Outcomes of patients with COVID-19 in the setting of chronic opioid use disorder.

BACKGROUND: There are limited studies regarding the effects of COVID-19 in patients with a concurrent diagnosis of opioid use disorder (OUD). Due to the rapidly developing nature and consequences of this disease, it is important to identify patients at an increased risk for serious illness. The aim of this study was to identify whether COVID-19 patients with OUD are at an increased risk of hospitalization and other adverse outcomes. METHODS: This retrospective chart review compared clinical parameters from patients with positive COVID-19 status as identified by a positive SARS-CoV-2 PCR test and diagnosed OUD at the University of Utah Health. The primary outcome variables were hospitalization for COVID-19, length of hospital stay, and the presence of comorbidities in the OUD patient population. Descriptive statistics and prevalence ratios (PRs) were generated. Log binomial models generated PRs adjusted by age, sex, and race, and comorbidities of asthma, pneumonia, hypertension, cardiovascular disease, and diabetes. RESULTS: COVID-19 patients with OUD were significantly more likely than patients without OUD to have asthma (p < 0.01), diabetes (p < 0.01), hypertension (p < 0.01), cardiovascular disease (p < 0.01), and chronic pneumonia (p < 0.01), and to be hospitalized (27.9 percent vs 3.6 percent; p < 0.01), admitted to the intensive care unit (11.5 percent vs 1.5 percent; p < 0.01), and receive mechanical ventilation (30.5 percent vs 0.1 percent; p < 0.01). After adjusting for age, sex, race, asthma, pneumonia, cardiovascular disease, hypertension, and diabetes, patients with OUD continued to be at increased risk for inpatient hospitalization (aPR = 4.27, 95 percent confidence interval [CI] = 1.66-10.94). Patients with OUD also averaged longer stays in the hospital than those without OUD (9.53 days vs 0.70 days, p < 0.001). CONCLUSION: Patients with a diagnosis of OUD in the presence of COVID-19 are more likely to be hospitalized, have underlying health issues, and have longer hospital inpatient stays compared to patients without OUD.

Extracorporeal cardiopulmonary resuscitation in adults: evidence and implications.

Rates of survival with functional recovery for both in-hospital and out-of-hospital cardiac arrest are notably low. Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a modality to improve prognosis by augmenting perfusion to vital end-organs by utilizing extracorporeal membrane oxygenation (ECMO) during conventional CPR and stabilizing the patient for interventions aimed at reversing the aetiology of the arrest. Implementing this emergent procedure requires a substantial investment in resources, and even the most successful ECPR programs may nonetheless burden healthcare systems, clinicians, patients, and their families with unsalvageable patients supported by extracorporeal devices. Non-randomized and observational studies have repeatedly shown an association between ECPR and improved survival, versus conventional CPR, for in-hospital cardiac arrest in select patient populations. Recently, randomized controlled trials suggest benefit for ECPR over standard resuscitation, as well as the feasibility of performing such trials, in out-of-hospital cardiac arrest within highly coordinated healthcare delivery systems. Application of these data to clinical practice should be done cautiously, with outcomes likely to vary by the setting and system within which ECPR is initiated. ECPR introduces important ethical challenges, including whether it should be considered an extension of CPR, at what point it becomes sustained organ replacement therapy, and how to approach patients unable to recover or be bridged to heart replacement therapy. The economic impact of ECPR varies by health system, and has the potential to outstrip resources if used indiscriminately. Ideally, studies should include economic evaluations to inform health care systems about the cost-benefits of this therapy.

Development and validation of a machine learning method to predict intraoperative red blood cell transfusions in cardiothoracic surgery.

Accurately predicting red blood cell (RBC) transfusion requirements in cardiothoracic (CT) surgery could improve blood inventory management and be used as a surrogate marker for assessing hemorrhage risk preoperatively. We developed a machine learning (ML) method to predict intraoperative RBC transfusions in CT surgery. A detailed database containing time-stamped clinical variables for all CT surgeries from 5/2014-6/2019 at a single center (n = 2410) was used for model development. After random forest feature selection, surviving features were inputs for ML algorithms using five-fold cross-validation. The dataset was updated with 437 additional cases from 8/2019-8/2020 for validation. We developed and validated a hybrid ML method given the skewed nature of the dataset. Our Gaussian Process (GP) regression ML algorithm accurately predicted RBC transfusion amounts of 0 and 1-3 units (root mean square error, RMSE 0.117 and 1.705, respectively) and our GP classification ML algorithm accurately predicted 4 + RBC units transfused (area under the curve, AUC = 0.826). The final prediction is the regression result if classification predicted < 4 units transfused, or the classification result if 4 + units were predicted. We developed and validated an ML method to accurately predict intraoperative RBC transfusions in CT surgery using local data.

HEROES V-V-HEmorRhagic cOmplications in Veno-Venous Extracorporeal life Support-Development and internal validation of multivariable prediction model in adult patients.

