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.

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.

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.

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.

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.

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.

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.

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.

Metoclopramide versus hydromorphone for the emergency department treatment of migraine headache.

UNLABELLED: We conducted a retrospective cohort study to compare the effects of metoclopramide versus hydromorphone for the initial emergency department treatment of migraine headache at an urban teaching hospital. The primary outcome measure was the mean difference in the subjects' self-reported pain scores before and after the administration of the initial medication treatment. We also estimated crude and adjusted relative risks (using Poisson multivariate regression modeling) to assess and control potential confounding by age, gender, race, and pain score before initial medication. Two hundred subjects were included, with 51 (25.5%) receiving intravenous or intramuscular hydromorphone, 95 (47.5%) receiving intravenous metoclopramide, and 54 (27.0%) receiving 1 of several other medications. Using a standardized pain scale of 0 to 10, mean pain score reductions were 2.3 points for hydromorphone, 3.7 points for metoclopramide, and 2.8 points for all other medications combined (P < .001). When comparing metoclopramide versus hydromorphone, the crude relative risk for pain reduction of 3 or more points was 1.76 (95% CI, 1.12-2.75, P = .01), and the adjusted relative risk was 1.60 (95% CI, 0.84-3.03, P = .15). Metoclopramide also resulted in less use of rescue medications, faster times to discharge, and no difference in the frequency of adverse reactions. PERSPECTIVE: Metoclopramide appears to be an effective initial medical treatment for migraine headaches in the emergency department setting, but its pharmacologic mechanism remains incompletely understood. A double-blinded, randomized, controlled trial comparing standard dosages of hydromorphone versus metoclopramide will be needed to definitively determine which medication is more effective.

Responding to a small-scale bioterrorist anthrax attack: cost-effectiveness analysis comparing preattack vaccination with postattack antibiotic treatment and vaccination.

BACKGROUND: In 2001, a small-scale bioterrorism-related anthrax attack was perpetrated via the US mail. The optimal future response may require strategies different from those required in a large-scale attack. METHODS: We conducted a cost-effectiveness analysis using Monte Carlo simulation during a 10-year time frame from a societal perspective to determine the optimal response strategy for a small-scale anthrax attack perpetrated against US Postal Service distribution centers in a large metropolitan area. Three strategies were compared: preattack vaccination of all US distribution center postal workers, postattack antibiotic therapy followed by vaccination of exposed personnel, and postattack antibiotic therapy without vaccination of exposed personnel. Outcome measures were costs, quality-adjusted life-years, and incremental cost-effectiveness. The probabilities for anthrax exposure and infection; vaccine and antibiotic benefits, risks, and costs; and associated clinical outcomes were derived from the medical literature and from bioterrorism experts. RESULTS: Postattack antibiotic therapy and vaccination of exposed postal workers is the most cost-effective response compared with other strategies. The incremental cost-effectiveness is $59 558 per quality-adjusted life-year compared with postattack antibiotic therapy alone. Preattack vaccination of all distribution center workers is less effective and more costly than the other 2 strategies. Assuming complete adherence to preattack vaccination, the incremental cost-effectiveness compared with postattack antibiotic therapy alone is almost $2.6 million per quality-adjusted life-year. CONCLUSION: Despite uncertainties about a future anthrax attack and exposure risk, postattack antibiotic therapy and vaccination of exposed personnel seems to be the optimal response to an attack perpetrated through the US Postal Service.

Discriminating inhalational anthrax from community-acquired pneumonia using chest radiograph findings and a clinical algorithm.

BACKGROUND: Limiting the effects of a large-scale bioterrorist anthrax attack will require rapid and accurate detection of the earliest victims. We undertook this study to improve physicians' ability to rapidly detect inhalational anthrax victims. METHODS: We conducted a case-control study to compare chest radiograph findings from 47 patients from historical inhalational anthrax cases and 188 community-acquired pneumonia control subjects. We then used classification tree analyses to derive an algorithm of chest radiograph findings and clinical characteristics that accurately and explicitly discriminated between inhalational anthrax and community-acquired pneumonia. RESULTS: Twenty-two of the 47 patients from historical inhalational anthrax cases (46.8%) had reported chest radiograph findings. All 22 case patients (100%) had mediastinal widening, pleural effusion, or both. However, 16 case patients (72.7%) also had infiltrates. In comparison, all 188 community-acquired control subjects had reported chest radiographs. Of these, 127 control subjects (67.6%) had infiltrates, 43 control subjects (22.9%) had pleural effusions, and 15 control subjects (8.0%) had mediastinal widening. A derived algorithm with three predictor variables (chest radiograph finding of mediastinal widening, altered mental status, and elevated hematocrit) is 100% sensitive (95% confidence interval [CI], 73.5 to 100) and 98.3% specific (95% CI, 95.1 to 99.6). The derivation process used 12 patients with inhalational anthrax and 177 control subjects with community-acquired pneumonia who had information available for all three variables. CONCLUSIONS: There are significant chest radiograph differences between inhalational anthrax and community-acquired pneumonia, but none of the chest radiograph findings are both highly sensitive and highly specific. The derived clinical algorithm can improve physicians' ability to discriminate inhalational anthrax from community-acquired pneumonia, but its utility is limited to previously healthy individuals and its accuracy may be limited by missing values.

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.

Serum biochemical markers for post-concussion syndrome in patients with mild traumatic brain injury.

Mild traumatic brain injury (MTBI) is a major public health problem in the United States. A significant subset of MTBI patients develop persistent and distressing neurological, cognitive, and behavioral symptoms, known as the post-concussion syndrome (PCS). To date, multiple studies have assessed the relationship between brain-related proteins found in the serum at the time of injury, and the development of PCS. We conducted a systematic review of prospective cohort studies that assessed the ability of serum biochemical markers to predict PCS after MTBI. A total of 11 studies assessing three different potential biochemical markers of PCS--S100 proteins, neuron-specific enolase (NSE), and cleaved Tau protein (CTP)--met selection criteria. Of these markers, S100 appeared to be the best researched. We conclude that no biomarker has consistently demonstrated the ability to predict PCS after MTBI. A combination of clinical factors in conjunction with biochemical markers may be necessary to develop a comprehensive decision rule that more accurately predicts PCS after MTBI.