Disparities in Unilateral Do Not Resuscitate Order Use During the COVID-19 Pandemic.

OBJECTIVES: A unilateral do-not-resuscitate (UDNR) order is a do-not-resuscitate order placed using clinician judgment which does not require consent from a patient or surrogate. This study assessed how UDNR orders were used during the COVID-19 pandemic. DESIGN: We analyzed a retrospective cross-sectional study of UDNR use at two academic medical centers between April 2020 and April 2021. SETTING: Two academic medical centers in the Chicago metropolitan area. PATIENTS: Patients admitted to an ICU between April 2020 and April 2021 who received vasopressor or inotropic medications to select for patients with high severity of illness. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 1,473 patients meeting inclusion criteria were 53% male, median age 64 (interquartile range, 54-73), and 38% died during admission or were discharged to hospice. Clinicians placed do not resuscitate orders for 41% of patients ( n = 604/1,473) and UDNR orders for 3% of patients ( n = 51/1,473). The absolute rate of UDNR orders was higher for patients who were primary Spanish speaking (10% Spanish vs 3% English; p ≤ 0.0001), were Hispanic or Latinx (7% Hispanic/Latinx vs 3% Black vs 2% White; p = 0.003), positive for COVID-19 (9% vs 3%; p ≤ 0.0001), or were intubated (5% vs 1%; p = 0.001). In the base multivariable logistic regression model including age, race/ethnicity, primary language spoken, and hospital location, Black race (adjusted odds ratio [aOR], 2.5; 95% CI, 1.3-4.9) and primary Spanish language (aOR, 4.4; 95% CI, 2.1-9.4) had higher odds of UDNR. After adjusting the base model for severity of illness, primary Spanish language remained associated with higher odds of UDNR order (aOR, 2.8; 95% CI, 1.7-4.7). CONCLUSIONS: In this multihospital study, UDNR orders were used more often for primary Spanish-speaking patients during the COVID-19 pandemic, which may be related to communication barriers Spanish-speaking patients and families experience. Further study is needed to assess UDNR use across hospitals and enact interventions to improve potential disparities.

Dose optimisation and scarce resource allocation: two sides of the same coin.

OBJECTIVE: A deep understanding of the relationship between a scarce drug's dose and clinical response is necessary to appropriately distribute a supply-constrained drug along these lines. SUMMARY OF KEY DATA: The vast majority of drug development and repurposing during the COVID-19 pandemic - an event that has made clear the ever-present scarcity in healthcare systems -has been ignorant of scarcity and dose optimisation's ability to help address it. CONCLUSIONS: Future pandemic clinical trials systems should obtain dose optimisation data, as these appear necessary to enable appropriate scarce resource allocation according to societal values.

Errors in Converting Principles to Protocols: Where the Bioethics of U.S. Covid-19 Vaccine Allocation Went Wrong.

For much of 2021, allocating the scarce supply of Covid-19 vaccines was the world's most pressing bioethical challenge, and similar challenges may recur for novel therapies and future vaccines. In the United States, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) identified three fundamental ethical principles to guide the process: maximize benefits, promote justice, and mitigate health inequities. We argue that critical components of the recommended protocol were internally inconsistent with these principles. Specifically, the ACIP violated its principles by recommending overly broad health care worker priority in phase 1a, using being at least seventy-five years of age as the only criterion to identify individuals at high risk of death from Covid-19 during phase 1b, failing to recommend place-based vaccine distribution, and implicitly endorsing first-come, first-served allocation. More rigorous empirical work and the development of a complete ethical framework that recognizes trade-offs between principles may have prevented these mistakes and saved lives.

Association of Zip Code Vaccination Rate With COVID-19 Mortality in Chicago, Illinois.

