Association of patient and health care organization factors with incidental nodule guidelines adherence: A multi-system observational study.

BACKGROUND: Health care organizations are increasingly developing systems to ensure patients with pulmonary nodules receive guideline-adherent care. Our goal was to determine patient and organization factors that are associated with radiologist adherence as well as clinician and patient concordance to 2005 Fleischner Society guidelines for incidental pulmonary nodule follow-up. MATERIALS: Trained researchers abstracted data from the electronic health record from two Veterans Affairs health care systems for patients with incidental pulmonary nodules as identified by interpreting radiologists from 2008 to 2016. METHODS: We classified radiology reports and patient follow-up into two categories. Radiologist-Fleischner Adherence was the agreement between the radiologist's recommendation in the computed tomography report and the 2005 Fleischner Society guidelines. Clinician/Patient-Fleischner Concordance was agreement between patient follow-up and the guidelines. We calculated multivariable-adjusted predicted probabilities for factors associated with Radiologist-Fleischner Adherence and Clinician/Patient-Fleischner Concordance. RESULTS: Among 3150 patients, 69% of radiologist recommendations were adherent to 2005 Fleischner guidelines, 4% were more aggressive, and 27% recommended less aggressive follow-up. Overall, only 48% of patients underwent follow-up concordant with 2005 Fleischner Society guidelines, 37% had less aggressive follow-up, and 15% had more aggressive follow-up. Radiologist-Fleischner Adherence was associated with Clinician/Patient-Fleischner Concordance with evidence for effect modification by health care system. CONCLUSION: Clinicians and patients seem to follow radiologists' recommendations but often do not obtain concordant follow-up, likely due to downstream differential processes in each health care system. Health care organizations need to develop comprehensive and rigorous tools to ensure high levels of appropriate follow-up for patients with pulmonary nodules.

Variation in Reporting of Incidental Findings on Initial Lung Cancer Screening and Associations With Clinician Assessment.

PURPOSE: The aim of this study was to quantify the distribution, frequency, and clinical significance of incidental findings (IFs) on initial lung cancer screening (LCS) and the association of report characteristics with subsequent assessment. METHODS: Health records of patients undergoing initial LCS from 2015 to 2018 in the Minneapolis VA Health Care System were retrospectively reviewed for demographics, Lung CT Screening Reporting & Data System coding, IFs, and subsequent clinical assessment. IFs were considered potentially significant if they were likely to require any follow-up. High-risk significant IFs (SIFs) were potentially malignant. The primary outcome was the SIF being addressed. Outcomes were analyzed using a mixed-effects model. RESULTS: Patients (n = 901) were primarily male (94.1%) smokers (62.1%) with a mean age of 65.2 years. IFs were extremely common (93.9%), with an average of 2.6 IFs per scan (n = 2,296). Seven hundred eighty-six IFs (34.2%) were deemed likely SIFs, of which 58 (7.4%) were high risk. Two hundred twenty-two (28.2%) were addressed by clinicians, of which 104 (13.2%) underwent testing. Reporting of SIFs varied among radiologists, with at least one SIF in the impression in 24% to 78% of low-dose CT studies with the S modifier, used to indicate the presence of a SIF, applied to 0% to 51% of reports. In the mutually adjusted model, radiologist recommendation (adjusted odds ratio [OR], 4.67; 95% confidence interval [CI], 2.23-9.76), high-risk finding (adjusted OR, 4.35; 95% CI, 1.81-10.45), and reporting in the impression (adjusted OR, 2.58; 95% CI, 1.28-5.18) were associated with increased odds of the SIF's being addressed. CONCLUSIONS: Radiologists vary in their reporting of IFs on LCS. Further standardization of reporting of SIFs may improve this process, with the simultaneous goals of generating appropriate testing when needed and minimizing low-value care.

Optimizing Longitudinal Tobacco Cessation Treatment in Lung Cancer Screening: A Sequential, Multiple Assignment, Randomized Trial.

