Multidisciplinary Management of Adult Patients with Chylothorax: A Consensus Statement.

The management of chylothorax remains challenging given the limited evidence and significant heterogeneity in practice. In addition, there are no practical guidelines on the optimal approach to manage this complex condition. We convened an international group of 27 experts from 20 institutions across five countries and 4 specialties (Pulmonary, Interventional Radiology, Thoracic Surgery & Nutrition) with experience and expertise in managing adult patients with chylothorax. We performed a literature and internet search for reports addressing 7 clinically relevant questions pertaining to the management of adult patients with chylothorax. This consensus statement, consisting of best practice statements based on expert consensus addressing these 7 PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience. Panel members participated in the development of the final best practice statements using the modified Delphi technique. Our consensus statement aims to offer guidance in clinical decision making when managing patients with chylothorax while also identifying gaps in knowledge and inform future research.

Malignant Pleural Effusions in the Era of Immunotherapy and Antiangiogenic Therapy.

Malignant pleural effusions (MPE) have historically been associated with a poor prognosis, and patients often require a series of invasive procedures and hospitalizations that significantly reduce quality of life at the terminus of life. However, advances in the management of MPE have coincided with the era of immunotherapies, and to a lesser extent, antiangiogenic therapies for the treatment of lung cancer. Landmark studies have shown these drugs to improve overall survival and progression-free survival in patients with lung cancer, but a paucity of phase III trial data exists for the impact of immune checkpoint inhibitors (ICI) on lung cancers associated with MPE. This review will focus on the leading studies investigating the impact of ICI and antiangiogenic therapies in patients with lung cancer and MPE. The diagnostic and prognostic values of vascular endothelial growth factor and endostatin expression levels in malignancy will also be discussed. These advancements are changing the paradigm of MPE management from palliation to treatment for the first time since 1767 when MPE was first reported. The future holds the promise of durable response and extended survival in patients with MPE.

Healthcare Costs and Utilization among Patients Hospitalized for Malignant Pleural Effusion.

BACKGROUND: Malignant pleural effusion (MPE) poses a considerable healthcare burden, but little is known about trends in directly attributable hospital utilization. OBJECTIVE: We aimed to study national trends in healthcare utilization and outcomes among hospitalized MPE patients. METHODS: We analyzed adult hospitalizations attributable to MPE using the Healthcare Cost and Utilization Project - National Inpatient Sample (HCUP-NIS) databases from 2004, 2009, and 2014. Cases were included if MPE was coded as the principal admission diagnosis or if unspecified pleural effusion was coded as the principal admission diagnosis in the setting of metastatic cancer. Annual hospitalizations were estimated for the entire US hospital population using discharge weights. Length of stay (LOS), hospital charges, and hospital mortality were also estimated. RESULTS: We analyzed 92,034 hospital discharges spanning a decade (2004-2014). Yearly hospitalizations steadily decreased from 38,865 to 23,965 during this time frame, the mean LOS decreased from 7.7 to 6.3 days, and the adjusted hospital mortality decreased from 7.9 to 4.5% (p = 0.00 for all trend analyses). The number of pleurodesis procedures also decreased over time (p = 0.00). The mean inflation-adjusted charge per hospitalization rose from USD 41,252 to USD 56,951, but fewer hospitalizations drove the total annual charges down from USD 1.51 billion to USD 1.37 billion (p = 0.00 for both analyses). CONCLUSIONS: The burden of hospital-based resource utilization associated with MPE has decreased over time, with a reduction in attributable hospitalizations by one third in the span of 1 decade. Correspondingly, the number of inpatient pleurodesis procedures has decreased during this time frame.

Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline.

