Preferred Language Mediates Association Between Race, Ethnicity, and Delayed Presentation in Critically Ill Patients With COVID-19.

Which social factors explain racial and ethnic disparities in COVID-19 access to care and outcomes remain unclear. OBJECTIVES: We hypothesized that preferred language mediates the association between race, ethnicity and delays to care. DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective cohort study of adults with COVID-19 consecutively admitted to the ICU in three Massachusetts hospitals in 2020. MAIN OUTCOME AND MEASURES: Causal mediation analysis was performed to evaluate potential mediators including preferred language, insurance status, and neighborhood characteristics. RESULTS: Non-Hispanic White (NHW) patients (157/442, 36%) were more likely to speak English as their preferred language (78% vs. 13%), were less likely to be un- or under-insured (1% vs. 28%), lived in neighborhoods with lower social vulnerability index (SVI) than patients from racial and ethnic minority groups (SVI percentile 59 [28] vs. 74 [21]) but had more comorbidities (Charlson comorbidity index 4.6 [2.5] vs. 3.0 [2.5]), and were older (70 [13.2] vs. 58 [15.1] years). From symptom onset, NHW patients were admitted 1.67 [0.71-2.63] days earlier than patients from racial and ethnic minority groups (p < 0.01). Non-English preferred language was associated with delay to admission of 1.29 [0.40-2.18] days (p < 0.01). Preferred language mediated 63% of the total effect (p = 0.02) between race, ethnicity and days from symptom onset to hospital admission. Insurance status, social vulnerability, and distance to the hospital were not on the causal pathway between race, ethnicity and delay to admission. CONCLUSIONS AND RELEVANCE: Preferred language mediates the association between race, ethnicity and delays to presentation for critically ill patients with COVID-19, although our results are limited by possible collider stratification bias. Effective COVID-19 treatments require early diagnosis, and delays are associated with increased mortality. Further research on the role preferred language plays in racial and ethnic disparities may identify effective solutions for equitable care.

Prolonged Prone Position Ventilation Is Associated With Reduced Mortality in Intubated COVID-19 Patients.

BACKGROUND: Prone position ventilation (PPV) is resource-intensive, yet the optimal strategy for PPV in intubated patients with COVID-19 is unclear. RESEARCH QUESTION: Does a prolonged (24 or more h) PPV strategy improve mortality in intubated COVID-19 patients compared with intermittent (∼16 h with daily supination) PPV? STUDY DESIGN AND METHODS: Multicenter, retrospective cohort study of consecutively admitted intubated COVID-19 patients treated with PPV between March 11 and May 31, 2020. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 90-day all-cause mortality and prone-related complications. Inverse probability treatment weights (IPTW) were used to control for potential treatment selection bias. RESULTS: Of the COVID-19 patients who received PPV, 157 underwent prolonged and 110 underwent intermittent PPV. Patients undergoing prolonged PPV had reduced 30-day (adjusted hazard ratio [aHR], 0.475; 95% CI, 0.336-0.670; P < .001) and 90-day (aHR, 0.638; 95% CI, 0.461-0.883; P = .006) mortality compared with intermittent PPV. In patients with Pao2/Fio2 ≤ 150 at the time of pronation, prolonged PPV was associated with reduced 30-day (aHR, 0.357; 95% CI, 0.213-0.597; P < .001) and 90-day mortality (aHR, 0.562; 95% CI, 0.357-0.884; P = .008). Patients treated with prolonged PPV underwent fewer pronation and supination events (median, 1; 95% CI, 1-2 vs 3; 95% CI, 1-4; P < .001). PPV strategy was not associated with overall PPV-related complications, although patients receiving prolonged PPV had increased rates of facial edema and lower rates of peri-proning hypotension. INTERPRETATION: Among intubated COVID-19 patients who received PPV, prolonged PPV was associated with reduced mortality. Prolonged PPV was associated with fewer pronation and supination events and a small increase in rates of facial edema. These findings suggest that prolonged PPV is a safe, effective strategy for mortality reduction in intubated COVID-19 patients.

Code status orders in patients admitted to the intensive care unit with COVID-19: A retrospective cohort study.