BACKGROUND: During extracorporeal life support (ECLS), bleeding is one of the most frequent complications, associated with high morbidity and increased mortality, despite continuous improvements in devices and patient care. Risk factors for bleeding complications in veno-venous (V-V) ECLS applied for respiratory support have been poorly investigated. We aim to develop and internally validate a prediction model to calculate the risk for bleeding complications in adult patients receiving V-V ECLS support. METHODS: Data from adult patients reported to the extracorporeal life support organization (ELSO) registry between the years 2010 and 2020 were analyzed. The primary outcome was bleeding complications recorded during V-V ECLS. Multivariable logistic regression with backward stepwise elimination was used to develop the predictive model. The performance of the model was tested by discriminative ability and calibration with receiver operating characteristic curves and visual inspection of the calibration plot. RESULTS: In total, 18 658 adult patients were included, of which 3 933 (21.1%) developed bleeding complications. The prediction model showed a prediction of bleeding complications with an AUC of 0.63. Pre-ECLS arrest, surgical cannulation, lactate, pO2 , HCO3 , ventilation rate, mean airway pressure, pre-ECLS cardiopulmonary bypass or renal replacement therapy, pre-ECLS surgical interventions, and different types of diagnosis were included in the prediction model. CONCLUSIONS: The model is based on the largest cohort of V-V ECLS patients and reveals the most favorable predictive value addressing bleeding events given the predictors that are feasible and when compared to the current literature. This model will help identify patients at risk of bleeding complications, and decision making in terms of anticoagulation and hemostatic management.

Safety and feasibility of using acellular sterile filtered amniotic fluid as a treatment for patients with COVID-19: protocol for a randomised, double-blinded, placebo-controlled clinical trial.

INTRODUCTION: Human amniotic fluid (hAF) has been shown to reduce inflammation in multiple experimental models. hAF has previously been approved by the US Food and Drug Administration (FDA) as a human cellular and tissue product for tissue injury for human administration, and used safely in thousands of patients as a therapeutic treatment for diverse conditions. Given the profound inflammatory response observed in patients with COVID-19, and the successful completion of 10-patient pilot study of intravenous hAF, we present a trial design for a larger clinical trial of intravenous hAF for the treatment of COVID-19. METHODS AND ANALYSIS: This paper describes the methodology of a phase I/II randomised, double-blinded, placebo-controlled clinical trial to determine the safety and feasibility of using acellular sterile filtered amniotic fluid as a treatment for patients with COVID-19. Primary outcome will be the change in C-reactive protein. Secondary outcomes include safety, biomarker inflammatory levels and clinically relevant outcomes at 30 days, including mortality, ventilator-free days and hospital and intensive care unit length of stay. Exploratory outcomes of health-related quality-of-life patient-reported outcomes will be collected. Hospitalised patients with laboratory-confirmed COVID-19 will be recruited. ETHICS AND DISSEMINATION: This study was approved by the University of Utah Institutional Review Board (IRB_0013292), approved by the US FDA under Investigational New Drug (No 23369) and is registered on ClinicalTrials.gov. Results will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04497389; Pre-results.

A pilot trial of human amniotic fluid for the treatment of COVID-19.

OBJECTIVE: Vertical transmission from SARS CoV-2-infected women is uncommon and coronavirus has not been detected in amniotic fluid. Human amniotic products have a broad immune-mediating profile. Observing that many COVID-19 patients have a profound inflammatory response to the virus, we sought to determine the influence of human amniotic fluid (hAF) on hospitalized patients with COVID-19. RESULTS: A 10-patient case series was IRB-approved to study the impact of hAF on hospitalized patients with documented COVID-19. Nine of the 10 patients survived to discharge, with one patient succumbing to the disease when enrolled on maximal ventilatory support and severe hypoxia. The study design was altered by the IRB such that the last 6 patients received higher dose of intravenous hAF. In this latter group, patients that had observed reductions in C-reactive protein were associated with improved clinical outcomes. No hAF-related adverse events were noted. Acknowledging some of the inherent limitations of this case series, these results inform and catalyze a larger scaled randomized prospective trial to further investigate hAF as a therapy for COVID-19. Trial Registration ClinicalTrials.gov: NCT04319731; March 23, 2020.

Balancing revenue generation with capacity generation: case distribution, financial impact and hospital capacity changes from cancelling or resuming elective surgeries in the US during COVID-19.

BACKGROUND: To increase bed capacity and resources, hospitals have postponed elective surgeries, although the financial impact of this decision is unknown. We sought to report elective surgical case distribution, associated gross hospital revenue and regional hospital and intensive care unit (ICU) bed capacity as elective surgical cases are cancelled and then resumed under simulated trends of COVID-19 incidence. METHODS: A retrospective, cohort analysis was performed using insurance claims from 161 million enrollees from the MarketScan database from January 1, 2008 to December 31, 2017. COVID-19 cases were calculated using Institute for Health Metrics and Evaluation models. Centers for Disease Control (CDC) reports on the number of hospitalized and intensive care patients by age estimated the number of cases seen in the ICU, the reduction in elective surgeries and the financial impact of this from historic claims data, using a denominator of all inpatient revenue and outpatient surgeries. RESULTS: Assuming 5% infection prevalence, cancelling all elective procedures decreases ICU overcapacity from 160 to 130%, but these elective surgical cases contribute 78% (IQR 74, 80) (1.1 trillion (T) US dollars) to inpatient hospital plus outpatient surgical gross revenue per year. Musculoskeletal, circulatory and digestive category elective surgical cases compose 33% ($447B) of total revenue. CONCLUSIONS: Procedures involving the musculoskeletal, cardiovascular and digestive system account for the largest loss of hospital gross revenue when elective surgery is postponed. As hospital bed capacity increases following the COVID-19 pandemic, restoring volume of these elective cases will help maintain revenue. In these estimates, adopting universal masking would help to avoid overcapacity in all states.

Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry.

BACKGROUND: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date. METHODS: We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality. FINDINGS: Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4-40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20-2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6-41·5). INTERPRETATION: In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19. FUNDING: None.