Immune-related adverse event in the emergency department: methodology of the immune-related emergency disposition index (IrEDi).

For many cancer patients, immune checkpoint inhibitors (ICIs) can be life-saving. However, the immune-related adverse events (irAEs) from ICIs can be debilitating and can quickly become severe or even be fatal. Often, irAEs will precipitate visits to the emergency department (ED). Therefore, early recognition and the decision to admit, observe, or discharge these patients from the ED can be key to a cancer patient's morbidity and mortality. ED clinicians typically make their decision for disposition (admit, observe, or discharge) within 2-6 h from their patient's ED presentation. However, irAEs are particularly challenging in the ED because of atypical presentations, the absence of classic symptoms, the delayed availability of diagnostic tests during the ED encounter, and the fast pace in the ED setting. At present, there is no single sufficiently large ED data source with clinical, biological, laboratory, and imaging data that will allow for the development of a tool that will guide early recognition and appropriate ED disposition of patients with potential irAEs. We describe an ongoing federally funded project that aims to develop an immune-related emergency disposition index (IrEDi). The project capitalizes on a multi-site collaboration among 4 members of the Comprehensive Oncologic Emergency Research Network (CONCERN): MD Anderson Cancer Center, Ohio State University, Northwestern University, and University of California San Diego. If the aims are achieved, the IrEDi will be the first risk stratification tool derived from a large racial/ethnically and geographically diverse population of cancer patients. The future goal is to validate irEDi in general EDs to improve emergency care of cancer patients on ICIs.

A case series of adrenal insufficiency (likely due to hypophysitis) in cancer patients treated with immune checkpoint inhibitors.

The number of approved immune checkpoint inhibitors (ICIs) and their indications have significantly increased over the past decade. Immune-related adverse effects (irAEs) of ICIs vary widely in presentation and symptoms and can present diagnostic challenges to emergency department (ED) physicians. Moreover, when ICIs are combined with radiotherapy, cytotoxic chemotherapy, or targeted therapy, the attribution of signs and symptoms to an immune-related cause is even more difficult. Here, we report a series of 5 ED cases of adrenal insufficiency in ICI-treated cancer patients. All 5 patients presented with severe fatigue and nausea. Four patients definitely had and one patient possibly had central adrenal insufficiency, and 4 patients had undetectable serum cortisol levels. The majority of the patients had nonspecific symptoms that were not recognized at their first ED presentation. These cases illustrate the need for a heightened level of suspicion for adrenal insufficiency in ICI-treated cancer patients with hypotension, nausea and/or vomiting, abdominal pain, fatigue, or hypoglycemia. As ICI use increases, irAE-associated oncologic emergencies will become more prevalent. Thus, ED physicians must update their knowledge regarding the diagnosis and management of irAEs and routinely inquire about the specific antineoplastic therapies that their ED patients with cancer are receiving. A random cortisol level (results readily available in most EDs) with interpretation taking the circadian rhythm and the current level of physiological stress into consideration can inform the differential diagnosis and whether further investigation of this potential irAE is warranted.

Using Causal Diagrams for Biomedical Research.

Causal diagrams are used in biomedical research to develop and portray conceptual models that accurately and concisely convey assumptions about putative causal relations. Specifically, causal diagrams can be used for both observational studies and clinical trials to provide a scientific basis for some aspects of multivariable model selection. This methodology also provides an explicit framework for classifying potential sources of bias and enabling the identification of confounder, collider, and mediator variables for statistical analyses. We illustrate the potential serious miscalculation of effect estimates resulting from incorrect selection of variables for multivariable modeling without regard to their type and causal ordering as demonstrated by causal diagrams. Our objective is to improve researchers' understanding of the critical variable selection process to enhance their communication with collaborating statisticians regarding the scientific basis for intended study designs and multivariable statistical analyses. We introduce the concept of causal diagrams and their development as directed acyclic graphs to illustrate the usefulness of this methodology. We present numeric examples of effect estimate calculations and miscalculations based on analyses of the well-known Framingham Heart Study. Clinical researchers can use causal diagrams to improve their understanding of complex causation relations to determine accurate and valid multivariable models for statistical analyses. The Framingham Heart Study dataset and software codes for our analyses are provided in Appendix E1 (available online at http://www.annemergmed.com) to allow readers the opportunity to conduct their analyses.

Oncologic emergencies and urgencies: A comprehensive review.

