Benefit-Harm Analysis of Earlier Initiation of Triple Therapy for Prevention of Acute Exacerbation in Patients with COPD.

Rationale: Reducing the risk of exacerbation is a fundamental goal in managing stable COPD. Guidelines recommend triple therapy (inhaled corticosteroids, long-acting muscarinic antagonists, and long-acting beta-agonists [ICS/LAMA/LABA]) only as a step-up from dual therapy (LAMA/LABA) for patients at continued high risk of exacerbation, due to the trade-off of an increased risk of pneumonia associated with ICS-containing therapies. However, there is little evidence on the optimum timing of initiating triple therapy. Objectives: To perform a benefit-harm analysis to evaluate the net benefit of earlier initiation of triple therapy for the prevention of acute exacerbations in patients with COPD, compared to standard timing recommended in current guidelines. Methods: We used a validated whole disease microsimulation model of COPD in the Canadian general population aged ≥40 years to determine the benefit-harm of earlier initiation of triple therapy over a 20-year time horizon, compared to standard care. We assessed net change in quality-adjusted life-years (QALYs) from the reduction in risk of acute exacerbations and the increased risk of treatment-related pneumonia in subgroups of patients with COPD defined by exacerbation history, symptoms, and disease severity. Model parameters were determined from clinical trials and other published literature. Key parameters were varied in one-way sensitivity analysis. Results: In patients at high risk of acute exacerbation (54.7% female, mean age 74.0, 68% GOLD grade I-II), earlier initiation of triple therapy was associated with a net QALY gain of 4.8 per 100 COPD patients over 20 years, compared to standard care. The net QALY gain increased to 5.9 per 100 patients in the subgroup of patients with a high symptom burden (mMRC>1). Earlier initiation remained net beneficial in all subgroup and sensitivity analysis scenarios. Conclusions: Modeling suggests that earlier initiation of triple therapy is likely to be net beneficial for patients at high risk of acute exacerbation, with an even greater benefit to patients with a high symptom burden. Further clinical research is needed to verify these findings in empirical studies.

Risks of Zolpidem among Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Nonbenzodiazepine benzodiazepine receptor agonists (NBZRA, e.g., zolpidem) are frequently used to treat insomnia among patients with chronic obstructive pulmonary disease (COPD). However, multiple observational studies find that patients with COPD who are prescribed NBZRAs have greater risks for mortality and respiratory complications than patients without such prescriptions. Without an active comparator, these studies are susceptible to confounding by indication. Objectives: Compare the risk of death or inpatient COPD exacerbation among patients receiving zolpidem relative to patients receiving other hypnotics. Methods: Using nationwide Veterans Health Administration (VA) data, we identified patients with clinically diagnosed COPD and new receipt of zolpidem or another hypnotic available on VA formulary without prior authorization (melatonin, trazodone, doxepin). We excluded those receiving traditional benzodiazepines or multiple concurrent hypnotics. We propensity-matched patients receiving zolpidem to other hypnotics on 32 variables, including demographics, comorbidities, and markers of COPD severity. We compared risk of the primary composite outcome of death or inpatient COPD exacerbation over 1 year. In secondary analyses, we propensity-matched patients receiving zolpidem to those without hypnotic receipt. Results: Among 283,740 patients meeting inclusion criteria, 1,126 (0.4%) received zolpidem and 3,057 (1.1%) received other hypnotics. We propensity-matched patients receiving zolpidem 1:1 to peers receiving other hypnotics. We did not find a difference in the primary composite outcome of death or inpatient exacerbation (hazard ratio, 0.97; 95% confidence interval [CI], 0.77-1.23). In secondary analyses comparing patients receiving zolpidem to matched peers without hypnotic receipt, we observed greater risk of death or inpatient exacerbation with zolpidem (hazard ratio, 1.40; 95% CI, 1.09-1.81). Conclusions: Among patients with COPD, we did not observe greater risks after new receipt of zolpidem relative to other hypnotics. However, we did observe greater risks relative to those without hypnotic receipt. This latter finding may reflect: 1) residual, unmeasured confounding related to insomnia; or 2) true adverse effects of hypnotics across classes. Future work is needed to better understand the risks of hypnotics in COPD.

Inhaler Formulary Change in COPD and the Association with Exacerbations, Health Care Utilization, and Costs.