BACKGROUND: This Guideline, a collaborative effort from the American Thoracic Society, Society of Thoracic Surgeons, and Society of Thoracic Radiology, aims to provide evidence-based recommendations to guide contemporary management of patients with a malignant pleural effusion (MPE). METHODS: A multidisciplinary panel developed seven questions using the PICO (Population, Intervention, Comparator, and Outcomes) format. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the Evidence to Decision framework was applied to each question. Recommendations were formulated, discussed, and approved by the entire panel. RESULTS: The panel made weak recommendations in favor of: 1) using ultrasound to guide pleural interventions; 2) not performing pleural interventions in asymptomatic patients with MPE; 3) using either an indwelling pleural catheter (IPC) or chemical pleurodesis in symptomatic patients with MPE and suspected expandable lung; 4) performing large-volume thoracentesis to assess symptomatic response and lung expansion; 5) using either talc poudrage or talc slurry for chemical pleurodesis; 6) using IPC instead of chemical pleurodesis in patients with nonexpandable lung or failed pleurodesis; and 7) treating IPC-associated infections with antibiotics and not removing the catheter. CONCLUSIONS: These recommendations, based on the best available evidence, can guide management of patients with MPE and improve patient outcomes.

Development and validation of a quality-of-life questionnaire for mechanically ventilated ICU patients.

OBJECTIVE: To develop and validate a new instrument for measuring health-related quality of life in mechanically ventilated patients in the ICU. DESIGN: Expert panel consensus and a prospective longitudinal survey. SETTING: Urban, academic, tertiary care medical center. PATIENTS: One hundred fifteen awake, mechanically ventilated, ICU patients who either received a tracheostomy or remained endotracheally intubated. INTERVENTIONS: A new quality-of-life instrument was developed and validated by using pilot study data; informal interviews of patients, families, and nurses; expert panel consensus; and item analyses. The new instrument was used to measure quality of life at three time points (5 d, 10 d, and 15 d after intubation). MEASUREMENTS AND MAIN RESULTS: A new 12-item quality-of-life questionnaire for mechanically ventilated patients was developed. Patients' responses to the quality-of-life questionnaire revealed moderate-to-high correlations with EuroQol scores (r = -0.4 to -0.9) and the EuroQol Visual Analog Scale (r = 0.6-0.9) across the three times and a moderate correlation with the Sequential Organ Failure Assessment tool (r = 0.5) at 10 days after intubation. Cronbach α ranged from 0.80 to 0.94 across the three times. The quality-of-life questionnaire for mechanically ventilated patients was responsive to changes in treatment modalities (tracheostomy vs no tracheostomy and early vs late tracheostomy demarcated by 10 d of intubation). Exploratory factor analysis revealed that this instrument was unidimensional in nature. CONCLUSIONS: The new quality-of-life questionnaire for mechanically ventilated patients is valid and can reliably measure quality of life in mechanically ventilated ICU patients. It may provide clinicians with an accurate assessment of patients' quality of life and facilitate optimal decision making regarding patients' ICU plan of care.

Difficult airway response team: a novel quality improvement program for managing hospital-wide airway emergencies.

BACKGROUND: Difficult airway cases can quickly become emergencies, increasing the risk of life-threatening complications or death. Emergency airway management outside the operating room is particularly challenging. METHODS: We developed a quality improvement program-the Difficult Airway Response Team (DART)-to improve emergency airway management outside the operating room. DART was implemented by a team of anesthesiologists, otolaryngologists, trauma surgeons, emergency medicine physicians, and risk managers in 2005 at The Johns Hopkins Hospital in Baltimore, Maryland. The DART program had 3 core components: operations, safety, and education. The operations component focused on developing a multidisciplinary difficult airway response team, standardizing the emergency response process, and deploying difficult airway equipment carts throughout the hospital. The safety component focused on real-time monitoring of DART activations and learning from past DART events to continuously improve system-level performance. This objective entailed monitoring the paging system, reporting difficult airway events and DART activations to a Web-based registry, and using in situ simulations to identify and mitigate defects in the emergency airway management process. The educational component included development of a multispecialty difficult airway curriculum encompassing case-based lectures, simulation, and team building/communication to ensure consistency of care. Educational materials were also developed for non-DART staff and patients to inform them about the needs of patients with difficult airways and ensure continuity of care with other providers after discharge. RESULTS: Between July 2008 and June 2013, DART managed 360 adult difficult airway events comprising 8% of all code activations. Predisposing patient factors included body mass index >40, history of head and neck tumor, prior difficult intubation, cervical spine injury, airway edema, airway bleeding, and previous or current tracheostomy. Twenty-three patients (6%) required emergent surgical airways. Sixty-two patients (17%) were stabilized and transported to the operating room for definitive airway management. There were no airway management-related deaths, sentinel events, or malpractice claims in adult patients managed by DART. Five in situ simulations conducted in the first program year improved DART's teamwork, communication, and response times and increased the functionality of the difficult airway carts. Over the 5-year period, we conducted 18 airway courses, through which >200 providers were trained. CONCLUSIONS: DART is a comprehensive program for improving difficult airway management. Future studies will examine the comparative effectiveness of the DART program and evaluate how DART has impacted patient outcomes, operational efficiency, and costs of care.