Patients with advanced cancer generate 4 million visits annually to emergency departments (EDs) and other dedicated, high-acuity oncology urgent care centers. Because of both the increasing complexity of systemic treatments overall and the higher rates of active therapy in the geriatric population, many patients experiencing acute decompensations are frail and acutely ill. This article comprehensively reviews the spectrum of oncologic emergencies and urgencies typically encountered in acute care settings. Presentation, underlying etiology, and up-to-date clinical pathways are discussed. Criteria for either a safe discharge to home or a transition of care to the inpatient oncology hospitalist team are emphasized. This review extends beyond familiar conditions such as febrile neutropenia, hypercalcemia, tumor lysis syndrome, malignant spinal cord compression, mechanical bowel obstruction, and breakthrough pain crises to include a broader spectrum of topics encompassing the syndrome of inappropriate antidiuretic hormone secretion, venous thromboembolism and malignant effusions, as well as chemotherapy-induced mucositis, cardiomyopathy, nausea, vomiting, and diarrhea. Emergent and urgent complications associated with targeted therapeutics, including small molecules, naked and drug-conjugated monoclonal antibodies, as well as immune checkpoint inhibitors and chimeric antigen receptor T-cells, are summarized. Finally, strategies for facilitating same-day direct admission to hospice from the ED are discussed. This article not only can serve as a point-of-care reference for the ED physician but also can assist outpatient oncologists as well as inpatient hospitalists in coordinating care around the ED visit.

Association of an emergency department febrile neutropenia intervention protocol with time to initial antibiotic treatment.

BACKGROUND: Earlier initial antibiotic treatment for febrile neutropenia is associated with improved clinical outcomes. This study was conducted to evaluate the association of an emergency department (ED) intervention protocol with time to initial antibiotic treatment for febrile neutropenia patients. METHODS: We conducted a cohort study of adult ED febrile neutropenia patients before and after implementation of an intervention protocol. Analyses included comparison of means and medians, Kaplan-Meier estimates, multivariable regression analyses, interrupted time-series analyses, and causal mediation analyses. The intervention protocol included specific triage and process-of-care actions to reduce the primary outcome of time to initial antibiotic treatment. RESULTS: There were 69 patients in the 12-month preintervention period and 52 patients in the 8-month postintervention period. The mean (±SD) times to initial antibiotics were 197.6 (±85.4) min for the preintervention group and 97.7 (±51.0) min for the postintervention group (difference of 99.9 min with 95% confidence interval [CI] = 73.5 to 126.4, p < 0.001). The patients' probability for receiving initial antibiotics within 90 min was severalfold greater (adjusted risk ratio = 10.31, 95% CI = 4.99 to 21.30, p < 0.001) for the postintervention group versus preintervention group. ED length of stay, hospital length of stay, 30-day readmissions, and 30-day all-cause mortality were not different between the study groups. The association of the intervention protocol with time to initial antibiotics appeared to be mediated through times to treatment room placement, report of absolute neutrophil count, and initial antibiotic order. CONCLUSIONS: The intervention protocol was associated with a significant reduction in time to initial antibiotics for ED patients with febrile neutropenia. This association appears to be facilitated through specific intermediate process-of-care variables. A larger multicenter study is needed to assess the potential effects of an ED febrile neutropenia protocol on patient-centered clinical outcomes and resource utilization.

Clinical characteristics, laboratory findings, radiographic signs and outcomes of 61,742 patients with confirmed COVID-19 infection: A systematic review and meta-analysis.

INTRODUCTION: In the current time where we face a COVID-19 pandemic, there is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. METHOD: We searched all relevant literature published up to February 28, 2020. We used Random-effect models to analyze the appropriateness of the pooled results. RESULT: Eighty studies were included in the meta-analysis, including 61,742 patients with confirmed COVID-19 infection. 62.5% (95% CI 54.5-79, p < 0.001) of patients had a history of recent travel endemic area or contact with them. The most common symptoms among COVID-19 infected patients were fever 87% (95% CI 73-93, p < 0.001), and cough 68% (95% CI 55.5-74, p < 0.001)), respectively. The laboratory analysis showed that thrombocytosis was present in 61% (95% CI 41-78, p < 0.001) CRP was elevated in 79% (95% CI 65-91, p < 0.001), and lymphopenia in 57.5% (95% CI 42-79, p < 0.001). The most common radiographic signs were bilateral involvement in 81% (95% CI 62.5-87, p < 0.001), consolidation in 73.5% (95% CI 50.5-91, p < 0.001), and ground-glass opacity 73.5% (95% CI 40-90, p < 0.001) of patients. Case fatality rate (CFR) in <15 years old was 0.6%, in >50 years old was 39.5%, and in all range group was 6%. CONCLUSIONS: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases.

Trends in Adult Cancer-Related Emergency Department Utilization: An Analysis of Data From the Nationwide Emergency Department Sample.