Rationale: Prescription formularies specify which medications are available to patients. Formularies change frequently, potentially forcing patients to switch medications for nonclinical indications (nonmedical switching). Nonmedical switching is known to impact disease control and adherence. The consequences of nonmedical switching have not been rigorously studied in COPD. Methods: We conducted a cohort study of Veterans with COPD on inhaler therapy in January 2016 when formoterol was removed from the Department of Veterans Affairs (VA) national formulary. A 2-point difference-in-differences analysis using multivariable negative binomial and generalized linear models was performed to estimate the association of the formulary change with patient outcomes in the 6 months before and after the change. Our primary outcome was the number of COPD exacerbations in 6 months, with secondary outcomes of total health care encounters and encounter-related costs in 6 months. Results: We identified 10,606 Veterans who met our inclusion criteria, of which 409 (3.9%) experienced nonmedical switching off formoterol. We did not identify a change in COPD exacerbations (-0.04 exacerbations; 95% confidence interval [CI] -0.12, 0.03) associated with the formulary change. In secondary outcome analysis, we did not observe a change in the number of health care encounters (-0.12 visits; 95% CI -1.00, 0.77) or encounter-related costs ($369; 95% CI -$1141, $1878). Conclusions: Among COPD patients on single inhaler therapy, nonmedical inhaler switches due to formulary discontinuation of formoterol were not associated with changes in COPD exacerbations, encounters, or encounter-related costs. Additional research is needed to confirm our findings in more severe disease and other settings.

Assessment of Obstructive Sleep Apnea Among Patients With Chronic Obstructive Pulmonary Disease in Primary Care.

Study Objectives: Observational studies link untreated obstructive sleep apnea (OSA) with adverse outcomes in chronic obstructive pulmonary disease (COPD). The first step in addressing OSA is a clinical assessment. However, given competing demands and a lack of high-quality evidence, it is unclear how often such assessments occur. We explored the documentation of OSA assessment among patients with COPD in primary care, and the patient and provider characteristics associated with these assessments. Methods: We conducted a cross-sectional study of patients with clinically diagnosed COPD at two primary care practices. We abstracted charts to determine whether providers assessed OSA, defined as documentation of: symptoms, treatment, or referral to sleep medicine. We performed multivariable mixed-effects logistic regression to assess the associations of patient and provider characteristics with OSA assessment. Results: Among 641 patients with clinically diagnosed COPD, 146 (23%) had OSA assessed over a one-year period. Positive associations with OSA assessment included BMI ≥ 30 (OR 3.5, 95%CI 1.8-7.0), pulmonary subspecialist visits (OR 3.9, 95%CI 2.4-6.3), and a prior sleep study demonstrating OSA documented within the electronic medical record (OR 18.0, 95%CI 9.0-35.8). Notably, patients identifying as Black were less likely to have OSA assessed than those identifying as White (OR 0.5, 95%CI 0.2-0.9). Conclusions: Providers document an assessment of OSA among a quarter of patients with COPD. Our findings highlight the importance of future work to rigorously test the impact of assessment on important health outcomes. Our findings also reinforce that additional strategies are needed to improve the equitable delivery of care.

Sleep Testing and Mortality in a Propensity-matched Cohort of Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Many advocate the application of propensity-matching methods to real-world data to answer key questions around obstructive sleep apnea (OSA) management. One such question is whether identifying undiagnosed OSA impacts mortality in high-risk populations, such as those with chronic obstructive pulmonary disease (COPD). Objectives: Assess the association of sleep testing with mortality among patients with COPD and a high likelihood of undiagnosed OSA. Methods: We identified patients with COPD and a high likelihood of undiagnosed OSA. We then distinguished those receiving sleep testing within 90 days of index COPD encounters. We calculated propensity scores for testing based on 37 variables and compared long-term mortality in matched groups. In sensitivity analyses, we compared mortality using inverse propensity weighting and instrumental variable methods. We also compared the incidence of nonfatal events including adverse outcomes (hospitalizations and COPD exacerbations) and routine services that are regularly indicated in COPD (influenza vaccination and pulmonary function testing). We compared the incidence of each nonfatal event as a composite outcome with death and separately compared the marginal probability of each nonfatal event independently, with death as a competing risk. Results: Among 135,958 patients, 1,957 (1.4%) received sleep testing. We propensity matched all patients with sleep testing to an equal number without testing, achieving excellent balance on observed confounders, with standardized differences < 0.10. We observed lower mortality risk among patients with sleep testing (incidence rate ratio, 0.88; 95% confidence interval [CI], 0.79-0.99) and similar results using inverse propensity weighting and instrumental variable methods. Contrary to mortality, we found that sleep testing was associated with a similar or greater risk for nonfatal adverse events, including inpatient COPD exacerbations (subhazard ratio, 1.29; 95% CI, 1.02-1.62) and routine services like influenza vaccination (subhazard ratio, 1.26; 95% CI, 1.17-1.36). Conclusions: Our disparate findings can be interpreted in multiple ways. Sleep testing may indeed cause both reduced mortality and greater incidence of nonfatal adverse outcomes and routine services. However, it is also possible that our findings stem from residual confounding by patients' likelihood of accessing care. Given the limitations of propensity-based analyses, we cannot confidently distinguish these two possibilities. This uncertainty highlights the limitations of using propensity-based analyses to guide patient care and policy decisions.