Optimizing Communication in Mechanically Ventilated Patients.

PURPOSE: To describe the types of talking tracheostomy tubes available, present four case studies of critically ill patients who used a specialized tracheostomy tube to improve speech, discuss their advantages and disadvantages, propose patient selection criteria, and provide practical recommendations for medical care providers. METHODS: Retrospective chart review of patients who underwent tracheostomy in 2010. RESULTS: Of the 220 patients who received a tracheostomy in 2010, 164 (74.55%) received a percutaneous tracheostomy and 56 (25.45%) received an open tracheostomy. Among the percutaneous tracheostomy patients, speech-language pathologists were consulted on 113 patients, 74 of whom were on a ventilator. Four of these 74 patients received a talking tracheostomy tube, and all four were able to speak successfully while on the mechanical ventilator even though they were unable to tolerate cuff deflation. CONCLUSIONS: Talking tracheostomy tubes allow patients who are unable to tolerate-cuff deflation to achieve phonation. Our experience with talking tracheostomy tubes suggests that clinicians should consider their use for patients who cannot tolerate cuff deflation.

A Nasal Swab Classifier to Evaluate the Probability of Lung Cancer in Patients With Pulmonary Nodules.

BACKGROUND: Accurate assessment of the probability of lung cancer (pCA) is critical in patients with pulmonary nodules (PNs) to help guide decision-making. We sought to validate a clinical-genomic classifier developed using whole-transcriptome sequencing of nasal epithelial cells from patients with a PN ≤ 30 mm who smoke or have previously smoked. RESEARCH QUESTION: Can the pCA in individuals with a PN and a history of smoking be predicted by a classifier that uses clinical factors and genomic data from nasal epithelial cells obtained by cytologic brushing? STUDY DESIGN AND METHODS: Machine learning was used to train a classifier using genomic and clinical features on 1,120 patients with PNs labeled as benign or malignant established by a final diagnosis or a minimum of 12 months of radiographic surveillance. The classifier was designed to yield low-, intermediate-, and high-risk categories. The classifier was validated in an independent set of 312 patients, including 63 patients with a prior history of cancer (other than lung cancer), comparing the classifier prediction with the known clinical outcome. RESULTS: In the primary validation set, sensitivity and specificity for low-risk classification were 96% and 42%, whereas sensitivity and specificity for high-risk classification was 58% and 90%, respectively. Sensitivity was similar across stages of non-small cell lung cancer, independent of subtype. Performance compared favorably with clinical-only risk models. Analysis of 63 patients with prior cancer showed similar performance as did subanalyses of patients with light vs heavy smoking burden and those eligible for lung cancer screening vs those who were not. INTERPRETATION: The nasal classifier provides an accurate assessment of pCA in individuals with a PN ≤ 30 mm who smoke or have previously smoked. Classifier-guided decision-making could lead to fewer diagnostic procedures in patients without cancer and more timely treatment in patients with lung cancer.

Reporting Standards for Diagnostic Testing: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals.