Importance: Nearly half of the 14.8 million US adults eligible for lung cancer screening (LCS) smoke cigarettes. The optimal smoking cessation program components for the LCS setting are unclear. Objective: To assess the effect of adding a referral to prescription medication therapy management (MTM) to the tobacco longitudinal care (TLC) program among patients eligible for LCS who smoke and do not respond to early tobacco treatment and to assess the effect of decreasing the intensity of TLC among participants who do respond to early treatment. Design, Setting, and Participants: This randomized clinical trial included patients who currently smoked cigarettes daily and were eligible for LCS. Recruitment took place at primary care centers and LCS programs at 3 large health systems in the US and began in October 2016, and 18-month follow-up was completed April 2021. Interventions: (1) TLC comprising intensive telephone coaching and combination nicotine replacement therapy for 1 year with at least monthly contact; (2) TLC with MTM, MTM offered pharmacist-referral for prescription medications; and (3) Quarterly TLC, intensity of TLC was decreased to quarterly contact. Intervention assignments were based on early response to tobacco treatment (abstinence) that was assessed either 4 weeks or 8 weeks after treatment initiation. Main outcomes and Measures: Self-reported, 6-month prolonged abstinence at 18-month. Results: Of 636 participants, 228 (35.9%) were female, 564 (89.4%) were White individuals, and the median (IQR) age was 64.3 (59.6-68.8) years. Four weeks or 8 weeks after treatment initiation, 510 participants (80.2%) continued to smoke (ie, early treatment nonresponders) and 126 participants (19.8%) had quit (ie, early treatment responders). The 18 month follow-up survey response rate was 83.2% (529 of 636). Across TLC groups at 18 months follow-up, the overall 6-month prolonged abstinence rate was 24.4% (129 of 529). Among the 416 early treatment nonresponders, 6-month prolonged abstinence for TLC with MTM vs TLC was 17.8% vs 16.4% (adjusted odds ratio [aOR] 1.13; 95% CI, 0.67-1.89). In TLC with MTM, 98 of 254 participants (39%) completed at least 1 MTM visit. Among 113 early treatment responders, 6-month prolonged abstinence for Quarterly TLC vs TLC was 24 of 55 (43.6%) vs 34 of 58 (58.6%) (aOR, 0.54; 95% CI, 0.25-1.17). Conclusions and Relevance: In this randomized clinical trial, adding referral to MTM with TLC for participants who did not respond to early treatment did not improve smoking abstinence. Stepping down to Quarterly TLC among early treatment responders is not recommended. Integrating longitudinal tobacco cessation care with LCS is feasible and associated with clinically meaningful quit rates. Trial Registration: ClinicalTrials.gov Identifier: NCT02597491.

National Survey of Lung Cancer Screening Practices in Veterans Health Administration Facilities.

INTRODUCTION: Lung cancer screening can save lives through the early detection of lung cancer, and professional societies recommend key lung cancer screening program components to ensure high-quality screening. Yet, little is known about the key components that comprise the various screening program models in routine clinical settings. The objective was to compare the utilization of these key components across centralized, hybrid, and decentralized lung cancer screening programs. METHODS: The survey was designed to identify current structures and processes of lung cancer screening programs. It was administered electronically to Veterans Health Administration facilities nationally (N=122) between August and December 2021. Results were analyzed between March and August 2022 and stratified by self-identified lung cancer screening program type, and we tested the hypothesis that centralized screening programs would be more likely to have implemented practices that support lung cancer screening, followed by hybrid and decentralized programs, using the Cochran-Armitage trend test. RESULTS: Overall, 69 (56.6%) facilities completed the survey, and respondents were lung cancer screening coordinators (39.1%), pulmonologists (33.3%), and oncologists (10.1%). Facilities most frequently self-identified as having a centralized (37.7%) program model, followed by identifying as having hybrid (30.4%) and decentralized (20.3%) programs. There was varying implementation of practices to support lung cancer screening, with hybrid and decentralized programs less likely to have lung cancer screening registries, lung cancer screening steering committees, or dedicated lung cancer screening coordinators. CONCLUSIONS: Although there is overlap between the components of various lung cancer screening program types, centralized programs more frequently implemented practices before the initial screening to support lung cancer screening. This work provides a path for future investigations to identify which lung cancer screening practices are effective to improve lung cancer screening outcomes, which could help inform implementation in settings with limited resources.

Use of Veterans Health Administration Structured Data to Identify Patients Eligible for Lung Cancer Screening.

INTRODUCTION: Lung cancer screening (LCS) uptake is low. Assessing patients' cigarette pack-years and years since quitting is challenging given the lack of documentation in structured electronic health record data. MATERIALS AND METHODS: We used a convenience sample of patients with a chest CT scan in the Veterans Health Administration. We abstracted data on cigarette use from electronic health record notes to determine LCS eligibility based on the 2021 U.S. Preventive Services Task Force age and cigarette use eligibility criteria. We used these data as the "ground truth" of LCS eligibility to compare them with structured data regarding tobacco use and a COPD diagnosis. We calculated sensitivity and specificity as well as fast-and-frugal decision trees. RESULTS: For 50-80-year-old veterans identified as former or current tobacco users, we obtained 94% sensitivity and 47% specificity. For 50-80-year-old veterans identified as current tobacco users, we obtained 59% sensitivity and 79% specificity. Our fast-and-frugal decision tree that included a COPD diagnosis had a sensitivity of 69% and a specificity of 60%. CONCLUSION: These results can help health care systems make their LCS outreach efforts more efficient and give administrators and researchers a simple method to estimate their number of possibly eligible patients.