IMPORTANCE: The emergency department (ED) is used to manage cancer-related complications among the 15.5 million people living with cancer in the United States. However, ED utilization patterns by the population of US adults with cancer have not been previously evaluated or described in published literature. OBJECTIVE: To estimate the proportion of US ED visits made by adults with a cancer diagnosis, understand the clinical presentation of adult patients with cancer in the ED, and examine factors related to inpatient admission within this population. DESIGN, SETTING, AND PARTICIPANTS: Nationally representative data comprised of 7 survey cycles (January 2006-December 2012) from the Nationwide Emergency Department Sample were analyzed. Identification of adult (age ≥18 years) cancer-related visits was based on Clinical Classifications Software diagnoses documented during the ED visit. Weighted frequencies and proportions of ED visits among adult patients with cancer by demographic, geographic, and clinical characteristics were calculated. Weighted multivariable logistic regression was used to examine the associations between inpatient admission and key demographic and clinical variables for adult cancer-related ED visits. MAIN OUTCOMES AND MEASURES: Adult cancer-related ED utilization patterns; identification of primary reason for ED visit; patient-related factors associated with inpatient admission from the ED. RESULTS: Among an estimated 696 million weighted adult ED visits from January 2006 to December 2012, 29.5 million (4.2%) were made by a patient with a cancer diagnosis. The most common cancers associated with an ED visit were breast, prostate, and lung cancer, and most common primary reasons for visit were pneumonia (4.5%), nonspecific chest pain (3.7%), and urinary tract infection (3.2%). Adult cancer-related ED visits resulted in inpatient admissions more frequently (59.7%) than non-cancer-related visits (16.3%) (P < .001). Septicemia (odds ratio [OR], 91.2; 95% CI, 81.2-102.3) and intestinal obstruction (OR, 10.94; 95% CI, 10.6-11.4) were associated with the highest odds of inpatient admission. CONCLUSIONS AND RELEVANCE: Consistent with national prevalence statistics among adults, breast, prostate, and lung cancer were the most common cancer diagnoses presenting to the ED. Pneumonia was the most common reason for adult cancer-related ED visits with an associated high inpatient admission rate. This analysis highlights cancer-specific ED clinical presentations and the opportunity to inform patient and system-directed prevention and management strategies.

The Emergency Care of Patients With Cancer: Setting the Research Agenda.

To identify research priorities and appropriate resources and to establish the infrastructure required to address the emergency care of patients with cancer, the National Institutes of Health's National Cancer Institute and the Office of Emergency Care Research sponsored a one-day workshop, "Cancer and Emergency Medicine: Setting the Research Agenda," in March 2015 in Bethesda, MD. Participants included leading researchers and clinicians in the fields of oncology, emergency medicine, and palliative care, and representatives from the National Institutes of Health. Attendees were charged with identifying research opportunities and priorities to advance the understanding of the emergency care of cancer patients. Recommendations were made in 4 areas: the collection of epidemiologic data, care of the patient with febrile neutropenia, acute events such as dyspnea, and palliative care in the emergency department setting.

Timing of initial antibiotic treatment for febrile neutropenia in the emergency department: the need for evidence-based guidelines.

Guidelines for the treatment of febrile neutropenia (FN) universally recommend the prompt initiation (<60 minutes) of antibiotic therapy for patients with this complication presenting to medical settings. Unfortunately, administration delays exist in emergency departments where patients with FN frequently seek care. Future guidelines should be based on investigations that clearly indicate the effectiveness of rapid antibiotic therapy. If definitive investigations identify an optimal time period for the initial administration of antibiotics for patients with FN, administrative efforts will be developed to improve the emergency department care of these critically ill patients with cancer.

Predictors of Mortality in a Clinic Cohort of HIV-1 Infected Children Initiated on Antiretroviral Therapy in Jos, Nigeria.