Trends and Rural-Urban Differences in the Initial Prescription of Low-Value Inhaled Corticosteroids among U.S. Veterans with Chronic Obstructive Pulmonary Disease.

Rationale: Guidelines recommend inhaled corticosteroids (ICS) for patients with chronic obstructive pulmonary disease (COPD) and select indications, including asthma history, high exacerbation risk, or high serum eosinophils. ICS are commonly prescribed outside of these indications, despite evidence of harm. We defined a "low-value" ICS prescription as the receipt of an ICS without evidence of a guideline-recommended indication. ICS prescription patterns are not well characterized and could inform health system interventions to reduce low-value practices. Objectives: To evaluate the national trends in initial low-value ICS prescriptions in the U.S. Department of Veterans Affairs and to determine whether rural-urban differences in low-value ICS prescribing exist. Methods: We performed a cross-sectional study between January 4, 2010, and December 31, 2018, identifying veterans with COPD who were new users of inhaler therapy. We defined low-value ICS as prescriptions in patients with 1) no asthma, 2) low risk of future exacerbation (Global Initiative for Chronic Obstructive Lung Disease group A or B), and 3) serum eosinophils <300 cells/µl. We performed multivariable logistic regression to evaluate trends in low-value ICS prescription over time, adjusting for potential confounders. We performed fixed effects logistic regression to assess rural-urban prescribing patterns. Results: We identified a total of 131,009 veterans with COPD starting inhaler therapy, 57,472 (44%) of whom were prescribed low-value ICS as initial therapy. From 2010 to 2018, the probability of receiving low-value ICS as initial therapy increased by 0.42 percentage points per year (95% confidence interval, 0.31-0.53). Compared with urban residence, rural residence was associated with a 2.5-percentage-point (95% confidence interval, 1.9-3.1) higher probability of receiving low-value ICS as initial therapy. Conclusions: The prescription of low-value ICS as initial therapy is common and increasing slightly over time for both rural and urban veterans. Given the widespread and persistent nature of low-value ICS prescribing, health system leaders should consider system-wide approaches to address this low-value prescribing practice.

Impact of mail-based continuous positive airway pressure initiation on treatment usage and effectiveness.

PURPOSE: In-person visits with a trained therapist have been standard care for patients initiating continuous positive airway pressure (CPAP). These visits provide an opportunity for hands-on training and an in-person assessment of mask fit. However, to improve access, many health systems are shifting to remote CPAP initiation with equipment mailed to patients. While there are potential benefits of a mailed approach, relative patient outcomes are unclear. Specifically, many have concerns that a lack of in-person training may contribute to reduced CPAP adherence. To inform this knowledge gap, we aimed to compare treatment usage after in-person or mailed CPAP initiation. METHODS: Our medical center shifted from in-person to mailed CPAP dispensation in March 2020 during the COVID-19 pandemic. We assembled a cohort of patients with newly diagnosed obstructive sleep apnea (OSA) who initiated CPAP in the months before (n = 433) and after (n = 186) this shift. We compared 90-day adherence between groups. RESULTS: Mean nightly PAP usage was modest in both groups (in-person 145.2, mailed 140.6 min/night). We did not detect between-group differences in either unadjusted or adjusted analyses (adjusted difference - 0.2 min/night, 95% - 27.0 to + 26.5). CONCLUSIONS: Mail-based systems of CPAP initiation may be able to improve access without reducing CPAP usage. Future work should consider the impact of mailed CPAP on patient-reported outcomes and the impact of different remote setup strategies.