The E-cigarette or Vaping Product Use-Associated Lung Injury Epidemic: Pathogenesis, Management, and Future Directions: An Official American Thoracic Society Workshop Report.

E-cigarette or vaping product use-associated lung injury (EVALI) is a severe pulmonary illness associated with the use of e-cigarettes or vaping products that was officially identified and named in 2019. This American Thoracic Society workshop was convened in 2021 to identify and prioritize research and regulatory needs to adequately respond to the EVALI outbreak and to prevent similar instances of disease associated with e-cigarette or vaping product use. An interdisciplinary group of 26 experts in adult and pediatric clinical care, public health, regulatory oversight, and toxicology were convened for the workshop. Four major topics were examined: 1) the public health and regulatory response to EVALI; 2) EVALI clinical care; 3) mechanisms contributing to EVALI; and 4) needed actions to address the health effects of EVALI. Oral presentations and group discussion were the primary modes used to identify top priorities for addressing EVALI. Initiatives including a national EVALI case registry and biorepository, integrated electronic medical record coding system, U.S. Food and Drug Administration regulation and enforcement of nicotine e-cigarette standards, regulatory authority over nontobacco-derived e-cigarettes, training in evaluating exogenous exposures, prospective clinical studies, standardized clinical follow-up assessments, ability to more readily study effects of cannabinoid e-cigarettes, and research to identify biomarkers of exposure and disease were identified as critical needs. These initiatives will require substantial federal investment as well as changes to regulatory policy. Overall, the workshop identified the need to address the root causes of EVALI to prevent future outbreaks. An integrated approach from multiple perspectives is required, including public health; clinical, basic, and translational research; regulators; and users of e-cigarettes. Improving the public health response to reduce the risk of another substantial disease-inducing event depends on coordinated actions to better understand the inhalational toxicity of these products, informing the public of the risks, and developing and enforcing regulatory standards for all e-cigarettes.

Use of Information and Communication Technology among Patients with Chronic Obstructive Pulmonary Disease Who Smoke: A Mixed Methods Study.

Rationale: Although overall use is on the rise, certain patient populations have persistently low technology use. Objectives: To inform the creation of a proactive tobacco treatment program, we assessed access to, use of, and barriers surrounding information and communication technology (ICT) among patients with chronic obstructive pulmonary disease (COPD) who currently smoke, examining associations between key predictors and electronic health (e-health) literacy. Methods: Single-center mixed-methods study of veterans with COPD who smoke. Eligible participants who smoked were identified by the e-health record and mailed a survey. E-health literacy was assessed by the eHEALS (Electronic Health Literacy Scale; 8-40). Low technology use was defined as no Internet-capable device and use of ICT less than monthly. Qualitative participants were purposively selected from survey respondents and interviewed using a semistructured guide. Interviews were transcribed and analyzed using directed content analysis. We used a Bayesian three-component joint model to identify predictors of low technology use and low eHEALS. Results: Participants (N = 204) were older (mean age, 65.8), primarily White (76.4%), men (87.1%), and with low income (44.9% income under $20,000). Low technology use was reported by 25.5%, and many reported low use of specific types of ICT. For example, only 36.3% had reliable in-home Internet, fewer than half (46.6%) accessed e-mail at least weekly, 58.3% texted at least weekly, and few used the secure patient portal (13.2% accessed it monthly). The mean eHEALS was 24.6 (±8.7), indicating low to moderate e-health literacy. In the Bayesian analysis, low technology use was associated with lower eHEALS (estimate: -8.5 [95% confidence interval, -12.13 to -4.81]). Attainment of at least a college graduate-level education was associated with higher eHEALS (3.83 [0.43-7.24]). Participants reported barriers to use of ICT, including struggles navigating account security, frequently lost login information, mistrust of providing personal information to the Internet, and lack of familiarity with processes. Many perceived ICT as not useful or necessary. Conclusions: Many patients with COPD who smoke report barriers to engagement with health promotion programs offered electronically, which may perpetuate health disparities. Health promotion programs must account for the low use of ICT and e-health literacy to ensure equitable access across the population.