Diagnostic testing is fundamental to medicine. However, studies of diagnostic testing in respiratory medicine vary significantly in terms of their methodology, definitions, and reporting of results. This has led to often conflicting or ambiguous results. To address this issue, a group of 20 respiratory journal editors worked to develop reporting standards for studies of diagnostic testing based on a rigorous methodology to guide authors, peer reviewers, and researchers when conducting studies of diagnostic testing in respiratory medicine. Four key areas are covered, including defining the reference standard of truth, measures of dichotomous test performance when used for dichotomous outcomes, measures of multichotomous test performance for dichotomous outcomes, and what constitutes a useful definition of diagnostic yield. The importance of using contingency tables for reporting results is addressed with examples from the literature. A practical checklist is provided as well for reporting studies of diagnostic testing.

The American Thoracic Society Guideline Methodology Training Program.

A new era in guideline creation began in 2011 with publication of the Institute of Medicine (now the National Academy of Medicine) Standards for Developing Trustworthy Clinical Practice Guidelines. The American Thoracic Society (ATS) was committed to developing guidelines in accordance with the new standards and decided that an experienced guideline methodologist would be required on ATS guideline projects to ensure correct implementation of the standards. The ATS Guideline Methodology Training Program was launched to increase the pool of trained methodologists. Each year, accepted trainees (methodology scholars) attend a workshop that introduces them to the terminology and process of guideline development and are given the option of participating in a guideline project. Scholars work with the mentorship of a lead methodologist to conduct and then present a systematic review to the guideline committee, discuss the evidence, and participate in the development of evidence-based graded recommendations. Scholars have participated in 22 ATS guidelines over the past 9 years, and most remain engaged in guideline development. For the past 2 years, the methodological aspects of all ATS guideline projects were led by graduates of the training program, and several scholars have accepted positions to lead guidelines for other professional societies. Guideline methodology is particularly suitable for clinician educators because the work is clinically oriented, and guidelines confer high academic capital. Those who elect not to continue in guideline development still acquire the skills to perform and publish systematic reviews, as well as to educate trainees in reading and reviewing literature.

Australasian Malignant PLeural Effusion (AMPLE)-3 trial: study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion.

INTRODUCTION: Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery. METHODS AND ANALYSIS: A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings. DISCUSSION: Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12618001013257 . Registered on 18 June 2018. PROTOCOL VERSION: Version 3.00/4.02.19.

Tracheostomy During the COVID-19 Pandemic: Comparison of International Perioperative Care Protocols and Practices in 26 Countries.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has led to a global surge in critically ill patients requiring invasive mechanical ventilation, some of whom may benefit from tracheostomy. Decisions on if, when, and how to perform tracheostomy in patients with COVID-19 have major implications for patients, clinicians, and hospitals. We investigated the tracheostomy protocols and practices that institutions around the world have put into place in response to the COVID-19 pandemic. DATA SOURCES: Protocols for tracheostomy in patients with severe acute respiratory syndrome coronavirus 2 infection from individual institutions (n = 59) were obtained from the United States and 25 other countries, including data from several low- and middle-income countries, 23 published or society-endorsed protocols, and 36 institutional protocols. REVIEW METHODS: The comparative document analysis involved cross-sectional review of institutional protocols and practices. Data sources were analyzed for timing of tracheostomy, contraindications, preoperative testing, personal protective equipment (PPE), surgical technique, and postoperative management. CONCLUSIONS: Timing of tracheostomy varied from 3 to >21 days, with over 90% of protocols recommending 14 days of intubation prior to tracheostomy. Most protocols advocate delaying tracheostomy until COVID-19 testing was negative. All protocols involved use of N95 or higher PPE. Both open and percutaneous techniques were reported. Timing of tracheostomy changes ranged from 5 to >30 days postoperatively, sometimes contingent on negative COVID-19 test results. IMPLICATIONS FOR PRACTICE: Wide variation exists in tracheostomy protocols, reflecting geographical variation, different resource constraints, and limited data to drive evidence-based care standards. Findings presented herein may provide reference points and a framework for evolving care standards.

Indwelling Pleural Catheter Drainage Strategy for Malignant Effusion: A Cost-Effectiveness Analysis.