Health Care Spending on Respiratory Diseases in the United States, 1996-2016.

Rationale: Respiratory conditions account for a large proportion of health care spending in the United States. A full characterization of spending across multiple conditions and over time has not been performed. Objectives: To estimate health care spending in the United States for 11 respiratory conditions from 1996 to 2016, providing detailed trends and an evaluation of factors associated with spending growth. Methods: We extracted data from the Institute of Health Metrics and Evaluation's Disease Expenditure Project Database, producing annual estimates in spending for 38 age and sex groups, 7 types of care, and 3 payer types. We performed a decomposition analysis to estimate the change in spending associated with changes in each of five factors (population growth, population aging, disease prevalence, service usage, and service price and intensity). Measurements and Main Results: Total spending across all respiratory conditions in 2016 was $170.8 billion (95% confidence interval [CI], $164.2-179.2 billion), increasing by $71.7 billion (95% CI, $63.2-80.8 billion) from 1996. The respiratory conditions with the highest spending in 2016 were asthma and chronic obstructive pulmonary disease, contributing $35.5 billion (95% CI, $32.4-38.2 billion) and $34.3 billion (95% CI, $31.5-37.3 billion), respectively. Increasing service price and intensity were associated with 81.4% (95% CI, 70.3-93.0%) growth from 1996 to 2016. Conclusions: U.S. spending on respiratory conditions is high, particularly for chronic conditions like asthma and chronic obstructive pulmonary disease. Our findings suggest that service price and intensity, particularly for pharmaceuticals, should be a key focus of attention for policymakers seeking to reduce health care spending growth.

A call to integrate health equity into learning health system research training.

In 2016, the Agency for Healthcare Research and Quality (AHRQ) recommended seven domains for training and mentoring researchers in learning health systems (LHS) science. Health equity was not included as a competency domain. This commentary from scholars in the Consortium for Applied Training to Advance the Learning health system with Scholars/Trainees (CATALyST) K12 program recommends that competency domains be extended to reflect growing demands for evidence on health inequities and interventions to alleviate them. We present real-life case studies from scholars in an LHS research training program that illustrate facilitators, challenges, and potential solutions at the program, funder, and research community-level to receiving training and mentorship in health equity-focused LHS science. We recommend actions in four areas for LHS research training programs: (a) integrate health equity throughout the current LHS domains; (b) develop training and mentoring in health equity; (c) establish program evaluation standards for consideration of health equity; and (d) bring forth relevant, extant expertise from the areas of health disparities research, community-based participatory research, and community-engaged health services research. We emphasize that LHS research must acknowledge and build on the substantial existing contributions, mainly by scholars of color, in the health equity field.

Radiographic Findings and Association With Clinical Severity and Outcomes in Critically Ill Patients With COVID-19.

PURPOSE: To describe evolution and severity of radiographic findings and assess association with disease severity and outcomes in critically ill COVID-19 patients. MATERIALS AND METHODS: This retrospective study included 62 COVID-19 patients admitted to the intensive care unit (ICU). Clinical data was obtained from electronic medical records. A total of 270 chest radiographs were reviewed and qualitatively scored (CXR score) using a severity scale of 0-30. Radiographic findings were correlated with clinical severity and outcome. RESULTS: The CXR score increases from a median initial score of 10 at hospital presentation to the median peak CXR score of 18 within a median time of 4 days after hospitalization, and then slowly decreases to a median last CXR score of 15 in a median time of 12 days after hospitalization. The initial and peak CXR score was independently associated with invasive MV after adjusting for age, gender, body mass index, smoking, and comorbidities (Initial, odds ratio [OR]: 2.11 per 5-point increase, confidence interval [CI] 1.35-3.32, P= 0.001; Peak, OR: 2.50 per 5-point increase, CI 1.48-4.22, P= 0.001). Peak CXR scores were also independently associated with vasopressor usage (OR: 2.28 per 5-point increase, CI 1.30-3.98, P= 0.004). Peak CXR scores strongly correlated with the duration of invasive MV (Rho = 0.62, P< 0.001), while the initial CXR score (Rho = 0.26) and the peak CXR score (Rho = 0.27) correlated weakly with the sequential organ failure assessment score. No statistically significant associations were found between radiographic findings and mortality. CONCLUSIONS: Evolution of radiographic features indicates rapid disease progression and correlate with requirement for invasive MV or vasopressors but not mortality, which suggests potential nonpulmonary pathways to death in COVID-19.

