons (CATS) system and 4 international databases were matched and compared. This consisted of reviewing the definition of each AE as described by their respective database and assessing compatibility with the CATS system. We developed a single set of 4 drop-down menus to enable clear classification and facilitated data entry, using 3 single-select mandatory lists and 1 multiselect optional list classifying type and severity of these events., Results: The CATS data elements were harmonized (ie, perfect or good) with 100% (European Society of Thoracic Surgeons), 89% (Society of Thoracic Surgeons), 74% (Esophagectomy Complications Consensus Group), and 73% (National Surgical Quality Improvement Program) of respective data elements. The addition of 17 AEs and 2 complication modifiers to the CATS system was implemented to achieve complete harmonization. Consequently, 100% of AE data elements currently included in all 4 international databases are perfectly or well-harmonized with the revised 4-choice drop down menu., Conclusions: We describe a framework for a ubiquitously applicable approach to AE monitoring following thoracic surgery harmonized with AE definitions of all major thoracic international associations. Use of this AE collection framework allows for comprehensive evaluation of both the incidence and severity of all AEs after thoracic surgery along with quality indicators., (© 2021 The Author(s).)

Background: Mean cerebral blood flow velocity (mean-CBFV) obtained from Transcranial Doppler (TCD) poorly predicts cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). Variability descriptors of mean-CBFV obtained during extended TCD recordings may improve this prediction. We assessed the feasibility of generating reliable linear and non-linear descriptors of mean-CBFV variability using extended recordings in aSAH patients and in healthy controls. We also explored which of those metrics might have the ability to discriminate between aSAH patients and healthy controls, and among patients who would go on to develop vasospasm and those who would not., Methods: Bilateral mean-CBFV, blood pressure, and heart rate were continuously recorded for 40 minutes in aSAH patients (n = 8) within the first 5 days after ictus, in age-matched healthy controls (n = 8) and in additional young controls (n = 8). We obtained linear [standard deviation, coefficient of variations, and the very-low (0.003-0.040 Hz), low (0.040-0.150 Hz), and high-frequency (0.15-0.4 Hz) power spectra] and non-linear (Fractality, deterministic Chaos analyses) variability metrics., Results: We successfully obtained TCD recordings from patients and healthy controls and calculated the desired metrics of mean-CBFV variability. Differences were appreciable between aSAH patients and healthy controls, as well as between aSAH patients who later developed vasospasm and those who did not., Conclusions: A 40-minute TCD recording provides reliable variability metrics in aSAH patients and healthy controls. Future studies are required to determine if mean-CBFV variability metrics remain stable over time, and whether they may serve to identify patients who are at greatest risk of developing cerebral vasospasm after aSAH.

Background: Despite curative intent resection in patients with non-small cell lung cancer (NSCLC), recurrence leading to mortality remains too common. Melatonin has shown promise for the treatment of patients with lung cancer; however, its effect following cancer resection has not been studied. We evaluated if melatonin taken after complete resection reduces lung cancer recurrence and mortality, or impacts quality of life (QOL), symptomatology or immune function., Methods: Participants received melatonin (20 mg) or placebo nightly for one year following surgical resection of primary NSCLC. The primary outcome was two-year disease-free survival (DFS). Secondary outcomes included five-year DFS, adverse events, QOL, fatigue, sleep, depression, anxiety, pain, and biomarkers assessing for immune function/inflammation. This study is registered at https://clinicaltrials.gov NCT00668707., Findings: 709 patients across eight centres were randomized to melatonin ( n  = 356) versus placebo ( n  = 353). At two years, melatonin showed a relative risk of 1·01 (95% CI 0·83-1·22), p  = 0·94 for DFS. At five years, melatonin showed a hazard ratio of 0·97 (95% CI 0·86-1·09), p  = 0·84 for DFS. When stratified by cancer stage (I/II and III/IV), a hazard reduction of 25% (HR 0·75, 95% CI 0·61-0·92, p  = 0·005) in five-year DFS was seen for participants in the treatment arm with advanced cancer (stage III/IV). No meaningful differences were seen in any other outcomes., Interpretation: Adjuvant melatonin following resection of NSCLC does not affect DFS for patients with resected early stage NSCLC, yet may increase DFS in patients with late stage disease. Further study is needed to confirm this positive result. No beneficial effects were seen in QOL, symptoms, or immune function., Funding: This study was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation., Competing Interests: Dr. Villeneuve reports ‘other’ from Minogue Medical, outside the submitted work. All other authors have no conflicts of interest to disclose., (© 2021 The Authors.)

