Validation of a Crisis Standards of Care Model for Prioritization of Limited Resources During the Coronavirus Disease 2019 Crisis in an Urban, Safety-Net, Academic Medical Center.

OBJECTIVES: The coronavirus disease 2019 pandemic has overwhelmed healthcare resources even in wealthy nations, necessitating rationing of limited resources without previously established crisis standards of care protocols. In Massachusetts, triage guidelines were designed based on acute illness and chronic life-limiting conditions. In this study, we sought to retrospectively validate this protocol to cohorts of critically ill patients from our hospital. DESIGN: We applied our hospital-adopted guidelines, which defined severe and major chronic conditions as those associated with a greater than 50% likelihood of 1- and 5-year mortality, respectively, to a critically ill patient population. We investigated mortality for the same intervals. SETTING: An urban safety-net hospital ICU. PATIENTS: All adults hospitalized during April of 2015 and April 2019 identified through a clinical database search. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 365 admitted patients, 15.89% had one or more defined chronic life-limiting conditions. These patients had higher 1-year (46.55% vs 13.68%; p < 0.01) and 5-year (50.00% vs 17.22%; p < 0.01) mortality rates than those without underlying conditions. Irrespective of classification of disease severity, patients with metastatic cancer, congestive heart failure, end-stage renal disease, and neurodegenerative disease had greater than 50% 1-year mortality, whereas patients with chronic lung disease and cirrhosis had less than 50% 1-year mortality. Observed 1- and 5-year mortality for cirrhosis, heart failure, and metastatic cancer were more variable when subdivided into severe and major categories. CONCLUSIONS: Patients with major and severe chronic medical conditions overall had 46.55% and 50.00% mortality at 1 and 5 years, respectively. However, mortality varied between conditions. Our findings appear to support a crisis standards protocol which focuses on acute illness severity and only considers underlying conditions carrying a greater than 50% predicted likelihood of 1-year mortality. Modifications to the chronic lung disease, congestive heart failure, and cirrhosis criteria should be refined if they are to be included in future models.

Performance of crisis standards of care guidelines in a cohort of critically ill COVID-19 patients in the United States.

Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial.

BACKGROUND: The antibacterial, anti-inflammatory, and antiviral properties of azithromycin suggest therapeutic potential against COVID-19. Randomised data in mild-to-moderate disease are not available. We assessed whether azithromycin is effective in reducing hospital admission in patients with mild-to-moderate COVID-19. METHODS: This prospective, open-label, randomised superiority trial was done at 19 hospitals in the UK. We enrolled adults aged at least 18 years presenting to hospitals with clinically diagnosed, highly probable or confirmed COVID-19 infection, with fewer than 14 days of symptoms, who were considered suitable for initial ambulatory management. Patients were randomly assigned (1:1) to azithromycin (500 mg once daily orally for 14 days) plus standard care or to standard care alone. The primary outcome was death or hospital admission from any cause over the 28 days from randomisation. The primary and safety outcomes were assessed according to the intention-to-treat principle. This trial is registered at ClinicalTrials.gov (NCT04381962) and recruitment is closed. FINDINGS: 298 participants were enrolled from June 3, 2020, to Jan 29, 2021. Three participants withdrew consent and requested removal of all data, and three further participants withdrew consent after randomisation, thus, the primary outcome was assessed in 292 participants (145 in the azithromycin group and 147 in the standard care group). The mean age of the participants was 45·9 years (SD 14·9). 15 (10%) participants in the azithromycin group and 17 (12%) in the standard care group were admitted to hospital or died during the study (adjusted OR 0·91 [95% CI 0·43-1·92], p=0·80). No serious adverse events were reported. INTERPRETATION: In patients with mild-to-moderate COVID-19 managed without hospital admission, adding azithromycin to standard care treatment did not reduce the risk of subsequent hospital admission or death. Our findings do not support the use of azithromycin in patients with mild-to-moderate COVID-19. FUNDING: National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford and Pfizer.