Cost analysis of a coaching intervention to increase use of transradial percutaneous coronary intervention.

BACKGROUND: The transradial approach (TRA) to cardiac catheterization is safer than the traditional transfemoral approach (TFA), with similar clinical effectiveness. However, adoption of TRA remains low, representing less than 50% of catheterization procedures in 2015. Peer coaching is one approach to facilitate implementation; however, the costs of this strategy for cardiac procedures such as TRA are unclear. METHODS: We conducted an activity-based costing analysis (ABC) of a multi-center, hybrid type III implementation trial of a coaching intervention designed to increase the use of TRA. We identified the key activities of the intervention and determined the personnel, resources, and time needed to complete each activity. The personnel cost per hour and the activity duration were then used to estimate the cost of each activity and the total variable cost of the implementation. Fixed costs related to designing and running the implementation were calculated separately. All costs are reported in 2019 constant US dollars. RESULTS: The total cost of the coaching intervention implementation was $374,863. Of the total cost, $367,752 were variable costs due to travel, preparatory work, in-person coaching, post-intervention evaluation, and administrative time. We estimated fixed costs of $7112. The mean marginal cost of implementing the intervention at only one additional medical center was $52,536. CONCLUSIONS: We provide granular cost estimates of a conceptually rooted implementation strategy designed to increase the uptake of TRA for cardiac catheterization. We estimate that implementation costs stemming from the coaching approach would be offset after the conversion of approximately 409 to 1363 catheterizations from TFA to TRA. Our estimates provide benchmarks of the expected costs of implementing evidence-based, but expertise-intensive, cardiac procedures. TRIAL REGISTRATION: ISRCTN, ISRCTN66341299 . Registered 7 July 2020-retrospectively registered.

Economic evaluation of a novel community-based diabetes care model in rural Mexico: a cost and cost-effectiveness study.

OBJECTIVES: Diabetes is the leading cause of disability-adjusted life years in Mexico, and cost-effective care models are needed to address the epidemic. We sought to evaluate the cost and cost-effectiveness of a novel community-based model of diabetes care in rural Mexico, compared with usual care. DESIGN: We performed time-driven activity-based costing to estimate annualised costs associated with typical diabetes care in Chiapas, Mexico, as well as a novel diabetes care model known as Compañeros En Salud Programa de Enfermedades Crónicas (CESPEC). We conducted Markov chain analysis to estimate the cost-effectiveness of CESPEC compared with usual care from a societal perspective. We used patient outcomes from CESPEC in 2016, as well as secondary data from existing literature. SETTING: Rural primary care clinics in Chiapas, Mexico. PARTICIPANTS: Adults with diabetes. INTERVENTIONS: CESPEC is a novel, comprehensive, diabetes care model that integrates community health workers, provider education, supply chain management and active case finding. OUTCOME MEASURE: The primary outcome was the incremental cost-effectiveness of CESPEC compared with care as usual, per quality-adjusted life year (QALY) gained, expressed in 2016 US dollars. RESULTS: The economic cost of the CESPEC diabetes model was US$144 per patient per year, compared with US$125 for diabetes care as usual. However, CESPEC care was associated with 0.13 additional years of health-adjusted life expectancy compared with usual care and 0.02 additional years in the first 5 years of treatment. This translated to an incremental cost-effectiveness ratio (ICER) of US$2981 per QALY gained over a patient's lifetime and an ICER of US$10 444 over the first 5 years. Findings were robust to multiple sensitivity analyses. CONCLUSIONS: CESPEC is a cost-effective, community-based model of diabetes care for patients in rural Mexico. Given the high prevalence and significant morbidity associated with diabetes in Mexico and other countries in Central America, this model should be considered for broader scale up and evaluation.

Low-Value Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease and the Association with Healthcare Utilization and Costs.