Education for Tobacco Use Disorder Treatment: Current State, Evidence, and Unmet Needs.

Background: Tobacco use is undertreated in the medical setting. One driver may be inadequate tobacco use disorder treatment (TUDT) training for clinicians in specialties treating tobacco-dependent patients. Objective: We sought to evaluate the current state of TUDT training for diverse professionals and how these skills are assessed in credentialing exams. Methods: We performed a focused review of current educational practices, evidence-based strategies, and accreditation exam contents focused on TUDT. Results: Among medical students, participants in reviewed studies reported anywhere from 45 minutes to 3 hours of TUDT training throughout their 4-year programs, most often in the form of didactic sessions. Similarly, little TUDT training was reported at the post-graduate (residency, fellowship, continuing medical education) levels, and reported training was typically delivered as time-based (expected hours of instruction) rather than competency-based (demonstration of mastery) learning. Multiple studies evaluated effective TUDT curricula at varied stages of training. More effective curricula incorporated longitudinal sessions and active learning, such as standardized patient encounters or proctored patient visits. Knowledge of TUDT is minimally evaluated on certification exams. For example, the American Board of Internal Medicine blueprint lists TUDT as <2% of one subtopic on both the internal medicine and pulmonary exams. Conclusion: TUDT training for most clinicians is minimal, does not assess competency, and is minimally evaluated on certification exams. Effective, evidence-based TUDT training incorporating active learning should be integrated into medical education at all levels, with attention paid to inclusion on subsequent certifying exams.

"It's a decision I have to make": Patient perspectives on smoking and cessation after lung cancer screening decisions.

Few studies exist showing that involvement in lung cancer screening (LCS) leads to a change in rates of cigarette smoking. We investigated LCS longitudinally to determine whether teachable moments for smoking cessation occur downstream from the initial provider-patient LCS shared decision-making discussion and self-reported effects on smoking behaviors. We performed up to two successive semi-structured interviews to assess the experiences of 39 individuals who formerly or currently smoked cigarettes who underwent LCS decision-making discussions performed during routine care from three established US medical center LCS programs. The majority of those who remembered hearing about the importance of smoking cessation after LCS-related encounters did not report communication about smoking influencing their motivation to quit or abstain from smoking, including patients who were found to have pulmonary nodules. Patients experienced little distress related to LCS discussions. Patients reported that there were other, more significant, reasons for quitting or abstinence. They recommended clinicians continue to ask about smoking at every clinical encounter, provide information comparing the benefits of LCS with those of quitting smoking, and have clinicians help them identify triggers or other motivators for improving smoking behaviors. Our findings suggest that there may be other teachable moment opportunities outside of LCS processes that could be utilized to motivate smoking reduction or cessation, or LCS processes could be improved to integrate cessation resources.

Design considerations and analytical framework for reliably identifying a beneficial individualized treatment rule.

An individualized treatment rule (ITR) formalizes personalized medicine by assigning treatment as a function of patients' clinical information, which contrasts with a static treatment rule that assigns everyone the same treatment. ITR identification has become a common aim in randomized clinical trials but sample size considerations for this aim are lacking. One approach is to select a sample size that will reliably identify an ITR with a performance close to the theoretical optimal rule. However, this approach could still lead to identifying ITRs that perform worse than the optimal static rule, particularly in the absence of substantial effect heterogeneity. This limitation motivates sample size considerations aimed at reliable identification of a beneficial ITR, which outperforms the optimal static rule, and analysis methods that identify the estimated optimal static rule when there is substantial uncertainty about whether an ITR will improve outcomes. To address these limitations, we propose a sample size approach based on the probability of identifying a beneficial ITR and introduce an approach for selecting the LASSO penalty parameter such that in the absence of treatment effect heterogeneity the estimated optimal static rule is identified with high probability. We apply these approaches to the PLUTO trial aimed at developing methods to assist with smoking cessation.

Study design for a proactive teachable moment tobacco treatment intervention among patients with pulmonary nodules.