Do standards of care and early outcomes of periprosthetic fractures change during the COVID-19 pandemic? A multicentre study.

BACKGROUND: Periprosthetic fractures (PPFs) are a growing matter for orthopaedic surgeons, and patients with PPFs may represent a frail target in the case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of this study is to investigate whether hospital reorganisations during the most severe phase of the SARS-CoV-2 pandemic affected standards of care and early outcomes of patients treated for PPFs in Northern Italy. MATERIALS AND METHODS: Data were retrieved from a multicentre retrospective orthopaedics and traumatology database, including 14 hospitals. The following parameters were studied: demographics, results of nasopharyngeal swabs, prevalence of coronavirus disease 2019 (COVID-19), comorbidities, general health status (EQ-5D-5L Score), frailty (Clinical Frailty Scale, CFS), pain (visual analogue scale, VAS), anaesthesiologic risk (American Society of Anaesthesiology Score, ASA Score), classification (unified classification system, UCS), type of operation and anaesthesia, in-hospital and early complications (Clavien-Dindo Classification, CDC), and length of stay (LOS). Data were analysed by means of descriptive statistics. Out of 1390 patients treated for any reason, 38 PPFs were included. RESULTS: Median age was 81 years (range 70-96 years). Twenty-three patients (60.5%) were swabbed on admission, and two of them (5.3%) tested positive; in three patients (7.9%), the diagnosis of COVID-19 was established on a clinical and radiological basis. Two more patients tested positive post-operatively, and one of them died due to COVID-19. Thirty-three patients (86.8%) presented a proximal femoral PPF. Median ASA Score was 3 (range, 1-4), median VAS score on admission was 3 (range, 0-6), median CFS was 4 (range, 1-8), median EQ-5D-5L Score was 3 in each one of the categories (range, 1-5). Twenty-three patients (60.5%) developed post-operative complications, and median CDC grade was 3 (range, 1-5). The median LOS was 12.8 days (range 2-36 days), and 21 patients (55.3%) were discharged home. CONCLUSIONS: The incidence of PPFs did not seem to change during the lockdown. Patients were mainly elderly with comorbidities, and complications were frequently recorded post-operatively. Despite the difficult period for the healthcare system, hospitals were able to provide effective conventional surgical treatments for PPFs, which were not negatively influenced by the reorganisation. Continued efforts are required to optimise the treatment of these frail patients in the period of the pandemic, minimising the risk of contamination, and to limit the incidence of PPFs in the future. LEVEL OF EVIDENCE: IV.

No evidence of tocilizumab treatment efficacy for severe to critical SARS-CoV2 infected patients: Results from a retrospective controlled multicenter study.

ABSTRACT: To assess tocilizumab (TCZ) efficacy associated to standard of care (SOC) compared to SOC alone in severe coronavirus associated disease 2019 (COVID-19) patients. In a matched case-control study from 3 French Hospital COVID-19 Departments, 27 patients with severe COVID-19 treated with TCZ and SOC were matched for baseline epidemiological and clinical features and compared to 27 severe COVID-19 patients treated with SOC alone. Baseline characteristics of the study population were comparable between groups. Eleven patients (20%) died. TCZ was not associated with clinical improvement as compared to SOC regarding oxygen-free status (44% vs 63%) and death (18.5% vs 22%), despite a higher decrease of the C-reactive protein at Day 7 (10.7 vs 52 mg/L; P < 10-3). Compared to the 43 patients alive at the end-of follow-up, patients who died were older (78 vs 64 years; P < 10-3), with 82% of them older than 72 years vs only 23% of live patients (P < 10-3). Age (OR = 1.15; 95%CI = 1.04-1.3; P = .008) and age over 72 years (OR) = 14.85; 95%CI = 2.7-80; P = .002) were independently associated with mortality. TCZ in addition to SOC for severe COVID-19 patients did not reduce mortality, subsequent need for invasive mechanical ventilation nor did it shorten the time of oxygen support, despite better control of the inflammatory response. More powerful and randomized controlled trials are warranted to determine if TCZ is effective in the management of COVID-19.