Rationale: Inhaled corticosteroids (ICS) are not first-line therapy for patients with chronic obstructive pulmonary disease (COPD) at low risk of exacerbations, but they are commonly prescribed despite evidence of harm. We consider ICS prescription in this population to be of "low value." The association of low-value ICS with subsequent healthcare utilization and costs is unknown. Understanding this relationship could inform efforts to reduce the delivery of low-value care. Objectives: To determine whether low-value ICS prescribing is associated with higher outpatient healthcare utilization and costs among patients with COPD who are at low risk of exacerbation. Methods: We performed a cohort study between January 1, 2010, and December 31, 2018, identifying a cohort of veterans with COPD who performed pulmonary function tests (PFTs) at 21 Veterans Affairs medical centers nationwide. Patients were defined as having low exacerbation risk if they experienced less than two outpatient exacerbations and no hospital admissions for COPD in the year before PFTs. Our primary exposure was the receipt of an ICS prescription in the 3 months before the date of PFTs. Our primary outcomes were outpatient utilization and outpatient costs in the 1 year after PFTs. For inference, we generated negative binomial models for utilization and generalized linear models for costs, adjusting for confounders. Results: We identified a total of 31,551 patients with COPD who were at low risk of exacerbation. Of these patients, 9,742 were prescribed low-value ICS (mean [standard deviation (SD)] age, 69 [9] yr), and 21,809 were not prescribed low-value ICS (mean [SD] age, 68 [9] yr). Compared with unexposed patients, those exposed to low-value ICS had 0.53 more encounters per patient per year (95% confidence interval CI, 0.23-0.83) and incurred $154.72 higher costs/patient/year (95% CI, $45.58-$263.86). Conclusions: Low-value ICS prescription was associated with higher subsequent outpatient healthcare utilization and costs. Potential mechanisms for the observed association are that 1) low-value ICS may be a marker of poor respiratory symptom control, 2) there is confounding by indication, or 3) low-value ICS results in increased drug costs or utilization. Health systems should identify low-value ICS prescriptions as a target to improve value-based care.

Comparison of Clinical Features and Outcomes in Critically Ill Patients Hospitalized with COVID-19 versus Influenza.

Rationale: No direct comparisons of clinical features, laboratory values, and outcomes between critically ill patients with coronavirus disease (COVID-19) and patients with influenza in the United States have been reported.Objectives: To evaluate the risk of mortality comparing critically ill patients with COVID-19 with patients with seasonal influenza.Methods: We retrospectively identified patients admitted to the intensive care units (ICUs) at two academic medical centers with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or influenza A or B infections between January 1, 2019, and April 15, 2020. The clinical data were obtained by medical record review. All patients except one had follow-up to hospital discharge or death. We used relative risk regression adjusting for age, sex, number of comorbidities, and maximum sequential organ failure scores on Day 1 in the ICU to determine the risk of hospital mortality and organ dysfunction in patients with COVID-19 compared with patients with influenza.Results: We identified 65 critically ill patients with COVID-19 and 74 patients with influenza. The mean (±standard deviation) age in each group was 60.4 ± 15.7 and 56.8 ± 17.6 years, respectively. Patients with COVID-19 were more likely to be male, have a higher body mass index, and have higher rates of chronic kidney disease and diabetes. Of the patients with COVID-19, 37% identified as Hispanic, whereas 10% of the patients with influenza identified as Hispanic. A similar proportion of patients had fevers (∼40%) and lymphopenia (∼80%) on hospital presentation. The rates of acute kidney injury and shock requiring vasopressors were similar between the groups. Although the need for invasive mechanical ventilation was also similar in both groups, patients with COVID-19 had slower improvements in oxygenation, longer durations of mechanical ventilation, and lower rates of extubation than patients with influenza. The hospital mortality was 40% in patients with COVID-19 and 19% in patients with influenza (adjusted relative risk, 2.13; 95% confidence interval, 1.24-3.63; P = 0.006).Conclusions: The need for invasive mechanical ventilation was common in patients in the ICU for COVID-19 and influenza. Compared with those with influenza, patients in the ICU with COVID-19 had worse respiratory outcomes, including longer duration of mechanical ventilation. In addition, patients with COVID-19 were at greater risk for in-hospital mortality, independent of age, sex, comorbidities, and ICU severity of illness.