Importance: There has been large geographic inequity in vaccination coverage across Chicago, Illinois, with higher vaccination rates in zip codes with residents who predominantly have high incomes and are White. Objective: To determine the association between inequitable zip code-level vaccination coverage and COVID-19 mortality in Chicago. Design, Setting, and Participants: This retrospective cohort study used Chicago Department of Public Health vaccination and mortality data and Cook County Medical Examiner mortality data from March 1, 2020, through November 6, 2021, to assess the association of COVID-19 mortality with zip code-level vaccination rates. Data were analyzed from June 1, 2021, to April 13, 2022. Exposures: Zip code-level first-dose vaccination rates before the Alpha and Delta waves of COVID-19. Main Outcomes and Measures: The primary outcome was deaths from COVID-19 during the Alpha and Delta waves. The association of a marginal increase in zip code-level vaccination rate with weekly mortality rates was estimated with a mixed-effects Poisson regression model, and the total number of preventable deaths in the least vaccinated quartile of zip codes was estimated with a linear difference-in-difference design. Results: The study population was 2 686 355 Chicago residents in 52 zip codes (median [IQR] age 34 [32-38] years; 1 378 658 [51%] women; 773 938 Hispanic residents [29%]; 783 916 non-Hispanic Black residents [29%]; 894 555 non-Hispanic White residents [33%]). Among residents in the least vaccinated quartile, 80% were non-Hispanic Black, compared with 8% of residents identifying as non-Hispanic Black in the most vaccinated quartile (P < .001). After controlling for age distribution and recovery from COVID-19, a 10-percentage point increase in zip code-level vaccination 6 weeks before the peak of the Alpha wave was associated with a 39% lower relative risk of death from COVID-19 (incidence rate ratio [IRR], 0.61 [95% CI, 0.52-0.72]). A 10-percentage point increase in zip code vaccination rate 6 weeks before the peak of the Delta wave was associated with a 24% lower relative risk of death (IRR, 0.76 [95% CI, 0.66-0.87]). The difference-in-difference estimate was that 119 Alpha wave deaths (72% [95% CI, 63%-81%]) and 108 Delta wave deaths (75% [95% CI, 66%-84%]) might have been prevented in the least vaccinated quartile of zip codes if it had had the vaccination coverage of the most vaccinated quartile. Conclusions and Relevance: These findings suggest that low zip code-level vaccination rates in Chicago were associated with more deaths during the Alpha and Delta waves of COVID-19 and that inequitable vaccination coverage exacerbated existing racial and ethnic disparities in COVID-19 deaths.

Coronavirus Disease 2019 Temperature Trajectories Correlate With Hyperinflammatory and Hypercoagulable Subphenotypes.

OBJECTIVES: Body temperature trajectories of infected patients are associated with specific immune profiles and survival. We determined the association between temperature trajectories and distinct manifestations of coronavirus disease 2019. DESIGN: Retrospective observational study. SETTING: Four hospitals within an academic healthcare system from March 2020 to February 2021. PATIENTS: All adult patients hospitalized with coronavirus disease 2019. INTERVENTIONS: Using a validated group-based trajectory model, we classified patients into four previously defined temperature trajectory subphenotypes using oral temperature measurements from the first 72 hours of hospitalization. Clinical characteristics, biomarkers, and outcomes were compared between subphenotypes. MEASUREMENTS AND MAIN RESULTS: The 5,903 hospitalized coronavirus disease 2019 patients were classified into four subphenotypes: hyperthermic slow resolvers (n = 1,452, 25%), hyperthermic fast resolvers (1,469, 25%), normothermics (2,126, 36%), and hypothermics (856, 15%). Hypothermics had abnormal coagulation markers, with the highest d-dimer and fibrin monomers (p < 0.001) and the highest prevalence of cerebrovascular accidents (10%, p = 0.001). The prevalence of venous thromboembolism was significantly different between subphenotypes (p = 0.005), with the highest rate in hypothermics (8.5%) and lowest in hyperthermic slow resolvers (5.1%). Hyperthermic slow resolvers had abnormal inflammatory markers, with the highest C-reactive protein, ferritin, and interleukin-6 (p < 0.001). Hyperthermic slow resolvers had increased odds of mechanical ventilation, vasopressors, and 30-day inpatient mortality (odds ratio, 1.58; 95% CI, 1.13-2.19) compared with hyperthermic fast resolvers. Over the course of the pandemic, we observed a drastic decrease in the prevalence of hyperthermic slow resolvers, from representing 53% of admissions in March 2020 to less than 15% by 2021. We found that dexamethasone use was associated with significant reduction in probability of hyperthermic slow resolvers membership (27% reduction; 95% CI, 23-31%; p < 0.001). CONCLUSIONS: Hypothermics had abnormal coagulation markers, suggesting a hypercoagulable subphenotype. Hyperthermic slow resolvers had elevated inflammatory markers and the highest odds of mortality, suggesting a hyperinflammatory subphenotype. Future work should investigate whether temperature subphenotypes benefit from targeted antithrombotic and anti-inflammatory strategies.