Purpose: Code status orders impact clinical outcomes as well as patients' and surrogates' experiences. This is the first multicenter cohort examining code status orders of ICU patients with COVID-19 reported to date. Materials and methods: This is a retrospective cohort study including adult patients who tested positive for SARS-CoV-2 and were admitted to the ICU at three hospitals in Massachusetts from March 11, 2020 - May 31, 2020. We examined differences in code status orders at multiple timepoints and performed multivariable regression analysis to identify variables associated with code status at admission. Results: Among 459 ICU patients with COVID-19, 421 (91.7%) were Full Code at hospital admission. Age and admission from a facility were positively associated with DNR status (adjusted OR 1.10, 95% CI 1.05-1.15, p < 0.001 and adjusted OR 2.68, CI 1.23-5.71, p = 0.011, respectively) while non-English preferred language was negatively associated with DNR status (adjusted OR 0.29, 95% CI 0.10-0.74, p = 0.012). Among 147 patients who died during hospitalization, 95.2% (140) died with DNR code status; most (86.4%) died within two days of final code status change. Conclusions: The association of non-English preferred language with Full Code status in critically ill COVID-19 patients highlights the importance of medical interpreters in the ICU. Patients who died were transitioned to DNR more than in previous studies, possibly reflecting changes in practice during a novel pandemic.

Characteristics and Outcomes of Latinx Patients With COVID-19 in Comparison With Other Ethnic and Racial Groups.

BACKGROUND: There is a limited understanding of the impact of coronavirus disease 2019 (COVID-19) on the Latinx population. We hypothesized that Latinx patients would be more likely to be hospitalized and admitted to the intensive care unit (ICU) than White patients. METHODS: We analyzed all patients with COVID-19 in 12 Massachusetts hospitals between February 1 and April 14, 2020. We examined the association between race, ethnicity, age, reported comorbidities, and hospitalization and ICU admission using multivariable regression. RESULTS: Of 5190 COVID-19 patients, 29% were hospitalized; 33% required the ICU, and 4.3% died. Forty-six percent of patients were White, 25% Latinx, 14% African American, and 3% Asian American. Ethnicity and race were significantly associated with hospitalization. More Latinx and African American patients in the younger age groups were hospitalized than whites. Latinxs and African Americans disproportionally required the ICU, with 39% of hospitalized Latinx patients requiring the ICU compared with 33% of African Americans, 24% of Asian Americans, and 30% of Whites (P < .007). Within each ethnic and racial group, age and male gender were independently predictive of hospitalization. Previously reported preexisting comorbidities contributed to the need for hospitalization in all racial and ethnic groups (P < .05). However, the observed disparities were less likely related to reported comorbidities, with Latinx and African American patients being admitted at twice the rate of Whites, regardless of such comorbidities. CONCLUSIONS: Latinx and African American patients with COVID-19 have higher rates of hospitalization and ICU admission than White patients. The etiologies of such disparities are likely multifactorial and cannot be explained only by reported comorbidities.

Early clinical and sociodemographic experience with patients hospitalized with COVID-19 at a large American healthcare system.

BACKGROUND: Despite over 4 million cases of novel coronavirus disease 2019 (COVID-19) in the United States, limited data exist including socioeconomic background and post-discharge outcomes for patients hospitalized with this disease. METHODS: In this case series, we identified patients with COVID-19 admitted to 3 Partners Healthcare hospitals in Boston, Massachusetts between March 7th, 2020, and March 30th, 2020. Patient characteristics, treatment strategies, and outcomes were determined. FINDINGS: A total of 247 patients hospitalized with COVID-19 were identified; the median age was 61 (interquartile range [IQR]: 50-76 years), 58% were men, 30% of Hispanic ethnicity, 21% enrolled in Medicaid, and 12% dual-enrolled Medicare/Medicaid. The median estimated household income was $66,701 [IQR: $50,336-$86,601]. Most patients were treated with hydroxychloroquine (72%), and statins (76%; newly initiated in 34%). During their admission, 103 patients (42%) required intensive care. At the end of the data collection period (June 24, 2020), 213 patients (86.2%) were discharged alive, 2 patients (0.8%) remain admitted, and 32 patients (13%) have died. Among those discharged alive (n = 213), 70 (32.9%) were discharged to a post-acute facility, 31 (14.6%) newly required supplemental oxygen, 19 (8.9%) newly required tube feeding, and 34 (16%) required new prescriptions for antipsychotics, benzodiazepines, methadone, or opioids. Over a median post-discharge follow-up of 80 days (IQR, 68-84), 22 patients (10.3%) were readmitted. INTERPRETATION: Patients hospitalized with COVID-19 are frequently of vulnerable socioeconomic status and often require intensive care. Patients who survive COVID-19 hospitalization have substantial need for post-acute services.

Compliance With the National SEP-1 Quality Measure and Association With Sepsis Outcomes: A Multicenter Retrospective Cohort Study.