Rationale: The likelihood of achieving pleurodesis after indwelling pleural catheter (IPC) placement for malignant pleural effusion varies with the specific drainage strategy used: symptom-guided drainage, daily drainage, or talc instillation through the IPC (IPC + talc). The relative cost-effectiveness of one strategy over the other is unknown.Objectives: We performed a decision tree model-based analysis to ascertain the cost-effectiveness of each IPC drainage strategy from a healthcare system perspective.Methods: We developed a decision tree model using theoretical event probability data derived from three randomized clinical trials and used 2019 Medicare reimbursement data for cost estimation. The primary outcome was incremental cost-effectiveness ratio (ICER) over an analytical horizon of 6 months with a willingness-to-pay threshold of $100,000/quality-adjusted life-year (QALY). Monte Carlo probabilistic sensitivity analysis and one-way sensitivity analyses were conducted to measure the uncertainty surrounding base case estimates.Results: IPC + talc was a cost-effective alternative to symptom-guided drainage, with an ICER of $59,729/QALY. Monte Carlo probabilistic sensitivity analysis revealed that this strategy was favored in 54% of simulations. However, symptom-guided drainage was cost effective for pleurodesis rates >20% and for life expectancy <4 months. Daily drainage was not cost effective in any scenario, including for patients with nonexpandable lung, in whom it had an ICER of $2,474,612/QALY over symptom-guided drainage.Conclusions: For patients with malignant pleural effusion and an expandable lung, IPC + talc may be cost effective relative to symptom-guided drainage, although considerable uncertainty exists around this estimation. Daily IPC drainage is not a cost-effective strategy under any circumstance.

Voice-Related Quality of Life Increases With a Talking Tracheostomy Tube: A Randomized Controlled Trial.

OBJECTIVE: The primary objective of our study was to determine the quality of life (QOL) using a talking tracheostomy tube. METHODS: Randomized clinical trial (NCT2018562). Adult intensive care unit patients who were mechanically ventilated, awake, alert, attempting to communicate, English-speaking, and could not tolerate one-way speaking valve were included. Intervention comprised a Blue Line Ultra Suctionaid (BLUSA) talking tracheostomy tube (Smiths Medical, Dublin, OH, US). Outcome measures included QOL scores measured using Quality of Life in Mechanically Ventilated Patients (QOL-MV) and Voice-Related Quality of Life (V-RQOL), Speech Intelligibility Test (SIT) scores, independence, and satisfaction. RESULTS: The change in V-RQOL scores from pre- to postintervention was higher among patients using a BLUSA (Smiths Medical) compared to those who did not (P = 0.001). The QOL-MV scores from pre- to postintervention were significantly higher among patients who used a BLUSA (Smiths Medical) compared to patients who did not use BLUSA (Smiths Medical) or a one-way speaking valve (P = 0.04). SIT scores decreased by 6.4 points for each 1-point increase in their Sequential Organ Failure Assessment scores (P = 0.04). The overall QOL-MV scores correlated moderately with the overall V-RQOL scores (correlation coefficient = 0.59). Cronbach alpha score for overall QOL-MV was 0.71. Seventy-three percent of the 22 intervention patients reported the ability to use the BLUSA (Smiths Medical) with some level of independence, whereas 41% reported some level of satisfaction with the use of BLUSA (Smiths Medical). The lengths of stay was longer in the intervention group. CONCLUSION: Our study suggests that BLUSA (Smiths Medical) talking tracheostomy tube improves patient-reported QOL in mechanically ventilated patients with a tracheostomy who cannot tolerate cuff deflation. LEVEL OF EVIDENCE: I Laryngoscope, 130:1249-1255, 2020.

Impact of Video Game Cross-Training on Learning Bronchoscopy. A Pilot Randomized Controlled Trial.