Variation in COVID-19 Resource Allocation Protocols and Potential Implementation in the Chicago Metropolitan Area.

BACKGROUND: Scarce resource allocation policies vary across the United States. Little is known about regional variation in resource allocation protocols and variation in their application. We sought to evaluate how Covid-19 scarce resource allocation policies vary throughout the Chicago metropolitan area and whether there are differences in policy application within hospitals when prioritizing hypothetical patients who need critical care resources. METHODS: Two cross-sectional surveys were distributed to Chicago metropolitan area hospital representatives and triage officers. Survey responses and categorical variables are described by frequency of occurrence. Intra- and interhospital variation in ranking of hypothetical patients was assessed using Fleiss's Kappa coefficients. RESULTS: Eight Chicago-area hospitals responded to the survey assessing scarce resource allocation protocols (N = 8/18, response rate 44%). For hospitals willing to describe their ventilator allocation protocol (N = 7), most used the sequential organ failure assessment (SOFA) score (N = 6/7, 86%) and medical comorbidities (N = 4/7, 57%) for initial scoring of patients. A majority gave priority in initial scoring to pre-defined groups (N = 5/7, 71%), all discussed withdrawal of mechanical ventilation for adult patients (N = 7/7, 100%), and a minority had exclusion criteria (N = 3/7, 43%). Forty-nine triage officers from nine hospitals responded to the second survey (N = 9/10 hospitals, response rate 90%). Their rankings of hypothetical patients showed only slight agreement amongst all hospitals (Kappa 0.158) and fair agreement within two hospitals with the most respondents (Kappa 0.21 and 0.25). Almost half used tiebreakers to rank patients (N = 23/49, 47%). CONCLUSIONS: Although most respondents from Chicago-area hospitals described policies for resource allocation during the COVID-19 pandemic, the substance and application of these protocols varied. There was little agreement when prioritizing hypothetical patients to receive scarce resources, even among people from the same hospital. Variations in resource allocation protocols and their application could lead to inequitable distribution of resources, further exacerbating community distrust and disparities in health.Supplemental data for this article is available online at https://doi.org/10.1080/23294515.2021.1983667.

Hospital-Level Variation in Death for Critically Ill Patients with COVID-19.