OBJECTIVES: Many septic patients receive care that fails the Centers for Medicare and Medicaid Services' SEP-1 measure, but it is unclear whether this reflects meaningful lapses in care, differences in clinical characteristics, or excessive rigidity of the "all-or-nothing" measure. We compared outcomes in cases that passed versus failed SEP-1 during the first 2 years after the measure was implemented. DESIGN: Retrospective cohort study. SETTING: Seven U.S. hospitals. PATIENTS: Adult patients included in SEP-1 reporting between October 2015 and September 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 851 sepsis cases in the cohort, 281 (33%) passed SEP-1 and 570 (67%) failed. SEP-1 failures had higher rates of septic shock (20% vs 9%; p < 0.001), hospital-onset sepsis (11% vs 4%; p = 0.001), and vague presenting symptoms (46% vs 30%; p < 0.001). The most common reasons for failure were omission of 3- and 6-hour lactate measurements (228/570 failures, 40%). Only 86 of 570 failures (15.1%) had greater than 3-hour delays until broad-spectrum antibiotics. Cases that failed SEP-1 had higher in-hospital mortality rates (18.4% vs 11.0%; odds ratio, 1.82; 95% CI, 1.19-2.80; p = 0.006), but this association was no longer significant after adjusting for differences in clinical characteristics and severity of illness (adjusted odds ratio, 1.36; 95% CI, 0.85-2.18; p = 0.205). Delays of greater than 3 hours until antibiotics were significantly associated with death (adjusted odds ratio, 1.94; 95% CI, 1.04-3.62; p = 0.038), whereas failing SEP-1 for any other reason was not (adjusted odds ratio, 1.10; 95% CI, 0.70-1.72; p = 0.674). CONCLUSIONS: Crude mortality rates were higher in sepsis cases that failed versus passed SEP-1, but there was no difference after adjusting for clinical characteristics and severity of illness. Delays in antibiotic administration were associated with higher mortality but only accounted for a small fraction of SEP-1 failures. SEP-1 may not clearly differentiate between high- and low-quality care, and detailed risk adjustment is necessary to properly interpret associations between SEP-1 compliance and mortality.

Comparison of proteomic and transcriptomic profiles in the bronchial airway epithelium of current and never smokers.

BACKGROUND: Although prior studies have demonstrated a smoking-induced field of molecular injury throughout the lung and airway, the impact of smoking on the airway epithelial proteome and its relationship to smoking-related changes in the airway transcriptome are unclear. METHODOLOGY/PRINCIPAL FINDINGS: Airway epithelial cells were obtained from never (n = 5) and current (n = 5) smokers by brushing the mainstem bronchus. Proteins were separated by one dimensional polyacrylamide gel electrophoresis (1D-PAGE). After in-gel digestion, tryptic peptides were processed via liquid chromatography/ tandem mass spectrometry (LC-MS/MS) and proteins identified. RNA from the same samples was hybridized to HG-U133A microarrays. Protein detection was compared to RNA expression in the current study and a previously published airway dataset. The functional properties of many of the 197 proteins detected in a majority of never smokers were similar to those observed in the never smoker airway transcriptome. LC-MS/MS identified 23 proteins that differed between never and current smokers. Western blotting confirmed the smoking-related changes of PLUNC, P4HB1, and uteroglobin protein levels. Many of the proteins differentially detected between never and current smokers were also altered at the level of gene expression in this cohort and the prior airway transcriptome study. There was a strong association between protein detection and expression of its corresponding transcript within the same sample, with 86% of the proteins detected by LC-MS/MS having a detectable corresponding probeset by microarray in the same sample. Forty-one proteins identified by LC-MS/MS lacked detectable expression of a corresponding transcript and were detected in

Gene expression profiling of human lung tissue from smokers with severe emphysema.

The mechanism by which inhaled smoke causes the anatomic lesions and physiologic impairment of chronic obstructive pulmonary disease remains unknown. We used high-density microarrays to measure gene expression in severely emphysematous lung tissue removed from smokers at lung volume reduction surgery (LVRS) and normal or mildly emphysematous lung tissue from smokers undergoing resection of pulmonary nodules. Class prediction algorithms identified 102 genes that accurately distinguished severe emphysema from non-/mildly emphysematous lung tissue. We also defined a number of genes whose expression levels correlated strongly with lung diffusion capacity for carbon monoxide and/or forced expiratory volume at 1 s. Genes related to oxidative stress, extracellular matrix synthesis, and inflammation were increased in severe emphysema, whereas expression of endothelium-related genes was decreased. To identify candidate genes that might be causally involved in the pathogenesis of emphysema, we linked gene expression profiles to chromosomal regions previously associated with chronic obstructive pulmonary disease in genome-wide linkage analyses. Unsupervised hierarchical clustering of the LVRS samples revealed distinct molecular subclasses of severe emphysema, with body mass index as the only clinical variable that differed between the groups. Class prediction models established a set of genes that predicted functional outcome at 6 mo after LVRS. Our findings suggest that the gene expression profiles from human emphysematous lung tissue may provide insight into pathogenesis, uncover novel molecular subclasses of disease, predict response to LVRS, and identify targets for therapeutic intervention.