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., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Anastomotic leakage (AL) is a common and serious complication following esophagectomy. We aimed to provide an up-to-date review and critical appraisal of the efficacy and safety of all previous interventions aiming to reduce AL risk., Methods: We searched MEDLINE and Embase from 1946 to January 2019 for randomized controlled trials (RCTs) evaluating interventions to minimize esophagogastric AL. Pooled risk ratios (RR) for AL were obtained using a random effects model., Results: Two reviewers screened 441 abstracts and identified 17 RCTs eligible for inclusion; 11 studies were meta-analyzed. Omentoplasty significantly reduced the risk of AL by 78% [RR: 0.22; 95% CI: 0.10, 0.50] compared to conventional anastomosis (3 studies, n = 611 patients). Early removal of NG tube significantly reduced the risk of AL by 62% [RR: 0.38; 95% CI: 0.02, 0.65] compared to prolonged NG tube removal (2 studies, n = 293 patients); Stapled anastomosis did not significantly reduce the risk of AL [RR: 0.92; 95% CI: 0.45, 1.87] compared to hand-sewn anastomosis (6 studies, n = 1454 patients). The quality of evidence was high for omentoplasty (vs. conventional anastomosis), moderate for early NG tube removal (vs. prolonged NG tube removal), and very low for stapled anastomosis (vs. hand-sewn anastomosis)., Conclusions: This is the first meta-analysis to summarize the graded quality of evidence for all RCT interventions designed to reduce the risk of AL following esophagectomy. Our findings demonstrated that omentoplasty significantly reduced the risk of AL with a high quality of evidence. Although early NG tube removal significantly reduced AL risk, there is a need for further research to strengthen the quality of evidence for this finding. Evidence profiles presented in our review may help inform the development of future clinical practice recommendations. Systematic review registration: CRD42019127181.

Background: Prior studies of rapid response team (RRT) implementation for surgical patients have demonstrated mixed results with respect to reductions in poor outcomes. The aim of this study was to identify predictors of in-hospital mortality and hospital costs among surgical inpatients requiring RRT activation., Methods: We analyzed data prospectively collected from May 2012 to May 2016 at The Ottawa Hospital. We included patients who were at least 18 years of age, who were admitted to hospital, who received either preoperative or postoperative care, and and who required RRT activation. We created a multivariable logistic regression model to describe mortality predictors and a multivariable generalized linear model to describe cost predictors., Results: We included 1507 patients. The in-hospital mortality rate was 15.9%. The patient-related factors most strongly associated with mortality included an Elixhauser Comorbidity Index score of 20 or higher (odds ratio [OR] 3.60, 95% confidence interval [CI] 1.96-6.60) and care designations excluding admission to the intensive care unit and cardiopulmonary resuscitation (OR 3.52, 95% CI 2.25-5.52). The strongest surgical predictors included neurosurgical admission (OR 2.09, 95% CI 1.17-3.75), emergent surgery (OR 2.04, 95% CI 1.37-3.03) and occurrence of 2 or more operations (OR 1.73, 95% CI 1.21-2.46). Among RRT factors, occurrence of 2 or more RRT assessments (OR 2.01, 95% CI 1.44-2.80) conferred the highest mortality. Increased cost was strongly associated with admitting service, multiple surgeries, multiple RRT assessments and medical comorbidity., Conclusion: RRT activation among surgical inpatients identifies a population at high risk of death. We identified several predictors of mortality and cost, which represent opportunities for future quality improvement and patient safety initiatives., Competing Interests: Andrew Seely holds patents related to multiorgan variability analysis and is the founder and CEO of Therapeutic Monitoring Systems Inc. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)

Background: Up to 50% of patients suffer short-term postoperative adverse events (AEs) and metastatic recurrence in the long-term following curative-intent lung cancer resection. The association between AEs, particularly infectious in nature, and disease recurrence is controversial. We sought to evaluate the association of postoperative AEs on risk of developing recurrence and recurrence-free survival (RFS) following curative-intent lung resection surgery., Methods: All lung cancer resections at a single institution (January 2008-July 2015) were included, with prospective collection of AEs using the Thoracic Morbidity & Mortality System. Cox proportional hazards models were used to estimate the effect of AEs on recurrence, with results presented as hazard ratio (HR) with 95% confidence interval (CI). An a priori, clinically driven approach to predictor variable selection was used. Kaplan-Meier curves were used examine the relationship between AE and RFS. p < 0.05 was considered statistically significant., Results: 892 patients underwent curative-intent resection. 342 (38.3%) patients experienced an AE; 69 (7.7%) patients developed infectious AEs. 17.6% (n = 157) of patients had disease recurrence after mean follow-up of 26.5 months. Severe (Grade IV) AEs were associated with increased risk of recurrence (3.40; 95% CI 1.56-7.41) and a trend to decreased RFS. Major infectious AEs were associated with increased risk of recurrence (HR 1.71; CI 1.05-2.8) and earlier time to recurrence (no infectious AE 66 months, minor infectious 41 months, major infectious 54 months; p = 0.02)., Conclusion: For patients undergoing curative-intent lung cancer resection, postoperative AEs associated with critical illness or major infection were associated with increased risk of oncologic recurrence.