RATIONALE: Variation in hospital mortality has been described for coronavirus disease 2019 (COVID-19), but the factors that explain these differences remain unclear. OBJECTIVE: Our objective was to utilize a large, nationally representative dataset of critically ill adults with COVID-19 to determine which factors explain mortality variability. METHODS: In this multicenter cohort study, we examined adults hospitalized in intensive care units with COVID-19 at 70 United States hospitals between March and June 2020. The primary outcome was 28-day mortality. We examined patient-level and hospital-level variables. Mixed-effects logistic regression was used to identify factors associated with interhospital variation. The median odds ratio (OR) was calculated to compare outcomes in higher- vs. lower-mortality hospitals. A gradient boosted machine algorithm was developed for individual-level mortality models. MEASUREMENTS AND MAIN RESULTS: A total of 4,019 patients were included, 1537 (38%) of whom died by 28 days. Mortality varied considerably across hospitals (0-82%). After adjustment for patient- and hospital-level domains, interhospital variation was attenuated (OR decline from 2.06 [95% CI, 1.73-2.37] to 1.22 [95% CI, 1.00-1.38]), with the greatest changes occurring with adjustment for acute physiology, socioeconomic status, and strain. For individual patients, the relative contribution of each domain to mortality risk was: acute physiology (49%), demographics and comorbidities (20%), socioeconomic status (12%), strain (9%), hospital quality (8%), and treatments (3%). CONCLUSION: There is considerable interhospital variation in mortality for critically ill patients with COVID-19, which is mostly explained by hospital-level socioeconomic status, strain, and acute physiologic differences. Individual mortality is driven mostly by patient-level factors. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

COVID-19 Among African Americans: An Action Plan for Mitigating Disparities.

As the COVID-19 pandemic has unfolded across the United States, troubling disparities in mortality have emerged between different racial groups, particularly African Americans and Whites. Media reports, a growing body of COVID-19-related literature, and long-standing knowledge of structural racism and its myriad effects on the African American community provide important lenses for understanding and addressing these disparities.However, troubling gaps in knowledge remain, as does a need to act. Using the best available evidence, we present risk- and place-based recommendations for how to effectively address these disparities in the areas of data collection, COVID-19 exposure and testing, health systems collaboration, human capital repurposing, and scarce resource allocation.Our recommendations are supported by an analysis of relevant bioethical principles and public health practices. Additionally, we provide information on the efforts of Chicago, Illinois' mayoral Racial Equity Rapid Response Team to reduce these disparities in a major urban US setting.

Variation in Ventilator Allocation Guidelines by US State During the Coronavirus Disease 2019 Pandemic: A Systematic Review.

Importance: During the coronavirus disease 2019 pandemic, there may be too few ventilators to meet medical demands. It is unknown how many US states have ventilator allocation guidelines and how these state guidelines compare with one another. Objective: To evaluate the number of publicly available US state guidelines for ventilator allocation and the variation in state recommendations for how ventilator allocation decisions should occur and to assess whether unique criteria exist for pediatric patients. Evidence Review: This systematic review evaluated publicly available guidelines about ventilator allocation for all states in the US and in the District of Columbia using department of health websites for each state and internet searches. Documents with any discussion of a process to triage mechanical ventilatory support during a public health emergency were screened for inclusion. Articles were excluded if they did not include specific ventilator allocation recommendations, were in draft status, did not include their state department of health, or were not the most up-to-date guideline. All documents were individually assessed and reassessed by 2 independent reviewers from March 30 to April 2 and May 8 to 10, 2020. Findings: As of May 10, 2020, 26 states had publicly available ventilator guidelines, and 14 states had pediatric guidelines. Use of the Sequential Organ Failure Assessment score in the initial rank of adult patients was recommended in 15 state guidelines (58%), and assessment of limited life expectancy from underlying conditions or comorbidities was included in 6 state guidelines (23%). Priority was recommended for specific groups in the initial evaluation of patients in 6 states (23%) (ie, Illinois, Maryland, Massachusetts, Michigan, Pennsylvania, and Utah). Many states recommended exclusion criteria in adult (11 of 26 states [42%]) and pediatric (10 of 14 states [71%]) ventilator allocation. Withdrawal of mechanical ventilation from a patient to give to another if a shortage occurs was discussed in 22 of 26 adult guidelines (85%) and 9 of 14 pediatric guidelines (64%). Conclusions and Relevance: These findings suggest that although allocation guidelines for mechanical ventilatory support are essential in a public health emergency, only 26 US states provided public guidance on how this allocation should occur. Guidelines among states, including adjacent states, varied significantly and could cause inequity in the allocation of mechanical ventilatory support during a public health emergency, such as the coronavirus disease 2019 pandemic.