Assessment of Disparities Associated With a Crisis Standards of Care Resource Allocation Algorithm for Patients in 2 US Hospitals During the COVID-19 Pandemic.

Importance: Significant concern has been raised that crisis standards of care policies aimed at guiding resource allocation may be biased against people based on race/ethnicity. Objective: To evaluate whether unanticipated disparities by race or ethnicity arise from a single institution's resource allocation policy. Design, Setting, and Participants: This cohort study included adults (aged ≥18 years) who were cared for on a coronavirus disease 2019 (COVID-19) ward or in a monitored unit requiring invasive or noninvasive ventilation or high-flow nasal cannula between May 26 and July 14, 2020, at 2 academic hospitals in Miami, Florida. Exposures: Race (ie, White, Black, Asian, multiracial) and ethnicity (ie, non-Hispanic, Hispanic). Main Outcomes and Measures: The primary outcome was based on a resource allocation priority score (range, 1-8, with 1 indicating highest and 8 indicating lowest priority) that was assigned daily based on both estimated short-term (using Sequential Organ Failure Assessment score) and longer-term (using comorbidities) mortality. There were 2 coprimary outcomes: maximum and minimum score for each patient over all eligible patient-days. Standard summary statistics were used to describe the cohort, and multivariable Poisson regression was used to identify associations of race and ethnicity with each outcome. Results: The cohort consisted of 5613 patient-days of data from 1127 patients (median [interquartile range {IQR}] age, 62.7 [51.7-73.7]; 607 [53.9%] men). Of these, 711 (63.1%) were White patients, 323 (28.7%) were Black patients, 8 (0.7%) were Asian patients, and 31 (2.8%) were multiracial patients; 480 (42.6%) were non-Hispanic patients, and 611 (54.2%) were Hispanic patients. The median (IQR) maximum priority score for the cohort was 3 (1-4); the median (IQR) minimum score was 2 (1-3). After adjustment, there was no association of race with maximum priority score using White patients as the reference group (Black patients: incidence rate ratio [IRR], 1.00; 95% CI, 0.89-1.12; Asian patients: IRR, 0.95; 95% CI. 0.62-1.45; multiracial patients: IRR, 0.93; 95% CI, 0.72-1.19) or of ethnicity using non-Hispanic patients as the reference group (Hispanic patients: IRR, 0.98; 95% CI, 0.88-1.10); similarly, no association was found with minimum score for race, again with White patients as the reference group (Black patients: IRR, 1.01; 95% CI, 0.90-1.14; Asian patients: IRR, 0.96; 95% CI, 0.62-1.49; multiracial patients: IRR, 0.81; 95% CI, 0.61-1.07) or ethnicity, again with non-Hispanic patients as the reference group (Hispanic patients: IRR, 1.00; 95% CI, 0.89-1.13). Conclusions and Relevance: In this cohort study of adult patients admitted to a COVID-19 unit at 2 US hospitals, there was no association of race or ethnicity with the priority score underpinning the resource allocation policy. Despite this finding, any policy to guide altered standards of care during a crisis should be monitored to ensure equitable distribution of resources.

A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial.

BACKGROUND: The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. METHODS: DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. DISCUSSION: This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04429854 . Registered on 12 June 2020 - Retrospectively registered.

Caution With the Use of Lopinavir/Ritonavir in Severely Ill Patients for the Treatment of SARS-CoV-2: A Report of Severe Jaundice.

INTRODUCTION: We investigated the potential hepatotoxicity of lopinavir/ritonavir recently used in the treatment of Severe Acute Respiratory Syndrome Coronavirus. METHODS: This is a retrospective cohort of critical patients in a teaching hospital: 12 treated with lopinavir/ritonavir and 30 in the standard-of-care group. RESULTS: Elevation occurred more frequently in patients treated with lopinavir/ritonavir (33% vs 6.7%). DISCUSSION: Caution is advised regarding the use of lopinavir/ritonavir in the most severe cases of Severe Acute Respiratory Syndrome Coronavirus.