INTRODUCTION: We developed Teachable Moment to Opt-Out of Tobacco (TeaM OUT) as a tobacco treatment intervention based on a foundation of a theoretical model of teachable moments, "naturally occurring life transitions or health events thought to motivate individuals to spontaneously adopt risk-reducing health behaviors". The TeaM OUT intervention combines a teachable moment for patients with newly detected incidental pulmonary nodules with a proactive interactive voice response (IVR) system to increase connections to evidence-based tobacco treatment interventions. METHODS: We will perform a convergent, nested observational mixed-methods study utilizing both randomized trial and observational methods to test the effectiveness and generalizability of the TeaM OUT intervention through three aims. AIM 1: Among patients recently diagnosed with a pulmonary nodule, we will utilize a pragmatic, stepped wedge randomized controlled design to evaluate the effectiveness of a proactive, teachable moment-based, tobacco treatment outreach intervention (TeaM OUT) on increasing engagement with tobacco treatment resources compared to Enhanced Usual Care. AIM 2: Using a longitudinal observational design, we will evaluate the association of receipt of the TeaM OUT intervention with seven-day point abstinence prevalence and quit motivation compared to Enhanced Usual Care. AIM 3: Qualitatively elicit perspectives from key stakeholders to inform acceptability and utility, implementation barriers and facilitators, and scalability of the TeaM OUT intervention. DISCUSSION: We are hopeful that implementation of TeaM OUT will increase the number of patients who quit using cigarettes with subsequent improvements in their health.

COVID-19 postacute care major organ damage: a systematic review.

BACKGROUND: Major organ complications have been reported in patients hospitalised for COVID-19; most studies lacked controls. OBJECTIVE: Examine major organ damage postdischarge among adults hospitalised for COVID-19 versus non-COVID-19 controls. DATA SOURCES: MEDLINE, Embase and Cochrane Library from 1 January 2020 to 19 May 2021. STUDY ELIGIBILITY CRITERIA: English language studies of adults discharged from hospital for COVID-19; reporting major organ damage. Single review of abstracts; independent dual review of full text. STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed using the Joanna Briggs Institute Appraisal Checklist for Cohort Studies. Outcome data were not pooled due to heterogeneity in populations, study designs and outcome assessment methods; findings are narratively synthesised. RESULTS: Of 124 studies in a full evidence report, 9 included non-COVID controls and are described here. Four of the nine (three USA, one UK) used large administrative databases. Four of the remaining five studies enrolled <600 COVID-19 patients. Mean or median age ranged from 49 to 70 years with 46%-94% male and 48%-78% White race; 10%-40% had been in intensive care units. Follow-up ranged from 4 weeks to 22 weeks postdischarge. Four used hospitalised controls, three non-hospitalised controls and two were unclear. Studies used various definitions of, and methods to assess, major organ damage outcomes. While the magnitude of effect differed across studies, incident cardiac, pulmonary, liver, acute and chronic kidney, stroke, diabetes, and coagulation disorders were consistently greater in adults hospitalised for COVID-19 compared with non-COVID-19 controls. LIMITATIONS: Applicability to subgroups (age, gender, COVID-19 severity, treatment, vaccination status) and non-hospitalised patients is unknown. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Postacute COVID-19 major organ damage is common and likely higher than controls. However, there is substantial uncertainty. More consistent reporting of clinical outcomes and pre-COVID health status along with careful selection of control groups are needed to address evidence gaps. PROSPERO REGISTRATION NUMBER: CRD42020204788.

The Chain of Adherence for Incidentally Detected Pulmonary Nodules after an Initial Radiologic Imaging Study: A Multisystem Observational Study.

Rationale: Millions of people are diagnosed with incidental pulmonary nodules every year. Although most nodules are benign, it is universally recommended that all patients be assessed to determine appropriate follow-up and ensure that it is obtained. Objectives: To determine the degree of concordance and adherence to 2005 Fleischner Society guidelines among radiologists, clinicians, and patients at two Veterans Affairs healthcare systems with incidental nodule tracking systems. Methods: Trained researchers abstracted data from the electronic health records of patients with incidental pulmonary nodules as identified by interpreting radiologists from 2008 to 2016. We classified radiology reports and patient follow-up into three categories. Radiologist-Fleischner adherence was the agreement between the radiologist's recommendation in the computed tomography (CT) report and the 2005 Fleischner Society guidelines. Clinician/patient-Fleischner concordance was agreement between patient follow-up and the guidelines. Clinician/patient-radiologist adherence was agreement between the radiologist's recommendation and patient follow-up. We evaluated whether the recommendation or follow-up was more (e.g., sooner) or less (e.g., later) aggressive than recommended. Results: After exclusions, 4,586 patients with 7,408 imaging tests (n = 4,586 initial chest CT scans; n = 2,717 follow-up chest CT scans; n = 105 follow-up low-dose CT scans) were included. Among radiology reports that could be classified in terms of Fleischner Society guidelines (n = 3,150), 80% had nonmissing radiologist recommendations. Among those reports, radiologist-Fleischner adherence was 86.6%, with 4.8% more aggressive and 8.6% less aggressive. Among patients whose initial scans could be classified, clinician/patient-Fleischner concordance was 46.0%, 14.5% were more aggressive, and 39.5% were less aggressive. Clinician/patient-radiologist adherence was 54.3%. Veterans whose radiology reports were adherent to Fleischner Society guidelines had a substantially higher proportion of clinician/patient-Fleischner concordance: 52.0% concordance among radiologist-Fleischner adherent versus 11.6% concordance among radiologist-Fleischner nonadherent. Conclusions: In this multi-health system observational study of incidental pulmonary nodule follow-up, we found that radiologist adherence to 2005 Fleischner Society guidelines may be necessary but not sufficient. Our results highlight the many facets of care processes that must occur to achieve guideline-concordant care.