BACKGROUND: Mortality among human immunodeficiency virus-1 (HIV-1) infected children initiated on antiretroviral therapy (ART) though on a decline still remains high in resource-limited countries (RLC). Identifying baseline factors that predict mortality could allow their possible modification in order to improve pediatric HIV care and reduce mortality. METHODS: We conducted a retrospective cohort study analyzing data on 691 children, aged 2 months-15 years, diagnosed with HIV-1 infection and initiated on ART between July 2005 and March 2013 at the pediatric HIV clinic of Jos University Teaching Hospital. Lost to follow-up children were excluded from the analyses. A multivariate Cox proportional hazards model was fitted to identify predictors of mortality. RESULTS: Median follow-up time for the 691 children initiated on ART was 4.4 years (interquartile range (IQR), 1.8-5.9) and at the end of 2752 person-years of follow-up, 32 (4.6%) had died and 659 (95.4%) survived. The mortality rate was 1.0 per 100 child-years of follow-up period. The median age of those who died was about two times lower than that of survivors [1.7 years (IQR, 0.6-3.6) versus 3.9 years (IQR, 3.9-10.3), p<0.001]. On unadjusted Cox regression, the risk of dying was about three and half times more in children <5 years of age compared to those >5 years (p=0.02) Multivariate modeling identified age as the main predictor of death with mortality decreasing by 24% for every 1 year increase in age (Adjusted Hazard Ratio (AHR)=0.76 [0.62-0.94], p=0.013. CONCLUSION: The lower mortality rate for our study suggests that even in RLC, mortality rates could be reduced given a good standard of care. Early initiation of ART in younger children with close monitoring during follow-up could further reduce mortality.

Cost-effectiveness comparison of response strategies to a large-scale anthrax attack on the chicago metropolitan area: impact of timing and surge capacity.

Rapid public health response to a large-scale anthrax attack would reduce overall morbidity and mortality. However, there is uncertainty about the optimal cost-effective response strategy based on timing of intervention, public health resources, and critical care facilities. We conducted a decision analytic study to compare response strategies to a theoretical large-scale anthrax attack on the Chicago metropolitan area beginning either Day 2 or Day 5 after the attack. These strategies correspond to the policy options set forth by the Anthrax Modeling Working Group for population-wide responses to a large-scale anthrax attack: (1) postattack antibiotic prophylaxis, (2) postattack antibiotic prophylaxis and vaccination, (3) preattack vaccination with postattack antibiotic prophylaxis, and (4) preattack vaccination with postattack antibiotic prophylaxis and vaccination. Outcomes were measured in costs, lives saved, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We estimated that postattack antibiotic prophylaxis of all 1,390,000 anthrax-exposed people beginning on Day 2 after attack would result in 205,835 infected victims, 35,049 fulminant victims, and 28,612 deaths. Only 6,437 (18.5%) of the fulminant victims could be saved with the existing critical care facilities in the Chicago metropolitan area. Mortality would increase to 69,136 if the response strategy began on Day 5. Including postattack vaccination with antibiotic prophylaxis of all exposed people reduces mortality and is cost-effective for both Day 2 (ICER=$182/QALY) and Day 5 (ICER=$1,088/QALY) response strategies. Increasing ICU bed availability significantly reduces mortality for all response strategies. We conclude that postattack antibiotic prophylaxis and vaccination of all exposed people is the optimal cost-effective response strategy for a large-scale anthrax attack. Our findings support the US government's plan to provide antibiotic prophylaxis and vaccination for all exposed people within 48 hours of the recognition of a large-scale anthrax attack. Future policies should consider expanding critical care capacity to allow for the rescue of more victims.

Cost-effectiveness of influenza vaccination of older adults in the ED setting.

OBJECTIVES: Adults older than 50 years are at greater risk for death and severe disability from influenza. Persons in this age group, however, are frequently not vaccinated, despite extensive efforts by physicians to provide this preventive measure in primary care settings. We performed this study to determine if influenza vaccination of older adults in the emergency department (ED) may be cost-effective. METHODS: Using a probabilistic decision model with quasi-Markov modeling of a typical influenza season, we calculated costs and health outcomes for a hypothetical cohort of patients using parameters from the literature. Three ED-based intervention strategies were compared: (1) no vaccination offered, (2) vaccination offered to patients older than 65 years (limited strategy), and (3) vaccination offered to all patients who are 50 years and older (inclusive strategy). Outcomes were measured as costs, lives saved, and incremental costs per life saved. We performed deterministic and probabilistic sensitivity analyses. RESULTS: Vaccination of patients 50 years of age and older results in an incremental cost of $34,610 per life saved when compared with the no-vaccination strategy. Limiting vaccination to only those older than 65 years results in an incremental cost of $13,084 per life saved. Results were sensitive to changes in vaccine cost but were insensitive to changes in other model parameters. CONCLUSIONS: Vaccination of older adults against influenza in the ED setting is cost-effective, especially for those older than 65 years. Emergency departments may be an important setting for providing influenza vaccination to adults who may otherwise have remained unvaccinated.

International variations in the clinical, diagnostic, and treatment characteristics of emergency department patients with acute heart failure syndromes.