Introduction: Vasodilatory hypotension is common among intensive care unit (ICU) patients; vasopressors are considered standard of care. However, optimal mean arterial pressure (MAP) targets for vasopressor titration are unknown. The objective of the Optimal VAsopressor TitraTION in patients 65 years and older (OVATION-65) trial is to ascertain the effect of permissive hypotension (vasopressor titration to achieve MAP 60-65 mm Hg) versus usual care on biomarkers of organ injury in hypotensive patients aged ≥65 years., Methods and Analysis: OVATION-65 is an allocation-concealed randomised trial in 7 Canadian hospitals. Eligible patients are ≥65 years of age, in an ICU with vasodilatory hypotension, receiving vasopressors for ≤12 hours to maintain MAP ≥65 mm Hg during or after adequate fluid resuscitation, and expected to receive vasopressors for ≥6 additional hours. Patients are excluded for any of the following: active treatment for spinal cord or acute brain injury; vasopressors given solely for bleeding, ventricular failure or postcardiopulmonary bypass vasoplegia; withdrawal of life-sustaining treatments expected within 48 hours; death perceived as imminent; previous enrolment in OVATION-65; organ transplant within the last year; receiving extracorporeal life support or lack of physician equipoise. Patients are randomised to permissive hypotension versus usual care for up to 28 days. The primary outcome is high-sensitivity troponin T, a biomarker of cardiac injury, on day 3. Secondary outcomes include biomarkers of injury to other organs (brain, liver, intestine, skeletal muscle); lactate (a biomarker of global tissue dysoxia); resource utilisation; adverse events; mortality (90 days and 6 months) and cognitive function (6 months). Assessors of biomarkers, mortality and cognitive function are blinded to allocation., Ethics and Dissemination: This protocol has been approved at all sites. Consent is obtained from the eligible patient, the substitute decision-maker if the patient is incapable, or in a deferred fashion where permitted. End-of-grant dissemination plans include presentations, publications and social media platforms and discussion forums., Trial Registration Number: NCT03431181., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Prenatal stress (PS) impacts early postnatal behavioural and cognitive development. This process of 'fetal programming' is mediated by the effects of the prenatal experience on the developing hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). We derive a multi-scale multi-species approach to devising preclinical and clinical studies to identify early non-invasively available pre- and postnatal biomarkers of PS. The multiple scales include brain epigenome, metabolome, microbiome and the ANS activity gauged via an array of advanced non-invasively obtainable properties of fetal heart rate fluctuations. The proposed framework has the potential to reveal mechanistic links between maternal stress during pregnancy and changes across these physiological scales. Such biomarkers may hence be useful as early and non-invasive predictors of neurodevelopmental trajectories influenced by the PS as well as follow-up indicators of success of therapeutic interventions to correct such altered neurodevelopmental trajectories. PS studies must be conducted on multiple scales derived from concerted observations in multiple animal models and human cohorts performed in an interactive and iterative manner and deploying machine learning for data synthesis, identification and validation of the best non-invasive detection and follow-up biomarkers, a prerequisite for designing effective therapeutic interventions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Understanding how nature drives entropy production offers novel insights regarding patient care. Whilst energy is always preserved and energy gradients irreversibly dissipate (thus producing entropy), increasing evidence suggests that they do so in the most optimal means possible. For living complex non-equilibrium systems to create a healthy internal emergent order, they must continuously produce entropy over time. The Maximum Entropy Production Principle (MEPP) highlights nature's drive for non-equilibrium systems to augment their entropy production if possible. This physical drive is hypothesized to be responsible for the spontaneous formation of fractal structures in space (e.g., multi-scale self-similar tree-like vascular structures that optimize delivery to and clearance from an organ system) and time (e.g., complex heart and respiratory rate variability); both are ubiquitous and essential for physiology and health. Second, human entropy production, measured by heat production divided by temperature, is hypothesized to relate to both metabolism and consciousness, dissipating oxidative energy gradients and reducing information into meaning and memory, respectively. Third, both MEPP and natural selection are hypothesized to drive enhanced functioning and adaptability, selecting states with robust basilar entropy production, as well as the capacity to enhance entropy production in response to exercise, heat stress, and illness. Finally, a targeted focus on optimizing our patients' entropy production has the potential to improve health and clinical outcomes. With the implications of developing a novel understanding of health, illness, and treatment strategies, further exploration of this uncharted ground will offer value.