Background: Video game playing requires many of the same skill sets as medical procedures such as bronchoscopy. These include visual-spatial awareness, rapid decision making, and psychomotor skills. The role of video game cross-training on learning bronchoscopy is unknown. Objective: We studied the association of baseline video gaming experience with, and the impact of short-term video game playing on, visual-spatial awareness and acquisition of basic bronchoscopic skills among medical trainees. Methods: Bronchoscopy-naive medical trainees underwent formal didactic and hands-on instruction on basic bronchoscopy, along with a baseline assessment measuring bronchoscopic and visual-spatial skills. Half of the subjects were subsequently randomized to playing a videogame (Rocket League) for 8 weeks. All participants returned at 4 weeks for a refresher course and at 8 weeks for a final assessment. Results: Thirty subjects completed the study, 16 of them in the intervention arm who all met the minimum video game playing time requirement. At baseline, video game players had significantly lower airway collision rates (6.82 collisions/min vs. 11.64 collisions/min; P = 0.02) and higher scores on the Purdue Visual Spatial Test: Visualization of Rotations test (27.5 vs. 23.54; P = 0.04). At completion, the intervention group had no significant differences in airway collisions, bronchoscopy time, or Bronchoscopy Skills and Tasks Assessment Tool scores. There was moderate correlation between airway collision rate and mean Purdue Visual Spatial Test: Visualization of Rotations score (Spearman's rho, -0.59; P < 0.001). Conclusion: At baseline, learners with former video game-playing experience have higher visual-spatial awareness and fewer airway collisions. The impact of video game playing as an aid to simulation-based bronchoscopic education is uncertain.

Tracheostomy in the COVID-19 era: global and multidisciplinary guidance.

Global health care is experiencing an unprecedented surge in the number of critically ill patients who require mechanical ventilation due to the COVID-19 pandemic. The requirement for relatively long periods of ventilation in those who survive means that many are considered for tracheostomy to free patients from ventilatory support and maximise scarce resources. COVID-19 provides unique challenges for tracheostomy care: health-care workers need to safely undertake tracheostomy procedures and manage patients afterwards, minimising risks of nosocomial transmission and compromises in the quality of care. Conflicting recommendations exist about case selection, the timing and performance of tracheostomy, and the subsequent management of patients. In response, we convened an international working group of individuals with relevant expertise in tracheostomy. We did a literature and internet search for reports of research pertaining to tracheostomy during the COVID-19 pandemic, supplemented by sources comprising statements and guidance on tracheostomy care. By synthesising early experiences from countries that have managed a surge in patient numbers, emerging virological data, and international, multidisciplinary expert opinion, we aim to provide consensus guidelines and recommendations on the conduct and management of tracheostomy during the COVID-19 pandemic.

A practical framework for patient care teams to prospectively identify and mitigate clinical hazards.

BACKGROUND: One of the greatest challenges facing both practitioners and risk managers is the identification of previously unknown clinical hazards and defects. With the rapid proliferation of new health care services, unknown hazards may propagate as new therapies are integrated into the existing health care system. The main goal of risk analysis is to make these hazards visible by proactively searching and probing the system. Yet, a comprehensive approach by which to safely integrate new therapies into the existing clinical environment has yet to be clearly articulated. Patient care teams can use the proposed framework when introducing new therapies. A PRACTICAL FRAMEWORK: The framework includes a background investigation and literature search; an in situ simulation (in the actual clinical setting used for patients); a Failure Mode and Effects Analysis to determine the severity, probability, and risk of the potential hazards; and a multidisciplinary protocol and safety checklist to standardize practice and ensure provider accountability. CASE EXAMPLES: Application of this framework to three operative scenarios--intraoperative radiation therapy (IORT), hyperthermic intraperitoneal chemotherapy (HIPEC), and an interventional pulmonology program--demonstrates its flexibility. Its use prospectively identified and mitigated 20 IORT, 5 HIPEC, and 18 interventional pulmonology hazards/defects. Subsequent patient cases were largely uneventful. All cases and patient safety reporting systems are monitored to identify any new defects in an effort to continuously improve patient care. CONCLUSION: The use of a comprehensive framework to identify and mitigate hazards in an on-site simulated environment promotes safer care for target patient populations; results in familiarity with procedures, amelioration of staff concerns, and standardization of practice; and facilitates teamwork and communication.