Self-reported exercise capacity among current smokers eligible for lung cancer screening: Distribution and association with key comorbidities.

ONE CONCERN: as lung cancer screening (LCS) is implemented is that patients will be screened who are too ill to benefit. Poor exercise capacity (EC) predicts adverse outcomes following lung resection. OBJECTIVE: Describe the distribution of EC among smokers eligible for LCS and examine associations with comorbidities. METHODS: Cross-sectional analysis of baseline data from a randomized controlled trial of tobacco treatment in the context of LCS. Participants responded regarding limitations in moderate activities, ability to climb stairs, and frequency of dyspnea on a scale from never/almost never to all or most of the time. Responses were assigned a numeric score and summed to categorize exercise limitation. Associations between poor EC and key comorbidities were examined using adjusted logistic regression. RESULTS: 660 participants completed a survey with the following characteristics: 64.4% male, 89.5% white, mean age 64.5. Overall EC categories were: good 39.0%, intermediate 41.6%, and poor 19.4%.  Prevalence of poor EC was higher among patients with COPD (OR 4.62 95%CI 3.05-7.02), heart failure (OR 3.07 95%CI 1.62-5.82) and cardiovascular disease (OR 2.24, 95%CI 1.45-3.47), and was highest among patients with multimorbidity. Among patients with COPD and heart failure, 57% had poor and 0% had good EC. In adjusted logistic regression, only COPD and Charlson comorbidity index remained significantly associated with poor EC. CONCLUSIONS: Many patients eligible for LCS reported poor EC, with increased odds of poor EC among patients with comorbidities. More research is needed to determine how to best integrate EC and comorbidity into eligibility and shared decision-making conversations.

Effectiveness and Harms of High-Flow Nasal Oxygen for Acute Respiratory Failure: An Evidence Report for a Clinical Guideline From the American College of Physicians.

BACKGROUND: Use of high-flow nasal oxygen (HFNO) for treatment of adults with acute respiratory failure (ARF) has increased. PURPOSE: To assess HFNO versus noninvasive ventilation (NIV) or conventional oxygen therapy (COT) for ARF in hospitalized adults. DATA SOURCES: English-language searches of MEDLINE, Embase, CINAHL, and Cochrane Library from January 2000 to July 2020; systematic review reference lists. STUDY SELECTION: 29 randomized controlled trials evaluated HFNO versus NIV (k = 11) or COT (k = 21). DATA EXTRACTION: Data extraction by a single investigator was verified by a second, 2 investigators assessed risk of bias, and evidence certainty was determined by consensus. DATA SYNTHESIS: Results are reported separately for HFNO versus NIV, for HFNO versus COT, and by initial or postextubation management. Compared with NIV, HFNO may reduce all-cause mortality, intubation, and hospital-acquired pneumonia and improve patient comfort in initial ARF management (low-certainty evidence) but not in postextubation management. Compared with COT, HFNO may reduce reintubation and improve patient comfort in postextubation ARF management (low-certainty evidence). LIMITATIONS: Trials varied in populations enrolled, ARF causes, and treatment protocols. Trial design, sample size, duration of treatment and follow-up, and results reporting were often insufficient to adequately assess many outcomes. Protocols, clinician and health system training, cost, and resource use were poorly characterized. CONCLUSION: Compared with NIV, HFNO as initial ARF management may improve several clinical outcomes. Compared with COT, HFNO as postextubation management may reduce reintubations and improve patient comfort; HFNO resulted in fewer harms than NIV or COT. Broad applicability, including required clinician and health system experience and resource use, is not well known. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42019146691).