AIMS: Results from investigations in one area of the world may not translate to another if patient characteristics and practices differ. We examine differences in the presentation and management of emergency department (ED) patients with dyspnoea from acute heart failure syndromes (AHFS) between the USA, Western Europe, and Eastern Europe. METHODS AND RESULTS: The URGENT Dyspnoea study was a multinational prospective observational study of dyspnoeic ED patients with AHFS from 18 countries. Acute heart failure syndrome patients from the USA and Western and Eastern Europe underwent dyspnoea assessments within 1 h of the first physician evaluation. Patient characteristics, evaluation, and treatments were compared between geographical regions using analysis of variance and χ(2) tests. Four hundred and ninety-three patients with AHFS met the inclusion criteria. Participants in the USA were more frequently non-white, younger, on chronic beta-blocker therapy, and with an ejection fraction ≤40% when compared with Eastern and Western Europe. Patients from Eastern Europe were more likely to present with de novo heart failure and have ischaemic electrocardiogram changes. Pulmonary oedema was more common on chest radiograph in Western Europe, but natriuretic peptide levels were elevated in all three regions. Diuretic use was similar across all the regions. Intravenous nitroglycerin was used more frequently in Eastern (32.8%) and Western Europe (24.4%) compared with the USA (2.5%). CONCLUSION: International differences in AHFS presentations and management between regions suggest results from clinical trials in one region may not translate directly to another. These differences should be considered when designing trials and interpreting the results from clinical investigations.

Effects of an intervention brochure on emergency department patients' safe alcohol use and knowledge.

Alcohol abuse is a leading cause of morbidity and mortality in the United States, contributing to over 100,000 deaths and costing society over 185 billion dollars each year. The objective of this study was to evaluate the effects of the American College of Emergency Physician's brief alcohol use intervention brochure on patients' hazardous drinking behavior and knowledge of safe alcohol use. We conducted a controlled trial comparing Emergency Department (ED) subjects receiving the alcohol use intervention brochure vs. receiving no brochure. One-month outcome measures included the following: 1) change in days of hazardous drinking; 2) change in knowledge of safe alcohol use; and 3) movement along a readiness-to-change continuum for excessive alcohol use. Of 277 subjects, 252 (91.0%) agreed to participate, and 188 of these (74.6%) were successfully contacted for 1-month follow-up assessment. We did not find any significant decreases in days of hazardous drinking or increases in knowledge of safe drinking limits for either the intervention or comparison groups. However, among the subgroup of excessive alcohol users (n = 100), we found that significantly more intervention subjects had advanced along the readiness-to-change continuum than comparison subjects (p < 0.01). This effect was even greater among the intervention group subjects who stated that they read the brochure (p < 0.001). A brief alcohol use intervention brochure does not affect ED patients' hazardous drinking behavior or knowledge of safe alcohol use. The brochure, however, may affect certain patients' motivation to change their drinking behavior. Changing drinking behavior requires more than simply handing out a brochure in the ED; referral to community resources for those motivated to change is likely an important component to successful management of this problem.

Derivation of a triage algorithm for chest radiography of community-acquired pneumonia patients in the emergency department.

BACKGROUND: Community-acquired pneumonia (CAP) accounts for 1.5 million emergency department (ED) patient visits in the United States each year. OBJECTIVES: To derive an algorithm for the ED triage setting that facilitates rapid and accurate ordering of chest radiography (CXR) for CAP. METHODS: The authors conducted an ED-based retrospective matched case-control study using 100 radiographic confirmed CAP cases and 100 radiographic confirmed influenzalike illness (ILI) controls. Sensitivities and specificities of characteristics assessed in the triage setting were measured to discriminate CAP from ILI. The authors then used classification tree analysis to derive an algorithm that maximizes sensitivity and specificity for detecting patients with CAP in the ED triage setting. RESULTS: Temperature greater than 100.4 degrees F (likelihood ratio = 4.39, 95% confidence interval [CI] = 2.04 to 9.45), heart rate greater than 110 beats/minute (likelihood ratio = 3.59, 95% CI = 1.82 to 7.10), and pulse oximetry less than 96% (likelihood ratio = 2.36, 95% CI = 1.32 to 4.20) were the strongest predictors of CAP. However, no single characteristic was adequately sensitive and specific to accurately discriminate CAP from ILI. A three-step algorithm (using optimum cut points for elevated temperature, tachycardia, and hypoxemia on room air pulse oximetry) was derived that is 70.8% sensitive (95% CI = 60.7% to 79.7%) and 79.1% specific (95% CI = 69.3% to 86.9%). CONCLUSIONS: No single characteristic adequately discriminates CAP from ILI, but a derived clinical algorithm may detect most radiographic confirmed CAP patients in the triage setting. Prospective assessment of this algorithm will be needed to determine its effects on the care of ED patients with suspected pneumonia.